Two scientists whose work ushered in the first approved therapy using the gene-editing tool CRISPR have won the $3 million Breakthrough Prize in Life Sciences.

The prize winners ‪—‬ Dr. Swee Lay Thein, of the National Heart, Lung and Blood Institute (NHLBI), and Dr. Stuart H. Orkin, of Harvard University — shared the award for basic research that led to the development of a gene therapy that treats the blood disorders sickle cell disease and beta-thalassemia.

The treatment, called Casgevy, functionally cures patients of the painful and potentially deadly diseases by disabling a single gene. Thein and Orkin received their awards at a ceremony in Los Angeles Saturday (April 18).

"I feel extremely honored, overwhelmed and humbled," Thein told Live Science.

The Breakthrough Prize in Life Sciences has been awarded since 2013 to recognize accomplishments in the life sciences.

Deadly blood disorders

Sickle cell disease affects around 7 million to 8 million people globally, predominantly in Africa. In people with the disorder, red blood cells take on a characteristic crescent shape because hemoglobin, the oxygen-carrying molecule inside the cells, forms stiff, long fibrils that deform the cells. These sickled cells stick to one another, triggering blood clots, and they also burst and die easily, causing low red-blood-cell counts.

Patients often face excruciating episodes of pain, known as "crises," when the red blood cells block blood vessels. These blockages can damage organs like the lungs, liver and spleen. The blockages in the lungs can also trigger "acute chest syndrome," which depletes oxygen levels and is the leading cause of death in sickle cell patients.

In beta-thalassemia, the body either does not make ‪—‬ or makes lower amounts of ‪—‬ one portion of the hemoglobin molecule, meaning people with severe forms of the disease must receive blood transfusions for life. Casgevy is approved to treat this severe form of the disease.

Thein, who is a senior investigator at the NHLBI, began her work in the 1980s trying to figure out why some people with these disorders had much milder forms of the diseases than others.

The question had emerged decades earlier, when Dr. Janet Watson, a New York-based pediatrician, showed that infants who later developed sickle cell disease didn't show symptoms and had red blood cells that did not sickle.

Once children were toddlers, symptoms of the disease emerged.

Follow-up work showed that people produce different types of hemoglobin at different stages of development: "Fetal hemoglobin" is produced in the womb, and its production is turned off as babies mature and "adult hemoglobin" takes over.

"I started collecting families — patients — with mild thalassemia, to try to at least unravel the genetics behind it," Thein told Live Science. "It seemed obvious that they have an innate ability, or natural ability, to continue producing fetal hemoglobin."

She analyzed the genes of several families that had a history of disease, including a family of Indian origin that included more than 200 members, spanned seven generations and lived on multiple continents.

Repressing the repressor

A crucial insight came from a study of pairs of identical and fraternal twins who made either very high or very low levels of fetal hemoglobin. This enabled Thein and her colleagues to identify gene variants that affected fetal hemoglobin production. They zeroed in on a region of a gene on chromosome 11 called BCL11A.

Thein's team found that the gene turns off the production of fetal hemoglobin as babies grow. "It's a repressor," Thein said. But when people carried certain versions of BCL11A, the repressor didn't repress and fetal hemoglobin production continued at high levels throughout life.

From there, it wasn't a dramatic leap to conclude that repressing the repressor could be a good strategy to treat people with severe versions of sickle cell disease or beta-thalassemia. Orkin's research proved pivotal in making that leap.

Orkin ‪—‬ who is a pediatric hematologist and oncologist at Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, and Howard Hughes Medical Institute ‪—‬ showed how the repressor mediated the switch to adult hemoglobin, and that gene editing could target the region.

The biotech company Vertex then used the cut-and-paste gene-editing tool CRISPR to snip out the repressor region of BCL11A.

This work eventually led to the development of Casgevy. Administering the therapy involves extracting a person's bone marrow cells, editing the BCL11A repressor using CRISPR, and then reinfusing the gene-edited bone marrow cells back into the patient. The edited cells begin to make red blood cells with high levels of fetal hemoglobin.

It's the first "functional cure" for sickle cell disease, and it has transformed the lives of the few who have received it. But it's not a cure available for everyone with the disease, and there are some drawbacks, Thein said. The treatment process itself can take up to a year, costs a few million dollars, and requires harsh chemotherapy to make space in the bone marrow for the gene-edited stem cells to take root.

"Physically, it's very grueling for the patient," Thein said.

In addition, sickle cell disease and beta-thalassemia predominantly affect people in Africa, Asia and the Mediterranean, where the resources and facilities needed for such treatment may not be available. As a result, scientists working on gene therapy are pivoting to an "in vivo" approach, which involves "actually injecting the gene editing machinery into the patient," Thein said. This would cut out the need to extract, edit and reinfuse bone marrow cells.

Ultimately, the need for more drugs — including cheaper, more easily delivered pills, shots or infusions — is still pressing, Thein said.

Thein has studied a drug called Mitavipat. The drug, which is currently approved for the treatment of the blood disease pyruvate kinase deficiency and beta thalassemia, seems to work by improving the overall metabolic health of red blood cells, Thein said.

Some of the patients on this drug have "been on this treatment and with me for six years, and it has really made quite a big difference," she said, but further tests are needed to approve its use in people with sickle cell disease.

Millions of years ago, humans' ancestors lost the function of a specific gene — but switching that gene back on could help protect people from gout, a new experimental study suggests.

Gout is a type of arthritis that causes sudden, severe pain and swelling in the joints. It happens when there is too much uric acid in the blood, which can form sharp crystals in the joints, triggering painful inflammation. The painful attacks can come on quickly and may last for days or weeks.

While there are several drugs that have been developed to manage elevated uric acid levels, many have either seen limited success or significant drawbacks, including side effects like harmful immune responses.

But in a study published July 18 in the journal Scientific Reports, researchers developed a potential new method of reducing uric acid: They restored the function of a gene humans lost millions of years ago with the help of CRISPR gene editing.

"Human cells still know what to do with that protein" made by the lost gene, study co-author Eric Gaucher, a geneticist at Georgia State University, told Live Science. A postdoctoral scholar in Gaucher's lab, Lais de Lima Balico, was the second co-author on the study.

"Medications used to treat gout … are very effective when taken consistently, but adherence rates to these medications are among the lowest of any chronic disease," Dr. Chen Xie, a rheumatologist at UCLA who was not involved in the study, told Live Science in an email. "A gene editing-based treatment to lower uric acid could be a medication-free, curative therapy that could bypass a lot of practical treatment issues we currently face."

So far, the researchers have explored the idea only in lab studies with human cells, but they say their results suggest that a gene therapy could someday be a viable option for patients with gout.

While gout is a fairly common condition that affects 1 in 25 people worldwide, it is very rare in mammals other than primates. This is because other animals have an active gene for an enzyme called uricase, which breaks down uric acid in the blood and thereby prevents the formation of crystals. However, due to a number of mutations picked up over our evolutionary history, the uricase enzyme in humans cannot process uric acid. Some researchers believe this happened because increased levels of uric acid can also turn fruit sugar into fat, helping primates survive winters and grow bigger brains.

Related: US baby receives first-ever customized CRISPR treatment for genetic disease

Researchers had previously identified which ancient genes may have been responsible for producing uricase by inferring ancestral genes. This means figuring out what the genes of ancient organisms looked like by studying the DNA of living species today. Scientists compare the genes of different animals or people, use computer programs to build family trees, and then make educated guesses about what the original, ancient gene sequences were. Once they have a good idea of what those old genes looked like, they can recreate and "resurrect" the ancient proteins that the genes encode in the lab and possibly open the door to new therapies.

In the new study, researchers used CRISPR gene editing to insert the ancient uricase gene into the genomes of human liver spheroids. Spheroids are 3D blobs of lab-grown tissues that mimic complex, full-size organs found in the body. The insertion of the ancient gene resulted in a drop in uric acid, as well as a reduction in fat buildup related to fruit sugars.

There are existing gout therapies that use uricase to manage high levels of uric acid; for example, the treatment Krystexxa involves injections of uricase proteins made using a combination of pig and baboon gene sequences. However, these protein-based therapeutics often elicit strong immune responses and require clinical monitoring due to the risk of anaphylactic shock.

By contrast, a gene therapy that restores the original, ancient human gene sequence could enable the body's own cells to produce uricase. In theory, the immune reactions could be minimized because much of the uricase protein sequence is already recognized and accepted by the human body.

But the researchers have a long way to go before such a gene therapy could be used in human patients. For next steps, they are transitioning from liver spheroids to lab mice, and they're using nanoparticle delivery systems that introduce CRISPR gene-editing components directly into liver cells.

Such a gene therapy has the potential to transform gout treatment by providing a long-lasting and possibly safer alternative to current therapies, the researchers say. Gene-editing therapies like this, however, are still in early stages of development.

The researchers hope that this approach — of taking and adapting ancient genes for modern therapies — could be more broadly applied in the future.

"My ultimate goal is to be able to wed molecular evolution and clinical medicine," Gaucher said. "Ideally we can use ancient proteins or ancient enzymes to develop therapeutics to help modern society."

Editor's note: This story was updated on Sept. 5, 2025, to add a comment from Dr. Chen Xie.

This article is for informational purposes only and is not meant to offer medical advice.

A man with type 1 diabetes has become the first patient to produce his own insulin after receiving genetically engineered cell transplants, without needing drugs to prevent rejection.

The case, published this month in the New England Journal of Medicine, marks a potential breakthrough in the treatment of the disease, which affects 9.5 million people worldwide.

Type 1 diabetes occurs when a patient's immune system destroys specialized cells, called islet cells, in their pancreas that are responsible for producing insulin, the hormone that regulates our blood sugar levels. The condition can be managed with regular doses of synthetic insulin, but there is no cure.

Islet cell transplants can provide a longer-term supply of insulin for people with type 1 diabetes. However, after receiving a transplant, the patient’s immune system can recognize the new organ as a foreign object, triggering a response that can destroy the transplanted tissue. As a result, transplant patients must take immunosuppressive drugs for the rest of their lives, which leaves them susceptible to infections.

To overcome these hurdles, scientists in Sweden and the United States transplanted islet cells from a donor's pancreas that had been genetically modified using CRISPR technology to suppress rejection by the recipient's immune system. This is the first time the treatment has been tested on a human.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

Twelve weeks after receiving the genetically-modified cells, the transplant recipient has continued to produce insulin without an immune response.

In their paper, the authors wrote that their study, although preliminary, suggested that genetically engineering transplant cells to evade the recipient's immune system was a valuable tool for avoiding rejection of new cells or organs by the immune system.

In this new approach, the researchers used CRISPR to create three changes to the genetic code of the donated cells so that they were less likely to have an immune response.

Two of these edits reduced the levels of proteins on the surface of the cells that signal to our white blood cells about whether a cell is foreign or not. A third edit boosted production of a protein that discourages attack from other immune cells called CD47.

The genetically edited cells were then injected into the man’s forearm. His body left the modified cells alone and the surviving cells produced insulin as normal.

Although the man was given a low dose of the edited cells and will still require daily insulin treatment, the case suggests that the procedure can be done safely.

The researchers’ next step is to carry out follow-up studies to find out whether the cells can survive in the long-term, which would make management of the disease easier and potentially provide a cure. They also need to do further tests to determine whether the approach works in other patients.

DNA that humans acquired from ancient viruses plays a key role in switching parts of our genetic code on and off, a new study has found.

Nearly half of the human genome consists of segments called transposable elements (TEs), also known as "jumping genes" because they can hop around the genome. Some of these TEs are remnants of ancient viruses that embedded themselves in our ancestors' genomes and have been passed down over millions of years.

For decades after TEs were discovered, scientists assumed they served no useful purpose — that they were "junk" DNA. But this new study adds to the mounting evidence that this description was far from correct.

Far from being functionless fossils, these ostensibly dormant stretches of our DNA could be crucial in regulating gene expression, especially during early development, the research suggests. The scientists published their findings July 18 in the journal Science Advances.

"Our genome was sequenced long ago, but the function of many of its parts remain unknown," study co-author Hiromi Nakao-Inoue, a research coordinator at Kyoto University's Institute for the Advanced Study of Human Biology, said in a statement. "Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance."

Not so junky after all

TEs were deemed "junk" because they seemed irrelevant to the creation of proteins — the molecules that build cells and keep them running. While genes carry blueprints for proteins, these repetitive, transposable elements had long been dismissed as "nonfunctional" DNA.

Related: Best-ever map of the human genome sheds light on 'jumping genes,' 'junk DNA' and more

Yet in recent years, evidence has begun to pile up that these repetitive portions of our genomes play a role in gene regulation. For instance, their codes are often used to make noncoding RNA, a molecule that can act upon other genes to differentiate cells and regulate the growth of embryos.

More detailed study of transposable elements has also been made possible by CRISPR. The famous gene-editing tool has enabled scientists to peer into how TEs influence the structure of chromatin — the mixture of DNA and proteins from which chromosomes are made — and jump-start an embryo's gene activity after fertilization.

The scientists behind the new research focused on a specific family of TEs called MER11. The family belongs to a larger class of TEs that entered primate genomes some 40 million years ago.

The researchers classified sequences within the MER11 family based on their evolutionary relationships to one another. This produced four subgroups from MER11_G1 (the oldest) to MER11_G4 (the youngest).

To see what effects these TEs have on cells, they inserted nearly 7,000 of the sequences into cells in lab dishes. The sequences, taken from humans and other primates, were placed inside stem cells and early-stage neural cells, whose gene activity was then measured.

Their results showed that the youngest members of the MER11 family — MER11_G4 — had a strong ability to activate genes. They came equipped with unique "transcription factor binding sites," which are DNA motifs that are key to development and act as docking pads for proteins that control gene expression.

Subtle variations in MER11_G4 sequences also existed between humans, chimps and macaques, with variations changing the sequences' regulatory effect from species to species.

"The study highlights how much there is still to learn from the genome sequence," Cristina Tufarelli, a geneticist at the University of Leicester's University's Cancer Research Centre who was not involved in the study, told Live Science. "Especially when it comes to virus-like transposon repeats whose variety between and within families has been largely overlooked."

She added that the work opens up several avenues for future investigation. "The approach could be applied to any transposable element with the potential to help gain a deeper knowledge of other elements with potential regulatory functions," she said.

Tufarelli added that future experiments could involve deleting certain parts of the TEs with CRISPR to help unravel their roles in regulating gene expression in both health and disease.

An experimental gene therapy for high cholesterol is showing promise in clinical trials and inching closer to approval.

The treatment, called VERVE-102, is being tested in people with familial hypercholesterolemia (FH), an inherited condition that raises the levels of low-density lipoprotein (LDL) cholesterol — the "bad" kind — in the blood. It's also being tested in people with premature coronary artery disease (CAD), in which the arteries narrow and can't deliver enough oxygenated blood to heart muscle. The age at which CAD is considered "premature" varies, but it generally occurs before age 65 in women and age 55 in men.

Both groups "require deep and durable reductions" of LDL in the blood, Verve Therapeutics, the treatment's maker, noted in an April statement. In an ongoing clinical trial, the company tested the treatment in 14 people with FH and/or premature CAD, and found that a single dose of the therapy led to a 53% reduction in LDL, on average.

These early data are drawn from three groups of people who received different doses of the treatment. The four participants given the highest dose saw the largest benefit: a 69% reduction in LDL, at maximum.

Across the groups, "VERVE-102 was well-tolerated, with no treatment-related serious adverse events (SAEs) and no clinically significant laboratory abnormalities observed," Verve's statement noted.

VERVE-102 uses a modified version of CRISPR, the famous gene-editing system. The CRISPR systems developed originally introduce a "break" in both strands of a DNA molecule, and then, the cell's built-in repair system swoops in to repair the break. However, this comes with the risk of adding unwanted mutations to the DNA.

Related: New CRISPR alternative can 'install' whole genes, paving the way to treatment for many genetic disorders

The new cholesterol-lowering therapy instead uses "base editing," which swaps out just one letter in DNA's code, thus sidestepping the danger of a double-stranded break. Like classic CRISPR, the base editor still includes a "guide" molecule to fix its aim at the correct gene, and from there, an enzyme tweaks just one letter in DNA's code.

VERVE-102 targets a gene called PCSK9, which controls the number of LDL receptors on the surfaces of cells. The quantity of these receptors dictates how quickly LDL gets cleared from the blood. When PCSK9 is too active — as it is in the genetic disease FH — it breaks down LDL receptors before they can make it to the cell surface, thus causing LDL to accumulate in the bloodstream instead.

The new therapy, given in a single intravenous infusion over two to four hours, is designed to turn off PCSK9, especially in the liver, where LDL receptors are abundant. Across the three dosing groups, there was a decrease in both PCSK9 activity and LDL levels in the 28 days following the treatment, with higher doses tied to greater reductions.

Now, the company is enrolling a fourth group of patients who will receive an even higher dose, and who are being recruited in the United Kingdom, Canada, Israel, Australia and New Zealand. As of April, two people in the group had been treated.

Verve expects to release data from this portion of the trial later this year, as well as start its next clinical trial, which will include more participants. The next trial will likely enroll U.S. participants, as the Food and Drug Administration granted the therapy "Fast Track Designation" to help expedite its development and approval.

Notably, in June, Verve was acquired by the drug company Lilly, which aims to continue the development of the treatment.

"VERVE-102 has the potential to be the first in vivo [in the body] gene editing therapy for broad patient populations and could shift the treatment paradigm for cardiovascular disease from chronic care to one-and-done treatment," Ruth Gimeno, Lilly group vice president of diabetes and metabolic research and development, said in a statement.

Larger and longer clinical trials will be needed before VERVE-102 can earn approval and reach more patients.

This article is for informational purposes only and is not meant to offer medical advice.

A baby born with a rare and devastating genetic condition has become the first person ever to be successfully treated with a personalized CRISPR therapy. After receiving three doses of the therapy in the past few months, the infant is now 9.5 months old and thriving, his doctors report.

"We want each and every patient to have the potential to experience the same results we saw in this first patient," Dr. Kiran Musunuru, a professor for translational research at the University of Pennsylvania's Perelman School of Medicine, said in a statement. "The promise of gene therapy that we've heard about for decades is coming to fruition, and it's going to utterly transform the way we approach medicine."

Musunuru is a co-author of a new paper describing the procedure, which was published Thursday (May 15) in The New England Journal of Medicine. The results were also presented at the American Society of Gene & Cell Therapy's annual meeting in New Orleans this week.

The treated child, referred to as KJ, was born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. The inherited condition is estimated to affect 1 in 1.3 million people worldwide. It's inherited in an autosomal recessive pattern, meaning a person must inherit two mutant copies of the gene — one from each parent — to develop the condition.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

The condition arises from mutations in the CPS1 gene, which codes for a protein the liver uses to process nitrogen compounds in the blood. This nitrogen, generated as the body breaks down proteins, needs to be processed and detoxified into a product called urea to be excreted in urine. But when the CPS1 gene is mutated, the nitrogen-containing compound ammonia builds up in the body and causes damage, especially in the brain.

The severity of CPS1 deficiency depends on whether the affected person has complete or partial absence of the gene's encoded protein. Those with a complete lack of the enzyme, like KJ, have the most severe form of the disease. This causes symptoms to show up shortly after birth, including unusual sleepiness, a poorly regulated breathing rate, unwillingness to feed, vomiting after feeding, unusual body movements, seizures or coma.

About half of children with this form of the condition die in early infancy. Children who survive to older ages then need to follow a tightly regulated diet, to limit their protein intake, and they may have developmental delays and intellectual disability due to neurological damage.

For KJ, symptoms emerged within the first 48 hours of birth. A rapid genetic analysis revealed that both his maternal and paternal copies of the CPS1 gene were shorter than usual, meaning they were "truncating" gene variants. The paternal mutation, called Q335X, had been reported to cause the disease in a previous case.

Renal-replacement therapy was used to filter KJ's blood. Later, he was switched to a drug that captured the extra nitrogen in his blood, and he was put on a protein-restricted diet. "Given the severity of his disease, the patient was listed for liver transplantation at 5 months of age," the report notes, but he would have had to grow big enough — and be medically stable enough — to receive one.

In the years prior to KJ's birth, Musunuru and Dr. Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at Children's Hospital of Philadelphia, had begun exploring the feasibility of customized gene therapies built using the gene-editing technique known as CRISPR.

The two CRISPR-based therapies approved to date have a one-size-fits-all approach: They work by completely disabling a specific gene. But in many genetic disorders, function needs to be restored to a broken gene, and the way that gene is broken differs from patient to patient. One way to address such disorders is through personalized therapies designed to address a patient's unique mutation.

The duo had focused on urea cycle disorders, such as CPS1 deficiency, and demonstrated success in animal experiments. When KJ was born, Ahrens-Nicklas approached his parents — Kyle and Nicole Muldoon — with the idea of designing their newborn a custom gene therapy built on their prior work. After discussing the details of the experimental treatment, the Muldoons agreed, Genetic Engineering and Biotechnology News (GEN) reported.

The team rapidly developed a customized therapy built upon base editing, which works by changing just one letter in DNA's code. The therapy was designed to fix the Q335X mutation KJ carried, and it was ready to administer within six months of his birth. The infant received his first dose of the therapy in February 2025, at between 6 and 7 months of age, and he received follow-up doses in March and April.

These three doses had no serious side effects. KJ can now consume more protein safely and take less of the nitrogen-scavenging drug. He's started sitting up by himself — a sign that he's gaining motor function that may not have been possible otherwise.

"Seeing him reach milestones that are important for any infant blows us away even more because we know what was stacked up against him from the very beginning," KJ's mother told reporters during a news conference, GEN reported.

Although the effects of the treatment have been promising, KJ will need to be carefully monitored for the rest of his life, Ahrens-Nicklas said in the statement.

"Although this has been a very specific approach, partly motivated by the devastating nature of the disease, it represents a milestone that demonstrates these therapies are now a reality," Miguel Ángel Moreno-Mateos, a geneticist at Pablo de Olavide University in Seville, Spain, told The Guardian. "As the article reports, the patient will be monitored for a long time to ensure his wellbeing and determine whether additional doses are needed to further improve the symptoms of the disease."

This article is for informational purposes only and is not meant to offer medical advice.

Scientists have developed a new gene-editing system that can weave whole genes into human DNA. It could one day lead to a better method of treating genetic diseases triggered by a diverse range of mutations.

So far, the approach has been tested only in human cells in the laboratory. But if it's shown to be safe and effective for patients, it could provide an alternative to gene-editing tools that target only specific typos in DNA. Rather than correcting a single gene mutation, the new technique would instead introduce a working copy of the gene into a person's cells.

"A single genetic disease can be caused by many different mutations in that gene," said Isaac Witte, a doctoral student at Harvard University and co-lead author of the new research. For example, cystic fibrosis can be triggered by more than 2,000 different mutations in a specific gene. "Treating it [these types of conditions] with genome editing often requires many, mutation-specific approaches. That's labor-intensive, and also intensive from a regulatory standpoint" to get all those approaches approved, Witte told Live Science.

An alternative strategy is to introduce a whole new gene to make up for the broken one. The gene editor, described in a report published Thursday (May 15) in the journal Science, enables these types of edits and can insert the new gene directly "upstream" of where the broken one is found in human DNA. More work is needed to get the new gene editor out of the lab and into medical practice, but "we are quite excited by this," Witte said.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

Directing evolution in the lab

Classical CRISPR systems are often nicknamed "molecular scissors" because they use proteins to cut DNA. These systems are found naturally in bacteria, which use CRISPR to defend themselves against invaders, such as viruses.

The core of the new gene editor is also borrowed from bacteria, but it does not cut DNA. Rather, it moves large sections of a host's DNA from one location to another in a highly targeted manner. These systems — called CRISPR-associated transposases (CASTs) — have been known about since 2017 and act as a way for "jumping genes" to leap around, either within the same cell's DNA or possibly into other cells' genomes.

CASTs are attractive for gene editing because, unlike molecular scissors, they don't cut DNA and thus don't rely on cellular machinery to patch up the DNA that's sustained the cut. That repair process makes it tricky to add new DNA to the genome, in part because it can introduce unwanted mutations. CASTs, on the other hand, sidestep that issue.

But CASTs found naturally in bacteria don't play well with human cells. In previous studies led by Samuel Sternberg, an associate professor of biochemistry and molecular biophysics at Columbia University and a co-senior author of the new paper, researchers characterized naturally occurring CASTs and then attempted to use them to edit DNA in human cells. But the systems proved very inefficient, inserting DNA into only 0.1% or less of the cells, Witte said.

So Witte, Sternberg and colleagues set out to make CASTs more useful for human therapies. They started with a CAST from Pseudoalteromonas bacteria, which, in previous studies, had shown a teensy bit of activity in human cells. Then, they used an experimental approach called PACE to speed up the evolution of that CAST, introducing new tweaks to the system in each successive round.

Through this process, the team evolved a new CAST that could integrate DNA into human cells with 200-fold more efficiency than the original, on average.

"It took over 200 hours in PACE, which corresponds to several hundreds of evolutionary generations," Witte said. The same process would have taken years with more conventional methods of directing evolution in lab dishes.

Related: 188 new types of CRISPR revealed by algorithm

Next steps

The evolved CAST — dubbed evoCAST — includes 10 key mutations that are needed for it to work well in human cells, Witte said. However, the system works better in some types of human cells than in others, and more research will be needed to understand why that is, he said.

The team assessed how well evoCAST worked at regions of the genome that carry genes that are mutated in certain diseases, such as Fanconi anemia, Rett syndrome and phenylketonuria. The team found evoCAST worked in about 12% to 15% of treated cells. Although 100% efficiency is likely not necessary to treat genetic diseases, Witte noted, the exact efficiency needed to cure a given condition likely varies and will require study.

The team also tested evoCAST as a method for editing immune cells used in CAR T-cell therapy, a cancer treatment, and found it was similarly efficient for that purpose. That raises the idea of using this gene-editing approach not only inside the human body, but also in the lab to manufacture these types of cell-based therapies.

Future research will need to figure out how to best deliver evoCAST to the right cells in the body. "There are a lot of areas for further studies," Witte said.

