Alan Brown is a writer and blogger for the Kavli Foundation. Read more perspective pieces on the Kavli Expert Voices landing page. Brown contributed this article to Live Science's Expert Voices: Op-Ed & Insights.

Microbes could soon be at the top of the world's big-science list. Late last year, a consortium of scientists from 50 U.S. institutions proposed the "Unified Microbiome Initiative," a national effort to advance our understanding of microbiomes, communities of single-celled organisms such as bacteria, viruses and fungi. 

With a unified focus, researchers hope to learn how microbiomes could not only cure infectious diseases and reduce antibiotic drug resistance, but also reclaim exhausted farmland, cut fertilizer and pesticide use, and produce new fuels and carbon-based chemicals.

Reaching those ambitious goals will require an equally ambitious effort to develop new tools and collaborations, building on breakthroughs in the analysis of microbial DNA, proteins and metabolites. Such analyses show that microbial communities can be incredibly diverse , including hundreds of thousands of different microbial species, all interacting with one another. In the human gut, those microbes aid digestion, but they may also impact obesity, allergies and even brain development. Beyond our bodies, microbes created the Earth's oxygen-rich atmosphere, and enable plant and ocean life to thrive.

While today's tools can tell us a great deal about the molecules in microbial communities, they cannot explain the function of these molecules and how they enable microorganisms to work together. Only with that level of understanding, will scientists be able to harness microbiomes to improve human health and the environment.

Recently, The Kavli Foundation hosted a Google+ Hangout about the potential of nature's microbiomes and how we can tap into it. The participants included: 

Janet Jansson is chief scientist of biology in the Earth and Biological Sciences Directorate at Pacific Northwest National Laboratory (PNNL) and sector lead for PNNL research in the Department of Energy's Biological Systems Science Division. She coordinates two of PNNL’s biology programs: the Microbiomes in Transition (MinT) initiative to study how climate and environmental changes impact natural and human microbiomes and the DOE Foundational Scientific Focus Area, Principles of Microbial Community Design.

Rob Knight is the founder of the American Gut Project, an open-access project to survey the digestive system’s microbiome and its effect human health and development. He holds appointments at the University of California, San Diego School of Medicine and Department of Computer Science and Engineering, where he develops bioinformatics systems to classify and interpret large sets of biological data.

Jeff F. Miller is director of the California NanoSystems Institute, a multidisciplinary research organization, and the corresponding author of the consortium’s Science paper. Based at University of California, Los Angeles, Miller holds the Fred Kavli Chair in NanoSystems Sciences and is a professor of Microbiology, Immunology & Molecular Genetics.

Below is a modified transcript of the discussion. Edits and changes have been made by the participants to clarify spoken comments recorded during the live webcast.

The Kavli Foundation: So, let's start with a question. There's been a Cambrian Explosion in microbiome research. Ten years ago, microbiomes were hardly on the map. Last year, 25,000 papers contained the term. Why is this happening now? Is it just because we can read microbial DNA, or are other technologies making this possible?

Jeff Miller: There are a lot of factors that came together to cause this explosion of interest. One, certainly, is the ability to rapidly sequence DNA. And over the past 10 years or so, we've seen a progression of technologies that allow us to characterize microbial communities with increasing resolution and sophistication. But we've also encountered many bottlenecks along the way. And interpreting this massive amount of sequenced data is one of those bottlenecks. 

Rob Knight: I agree. I think it's really the combination of the DNA sequencing tools getting much cheaper, and the computational tools, including the toolkits that we developed, that make the information much more accessible to a broad community of users. I think what we will see in the future are tools that will go beyond taking inventories of species or inventories of genes and instead provide much more insight about how these species and genes function. But that is going to require a whole lot of additional development of both the software and the knowledge base to use that software. 

TKF: Janet, do you have any additional thoughts on that?

Janet Jansson: Yes. With DNA sequencing we get information about the composition of microbiomes, but it's also interesting to know what those microbes are doing. For example, if we could understand their protein or metabolite composition, we could get a better understanding of what they're doing in different kinds of habitats and inside our bodies. There are a lot of developments in these areas, but those tools are still lagging behind the sequencing technologies. 

TKF: So, do we need a major program, a Unified Microbiome Initiative, to develop these capabilities? Couldn't we build on existing technologies or do we need to invent radically new types of science? 

Miller: The likely answer is, "both." There's certainly a lot of room for incremental advances leading to better sequencing technology and the like. But we also need some quantum leaps at the same time. 

The field has progressed rapidly. But we've reached a plateau that has to do with the limitations of the current technologies. We need to be able to see microbial communities where they live, in real time. We want to know what are they doing. What genes are they expressing? What proteins are they making? What metabolites are they synthesizing? How are they responding to each other and their environments? 

Then we need to be able to take all this data and interpret it in a way that allows us to ask questions and formulate new hypotheses that we can test and falsify or prove correct. 

These are really tall orders. They're going to require not only new technologies, but also the input of collaborators in engineering, physics, and chemistry, as well as the life sciences, environmental sciences, computer sciences, and more. 

TKF: I'm curious about the computer science side of it. Rob, you have a joint appointment UC San Diego's medical school and computer science department. Is it such a tall order? I mean, we have big data. Are we going to need something more?

Knight: Well, the issue is that big data and magic are not quite the same thing. There's a lot of advances that need to happen on the algorithm side. In general, machine learning and generic algorithms will give you a good, but not ideal, answer to a particular scientific question. And the more information you can put in at the beginning to tailor those algorithms to your specific problem, the better you'll do. 

The other thing is that although we're producing a tremendous amount of data, we're still limited by the amount of data—it’s still not enough—and by our ability to interpret it. The problem a lot of people are facing right now is that they have collected so much microbial community information. They have over a thousand species that they don't understand. They are listing a million genes they don't understand. Then they are going onto measuring other types of molecules using metatranscriptomics or metaproteomics or metabolomics where, again, they create very large inventories that they also don't understand. 

But even with all that data, we're still limited by the number of samples, and by our ability to annotate and understand those entities. There's a huge role for both existing algorithms that can be applied more effectively as we get more data, and for fundamentally new algorithms as well as new ways of computing that radically change how we think about computation itself. 

TKF: Part of the challenge is that we need a better way to get closer to the inhabitants of metaphorical city I mentioned earlier. It is as if we are looking at that city from space and trying to figure out people's roles when we cannot even see these individuals, isn't it?

Knight: It's a little worse than that. You're flying out there in your UFO, and you just take a big chunk of that city, grind it up, look at all the DNA and chemicals, and try to make sense of it. That can be an effective or ineffective way to understand the city. You will get an understanding of some of the chemical processes that are going on, and some of the genes that are expressed. But you're not going to learn a lot about the sociology or how those organisms communicate.

Jansson: Yes, and another way to tackle that problem is to use simpler model communities. That way, if we don't have the instruments and data tools to deal with these highly complex communities, at least have a model community that will let us study specific interactions.

TKF: In other words, it's easier to study something much simpler? 

Jansson: Yes, at least for now. Full communities are some of the most diverse types of habitats for microorganisms on earth. We go so much data, that we're not limited by the amount of data we produce, but by our ability to process the data. Even with supercomputers, it can take weeks, if not months, to just run all of that data through our computers. 

Knight: With all due respect, I think we're still data limited because we don't have enough samples. 

So, it's as if we had, say, five photos, and we're taking them at higher and higher resolution. That generates a lot of data, but not enough to create a movie. What we really need is, say, 100,000 frames. And no matter how much more information we get out of the smaller number of frames you have, we'll never be able to put that movie together. 

So, that's a lot of what we're facing. Right now, it's so expensive to process each sample, it's really difficult to get enough samples. This is really why we need to be able to read out microbes much, much faster, much, much cheaper. And we also need to use higher and higher resolution techniques, to get that full movie of how the interactions are taking place. 

Jansson: I agree we need more samples. But even then, it's very difficult to process the information from one sample. 

Miller: Right. In fact, we know the functions of only about half of the genes that we detect in these communities. And of the half we think we know, the amount of mis-annotation and improper context annotation, are also significant. So we're trying to put a puzzle together with only some of the pieces. And if you look at small molecules, this situation is even worse. About two percent of the metabolites that are found in the typical microbial community map to known structures. And only a fraction of those two percent are on known biochemical pathways. So we need more information. 

TKF: Those metabolites are involved in bacterial digestion. Are they how bacteria communicate with one another?

Miller: Yes, that how they communicate, and how they acquire energy. They are the waste products they release, and the small molecules they use to compete with other microbes and interact with their environments. And many other things that have yet to be discovered. These small molecules are the language of microbial communities.

TKF: Getting a handle on all this sounds like an imposing research project. But suppose you had these tools today. What is it that you'd like to study? Jeff, you study the evolution of bacteria that cause disease. What would you do with those tools?

Miller: Boy, great question. I think one area that is prime for progress -- and some progress has been made already -- is the idea of taking a community that may be somewhat robust but not really optimal for its environment or host and engineering it so that it has more beneficial properties and fewer non-beneficial properties. 

Doing that really requires an understanding of the ecological principals that govern the community's composition, robustness, response to changes, etcetera. So, being able to reprogram microbial communities is really one of our ultimate goals. 

There are various steps along that pathway that one can imagine. But we're just at the very early stages of being able to do that. So if I were to choose one thing to study, it would be to understand how microbial communities are constructed well enough to enable predictive reliable, reengineering of those communities in order to optimize their functions. 

TKF: Very interesting. Janet, I know you collaborate on human microbiome work. But you've also developed a reputation for investigating how environmental changes affect microbiomes in the Alaskan permafrost and on the Gulf of Mexico. What types of things have you learned and what would new tools tell you that you don't already know?

Jansson: For environmental studies, we want to understand how events, such as the Deepwater Horizon oil spill on the Gulf or the thawing of permafrost due to global warming in Alaska, is impacting microbes and the processes that they carry out in those systems. 

With the Gulf oil spill, we had organisms that were enriched during the spill, and that were able to degrade oil. So that was interesting, from that perspective. 

In the permafrost, we have a huge reserve of carbon that is currently trapped in that environment. So what happens to that carbon as the permafrost thaws and the microorganisms start to become active and degrade the carbon? Are they going to release a lot more carbon dioxide to the atmosphere and make the global warming process worse? At a very fundamental level, we need to understand what those microorganisms are doing.

TKF: Very good. I'd like to move to some listener questions. You know, microbiomes are suddenly in the news, and several listeners want to know about products that promise to improve our health and cure certain conditions by altering our microbiomes. Rob, you've been studying the American gut for a while now. Do we know enough about microbiomes for anybody to make that kind of a claim?

Knight: Yes, but so far, that's limited to just a very small number of people. For example, there was a really nice paper in Cell by Eran Segal and Eran Elinav of Israel's Weizmann Institute of Science. It showed that based on your microbiome, you can predict what foods will have good or bad impacts on your blood sugar. The drawback, so far, is that they can only do that in the Israeli population, where the food item inventory is somewhat different from what you would see in the United States, for example. But that technology is on the horizon and improving very rapidly. 

As far as probiotics go, there's not a lot of evidence that probiotics improve general health in humans, though there is some intriguing data in mice. On the other hand, there's a fair number of probiotics that have been clinically studied in well-conducted randomized controlled trials. For a number of conditions, like, irritable bowel syndrome, post-antibiotic diarrhea, and so forth, there are particular probiotics on the market that have been clinically validated. 