Of course, those studies will need to be funded, and on that front, "it's a difficult time," he added. The new Science study was supported, in part, by the National Institutes of Health (NIH). Now, the NIH's funding has been slashed by sweeping cuts, some of which specifically singled out Ivy League universities like Harvard. "It is something that we're actively dealing with," Witte said.

In an announcement on Monday (April 7), scientists revealed to the world that they have "brought back" long-extinct dire wolves with genetic engineering.

Researchers with the biotechnology company Colossal Biosciences shared images of three adorable, snow-white pups, which they said mark the "world's first de-extinction."

Dire wolves (Aenocyon dirus), which were made famous by the HBO television series "Game of Thrones," went extinct at the end of the last ice age. By creating lookalike pups, Colossal's CEO Ben Lamm said the company has "made healthy dire wolf puppies" and resurrected these predators after more than 10,000 years of extinction.

But many experts say the language used by Colossal to describe their creation is misleading. "What Colossal have produced is a gray wolf with dire wolf-like characteristics," Nic Rawlence, an associate professor and co-director of the Otago Palaeogenetics Laboratory at the University of Otago, told the New Zealand Science Media Center (NZ SMC). "This is not a de-extincted dire wolf, rather it's a 'hybrid.'"

To make the pups, scientists extracted DNA from two prehistoric dire wolf fossils: a 13,000-year-old tooth discovered in Sheridan Pit, Ohio, and a 72,000-year-old inner ear bone from American Falls in Idaho. Using this DNA, the researchers pieced together a partial dire wolf genome, which they then compared with the genomes of the dire wolf's closest living relatives, including wolves, jackals and foxes.

Related: 'Closer than people think': Woolly mammoth 'de-extinction' is nearing reality — and we have no idea what happens next

Based on their results, the scientists selected the gray wolf (Canis lupus) as an egg donor to "bring back" dire wolves — despite the two species not actually being that closely related, experts said.

"New information shows that the original dire wolf itself was not really a wolf," David Mech, an adjunct professor specializing in wolf ecology and behavior at the University of Minnesota and senior research scientist with the U.S. Geological Survey, told Live Science in an email.

Evolutionarily speaking, dire wolves split from wolves roughly 6 million years ago, forming an entirely separate group from modern-day gray wolves. "Dire wolves are in their own genus, so a very different species," Philip Seddon, a professor of zoology at the University of Otago, told NZ SMC. "The African jackal might be more closely related to dire wolves."

"GMO wolves"

De-extinction requires egg cells from a living animal to hold and "grow" the genetic material of the animal scientists want to create. Having selected gray wolves to perform this step, Colossal scientists then collected cells from gray wolf blood samples and modified them to resemble the cells they found in the dire wolf fossils. Using CRISPR gene-editing technology, the team made a total of 20 edits in 14 genes that they identified as important in giving dire wolves their distinctive traits.

Next, in a similar process as the one used to clone Dolly the sheep in 1996, the scientists inserted the modified cells' DNA into gray wolf egg cells, whose own genetic material had previously been removed. At this point, the gray wolf egg cells contained all the genetic information required to build wolves with some of the defining characteristics of dire wolves. The egg cells were then left to mature in the lab, and the resulting embryos were implanted into the wombs of domestic dogs, which are technically a subspecies of the gray wolf.

Colossal's first "dire wolf" puppies, Romulus and Remus, were born Oct. 1, 2024, meaning they are now 5-month-old adolescents. According to Colossal, they are being held and continually monitored in a nature preserve surrounded by 10-foot-tall (3 meters) fencing.

"They will live out their life in a luxurious preserve under human care," Bridgett vonHoldt, a professor of evolutionary genomics and epigenetics at Princeton University who collaborates with Colossal on this project, told Live Science in an email. "As many have seen with previously cloned animals, their health always remains unpredictable and of potential concern."

A third pup, Khaleesi, was born Jan. 30, 2025. It's unclear how dangerous these animals are, but their behavior is unlikely to differ dramatically from that of a captive gray wolf, especially as they have been constantly surrounded by humans, vonHoldt said. "Lots of captive wolves are handled by humans. Some remain submissive with their humans even as adults while others mature into a more aloof, standoffish animal. I expect the DW [dire wolves] will be no different."

Romulus, Remus and Khaleesi will not be released into the wild, but in the future, Colossal said it will consider options to introduce animals into "secure and expansive ecological preserves potentially on Indigenous land."

But some experts doubt very much that these introductions would be successful. "Any release to the wild would be fraught with negative PR and legal consequences, which would probably also be the case with any of the other types of newly created animals," Mech said.

Regarding the dire wolf specifically, Mech said there is a question mark over how they might fit into modern ecosystems. "They occupied an entirely different ecological niche than exists today," he said.

Many experts have criticized Colossal's announcement, but some have also praised the technological breakthroughs the company made along the way. "Certainly, this involves advances in genetic technology, and these might have applications for the conservation of existing species," Seddon said.

One species that is already benefiting from Colossal's breakthroughs is the red wolf (Canis rufus), the world's most endangered wolf. The company announced the birth of two litters of cloned red wolves on Monday, boosting the number of red wolves held in captivity in the U.S. and offering new hope for the species.

But at the end of the day Colossal's claim that it has resurrected the dire wolf is spurious, Seddon and others said. "Colossal compared the genomes of the dire wolf and the gray wolf, and from about 19,000 genes, they determined that 20 changes in 14 genes gave them a dire wolf," Rawlence said.

Moreover, Colossal's "dire wolves" aren't technically the world's first de-extinction. In 2003, scientists in Spain cloned an extinct wild goat species known as the bucardo, or the Pyrenean ibex (Capra pyrenaica pyrenaica). A baby goat was born, but it died seven minutes later due to a lung defect.

The announcement on Monday means that "we have GMO wolves and might one day have GMO Asian elephants, but for now extinction really is for ever," Seddon said.

The legacy of our ancient human relatives, "brain-eating-amoeba" infections, emerging viral threats, the promise and peril of genome editing, and much, much more — in 2024, Live Science covered a plethora of fascinating, and occasionally concerning, health studies. Research granted new insight into the human body's inner workings, the germs that can push our physiology off the rails, and the emerging technologies and drugs that could change medicine as we know it.

Here are some of my favorite stories from the past year. Keep up with us in 2025 to see how these diverse lines of research progress!

Bird flu

H5N1, a subtype of bird flu, reached the U.S. in late 2021, when it began inflecting wild birds, domestic poultry and the occasional mammal. This year, we learned for the first time that the virus can infect cows — and that it can jump from cows to people. At this point, there's been no evidence of H5N1 spreading from one person to another — an ability that could set the stage for a major outbreak, or even a pandemic. But Live Science has closely followed new discoveries about the virus: how it lingers in raw milk, is evolving to better infect mammals, could become deadlier if it mingles with seasonal flu, and is just one mutation away from being a "good match" for humans. We'll keep up with H5N1 in 2025, when mounting surveillance efforts by scientists should give a better sense of how big this problem could become.

Related: 9 of the most 'genetically isolated' human populations in the world

Our ancient ancestry

Modern humans mated with Neanderthals at several points in our history, and today, you can dust for genetic "fingerprints" left by our Neanderthal relatives. Some regions of the human genome contain up to 80% Neanderthal genes, while others, such as the X and Y chromosomes, are nearly or completely Neanderthal-free. These genes influence our face shape, skin color, circadian clock and immune function — and, in some contexts, they may do more harm than good. In an intriguing feature story, staff writer Emily Cooke explores the ways our Neanderthal genes may affect our health and biology today.

Battling brain-eaters

"Brain-eating" amoebas kill nearly everyone they infect, but new and emerging treatments could change that. A drug called miltefosine — originally designed to treat the parasitic disease leishmaniasis — has saved some patients' lives. And scientists are investigating other possible treatments, including antibiotics, mRNA vaccines and even a pigment derived from algae. Hopefully, someday, these rare infections won't be a nearly assured death sentence.

CRISPR

Scientists unveiled a new CRISPR system that reversibly "pauses" genes, rather than permanently disabling them. CRISPR innovator Virginijus Šikšnys spoke with Live Science about the future of the field and how the technology could render incurable diseases curable. On the flip side, doctor and science communicator Dr. Neal Baer discussed how, in the wrong hands and without adequate regulation, CRISPR could also become an instrument of eugenics.

Honorable mentions

To stop antibiotics from becoming obsolete, researchers are seeking ways to reverse antibiotic resistance. Researchers discovered a new hormone that helps build strong bones, particularly after pregnancy. A study highlighted how a quirk in forensic DNA analysis could end up linking the wrong people to crimes. Psychedelics are being tested as therapies, but major trial issues are hindering their approval. The male hormone cycle is linked to brain shrinkage over the course of the day, while pregnancy is tied to brain shrinkage across gestation. Several studies found that human aging might happen in distinct waves — but we're not sure why.

Scientists have unveiled a new version of the famous gene-editing tool CRISPR, one that can "pause" a given gene temporarily rather than permanently turning it off.

The CRISPR revolution started in 2012, when Jennifer Doudna and Emmanuelle Charpentier — now Nobel winners — published their discovery of a new gene-editing technique more accurate and efficient than anything tried before. CRISPR has since transformed genetic research and was recently approved for a first-of-its-kind gene therapy for people with blood disorders.

The original CRISPR system works by recognizing a specific sequence of DNA and then cutting that portion of the DNA strand, effectively turning off the gene permanently. Unfortunately, this technique comes with risks, such as "off-target" cuts that slice through the wrong genes.

Now, however, researchers at Vilnius University in Lithuania introduced a new, more versatile genetic toolkit called the type IV-A CRISPR system. Described in a study published Oct. 29 in the journal Nature Communications, the system deactivate genes in an impermanent manner, giving researchers more control over gene activity.

The type IV-A CRISPR system doesn't cut the DNA. "Type IV-A systems are truly unique in their molecular activity," senior study author Patrick Pausch, a genetics researcher and professor at Vilnius University, told Live Science in an email. "Most other CRISPR systems … once they locate a gene, they cut it, and that's it! In contrast, type IV-A systems continuously act on a gene of interest, effectively massaging its DNA, if you will."

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

The type IV-A system was first discovered in 2018, and in multiple publications, scientists have reported how the system generally functions. In their new study, Pausch and his colleagues revealed the detailed structure of the molecules within the type IV-A CRISPR system. They used cryo-electron microscopy, a technique in which frozen proteins are bombarded with electrons to create a 3D image of the molecule.

The researchers showed that, by unraveling DNA's double helix, the type IV-A system can stably but reversibly suppress a gene's activity without having to cut its DNA.

"The power of this technique is that it silences gene expression without changing the DNA sequence," Ryan Jackson, a biochemist at Utah State University and not involved in the study, told Live Science in an email. "This strategy could be especially useful in the research lab where a scientist may want to silence expression for a while, but then turn expression back on to observe the results."

Pausch said that their study lays the groundwork for future iterations of this system. "We describe the molecular processes underlying this activity, enabling us to adapt this system for next generation genome editing applications," he said. The system described in the paper uses one class of enzyme to unwind DNA, but different enzymes could also be used. For example, there are enzymes that can tweak the epigenetics affecting a given gene, meaning the factors that affect the gene's activity without changing its DNA sequence.

This system can also silence genes located far away from the original DNA target sequence. That's because researchers use an enzyme called DinG, which has the ability to unwind the DNA double helix and then move along the DNA strand.

"This 'long-distance' silencing mechanism is different from other existing methods that rely on direct interactions with the sequence to be silenced, Jackson noted. Such a tool could help scientists better understand the complex ways in which gene activity is controlled, he said.

In the future, Pausch and his colleagues hope to fill in more of the missing details of how the system works, especially how the CRISPR and enzyme molecules change shape as they suppress genes. Following this, the team hopes to begin exploring potential therapeutic applications of the technology.

One way they could see the system being applied in medicine is as a platform for the next generation of genome editors. These editors could directly edit a pair of letters in DNA's code; temporarily increase or decrease the expression of specific genes; or edit the "epigenome." These tools could be used in the clinic to treat disease, as well as in agriculture to increase yields or reduce food waste.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

With their primary goal to advance scientific knowledge, most scientists are not trained or incentivized to think through the societal implications of the technologies they are developing. Even in genomic medicine, which is geared toward benefiting future patients, time and funding pressures make real-time ethics oversight difficult.

In 2015, three years after scientists discovered how to permanently edit the human genome, U.S. scientists issued a statement to halt applications of germline genome editing, a controversial type of gene editing where the DNA changes also transfer to the patient's future biological descendants. The scientists' statement called for "open discussion of the merits and risks" before experiments could begin. But these discussions did not happen.

By 2018, at least two babies had been born from germline editing with embryos that had been genetically modified in China. With no preemptive ethics or clear regulatory guidance, you get the occasional "cowboy scientist" who pushes the boundaries of experiments until they are told to stop.

After finding out about the babies, scientists continued to talk — but mostly among themselves. Then in 2020, an international commission report that brought together expert views resounded the same call for societal discussions about whether germline editing could be ethical.

Related: 'Who are we to say they shouldn't exist?': Dr. Neal Baer on the threat of CRISPR-driven eugenics

I'm a medical anthropologist and bioethicist who studies the values and experiences driving prenatal gene therapy developments, including genome editing.

Human prenatal genome editing has not happened yet — as far as we know. Prenatal genome editing isn't the same as editing ex vivo embryos, like the Chinese scientist did, because prenatal editing involves editing the DNA of a fetus visible inside a pregnant person's womb — without the intent to affect future descendants.

But the societal implications of this technology are still vast. And researchers can already start exploring the ethics by engaging communities well ahead of time.

Engaging communities

You can't really anticipate how technologies might benefit society without any input from people in society. Prospective users of the technology in particular might have their own experiences to offer. In 2022 in the U.K., a citizens' jury composed of people affected by genetic disease deliberated. They voted that germline editing of human embryos could be ethical — if a series of specific conditions could be met, such as transparency and equality of access.

Recently in the U.S., the National Council on Disability published a report on their concerns about embryo and prenatal editing. Their key concern was about the potential for more discrimination against people with disabilities.

Some people see preventing the birth of people with certain genetic traits as a form of eugenics, the troubling practice of treating a social group's genetic traits as unwanted and attempting to remove them from the human gene pool. But genetic traits are often associated with a person's social identity — treating certain traits as unwanted in the human gene pool can be deeply discriminatory.

Losing a baby to severe genetic disease leads to profound suffering for families. But the same genes that cause disease may also create human identity and community. As the National Council on Disability outlined in its report, people with disabilities can have a good quality of life when given enough social support.

It's not easy to engage nonscientists in discussions about genetics. And people have diverse values, which means community deliberations that work in one context might not work in another. But from what I've seen, scientific developments are more likely to benefit prospective users when the developers of the technology consider the users' concerns.

Not just about the fetus

Prenatal human genome editing, also known as fetal genome surgery, offers a chance to address cellular disease processes early, perhaps even preventing symptoms from ever appearing. The delivery of treatment could be more direct and efficient than what is possible after birth. For example, gene therapy delivered into the fetal brain could reach the whole central nervous system.

Related: Most Americans support gene editing for babies to treat diseases, poll finds

But editing a fetus necessarily involves the pregnant person.

In the 1980s, scientists managed to conduct surgery on a fetus for the first time. This established the fetus as a patient and direct recipient of health care.

Seeing the fetus as a separate patient oversimplifies the maternal-fetal relationship. Doing so has historically downgraded the interests of the pregnant person.

And since editing the fetal genome could harm the expectant parent or require an abortion, any discussion about prenatal genetic interventions also becomes a discussion about abortion access. Editing the genes of a fetus isn't only about editing that fetus and preventing genetic disease.

Prenatal genome editing versus editing embryos

Prenatal genome editing sits within the broader spectrum of human genome editing, which ranges from germline, where the changes are heritable, to somatic cell, where the patient's descendants won't inherit the changes. Prenatal genome editing is, in theory, somatic cell editing.

There's still a small potential for accidental germline editing. "Editing" a genome can be a misleading metaphor. When first developed, gene editing was less like cutting and pasting genes and more like sending in a drone that can hit or miss its target — a piece of DNA. It may change the genome in intended and sometimes unintended ways. As the technology advances, gene editing is becoming less like a drone and more like a surgeon's cut.

Ultimately, researchers can't know whether there would be unintentional, collateral germline edits until decades into the future. It would require editing a significant number of fetuses' genomes, waiting for these fetuses to be born, and then waiting to analyze the genomes of their future descendants.

Related: 'Enhancing' future generations with CRISPR is a road to a 'new eugenics,' says ethicist Rosemarie Garland-Thomson

Unresolved health equity issues

Another major ethical question has to do with who would get access to these technologies. To distribute prenatal genome therapies equitably, technology developers and health care systems would need to address both cost and trust issues.

Take, for example, new gene-editing treatments for children with sickle cell disease. This disease mostly affects Black families, who continue to face significant disparities and barriers in access to both prenatal care and general health care.

Editing the fetus instead of a child or adult could potentially reduce health care costs. Since a fetus is smaller, practitioners would use fewer gene-editing materials with lower manufacturing costs. More than that, treating the disease early could reduce costs that the patient might accrue over a lifetime.

Nonetheless, all genome editing procedures are expensive. Treating a 12-year-old with sickle cell disease with gene editing currently costs US$3.1 million. While some academics want to make gene editing more affordable, there hasn't been much progress yet.

There's also the issue of trust. I've heard from families in groups that are underrepresented in genomics research that say they're hesitant to participate in prenatal diagnostic research if they don't trust the health care team doing the research. This type of research is the first step to building models for treatments such as prenatal genome editing. Moreover, these underrepresented families tend to have less trust in the health care system at large.

Although prenatal gene editing holds immense potential for scientific discovery, scientists and developers could invite the prospective users — the people who stand to gain or lose the most from this technology — to the decision-making table for the clearest picture of how these technologies could affect society.

This edited article is republished from The Conversation under a Creative Commons license. Read the original article.

The gene-editing tool CRISPR enabled a groundbreaking new treatment for sickle-cell disease, and in the future, scientists anticipate that it could be used to tackle cancer, forms of inherited blindness, various superbug infections and even HIV. These uses of CRISPR are fairly uncontroversial — but in the background, ethicists worry that the tool could be used to edit away other, nonpathological features of humankind that are deemed "abnormal" or "unacceptable."

In the book excerpt below, Rosemarie Garland-Thomson, a bioethicist, author and thought leader in disability justice, discusses the danger of using CRISPR to enact what she calls "velvet eugenics." The passage is part of an essay featured in the new book "The Promise and Peril of CRISPR" (2024, Johns Hopkins University Press), edited by Dr. Neal Baer.

Related: 'Who are we to say they shouldn't exist?': Dr. Neal Baer on the threat of CRISPR-driven eugenics

A New Eugenics

What does this meditation on eugenic science and its medical practice have to do with CRISPR, the newest and most promising tool in the suite of medical technology with which our fast-paced system of research, development, and commerce has presented us? Much of the public and professional conversation about CRISPR centers on explaining how it works, debating its safety, assessing its potential benefits, considering its targets, or warning against its unintended consequences. My concern is not with the efficacy or ingenuity of the technology, but rather with epistemological questions about what the existence of CRISPR technology suggests about the limits of being human — and what it means for my friend who someday might alter an embryo to align with what is considered a healthy child.

I have invoked the history of eugenics in modernity to support the position in the public and academic debates that much current reproductive technology, including gene editing, carries out a new eugenics in the name of health and reproductive liberty. The other side of the debate supports the free development and use of these reproductive technologies, often amplified by commercial interests. An ethics grounded in liberty interests strongly supports the growth of this laissez-faire medicine in today's moment when public sector or common good enterprises and private commercial interests are increasingly entangled. The commercial logic of free choice enters the obstetrical medical environment not only in support of reproductive liberty, but also in the name of a parental and medical obligation to fulfill the best interests of future children. For instance, a fetus, diagnosed by reproductive technology with spina bifida, can potentially receive in utero surgical treatment or be aborted, depending on the mother's exercise of her medical autonomy, within the limits of state law and local medical protocol. The burden of such a choice falls heavily on the mother trying to weigh the harms and benefits regarding the parental obligation to give one's child a good life. Many of these stories enter public conversation as books and articles about the complex network of suffering and joy as well as trouble and reward when a child with an unexpected medical condition or disability enters a family. The opportunity to operate on the fetus is a choice a mother can make, but her choice is influenced by the opposing societal views of the fetus's future health versus the mother's reproductive freedom.

The ethical issues today's new eugenics bring forward concern the dynamics among correction, repair, improvement, and elimination as approaches to the development and use of medical technologies such as CRISPR. If the broadest ethical goal of any medical technology is to improve human lives, we must untangle some of the aspirations of eugenics from the enterprise of genetic technology and other medical interventions aimed at bringing all humans to a standard, "normal" form and function. Characteristics that depart from that standard in ways we understand as disadvantageous are human variations we think of as disease. Characteristics we understand as advantages that depart from that standard are often sought after as enhancements. Eugenics seeks to improve by eliminating the characteristics considered at a particular time and place to be disadvantages and to maximize those considered normal. Enhancement premises intensify the benefits of normal to create forms of super advantage. Genetic manipulation provides a seductive opportunity to improve society and individuals by bringing the abnormal toward normal and lifting the advantage of normal toward an intensified advantage of an imagined supernormal. Such a mechanical understanding of humans as compilations of individual characteristics that can be added or subtracted by way of medical intervention reduces us to the sum of our genetic profiles. Because the body-mind characteristics we think of as disease or disadvantageous traits are always parts of a whole living human being, snipping them away or fastening on supposedly better traits — to use the metaphors of editing and cutting employed to understand and explain CRISPR — promotes a crude understanding of human lived embodiment. The application of eugenic thinking in the first decades of the twentieth century ended because it failed to recognize that human beings could not simply be improved by wiping away specific characteristics deemed disadvantages from whole human beings embedded in lives and worlds.

A collective caution against the enthusiasm for this reductive understanding of improving human lives comes from historians such as Daniel Kevles, bioethicists such as Nathaniel Comfort, Nicholas Agar, Inmaculada de Melo-Martín, and Françoise Baylis, political theorists such as Michael Sandel, and philosophers such as Jürgen Habermas, who all argue against the liberal eugenics that genetic editing seeks to achieve. These thinkers hold that genetic manipulation for the enhancement or improvement of future persons or communities creates morally unacceptable consequences, ranging from producing medical harm to abrogating consent, intensifying genetic discrimination, increasing social inequality, promoting conditional parental acceptance, turning people into products, fostering a commercial medical industrial complex, and encouraging rogue scientific and medical practice. Many who oppose genetic editing understand it as scientific paternalism and a resource grab that saps funding from other initiatives that support the public good. Habermas speaks strongly for them all with the conclusion that genetic editing is "liberal eugenics regulated by supply and demand."

Commercialized medical technology development in the interest of this liberal eugenics produces a culture of what de Melo-Martín calls reprogenetics that standardizes human variation in the interest of individual, market-driven liberty at the expense of social justice and the robust diversity and inclusion upon which modern egalitarian social orders depend. Such technology development and use go beyond genetic editing to a range of reproductive testing and selection practices that carry out what I call a velvet eugenics. Velvet eugenics takes its reference from the Velvet Revolution, beginning in 1989, that overturned many of the communist republics in Central and Eastern Europe without overt violence. Velvet as a metaphor suggests making a smooth change, using only the finest, commercially available product for the well-resourced consumer. This modern laissez-faire striving for what is understood by an individual at a specific time and place as the best drives much of the market for healthy conceptions, pregnancies, and curated offspring that for-profit genetic testing companies cultivate.

By recognizing the eugenic work of medical science in the modern era, these historians, bioethicists, and philosophers offer a collective caution that recognizes the limits of the human capacity to control the future through actions in the present, no matter how well intended, carefully conceived, morally considered, or rigorously monitored.

In opposition to these existential realists are techno-optimists, who cling to the conviction that the technologies medical science develops and uses can control outcomes beneficial to both future individuals and the human community. Sanguine futuristic aspirations, such as eliminating all human disease, enthusiastically supported by the psychologist Steven Pinker, or creating a future population composed of what the philosophers Julian Savulescu and Guy Kahane call "the best," ignore or even dismiss both rogue uses of these eugenic technologies and unintended consequences. Such faith in what the twentieth century named as progress flies in the face of what the twenty-first century knows about the collateral damage ensuing from innovations ranging from nuclear energy to gasoline-powered engines to the ubiquity of plastic, sugary drinks, and opioid pain medication — all aimed at making a better future for everybody. Just as we collectively failed in the past to anticipate the future harms of what we took to be progressive benefits, many advocates of genetic manipulation technologies today refuse to consider the complexities of how and who these technologies may harm.

This piece is adapted from "Velvet Eugenics" by Rosemarie Garland-Thomson, which appears in the new book "The Promise and Peril of CRISPR," edited by Dr. Neal Baer. Copyright 2024. Published with permission of Johns Hopkins University Press.

Since CRISPR was first conceived as a gene-editing tool in 2012, scientists have seen its awesome potential.

It promises to revolutionize the treatment of genetic disorders. It's being used to genetically engineer pig organs for transplant surgeries and to develop new antibacterial treatments. It's being used to breed crops and livestock, as well as modified mosquitoes that thwart the spread of disease.

But CRISPR also has a dark side — it could become an instrument of eugenics.

The ability to easily edit genes comes with the theoretical potential to pare down the diversity of humankind, categorizing some traits as acceptable and others as diseased or "unfit."

This dark side rears its head when scientists consider editing germline cells, which give rise to eggs and sperm, said pediatrician Dr. Neal Baer, a co-director of Harvard's Master of Science in Media, Medicine, and Health, who edited a new book called "The Promise and Peril of CRISPR" (2024, Johns Hopkins University Press). Edits to germline cells can be passed down to successive generations, he emphasized.

"That's where I became a bit worried — who would decide what was passed on or what wasn't passed on?" Baer told Live Science. That question became a focus of the new book, which features essays from bioethicists, scientists, philosophers and activists. Live Science spoke with Baer about the text and the many ethical quandaries raised by CRISPR technology.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

Nicoletta Lanese: Why did you choose to pursue this book now, in particular?

Dr. Neal Baer: As CRISPR was being developed, I saw that there was a potential to make just remarkable inroads, particularly for instance, in treating sickle cell disease — which as we all know, reading the headlines, can be cured with CRISPR by turning on a fetal hemoglobin gene. So I started to read about CRISPR more and more and talk to folks who were doing it. And I saw that there was a change in attitude about CRISPR from about 2015 to the present, and that change was in terms of editing germline cells.

The "promise" is the great things that can come out of this in terms of really annihilating horrible diseases. The "peril" is how far we go in possibly changing human evolution.

NL: I appreciated that, in the text, it was very deliberate that you're pulling in a variety of perspectives. Why was that important to the book?

NB: I did want to expand the viewpoints to positions that hadn't been written about, hear from people we hadn't heard from. For instance, one of very few trans bioethicists, Florence Ashley from Toronto, writes about [whether people might try to use] CRISPR in some way to "treat" trans people, or make them not trans? That's a complicated question because there's not really a gene that makes one trans, but there might be elements that are common amongst trans people.

She [Ashley] also promotes something very provocative in the essay, which I thought was really interesting, as maybe it would be a good thing. That's somatic editing so that people wouldn't have to take hormones, that there could be a way to turn on hormone production, or to give people the kinds of bodies they want.

[As another example] Carol Padden, a dean at the University of California, San Diego, is deaf and she argues that not everything that is genetic and seen as a syndrome is pathological. She says she's deaf, that's human variation — accept it.

But R. Alta Charo's piece is one that argues that we shouldn't really be worried about all this — that we were worried about IVF and sex selection and it really hasn't happened. So that's a very different perspective from many of the other pieces.

I think it's important to raise both the promise and the peril because there really is no oversight, per se — have you heard anyone, any politician ever talk about CRISPR and germline editing?

NL: I can't think of an instance, no.

NB: The answer is no, and yet it's going on and supposedly we're [scientists are] supposed to self-regulate. I've heard this from very famous people who do CRISPR that the people involved will make the ones who don't follow the rules pariahs. But look, Dr. He [Jiankui, the scientist who engineered CRISPR babies] did this. And Ben Hurlbut in his piece talks about geneticists and scientists at a well-known university who encouraged Dr. He to do this work because they knew they couldn't do it. It is illegal in the United States.

(Editor's note: Following his experiment, He received a fine and was sentenced to three years in prison for "illegal medical practices." He, who is not a medical doctor, was then released from prison in 2022 and returned to research. Since the case, China has tightened its regulations around gene editing, explicitly forbidding gene editing for reproductive uses in humans.)

I don't want to be pegged as someone against CRISPR at all; I just want us to think hard about the germline.

But we do talk about people who are very much on the side of doing germline editing, like George Church, renowned geneticist at Harvard, who says, "Look, ultimately, it's going to be cheaper to just get rid of these diseases, so why fool around somatically — let's just edit them."

Related: Could CRISPR cure HIV someday?

Then, we get Rosemarie Garland-Thomson's piece about who decides which genetic syndromes should be eliminated and which should not. We get the case of Down syndrome … should we be eliminating these genetic syndromes that are compatible with life?

I don't know anyone who would say they want to have a child with Tay-Sachs disease, where they know for sure that their child will die before the age of 5. But life is not that easy in terms of black and white. There are a lot of syndromes that people live with and they have very fulfilling, rich lives, and who are we to say they shouldn't exist?

NL: Is there one standout message that you hope readers take away from the book? You'd mentioned this is really aimed at high school- and college-aged students.

NB: For me, the most important element of the book is dual-use technology, which is when we do things to improve health [and] there really positive things come out of it, as we've been talking about, but we also have to be aware that this technology could be used in very negative ways.

That, to me, is like a way of understanding the world more clearly — is that it's not black and white. It's not, "Let's do this because it's good" or "Let's not do it because it's bad." Let's really try to understand what we're jumping into before we tout it as you know, the best thing that's ever happened.

The dual-use technology is fundamental to understanding not only CRISPR but AI [artificial intelligence] and many other technologies within this, especially the ideas of enhancement [of the human body].

NL: I saw that, of course, "Gattaca" (1997) was referenced briefly in the book. How does some people's desire for "designer babies" fit into this discussion, and is that goal even feasible?

NB: The answer is we don't know.

Because our genes are so complex and there's not one gene for eye color [for example] — like if I want a child to have blue eyes. And of course, then it's all cultural. "Why do I want my child to have blue eyes or blonde hair or light skin, or things like that?"

Does that mean we can't ever do it? I don't know. Are there things we can manipulate? Yes, and should we be doing that? That's the question I want to ask.

The environment has an impact too — nutrition, things like that. So I don't really worry so much about enhancement right now … we can't really enhance and in ways that are Gattaca-like. But you know, research is going on, supposedly, in Russia and China about this, that we could possibly make people pain-free. Should we be doing that?

[Conversely] should we cure progeria with CRISPR? (Editor's note: Progeria causes rapid aging in children.)

Of course. It's a horrible disease.

Editor's note: This interview has been condensed and edited for clarity.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

Viruses armed with the gene-editing tool CRISPR could someday be used to treat urinary tract infections (UTIs), results from an early clinical trial suggest.

However, the experimental treatment, which would be used in tandem with traditional antibiotics, still has more tests to undergo before it could be approved for clinical use.

The treatment harnesses bacteriophages, or viruses that infect bacteria. Also called "phages" for short, the viruses are being developed as a potential alternative to conventional antibiotic drugs.

One reason phages are appealing is they can be incredibly selective, taking aim at only specific bacterial strains. This sidesteps problems posed by broader-spectrum antibiotics, which can kill a range of bacteria and thus pressure many microbes to evolve antibiotic resistance. Broad-spectrum antibiotics can also inflict collateral damage on helpful bacteria, including those in the gut microbiome.

Related: Dangerous 'superbugs' are a growing threat, and antibiotics can't stop their rise. What can?

Phages aren't totally immune to resistance; bacteria can evolve strategies to survive the attack of individual viruses. However, multiple phages can be combined into one treatment, forcing the bacteria into a corner.

That's the case for LBP-EC01, the new phage therapy being tested for UTIs. Specifically, LBP-EC01 is designed to kill Escherichia coli, the main culprit behind UTIs.

Made by the company Locus Biosciences, the experimental treatment was described in a paper published Aug. 9 in the journal The Lancet Infectious Diseases. LBP-EC01 would be used alongside a traditional antibiotic to boost that antibiotic's effectiveness and thus reduce the dose needed to cure an infection. (Some other phage therapies are being considered as standalone treatments.)

LBP-EC01 contains six phages, three of which are "lytic," meaning they invade bacterial cells and split them open. The three remaining phages are engineered to carry genes for a CRISPR system. CRISPR is a precise tool that can be used to cut through specific sequences within DNA. Once it's inside an E. coli cell, this CRISPR machinery goes after bits of the bacterial genome that are crucial to the microbe's survival.

"The real draw of it is that it is a sequence-specific tool," meaning the treatment targets only the DNA you tell it to and not sequences present in other cells, Chase Beisel, co-founder and scientific adviser of Locus Biosciences, told Live Science in 2023. So, once administered to a patient, "the CRISPR machinery gets into a set of cells, but only those that have the sequence or sequences you picked will be attacked and killed," he explained.

Locus Biosciences has just completed the first part of a two-part trial of LBP-EC01. The treatment is being tested for uncomplicated UTIs, meaning those that don't involve structural abnormalities in the urinary tract or additional medical problems, such as having a weakened immune system.

The first part of the trial, which included 39 adult female patients, was aimed at identifying a safe dose of the treatment to move into further testing. All of the patients had a history of at least one drug-resistant UTI caused by E. coli in the year prior to the trial.

Tests conducted in the trial ultimately zeroed in on a quick, three-day course of the treatment that's given alongside an antibiotic called trimethoprim-sulfamethoxazole (common brand name Bactrim). No serious side effects were observed with this dosing regimen. In addition, samples of the patients' UTI bacteria didn't show signs of evolving resistance after the treatment.

Related: New UTI vaccine wards off infection for years, early studies suggest

In a subset of 16 patients, the scientists looked more closely at how well the treatment worked against the UTIs. They saw a "rapid reduction of E. coli" in patients' urine within four hours of the first dose. All 16 patients' UTI symptoms had completely resolved by the 10th day after starting treatment. By then, 14 of the 16 had low enough E. coli levels in their urine to be considered cured of the infection, as well.

Eleven of these 16 patients were infected by bacteria that were resistant to TMP-SMX at baseline, the study authors noted. That suggests that the phage treatment worked synergistically with the antibiotic, lowering the bacteria's defenses so even antibiotic-resistant infections could be cleared.

However, because the main goal of this study was to select a dose, not to test the treatment's efficacy, the second phase of the trial will now compare LBP-EC01 to a placebo. In addition, the first leg of the trial was quite small, the study authors noted, but the next phase will include up to 288 participants.

There's more work to be done to move LBP-EC01 toward an official approval. However, broadly speaking, "I can see these [types of treatments] coming about in the five- to 10-year time frame," Beisel previously told Live Science.

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A CRISPR therapy injected directly into the eye shows promise in treating the most common form of inherited vision loss in children, an early trial suggests.

This form of vision loss, called Leber congenital amaurosis (LCA), is often evident at birth and results from the dysfunction or death of light-sensing cells called photoreceptors in the retina, at the back of the eye. Such problems happen due to mutations in any of at least 20 genes. 

Some of the most common causes of LCA are mutations in the gene that codes for centrosomal protein 290 (CEP290). More than three-quarters of the people with the disease carry a particular mutation that affects CEP290, which is crucial for photoreceptors to function properly.

LCA currently has no cure — but now, there's evidence that the famous CRISPR gene-editing tool could be safely used to improve the vision of some people with the condition. The results of the early-stage trial were published May 6 in The New England Journal of Medicine. 

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

The results show the promise of using CRISPR to treat inherited eye diseases, Dr. Mark Pennesi, co-author of the report and a researcher at Oregon Health & Science University, told Live Science in an email. 

"This is just a start and more work is needed, but the proof of concept is exciting," he said. (Pennesi is a consultant with Editas Medicine, the trial's sponsor.)

The trial is also notable in that it included the first person to ever receive a CRISPR-based treatment directly into the body. By comparison, the first approved CRISPR therapy involves removing cells from the body, editing them in a lab and then returning them to the patient.

The trial included 14 participants — 12 adults and two children. All carried the specific mutation in the CEP290 gene that affects a majority of LCA patients. The participants received a single injection of the CRISPR treatment, called EDIT-101, into the eye with the most significant vision loss. The other eye served as a comparison.

EDIT-101 contains tiny guides that lead pairs of "molecular scissors" — called Cas9 enzymes — to the mutant gene CEP290. The scissors snip out the faulty portion of the gene, thus restoring its function. 

The team used a CRISPR-based strategy because CEP290 is a large gene, making it a difficult target for conventional gene therapy, Pennesi said. Some gene therapies use modified viruses to deliver functional genes into cells, to replace faulty genes, but the CEP290 gene is too large to fit into such a delivery system.

Following this treatment, all of the participants underwent vision tests, which were conducted every three months for one year and then followed by less frequent monitoring for two years. By the end of the trial period, 11 of the 14 volunteers had measurable improvements on at least one vision test, while six experienced improvements in two or more tests. One trial participant shared that they could find their phone after misplacing it and could see the small lights on their coffee machine, which they couldn't do before treatment.

Related: Gene therapies restore hearing in several kids with inherited deafness 

Those who didn't show measurable improvements were generally at a more advanced stage of the disease, in which their cells showed a high level of dysfunction at baseline, the trial runners noted. None of the participants experienced adverse side effects of the treatment.

Although EDIT-101 can treat the cells that are present in the retina, it cannot reverse the loss of cells that have already died, Pennesi said. That means participants can experience some improvement in their vision, but it remains decreased, he explained. 

"The therapy is not a cure," he said. 

The next step would be to test the therapy in a larger number of patients. The team specifically hopes to test the drug in younger patients, "who we hope might have even better outcomes," Pennesi said. 

This article is for informational purposes only and is not meant to offer medical advice.

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The first person to receive a pig kidney transplant has died just two months after he underwent the groundbreaking procedure. 

Rick Slayman, a 62-year-old from Weymouth, Massachusetts, had a genetically modified pig kidney placed in his body as part of a four-hour, pioneering surgery at Massachusetts General Hospital on March 16. 

Slayman had end-stage kidney disease and had previously received a human kidney transplant, which showed signs of failure after a few years. His doctors proposed the experimental pig kidney transplant as Slayman was restarting dialysis and experiencing severe complications. 

The doctors hoped that the pig kidney could last years, CNN reported, but, as such a transplant hasn't been done before, there was uncertainty about how well it would take. Slayman died just weeks after his surgery, but his medical team says there's no evidence the transplant was related to Slayman's death. 

Related: 1st partial-heart transplant growing with baby 1 year later

"The Mass General transplant team is deeply saddened at the sudden passing of Mr. Rick Slayman," the hospital shared in a statement on Saturday (May 11). "We have no indication that it was the result of his recent transplant." The statement did not detail Slayman's cause of death.

As of March 2024, more than 100,000 Americans are on the waiting list for organ transplants, 89,000 of which require a kidney. Each day, 17 people on these lists die. Transplanting genetically modified organs from animals into humans, a process known as xenotransplantation, is seen as a promising new way to potentially address the shortage of available organs from human donors. 

Before Slayman's procedure, scientists had only conducted experimental pig kidney transplants in brain-dead organ donors, as a proof-of-concept for the surgeries. However, since then, another living patient has since received one — a 54-year-old who also received a heart pump along with the pig kidney. 

The first person to receive a pig organ of any kind was a Maryland man who underwent the world's first pig-heart transplant in 2022. He died shortly after the surgery, likely as a result of being infected with a pig virus that triggered an inflammatory response.  

In Slayman's case, scientists used CRISPR gene-editing technology to modify the genes of the donor pig, removing ones that could prompt the human immune system to attack the kidney and adding ones that could help prevent transplant rejection. The patient also simultaneously received antibody-based treatments and immune-suppressing drugs to help prevent organ rejection. 

The kidney itself came from a company called eGenesis, which previously successfully tested the transplant in monkeys. On average, the monkeys lived for around 176 days, or nearly six months, after surgery in these experiments. 

In the hospital's statement, Slayman's family said they were thankful to spend his last few weeks with him. 

"[The medical team's] enormous efforts leading the xenotransplant gave our family seven more weeks with Rick, and our memories made during that time will remain in our minds and hearts," they wrote. 

"Millions of people worldwide have come to know Rick's story," they added. "We felt — and still feel — comforted by the optimism he provided patients desperately waiting for a transplant." 

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Scientists introduced CRISPR to the world as a gene-editing tool in summer 2012, when landmark papers from two independent groups demonstrated how the system could be wielded to make cuts in DNA. Now, less than 12 years later, we're seeing CRISPR put to use in groundbreaking medical treatments.

Virginijus Šikšnys was a senior author of one of those paradigm-shifting papers.

"It's really rewarding to see how fast the fundamental discoveries that were made in the lab actually are translated into the clinics," said Šikšnys, who is chief scientist and head of the Department of Protein-DNA Interactions at the Vilnius University Institute of Biotechnology in Lithuania.

Prior to those seminal papers, other researchers had begun unraveling how CRISPR works inside microbes. Although best known as a gene-editing tool, CRISPR was first found in bacteria, and scientists realized that it acts as a kind of immune system — a defense against viruses. In this immune system, the bacterium has a memory bank full of virus' genetic material. The bacterium will stash away this material after being attacked by a virus so it can guard against future invasions.

This memory bank is paired with tiny, molecular scissors called Cas proteins that snip through DNA, and a molecule that guides the scissors to their target. In bacteria, that target is a viral invader. But Šikšnys and his colleagues demonstrated that scientists could co-opt these scissors for their own purposes, targeting any DNA they want to edit. They specifically showed this with the protein Cas9.

Alongside Jennifer Doudna and Emmanuelle Charpentier — authors of the other groundbreaking CRISPR paper published in 2012 — Šikšnys was awarded the 2018 Kavli Prize in Nanoscience for the invention of CRISPR-Cas9, "a precise nanotool for editing DNA." Nowadays, he and his team are investigating the diversity of CRISPR systems that exist in nature to see which others might be useful for engineering genomes.

Live Science spoke with Šikšnys about what it's been like to see CRISPR enter clinical use and how he thinks the system might be applied and improved upon in the future.

Editor's Note: This interview has been condensed and edited for clarity.

Related: Gene therapy: What is it and how does it work?

Nicoletta Lanese: Could you describe when you first began working with CRISPR-Cas? And could you give a sense of when you clued into the idea that this could be "a big deal" — a big-ticket technology that kind of shifts gene-editing as we know it?

Virginijus Šikšnys: We jumped into the CRISPR field, I would say, from the very beginning. It happened probably in 2007 when a paper appeared in Science, describing for the first time the possible function of the CRISPR-Cas system as an antiviral defense system in bacteria. And we decided to look, actually, at how this system functioned. This is how we started our CRISPR journey.

Of course, in the very beginning, we were very much interested in very basic biological questions. ... It took us a while to understand the mechanisms behind the CRISPR-Cas systems. …

In [our 2012] paper, we showed that we can reprogram Cas9 protein and address it to any sequence in the genome. This was probably the moment where we understood that, indeed, this is a kind of really versatile system that could be employed for genome editing in different model organisms. And this is how, then, this kind of gene-editing field started.

NL: Did you envision right away that this might be applied in the treatment of genetic disorders? Did you see that as a possibility, even early on?

VS: If I recall, what we put in our paper at that time — we said that these CRISPR-Cas systems, or Cas9 protein programmed by CRISPR RNA, could be used for precise "DNA surgery."

It means that, actually, you can direct Cas9 to any sequence in the genome, including the sequences where [there are] mutations that cause genetic disease.

NL: Having seen, within the last year, the first CRISPR-based therapies come to market — I'm wondering how it feels to have seen the progression of the field from that basic research to now seeing it applied at that level?

VS: Indeed, looking backwards, it's really amazing to see that Cas9 made it into the clinics, nearly, in 10 years. I think it's a really great achievement, and I'm sure that more therapeutic applications will follow in the near future and will provide cure[s] for genetic diseases that were incurable before.

And if you look at the list of clinical trials that are currently ongoing, where the Cas9 genome-editing tool is employed to treat different genetic diseases — the list is really very impressive. And it's really rewarding to see how fast the fundamental discoveries that were made in the lab actually are translated into the clinics. 

NL: Having seen the graduation into the clinic now, how do you anticipate the gene-editing systems borne of CRISPR-Cas might be refined in the future?

VS: Indeed, the CRISPR-Cas9 technology is a great tool that is rapidly advancing into the clinics. But still, there are several challenges that need to be overcome, and there are, of course, avenues for improvement of this tool. …

Recently, it made headlines that that CRISPR tool was used for treatment of SCD disease [sickle-cell disease]. In fact, [it] showed that this is really a tool that could be used in the clinics for the treatment of the patients.

But of course, this treatment has several limitations, because, in this case, the treatment is occuring ex vivo. It means that the cells that need to be treated are removed from the patient's body, then Cas9 tool is applied to correct the mutation — or actually, trigger production of fetal hemoglobin. And then these engineered cells, they have to be delivered back to the patient's body. And of course, this is kind of a challenging and time-consuming procedure.

So of course, it would be great if the CRISPR treatment could be done directly in [the] human body — we call it in vivo. But actually, to do that, you have to overcome several challenges: First, you have to deliver this CRISPR tool into specific tissues or organs in human body. And of course, there are many ways to deliver CRISPR tools, but after COVID, mRNA vaccines were approved as a therapeutic modality for treatment [prevention] of COVID. And currently, mRNA coupled with lipid nanoparticles became one of the key modalities that could deliver Cas9 into different cells and tissues in a human body.

[Other] delivery systems are also [being] explored, including virus-like particles and adeno-associated viruses. So AAVs are also used as delivery tools and they are approved as safe delivery tools into human body — but, for example, in the case of AAV, there is a packaging cargo limitation and you need to find smaller gene editing tools that could be packaged into a single AAV particle.

In my lab, in fact, we are looking at the avenues — how do you improve the existing tools or, actually, find new tools? To find new tools, we look at the diversity of CRISPR-Cas systems. These CRISPR-Cas systems [in nature] are very, very diverse, and we aim to understand this diversity of CRISPR-Cas systems from a fundamental perspective. And also, we hope that, looking at this diversity, we'll be able to find new tools for genome editing applications.

Related: Meet 'Fanzor,' the 1st CRISPR-like system found in complex life

NL: Could you paint a picture of what it looks like to dig into the diversity of these systems?

VS: In my lab, we're using a combined bioinformatics-based, biochemical approach. So we try to identify putative new CRISPR-Cas systems bioinformatically, and then, we try to characterize them biochemically using the tools available in the wet lab. …

First, we look at [microbial DNA] sequences that are present in really huge databases — you can just try to find new CRISPR systems there. Then, we try to express them in different bacteria, isolate them, characterize, and then move them to human cells to see whether they can be applied as new genome modification tools.

NL: We touched on the sickle cell treatments that have just been approved — I'm wondering if you, like others, anticipated that sickle cell would be one of the first diseases to get a CRISPR treatment? And what diseases do you see as the next frontier?

VS: I would say that it was clear from the very beginning that genetic diseases that are caused by a single mutation, like sickle-cell disease, will be the first target. It looked like low-hanging fruit, because you have to correct just a single mutation in the genome. And of course, I think part of the credit for this Cas9-based treatment of sickle-cell disease should also go toward the people who were studying sickle-cell disease for decades. They were providing us with understanding of the mechanisms of the disease that were harnessed into the treatment.

The other reason why SCD was a clear target was because, as I mentioned before, you can do the treatment [ex] vivo. You can remove cells that contain [the] mutation, actually engineer them in the lab, and put the cells back into human body. So that makes manipulations easier.

But of course, when you think about the next step — treatment of genetic diseases that are caused by multiple mutations, like cancer, for example, is still a challenge. But of course, scientists are trying to develop approaches how to tackle such complex genetic disease. And, for example, T-cell-based therapies are already in the clinics, and CRISPR [systems] are used there to facilitate engineering of these T cells … that could be used to treat cancers like lymphomas and solid tumors.

And of course, the CRISPR treatments in the human body, as I discussed before, is the next big step.

NL: This is somewhat tangential, but we've covered the idea of developing CRISPR as an antibacterial, as a kind of alternate antibiotic — do you see that as a fruitful research area?

VS: The beauty of CRISPR-Cas9 technology is that it's a kind of versatile, or universal technology, because you can use this tool to engineer any living organism. You are just trying to engineer DNA, and DNA is the blueprint of every living organism. So instead of doing gene-editing in human cells, you can also think about doing editing of bacterial population — let's say, that are present in [the] human gut. And these bacterial populations could be engineered. …

And as you mentioned, Cas9, CRISPR technologies could be used also as antiviral agents. Currently, the problem with antibiotics is pretty clear — we are probably losing our battle against bacteria using antibiotics. Novel antibiotics are always required and it's really difficult to find them, and challenging and costly. So therefore, alternative technologies like viral therapies or CRISPR antibacterial systems are developed.

NL: Obviously CRISPR has so much potential, especially in the realm of treating genetic disease — I think people also have a lot of questions about the ethics of applying CRISPR in different contexts. Could you speak on that?

VS: I think it's a very important question, and of course, CRISPR is a very important technology, and you can use CRISPR to do many things. But of course, you should keep in mind what you are doing and you need to be in touch and in conversation with society — Are these things acceptable? Or, what are the societal views on these technologies that scientists are developing in the lab? And I think it's very important to communicate with people and explain, actually, what are these technologies, what they can achieve, and then what can be downsides, also, of these technologies.

We already heard about these stories that CRISPR was used several years ago in China for engineering human embryos — so that's a line that scientists actually agree not to cross, because this could be a really dangerous thing.

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In a historic first, the Food and Drug Administration (FDA) has approved America's first gene therapies for sickle-cell disease (SCD), one of which uses the gene-editing tool CRISPR.

"Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need [for better, long-lasting treatments], and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today," Dr. Nicole Verdun, director of the Office of Therapeutic Products within the FDA's Center for Biologics Evaluation and Research, said in a statement released Friday (Dec. 8).

"Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited," she said.

The U.K. became the first country to approve the CRISPR-based therapy, called Casgevy, in mid-November. Experts anticipated that the FDA would soon echo the decision made by U.K. regulators, as advisors to the FDA had deemed the treatment safe for clinical use back in October.

Related: The world's 1st CRISPR therapy has just been approved. Here's everything you need to know

SCD is caused by genetic mutations that change the shape of the protein hemoglobin, which carries oxygen in red blood cells. Red blood cells then become sickle-shaped, rather than round, which causes them to die off quickly and also stick together, blocking blood vessels.

The CRISPR-based therapy Casgevy stops the sickling of cells by switching off a gene called BCL11A.

The CRISPR system can precisely guide a pair of molecular scissors to the gene doctors want to disable and then cut that gene out of a person's DNA. Disabling the BCL11A gene makes it so a patient's cells can make a version of hemoglobin normally made only in the womb. Only the adult version of hemoglobin is affected in SCD, so enabling the body to make this fetal hemoglobin reverses the patient's anemia.

"In patients with sickle cell disease, increased levels of HbF [fetal hemoglobin] prevent the sickling of red blood cells," the FDA stated.

To apply the treatment, doctors first draw a patient's blood stem cells — unspecialized cells that can transform into different cells in the blood. They then edit the cells to disable the BCL11A gene and return them to the patient's body. Before the infusion, the patient must take a chemotherapy drug to eliminate the unedited stem cells still in their bone marrow.

The second gene therapy approved by the FDA, called Lyfgenia, does not use CRISPR. Instead, the treatment uses a harmless virus, called a lentiviral vector, to deliver new DNA into patients' blood stem cells.