However, it's kind of like drugs, where certain probiotics are good for particular conditions, but not something that you should take generally. And in the same way that you would expect for drugs, most people don't need to take most probiotics most of the time, or at least not the ones that have been studied so far. So, I think it's fair to say that public enthusiasm is greatly outstripping the actual evidence. But there is some evidence underlying that enthusiasm. 

TKF: Jeff, what about the future? Are we going to be able to cure diseases? Will I be able to speed up my microbiome's metabolism so I can eat ice cream and never gain an ounce? 

Miller: When you look at the probiotics that are out there, they date way back. They have their origins in food production, fermentation, cheese making, and other processes. So the question is, do they have a health benefit or not? And the results are often equivocal. 

But that's very different than looking at what we know now, and asking, okay, how would you engineer or reengineer this system? Would a small consortia of bacteria be a good way to decrease fatty tissue and increase muscle mass with diet? So, as Rob said, we haven't yet gotten to the point where we have applied our modern understanding of microbiomes to probiotics now in the marketplace. But the potential for doing that is definitely there. 

So, to answer your question, it could cure infectious diseases. A great example is Clostridium difficile-induced diarrhea, which is caused by antibiotics. The best cure that we know is fecal microbiome transplantation from a healthy donor. It is about 90 percent effective, so we know it can work. It's very crude, and so the question now is how to make it better through more refined science, rather than hit-and-miss empirical testing. 

Knight: It's important to remember that this is not just for the future. There are people walking around, alive now, who would be dead had they not received fecal microbiome transplants. This is really a current technology that works and is being clinically applied now. And what we need to do is to refine it. But it's not something that's in the future, it's something that's here today. [Body Bugs: 5 Surprising Facts About Your Microbiome ]

TKF: This opens up some very interesting questions. One of the things we've discovered about the human microbiome is that it influences all kinds of things, from brain development and obesity to behavior. These are the very things that define who we are. Now we're talking about possibly synthesizing artificial microbiomes. This raises some ethical issues, doesn't it?

Miller: Definitely. Ethics is a huge, huge area. "Do no harm" is the first principal, whether we're talking about permafrost, agriculture or the human gastrointestinal tract. And so, the requirements for reengineering microbiota to use as a drug have got to be stringent and carefully controlled. And safety, obviously, is going to be the first issue. 

But it's complicated, because these are dynamic systems. And the question is, how long will any changes last? What else would change the result of making these perturbations, etcetera? So we need to understand a great deal more before we try to engineer and manipulate at a large scale. 

TKF: Janet, you study ecology. Could you imagine a large scale ecological intervention using microbiomes?

Jansson: Before I address that, I just want to go back to our earlier discussion about probiotics. In addition to changing our microbiome, we can also influence it through the food we put into it. This is also a strategy that is sometimes successful, though not very well understood. Instead of a probiotic, it’s called a prebiotic. For example, you can eat what is called a resistant carbohydrate or starch, which is not easy to digest. So it makes it to your intestine relatively intact. This allows the microorganisms in your gut to consume and ferment it, and that's beneficial for the colonic health. 

As for actually manipulating an ecosystem on a large scale, this is, of course, difficult. There have been people who have talked about fertilizing the oceans by adding iron, to buffer or mitigate the impact of increasing CO2 concentrations. But when it comes to permafrost, how to prevent the degradation of the carbon that is trapped there? That is difficult. But by gaining knowledge about the types of organisms that are there and the ones that become active when the permafrost does begin to thaw, we can at least predict the implications of those changes.

Knight: Just to build on what Janet said, it's important to remember that we've already radically reengineered, through agriculture, both soil and human microbiomes over most of the planet. We're brought them into states that have no precedent in nature. 

The issue is that we didn't understand at all what we were doing or what our impacts on those microbiomes were. So, it's not that we can't change them. We are already changing them. And have already changed them. The question's more, "Can we change them in a more nuanced and directed way, where we have a better understanding of the ways that we can change them, at the microbiome level as opposed to the industrial or occupational level?"

TKF: We've talked about microbiomes impacting out development and behavior. These are the things that determine our personality. For a long time, researchers thought that our genetic makeup determined these things. Do we understand the interaction between microbiomes and genome? Janet, you're shaking your head, so why don't you start.

Jansson: I can tell you that this is a real hot area of research right now. My group and several other groups are trying to establish the link between the host's genome and the microbiome. I can say that preliminary evidence – there have been a few publications mainly looking at mouse models – suggest that there is a link. Rob's taken a more historical perspective, looking at different types of human populations and the impact of ancestral lifestyles on microbiomes. Rob, maybe you want to comment on that?

Knight: Yes. We know that both in mice and in humans, lifestyle behaviors, like diet and hygiene especially, have had a much larger impact than host genetics. This is true, even though host genetics still has a highly statistically significant impact on particular features of the microbiome, including, interestingly, features that are associated with obesity in humans.

Miller: To add one thing to what Rob said, we've coevolved with our microbial communities since long before we became Homo sapiens. We have only about a dozen genes in our genome to digest complex carbohydrates. The microbiota in our gastrointestinal tract brings hundreds of genes that do that for us. And so, when we eat a healthy high fiber diet, what we're really doing is relying on these microbial consortia to digest that food for us, so that we can take some of the products and use them for energy and other purposes. 

TKF: So, as one listener asks, maybe it's not such a great idea to use bactericides to kill microbes on every surface in our homes?

Miller: Not a good idea for a lot of reasons. Rob, you shook your head, so I'll let you start. 

Knight: Well, it's bad for so many reasons. Both in terms of increasing antimicrobial-resistant bacteria, because the bacteria that survive your attempts to kill them can then spread those resistant genes to other bacteria that infect us directly. And also because there's evidence, increasingly, that keeping your house too clean increases the risk of autoimmune diseases, especially in children. 

TKF: We're drawing to the end of our discussion, so I want to ask you a final question. You know, our understanding of the microbiome has changed dramatically over the past 10 or 15 years. Tell me, what has surprised you most about what you have discovered? Janet, why don't we start with you?

Jansson: I think the thing that has surprised me the most is the importance of the microbiome with respect to our health, in so many different ways. This was something that was not known at all just a decade ago. And so that's what I'll say.

TKF: Okay. Rob?

Knight: Links between the microbiome and behavior. A decade ago we had hints that the microbiome was linked to health. But no one predicted, at all, that it would have a key role in behavior, especially in mammals.

TKF: And Jeff?

Miller: Diversity. Microbes – whether you're studying pathogens, beneficial microbes, or microbes in any context – are enormously diverse. The concept of a species has to be reconsidered when you're talking about microbes, because they're not only diverse, but constantly exchanging genetic information. They are truly a constantly moving target, and the extent of their functional diversity is mind-boggling.

TKF: Excellent. This is certainly an exciting time for microbial research. And I didn't even get to ask the best question, which is, “How does the microbiome in our gut determine our behavior?”

Knight: We don't know how it happens, and that's why we need a Unified Microbiome Initiative.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science .

Alan Brown, writer and blogger for the Kavli Foundation, contributed this article to Live Science's Expert Voices: Op-Ed & Insights.

Late last year, 48 scientists from 50 U.S. institutions proposed the "Unified Microbiome Initiative," a national effort to decipher the nature, and applications, of microbiomes, ecosystems of microscopic life forms such as bacteria, viruses, archaea and fungi. Other scientists from the United States, Germany and China echoed that call. Ultimately, the researchers hope to harness microbiomes to cure disease, fight drug resistance, reclaim exhausted farmland, reduce (or even eliminate) the use of agricultural fertilizers and pesticides, and produce chemicals using synthetic biology. 

Scientists can now identify microbes by the organisms' DNA, and have thereby discovered that microbiomes are far more diverse than anyone ever imagined. Each microbiome potentially includes hundreds of thousands of microbial species, all interacting with one another. In fact, wherever scientists have looked, they have found influential microbiomes: In the human gut, microbes not only aid digestion, but also affect obesity, allergies and even brain development; beyond people's bodies, microorganisms have created the Earth's oxygen-rich atmosphere, and also enable plant and ocean life to thrive.

But DNA testing cannot explain how microbial genes function and how these organisms work together. Only with that level of understanding, will scientists be able to harness microbiomes to improve human health and the environment.

On Tuesday, Jan. 19, from 1:30 p.m. to 2 p.m. EST (10:30 a.m. to 11 a.m. PST), the Kavli Foundation will host a live webcast about the potential of nature's microbiomes and how humanity can tap into that potential. 

Submit questions ahead of and during the webcast by emailing info@kavlifoundation.org or by using the hashtag #KavliLive on Twitter or Google+.

About the participants:

• Janet Jansson is chief scientist of biology in the Earth and Biological Sciences Directorate at Pacific Northwest National Laboratory (PNNL) in Washington state and sector lead for PNNL research in the U.S. Department of Energy (DOE) Biological Systems Science Division. She coordinates two of PNNL's biology programs: the Microbiomes in Transition (MinT) initiative, to study how climate and environmental changes affect natural and human microbiomes, and the DOE Foundational Scientific Focus Area Principles of Microbial Community Design.

• Rob Knight is the founder of American Gut, an open-access project to survey the digestive system's microbiome and its effects on human health and development. He holds appointments at the University of California, San Diego School of Medicine and Department of Computer Science and Engineering, where he develops bioinformatics systems to classify and interpret large sets of biological data.

• Jeff Miller is director of the California NanoSystems Institute, a multidisciplinary research organization, and the corresponding author ofthe consortium's Science paper. Based at University of California, Los Angeles, Miller holds the Fred Kavli Chair in NanoSystems Sciences and is a professor in the Department of Microbiology, Immunology & Molecular Genetics.

• Alan Brown (moderator) is a freelance journalist and writer who specializes in science, engineering and technology. He has been covering nanoscience and nanotechnology for more than 25 years.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Alan Brown, writer and blogger for The Kavli Foundation contributed this article to Live Science's Expert Voices: Op-Ed & Insights.

Imagine using plants to grow the natural gas that heats homes and the gasoline that powers cars. People could store it this form of solar energy in cars' fuel tanks, distribute it through pipelines, and buy it in gas stations. And everyone could use it without adding a single molecule of the greenhouse gas carbon dioxide (CO2) to the atmosphere.

Green plants and some bacteria basically do this every day, through photosynthesis, turning water and carbon dioxide into sugar. Sugar is an organic fuel that stores the sun's energy for plants to use at night or when they awake leafless in the spring. But suppose engineers could tweak this natural process to produce natural gas or gasoline? 

Advances in nanoscience are rapidly bringing that vision closer to reality. In a recent paper published in Nano Letters, Peidong Yang, co-director of the Kavli Energy NanoSciences Institute and professor of chemistry at the University of California, Berkeley, led a team that achieved synthetic photosynthesis by combining nanoscale semiconductors and genetically modified bacteria. 

By marrying nanoscience and biology, Yang and his colleagues created a biologically inspired, but completely artificial, system that converts the sun's rays into fuel and chemicals. The system uses long, nanoscale filaments to turn sunlight into electrons, which bacteria use to convert carbon dioxide and water into butanol fuel and more complex molecules such as acetate, a chemical building block, and amorphadiene, which is used to make antimalarial drugs. 

This past August, Yang's team used a similar approach to make methane, the most important component of natural gas. It used nanowires to split water into oxygen and hydrogen, and hydrogen-loving bacteria to turn CO2 into methane.