The virus inserts a functional hemoglobin gene to replace patients' mutant one. The functional gene makes a version of hemoglobin that's very similar to that seen in adults without SCD, but it has additional properties that help limit the sickling of blood cells. Blood cells change shape in SCD when the abnormal hemoglobin clumps together, or "polymerizes," to form stiff chains within the cells. The tweaked hemoglobin used in Lyfgenia is more resistant to that polymerization than normal hemoglobin, due to its structure.

As with Casgevy, patients take a chemotherapy drug before receiving their new cells treated with Lyfgenia.

Casgevy is approved for SCD patients ages 12 and older with "recurrent vaso-occlusive crises," meaning events where sickled red blood cells block the oxygen flow into organs, causing tissue damage and severe pain. Lyfgenia is approved for patients ages 12 and older with a history of vaso-occlusive events, the broader category of complications that crises fall under.

"Today's actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA's commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health," Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.

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In an ongoing clinical trial, researchers are testing whether just one dose of a new gene therapy that might effectively cure human immunodeficiency virus (HIV) infections is safe in humans. 

The therapy, named EBT-101, involves using CRISPR-Cas9 gene editing to treat HIV. This potential treatment strategy has been studied in animal models since the development of CRISPR-Cas9 in 2012. However, this is the first time such a gene-editing treatment for HIV has been tried in humans. The latest data from the trial suggest that EBT-101 is safe at the doses tested, but we don't yet know if it cures HIV.

According to the United Nations Programme on HIV/AIDS (UNAIDS), approximately 39 million people globally were living with HIV in 2022, and there were about 630,000 AIDS-related deaths that year, making HIV a continued public health burden. There is no vaccine or easily accessible cure for HIV, although a handful of people have been effectively cured through intensive stem-cell transplants. 

The EBT-101 trial "is an important step forward in the development of this technology to treat human disease and infection, including HIV," Thomas Hope, a professor of cell and developmental biology at Northwestern University who was not involved in the work, told Live Science in an email. 

But how likely is it, really, that we could use CRISPR to cure HIV someday?

Related: We could end the AIDS epidemic in less than a decade. Here's how.

How CRISPR could (theoretically) cure HIV

HIV infects immune cells that are normally used to fight infection in the virus's host. The virus uses an immune cell's machinery to insert its own DNA into the host's genome, allowing the virus to replicate. If an HIV infection is not treated, it can lead to acquired immunodeficiency syndrome (AIDS), which results in a severely weakened immune system and leaves the infected person highly vulnerable to other infections, cancers and early death.

Combination antiretroviral therapies (cARTs) are the mainstay in HIV treatment and limit the virus' replication, thus extending people's lives to near-normal lengths and cutting their chance of spreading HIV. However, these therapies must be taken for a lifetime and fall short of being a cure.

"The existing challenge in HIV treatment lies in the virus creating resilient genetic reservoirs within human cells," Elena Herrera-Carrillo, an associate professor of infectious disease at Amsterdam University Medical Centers, told Live Science. Herrera-Carrillo's lab focuses on using CRISPR to edit cells that harbor HIV reservoirs, despite ongoing cART therapy. This phenomenon is known as "latent HIV" and occurs when the virus infects a type of immune cell called CD4+ memory T cells, which can persist for decades.

cART therapies can suppress viral replication, but if the treatment is interrupted, "the dormant proviruses can reactivate, making a cure elusive," Herrera-Carrillo told Live Science.

CRISPR works by targeting and cleaving specific sequences of DNA from the genome; a "guide" leads CRISPR's famous "molecular scissors" to the targeted gene. This either deactivates the gene or allows it to be removed and swapped for different DNA. Research groups believe this strategy could be effective in removing latent HIV infections, because it can target the viral DNA embedded in the genome, rather than only stopping replication.

Using CRISPR for HIV gene therapy has shown promise in several test-tube studies, a 2020 review in The Journal of Clinical Investigation notes. Various groups have been working to bring the therapies from test tubes to human patients — and that brings us to EBT-101.

Related: The world's 1st CRISPR therapy has just been approved. Here's everything you need to know

All about EBT-101

According to a recent presentation at the annual meeting of the European Society for Gene and Cell Therapy in Brussels, EBT-101 uses multiple guides to target multiple sites in the genome and snip out large sections of latently integrated HIV DNA. This stops HIV from replicating.

Kamel Kahlili, a professor of neurovirology and gene editing at Temple University and co-founder of Excision BioTherapeutics, has been working with the company to develop EBT-101 for a decade. In 2020 and 2023, Khalili and his team published reports that showed that EBT-100, a precursor to EBT-101, safely targeted and removed HIV DNA in infected primates.

Now, they're testing their EBT-101 targeting strategy in humans in an early-stage clinical trial that primarily focuses on the safety of the treatment. Initial results from three treated patients showed no toxic effects or serious adverse events. All of the patients' HIV is currently suppressed with cART.

"The initial safety results are promising because no adverse outcomes have been observed to date," said Hope, whose lab studies the mechanisms behind HIV infections. "But more time is needed to be sure because of the way genetic off-target mutations can take years to manifest into complications," he added.

Off-target effects of CRISPR refer to when the CRISPR molecule alters DNA at sites other than those targeted. These unintended snips have long been a worry for researchers designing CRISPR treatments, so they'll be something to watch for with EBT-101, especially since the treatment targets multiple sites in the genome.

Additionally, experts told Live Science that even though the ongoing trial hints that the therapy has a positive safety profile, we still don't know whether one dose can effectively target latent HIV cells and whether it can control HIV in humans.

"It is crucial to approach this with caution," Herrera-Carrillo said. "While optimism about being on the right track is justified, it's important to recognize the substantial work that still needs to be done."

The clinical trial will next test additional doses of EBT-101 for safety and then determine whether the virus stays suppressed when patients are taken off cART. cART therapies pump the brakes on HIV replication, so the only way to determine whether the latent cell reservoirs have been disabled is to temporarily lift those brakes.

Interruptions to HIV treatment are necessary to determine whether a patient is in remission — as has occurred in the few people cured of HIV — but in general, purposeful treatment interruptions have been debated due to their inherent risks.

Following these tests, EBT-101 trial participants will be enrolled in a long-term follow-up study for 15 years following their initial dose to check for long-term adverse effects. So the data is on its way, but will take years to arrive.

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Scientists have unearthed 188 previously unknown types of CRISPR systems buried in the genomes of simple microorganisms.

Best known as a powerful gene-editing tool, CRISPR actually comes from an inbuilt defense system found in bacteria and simple microbes called archaea. CRISPR systems include pairs of "molecular scissors" called Cas enzymes, which allow microbes to cut up the DNA of viruses that attack them. CRISPR technology takes advantage of these scissors to cut genes out of DNA and paste new genes in.

The new study, published Nov. 23 in the journal Science, expands the known diversity of CRISPR systems in microorganisms and could open new avenues for precise gene editing with fewer "off-target" effects, the researchers said.

The team discovered the new CRISPR systems by scanning millions of genomes of microorganisms using an algorithm called fast locality-sensitive hashing-based clustering, or FLSHclust (pronounced "flash clust"). The algorithm works by very efficiently grouping similar objects together and is designed to hunt down genes related to CRISPR. The researchers used FLSHclust on three massive public datasets that contain billions of DNA and protein sequences from bacteria.

Related: The world's 1st CRISPR therapy has just been approved. Here's everything you need to know

"This new algorithm allows us to parse through data in a time frame that's short enough that we can actually recover results and make biological hypotheses," co-first study author Soumya Kannan, formerly a doctoral student and now a postdoctoral scholar in the Broad Institute/MIT Department of Biology, told MIT News.

FLSHclust accomplishes in weeks what previous algorithms would achieve in months, MIT News reported.

After finding the new types of CRISPR, the researchers experimented with four of the systems to start understanding how they work.

The CRISPR systems that scientists previously knew about came in six flavors — types I through VI — which differ in size, the enzymes they use and how they latch onto genetic material, Nature reported. (The first CRISPR system ever identified is a type II system and uses a single enzyme called Cas9 to cut through DNA, while other types use different or multiple Cas enzymes.)

Out of the four CRISPR clusters the team experimented with, two were variants of type I CRISPR systems and one was type IV. Both type I systems made small, precise cuts in DNA in human cells, the team demonstrated. Scientists think that type I systems could potentially be less prone to making accidental, off-target cuts than CRISPR-Cas9, so they could be useful for gene editing, according to MIT News.

The final cluster was a whole new type of CRISPR, which the team dubbed type VII. Like some other CRISPR types, it targets RNA, a molecular cousin of DNA that's key for building proteins. So in theory, type VII systems could be useful for RNA editing.

That said, it's too soon to say whether type VII CRISPR systems or any of the other genes identified by FLSHclust will be helpful for genetic engineering, co-first study author Han Altae-Tran, formerly a graduate student at Broad Institute/MIT Department of Biology and now a postdoctoral scholar at the University of Washington, told Nature.

The next step will be to sift through more of the newfound systems to see how their component parts work and whether they could feasibly be used in gene editing, Nature reported.

Read more in MIT News and Nature.

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The world's first treatment that uses CRISPR gene-editing technology has been approved.

Exa-cel, also known by its brand name Casgevy, received its first regulatory approval on Nov. 16, 2023 from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to treat two debilitating blood disorders: sickle-cell disease and transfusion-dependent beta-thalassemia. The U.S. Food and Drug Administration (FDA) later approved the therapy as a treatment for both disorders. 

The regulators' historic decision to approve Casgevy may signal the start of a new era of gene therapy. However, questions remain surrounding the treatment's affordability and its long-term safety.

Here's what we know so far about Casgevy. 

Related: A teen's cancer is in remission after she received new cells edited with CRISPR

In addition, a tweaked version of CRISPR called "base editing" that can target the individual building blocks of DNA is being tested as a way to treat disease. For example, Verve Therapeutics is testing such an experimental treatment for heart disease. Another promising new type of therapy, called "prime editing," involves CRISPR but also "incorporates additional enzymes and genetic instructions to insert, delete or rewrite short segments of DNA," STAT News reported.

This article is for informational purposes only and is not meant to offer medical advice.

Editor's note: This story was last updated on Jan. 18, 2024 to reflect the FDA's approval of Casgevy for beta-thalassemia. The article was first published on Nov. 22, 2023 and previously updated on Dec. 8 2023. 

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A one-time, CRISPR-based gene therapy lowered people's levels of "bad" cholesterol in a small trial, the treatment's maker announced. While the new therapy shows promise, it still has a long way to go before it can be approved for use in patients.

The gene therapy, called VERVE-101, reduced the levels of low-density lipoprotein (LDL) cholesterol in the blood of people with familial hypercholesterolemia (FH), an inherited condition that boosts their LDL levels and their risk of heart disease, according to a statement from Massachusetts-based biotech company Verve Therapeutics, which makes the treatment.

FH is caused by mutations in a key gene that helps control the rate at which the liver clears LDL from the blood. Usually, these mutations change a single building block in the protein encoded by the gene.

The gene, called PCSK9, essentially works overtime in the context of this disease, and its hyperactivity rapidly breaks down proteins on the surface of liver cells that would normally remove LDL from the bloodstream. As a result, cholesterol levels skyrocket, so people with the disease need cholesterol-lowering medications to keep their levels in check.

Related: CRISPR used to 'reprogram' cancer cells into healthy muscle in the lab

Verve hopes to change this with the new treatment, and on Sunday (Nov. 12), the company released preliminary data from its ongoing clinical trial.

VERVE-101 uses a modified version of CRISPR gene editing, which allows researchers to alter DNA sequences and thus modify gene function. CRISPR gene-editing techniques typically snip through both strands in DNA's twisted double helix and then rely on a cell's repair mechanisms to fix that cut. However, this raises the risk that unwanted mutations will enter the DNA.

By contrast, VERVE-101 uses a different CRISPR-guided approach, called "base editing," which precisely changes just one "letter" in DNA's code, thus cutting the risk of unintentional mutations.

"It is a breakthrough to have shown in humans that in vivo base editing works efficiently in the liver," Gerald Schwank, a gene-editing researcher at the University of Zurich who wasn't involved in the clinical trial, told Science. Plus, it's the first time a base-editing therapy has been administered via infusion, Science reported.

The 10 trial participants treated so far range from 29 to 69 years old, NPR reported. The patients received different doses of VERVE-101. Six people given lower doses showed no response to treatment, while three people in the higher-dose groups saw a drop in LDL. (One person in a higher-dose group is still being monitored and was not included in this initial analysis.)

The high-dose patients' LDL fell by about 39% to 55%, and in the person who saw the largest effect, their LDL stayed low for six months. If VERVE-101 works as intended, the change will be permanent. 

Two participants in the trial — one in a low-dose group and one in a high-dose group — experienced severe heart problems. Both had severe underlying cardiovascular disease prior to the trial. The person in the low-dose group died from cardiac arrest weeks after treatment, but the event was deemed unrelated to the gene therapy. Another person had a heart attack the day after treatment, and the event was "considered potentially related to treatment due to the proximity to dosing," Verve reported.

Beyond these cardiovascular events, there's some additional safety concerns around whether base editing could have "off-target" effects in genes that it's not intended to edit, Nature reported.

"This is a gene editing study — you are changing the genome forever," Dr. Karol Watson, a UCLA cardiologist who was involved in the trial, said at a news conference, according to Nature. "Safety is going to be of the utmost importance, especially because there are currently safe and efficacious strategies available for lipid lowering."

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The bacteria may have entered her flesh along with shrapnel from the bomb detonated in Brussels Airport in 2016. Or perhaps the microbes hitched a ride on the surgical instruments used to treat her wounds. Either way, the "superbug" refused to be vanquished, despite years of antibiotic treatment.

The woman had survived a terrorist attack but was held hostage by drug-resistant Klebsiella pneumoniae, a bacterial strain often picked up by surgery patients in hospitals. Only by combining antibiotics with a new, experimental treatment did doctors finally rid her of the superbug.

Devastating drug-resistant bacterial infections like this one are all too common, and they represent an ever-growing threat to global health. In 2019, antibiotic-resistant bacteria directly killed roughly 1.27 million people worldwide and contributed to an additional 3.68 million deaths. In the U.S. alone, drug-resistant bacteria and fungi together cause an estimated 2.8 million infections and 35,000 deaths each year.

And the problem is getting worse: Seven of the 18 concerning bacteria tracked by the Centers for Disease Control and Prevention (CDC) are becoming more resistant to common antibiotics considered essential for maintaining public health. Meanwhile, drug companies have been slow to make new antibiotics capable of beating the microbes. Fewer than 30 antibiotics currently in the development pipeline target "priority" bacteria, as defined by the World Health Organization (WHO), and most of those drugs are still vulnerable to resistance, just like their predecessors.

So some scientists are looking beyond traditional antibiotics for new weapons that won't fuel the rise of superbugs. Their emerging arsenal features viruses that kill bacteria; CRISPR; and microbe-slaying molecules. They hope that these experimental treatments, some of which have been tested in patients, will kill superbugs without promoting resistance.

"The vision, for me, is that we move beyond antibiotics and really just see a much broader palate of options," Chase Beisel, leader of the RNA synthetic biology research group at the Helmholtz Institute for RNA-based Infection Research in Germany, told Live Science.

But until these new therapeutics are ready for prime time, the world needs to curtail its overuse and misuse of antibiotics, which experts say is speeding up the rate at which these lifesaving drugs become obsolete.

Related: Superbugs are on the rise. How can we prevent antibiotics from becoming obsolete?

How antibiotic resistance emerges and spreads

Antibiotics either directly kill bacteria or slow their growth, leaving the immune system to finish the job. The drugs work in several ways — by preventing bacteria from building sturdy walls or making copies of their DNA, for instance. Growth-slowing antibiotics usually disrupt ribosomes, the factories in which bacterial cells make proteins.

Many antibiotics shoot for the exact same molecular targets, and so-called broad-spectrum antibiotics' mechanisms are so universal that they work on both major classes of bacteria: gram-positive and gram-negative, which are distinguished by the makeup and thickness of their cell walls. Broad-spectrum antibiotics, in particular, pressure both harmful and helpful bacteria in the body to evolve defensive strategies that eject or disable the drugs, or else alter their targets.

Bacteria can pick up such defenses through random DNA mutations, or by swapping "resistance genes" with other bacteria via a process called horizontal gene transfer. By making these gene transfers, bacteria can quickly spread such mutations to additional bacterial populations in the body and in the environment.

The misuse of antibiotics in health care, as well as in agriculture, has given bacteria endless opportunities to develop resistance, raising the chance that once-treatable infections will become life-threatening.

Related: New 'concerning' strain of drug-resistant gonorrhea found in U.S. for 1st time

Harnessing viruses to fight bacteria

One of the proposed alternatives to antibiotics was first conceived more than a century ago, before the 1928 discovery of penicillin. Called phage therapy, it uses bacteria-infecting viruses called bacteriophages, or simply "phages," which typically kill the germs by invading their cells and splitting them open from the inside.

Phages can also pressure bacteria into giving up key tools in their drug resistance tool kits. For example, a phage called U136B can have this effect on E. coli. To infiltrate E. coli, the phage uses an efflux pump, a protein E. coli normally uses to pump antibiotics out of the cell. If the E. coli tries to change this pump to escape the phage, it reduces the bacterium's ability to pump out antibiotics.

And unlike with antibiotics, bacteria are unlikely to gain widespread resistance to phage therapy, said Paul Turner, director of the Center for Phage Biology and Therapy at Yale University.

Turner and other experts have concluded that, "if phage therapy were used at a global scale, that it would not lead to the same problem of widespread resistance to it, the way that antibiotic use has led to that problem," he told Live Science.

Here's why: Antibiotic resistance has been dramatically accelerated by the misuse and overuse of antibiotics, especially broad-spectrum antibiotics that work on a variety of bacteria. Phages, by contrast, can have much narrower targets than even narrow-spectrum antibiotics — for instance, targeting a protein found in only one or a few strains within one bacterial species.

Related: New drugs could stymie superbugs by freezing evolution

The target bacterium can still evolve resistance to an individual phage — but by picking the right combination of phages, scientists can make it so that the bacterium's evolution comes at a cost, Turner said. This cost might be a decrease in virulence or an increased vulnerability to antibiotics.

To date, phage therapy has mostly been tested through a regulatory framework known as "compassionate use" in patients like the Brussels Airport bombing victim, whose infections had no other treatment options. Phage therapy has shown success in these settings, and in a recent observational study of 100 patients who received phages alongside antibiotics.

So far in clinical trials, though, phage therapy generally hasn't worked better than standard antibiotics or a placebo. Topline results from two recent trials hint at the treatment's effectiveness in specific lung and foot infections, but the full results have yet to be released.

Success in future trials will be key to getting phages into the clinic, Turner said. Those trials will have to show the therapy works for multiple types of infections, determine dosage and confirm phage therapies don't hurt helpful bacteria in the body, he added.

Turning bacteria's defenses against them

Although made famous as a powerful gene-editing tool, CRISPR technology was actually adapted from an immune system found in many bacteria: CRISPR-Cas.

The key components of this immune system include molecular scissors, known as Cas proteins, and a memory bank of DNA snippets that a bacterium has collected from phages that once infected it. By tapping its memory bank, CRISPR-Cas can guide its lethal scissors to a precise point in an invading phage's DNA and snip it like a piece of ribbon.

On occasion, though, rather than attacking phages, CRISPR-Cas can accidentally go after the bacterial cell's own DNA, triggering a lethal autoimmune reaction. This phenomenon inspired Beisel and his colleagues to explore using CRISPR-Cas to shred bacterial cells' DNA.

"The real draw of it is that it is a sequence-specific tool," meaning it targets only the DNA you tell it to, and not sequences present in other bacteria, Beisel told Live Science. So, once administered to a patient, "the CRISPR machinery gets into a set of cells, but only those that have the sequence or sequences you picked will be attacked and killed."

How do you get CRISPR-Cas into the right bacteria? Various research groups are testing different delivery methods, but at present, the best strategy seems to be loading CRISPR machinery into a phage that infects the target bacterium, Beisel said.

Related: Scientists invent 'shape-shifting' antibiotic to fight deadly superbugs

Beisel is a co-founder and scientific adviser of Locus Biosciences, a biotech company that's currently testing a CRISPR-enhanced phage therapy in a midstage, roughly 800-person trial. This approach couples the bacteria-killing prowess of phages with the ability of CRISPR-Cas to destroy essential bacterial genes. As with CRISPR-less phage therapies, clinical trials are needed to determine the treatment's safety profile and appropriate dosing.

"I can see these [treatments] coming about in the five- to 10-year time frame," Beisel said.

Designer molecules to kill bacteria

Beyond phages and CRISPR, scientists are developing antibiotic alternatives that harness bacteria-slaying peptides — short chains of protein building blocks— and enzymes, specialized proteins that jump-start chemical reactions. These molecules differ from antibiotics because they can kill a very narrow range of bacteria by targeting bacterial proteins that cannot easily gain resistance to their attacks.

Lab-made molecules called peptide nucleic acids (PNAs) are some of the most promising candidates. These engineered molecules can be designed to block bacterial cells from building essential proteins that are crucial to their survival. PNAs do this by latching onto specific mRNA, genetic molecules that carry the instructions for building proteins from the cell's control center to its protein construction sites. PNAs cannot enter bacterial cells on their own, though, so they're typically attached to other peptides that easily pass through the bacterial cell wall.

By targeting proteins that cells cannot change without harming themselves, PNAs can avoid triggering drug resistance, Beisel explained. The engineered molecules could also be made to target proteins that directly contribute to antibiotic resistance, for example, the efflux pumps used to push antibiotics out of cells or the enzymes capable of disabling the drugs. By emptying a germ's drug resistance tool kit, PNAs can then make it vulnerable to standard treatments.

Antibacterial PNAs are still being tested in lab dishes and animals and have not yet moved into human trials. And, scientists need to make sure PNA-based treatments don't inadvertently mess with human cells or helpful bacteria.

Related: 'Death screams' of swarming bacteria help their comrades survive antibiotic attacks

In addition to peptides like PNAs, enzymes called lysins are another promising treatment option. Lysins are used in nature by phages to split bacteria open from the inside. They act like tiny swords that slice through the outer wall of a bacterial cell, spilling its guts. The molecular sabers are unlikely to promote resistance because bacteria cannot easily change the essential cell-wall components that lysins target.

Lysins slaughter bacteria quickly upon contact, and they can be very specific, killing some types of bacteria while sparing others. Furthermore, lysins can be tweaked in the lab to change which bacteria they target, boost their potency and improve their durability in the body.

Some lysins have entered mid- and late-stage human trials with hundreds of participants, in which they've been tested as supplementary treatments to antibiotics but garnered mixed results.

Antibiotic stewardship can save lives, in the meantime

Until these next-gen bacteria slayers make it to market, immediate measures must be taken to stall the rise of superbugs, by preventing the misuse of antibiotics that pressures bacteria to evolve resistance in the first place.

For example, doctors can be more diligent about confirming that bacteria, not viruses, are behind a patient's infection before prescribing antibiotics, said Dr. Shruti Gohil, a lead investigator of four INSPIRE-ASP Trials, federally funded research aimed at improving hospitals' antibiotic use. Other safeguards can include auditing doctors' prescriptions to see if narrower-spectrum drugs could be used instead of broad ones, or requiring special clearance for the broadest-spectrum drugs. These steps are essential not only in hospitals but everywhere antibiotics are prescribed, from primary care to dentistry, Gohil said.

Each interaction between a doctor and their patient matters.

Gohil stressed that "by reducing individual risk, you anticipate that you will drop the overall population-level risk," and eventually slash the prevalence of multidrug-resistant bugs.

Scientists have transformed cancer cells into healthy muscle tissue in the lab using CRISPR gene-editing technology — and they hope new cancer treatments can be built on the back of this experiment.

In a study published Aug. 28 in the journal PNAS, researchers found that disabling a particular protein complex in cells of rhabdomyosarcoma (RMS) — a rare cancer in skeletal muscle tissue that mainly affects children under age 10 — in the laboratory causes the tumor cells to turn into healthy muscle cells.

Although the research is still in its early days, this process of "resetting" cancer cells into healthy cells, broadly known as differentiation therapy, has already been tested in other types of cancer, such as bone and blood cancer. Four drugs have been approved by the U.S. Food and Drug Administration (FDA) to treat the latter disease and generally work by inhibiting a specific protein in the cancer cells.

The protein complex pinpointed in the new research could serve as a target for such a therapy, the study authors wrote, and with further development, it could be a promising new treatment option for patients with RMS, which is normally treated with surgery, radiation and chemotherapy.

"This technology can allow you to take any cancer and go hunting for how to cause it to differentiate," or cause it to stop multiplying uncontrollably and turn into normal, noncancerous cells, Christopher Vakoc, lead author and professor at Cold Spring Harbor Laboratory, said in a statement. "This might be a key step toward making differentiation therapy more accessible."

Related: Meet 'Fanzor,' the 1st CRISPR-like system found in complex life

Differentiation is a process in which stem cells divide and form the various types of cells in the body, such as muscle or fat cells, which each have a unique pattern of gene expression that enables them to carry out particular functions. In RMS, however, patients have genetic mutations that cause their cells to make a specific protein, called PAX3-FOXO1, which stops differentiation from happening in skeletal muscle cells. So instead of turning into muscle, the cells form a mass of cancerous tissue.

In the new study, the researchers used CRISPR to disable, or "knock out," different genes to see which ones make proteins that work together with PAX3-FOXO1 to stop RMS cells from differentiating. Their analysis revealed that, if RMS cells lose the ability to make nuclear factor Y (NF-Y) — a protein that regulates gene expression — the cells instead differentiate into muscle cells. Knocking out PAX3-FOXO1 directly has the same effect.

"The tumor loses all cancer attributes," Vakoc said in the statement. "They're switching from a cell that just wants to make more of itself to cells devoted to contraction."

Although deactivating PAX3-FOXO1 and NF-Y has similar effects, the researchers discovered that the proteins don't physically interact with each other. Instead, in RMS cells, NF-Y switches on the genes needed to make PAX3-FOXO1 by binding to a specific sequence of DNA. So by blocking NF-Y, the researchers also blocked production of PAX3-FOXO1.

The findings are still a long way from being translated into a treatment for RMS. However, drugs that inhibit NF-Y are already being developed, including those that stop the protein complex from forming or binding to DNA.