The Kavli Foundation invited three leading researchers to discuss this promising technology, the roadblocks that remain before it becomes commonplace, and how science might learn from nature's genius.

The participants were:

Peidong Yang, co-director of the Kavli Energy NanoScience Institute at Berkeley National Laboratory and a professor of chemistry at the University of California, Berkeley. Yang serves as director of the California Research Alliance by BASF and was a founding member of the U.S. Department of Energy (DOE) Joint Center for Artificial Photosynthesis (JCAP).

Thomas Moore is a professor of chemistry and biochemistry and past director of the Center for Bioenergy & Photosynthesis at Arizona State University. He is a past president of the American Society for Photobiology, and a team leader at the DOE Center for Bio-Inspired Solar Fuel Production.

Ted Sargent is a professor of electrical and computer engineering at the University of Toronto where he is chair for nanotechnology and vice-dean for research for the Faculty of Applied Science and Engineering. He is also the founder of two nanotechnology companies: InVisage Technologies and Xagenic. 

The following is an edited transcript of their roundtable discussion. The participants have had the opportunity to amend or edit their remarks.

TKF: Solar cells do a good job of converting sunlight into electricity. Converting light into fuel seems far more complicated. Why go through the bother? 

Thomas Moore: That's a good question. In order to create sustainable, solar-driven societies, we need a way to store solar energy. With solar cells, we can make electricity efficiently, but we cannot conveniently store that electricity to use when it is cloudy — or at night. If we want to stockpile large quantities of energy, we have to store it as chemical energy, the way it is locked up in coal, oil, natural gas, hydrogen and biomass. 

Peidong Yang: I agree. Perhaps, one day, researchers will come up with an effective battery to store photoelectric energy produced by solar cells. But photosynthesis can solve the energy conversion and storage problem in one step. It converts and stores solar energy in the chemical bonds of organic molecules.

Ted Sargent: Much of the globe's power infrastructure — from automobiles, trucks and planes to gas-fired electrical generators — is built upon carbon-based fossil fuels. So creating a new technology that can generate liquid fuels that can use this infrastructure is a very powerful competitive advantage for a renewable energy technology. 

Also, our energy needs change with the seasons. Here in Canada, heating drives up energy use in winter. Maybe we could build a battery to store enough energy to heat our homes overnight, but the greater long-term challenge is to store energy we capture in the summer and use it to heat our nation of 35 million people in the winter. 

The remarkable energy density of fossil fuels, all of which store energy created by ancient photosynthesis, make this possible. So while converting sunlight to fuels will always have a greater energy cost than making electricity, liquid fuels have a notably higher value because they can meet seasonal gaps between the supply and demand of renewables. 

And, finally, synthetic photosynthesis is a carbon-neutral solution, because we take one CO2 molecule out of the atmosphere for every CO2 molecule that we return during combustion. 

T.M.: As Ted implied, the driver behind this is that the global carbon cycle is completely out of control. Burning fossil fuels is putting CO2 in the atmosphere much faster than photosynthesis can take it out. A system that pulls every carbon [atom] that we burn out of the air and converts it into fuel is truly carbon neutral. 

[Atmospheric] CO2 levels surpassed 400 parts per million this year. If they reach 500 or 600 parts per million, the environmental impact is going to be severe. We will need some form of carbon capture and storage. This leads right into Peidong's system, because it could remove copious amounts of CO2 from the atmosphere, use some for fuel, and make carbon rocks out of the excess. In that way, it could reduce atmospheric CO2 to pre-industrial levels. 

TKF: Professor Yang, you created a photosynthesis system that is half synthetic and half natural. What gave you the idea?

P.Y.: The story starts more than 10 years ago, when Berkeley designed a fully integrated solar-to-fuel generator. We tried to mimic what goes on in natural photosynthesis. 

We used semiconductors to capture solar energy and generate current. We used the current to energize two catalysts — materials that speed up chemical reactions without actually taking part in them. One catalyst reduced, or added electrons to, CO2, and the second oxidized [took electrons from] water to produce oxygen, which is what happens in natural photosynthesis. The synthetic CO2 catalysts were the problem, because they were simply not very efficient. 

So about five years ago, we decided to try using nature to play the role of those CO2 catalysts. Some bacteria, such as Sporomusa ovata (S. ovata) actually have the capability to reduce CO2 with very, very high selectivity, meaning they deliver electrons to CO2 to make one specific organic molecule and nothing else. 

In our system, we still use inorganic materials to capture sunlight and generate electrons. But we send the electrons to the S. ovata, which use them to turn CO2 into acetate, a more complex molecule. Then we use a second bacterium, Escherichia coli (E. coli) to turn acetate into more complex chemicals. 

TKF: Do you think this type of hybrid system — a combination of synthetic light converters and natural catalysts — is the way of the future?

P.Y.: Honestly, I'm not so sure this is the best way to create an artificial photosynthetic system. 

We're good at generating electrons from light efficiently, but chemical synthesis always limited our systems in the past. One purpose of this experiment was to show we could integrate bacterial catalysts with semiconductor technology. This lets us understand and optimize a truly synthetic photosynthesis system.

Ultimately, we would like to take what we learn and develop a synthetic catalyst with performance similar to the bacteria. That would let us put together a much more robust, fully integrated solar-to-fuel generator. Meanwhile, our current approach represents an intermediate step that lets us learn about artificial photosynthesis in new ways. 

T.S.: Peidong's right to put the focus on exactly this question: What can biology teach us about making fuels? His model system makes it possible to explore some really important physics and chemistry. This is not about mimicking nature directly or literally. Instead, it is about learning nature's guidelines, its rules on how to make a compellingly efficient and selective catalyst, and then using these insights to create better-engineered solutions.

TKF: Is there a way to create the type of synthetic catalysts Professor Yang envisions? 

T.S.: Nature has figured out efficient CO2-to-liquid-fuel catalysts. We have not yet managed to do that. In particular, as Peidong noted, we need high selectivity to make the product we want without undesired side products. We also need catalysts that convert chemicals quickly, and without making us pay an energy penalty for their high throughput. Finally, nature builds catalysts using abundant materials. On all these fronts, nature has us beat. But it is also exciting, because nature proves it's possible. This is a problem that has been solved before. 

T.M.: Those are extremely good points. Nature's catalysts are remarkable for a number of reasons. They self-assemble, and nature repairs any damage to them. They always use abundant materials because nature does not mess with anything that is rare or expensive. They always work at ambient temperatures. 

As Ted said, nature's catalysts do not require a lot of excess energy. When chemists want a chemical reaction to go faster, we heat it up or apply more voltage. Nature did not have either option, so it had to solve the problem by finding a low-energy pathway. 

Again, as Ted and Peidong mentioned, selectivity is hugely important. Our industrial society expends lots of energy separating desired chemicals from all the other junk we make along the way. Nature makes what it wants, and it's nearly always already pure. 

Nature proves it's possible, but we are still a ways away from having nature's catalytic prowess. But Peidong's work establishes that technology and nature can work together. 

TKF: Let me return to something Professor Yang mentioned earlier. Your system is making a chemical called acetate. Why is that important?

P.Y.: CO2 has one carbon atom, so it is relatively easy to make a chemical with one carbon atom from CO2. But it is much more desirable — and difficult — to create a chemical with more than one carbon atom. Acetate has two carbons, and our hybrid system proves that we can create a molecule like this. 

While acetate is not necessarily our most desired end product, it is a common building block in biosynthesis. In our study, my Berkeley collaborator, Michelle Chang, genetically modified E. coli to turn acetate into more interesting chemicals, such as butanol fuel, biodegradable polymers and drug precursors. 

If we could design a synthetic catalyst that did this sort of carbon-carbon coupling at room temperatures and pressures, that would be fantastic. However, we do not know how to do that yet.

T.M.: I think that Peidong is being a little modest about making acetates. I mean, if you go from CO2 to acetate, all the heavy lifting is already done. You've produced a carbon-carbon bond. 

TKF: Why is that so important? 

T.M.: Because the two-carbon unit is the fundamental feedstock for a whole mess of different metabolic pathways. For example, when our body metabolizes the fatty acids we eat, it chops them up into two-carbon units. From those two-carbon units, it makes everything it needs. So carbon-carbon units are very important in metabolism, much more common than single carbon units. 

TKF: So acetate is a good building block?

T.M.: Yes, and there are organisms that would love to build with it. Plus, as we learn more, we can use that knowledge to create synthetic catalysts to make butanol, gasoline, longer chain hydrocarbons — it is all thermodynamically possible once you get acetate. So it is a big deal. 

T.S.: It is, especially for fuels.

TKF: Professor Yang, one of the unusual aspects of your hybrid system is that it uses nanowires to convert light into electrons. Why use nanowires instead of more conventional solar panels? 

P.Y.: That relates to the one key requirement of the original design: We want transfer electrons from our semiconductors to our S. ovata bacteria, which act as our CO2 catalysts. To do that, we want the highest possible surface area, so that we put more bacteria in contact with the semiconductors and reduce more CO2. Nanowires do that because they extend upwards, like trees. They create a forest, and you can squeeze a lot more bacteria into a three-dimensional forest than onto a two-dimensional flat surface.

TKF: And this has to take place in liquid?

P.Y.: Yes. We do this chemistry in water, where the bacteria live. 

T.S.: Peidong has been a pioneer in nanowires for more than a decade. His ability to grow tall, thin nanowires is a very powerful technology that makes dense bacterial growth possible. It is the fundamental reason why this system can transfer the right number of electrons per second to the right number of bacteria.

T.M.: Catalysts, which mediate chemical reactions, generally operate more efficiently when we don't try to rush them. So the more volume these nanowires create, the more bacteria we could fit in. Then, even if each bacterial catalyst reacts slowly, you can still have a lot of output without putting in a lot of energy. And that's the whole ballgame — use less power to get more product. 

TKF: I never thought of bacteria as absorbing electrons. How do they do that?

T.M.: All living things take in electrons as part of the molecules they ingest and metabolize to extract energy. We've learned now that certain bacteria can actually gather electrons through specialized thread-like structures called pili that reach out through their membranes. Those pili could play a key role in the interface between technology and biology.

Peidong, how did the electrons get into the bacteria?

P.Y.: Based on early studies, S. ovata absorb electrons directly from the nanowires, rather than through a chemical mediator. In fact, there are a host of bacteria that can do this routinely.

T.M.: Absolutely. They are just doing what life does, taking in energetic electrons, giving them to oxygen or another electron acceptor, and extracting the energy difference between these two processes to stay alive.

TKF: Did you have to genetically modify Sporomusa to do that?

P.Y.: No. S. ovata, the bacterial strain we're using, just has the amazing ability to absorb electrons and use them to process carbon dioxide into acetate.

TKF: So, what about generating fuel? Right now S. ovata transforms electrons into acetate, and E coli turns that into butanol or something else. Do you think you could do this in one step?

P.Y.: I would assume so, right, Tom?

T.M.: Sure. The ways in which we can use synthetic biology to reengineer things is almost unimaginable. Already, Pete Schultz at Scripps Research Institute has bacteria that run on 21 amino acids, one of which is completely new. The bacteria have been programed with all the genetic material and information necessary to copy this unnatural amino acid and include it as part of its metabolism. And right there at Berkeley, you've got Jay Keasling. He has bacteria that can make almost anything from acetate.

TKF: Professor Yang, could we ever make your system efficient and compact enough to use industrially?

P.Y.: In principle, it is capable of scaling up. But we would need to raise the solar-to-fuel conversion efficiency by 5 to 10 percent before we could think about commercial viability. 

TKF: That conversion rate does not sound very high. How does it compare with the conversion rate of natural plants and bacteria?

P.Y.: Actually, efficiency in green plants is quite low, typically below 1 percent. 

T.M.: Yes, less than 1 percent of the average annual solar energy falling on a field of crops is conserved and stored as chemical energy. That is far lower than commercially available solar cells, which produce electrical energy at 20 percent or better efficiencies, but solar cells cannot store their energy.

P.Y.: True, and by combining the best of technology and biology, we can do something similar to natural photosynthesis, but potentially at much higher efficiency.

TKF: Yes, we have talked a lot about learning from nature. Do we have the right tools to do this? 

T.M.: We need all the tools we can get. We need to rededicate ourselves to basic research. 

T.S.: I'm with Tom. We need more tools, and those tools come from basic science. Let me mention one that really excites me. Computational models that let us understand and predict the energetic states and reactivities of molecules, materials and catalysts. 

It is a tool that brings together different researchers who frankly have a hard time talking with each other. In a room of people who study enzymes — proteins that serve at nature's catalysts — and people who research synthetic heterogeneous catalysts, the systems are so different, it can be hard to know where to start the conversation. Computational material science helps us learn from each other about how nature's catalysts differ from the ones we build artificially. 

T.M.: I absolutely agree. Only a few points in a chemical reaction are actually observable experimentally, sometimes very few. Models help us understand those reactions, and how to move atoms and electrons over the low-energy pathways through these high-energy mountains. It has opened all sorts of doors already. 

P.Y.: I totally agree. To come up with better synthetic catalysts, we need to learn from nature on the atomic and molecular scale. So it's very important for researchers from different research communities to come together, talk to each other, and exchange ideas. 

TKF: So, what do you think you will be working on and doing in five years?

P.Y.: I think I will be trying to enhance our bacteria's efficiency and the range of chemicals they produce. More importantly, I'm very, very interested in learning how these bacteria process CO2. Hopefully, we can learn from their design and develop synthetic catalysts with decent selectivity, activity and energy efficiency .

T.S.: I don't want to repeat what Peidong just said, but I will because he is really aiming at the heart of the most important problem, learning from nature. And I'll add one additional problem that I'm really excited to study. Though we are more advanced than nature on the light harvesting side, we still have a lot to learn about how to manipulate electrons in our systems. 

We also need to learn how to make light harvesting systems from materials that are not costly, toxic or energy-intensive to make. Nature synthesizes those materials at room temperature, with very low energy costs, and they use coherence effects to move energy efficiently over long distances to centers where reactions take place. I'm very excited to work on robust, biologically inspired energy transport. 

T.M.: Those are profound goals. I'm not sure what I'm going to be doing in five years. I will be following what Ted and Peidong are doing, and I'm sure their discoveries will make me think about things in new ways. Out of that, I am sure I will find some new fundamental problems to work on, and I hope that work will be useful. 

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Alan Brown, writer and blogger for the Kavli Foundation, contributed this article to Live Science's Expert Voices: Op-Ed & Insights. 

From inside our bodies to under the ocean floor, microbiomes — communities of bacteria and other one-celled organisms — thrive everywhere in nature. Emerging at least 3.8 billion years ago, they molded our planet and created its oxygen-rich atmosphere. Without them, life on Earth could not exist. 

Yet we know surprisingly little about the inner workings of nature's smallest and most complex ecosystems. 

Microbiomes have a great deal to teach us. By learning how members of microbiomes interact with one another, scientists might discover innovative green chemistry and life-saving pharmaceuticals, or learn how to reduce hospital infections, fight autoimmune diseases, and grow crops without fertilizers or pesticides.

The sheer complexity of microbiomes makes them difficult to study by conventional biochemical means. Nanoscience provides a different and complementary set of tools that promises to open a window into this hidden world. [The Nanotech View of the Microbiome]

Earlier this month, The Kavli Foundation hosted a Google Hangout with two leaders in the emerging applications of nanoscience for studying microbiomes. They discussed the potential of natural biomes, why they are so difficult to understand, and how nanoscience may help us unlock microbiome secrets. 

Joining the conversation were:

Eoin Brodie, a staff scientist in the Ecology Department at Lawrence Berkeley National Laboratory. He was part of the team that pioneered a device capable of identifying thousands of the bacterial species found in microbiomes, and is currently developing ways to combine data from many different types of measurement tools into a more coherent picture of those ecosystems.

Jack Gilbert is a principal investigator in the Biosciences Division of Argonne National Laboratory and an associate professor of ecology and evolution at the University of Chicago. He has studied the microbiomes of hospitals and is working on ways to use nanostructures containing bacteria to help infants fight immune diseases.

Below is a modified transcript of their discussion. Edits and changes have been made by the participants to clarify spoken comments recorded during the live webcast. To view and listen to the discussion with unmodified remarks, you can watch the original video.

The Kavli Foundation: So let's start with an obvious question, what exactly is a microbiome?

Eoin Brodie: A microbiome is a connection of organisms within an ecosystem. You can think of the ecosystem of microbes in the same way you think of a terrestrial ecosystem, like a tropical forest, a grassland, or something like that. It is a connection of organisms working together to maintain the function of a system. 

Jack Gilbert: Yes. In a microbiome, the bacteria, the archaea (one-celled organisms similar to bacteria), the viruses, the fungi, and other single-celled organisms come together as a community, just like a population of humans in a city. These different organisms and species all play different roles. Together, they create an emergent property, something that the whole community does together to facilitate a reaction or a response in an environment. 

TKF: How complex can these microbiomes? Are they like tropical forests? Are they more complex, less complex?

J.G.: The diversity of eukaryotic life — all the living animals and plants that you can see — pales into insignificance beside the diversity of microbial life. These bacteria, these archaea, these viruses — they've been on the earth for 3.8 billion years. They are so pervasive, they have colonized every single niche on the planet. 

They shaped this planet. The reason we have oxygen in the atmosphere is because of microbes. Before they started photosynthesizing light into biomass, the atmosphere was mostly carbon dioxide. The reason the plants and animals exist on Earth is because of bacteria. The diversity of all the plants and animals — everything that's alive today that you can see with your eyes — that's a drop in the proverbial ocean of diversity contained in the bacterial and microbial world. [Can Microbes in the Gut Influence the Brain?]

E.B.: We tend to think of the earth as being a human planet and that we're the primary organism, or the alpha species. But we're really passengers, we're just blow-in's on a microbial planet. We're recent, recent additions.

TKF: You both wax so poetic about it. Yet we know so little about microbiomes. Why is it so hard to understand what goes on in these ecosystems?

E.B.: Jack eluded to it. The first problem is that microbiomes are very small. We can't see them, and it's very difficult to understand how things work when you can't see them. So tools are needed to be able to see these organisms. 

We also can't grow them. It's very hard to bring them from the natural ecosystem into the lab for study. Probably less than one percent, depending on the ecosystem, can actually be cultivated on growth media in the lab so that we can do experiments and understand what functions they carry out. That leaves 99 percent — the vast majority of the microbes on Earth and most of their ecosystems — unknown to us, apart from their DNA signatures and things like that. 

Now, Jack has pioneered DNA analyses. When you look at the DNA signatures from these environments, there are all these new organisms, new proteins, and new functions that we have never really seen before. This has been called earth's microbial dark matter. Just like dark matter and energy in the universe, this has been unknown to us, but it is extremely important if the planet — and humans — are to continue to function. 

TKF: So, what makes it so hard to grow these microbes in a Petri dish? 

E.B.: They're very fussy. You can think of it that way. They don't like to eat the food that we give them, in many cases. They eat things that we don't know they can eat. They breathe things that we don't know that they can breathe. 

We breathe oxygen, they breathe oxygen, but they also breathe nitrates, iron, sulfur, even carbon dioxide. Getting the right concentrations and combinations of what they eat and breathe is very difficult. 

In some cases, even if you can work that out, there may be something that they need to get from another member of the ecosystem. That member may supply an essential nutrient or a cofactor for them to grow. 

So getting all of those possible permutations and combinations right is extremely challenging. A lot of people are working on it, and there's a lot of expertise being put into this, but it's extremely difficult and complicated. 

J.G.:& That's an interesting point. I liken it to having a baker. You know, if you have a baker in a human community, the baker needs somebody who can make the flour, somebody who can provide a bit of yeast, and someone who will buy the bread. They exist as a network of individuals living in a community. 

If you take the baker out of the community, he or she cannot make the bread and so they are no longer a baker. Removing a microbe from its community reduces the likelihood that it will be able to perform the roles and tasks that it does in that environment.

So it's almost like you don't want to try and grow these things in isolation. Because, while isolating them makes our job as a microbiologist easier, it's also much more difficult to understand what they actually do in the environments in which they live. We can't figure that out in isolation because they are community players. 

TKF: What are some of the tools that we can use today to look at microbiomes? Is there a state of the art? 

J.G.: So I'll take on that. I mean this is a very dynamic evolving field. It is not a field where everyone seems to rest on their laurels. 

To understand microbes, we have a couple of tools that are available to us. One of those tools is genomics, so we can sequence the genome of bacteria, archaea, viruses and fungi, just as we've done for the human genome. 

The second one is the transcriptome, which looks at RNA, a transient molecule that creates the cell by translating what's in the genome into proteins. That's useful, because it tells us which genes are being turned on and off when we put those microbes under different conditions. 

Then we have the proteome, the proteins that actually make up the cell. They are the enzymes that enable the organism to interact with its environment, to consume its food, to respire carbon dioxide, oxygen or iron, and so on.

Then you have the metabolome, the metabolic molecules living organisms consume as food and produce as waste products. 

The genome, transcriptome, proteome, and metabolome are four of the tools in our toolbox that we can actually use to examine the microbial world. But they are by no means the limit of our tools or our goals. We have ambitions far beyond just examining those components. Eoin is developing some of these, and maybe Eoin, you want to jump in now? 

E.B.: Yes, I'd add to that. The challenge of understanding the microbiome, and even individual microbes, is that they're just so small. They're complicated and small, so understanding their activity — their transcriptomes or proteins or metabolites — at the scale at which they exist, is extremely challenging. 

All the technologies that Jack mentioned are being developed with larger organisms in mind. Scaling them down to deal with the size of microbes, but then increasing their throughput to deal with the complexity of microbes, is a huge, huge challenge. 

I'll give you an example. When you look at the activity of an ecosystem, say a tropical forest, you look at the distribution of trees and animals, and look for the association between the vegetation and animals. 

So if you want to understand insects, you have a space in mind. You think, "This lives near this. It interacts in this area." So there's an interaction, a fundamental association between those members of the ecosystem. 

The way we typically looked at microbiomes — though this is changing now — was to mash up the entire forest in a blender. Then we would sequence all of the DNA, and look at the RNA and proteins, and the metabolites. 

Then we try to go back and say, "This tree is interacting with this insect." Whereas, in reality, that tree is hundreds or thousands of kilometers away from that insect, and they never see each other. 