One hurdle that will need to be overcome is that NF-Y also regulates important processes in healthy cells, such as metabolism and the cell cycle, the series of steps that cells go through as they grow and divide. However, Vakoc and team hypothesize that because RMS cells are "highly sensitive" to changes in PAX3-FOXO1 expression, there could be a "window of opportunity" in which a drug inhibits NF-Y long enough for RMS cells to differentiate but not so long that healthy tissues get damaged. More research will be needed to confirm that this is a viable treatment strategy, they wrote.

Human skin, hair, and eyes come in a huge variety of colors, but until now, scientists have only known a fraction of the genetic diversity driving this variation. Now, new research finds many dozens of genes that may produce this broad diversity. 

In a genome-wide screening, researchers pinpointed 169 genes that are likely involved in human pigmentation, including 135 previously not known to play a role. Because of the wide distribution of pigments within the human body, some of these genes might be involved in disorders such as the skin cancer melanoma and even Parkinson's disease, which affects pigmented cells in a region of the brain important for movement, the study authors reported. 

"Pigmentation by itself is interesting both in the context of human variation and evolution, but also in the context of disease," study leader Joanna Wysocka, a developmental biologist at Stanford University and the Howard Hughes Medical Institute, told Live Science. 

Related: 10 common skin conditions

The diversity of coloration

Humans get their skin, eye and hair colors from a pigment called melanin, which comes in a brown-and-black form, called eumelanin, and a yellow-and-red form, called pheomelanin. How much of each melanin type is expressed, and in what balance, determines whether someone will have, for example, jet-black hair or fiery-red locks, and the same goes for skin tone and eye color. (The more melanin in the eye, the darker it is. People with blue eyes lack melanin in the iris, while people with green eyes have it in only one layer.)

Cells called melanocytes make melanin, but the difference in a dark-featured person and a light-featured person isn't in the number of melanocytes but in how much melanin those melanocytes produce, Wysocka said.

Previous studies had revealed some genes behind melanocyte maturation and melanin production, but only enough to explain between 23% and 35% of the variation in human skin color, Wysocka and her team wrote Thursday (Aug. 10) in the journal Science. To find out which other genes might contribute to human pigmentation, the researchers conducted a whole-genome study.

First, they had to differentiate high- and low-melanin melanocytes. To do so, they sorted cells in lab dishes, using the light-scattering properties of melanin, which describe how light behaves when it strikes the pigment. This new method, which involves shining fluorescent light on cells flowing through a channel, efficiently sorted both human melanocyte cells and melanoma cells, a cancerous version of melanocytes, by their melanin levels.

Next, the researchers used CRISPR-Cas9 gene-editing technology to systematically go into cells and mutate every gene, one at a time. If the broken gene was associated with melanin production or melanocyte maturation, the team reasoned, pigment levels in the melanocyte would fall and then be detected by the sorting tool.

This method returned the list of 169 genes, whose activity levels the researchers then checked in real human tissue — in this case, samples of infant foreskin donated after circumcisions. They found that nearly 70% of the genes were more active in babies with darker skin tones than in those with lighter skin tones.

Protective pigments

Not every gene necessarily drives melanin production, Wysocka said. While some determine how melanocytes mature and how much pigment they make, others are likely involved in a more peripheral way.

The genes largely fell into two categories: One group helped regulate genes, while the other influenced endosome trafficking. Endosomes are tiny transport packets within cells that shuttle materials around. The researchers closely analyzed one gene from each group and discovered that one was involved in the maturation of melanosomes, the tiny cellular organs that make and store the pigment within melanocytes. The other regulates the pH of the melanosomes, ensuring that the enzymes that piece together the pigments can function properly, Wysocka said.

Melanin isn't just ornamental; it protects the skin and eyes from sun damage. It also shows up in the brain in a structure called the substantia nigra, whose name means "black substance." The structure's high melanin content protects cells from reactive molecules, but in Parkinson's disease, substantia nigra cells die off, and thus melanin declines.

"It's an interesting question whether some of these pathways we have identified in melanocytes will also be important for neuroprotection in the brain," Wysocka said.

Researchers have identified a new gene-editing system similar to CRISPR in complex organisms, demonstrating for the first time that DNA-modifying proteins exist across all kingdoms of life.

Feng Zhang, a biochemist at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, led the team and previously co-discovered the gene-editing potential of the CRISPR-Cas9 system, which functions as a kind of "molecular scissors" that remove sections of DNA, thus disabling genes or allowing new ones to be swapped in. 

Prior to this discovery, such systems had only been found in simple organisms such as bacteria and archaea, which wield them as a sort of rudimentary immune system for chopping up the DNA of invaders. Researchers detected the newfound system, called Fanzor, in fungi, algae, amoebas and a species of clam, vastly broadening the groups known to use these genetic tools. 

"People have been saying with such certainty for so long that eukaryotes [organisms whose complex cells contain nuclei] couldn't have a similar system," said Ethan Bier, a geneticist at the University of California San Diego, who uses gene editing in his work but was not involved in the study. "But it's typical cleverness from the Zhang lab, proving them wrong," Bier told Live Science.

Related: CRISPR-edited fat shrank tumors in mice. Someday, it could work in people, scientists say. 

After publishing their first paper on CRISPR in 2013, Zhang and colleagues began studying how these systems evolve. During this work, the group identified a class of proteins in bacteria called OMEGAs, thought to be early ancestors of Cas9 proteins, the "scissors" of the CRISPR system. They began to suspect that Fanzor proteins, a type of OMEGA, could also be modifying DNA.

The group screened online databases for the proteins and were surprised to find several in samples isolated from fungi, protists, arthropods, plants and giant viruses. The thinking, Zhang said, is that the genes needed to make Fanzor proteins got shuffled from bacteria into complex organisms through a process known as horizontal gene transfer. Genes that encode for Fanzor proteins were integrated into the genomes of eukaryotic organisms within transposable elements, meaning bits of DNA that can move about the genome and replicate themselves.

In experiments, the researchers found that Fanzor proteins share some similarities with CRISPR. Fanzor proteins also interact with guide RNA, a molecule that guides the proteins to the DNA destined to be cut. This molecule, called an omegaRNA, complements the strand of target DNA. When they match up, the two pieces zip together and Fanzor can then cut the DNA. 

The team tested the Fanzor system in human cells but at first found that it was relatively inefficient at adding or removing bits of DNA, completing the process successfully about 12% of the time. After some creative engineering to enhance and stabilize the system, however, the researchers bumped the efficiency up to just over 18%.

This inefficiency isn't surprising, according to Bier, nor a sign that Fanzor isn't as good as CRISPR. Scientists have engineered CRISPR so that it can make the desired substitutions almost every time, but "it certainly didn’t start out that way," he said. But Bier added it will be hard for Fanzor to match Cas9, which he called "the most adaptable and forgiving protein for the types of things you want to do to it."

Fanzor will instead likely complement CRISPR, which has been used both in research and in experimental medical treatments for conditions like blindness and cancer. 

Compared with CRISPR, "the Fanzor systems are more compact and therefore have the potential to be more easily delivered to cells and tissues," Zhang said, and they're less prone to accidentally degrading nearby RNA or DNA — so-called off-target or collateral effects. This makes Fanzor attractive for use in gene therapy.

Zhang told Live Science he's now excited to go looking for similar systems in new places.

"This work really underscores the power of studying biodiversity," Zhang said. "There are likely more RNA-guided systems out there in nature that hold future promise for gene editing."

For the first time ever, scientists have created genetically modified snakes. The CRISPR-edited reptiles are providing new insight into how corn snakes (Pantherophis guttatus) develop their precisely patterned scales.

Much like feathers on birds or hairs on mammals, snake scales are the result of placodes — small, thickened structures on the skin that develop at the embryonic level, according to a new study published Wednesday (June 14) in the journal Sciences Advances.  

But unlike most other species including mice, where the placodes are random, a snake's placodes develop in a highly organized fashion, laying out the positioning of every single scale. Rather, the spatial organization of these placodes follows a  pattern in nature first explained by mathematician Alan Turing, the researchers added.

Scientists from Geneva wanted to know exactly how and why these "near-perfect hexagonal pattern[s]" developed on the dorsal scales located on the snakes' backs and flanks, but not on the ventral scales that form as a single row on the animals' underbellies.

The researchers found that an embryo's ventral scales develop first and align with the position of somites — blocks of cells that determine the location of the vertebrae, ribs, muscles and dermis of the skin. Once the ventral scales are established, two separate "waves" of placodes develop, traveling toward each other. 

The waves meet laterally, creating the tidy hexagonal patterns that are the hallmark of a snake's skin, according to a statement.

Related: Scientists changed scales on chicken feet to feathers by tweaking a single gene

"To confirm our work, we used computer simulations and received similar results," lead author Athanasia Tzika, a postdoctoral fellow in the Department of Genetics and Evolution at the University of Geneva, told Live Science. "This is surprising because the pathway is essential for proper development of skin appendages in birds, reptiles and mammals."

Tzika pointed to lizards with a mutated EDA gene, which were previously studied in her university's lab, as an example of a reptile that never developed scales.

This led researchers to create the world's first genetically modified snakes. Using CRISPR-Cas9, which edits genes by severing the DNA and letting the natural DNA repair itself, Tzika and her team successfully created "mutant" snakes that lacked dorsal-lateral (hexagonal) scales, but still had ventral scales. 

She said that this proved that the scales aren't "self-organizing" and occur "without a functional canonical EDA pathway."

In total, the scientists created four corn snakes, all of which are currently two years of age and "are doing well," Tzika said.

"The animals we produced are exactly the same as the naturally occurring snakes; we were able to reproduce the same phenotype," Tzika said. 

She said they plan to conduct another round of CRISPR edits on the genetically modified snakes in two years, once they reach sexual maturity, "to see if the mutation will transmit to the next generation."

The most lethal mushroom in the world is the death cap mushroom, and now scientists have discovered a possible antidote from an unlikely source: a fluorescent dye.

Called indocyanine green (ICG), the dye is commonly used in medical imaging to help assess the functionality of the heart and liver, but an international team of scientists have found that it also stops alpha-amanitin (AMA), the death cap mushroom's primary toxin, dead in its tracks, according to a study published May 16 in the journal Nature Communications. So far, this antidote has worked in human cells, mini models of the liver and in mice, but it hasn't been tested in humans. 

Greenish-yellow, umbrella-shaped death cap mushrooms (Amanita phalloides) are responsible for 90% of all poisonous mushroom fatalities in humans, according to the study. While death cap mushrooms are native to Europe, they can be found throughout North America, according to The Atlantic. 

When ingested, the fungus' toxins can cause vomiting, bloody diarrhea or urine, liver and kidney damage, and even death. Treatments vary depending on when the toxins were ingested, but can include stomach pumping and surgical removal of parts of the mushroom, according to WebMD. 

"So far, it remains unclear how exactly death cap mushrooms kill people," study co-author Qiao-Ping Wang, a professor and department head at the School of Pharmaceutical Sciences at Sun Yat-Sen University in Shenzhen, China, told Live Science in an email. "But it was thought to have the most toxic toxin, AMA, responsible for its cytotoxicity," or ability to kill cells.

Wang added that previous research showed that AMA "could block RNA transcription," which is when information from a strand of DNA is copied into a new molecule on its way to getting used to build new proteins. Thus, RNA transcription is "an essential biological process for cell function and survival."

Related: World's deadliest mushroom conquered California with a clone army, study reveals

To see which genes and proteins were key to death caps' toxicity, the scientists used CRISPR, a genome-editing technology, to create a pool of human cells, each with a different mutation. Next, they tested which of the mutant cells could survive being exposed to AMA. Through this process, they found that AMA likely requires an enzyme known as STT3B to exert its toxic effects.

"We found the STT3B protein and its biological pathway is critical for toxin cytotoxicity," Wang said. STT3B is involved in the production of N-glycans, which are key for making sure proteins "fold" into their correct shapes; getting rid of the gene for STT3B in cells dramatically boosted cells' resistance to AMA and also hindered the toxin's ability to enter cells.

"We confirmed these findings in liver cells and liver organoids" — miniature models of the human liver — "since the liver is the target organ of mushroom toxins," Wang said.

To find a potential antidote for AMA, the team consulted the U.S. Food and Drug Administration's list of approximately 3,200 approved compounds, narrowing it down to 34 possible inhibitors of the STT3B protein.

Of the potential candidates, "we only found indocyanine green can effectively prevent cell death from amanitin toxin" in human liver cells and mice cells, Wang said. "The results demonstrated that ICG can prevent liver damage as well as kidney induced by [AMA]. Importantly, ICG could improve survival after [AMA] poisoning." 

Wang said that the team is currently "investigating how STT3B may contribute to resistance against mushroom toxins, but the exact mechanism is still unknown." 

Preliminary data suggest that STT3B is required for AMA to enter cells, Wang said. "ICG has demonstrated significant potential in mitigating the toxic impact of [AMA] in liver cells and mice. However, further research is necessary to ascertain whether [ICG] possesses the same therapeutic benefits in human subjects." 

"If successful, ICG could represent a groundbreaking, life-saving treatment for individuals suffering from mushroom poisoning," he said.

Wang added that the research team plans to eventually conduct human trials to assess ICG's efficacy in people who recently ingested death cap mushrooms. "These tests will yield more definitive results and provide a clearer picture of ICG's potential to revolutionize the treatment of mushroom poisoning," he said.

Gene therapy has been headline news in recent years, in part due to the rapid development of biotechnology that enables doctors to administer such treatments. Broadly, gene therapies are techniques used to treat or prevent disease by tweaking the content or expression of cells' DNA, often by replacing faulty genes with functional ones.

The term "gene therapy" sometimes appears alongside misinformation about mRNA vaccines, which include the Pfizer and Moderna COVID-19 vaccines. These vaccines contain mRNA, a genetic cousin of DNA, that prompts cells to make the coronavirus "spike protein." The vaccines don't alter cells' DNA, and after making the spike, cells break down most of the mRNA. Other COVID-19 shots include the viral vector vaccines made by AstraZeneca and Johnson & Johnson, which deliver DNA into cells to make them build spike proteins. The cells that make spike proteins, using instructions from either mRNA or viral vector vaccines, serve as target practice for the immune system, so they don't stick around long. That's very, very different from gene therapy, which aims to change cells' function for the long-term.

Let's take a dive into what gene therapy actually is, addressing some common questions along the way.

What is gene therapy, and what does it do to your DNA?

DNA is a molecule that stores genetic information, and genes are pieces of genetic information that cells use to make a particular product, such as a protein. DNA is located inside the nucleus of a cell, where it's packaged into chromosomes, and also inside mitochondria, the "power plant" organelles located outside the nucleus. 

Although there are mitochondrial diseases that could someday be cured with gene therapy, currently, the term gene therapy refers to treatments that target nuclear genes — the genes on the 23 pairs of chromosomes inside the nucleus.

Classically, gene therapy has referred to the process of either "knocking out" a dysfunctional gene or adding a copy of a working gene to the nucleus in order to improve cell function. Gene therapy is currently directed at diseases stemming from a problem with just one gene, or at most a few genes, rather than those that involve many genes.

However, the field of gene therapy is now expanding to include strategies that don't all fall into the classic categories of knocking out bad genes or adding good genes. For example, researchers at Sangamo Therapeutics are developing genetic techniques for treating Parkinson, Alzheimer and Huntington diseases that work by ramping up or suppressing the activity of specific genes.

While the treatments may add genes to body cells, knock out genes or act in some way to change the function of genes, each gene therapy is directed to the cells of particular body tissues. Thus, when scientists and doctors talk about what gene therapy does to DNA, they are not talking about all of the DNA in the body, but only some of it.

How does gene therapy work?

Gene therapy can be either ex vivo or in vivo.

Ex vivo gene therapy means that cells are removed from the body, treated and then returned to the body. This is the approach used to treat genetic diseases of blood cells, because bone marrow can be harvested from the patient, stem cells from that bone marrow can be treated with gene therapy — for instance, to supply a gene that is missing or not working correctly — and the transformed cells can be infused back into the patient.

In vivo gene therapy means that the gene therapy itself is injected or infused into the person. This can be through injection directly to the anatomic site where the gene therapy is needed (a common example being the retina of the eye), or it can mean injection or infusion of a genetic payload that must travel to the body tissues where it is needed.

In both ex vivo and in vivo gene therapy, the genetic payload is packaged within a container, called a vector, before being delivered into cells or the body.  One such vector is adeno-associated virus (AAV). This is a group of viruses that exist in nature but have had their regular genes removed and replaced with a genetic payload, turning them into gene therapy vectors.

Is gene therapy safe?

AAV has been used to deliver gene therapy for many years, because it has a good safety record. It is much less likely to cause a dangerous immune response than other viruses that were used as vectors several decades ago, when gene therapy was just getting started. Additionally, packaging genetic payloads within AAV carriers allows for injected or infused gene therapy to travel to particular body tissues where it is needed. This is because there are many types of AAV, and certain types are attracted to certain tissues or organs. So, if a genetic payload needs to reach liver cells, for example, it can be packaged into a type of AAV that likes to go to the liver.

In the early days of gene therapy, which began in 1989, researchers used retroviruses as vectors. These viruses delivered a genetic payload directly into the nuclear chromosomes of the patient. However, there was concern that such integration of new DNA into chromosomes might cause changes leading to cancer, so the strategy was initially abandoned. (More recently, scientist have successfully used retroviruses in experimental gene therapies without causing cancer; for example, a retrovirus-based therapy was used to treat infants with "bubble boy disease.")

After moving away from retroviruses, researchers turned to adenoviruses, which offered the advantage of delivering the genetic payload as an episome — a piece of DNA that functions as a gene inside the nucleus but remains a separate entity from the chromosomes. The risk for cancer was extremely low with this innovation, but adenovirus vectors turned out to stimulate the immune system in very powerful ways. In 1999, an immune reaction from adenovirus-carrying gene therapy led to the death of 18-year-old Jesse Gelsinger, who'd volunteered for a clinical trial. 

Gelsinger's death shocked the gene therapy community, stalling the field for several years, but the current gene therapies that have emerged over the years based on AAV are not dangerous. However, they tend to be expensive and the success rate varies, so they typically are used as a last resort for a growing number of genetic diseases.

What conditions are currently treated with gene therapy?

Gene therapy can treat certain blood diseases, such as hemophilia A, hemophilia B, sickle cell disease, and as of 2022, beta thalassemia. What these diseases have in common is that the problem comes down to just one gene. This made beta thalassemia and sickle cell disease low-hanging fruits for ex vivo gene therapies that involve removing and modifying bone marrow stem cells, whereas hemophilia A and hemophilia B are treated with in vivo gene therapies that target liver cells. That said, other treatments exist for these blood diseases, so gene therapy is more of a last resort.

Numerous enzyme deficiency disorders also come down to one bad gene that needs to be replaced. Cerebral adrenoleukodystrophy, which causes fatty acids to accumulate in the brain, is one such disorder that can be treated with gene therapy, according to Boston Children's Hospital. CAR T-cell therapy, which is approved for certain cancers, involves removing and modifying a patient's immune cells and is known as a "cell-based gene therapy." 

Gene therapy has also been useful in treating hereditary retinal diseases, for which other treatments have not been useful.

What gene therapies are in development?

Another group of targets for gene therapy are diseases of the nervous system. 

"We are at a remarkable time in the neurosciences, where treatments for genetic forms of neurological disorders are being developed," Dr. Merit Cudkowicz, the chief of neurology at Massachusetts General Hospital and a professor at Harvard Medical School, told Live Science.

For example, gene therapies are being developed to treat a pair of genetic diseases called Tay-Sachs disease and Sandhoff disease. Both conditions result from organelles called lysosomes filling up with fat-like molecules called gangliosides. The effects of these diseases include delay in reaching developmental milestones, loss of previously acquired skills, stiffness, blindness, weakness and lack of coordination with eventual paralysis. Children born with Tay-Sachs disease and Sandhoff disease generally don’t make it past 2 to 5 years of age.

"There has been no routine antenatal or neonatal test for Tay-Sachs and Sandhoff, because there has been no available treatment whatsoever," said Dr. Jagdeep Walia, a clinical geneticist and head of the Division of Medical Genetics within the Department of Pediatrics and the Kingston Health Sciences Centre and Queen's University in Ontario, Canada. Walia is developing a gene therapy aimed at replacing the gene for Hex A, the enzyme that is deficient in these children. So far, the treatment has shown good efficacy and safety in animal models, but it still needs to be tested in human patients.

The future looks hopeful when it comes to gene therapy overall, on account of new technological developments, including CRISPR gene editing. This is an extremely powerful technique for cutting out parts of DNA molecules and even pasting new parts in — analogous to what you do with text in word processing applications. CRISPR is not the first method that scientists have used to edit DNA, but it is far more versatile that other techniques. It is not yet quite ready for in vivo chromosomal manipulation, but it is advancing exponentially. 

Perhaps even closer to the horizon is the prospect of delivering larger genetic payloads into cells. One big drawback of the AAV vector is that each virus particle can carry just a small amount of DNA, but recent research has revealed that a different type of virus, called cytomegalovirus, can be adapted to carry gene therapies with a much bigger payload than AAV. Not only might this some day expand gene therapy to more diseases requiring larger genes than AAV can carry, but it also could enable more than one gene to be delivered in a single therapy. 

A teenager with an aggressive form of leukemia now has no detectable cancer cells in her body, thanks to an experimental therapy in which the 13-year-old received new, genetically-tweaked immune cells. 

The patient, named Alyssa, seems to be in remission but will need to be closely monitored in the upcoming months to confirm that she's truly leukemia-free, according to Great Ormond Street Hospital for Children (GOSH) in the U.K., which provided the treatment. Previously, Alyssa had undergone chemotherapy and a bone marrow transplant, but her cancer kept coming back. Had she not entered a clinical trial for the experimental treatment, her only remaining option was palliative care to relieve her symptoms, rather than cure her cancer. 

"I'm very honored, and it feels good to have helped other people as well," Alyssa said in a video released by GOSH. She was the first patient to receive the new therapy. In all, her doctors aim to enroll a total of 10 patients between the ages of 6 months and 16 years old in their ongoing trial. 

The team presented Alyssa's preliminary results on Saturday (Dec. 10) at the American Society of Haematology annual meeting in New Orleans, Louisiana.

Related: Experimental rectal cancer drug caused all patients' tumors to disappear in small trial 

Alyssa was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) in May 2021, according to GOSH. T-ALL affects stem cells in the bone marrow that would normally give rise to T-cells, white blood cells that guard the body against infection. In T-ALL, however, abnormal and immature T-cells build up in the body and crowd out the healthy T-cells, leaving patients prone to infections.

Treatments for T-ALL include chemotherapy, which kills the cancer cells, and bone marrow transplants, which replace patients' diseased stem cells with healthy ones from a donor. Unfortunately, as in Alyssa's case, these strategies don't always keep the disease under control. 

"Approximately 20% of patients with T-ALL will relapse, and the prognosis for relapsed T-ALL is poor," according to a 2016 review in the journal Hematology ASH Education Program. 

A different treatment, called CAR-T cell therapy, has previously worked for other forms of ALL but not T-ALL. That therapy involves removing some of the patient's T-cells, tweaking their DNA in the lab and then reintroducing them into the body. The tweaked T-cells are meant to hunt down and kill cancer cells, but in T-ALL, the T-cells mistake each other for the enemy. Researchers at GOSH and the University College London (UCL) Great Ormond Street Institute of Child Health have been working on a way to prevent this friendly-fire. 

For the new therapy, scientists stripped donated T-cells of certain receptors that would make them look foreign to the recipient's immune system. The cells also lost CD7, a protein found on all T-cells, and another protein called CD52, which is targeted by certain cancer treatments. Finally, the T-cells got a new receptor that let them target CD7-carrying T-cells, including cancerous ones, according to UCL.  

To apply all these genetic changes, the team used a modified form of the famous gene-editing tool CRISPR to swap out individual letters in the T-cells' DNA code. This technique is called "base editing." Alyssa is the first patient to receive a base-edited CAR-T cell therapy. 

(Several base-edited cell therapies for other diseases, including an inherited cholesterol-processing disorder, are currently underway, New Scientist reported.)

Within a month of treatment, Alyssa entered remission. She then received a second bone marrow transplant to restore her immune function, since the experimental therapy had wiped out her T-cells. Now, six months post-transplant, her cancer remains undetectable and she's recovering at home.

"The doctors have said the first six months are the most important and we don’t want to get too cavalier but we kept thinking 'If they can just get rid of it, just once, she’ll be ok,'" Alyssa's mother, Kiona, told GOSH. "And maybe we’ll be right." Alyssa is hoping to return to school and "that could be a reality soon," her mom said.

The CIA is funding research into resurrecting extinct animals — including the woolly mammoth and tiger-like thylacine — according to news reports.

Via a venture capital investment firm called In-Q-Tel, which the CIA funds, the American intelligence agency has pledged money to the Texas-based tech company Colossal Biosciences. According to Colossal's website, the company's goal is to "see the woolly mammoth thunder upon the tundra once again" through the use of genetic engineering — that is, using technology to edit an organism's DNA.

Colossal has also stated an interest in resurrecting the extinct thylacine, or Tasmanian tiger — a wolf-like marsupial that went extinct in the 1930s — as well as the extinct dodo bird.

For their part, the CIA is less interested in thundering mammoths and roaring thylacines than it is in the underlying genetic engineering technology that Colossal intends to develop, according to an In-Q-Tel blog post.

"Strategically, it's less about the mammoths and more about the capability," In-Q-Tel's senior officials wrote.

De-extinction may sound like science fiction — and, to an extent, it is. There is no way to bring back the woolly mammoth as it was ten thousand  years ago; however, by using DNA editing tools, scientists can insert cold-resistant characteristics into the DNA sequences of modern elephants, making them genetically similar to woolly mammoths. The resulting creature wouldn't be a mammoth, per se; rather, it would be a proxy animal that's more like an elephant with mammoth-like characteristics.