That's the problem we have in the microbiome. When we mash up those organisms to look at their DNA, RNA, proteins and metabolites, we get rid of that spatial structure and its associations. And we lose the importance of space in terms of facilitating interactions. [The Nanotech View of the Microbiome (Kavli Roundtable)]

So, really, I think the next wave in microbiome research has to target this microbial activity and interactions at the scale of the microbe. Do they see each other? Do they interact, and how do they interact? What chemicals do they exchange, and under what conditions? I think that's the real challenge. That's why we're talking to the Kavli Foundation, because that's where nanoscience comes in. 

TKF: This is an excellent transition to my next question: How do we use nanoscience to learn about microbiomes? For example, could we use some of the same nanoscale probes we are developing to study the brain to, say, investigate microbiomes in the ocean or soil?

E.B.: I think there are some interesting parallels. I mean, you can think of the brain as this extremely complicated network of neurons. The BRAIN Initiative is attempting to map those neurons and to follow their activity. 

Similarly, the microbiome is a network of interacting organisms that turn on and turn off. The connections and the structure of that network are extremely important to the functioning of the system, just as it is for the functioning of the brain. 

For the BRAIN Initiative, people got together and said, "Well what do we need to do to look at electrical charge and electrical flow through neurons, noninvasively, and in real time?" And they came up with some technologies, that can potentially, do remote sensing on a very small scale, and watch how the system changes noninvasively. 

So, one approach to understanding the brain is to use external imaging, and another approach is to embed sensors. 

In the BRAIN Initiative some sensors are being developed here at Berkeley lab and elsewhere that use RFID — radio frequency identity — technology. They are similar to tags used to track shipping containers, goods in department stores, and things like that. They both transmit information and harvest energy from radio frequencies, so they're autonomous devices. I think that the challenge now is coupling that technology to sensors that can monitor something in the environment and send that information autonomously — no batteries required — to receivers. Then, if these sensors are distributed in an intelligent way, just like with GPS, you can triangulate where that information is coming from.

How could you use this to understand a microbiome? Well, the sensors that are being developed are still relatively large scale, about one square millimeter in size. That's pretty small for us, but very large for a microbe. 

So you can think about this in soil. Let's say we want to understand what happens when a root grows through soil. The root stimulates microbes, and there are ten times more microbes near the root than there are away from the root in soil. They all have different chemistries and different functions that are very important for the nutrition and health of the plant. 

If you could distribute very small sensors in the soil and have them sense things like carbon from roots or oxygen consumed by microbes, then you can build a three dimensional picture of how the soil microbiome is changed and altered as a root moves through the soil. That's one example of how advances in other fields, driven by nanotechnology, could be applied to microbiome. 

TKF: These RFID sensors would be based on semiconductor chips, right? So you could take a wafer, make a lot of them cheaply, distribute them in the soil, and get a picture you couldn't get any other way?

E.B.: Yes. There's an emerging field called predictive agriculture. It's like personalized agriculture, where fertilizer addition, for example, in a field would not be uniform. Instead, you would deliver the fertilizer where it's needed. You would irrigate the field exactly where it's needed. So you have this massive network of distributed autonomous sensors, and that would allow us to more efficiently use fertilizer. Then it wouldn't be leached or lost from the system, and cause water pollution and things like that. These examples are not on a microbial scale, but microbial processes control the availability and uptake of these fertilizers.

TKF: Thank you. Hold that thought and we'll come back to it in a few moments. In the meantime, Jack has been studying microbiomes in a new hospital to see how they evolve and affect the spread of disease. Could you tell us what you are doing, and how nanotechnology might help?

J.G.: Yes. The microbes that exist in a hospital have been a focus of clinicians and medical researchers for a couple of hundred years. Ever since we uncovered that bacteria might actually be causing disease, we've been trying to eradicate as much microbial life as possible. 

That paradigm is shifting to one where we're more interested in trying to understand how bacterial communities in a hospital may facilitate the spread of disease and antibiotic resistance, and maybe promote health as well. 

We've been going into hospitals and, with a very, very high temporal resolution, exploring how their bacterial communities change over time. So, looking at a scale of hours to days, we're trying to understand how — when a patient moves into a new room to have an operation or to undergo a procedure — the microbes that are already in that room affect the outcome of the patient's stay in the hospital. We want to know if it makes them either healthier or sicker.

So, we've been cataloging the microbes at these very fine scales. And what we see is an exchange between the bacteria in the room and inside the patient's body. 

But we've also discovered that the vast majority of bacteria that we would normally associate with so-called healthcare-associated infections — pathogens that we thought people acquire during hospital stays — appear to be bacteria that patients brought into the hospital themselves. They're bacteria that we have inside us. 

Remember, we have one hundred trillion bacteria living inside us. They weigh about two pounds, about the same as the brain. So if you think that the BRAIN Initiative is important, well maybe a microbiome initiative would also be important, because it weighs about the same as the brain.

The human microbiome has a lot of players. Most of them are friendly to us, but they can turn on us too. I liken this to a riot spreading in the city. You know, if you take things away from people, they will generally rise up and try to overthrow the very thing which was supporting them in the first place.

Microbes are the same way. We give a hospital patient antibiotics and radiation therapy to kill bacteria. Then we cut open his or her intestine and expose the bacteria to oxygen, which they don't like, and stitch the gut back up. When we look at the bacteria, we see that previously friendly bacteria have started to riot. They've been insulted so many times by the patient's treatment that they've decided that they've had enough. Then they go and attack the host to regain the resources which are being taken away from them.

This is very important. Understanding a patient's hospital stay from the microbes' perspective is helping us to design better ways to treat patients and reduce the likelihood that those microbes inside us will rebel, attack us, and make us sick. 

Nanotechnology is helping us to achieve a finer scale of visual resolution, so we can see exactly when, during a surgical procedure, bacteria go rogue and start to attack the host, and the molecular mechanisms that underpin that behavior.

We have a great example that we found by placing nanoscale molecular biosensors in the gut. It measures phosphate levels. Phosphate is a very important molecule that is used to create the DNA and proteins in our body, and in the cells of those bacteria. 

When the phosphate level drops below a certain threshold, the microbes turn on a mechanism to acquire phosphate from their environment. And where's the best source of phosphate? It's in the gut lining of their host. So they migrate to the gut and start to break down the human cells. We experience that as a several pathogenic infection, which often kills us. 

Because we understand that process, we are developing mechanisms to release phosphate at exactly the right time during surgery to prevent those bacteria from ever experiencing that phosphate reduction. To do those micro phosphate releases, we're developing nanotech scaffolds to hold phosphate, and placing them into the gut during surgery. This will reduce the likelihood that microbes will become pathogenic. 

TKF: Not only is that interesting, but it leads one of our viewers to ask whether we can adjust microbiomes so that they can target diseases and other human conditions. Can they go beyond just adjusting acidity or phosphate levels and do something more aggressive?

J.G.: Yes. The case where we've had the best success is in treating chronic infections caused by Clostridium difficile bacteria. C. diff infections are chronic gastrointestinal infections. Our treatments use a shotgun approach. We take the bacteria from a healthy person and transplant them into somebody with a chronic C. diff infection. That's overridden the C. diff infection, and established a healthy microbiome in the patient's gut so that he or she is no longer sick. 

The Chinese did this about 2,000 to 3,000 years ago. They called it yellow soup, and they fed the stool from a healthy person to a sick person, and that made the sick person healthy. We just rediscovered this process, and we are now applying it in a more clinical setting.

So far, it's a very untargeted approach. What we're trying to do with our research arm, American Guts, and programs associated with autism, Alzheimer's, and Parkinson's, is to identify specific bacterial community members that are either absent or overgrown in those patients. Then we want to explore how to adjust them — maybe we implant one that is missing or knock one back that is over-grown, to make that person healthier. 

E.B.: I'd like to add something to that. There's an interesting analogy, I think, in what we're doing for C. diff — fecal transplants — and restoration ecology. That's where you weed out an invasive plant species and plant another species to out-compete that invasive plant species. It's the exact same process, so the same ecological principles and ecological theory that's used in restoration ecology can be used in medicine. In some cases, it may not be as simple as removing one organism or adding one or two other organisms. It might be a community function, where we may actually need that complexity to be able to out-compete the organism that's causing the disease. 

J.G.: That's a really interesting point. Both Eoin and I are microbial ecologist at our core. I started out in marine microbial ecology, and now I work in soils, plants, humans, and disease. Eoin does the same. And both of us can apply the ecological principles of microbes to any environment because microbes are everywhere. 

TKF: Good. So, Eoin, we have two questions for you from our audience. The first involves agriculture. A viewer want to know whether nanoscience help us alter microbiomes in ways that change how we grow, fertilize, and protect plants from pests? 

E.B.: That's a great question, and I think a really timely one as well. The world population is seven billion, heading to nine, and then 11 billion. We're going to run out of fertilizer, we're going to run out of space to grow food, and we're running out of water — we're in a severe drought in California. These are our challenges, feeding a global population and providing fuel for a global population. 

The things microbes and nanotechnology can do mainly revolve around improving the resistance of plants to stresses, such as drought. Microbes can help plants acquire water. For example, mycorrhiza fungi can increase the root system, improve its drought tolerance, and improve nutrition. 

We can also identify bacteria that can produce fertilizer in or near the plant. So bacteria that can take nitrogen from the atmosphere and fix nitrogen can potentially offset the use of nitrogen fertilizer, which takes a lot of energy and causes a lot of pollution to manufacture. 

Bacteria can also mine critical minerals from the soil. We can have bacteria growing with the plants that acquire phosphorous, like Jack was saying. We can choose bacteria so that they mine more phosphorous than they need and supply that to the plant. 

All of these things would reduce our reliance on mining phosphorous from strip mines or using five percent of our world's energy to product nitrogen fertilizer. I think it's a big, big challenge. 

Nanotechnology, as I mentioned earlier, can be used to characterize these organisms and understand how they work. We can also build sensor systems to identify when nutrients are limiting growth. So instead of spreading nutrients and fertilizer in a very inefficient way, we can use it in a very targeted, specific, and much more sustainable way.

TKF: Can we take a step beyond that, and perhaps use microbiomes to control pests?

E.B.: Actually, that's been done for a long time. As you know, there are GMO crops out there that have taken genes from microbes that are used to kill insects. This could be carried out in a more natural way, as well, for example, by growing these bacteria with the plants and potentially inhibiting insects from grazing and feeding on the plants. We can learn a lot from nature. Nature has already developed these strategies for pest control, and we can learn from that to design our protections in a more, controllable and intelligent way.

TKF: Another question from a viewer: Is it possible to make an artificial microbiome community do a particular task?

J.G.: Yes. We've actually been working in that area, trying to create what we call a simple minimal community. This is a community of organisms that performs a task, such as creating acetate or generating hydrogen or butanol as potential biofuel source. So we're looking at microbes that grow on the surface of cathodes, and take raw electrons from those cathodes and integrate them with a carbon dioxide source, such as blue gas from a factory. We want to create a community that drives it's metabolism towards a set goal. 

That will take a mathematical modeling approach. So metabolic modeling, trying to synthesize in a computer how these microbes interact to release a certain product. So, in that sense, you need nanotechnology to sense the metabolic relationships that exist between those organisms, so that you can engineer that community towards producing a particular product. That's going to be very important to achieve biotechnology results.

E.B.: Actually, I've got to turn that question on its head. I would like to take a natural microbial community and stop it doing something, in certain cases. 

Let's say, for example, you've got cattle livestock. They are a significant source of global methane that contributes to global warming. Part of that is because of their diets, which provide an excess energy. That results in increased hydrogen, which results in a lot of methane, and cows release a lot of methane.

So, could we go in and use targeted synthetic biology or chemical interference approaches to stop the production of methane? To alter the balance of the cow's rumen, the cow's gut microbial ecosystem? We could not only inhibit methane production, but improve nutrition to the animal, because it's microbes that control the flow of energy to the animal from the food that it eats. 

It's a complicated ecosystem, but specifically tweaking it for the benefit of the animal and the benefit of the planet, is an interesting challenge and there are people working on that.

J.G.: I'd like to take that exact system and apply it to coal, in order to make more methane that we can then capture and pump into people's homes as biofuel.

TKF: Interesting thought. I have another question from a viewer, and Jack, I think you are the one to answer this. She has of experimental treatments that involve implanting health gut bacteria into people with autism. Why might this work? And will this be something that we see soon?

J.G.: The bacteria in our gut have an impact upon neurological behavior — the way we behave — through our immune system. They elicit a certain immune response in our gut, which feeds back on our nervous system to create a certain characteristic behavior in our brain. 

We've known this in animal models for a number of years now. We're just starting to understand the extent to which neurological diseases, such as autism, Parkinson's, and conditions such as Alzheimer's, are attributable to a disruption in the bacterial community in somebody's intestine.

There have been several experiments with very low numbers of children. In several cases in South America and a number in Australia, the children have had a fecal microbiome transplant, a healthy microbial community implanted into their own gut. 

The results are variable, and not exactly something that you would want to try at home. But they do hint, in some instances, of a favorable outcome where the child's neurological disorder is lessened, or significantly reduced. 

There are groups at Cal Tech are generating probiotics, particular bacteria species, that they hope to add to a child's diet or put into a capsule that can be swallowed. They seem to have a benefit in reducing the neurological abnormalities associated with autism, though they are still in their early days. 

TKF: That leads to another question I wanted to ask you. Jack, you're also working on encapsulating microbiomes in some sort of nanostructure and applying them to homes or offices. Your hope is that these biomes will expose people to microbiomes that will help their immune system develop resistance to these neurological problems. Could you tell us about that?

J.G.: Yes, we're working on animal models at the moment. Imagine recreating structures that these animals can interact with. Imagine I build you a building that was biologically alive, where the walls were deliberately teeming with a healthy microbial community.

Now, we have only a very limited idea what healthy means, but essentially what we're doing is creating structures, 3D printable structures, impregnated with certain nutrients. We're working with Ramille Shah at Northwestern University to create a 3D structure which allows that bacterial community to thrive. 

We can then introduce these structures into a mouse's cage. The bacteria associated with the 3D surface will colonize that mouse, and reduce certain abnormalities that we see in that mouse, such as an allergy response. So we've been growing bacteria which can produce a chemical that, once released into the gut of the mouse, will form a colony and reduce the likelihood of that mouse having a food allergy. 

I'm also working with Cathy Nagler at the University of Chicago. We're hoping to prove that we don't have to pump kids full of probiotics. Instead, we can just redesign homes, schools, and maybe daycare centers, so that children will get an appropriate microbial exposure that would mirror how they would have grown up if they were in a natural ecosystem. Hopefully, that will be the future of architecture. 

E.B.: And, you know, as a possible alternative, we can send our kids outside to play more.

J.G.: You got it. 

E.B.: Not bad.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Alan Brown, writer and editor for the Kavli Foundation, edited this roundtable for Live Science's Expert Voices: Op-Ed & Insights.

Microbiomes — communities of microorganisms — exist nearly everywhere, from the soil and the sediment under oceans, rivers and lakes to the landscapes of the human body. They are ubiquitous, mediating the interactions of plants and animals with their environments, and yet we know very little about them. 

The Kavli Spotlight, a series of roundtables and live Internet events, has previously covered how the human microbiome influences brain development, and how the study of natural microbiomes drives the search for extraterrestrial life. Our latest roundtable looks at the role of nanoscience and nanotechnology in revealing microbiome communities.

The challenge is significant. Within only a few grams of soil or ocean sediment, rich and complex ecosystems exist that contain hundreds of thousands of different microbial species. Scientists cannot yet grow the vast majority of these single-celled organisms in a lab, and so they are immune to classification by conventional technologies. 

Nanoscience  may be able to help tease apart how the members of natural microbiomes interact with one another. To discuss this, the Kavli Foundation has invited two leaders in the field:

Eoin Brodie is staff scientist in the Ecology Department at the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory, and adjunct assistant professor in the Department of Environmental Science, Policy and Management at the University of California, Berkeley. He has pioneered technologies for accurately measuring microbiome community dynamics.

Jack Gilbert is principal investigator in the Biosciences Division at the DOE's Argonne National Laboratory and associate professor in the Department of Ecology and Evolution at the University of Chicago. He has studied the microbiomes that exist within hospitals and is working on ways to use bacteria-embedded nanostructures to rebuild infant microbiomes.

Below is an edited transcript of their discussion. The participants have also been provided the opportunity to amend or edit their remarks.

The Kavli Foundation: What makes a microbiome a microbiome? Is it only about size, or does it require a certain complexity?

Jack A. Gilbert: A microbiome is a community of single-celled microbes. It could include bacteria, fungi, protozoa, algae and viruses. It's a little community whose members are interacting with each other. It can be anything, from ten different species to 1,000 species to 200,000 species. 

Eoin Brodie: Consider this analogy: Think of all the different things you might find in a tropical forest. You've got different types of trees and animals and insects. All these things have evolved to work together to form some sort of stable system, in many cases, an ecosystem. So a microbiome is the microbial version of that forest ecosystem. Individually, each different species provides different functions that, together, are essential for the stability and activity of the system. [Body Bugs: 5 Surprising Facts About Your Microbiome Countdown]

TKF: Are there properties that emerge when microbiomes reach a certain size or level of complexity? Are they different from the properties of individual microbes?

J.G.: There are. This is an area of ongoing research, though we can start by looking at how ecological theory plays out in larger organisms. That helps us interpret and predict what microbiomes might do as they grow in complexity.

As complexity increases, we see more interconnections in the system. Think of it like a food web. If it combines multiple insects, trees, plants, and other things, it is potentially more stable than if it has only a single insect and a single tree. The more participants, the more interactions, and these interactions trigger still more interactions. Together, they regulate the abundance of specific types of organisms. Nothing takes over, they all share resources.

At exactly what point an ecosystem becomes stable or resilient is less clear. Macro-ecological theory suggests that when there are more connections, you build in redundancy. This makes the system more robust and resistant to disturbance, though there is a sweet-spot that may be hard to define. Larger ecosystems may have several organisms doing the same thing, though not necessarily at the same time or in the same place. But those organisms could step in when another organism performing that function cannot do so. 

J.G.: This is an interesting point. The very definition of a highly robust community or ecosystem is inherent flexibility. It's like a reed bending in a stream, flexing with changes in stress and pressure. Redundancy is part of that. There may be 20 organisms that produce methane, which is then used by other organisms. The members of that methane-producing community will respond differently to changing conditions. One might grow better at higher temperatures, another if temperatures drop. But the fundamental function of that assemblage producing methane, hasn't changed. 

TKF: Microbiomes are clearly complex and interconnected. They can have hundreds of thousands of different species. How do we begin to understand something like that? What's the current state of the art?

J.G.: There are multiple states of the art. 

E.B.: It's true. For example, we can only grow between 0.001 percent and maybe 10 percent of the microbes we find. For some systems, like the human gut, we are getting better because we know more about them. 

In soils, we're not very good. That's because it's very hard to predict what these microbes need to grow. They may have unusual nutritional requirements are, or need other organisms to grow. It almost impossible to grow them in a pure culture. 

One window into their function has been things that Jack has pioneered, using metagenomics and sequencing technologies that were developed for human genome sequencing. We can apply those technologies to these incredibly complicated microbial communities. 

So we take this community apart, just like an enormous jigsaw puzzle, and break it up into tiny, tiny molecular pieces that we can measure with sequencing machines. The real challenge, however, is putting those pieces back together again in a way that tells you something about the whole community. So, that's one approach. 

Another approach involves imaging organisms. You can see them using visible light or other wavelengths, identify their shapes, and learn about the chemistry associated with them. We have done that in some very simple artificial microbial communities we’ve grown in the lab. The challenge is finding ways to apply these technologies to increasingly more complicated systems.

J.G.: You know, you can put "omics" at the end of anything and get a new tool out of it. Genomics measures genes. Transcriptomics covers RNA transcribed from genes. Proteinomics looks at proteins folded by transcribed RNA. Metabolomics analyzes the chemicals and metabolites mediated by those proteins. There's a whole slew of them, and that means we have a lot of tools that can interrogate the components of the system. [The Hunt for Alien Extremophiles is Taking Off (Kavli Q+A) ]

One of our key challenges is to integrate all this information. Eoin's been developing some techniques to attack this problem by compiling this data into an interoperable data framework. It's all very well having a genome, a transcriptome, a metabolome — but pulling those together and creating knowledge out of the chaos can sometimes be an über challenge. 

E.B.: I'd say it's one of our grand challenges at the moment, and it is not going to be solved any time soon. 

TKF: Why so long? Are we talking weeks, months or years?

J.G.: Decades. 

TKF: For a single one?

J.G.: Sometimes. We're developing novel, high-throughput technologies that can help to alleviate that problem. But let's say I have a thousand genes. I don't know what function they encode. We may be able to express a small fraction of them and fold only some of their proteins. I might be able to figure out the function of maybe five of those proteins — I'm being generous. So out of 1,000 targets, today it would be reasonably simple for me to examine five of them. What about the other 99.95? What do we do with those? 

E.B.: It's a huge roadblock, but there's a whole new set of high-throughput technologies to automate this process. There are technologies for producing and folding proteins, screening protein function, and finding protein structures without crystallization. All of those things sort of exist, but there's no one lab or initiative that's pulling them together. And that's what we need to understand microbiomes.

J.G.: Even so, it's a big problem. Let me give you an example. E. coli has been our main microbial bacterial workhorse for 100 years, and we still don't know what one-third of the genes do. It's kind of crazy. I work on something called the Microbiome Project, which estimates that there are well over 50 million bacterial species on Earth. We know two-thirds of the genome of one of them. 

Still, we can study microbiomes in different contexts. For example, we can look at the emerging properties of an ecosystem, such as its ability to generate methane or consume carbohydrates. Then we can make and test predictions about the functions that community needs. It would be much better if we had all that genomic information, but we don't need it to advance our understanding. 

E.B.: Right, this glass really is half full. There are all these amazing chemistries that microbes perform that that can do really wonderful things for humanity, like providing new antibiotics and nutrients for crops. It's pretty much an unlimited resource of novelty and chemistry — if we can develop improved tools to tap into it.

TKF: How does nanoscience help?

E.B.: One of the great advances in sequencing a genome is parallelizing biological assays. So instead of sequencing 12 or 96 or even a few hundred strands of DNA at a time, we can sequence millions at a time. To characterize the biochemistry and chemistry of microbial communities, we have to scale in the same sort of way.

Using nanotechnology, we can build nanofluidic devices to run these assays. These would be the size of semiconductor chips, with nanoscale channels to capture tiny samples of DNA and test them with tiny amounts of reagents, all in parallel. We could use nanoscale imaging sensors to detect these reactions, instead of the large cameras we use today. And we can use semiconductor technologies to make tens of thousands of them from a single silicon wafer, which massively reduces the cost of those assays. 