The foundation of this process is a gene editing method called CRISPR — genetic "scissors" that scientists can use to cut, paste and replace specific gene sequences into an organism's DNA. (Several of the researchers behind CRISPR won the 2020 Nobel Prize in chemistry).

According to the In-Q-Tel blog post, investing in this project will help the U.S. government to "set the ethical, as well as the technological, standards" for genetic engineering technology, and keep the U.S. a step ahead of competing nations that may also be interested in reading, writing and altering genetic code.

Not everyone is so optimistic about using genetic engineering tools to revive extinct animals. Critics have warned that, even if a company is able to engineer a healthy proxy mammoth, the mammoth's natural habitat no longer exists — and, even if it did, genetic code cannot teach an animal how to thrive in an unfamiliar ecosystem, according to Gizmodo. Some scientists also argue that money spent on de-extinction projects could go much further if applied to the conservation of living animals.

Can an extinct species be brought back to life? Scientists are taking a "giant leap" in that direction by using gene-editing to resurrect the Tasmanian tiger, a carnivorous marsupial from Australia and the continent's only marsupial apex predator. It died out nearly a century ago, driven to extinction by human hunters and by the introduction of nonnative species to their grassland, wetland and forest habitats.

Researchers with the project, a collaboration between the University of Melbourne and the genetic engineering company Colossal Biosciences in Dallas, suggest that this so-called de-extinction could reinstall Tasmanian tigers (Thylacinus cynocephalus) to the wild within a decade, and could help restore balance to beleaguered Australian ecosystems where the animals once roamed, university representatives said in a statement.

However, such efforts also raise questions about prioritizing high-tech solutions for resurrecting charismatic animals that humans have already exterminated, while hundreds of species teeter on the brink of extinction today, The Guardian noted.

Related: Stunning colorized footage provides a glimpse of the last known Tasmanian tiger

Scientists in the Thylacine Integrated Genomic Restoration Research (TIGRR) Lab at the University of Melbourne have already sequenced the thylacine genome from preserved thylacine DNA and pinpointed which living marsupials are most genetically similar to thylacines, according to the statement. Colossal's CRISPR gene editing technology will enable the group to take cells from a closely related living marsupial species, the fat-tailed dunnart (Sminthopsis crassicaudata), create a template genome, and then edit it to produce a thylacine genome and grow viable thylacine embryos. 

"With this partnership, I now believe that in ten years' time we could have our first living baby thylacine since they were hunted to extinction close to a century ago," team member Andrew Pask, a professor of epigenetics at the University of Melbourne and leader of the TIGRR Lab, said in the statement. "We can now take the giant leaps to conserve Australia's threatened marsupials and take on the grand challenge of de-extincting animals we had lost."

Tasmanian tigers, or thylacines, appeared in Australia about 4 million years ago and were once widespread across the continent, according to the Australian Museum in Sydney. Despite their name, they didn't look much like tigers; in fact, they were sometimes referred to as "long dogs with stripes" because of their doglike heads and distinctively-marked rumps, according to the University of Melbourne. Thylacines had short ears and legs, and long, rigid tails, and they were about the size of an American coyote, standing approximately 24 inches (60 centimeters) tall and weighing 37 to 44 pounds (17 to 20 kilograms), scientists reported in 2020 in the journal Proceedings of the Royal Society B: Biological Sciences.

Thylacines vanished from most of the Australian mainland about 2,000 years ago, and an estimated population of about 5,000 were in Tasmania around the time of European colonization in the 1800s, according to the National Museum of Australia (NMA) in Canberra. But by the 1920s, thousands of Tasmanian tigers had been slaughtered by human hunters who mistakenly saw the marsupials as a threat to livestock. The last Tasmanian tiger seen in the wild was killed in 1930, and the last specimen in captivity — an individual nicknamed "Benjamin" — died in the Hobart Zoo in 1936, NMA says.

According to researchers with the de-extinction project, resurrecting Tasmanian tigers would be a conservation success story; not only for restoring a species lost to human activity, but also for building a lifeline for vulnerable and threatened species across Australia, "developing gestational and genetic rescue technologies for future marsupial conservation efforts," Colossal CEO and co-founder Ben Lamm said in a statement.

"With our planet's biodiversity at risk, we will continue to contribute scientific resources to preserving the species and ecosystems necessary to sustain life," Lamm said.

Originally published on Live Science.

Scientists discovered the "fingerprints" of mysterious viruses hidden in an ancient group of microbes that may have helped fuel the rise of all complex life on Earth: from fungi to plants to humans. 

These microbes — known as Asgard archaea after the abode of the gods in Norse mythology — lurk in the frigid sediments deep in the ocean and in boiling hot springs, and existed on Earth prior to the first eukaryotic cells, which carry their DNA inside a nucleus. By infecting Asgard archaea, viruses may have influenced how such life-forms first came to be, and may even have given rise to some of the first precursors to the nucleus, some scientists hypothesize. But before now, no Asgard-infecting viruses had been discovered.   

Now, in a trio of studies published Monday (June 27) in the journal Nature Microbiology, scientists have identified a slew of viruses that can infect the ancient archaea. 

"These are the first studies investigating Asgard archaeal viruses; there was nothing known before," said Susanne Erdmann, group leader of the archaeal virology research group at the Max Planck Institute for Marine Microbiology in Bremen, Germany, who was not involved in the studies. In the future, this line of research may reveal if and how viruses were involved in the emergence of eukaryotic cells on Earth, Erdmann told Live Science in an email.

Related: Scientists discover viruses that secretly rule the world's oceans 

Dusting for viral 'fingerprints' 

In the new research, scientists searched for evidence of viral infection embedded in the DNA of Asgard archaea. This embedded evidence comes in the form of short snippets of viral DNA, called "CRISPR spacers." 

Most people who hear the term CRISPR think of the famous gene-editing tool that allows scientists to easily manipulate genetic sequences, said Ian Rambo, a former doctoral candidate at the University of Texas at Austin Marine Science Institute and first author of one of the Nature Microbiology studies. However, this gene-editing tool was originally adapted from the natural defense mechanisms of bacteria and archaea, he told Live Science.

The acronym "CRISPR" stands for "clusters of regularly interspaced short palindromic repeats" and refers to a region of DNA made up of short, repeated sequences with "spacers" sandwiched between each repeat. Bacteria and archaea swipe these spacers from viruses that infect them, and thus, the cells maintain a memory bank of viral DNA that helps them recognize the viruses, should they attack again. "It's an adaptive immune system that remembers these previous infections," said Rambo, who is now a postdoctoral scholar with the USDA's Agricultural Research Service.

Rambo and his colleagues hunted in the Guaymas Basin in the Gulf of California — the body of water between Baja California and mainland Mexico — for such DNA spacers in Asgard archaea specimens collected from sediments near hydrothermal vents, roughly 1.25 miles (2 kilometers) beneath the water's surface. The team matched the spacers they found to longer stretches of viral DNA gathered from the deep-sea environment.  

Related: Are viruses alive?

"It is fairly easy to sequence viruses from deep-sea sediments … but the challenge is to recognize which hosts these viruses infect," said Mart Krupovic, head of the Archaeal Virology Unit at the Institut Pasteur in Paris and a co-author of the other two studies. "CRISPR spacer matching is the most convenient and most convincing and reliable approach to assign the host." 

In the end, Rambo's team uncovered six viruses that infect two types of Asgard archaea, named Lokiarchaeota and Helarchaeota for the Norse god Loki and goddess Hel, respectively. The researchers named the newfound viruses after Norse mythological creatures, including the giant wolf Fenrir and the dragon Nidhogg.

Similarly, in one study, Krupovic and his colleagues discovered two viruses that they named Huginn and Muninn, after the two ravens that serve as scouts for the Norse god Odin; these viruses were uncovered in an Asgard genome sampled from a hot spring in Yellowstone National Park. 

In the final study, Krupovic and his coauthors uncovered viruses in deep-sea sediments collected from the Shimokita Peninsula, the northeastern cape of the Japanese island of Honshū, as well as two other sites in the Pacific and one in the Indian Ocean. In these samples, they found three family-level groups of viruses, which they named after the three Norns — Wyrd, Verdandi and Skuld — which are supernatural beings that determine the destinies of gods and mortals in Norse mythology. 

Related: Out of deep-sea mud, a strange blob may hold secrets to the origins of complex life

Working from the viral DNA, the researchers could infer what kinds of proteins the various genes code for, and therefore, how the viruses might look and function. 

For example, the viruses named for the Norn Verdandi likely have tails that extend from their outer shells, or capsids, and the viruses named for Wyrd are likely lemon-shaped, Krupovic and his colleagues determined. Rambo's team also found evidence that Nidhogg viruses may be able to hijack key proteins in their host cells that would help the viruses pump out new copies of themselves. (Viruses that infect eukaryotic cells hijack their hosts in a similar fashion.)

Ultimately, the researchers could only figure out the functions of some of the viruses' genes; functions of the vast majority of the genes are still unknown, Erdmann said. In addition, because CRISPR doesn't work against all viruses, many more Asgard-infecting viruses are likely yet to be discovered, she said. 

One way to find these hidden viruses would be to grow Asgard archaea in the lab and isolate any viruses found within their cells. "However, culturing Asgard archaea has been proven very difficult,"  Erdmann noted. To date, only one research group has successfully cultured Asgard archaea, and it took them 12 long years to do it. That's partially because archaeal cells take weeks to replicate. (By comparison, the bacterium Escherichia coli, for example, takes about 20 minutes, according to Science News). 

Until more Asgards can be grown in the lab, CRISPR spacer matching is probably the most efficient way to find more viruses, Krupovic said. And as more and more viruses are found, their role in the emergence of eukaryotes — including humans — may become more clear, Rambo told Live Science.

Originally published on Live Science.

CRISPR, short for CRISPR-Cas9, is a genome-editing tool that allows scientists to precisely cut and modify DNA sequences. It has revolutionized the study of genes, helped to enhance crops and improved health care.

The gene-editing system was originally discovered in bacteria, where it limits infections by clipping viral DNA. Then, in Nobel prize-winning work, this bacterial defense apparatus was co-opted by scientists to devise a new approach to genome editing. 

"It's really the simplicity, the cost and the ease of use" that democratized this editing tool, Alison Van Eenennaam, a livestock geneticist at the University of California, Davis who uses CRISPR to alter the genetics of farm animals, told Live Science.

Recently, CRISPR has been approved to treat two blood disorders, and early-stage trials reveal its potential to treat inherited blindness. Here's everything you need to know about the groundbreaking technology.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys 

What is CRISPR?

The CRISPR system includes the following major components:  

CRISPR: "CRISPR" stands for "clusters of regularly interspaced short palindromic repeats." This unwieldy name describes a pattern of DNA sequences found in bacterial genomes that helps the bacteria fend off viruses.

"Short palindromic repeats" refers to sequences that read the same forward and backward, like the words "kayak" and "racecar." DNA consists of two paired strands twisted around each other in a helix. A DNA palindrome thus refers to a string of DNA letters, or bases — A (adenine), C (cytosine), G guanine) and T (thymine) — that are the same when read forward on one strand and read backward on the other. 

For example, if one strand reads "GATC" in one direction, these DNA bases will pair up with "CTAG" on the opposite strand because G always pairs with C and A always pairs with T. When read backward, CTAG becomes the original sequence, GATC.

These repeats are "regularly interspaced," meaning that these CRISPR regions in the genome contain an alternating pattern of palindromes with "spacer" sequences wedged between them. Bacteria co-opt the spacer sequences from the DNA of invading viruses and store them in their CRISPR regions to fight future infections.  

This system is often likened to the human adaptive immune system, which similarly stores a "memory" of previous infections in order to stave off repeat encounters. Rather than using immune cells, like humans do, bacteria use CRISPR.

CRISPR RNA (crRNA) and Cas9: CRISPR DNA serves as a permanent record of past infections, but for bacteria to use these sequences to thwart viruses, they must convert them into DNA's cousin, RNA. Through a process called transcription, bacteria first copy one of the two CRISPR DNA strands into a single complementary strand of RNA; the strand is complementary in that it matches the original DNA code, except it replaces T with U (uracil). Then, the microbes chop the lengthy strand into shorter crRNA snippets, each carrying one repeat and one spacer. 

The bacteria also make a second RNA molecule, called "trans-activating crRNA," or tracrRNA. This RNA contains a reversed version of the palindromic repeat on the crRNA molecule, allowing the two RNAs to bind together. 

The resulting complex can then latch onto viral DNA carrying the spacer sequence, calling forth an enzyme that cuts and disables that DNA. The enzyme, called "CRISPR-associated protein 9," or Cas9, is essentially a pair of molecular scissors.

There are also other types of Cas enzymes that can be utilized in gene editing. For example, one called Cas12a produces staggered cuts in DNA, in which one strand is longer than the other at each end. DNA sequences can then be paired with the overhanging strand. Cas14 makes cuts in RNA, instead of DNA, and could be useful for temporarily altering what proteins a cell makes without making permanent edits to its genome.

Related: Meet 'Fanzor,' the 1st CRISPR-like system found in complex life  

How does CRISPR edit DNA?

Researchers have taken advantage of the CRISPR system's ability to make precise cuts in DNA. By adapting CRISPR to make desirable genome edits in any cell type, researchers can alter genes or DNA sequences that regulate genes' activity, changing their function or expression.

To simplify the system, scientists combined the crRNA and tracrRNA molecules described in the previous section into a single molecule called "guide RNA." 

"All you need to do to target a new sequence is alter the guide," Van Eenennaam said, which is cheap and quick to do. In contrast, other genome-editing techniques require the time-consuming and expensive design of a lab-made protein that targets a sequence of interest. 

The guide RNA is paired with a Cas9 enzyme to make edits in the genome. Once the RNA binds to the desired sequence, the enzyme swoops in and cuts both strands of DNA. In response, the cell attempts to glue the strands back together, but it uses a fault-ridden process that often introduces mutations. For instance, it may add a few extra letters. This change often deactivates the gene, making CRISPR editing a simple strategy to switch off genes.

Scientists have also modified the Cas9 enzyme to make other types of edits. By disabling Cas9's genetic scissors and then fusing this "dead Cas9" to another enzyme, they can rig the machinery to alter single bases, converting a C into a T, for example. This CRISPR formulation is called "base editing," and it allows researchers to make fine changes that alter the structure of the product encoded by the gene, whether that's a protein or RNA. 

Dead Cas9 has also been paired with enzymes that activate or silence genes to tune their activity. Dead Cas9 has also been fused to fluorescent proteins, which light up when the guide RNA binds to a specific stretch of DNA, essentially revealing its post code in the cell. 

Related: Could CRISPR cure HIV someday? 

Who discovered CRISPR?

CRISPR's history goes back to 1987, when Yoshizumi Ishino and colleagues at Osaka University in Japan first reported the unusually repetitive sequences in Escherichia coli, a well-known bacterium. At the time, the scientists didn't know how these clusters were related to bacterial defense. 

In the 1990s, these clusters drew the attention of more scientists when Francisco Mojica (who coined the term "CRISPR") and his team at the University of Alicante in Spain spotted them in 20 other bacterial genomes, suggesting they had widespread importance in bacteria. 

In 2005, Alexander Bolotin and colleagues at the French National Institute for Agricultural Research came across genes for Cas enzymes located near the CRISPR region of a genome. Shortly after, Eugene Koonin's group at the National Institutes of Health revealed that the spacer sequences matched viral DNA, leading researchers to connect CRISPR with bacterial immunity.

Emmanuelle Charpentier, of the Max Planck Institute in Germany, and Jennifer Doudna, of the University of California, Berkeley, later adapted CRISPR for genome editing. Their work led them to share the 2020 Nobel Prize in chemistry. 

Shortly after the groundbreaking publication of Charpentier's and Doudna's work, Virginijus Šikšnys of the Vilnius University Institute of Biotechnology and his colleagues also demonstrated how CRISPR could be used in gene editing. Feng Zhang's group at the Broad Institute later developed other CRISPR systems into gene-editing tools, including an RNA-editing system involving an enzyme called Cas13. 

How has CRISPR been used in people? What about in plants and animals?

CRISPR has been used to correct genetic disorders, such as cystic fibrosis and cataracts, in laboratory-grown cells and in lab animals. It has also shown recent success as a treatment for other conditions in human trials. Notably, the U.K. and the U.S. have both approved a CRISPR-based gene therapy called Casgevy for two blood disorders: sickle cell disease and beta thalassemia. This is the first CRISPR-based therapy to ever be approved.

Casgevy works by cutting and disabling the gene BCL11A, which controls the switch from fetal hemoglobin to adult hemoglobin shortly after birth. 

The fetal version binds more strongly to oxygen, allowing a fetus to gather enough oxygen from its mother's bloodstream. The adult version normally takes over after birth, once oxygen can be obtained through breathing. However, in sickle cell disease and beta thalassemia, people have faulty versions of the adult gene. Casgevy reverses the switch to adult hemoglobin so that patients can continue using their fetal hemoglobin gene instead.

One form of inherited blindness may be among the next disorders treated using CRISPR. An early-stage trial tested injecting CRISPR components into the eye and suggested the approach to be safe and effective mode. The base-editing form of CRISPR also showed promising results in lowering cholesterol levels during a small trial. 

Beyond health care, CRISPR editing has been used to enhance at least 41 food crops, including rice and wheat, by improving their palatability, nutritional value and resistance to disease. It's also been used to edit the genes of pigs whose organs are then harvested for human transplant operations. 

In addition, Van Eenennaam uses CRISPR in proof-of-concept experiments to endow farmed animals with desirable traits. For example, she enhances meat yields in cattle so farmers can rear fewer livestock and thus limit their environmental impact. 

What are potential dangers and downsides of CRISPR?

CRISPR is a versatile and powerful genome editing tool, but at this juncture, it has some limitations and risks and also raises ethical quandaries. 

For instance, in regards to treating genetic disorders, some people embrace their conditions and don't regard them as disorders, Van Eenennaam said. For instance, "should you 'cure' hereditary deafness in the offspring of a deaf couple who don't believe deafness is a bad thing?" she questioned.

Regarding CRISPR's limitations, it can introduce "off-target effects" if the Cas9 enzyme cuts DNA at unintended places in the genome. This might occur if researchers don't customize the guide RNA sequence for a unique DNA target but instead target a common sequence found in a family of genes. Such off-target effects could have negative outcomes on health. For example, if the guide RNA matches a gene that suppresses tumor growth, there is a risk that disabling it could turn the cell cancerous.

Another issue is that CRISPR editing is not 100% efficient, so only a proportion of the targeted cells undergo the desired genetic change. This means that, in some scenarios, unedited cells might avoid harmful off-target effects and thus fare better than edited cells and eventually outnumber them. Researchers recently found that edited blood stem cells can die out overtime, suggesting blood-disorder treatments may become less effective in the long haul.

These risks also pose ethical considerations regarding the use of CRISPR in livestock. Van Eenennaam typically uses "germ-line editing" in livestock, which involves targeting sex cells, like eggs and sperm, or fertilized eggs. This makes CRISPR edits heritable between an animal and its offspring. Van Eenennaam's group doesn't insert newly engineered genes into cattle, but rather, they transfer existing, desirable genes from one cow into another.

Related: Gene therapy: What is it and how does it work? 

There is a chance that off-target edits could impair the animals' health. But Van Eenennaam argues these concerns are often exaggerated. "There are going to be literally millions of genetic variations between two bulls" arising from natural mutations, so off-target effects are just a drop in the ocean, she explained.

Still, the U.S. Food and Drug Administration (FDA) says genome-editing of farmed animals requires ample oversight, in part because other DNA sequences often accompany the new gene inserted into the genome. These carryovers should be scrutinized to ensure they aren't hazardous to the animal or to human consumers, the FDA says. If the agency deems an edited animal to be low-risk, they can grant "enforcement discretion" that allows it and its descendants to be commercialized, Van Eenennaam noted.

This type of germ-line editing has rarely been applied to humans, except in the controversial case in which a Chinese scientist infamously generated "CRISPR babies" in violation of regulations. One big reason human germ-line editing has been avoided is that future generations cannot consent to receiving a CRISPR treatment. 

Future generations also cannot consent to the possibility of harmful off-target effects, such as mutations that could predispose one to cancer. Nita Farahany, a bioethicist at Duke University, told the New York Times that editing embryos would be unethical "until we can figure out what the off-target effects are, and how we can control for them."

The National Academies of Sciences, Engineering and Medicine laid out criteria that should be met for germline editing clinical trials to go forward. The group advises restricting human germ-line editing to only genes whose mutations can lead to serious disease for which there are no other therapies.

Currently, gene therapies mainly use a technique called "somatic editing." This applies to Casgevy, for example. Somatic editing works by targeting a subset of non-sex cells in the body and thus doesn't pass any alterations down to additional generations.

"The benefit clearly outweighs any hypothetical risk" in these contexts, Van Eenennaam said, so somatic CRISPR editing is a "no-brainer" when it comes to gene therapy.

Editor's note: A new version of this article was published on July 1, 2024. The previous version had last been updated in March 2023.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website! 

Scientists have harnessed CRISPR gene-editing technology to block the replication of the novel coronavirus in human cells — an approach that could one day serve as a new treatment for COVID-19.

However, the study was performed in lab dishes and has not yet been tested on animals or people, meaning a treatment based on the method could be years away.

CRISPR is a tool that enables researchers to precisely edit DNA. It's based on a natural defense system used in bacteria that allows the microbes to target and destroy the genetic material of viruses, Live Science previously reported.

In the new study, published Tuesday (July 13) in the journal Nature Communications, the researchers used a CRISPR system that targets and destroys strands of RNA, rather than DNA. Specifically, their system uses an enzyme called Cas13b, which cleaves single strands of RNA, like those found in SARS-CoV-2, the virus that causes COVID-19. (Cas13b is similar to Cas9, the enzyme most commonly used in CRISPR gene-editing technology, but Cas9 cleaves DNA while Cas13b cleaves RNA.)

The researchers designed CRISPR-Cas13b to target specific sites on the RNA of SARS-CoV-2; once the enzyme binds to the RNA, it destroys the part of the virus needed to replicate, according to a statement from the Peter MacCallum Cancer Centre in Victoria, Australia, which collaborated on the research. 

"Once the virus is recognized, the CRISPR enzyme is activated and chops up the virus," study lead author Dr. Sharon Lewin, of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, told AFP.

Related: 10 amazing things scientists just did with CRISPR

The researchers also found that their method worked even when new mutations were introduced into the SARS-CoV-2 genome, including those seen in the alpha coronavirus variant, first discovered in the United Kingdom.

Effective COVID-19 vaccines are currently being distributed around the world, but there remains a "clear and urgent need" for effective treatments for the disease, the authors said. They noted that there are "serious concerns" that the virus will evolve to "escape" current vaccines.

An ideal treatment would be an antiviral drug that patients take shortly after being diagnosed with COVID-19. "This approach — test and treat —  would only be feasible if we have a cheap, oral and non-toxic antiviral. That's what we hope to achieve one day with this gene scissors approach," Lewin told AFP.

Although the new study is a first step toward such a treatment, it will likely be years before this method could be turned into a treatment that's widely available, AFP reported. The researchers now plan to test the method in animal models, and eventually conduct clinical trials in people.

Medicines that use CRISPR technology have not yet been approved to treat any diseases, but multiple studies are underway to test CRISPR-based therapies in people as a treatment for various diseases, including cancer and HIV.

Originally published on Live Science.  

Disembodied human tear glands, grown in petri dishes in a laboratory in the Netherlands, have the ability to cry — and the scientists who created them have already grafted them into the eyes of living mice.

The series of experiments, detailed in a new study published online March 16 in the journal Cell Stem Cell, could represent a major step forward in the science of treating dry eye — a condition that impacts about 5% of adults worldwide and can lead to blindness in severe cases. 

Petri-dish body parts have become more commonplace in laboratory experiments, but they're often much smaller and simpler than their natural counterparts. "Minibrains," for example, are smooth, pea-size, unconscious organoids that only loosely resemble the original organs, Live Science has reported. The petri-dish tear glands, however, were pretty close to the real thing, according to Marie Bannier-Hélaouët, a co-lead author of the study and researcher at the Hubrecht Institute in Utrecht, Netherlands.

Related: 11 body parts grown in the lab

Human tear glands, Bannier-Hélaouët told Live Science, have two components: acinar cells and ductal cells. 

"Both can make tears, but the ductal cells have an additional function: They act like a canal to bring the tears to the eye surface. The [lab-made] organoids look like this canal," she said. "The difference is that, as in the dish there is no eye to bring the tears to, the organoids look like a canal with dead ends. They are balloons."

Those balloons are similar in size to what you'd find in a human, growing up to about one-50th of an inch (half a millimeter) wide.

The researchers divided the study into three experiments. In the first they grew human tear glands in petri dishes and got them to produce tears. 

Growing the organoids was one thing, Bannier-Hélaouët said. Getting them to cry was another, since that involves brain chemicals called neurotransmitters.

"Working out the perfect cocktail [of neurotransmitters] to make the organoids cry was the most challenging part. It took me about three or four months and about seven to 10 trials," she said. "What is striking is that this final cocktail contains very few ingredients. One of them is simply an antioxidant molecule."

Once the cocktail had been perfected, the researchers observed the glands puffing up with tears that had nowhere to go.

Next, they implanted some of those lab-made glands into the tear ducts of living mice. They found that the implanted human cells could still produce tears, but they didn't release them into the ducts the way normal glands would. Eventually, she said, it will be important to figure out how to make the glands act normally in living tear ducts.

"We already have ideas on how to do this," Bannier-Hélaouët said.

In the final part of the study, the researchers focused on pinpointing the origin of a form of chronic dry eye known as Sjögren's syndrome, an autoimmune condition that also causes dry mouth.

In petri dishes, the researchers grew mouse tear glands that had been modified with gene-editing technology to not express a gene known as Pax6. Researchers had already established that people with dry eye often lack Pax6 in their eye tissue and that the gene plays an important role in eye development. Their experiment showed that the mouse organoids modified to lack Pax6 produced fewer tears, bolstering the idea that the gene is linked to the medical problem.

Originally published on Live Science.

The 2020 Nobel Prize in chemistry went to two women who developed a gene-editing tool called CRISPR-Cas9, which snips DNA like a pair of molecular scissors. 