There are clear paths to do this, but we need to rally around the challenge and bring different industries, like the semiconductor industry, together. 

J.G.: One of the most exciting things, from my perspective, is to use nanoscience to reduce the complexity of our datasets. Let's say I have 100,000 organisms in a few grams of ocean sediment or soil. I want to understand the role of a complex lipid in this community. If I knew which microbes were involved, I could target them and analyze which genes created or used that lipid. But I don't, so instead, I bind a quantum dot nanoparticle to a food particle used in making the lipid. The organisms that consume it will light up under x-ray analysis. 

That will show me the active organism. Then I can start looking for the genes that degrade or transform that lipid. We can use it to narrow down our search window to something that's a little bit more manageable. There are many ways we can deal with this, but this is a good nanotech route. 

E.B.: There've been some early successes, but also issues. A quantum dot may be tiny to us, but it is a big thing to a microbe. It can be hard to actually get it inside a cell. The organisms that ingest it in your experimental system may not be the ones that ingest it in nature. Still, variants of those approaches have a lot of potential. 

J.G.: As we've always said, my very act of observing this system has changed its nature. Still, either you don't bother or you try these techniques. You've just got to be careful interpreting what you see. Very careful. 

E.B.: Science is built on observation, manipulation, more observation, reforming your hypotheses, and repeating that cycle. Manipulation is a key part of that. 

Think about how we've manipulated individual microorganisms to understand their function. We start with a hypothesis about a gene's function, knock it out, and see if the organism has lost that function. We can then add that gene back and see if it regains that function, which would prove the hypothesis. 

We don't have an analogous way of doing that in a complicated microbial community. We need to knock out an entire species to see if they perform a particular function and observe what happens when that function is not present. 

A new approach to genetically engineering individual organisms might help. It's called CRISPR, and it is based on tricking bacteria into self-destructing. For this to work, you have to introduce a genetic construct, a plasmid or something like it, into the bacterial cell. Then it will create a protein that triggers a highly specific self-destruct mechanism. Many bacteria won't take up pieces of foreign DNA for that very reason, because it might mess them up. 

Nanoscience might be able to help us trick bacteria into ingesting this plasmid. For example, as Jack was saying, we can stick a quantum dot onto various molecules to identify compounds that bacteria will regularly ingest. We could also attach a CRISPR payload to those same molecules to trigger self-destruction, or knock out or potentially add a new function to the organism. CRISPR and a few other analogous technologies are potentially transformative for microbiome research, and nanotechnology could help us find the delivery mechanisms we need to make it work.

TKF: Is this something we can do relatively soon or are we talking about decades of research?

E.B.: People are doing it now, but they're using E. coli and other organisms that we know and can manipulate in the lab. We've already worked out the theory of how we could target a strain of microbes in a natural microbiome. We know it will work on some bacteria, but it will be difficult to inject these pieces of DNA into others. That's a big research challenge right now. 

TKF: What about applying some of the nanotechnology being developed to study the brain to investigate microbiomes in the soil or water?

E.B.: There's amazing work going on in developing miniaturized sensors based on radio frequency identification technology, or RFID. RFID tags are used by companies to track shipments. They can both transmit and acquire energy from radio waves, so they don't need batteries. It gives us a way of getting information from very small sensors without any wiring.

Researchers want to inject them into the brain to sense electrical impulses. I'm not exactly sure how that would work, but the idea is to wind up with a distributed network of sensors. You could read out their location and what they sense remotely.

Now, think about doing something like that in soil. We could make tens of thousands of them from a single silicon wafer, mix them with soil, and plant something. As the roots grow and pass the sensors, we would get a readout of things like temperature, moisture, pH, oxygen concentration, the presence of specific chemicals, and how that initial reading changes over time.

We could build these complicated three-dimensional pictures of how microbes are influencing the area around the root and soil. And perhaps we can use that in an agricultural setting to optimize things like water irrigation and fertilization.

J.G.: We could also use quantum dots here. We could, for example, tag an amino acid with a quantum dot, stick it in the community, and see which members take it up so we can determine who's active. 

The cool thing about this technology is that if you take a small sample of soil, maybe 10 microns by 10 microns, you could theoretically use this technique to identify where the active members of that community are. In a community of thousands of organisms, not all will be active at the same time. Some may be living with a very, very low level of activity, waiting for the right conditions to wake up. So we've got to map not only the 3D location of the organisms, but the fourth dimension of time to understand how that community is changing and responding to environmental stimuli. 

TKF: You've done something similar with hospital floors, correct?

J.G.: We had a grant to examine the microbiome of hospitals, specifically a new, $800 million facility being built in Chicago. We started looking at the floor when the building was an empty shell and watched as doctors and patients moved in and it became an active, functioning hospital.

We wanted to see how the ecology of that microbiome changed. That might give us some insights into health care-associated infections, the dissemination of antibiotic resistance, and the development of pathogen reservoirs.

It quickly became obvious that the vast majority of the bacteria released by people in the hospital die shortly after landing in what is a remarkably inhospitable ecosystem. We want to understand which ones remain active and which ones go dormant and could revive under different conditions. That's very important to understanding the transmission of diseases in hospitals, and how to control and manipulate microbial ecosystems in our homes, offices and public spaces.

TKF: So what happens next?

J.G.: It's a huge study. We're still working on it. It's an enormous study. We did it every day for 365 days, and generated 8.5 million data points. They included everything from activity assays and bacterial cultures and DNA sequencing to patient and staff medical records. We are teasing apart this complex database of interactions to see how this system actually developed and how it works. 

We would like to continue that monitoring. We would like to use some of these novel sensor technologies to continuously monitor this ecosystem and generate this data in a regular, detailed fashion. High-frequency spatial and temporal data is incredibly important if we want to discern trends and understand how to manipulate ecosystems. 

TKF: How would you use nanotechnology in your hospital project?

J.G.: As Eoin said, it's about shrinking our sensors down to very small scales. In a built environment, especially a hospital, people don't want to see these things. We need to take samples, process and analyze them, and transmit the data in a space smaller than a light switch. So we need to make everything incredibly small. That means immobilizing probes or primers on certain nanomaterial surfaces and using nanofluidics to reduce the amount of samples we need to capture. 

We would like to go even smaller, and compress these capabilities into a pill that you could swallow so you could analyze the human microbiome — or metabolome or even the proteinome — at any point in the gut. You could even put an RFID transmitter in there, so the pill could communicate with your phone and you could see what your microbiome was doing in real time. 

TKF: What other things might nanoscience do? Could it provide information that biologists typically cannot access? 

E.B.: You know, the same tools used in nanoscience to analyze materials and processes at the atomic scale are being used to understand microbial processes and microbial communication networks. One good example is electrical conductivity. Some microbes conduct electricity, which is how they make the energy they need to live. These processes are very diverse and varied, and researchers have used atomic force microscopy and similar nanoscience tools to understand how those electrons flow at the atomic scale. 

At the same time, researchers are studying how to couple these bacterial nanowires to inorganic or organic nonliving things. These nanowires can transfer electrons over long distances, and have incredible properties that are very different from our man-made wires. We can learn by biology, and we can also fuse biology with our electronics. 

TKF: What about using nanoscience to improve agriculture?

E.B.: We typically use chemicals, especially nitrogen in the form of ammonia, as fertilizer. Microbes can also generate nitrogen by taking carbon and using it fix atmospheric nitrogen into ammonia. Some bacteria do this within certain plant roots, but we'd like to look at nitrogen-fixing bacterial that live in other parts of many plants. Nanoscience has a role in understanding how those microbes talk to plants, how they share metabolites, and what regulates nitrogen fixation. If we could do that, we might be able to improve crop productivity and reduce or eliminate fertilizer use. 

TKF: What about manipulating the microbiomes in homes or people? Could nanoscience help with that?

J.G.: Eoin was just talking about restructuring the microbial environment for plants. We could do something similar in our buildings to give children the microbial exposure to develop a healthy immune system.

E.B.: Exactly. The early months of life are critical to the development of our immune system. The microbiome in our home may have a big impact on this. For example, if you have two large dogs that go outside, you're less likely to develop asthma. The hygiene hypothesis says this is because you are exposed to a greater diversity of microbes that the dogs bring inside. Cleaning and disinfecting prevents this exposure, and it may contribute to the rise of such inflammatory disorders as asthma and eczema.

J.G.: Exactly. We're interested in constructing new architectural interfaces and environments that give our children the right microbial exposures. That involves working with nanoscale interfaces. After all, a bacterial cell is only 700 or 800 nanometers across, and we're talking about creating nanostructures to understand and manipulate its surfaces. 

For example, we're very interested in constructing materials with pockets with embedded nanoparticles. These nanoparticles would have chemically modified interfaces that would attract the right kinds of microbes. 

TKF: How would you use these ideal microbiome environments?

J.G.: We might embed nanoparticles in 3D printing materials to promote an environment that enables the stable formation of biofilms of bacteria. We might be able to use them as probiotics that a child could take to reconfigure the microbiome in his or her gut. We might have microbial 3D printed walls or floors or carpets or even chairs or door handles. 

We're exploring ways to create very specific kinds of 3D printing inks that promote the development of specific kinds of microbiome. This may sound a little bit bizarre, but there's very hard science underneath it. You can't create a carpet and hope for the best. You have to understand how to appropriately manipulate microbiomes, and then create materials that interact with the right microbes and support a thriving microbiome. 

E.B.: That's a really interesting concept. You know, our buildings filter out everything below a certain particle size. Perhaps we could engineer intelligent filters that weed out dangerous toxins but allow more of the outdoor microbiome to enter. That would be an amazing contribution. There's no doubt that the microbiome we've evolved with has to have some impact on our heath, particularly in the early life stages. 

TKF: A final question. The use of nanoscience to study the microbiome is so new, I'm not even sure we can call it an emerging field yet. How do we achieve the critical mass of researchers we need to achieve significant breakthroughs?

E.B.: We clearly need to work across disciplines and keep extending our networks of researchers. Jack and I have a certain network, and then there are nanoscience researchers who are thinking about the intersection between their work and biology. We need to keep reaching out.

We also need to keep talking about the potential of the microbiome to improve the health of our planet, the health of humanity, our production of food, and our fundamental understanding of our world. No matter what discipline you're in, I think we're asking compelling questions and posing challenges that people can find scientifically interesting.

So we need to get our questions out there, seed the broader community with some potential ideas of where nanotechnology might fit, and I think people will find ways to use nanoscience in ways we never would have imagined. 

J.G.: Our team is working with Argonne National Labs and at the University of Chicago, which have large efforts in nanoscience, to implement some of the concepts we've been talking about. 

One of the major things we need to overcome is nomenclature. What I call the surface is not what they call the surface. What I call a biological agent is not what they call a biological agent. We have many words for which we have two separate meanings. Since we don't speak the same language, it is often much harder to get things started. 

We also need funding initiatives. When the U.S. National Institutes of Health committed $180 million to the Human Microbiome Project, lots of clinicians jumped at the opportunity. There has not been a similar initiative to use nanoscience to explore the microbiome. If someone put $200 million on the table, people would work harder at overcoming those communication barriers, and we'd see significant and rapid advances.

Which leads me to another point. We need to create a data commons — a stronger, much more cohesive capacity to analyze multiple data streams. Just as we need to overcome communication problems between people, we also need to overcome communications between data so we can use everything we generate. That is, in itself, another grand challenge. 