The technique "has not only revolutionized basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments," Claes Gustafsson, chair of the Nobel Committee for Chemistry, said in a statement. With the ability to deftly slice specific DNA sequences from the genome, scientists can pinpoint the functions of genes; these discoveries both add to our basic understanding of how those genes work and can have practical applications, such as for growing drought- and pest-resistant crops and developing therapies for cancer and genetic disorders. The genetic cut-and-paste system is also being used in new COVID-19 diagnostic tests.

The Nobel "for the development of a method for genome editing" went to Emmanuelle Charpentier, director of the Max Planck Unit for the Science of Pathogens, and Jennifer Doudna, a professor of biochemistry, biophysics and structural biology of the University of California, Berkeley. This is the first science Nobel to be awarded to an all-female team, according to Science Magazine. 

Related: Nobel Prize in Chemistry: 1901-Present 

The development of CRISPR-Cas9 began serendipitously when Charpentier was studying the bacteria Streptococcus pyogenes, which causes a range of diseases from tonsillitis to sepsis, according to a statement from the Nobel Committee. The bacteria contain a molecule called tracrRNA, Charpentier discovered, which protects S. pyogenes against infection by viruses, according to a 2011 report in the journal Nature. 

It turned out that tracrRNA was just one component in a larger defense mechanism known as the CRISPR/Cas system, which bacteria use to slice and dice the DNA of viruses that try to infect them, Live Science previously reported. After a viral attack, the bacteria incorporate a piece of viral DNA into their own genome; these battle trophies line up in the genome, appearing repeatedly, and are known as "clusters of regularly interspaced short palindromic repeats," abbreviated as CRISPR. These archived genes are thought to help bacteria recognize the viruses and ward off future attacks.  

But to first slice up the viral DNA, bacteria use "CRISPR-associated" proteins, called Cas proteins, under the guidance of tracrRNA and other molecules.

After her discovery of tracrRNA, Charpentier began collaborating with Doudna, and the two recreated the bacteria's genetic scissors in a test tube. In their seminal work, published in 2012 in the journal Science, they simplified the system into a handy gene-editing tool, capable of targeting and snipping specific DNA sequences from the genome. The tool has since been further refined and used for a wide range of applications, including the recent development of diagnostic tests for COVID-19, BBC reported.

"This discovery, originally derived from a natural defense mechanism in bacteria against viruses, will have untold applications in treating and curing genetic diseases and fighting cancer, as well as impacts on agricultural and other areas," Luis Echegoyen, president of the American Chemical Society, said in a statement. "The future for this technique is indeed bright and promising." 

Some scientists expected that biochemist Feng Zhang of the Broad Institute might share the Nobel with Charpentier and Doudna, as shortly after their discovery, he demonstrated that CRISPR also works in mammalian cells, Science Magazine reported. Based on Zhang's work, the Broad Institute received the first patent for the use of CRISPR gene-editing technology in eukaryotes — complex cells with nuclei to hold their DNA — but Charpentier's and Doudna's institutions continue to fight for their own patents, according to The Scientist Magazine. 

Originally published on Live Science.

A gene drive is a type of genetic engineering technique that modifies genes so that they don’t follow the typical rules of heredity. Gene drives dramatically increase the likelihood that a particular suite of genes will be passed onto the next generation, allowing the genes to rapidly spread through a population and override natural selection. Thanks to CRISPR-Cas9, the gene editing technology harnessed from bacteria, gene drives are becoming easier for researchers to build.

With gene drive technology "you can modify evolutionary trajectory. You can cause extinction," said Andrea Crisanti, a geneticist at Imperial College London. This could be an effective way to eradicate nuisance species, such as malaria-causing mosquitoes. But scientists are still working to determine the potential broader ecological and environmental impacts of using gene drives to eliminate an entire species.

How do gene drives work?

A gene drive consists of three key components: the gene that you want to spread; the Cas9 enzyme that can cut DNA; and CRISPR, a prommable DNA sequence that identifies where the enzyme should cut. The genetic material that encodes for those three elements gets inserted into an animal’s DNA, in place of the naturally occurring gene you want to replace in both chromosomes. 

The power of the gene drive is that it disrupts the laws of heredity, Crisanti said. In normal heredity, there is a 50% chance that any particular gene will be passed from parent to offspring. Gene drive technology turns a 50% chance into a nearly 100% guarantee. 

When an animal carrying the gene drive package mates with an animal that does not, their offspring gets one copy of DNA from either parent: a natural version and a gene drive version. When the sperm meets the egg and the chromosomes from the different parents line up for the first time, CRISPR in the gene drive DNA is activated. It recognizes the copy of the natural gene in the opposite chromosome, and directs the DNA-cutting Cas9 enzyme to cut out the natural copy before embryonic development begins.

Related: Prokaryotic vs. eukaryotic cells: What's the difference? 

Once the natural gene is damaged, the cell's special repair machinery is triggered. The repair machinery restores the missing DNA, but it uses the unbroken chromosome, which is the one carrying the gene drive, as its template. So when the repair is finished, both chromosomes carry a copy of the gene drive. From that point on, two copies of the gene drive will be in every cell and the animal will pass the gene drive on to the next generation. 

And so the process continues. Every time the drive is passed on, CRISPR cuts the natural version of the gene, cell repair machinery intervenes and one copy of the gene drive becomes two. In just a few generations the new gene becomes ubiquitous in the population, sometimes totally replacing the naturally occurring gene.

Gene-drive mosquitoes

In 2018, Crisanti and his colleagues published a study in the journal Nature Biotechnology describing how gene drive technology could cause population collapse of Anopheles gambiae, the mosquito species that causes malaria. The group built a gene drive that would change a sex-related gene and disrupt female fertility. The gene drive with the damaged female fertility gene spread through 100% of the test population in as little as seven generations. The species could not mate and the population collapsed. Some researchers believe this may be the approach that finally wipes out malaria — a brutal disease responsible for causing 280 million illnesses and 405,000 deaths globally in 2018, according to the World Health Organization. 

Related: 10 amazing things scientists just did with CRISPR

The gene drive approach is a uniquely affordable and sustainable way to eradicate malaria-causing mosquitoes, Cristanti said. Other approaches like insecticide and environmental management are effective but extremely expensive, and far beyond the economic capabilities of many countries, he said. "Gene drive allows the spreading of a genetic trait in a population from few individuals, addressing the problem of sustainability at its root." 

But wiping out an entire species is a big deal, and implementing a gene drive in nature is not an easy decision. 

Are gene drives dangerous? 

Scientists are working to predict what the elimination of a nuisance species might mean for the rest of the ecosystem. 

Eradicating malaria-causing mosquitoes using a gene drive seems likely to be a minimally-impactful plan. "So far, ecological tests show that the ecosystem doesn't collapse," when one species of mosquito is eliminated, said Fred Gould, an evolutionary biologist at North Carolina State University.

The ecological effects of other gene drive projects are more challenging to discern. For example, conservationists and geneticists are working on a gene drive that could eliminate invasive island rodents — a noble effort, considering that invasive island rodents have been linked to the extinction of 75 native species, according to 2016 a study published in the journal Proceedings of the National Academy of Science. 

But eradicating rodents with a gene drive comes with potentially bigger ecological risks than the eradication of a mosquito. If gene drive rodents ever escaped the island and made it back to the rodents' natural habitat, like North America, the drive could eliminate mice and rats where they are a critical part of the ecosystem. The rodents' absence could lead to ecosystem collapse. 

Related: Here's what we know about CRISPR safety

For that reason, Gould and his colleagues have been working on a strategy that would only target mice living on islands. Geographically distinct populations often carry the same variant of a gene, or allele, specific to their local population. If scientists can identify an allele specific to the population they want to eradicate, then they can create a gene drive specific to that population. The drive would spread only to individuals carrying that specific allele; it wouldn't work in individuals without that specific allele. The researchers described this method in a 2019 study published in the journal Scientific Reports. 

In addition, several scientists are studying potential remediation plans, or strategies for removing the gene drive from the environment in the event of undesired results. For example, Crisanti and his colleagues published a study in 2017 in the journal Plos Genetics describing how genetic mutations that are resistant to the gene drive could persist and eliminate the gene drive in just a few generations. The gene-drive resistant mutation would need to be avoided for the gene drive to persist, or it could be a way to eliminate an undesired gene drive.   

Although the concept of using a gene drive to protect human health and restore ecological balance is promising, research on the tool's implications and effectiveness has a ways to go.

Additional resources: 

• Keep up with the latest news about CRISPR on Live Science's CRISPR News page. 
• Watch this short video describing how a gene drive works from the Wyss Institute at Harvard University.
• Here's another short video that describes potential ways to safeguard a gene drive, also from the Wyss Institute at Harvard University.  

A month ago, there were countless commentaries on the one-year anniversary of the news that Chinese researcher He Jiankui had created the world's first genome-edited twins.

Read more: A year after the first CRISPR babies, stricter regulations are now in place

Now, commentaries are focused on the news that He has been sentenced to three years in prison and fined 3 million yuan ($560,000) for practicing medicine without a license, violating Chinese regulations on human-assisted reproductive technology and fabricating ethical review documents.

Zhang Renli and Qin Jinzhou, embryologists who participated in He's experiment, have also been given prison sentences and fines.

Some scientists believe that He's sentence should have been harsher. Others believe the penalties are sufficient and will be an effective deterrent.

Still other scientists bemoan the fact that scientists are being sent to jail. At the same time, they acknowledge that these are unusual circumstances. For example, Jennifer Doudna, one of the pioneers of CRISPR technology, told the Associated Press: "As a scientist, one does not like to see scientists going to jail, but this was an unusual case … [He's work was] clearly wrong in many ways."

Structural enabling

From my perspective, these comments miss the mark insofar as they fail to acknowledge that the birth of three genome-edited babies is not just the work of three scientists. A three-year jail term and a 3 million yuan fine will not bring closure to this affair. It is important that He and his colleagues have been held accountable for their actions, but it is equally (if not more) important that we critically examine the institutional structures and cultural context that facilitated He's actions.

In December 2015, the organizing committee of the First International Summit on Gene Editing — of which I was a member — issued a statement stipulating that "it would be irresponsible to proceed with heritable human genome editing unless and until (i) the relevant safety and efficacy issues have been resolved … and (ii) there is broad societal consensus."

This statement was widely, and in my view appropriately, described by the media as a call for a moratorium on heritable human genome editing. Almost immediately thereafter, however, prominent scientists insisted that a moratorium was uncalled for.

This perspective was crystalized in the February 2017 report Human Genome Editing: Science, Ethics and Governance by the U.S. National Academy of Science and National Academy of Medicine. This report concluded that "clinical trials using heritable germline genome editing should be permitted," provided there was a compelling reason and there was strict oversight limiting use of the technology to specific criteria.

Reference points

In November 2018, when He Jiankui was criticized for making CRISPR babies, he claimed to have satisfied the criteria set out in the 2017 report. While it is reasonable to dispute this claim, the fact remains that there was an authoritative document that He could point to as endorsing future use of heritable human genome editing.

Moreover, while the 2018 organizing committee of the Second International Summit on Human Genome Editing concluded that heritable genome editing "remains irresponsible at this time," it also called for a translational pathway forward — a roadmap — for moving from basic research in the lab to research involving humans. In this way, the committee both endorsed the future use of heritable genome editing and signalled that the pivotal ethical issue was how best to proceed.

In opposition to this view, in March 2019, prominent scientists and ethicists, including two of the three CRISPR pioneers (Feng Zhang and Emmanuel Charpentier) and several members of the organizing committee for the 2015 Summit, renewed the call to adopt a moratorium. A moratorium would allow for discussion on whether to proceed with germline editing while taking into consideration a wide range of "technical, scientific, medical, societal, ethical and moral issues."

Closure on the He saga requires more than an investigation, legal sanctions and better regulations. It requires us coming to terms with the fact that heritable human genome editing is "irresponsible at this time," not only because the science is premature, but also because widespread agreement on its merits is lacking. The absence of a widely agreed-upon, ethically sound reason to pursue this science very much matters.

[ Expertise in your inbox. Sign up for The Conversation's newsletter and get a digest of academic takes on today's news, every day. ]

This article was originally published at The Conversation. The publication contributed the article to Live Science's Expert Voices: Op-Ed & Insights.

Given the rapid pace of change in technology and science, it can be easy to forget what we didn't know just a few short years ago. The past decade has seen breakthroughs in physics, biology and astronomy, to name just a few. Which of these discoveries are the most important is probably for historians to judge, but some of the consequences of the discoveries early in the decade are beginning to reverberate. Here are our picks for the decade's biggest scientific advances and surprising discoveries. 

2010: The First Synthetic 'Life'

Scientists blurred the line between natural and man-made in 2010 with the creation of the first-ever organism with a synthetic genome. Scientists at the J. Craig Venter Institute assembled the genome of the bacterium Mycoplasma mycoides out of more than a million base pairs of DNA. Then, they inserted this human-engineered genome into another bacterium, Mycoplasma capricolum, which had been emptied of its DNA. The M. capricolum's machinery soon began to translate the instructions of this synthetic genome into action, reproducing just as M. mycoides would. 

Since this breakthrough, scientists have continued to make advances in synthetic biology. In 2016, scientists built the smallest synthetic microbe yet, with just 473 genes. In 2017, they announced the creation of five synthetic yeast chromosomes; the plan is to replace all of the 16 chromosomes in yeast with synthetic chromosomes that could be tweaked to perform certain tasks, such as mass-producing antibiotics or even creating lab-grown meat. 

2011: HIV Preventative Treatment

Today, many people at high risk for contracting the human immunodeficiency virus (HIV), which causes AIDS, pop a daily pill to reduce their risk. In 2012, the U.S. Food and Drug Administration approved a medication, called Truvada, for this purpose. But it was a large study released in 2011 that set the stage for this sea change in HIV prevention. 

That study, which the journal Science dubbed the "breakthrough of the year," was the first since 1994 to show a new way to prevent HIV transmission from one person to another. (In 1994, researchers reported that they'd found a pharmaceutical option to help prevent the transmission of HIV from a pregnant woman to her fetus.) The study began in 2005, and the 2011 findings were interim results. The researchers found a 96% reduction in HIV transmission in that data. The final data encompassing the entire 10-year study, reported in The New England Journal of Medicine in 2016, showed a 93% reduction in HIV transmission. 

2012: Higgs Boson

In July 2012, scientists working at the world's largest particle accelerator announced that they'd hit pay dirt. Experiments at the Large Hadron Collider (LHC) had, at long last, uncovered evidence of the last undiscovered particle predicted by the Standard Model of physics. 

The Higgs boson had been found. This is the particle associated with the Higgs field, an energy field at the root of why particles have mass. Particles gain mass by slogging across this three-dimensional field, creating tiny disturbances in the field. (The stronger their interactions with the field, the more mass they have.) When the field experiences a major energy flare-up in a particular spot, it emits a Higgs boson. In 2013, physicists confirmed that their 2012 observations were indeed the elusive particle, sometimes called the "God particle" because of its role in giving all other particles mass. 

The discovery of the Higgs raised new questions for physicists. The particle was a bit lighter than some of its interactions with other elementary particles would have predicted, meaning that either someone goofed up on the math or there's more than one type of Higgs — perhaps including a heavier Higgs that hasn't been discovered. Physicists are now using the LHC to search for these possible heavy Higgs. 

Lucas Taylor/CMS

After nearly 35 years of zinging past planets and moons, NASA's Voyager 1 probe made history in 2013, when scientists announced that the spacecraft had officially left the solar system in August 2012. 

The probe was launched from Earth in 1977 and spent the next decade exploring Jupiter, Saturn, Uranus, Neptune and their moons. In 2013, data sent back from the probe suggested changes in electron density around Voyager 1 — a major clue that the spacecraft had left the bounds of the solar system. Voyager 1 will continue to send information back to Earth about interstellar space until about 2025. After that, it's set for a long, quiet retirement in deep space, with the possibility that maybe, someday, some alien life-form will notice the little probe and its golden record, a time capsule that holds images of people, maps of our solar system and other clues to the existence of civilization on Earth. 

2014: Gravitational Waves

Before 2014, scientists had only indirect evidence of the Big Bang, the theory that describes a mind-boggling expansion of space that occurred 13.8 billion years ago and gave birth to our universe. But in 2014, for the first time, scientists observed direct evidence of this cosmic expansion, what some called a "smoking gun" for the beginning of the universe. 

This evidence came in the form of gravitational waves, literal ripples in space-time left over from the first fraction of a second after the Big Bang. These ripples generated changes in the polarization in the cosmic microwave background, which is radiation left over from the early universe. The polarization changes are called B-modes. It was these B-modes that scientists detected using the Background Imaging of Cosmic Extragalactic Polarization 2 (BICEP2) telescope in Antarctica. 

Since then, gravitational waves have continued to reveal mysteries of the universe, such as the dynamics of the collisions of black holes and crashes between neutron stars. Gravitational waves may even help to finally pin down just how fast the universe is expanding. 

2015: First CRISPR editing of human embryos

Possibly the biggest biomedical story of the decade is the emergence of a gene-editing technology called CRISPR from relative obscurity. This technology arises from the natural defense mechanisms of some bacteria; it's a series of repetitive gene sequences tied to an enzyme called Cas9 that acts like a pair of molecular scissors. The gene sequences can be edited to put a bull's-eye on a particular segment of DNA, directing the Cas9 enzyme to go in and start snipping.

Using this system, scientists can easily erase and insert bits of DNA in living organisms, an ability with obvious implications for curing genetic diseases — and possibly leading to custom-made babies. The first step along this potential road was taken in 2015, when scientists at Sun Yat-sen University in China announced that they'd made the first-ever genetic modifications to human embryos using CRISPR. The embryos weren't viable, and the procedure was only partially successful — but the experiment was the first to push an ethical line that the scientific community is debating to this day. 

2016: Exoplanet Discovered in a Habitable Zone

Earth's closest exoplanet neighbor, discovered in 2016, is not only a mere 4.2 light-years away — it has the potential to host life. 

That doesn't mean that the planet, dubbed Proxima b, is sure to be habitable, but it resides in the habitable zone of its star, meaning it orbits its star at a distance that would allow liquid water to exist on the planet's surface. The planet orbits Proxima Centauri; wobbles in that star's movements as the planet passed by hinted atProxima b's existence. 

Since the discovery, scientists have observed high-radiation superflares from Proxima Centauri blasting the exoplanet, drastically reducing the chances that life could survive on Proxima b. However, they've also found that there may be more planets orbiting near Proxima b. 

2017: Oldest Homo sapiens fossils push species back 100,000 years

How long has Homo sapiens roamed the planet? A discovery announced in 2017 pushed the timing back to 300,000 years. 

That's 100,000 years longer than had previously been believed. Researchers found the 300,000-year-old bones in a cave in Morocco, where at least five individuals may have taken shelter during a hunt. The discovery site — in northern Africa, not eastern Africa, where the previous oldest Homo sapiens fossils were found — hints that our species may not have evolved first in eastern Africa and then later radiated elsewhere. Instead, Homo sapiens  might have evolved all across the continent. 

2018: First living CRISPR babies

A mere three years after the first editing of nonviable human embryos with CRISPR, someone crossed another gene-editing line. This time, a Chinese scientist named Jiankui He announced that he'd edited the genomes of two embryos that were then implanted via IVF (in vitro fertilization) into the mother’s womb and born: twin girls who are the world's first CRISPR babies.

The edit he made was to a gene called CCR5 — a change that, theoretically, should make the children less vulnerable to contracting HIV. Many scientists were appalled that He would take the step of gene editing in this context, particularly given the available and less technologically intense methods of avoiding HIV (such as preventive antiretroviral treatment). Later, data released by the researchers suggested that they'd actually induced a previously unknown mutation in the girls rather than reproducing a known mutation. 

The potential side effects for the girls are still unknown, as is the fate of the scientist who did the editing. In January 2019, the The New York Times reported that He was likely to face criminal charges in China, though it was unclear under what laws he could be charged.

2019: First Black Hole Image

Black holes have always been an astronomical fascination: We know they're there, but because light can't escape from beyond their event horizons, they're also sort of invisible. 

Until this year: For the first time, scientists captured an image of a black hole. The portrait subject was black hole at the center of the Messier 87 galaxy that is as wide as our entire solar system. The picture looks like a glowing doughnut of matter surrounding an abyss of blackness; this is the dust and gas orbiting the black hole's point of no return. The discovery earned the researchers involved the 2020 Breakthrough Prize, one of the most prestigious awards in science. They're now working to capture not just images, but movies, of black holes. 

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Originally published on Live Science.

In the first clinical trial of its kind, researchers used the gene-editing tool CRISPR to fine-tune the DNA of people's immune cells, in hopes of fighting cancer. 

Now, preliminary data from the trial suggest that this technique is safe for use in cancer patients. 

"This is proof that we can safely do gene editing of these cells," study co-author Dr. Edward Stadtmauer, a professor of oncology at the University of Pennsylvania, told the Associated Press. 

Still, "this treatment is not ready for prime time," Stadtmauer added in an interview with NPR. "But it is definitely very promising." 

So far, only three patients have received the pioneering therapy — two with a blood cancer called multiple myeloma and one with sarcoma, a connective-tissue cancer, according to a statement from the University of Pennsylvania. Researchers were able to safely remove, edit and return the cells to patients' bodies. Safety was measured in terms of side effects, and the authors found that there were no serious side effects from the treatment. 

A Phase I clinical trial, like this one, usually only includes a handful of patients, according to the American Cancer Society. The small trial aims to determine how the body reacts to a new drug and whether patients experience any adverse reactions. Phase I trials don't address whether a drug actually works to treat a condition — that question crops up in later trials. As it stands, the CRISPR study suggests that the new cancer therapy is at least safe for three people, barring more data to come.    

"I'm just so excited about this," Jennifer Doudna, a biochemist at the University of California, Berkeley, whose team first discovered and developed the CRISPR technique, told NPR. (Doudna was not involved in the current study.)

Related: 10 Amazing Things Scientists Just Did with CRISPR

CRISPR allows scientists to cut specific snippets of DNA from a cell's genetic code and paste in new ones if desired. Stadtmauer and his colleagues applied this technique to T cells, a type of white blood cell that attacks diseased and cancerous cells in the body. Cancer uses several tricks to slip under the T-cell radar, but using CRISPR, researchers aim to help the immune cells spot elusive tumors and take them down. 

The technique resembles another cancer therapy, known as "CAR T", which also equips immune cells with new tools to latch onto tumors but doesn't use CRISPR, according to the National Cancer Institute. 

In the new study, scientistsfirst used CRISPR to snip three genes from the immune cells' DNA. Two of the genes contain instructions to build structures on the cell surface that had prevented the T cells from binding to tumors properly, according to the university statement. The third gene provided instructions for a protein called PD-1, a kind of "off switch" that cancer cells flip to stop immune cell attacks.

"Our use of CRISPR editing is geared toward improving the effectiveness of gene therapies, not editing a patient's DNA," co-author Dr. Carl June, a professor of immunotherapy at the University of Pennsylvania, said in the statement.

With these adjustments made, the researchers used a modified virus to place a new receptor on the T cells before injecting them back into patients. The new receptor should help the cells locate and attack tumors more efficiently. So far, the edited cells have survived inside patients' bodies and have been multiplying as intended, Stadtmauer told the AP. However, it's unclear if and when the cells will launch a lethal attack on the patients' cancer, he added.

Related: 7 Odd Things That Raise Your Risk of Cancer (and 1 That Doesn't)

Two to three months after treatment, one patient's cancer continued to worsen, as it had before the treatment, and another patient remained stable, the AP reported. The third patient received treatment too recently for her reaction to be assessed. Meanwhile, the researchers aim to recruit 15 more patients to the trial to assess both the technique's safety and its efficacy in taking down cancer. The early safety results will be presented next month at a meeting of the American Society of Hematology in Orlando, Florida, according to the university statement. 

"We'll want more patients and a longer follow-up to really make a call that the use of CRISPR is safe. But the data are certainly encouraging," Dr. Michel Sadelain, an immunologist at the Memorial Sloan Kettering Cancer Center in New York, told NPR. "So far, so good — but [it's] still early."

The study was funded in part by the biotech company Tmunity Therapeutics. Some of the study authors and the University of Pennsylvania have a financial stake in this company, the AP reported.

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Originally published on Live Science.

A widely publicized study suggesting that the first gene-edited babies could have shorter life spans has been retracted due to crucial errors in the analysis.

The study, which was originally published June 3 in the journal Nature Medicine, showed that a genetic mutation that protects against HIV infection was linked with an increased risk of death before age 76, Live Science previously reported. This mutation, known as CCR5-delta 32, is the same genetic tweak that a Chinese scientist attempted to make in twin babies born last year —  in a highly controversial experiment using CRISPR technology.

At the time the study was published, the authors of the Nature Medicine paper said that the work underscored concerns about the use of gene-editing technology in humans.

However, technical errors in the Nature Medicine paper caused the authors to undercount the number of people in their population who had the CCR5-delta 32 mutation, Nature News reported. The error directly affects the main result and thus invalidates the conclusion, according to the retraction note published Oct. 8 in Nature Medicine.

"I feel I have a responsibility to put the record straight for the public," study lead author Rasmus Nielsen, a population geneticist at the University of California, Berkeley, told Nature News.

Still, the retraction of the current paper doesn't mean that edits to the CCR5 gene, like the ones attempted in the CRISPR babies, are harmless.

"It's very reasonable to expect that [CCR5] might have a valuable function that we just don't know how to measure. It seems very unwise to edit it out,"  David Reich, a population geneticist at Harvard Medical School, who was not involved in the original study, told Nature News.

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Originally published on Live Science. 

Scientists in China have used CRISPR gene-editing technology to treat a patient with HIV, but it didn't cure the patient, according to a new study.

The work, published today (Sept. 11) in The New England Journal of Medicine, marks the first time this particular gene-editing tool has been used in an experimental HIV therapy, according to the authors, from Peking University in Beijing.

Even though the treatment didn't control the patient's HIV infection, the therapy appeared safe — the researchers did not detect any unintended genetic alterations, which have been a concern in the past with gene therapies.

Related: 10 Amazing Things Scientists Just Did with CRISPR

Experts praised the work as an important first step toward being able to use CRISPR, a tool that allows researchers to precisely edit DNA, to help patients with HIV.

"They did a very innovative experiment on a patient, and it was safe," said Dr. Amesh Adalja, an infectious disease specialist and a senior scholar at The Johns Hopkins Center for Health Security in Baltimore, who was not involved in the study. "It should be viewed as a success."

The new study is very different from the unrelated, controversial case of a Chinese scientist who used CRISPR to edit the genomes of twin babies in an attempt to make them resistant to HIV. In that case, the Chinese scientist edited the DNA of embryos, and these gene alterations can be passed down to the next generation. In the new study, the DNA edits were made in adult cells, which means they cannot be passed on. 

The study involved a single patient with HIV who had also developed leukemia, a type of blood cancer. As a result, the patient needed a bone marrow transplant. So the researchers used this opportunity to edit DNA in bone marrow stem cells from a donor before transplanting the cells into the patient. 

Specifically, the researchers used CRISPR to delete a gene known as CCR5, which provides instructions for a protein that sits on the surface of some immune cells. HIV uses this protein as a "port" to get inside cells. 

The small percentage of people who naturally have a mutation in the CCR5 gene are resistant to HIV infection. 

What's more, the only two people in the world thought to be "cured" of HIV — known as the Berlin patient and the London patient — had the virus seemingly eliminated from their bodies after receiving bone marrow transplants from donors who had the natural CCR5 mutation.

However, since it can be difficult to find bone marrow donors with this particular mutation, the researchers hypothesized that genetically edited donor cells might have the same effect.

One month after the patient received the transplant, his leukemia was in complete remission. Tests also showed that the genetically edited stem cells were able to grow in his body and produce blood cells. These genetically edited cells persisted in the patient's body for the entire 19 months that he was followed.

In addition, the researchers did not see any "off-target" effects of the CRISPR gene editing, meaning the tool did not introduce genetic changes in places where it wasn't intended or could cause problems.

However, when the patient briefly stopped talking his HIV medications as part of the study, levels of the virus increased in his body, and he had to start taking his medication again. This response was unlike that of the Berlin and London patients, who were able to remain HIV free without taking medications.

The low response in the Beijing patient likely occurred, in part, because the gene-editing process wasn't very efficient. In other words, the researchers weren't able to delete the CCR5 gene in all of the donor cells. 

Still, "we believe that this strategy [is] a promising approach for gene therapy" for HIV, study senior author Hongkui Deng, a professor of cell biology at Peking University, told Live Science.

One potential way to improve the gene-editing process would be to start with so-called pluripotent stem cells, which have the potential to form any cell type in the body, Deng said. The researchers would edit these cells with CRISPR to inactivate CCR5, and then coax the cells into becoming the blood stem cells used for bone marrow transplants. This strategy could result in a greater number of donor cells having the edited CCR5 gene, Deng said.

It's important to note that this type of gene-therapy treatment was only possible because the patient also happened to need a bone marrow transplant, and so it's not something that could be applied in its current form to the average HIV patient.

"These aren't ordinary individuals with HIV," Adalja told Live Science. "These are people who have HIV and also have a need for a bone marrow transplant," he said. Adalja added that a bone marrow transplant can be a dangerous procedure.

Although the CCR5 mutation protects against HIV, some studies suggest that the genetic modification might have other harmful effects. For example, a study published earlier this year found that the natural CCR5 mutation was linked with an increased risk of early death. However, the researchers note that with their HIV treatment, they are modifying the CCR5 gene only in blood stem cells, which wouldn't affect the CCR5 gene in other tissues in the body.

In an editorial accompanying the study, Dr. Carl June, director of the Center for Cellular Immunotherapies at the University of Pennsylvania Perelman School of Medicine, said that future research using CRISPR for HIV should follow participants for even longer periods, because harmful effects from gene therapy, such as cancer, may take years to show up. June, who was not involved in the new study, previously conducted gene therapy for HIV, although not with CRISPR.

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Originally published on Live Science. 

The first study to test the gene-editing technology CRISPR inside the human body is about to get underway in the United States, according to news reports.

The study plans to use CRISPR to treat an inherited eye disorder that causes blindness, according to the Associated Press.

People with this condition have a mutation in a gene that affects the function of the retina, the light-sensitive cells at the back of the eye that are essential for normal vision. The condition is a form of Leber congenital amaurosis, one of the most common causes of childhood blindness that affects about 2 to 3 newborns out of every 100,000, according to the National Institutes of Health.

The treatment will correct the mutation using CRISPR, a tool that allows researchers to precisely edit DNA in a specific spot, the AP reported.

Researchers will use an injection to deliver the treatment directly to the light-sensitive cells, according to a statement from Editas Medicine, the company that is conducting the study along with Allergan.

The trial will enroll a total of 18 patients, both children (ages 3 and up) and adults.

The new study is different from the controversial research of a Chinese scientist who used CRISPR to edit the genomes of twin babies last year. In that case, the Chinese scientist edited the DNA of embryos, and these gene alterations could be passed down to the next generation, the AP reported. In the new study, the DNA edits made in the children and adults cannot be passed down to their offspring, the AP said.

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Originally published on Live Science.

For the first time, researchers have used genetic engineering to almost completely eliminate male babies in the womb of a mammal— though that mammal was a mouse. And don't expect the treatment to wind up in an IVF clinic near you — the process also required genetically altering both parents.

The study was published July 1 in the journal EMBO Reports.

The researchers used CRISPR to selectively target and snip genes that code for three enzymes essential to embryonic development. The end result? A 95% reduction in the number of male babies born. [10 Amazing Things Scientists Just Did with CRISPR]

The researchers were able to suppress the enzymes in just male embryos by targeting the system most mammals use to determine sex.

Mice, like humans, inherit one sex chromosome from each parent. The mother contributes an X chromosome, and the father determines the offspring's sex by contributing either an X or a Y chromosome. Embryos that inherit an XX combination grow into females, and those that inherit an XY combination develop into males.

In this study, the researchers exploited the XY sex-determination system by inserting one part of the instructions to clip the enzymes' DNA on the X chromosome and the other half of the instructionson the Y chromosome. Female offspring would thus make two copies of the same half of the instructions for snipping the enzymatic DNA, which is harmless. In male embryos, however, the two halves of the instructions fit together and code for the molecular scissors that snip the critical enzyme DNA. That way, XX offspring (that is, females) were unharmed, while nearly all XY offspring failed to develop past the halfway point in the 20-day pregnancy of the mouse.

Anu Bashamboo, senior group leader in the Unit of Human Developmental Genetics at the Institut Pasteur in Paris, acknowledges the study as a breakthrough but notes the procedures need fine-tuning.

"It is clear from the data the system is still not perfect," Bashamboo, who was not involved in the study, told Live Science. "The protocols and experimental design need to be optimized to ensure the elimination of all male lineages as early as possible after fertilization."

And some of the males survived and one suffered severe deformities, Bashamboo added.

Agricultural uses

The researchers presented their study as a proof of concept that clears the way for use in agricultural settings, where either male or female livestock are preferred.

"The next step is to transfer it to other animals besides mice — like cows, goats and chickens," Qimron told Live Science.

For instance, in industrial farming, female chicks are kept as eventual egg-laying hens, while male chicks are killed in the billions, often gassed, electrocuted or ground up alive within hours of birth, National Geographic reported.

"It can also be the other way, because in the beef industry males are more wanted because they have more muscles and produce more meat," Qimron said.

Though their current work is focused on eliminating male offspring, the researchers believe they could engineer a similar system that prevents the development of female embryos.

Human potential?

Qimron said the method could "in principle" be used to select for sex in human offspring, but he is not worried that the research will lead to unethical use in humans.

"I find it hard to envision such a malpractice," he said.

Jiankui He's 2018 claim to have produced genetically edited infants has heightened global concern about the possibility of manipulating the genomes of embryos. Regulators in the United States and Europe have placed stark limits on what geneticists can do in humans.

"There are strict regulation[s] and guidelines in place for genetic editing of human embryos, and implantation of modified embryos is strictly forbidden as per FDA regulations," Bashamboo said.

What's more, this system requires genetically altering the parents as well.

Though he thinks it's unlikely, Qimron doesn't rule out the possibility that his work might be used somewhere in the world.

"If a mad ruler in some closed country decides that he wants two lines of human — one producing soldiers and the other producing females for other purposes — it may happen with this technology," he said. "The proof of concept is there."

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Originally published on Live Science.

UPDATE: On Oct. 8, the journal Nature Medicine retracted the paper described in the article below due to crucial errors in the analysis. The errors invalidate the conclusion that the first gene-edited babies could have shorter life spans. Live Science published the original article (below) on June 3.

When a Chinese scientist announced last year that he had used CRISPR technology to edit the genomes of twin babies in an attempt to make them resistant to HIV infection, the move was decried as both unethical and potentially harmful to the babies.

Now, a new study underscores some of these concerns: The results suggest that the genetic mutation that was attempted in the CRISPR babies is tied to an increased risk of early death.

Specifically, the study found that this mutation — which is known as CCR5-delta 32 and which occurs naturally in a small percentage of people — is tied to a 20% increase in the risk of death before age 76. [9 Absolutely Evil Medical Experiments]

"Beyond the many ethical issues involved with the CRISPR babies … it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do," study senior author Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley, said in a statement. In the case of the CCR5-delta 32 mutation, "it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it."

Shorter lives

CCR5 is a protein that sits on the surface of some immune cells. It just so happens that HIV uses this protein as a port to get inside those cells. But about 10% of people of European descent have a mutation in the CCR5 gene that alters this protein and protects against HIV infection.

Chinese scientist He Jiankui wanted to introduce this mutation into the genomes of the twin babies using the gene-editing technology CRISPR-Cas9. The available evidence suggests that He wasn't able to exactly replicate the natural mutation, but the scientist introduced a similar mutation that effectively would have the same result: an inactivated CCR5 protein.

Some previous studies have suggested that although the CCR5 mutation protects against HIV, it could have additional, harmful effects, such as an increased susceptibility to death from the flu.

In the new study, the researchers analyzed information from more than 400,000 people ages 41 to 78 in the United Kingdom whose health records and genomic data are part of a database known as the UK Biobank. The researchers looked for people who were "homozygous" for the CCR5 mutation, meaning that both of the person's copies of the CCR5 gene were mutated. (A person has two copies of every gene.)

People with two mutated copies of CCR5 were 20% less likely to reach the age of 76 compared with those who had one mutated copy or no mutated copies of this gene. In addition, the researchers found that fewer people than expected who had this mutation were enrolled in the database, suggesting that these individuals had died younger at a higher rate than the general population, the researchers said.

The new finding "underscores the idea that introduction of new or derived mutations in humans using CRISPR technology, or other methods for genetic engineering, comes with considerable risk, even if the mutations provide a perceived advantage," the researchers wrote in their paper, published today (June 3) in the journal Nature Medicine.

"In this case, the cost of resistance to HIV may be increased susceptibility to other, and perhaps more common, diseases," the researchers concluded.

• 10 Amazing Things Scientists Just Did with CRISPR
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Originally published on Live Science.

Genetic modification is the process of altering the genetic makeup of an organism. This has been done indirectly for thousands of years by controlled, or selective, breeding of plants and animals. Modern biotechnology has made it easier and faster to target a specific gene for more-precise alteration of the organism through genetic engineering.

The terms "modified" and "engineered" are often used interchangeably in the context of labeling genetically modified, or "GMO," foods. In the field of biotechnology, GMO stands for genetically modified organism, while in the food industry, the term refers exclusively to food that has been purposefully engineered and not selectively bred organisms. This discrepancy leads to confusion among consumers, and so the U.S. Food and Drug Administration (FDA) prefers the term genetically engineered (GE) for food.

A brief history of genetic modification

Genetic modification dates back to ancient times, when humans influenced genetics by selectively breeding organisms, according to an article by Gabriel Rangel, a public health scientist at Harvard University. When repeated over several generations, this process leads to dramatic changes in the species.

Dogs were likely the first animals to be purposefully genetically modified, with the beginnings of that effort dating back about 32,000 years, according to Rangel. Wild wolves joined our hunter-gatherer ancestors in East Asia, where the canines were domesticated and bred to have increased docility. Over thousands of years, people bred dogs with different desired personality and physical traits, eventually leading to the wide variety of dogs we see today.

The earliest known genetically modified plant is wheat. This valuable crop is thought to have originated in the Middle East and northern Africa in the area known as the Fertile Crescent, according to a 2015 article published in the Journal of Traditional and Complementary Medicine. Ancient farmers selectively bred wheat grasses beginning around 9000 B.C. to create domesticated varieties with larger grains and hardier seeds. By 8000 B.C., the cultivation of domesticated wheat had spread across Europe and Asia. The continued selective breeding of wheat resulted in the thousands of varieties that are grown today.

Corn has also experienced some of the most dramatic genetic changes over the past few thousand years. The staple crop was derived from a plant known as teosinte, a wild grass with tiny ears that bore only a few kernels. Over time, farmers selectively bred the teosinte grasses to create corn with large ears bursting with kernels.

Beyond those crops, much of the produce we eat today — including bananas, apples and tomatoes — has undergone several generations of selective breeding, according to Rangel.

The technology that specifically cuts and transfers a piece of recombinant DNA (rDNA) from one organism to another was developed in 1973 by Herbert Boyer and Stanley Cohen, researchers at the University of California, San Francisco, and Stanford University, respectively. The pair transferred a piece of DNA from one strain of bacteria to another, enabling antibiotic resistance in the modified bacteria. The following year, two American molecular biologists, Beatrice Mintz and Rudolf Jaenisch, introduced foreign genetic material into mouse embryos in the first experiment to genetically modify animals using genetic engineering techniques.

Researchers were also modifying bacteria to be used as medications. In 1982, human insulin was synthesized from genetically engineered E. coli bacteria, becoming the first genetically engineered human medication approved by the FDA, according to Rangel.

Genetically modified food

There are four primary methods of genetically modifying crops, according to The Ohio State University:

• Selective breeding: Two strains of plants are introduced and bred to produce offspring with specific features. Between 10,000 and 300,000 genes can be affected. This is the oldest method of genetic modification, and is typically not included in the GMO food category.
• Mutagenesis: Plant seeds are purposely exposed to chemicals or radiation in order to mutate the organisms. The offspring with the desired traits are kept and further bred. Mutagenesis is also not typically included in the GMO food category.
• RNA interference: Individual undesirable genes in plants are inactivated in order to remove any undesired traits.
• Transgenics: A gene is taken from one species and implanted in another in order to introduce a desirable trait.

The last two methods listed are considered types of genetic engineering. Today, certain crops have undergone genetic engineering to improve crop yield, resistance to insect damage and immunity to plant diseases, as well as to introduce increased nutritional value, according to the FDA. In the market, these are called genetically modified, or GMO crops.

"GMO crops presented a lot of promise in solving agricultural issues," said Nitya Jacob, crop scientist at Oxford College of Emory University in Georgia.

The first genetically engineered crop approved for cultivation in the U.S. was the Flavr Savr tomato in 1994. (In order to be grown in the U.S., genetically modified foods must be accepted by both the Environmental Protection Agency (EPA) and the FDA.) The new tomato had a longer shelf-life thanks to the deactivation of the gene that causes tomatoes to start becoming squishy as soon as they're picked. The tomato was also promised to have enhanced flavor, according to the University of California Division of Agriculture and Natural Resources.

Today, cotton, corn and soybeans are the most common crops grown in the U.S. Nearly 93 percent of soybeans and 88 percent of corn crops are genetically modified, according to the FDA. Many GMO crops, such as modified cotton, have been engineered to be resistant to insects, significantly reducing the need for pesticides that could contaminate groundwater and the surrounding environment, according to the U.S. Department of Agriculture (USDA).

In recent years, the widespread cultivation of GMO crops has become increasingly controversial.

"One concern is the impact of GMOs on the environment," Jacob said. "For example, pollen from GMO crops can drift to fields of non-GMO crops as well as into weed populations, which can lead to non-GMOs acquiring GMO characteristics due to cross-pollination."

A handful of large biotechnology companies have monopolized the GMO crop industry, Jacob said, making it difficult for individual, small-scale farmers to make a living. However, while some farmers may be driven out of business, those that work with the biotech companies may reap the economical benefits of increased crop yields and reduced pesticide costs, the USDA has said.

Labeling of GMO food is important to a majority of people in the U.S., according to polls conducted by Consumer Reports, The New York Times and The Mellman Group. People strongly in favor of GMO labeling believe that consumers should be able to decide whether they wish to purchase genetically modified foods.

However, Jacob said, there is no clear scientific evidence that GMOs are dangerous for human health.

Genetically modifying animals and humans

Today, livestock are often selectively bred to improve growth rate and muscle mass and encourage disease resistance. For example, certain lines of chickens raised for meat have been bred to grow 300 percent faster today than they did in the 1960s, according to a 2010 article published in the Journal of Anatomy. Currently, no animal products on the market in the U.S., including chicken or beef, are genetically engineered, and, therefore, none are classified as GMO or GE food products.

For the past several decades, researchers have been genetically modifying lab animals to determine ways the biotechnology could one day help in treating human disease and repairing tissue damage in people, according to the National Human Genome Research Institute. One of the newest forms of this technology is called CRISPR (pronounced "crisper").

The technology is based on the ability of the bacterial immune system to use CRISPR regions and Cas9 enzymes to inactivate foreign DNA that enters a bacterial cell. The same technique makes it possible for scientists to target a specific gene or group of genes for modification, said Gretchen Edwalds-Gilbert, associate professor of biology at Scripps College in California.

Researchers are using CRISPR technology to search for cures for cancer and to find and edit single pieces of DNA that may lead to future diseases in an individual. Stem cell therapy could also make use of genetic engineering, in the regeneration of damaged tissue, such as from a stroke or heart attack, Edwalds-Gilbert said.

In a highly controversial study, at least one researcher claims to have tested the CRISPR technology on human embryos with the goal of eliminating the potential for certain diseases. That scientist has faced harsh scrutiny and was placed under house arrest in their home country of China for some time.

The moral dilemma

The technology may be available, but should scientists pursue genetic modification studies in humans? It depends, said Rivka Weinberg, a professor of philosophy at Scripps College.

"When it comes to something like a [new] technology, you have to think about the intention and different uses of it," Weinberg said.

The majority of medical trials for treatments that make use of genetic engineering are performed on consenting patients. However, genetic engineering on a fetus is another story.

"Experimentation on human subjects without their consent is inherently problematic," Weinberg said. "There are not only risks, [but also] the risks are not mapped out. We don't even know what we are risking."

If the next-generation technology were available and shown to be safe, the objections to testing it in humans would be minimal, Weinberg said. But that's not the case.

"The big problem with all of these experimental technologies is that they are experimental," Weinberg said. "One of the main reasons why people were so horrified by the Chinese scientist who used CRISPR technology on embryos is because it is such an early stage of experimentation. It is not genetic engineering. You are just experimenting on them."

The vast majority of the proponents for genetic engineering realize that the technology isn't ready to be tested on humans yet, and state that the process will be used for good. The goal of genetic modification, Jacob said, "has always been to tackle problems currently facing human society."

Further reading:

• Read answers to the World Health Organization's FAQ's about GMO foods.
• See "How to Make a GMO" by Chelsea Powell, on Harvard University's graduate student blog.
• Read more on human genetic modification from the Center for Genetics and Society.

The researcher who created genetically modified babies behaved improperly, authorities in China said yesterday (Jan. 21).

Jiankui He, the Chinese scientist whose efforts produced the world's first gene-edited babies, did so through forgery and subterfuge, deliberately skirting the proper channels in the pursuit of personal fame, officials in China told Xinhua News (China's state-run press agency).

A task force from the Health Commission of China in Guangdong Province conducted an investigation into He's activities, according to Reuters. In a preliminary report, authorities stated that He "intentionally dodged supervision" to produce genetically manipulated infants, an action that was "explicitly banned" by Chinese regulations, Xinhua reported. [10 Amazing Things Scientists Just Did with CRISPR]

He drew severe criticism from scientists around the world in November 2018, when he announced the birth of twin girls whose embryos he had genetically modified. Using the gene-editing tool CRISPR/Cas9, He removed a gene linked to HIV. However, many criticized his work as premature and irresponsible, with unknown future repercussions for the twins.

Investigators found that He's work "seriously violated ethical principles and scientific integrity," Xinhua News reported. Technologies used for the experiments did not have adequate safety and effectiveness guarantees, and He presented a fake ethical review certificate when he recruited eight volunteer couples for experiments conducted from March 2017 to November 2018, according to the investigation.

For the study, He selected couples in which the men tested positive for HIV, while the women tested negative. In China, people who are HIV positive are prohibited from medically assisted reproduction; to sidestep that regulation, He submitted blood tests from volunteers who did not have HIV rather than using blood from his HIV-infected subjects, Xinhua News reported.

In addition to He, all organizations and personnel involved in the research "will receive punishment according to laws and regulations," according to Xinhua News.

Southern University of Science and Technology, where He conducted his experiments, rescinded He's contract and terminated his research and teaching activities "effective immediately," according to a statement released yesterday (Jan. 21) on the university website.

Though gene editing has significant potential to benefit human health, He's experiment with viable human embryos appeared to many to be "a poorly designed and regrettable effort to win a 'race' and grab attention," Dimitri Perrin, a senior lecturer and an expert in gene editing and CRISPR technology at Queensland University of Technology (QUT) in Australia, said in a statement.

"This latest report confirms what was feared," Perrin said. "The long-term effects are still unclear. This experiment should not have taken place, and must not open the door to other similar studies at this stage."

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Originally published on Live Science.

A Chinese researcher who ignited controversy in 2018 after claiming to have created the first genetically edited human infants was recently spotted in Shenzhen, China.

This is the first reported sighting of Jiankui He, an associate professor at the Southern University of Science and Technology of China, in weeks, The New York Times reported Dec. 28.

He was photographed while on the fourth-floor balcony of an apartment building — a university guesthouse — and was seen talking to a woman thought to be his wife. The apartment appeared to be monitored by "a dozen unidentified men," according to The Times. [10 Amazing Things Scientists Just Did with CRISPR]

He last appeared in public in November at the Second International Summit on Human Genome Editing in Hong Kong, where he spoke about his research and fielded outraged queries from the global scientific community. Since then, He's whereabouts have been uncertain, though rumors suggested he was under house arrest, The Times reported.

According to He, the babies — twin girls named Lulu and Nana — were genetically modified as embryos with a gene-editing tool called CRISPR-Cas9; He used CRISPR to snip out a gene and thereby render the infants resistant to HIV, he said in a video posted to YouTube on Nov. 25.

However, scientists around the world promptly denounced He's actions as highly irresponsible and potentially harmful to the babies. Genes perform more than one function and act in concert with many other genes, and it is not yet possible to say for sure that excising a single gene can be done safely and with no future consequences for human health, Live Science previously reported.

In fact, the gene that He deleted in the embryos — CCR5 — is known to assist in white blood cell function, Mazhar Adli, a geneticist at the University of Virginia School of Medicine, told Live Science. He may also have failed to adequately inform the babies' parents about potential risks prior to obtaining their consent to the gene editing.

Following the release of the video, He's university quickly denounced his research, issuing a statement the next day stating that it was "deeply shocked" at what He had done and claiming that He had been on unpaid leave from the university since February.

In the weeks after the Hong Kong conference and the launch of an investigation by the Chinese government, He's location was uncertain and university representatives denied that he was being held under house arrest on university grounds, Newsweek reported.

However, He's current location is a university hotel that houses visiting scholars, according to The Times. Four guards were stationed outside the door of He's apartment, but their affiliation is unknown. Neither Shenzhen's police department nor the university responded to The Times' requests for comments, The Times reported.

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Original article on Live Science.

A kid in France transcribed parts of the Hebrew book of Genesis and the Arabic-language Quran, into DNA and injected them into his body — one text into each thigh.

Adrien Locatelli, a 16-year-old high school student, posted a paper Dec. 3 on the preprint server OS, in which he claimed, "It is the first time that someone injects himself macromolecules developed from a text."

Locatelli, a student at the boarding school Lycée les Eaux Claires in Grenoble, France, told Live Science that he didn’t need any special equipment for his project. [10 Amazing Things Scientists Have Done with CRISPR]

"I just needed to buy saline solution and a syringe because VectorBuilder sent me liquid and ProteoGenix sent me powder," he told Live Science.

VectorBuilder is a company that creates viruses that can sneak DNA strands into cells for gene-editing purposes. ProteoGenix synthesizes, among other things, custom strands of DNA. Both companies primarily serve scientists, but their products are available to anyone who purchases them.

If you saw the texts that Locatelli injected into his body, they wouldn’t look like much. DNA is just a long molecule that can store information. Mostly, it stores the information living things use to go about their business. But it can be used to store just about any kind of information that can be written down.

Locatelli’s method for translating the texts into DNA was straightforward, if a bit crude. DNA encodes its information using repeating strings of four nucleotides, which scientists have abbreviated as A, G, T and C. Locatelli lined up each letter of the Hebrew and Arabic alphabets (which correspond closely to each other) with a nucleotide, so each nucleotide represented more than one letter. So if you were to write a Hebrew sentence using his scheme, every aleph, vav, yud, nun, tsade, and tav would become a G. Every dalet, khet, ayin, and resh would become a T. And so on.

So, is this a good idea? Locatelli thinks so.

"I did this experiment for the symbol of peace between religions and science," he said, adding, "I think that for a religious person it can be good to inject himself his religious text."

Locatelli said he didn’t experience any significant health problems following the procedure, though he reported some "minor inflammation" around the injection site on his left thigh for a few days.

This account of only minimal complications fits with what Sriram Kosuri, a professor of biochemistry at UCLA, told Live Science.

"[The injected texts] are unlikely to do anything except possibly cause an allergic reaction. I also don't know how likely the rAAV vector would be to make actual virus, given the way he injected. I honestly don't know enough about the vector he used and how he did it (details are scarce)," he wrote in a message.

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Originally published on Live Science.