TKF: Another grand challenge?

J.G.: We have thousands of grand challenges. But it's a worthwhile effort to try and overcome them, to do nanoscience at the largest scales, because the largest scales achieve the greatest rewards. 

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Lindsay Borthwick, writer and editor for The Kavli Foundation, contributed this article to Space.com's Expert Voices: Op-Ed & Insights.

The Earth's most extreme microbes, including bacteria that eat radioactive metals, tolerate lethal doses of radiation and thrive in the planet's driest desert, are fascinating in their own right. But it is what they are teaching scientists about how to hunt for life on other worlds that may be their most important legacy.

That search isn't hypothetical. Scientists at NASA are planning missions to Mars and Saturn's icy moon Enceladus that may yield conclusive evidence of life on those worlds. But to get there, the research teams first have to decide precisely where to look and what signs of life to target. 

That's where so-called "extremophiles," and the harsh environments they inhabit, come in. They serve as living laboratories here on Earth to study what scientists hope to discover beyond it.

The Kavli Foundation brought together three prominent astrobiologists to discuss microbes and the search for extraterrestrial life. It's the second of a three-part series of roundtable discussions on the microbiome, the microorganisms that inhabit the Earth's different environments, from the soil to the human body. Part one, "Can Microbes in the Gut Influence the Brain?," revealed how the gut microbiome can influence human behavior and brain health. 

Below is a roundtable about the latest in the hunt for extraterrestrial extremophiles, featuring:

Steven Benner, president and distinguished fellow at the Foundation for Applied Molecular Evolution, a not-for-profit research organization in Gainesville, Fl. Benner works to create alternative building blocks for life in the laboratory and to apply this knowledge to astrobiology. 

Jocelyne DiRuggiero, associate research professor in the Department of Biology at Johns Hopkins University in Baltimore and a member of the University's Institute for Planets and Life. She studies how microorganisms adapt to extreme environments and what that can teach us about searching for life on other planets. 

Christopher McKay is a senior scientist in the Space Science and Astrobiology Division at NASA Ames Research Center near San Jose, Calif., where he investigates life in Mars-like environments on Earth and plans astrobiology missions to other worlds.

The following is an edited transcript of the roundtable discussion, which took place via teleconference on January 12, 2014. The participants have been provided the opportunity to amend or edit their remarks. The roundtable preceded a webcast with McKay and DiRuggiero that took place on January 28.

The Kavli Foundation: Research on microbes that inhabit the Earth's most extreme environments has helped to expand our knowledge of the limits of life. Jocelyne, how have those boundaries shifted in recent years?

Jocelyne Diruggiero: We're pushing those boundaries in terms of extreme environmental conditions such as extreme cold, heat, pH and pressure. But we're also doing a lot of exploration in environments with extremely low nutrient [content]. Microorganisms are very creative at finding sources of energy. For example, there's a bacterium that was found deep in a gold mine in South Africa that derives its energy from the radioactive decay of uranium. We've also found organisms in very cold lakes in Antarctica , where there is no obvious source of energy, and yet they find a way. This is important because we don't know what other sources of energy might be available on other planets in our solar system or elsewhere. [Cold-Loving Bacteria Offer Clues for Life on Mars]

Christopher McKay: One particular area that Jocelyne has worked on that NASA is interested in right now is the ability of microorganisms to repair radiation damage. To me, it's one of the most fascinating and surprising extreme capabilities, and very relevant to going out in space where radiation levels are high. It's just unfathomable why these organisms would have the capability to survive extremely high doses of radiation when on Earth there is no such environment.

TKF: So why have these Earth-bound species developed radiation resistance?

J.D.: The idea is that those organisms are adapted to desiccation and that that adaptation also helps them resist radiation because the damage to cells is very similar.

Steven Benner: Radiation causes damage to DNA by way of specific molecules, in particular, reactive oxygen species. These are created by radiation of many kinds, some coming from above, such as cosmic rays, and some from rocks, such as the decay of radioactive minerals. It makes little difference what the source of the energy is to create those reactive species.

So while it's true that organisms living deep in the Earth are not exposed to the high-energy radiation found when you travel between planets, or more hypothetically between stars, the systems that cells have evolved to repair damage done by reactive oxygen species will be useful whether they arise from rocks or from cosmic rays.

C.M.: As you've heard from Steve and Jocelyne, the story that is emerging is that organisms on Earth face one kind of danger and build a shield against it, and then that shield proves to be useful against other hazards, which may not be present on Earth but generate related challenges to the organism's survival and in their chemistry.

S.B.: One of the most remarkable things that comes from this work on extreme microbes is that in all of the niches on Earth where Chris has looked for life — and he's certainly been looking among the farthest and broadest — you find that "life found a way": The basic chemistry that got life started has managed to adapt to fill whatever hazards exist in those niches. That's still correct, right, Chris?

C.M.: Yes, it is. And even more surprising is that the life forms we find in all these diverse and unusual places are all on the same tree of life. We haven't yet, to my disappointment, found an isolated, obscure, little niche with organisms on it that are completely different and would be candidates for a different type of life.

S.B.: Chris, what are the chances that you would recognize those as living organisms?

C.M.: That's the rub. We might not recognize them even if they were there.

TKF: I'll come back to that point, but first, can you tell me what technological changes have enabled the discovery of so many new forms of microbial life?

J.D.: It's the molecular tools that we can now use to explore microorganisms in the environment. Before the invention of these tools we had to rely on our ability to grow, or culture, these organisms in the lab. But now, just by looking at some of their DNA, we can identify what they might be, and then if we sequence some of their genomes we can even get an idea of what type of adaptations they have to a particular environment.

C.M.: What Jocelyne just said is fundamentally important. Literally 99 percent of what's out there wasn't being counted before, when we had only culture-dependent methods of identifying microorganisms. It's like looking in a room and seeing only one person in there until you turn on the lights and realize there are actually 100 people. That's roughly the change that these tools have caused. It may be even more than 100-fold, right, Jocelyne?

J.D.: Yes. We're getting to what we call the "rare biosphere" —microorganisms that are in such low abundance that we couldn't find them or cultivate them before, yet sometimes they are essential to their communities because they carry out specific functions that other members do not. It's very exciting.

TKF: "Follow the water" has been the mantra of the scientific search for extreme microbes. But Jocelyne and Chris, your research has shown that microbes can eek out an existence in the driest place on Earth, Chile's Atacama Desert. How do they do it?

J.D.: When we looked at the Atacama's soil we found very few microorganisms and they were dormant most of the time. But what Chris and others first discovered, and then what I did more molecular studies on, are rocks. We call these rocks our "islands of life in the desert."

The microorganisms take refuge inside rocks, which protect them against extreme environmental conditions such as UV radiation and temperature. Rocks also retain water. So the microorganisms' secret is finding refuge where they can be protected and access the last teeny bit of remaining water in the desert. ['Whale Rock' on Mars Shows Signs of Ancient Lake (Photo ) ]

C.M.: In dry deserts in the Atacama, the Sahara, the Namib and Antarctica, it takes us a while to figure out where the water is. But when we figure it out, the organisms are there. They followed the water before us.

S.B.: Chris, are you still of the opinion that if there is no water to be found, there'll be no life, full stop?

C.M.: Yes. Nothing grows or reproduces when the water activity falls below some pretty high value, actually. It's not like phosphorus or other nutrients where organisms can adapt strategies to work with less and less and less. Microorganisms need surprisingly wet conditions.

S.B.: So there's another limit to the chemistry that we all share.

J.D.: But the advantage of microorganisms, at least some of them, is that they can be desiccated for a long period of time and resume metabolic activity when water is available.

TKF: The human body plays host to about 10,000 different kinds of microorganisms. Jocelyne, how big are the microbial communities that you study in the Earth's most extreme environments?

J.D.: In the Atacama, we can find a few hundred species, but there are four or five dominant ones, and then a long list of very rare microorganisms that are cohabiting and might just be waiting for a better time to take over and start growing. So there are many fewer than you find in garden soil or in the human gut.

TKF: Chris, what has all this research taught you about how to search for life on other planets or moons?

C.M.: It tells us that we have to think like a microorganism especially when it comes to water. And that translates into an appreciation that the amount of water can change from one place to the next on a very small scale. In the Atacama, as Jocelyne pointed out, the soils can be extremely dry and lifeless in one place and then right next to that may be a rock that's soaking up water and supporting life.

The picture that we often have of life is as a big lawn spread uniformly over the hillside. Whereas in extreme environments, what we actually see is tiny niches that these microorganisms have found to exploit, and so we have to think that way when we search, particularly on Mars, for evidence of life or evidence of past life.

S.B.: But keep in mind that the environments that we call extreme on Earth are actually rather mild compared to the environments where you might go looking for life in the solar system. A couple of days ago it was warmer on Mars than it was in Minnesota, but Mars is overall colder than Earth, as are Jupiter and Titan, the largest moon of Saturn. At some point the temperature drops to the point that alternative liquids, such as the liquid hydrocarbons we find in Titan's seas, become conceivable substitutes for water.

We are exploring in the laboratory molecules that might support life in these environments, which are from our perspective far more extreme than any here on Earth. We're asking whether general principles that are not unique to life in Earth-like environments might guide our search for life that lives in very different environments.

For example, as Jocelyne's work shows, microorganisms very often manage difficult problems in adaptation by forming communities. That might very well be a general principle for life regardless of the underlying chemistry. And it is something that can we learn about by looking at life on Earth.

TKF: Steve, is that tendency to form communities a property that we could take advantage of to search for signs of life in other worlds?

S.B.: That's right. There's no real reason why the chemical particulars of our proteins and nucleic acids, which are almost certainly in part a reflection of an historical accident, will be universal to life on Titan, or in Klingon life or life on Vulcan, right? So we need to think about what is universal to biology, regardless of its underlying chemistry. Certainly Darwinian evolution is universal, and some management of information associated with that would presumably be universal as well.

TKF: Can we search for these universals?

C.M.: Take a meta-look at life?

TKF: Yes.

C.M.: It's very hard to do. My job is to fly to other worlds and I need to create instruments to search for life on those worlds. How do I create an instrument that detects information and the ability of a system to record information and change in response to its environment? We don't have good answers to that. The one thing that we've come up with is that life on Earth uses molecules with a certain handedness, or orientation. Using a metaphor, life on Earth drives on the left side of the road. And that may be a powerful tool.

S.B.: One could also look for metabolism signatures. If I examine a sample of the juice extracted from you, I will see a defined list of chemical compounds that have structural relationships between each other, reaction mechanisms that will convert one compound to the other and so on, and an energetic relationship between them as well. These are the signatures of an organized metabolism, and of life, no matter what the molecules that participate in that metabolism are.

TKF: Okay, so what signs of life, or biosignatures, should we be striving to detect and are within our grasp technologically?

C.M.: It's funny you ask because I'm giving a talk tomorrow in which I try to answer the question, If we do a mission to Enceladus, one of Saturn's moons, what should we look for? Enceladus has everything that we would have on our checklist for a habitable environment, including a plume of water vapor with organic material. If we were to fly through its plume, and we're proposing to do so, I'd suggest that the best molecules to measure are amino acids, the building blocks of proteins, because: one, we know how to measure them; two, there's lots of them and they occur naturally in the solar system, so we could expect them to be there; and three, life on Earth has made specific choices in amino acids. It uses a set of just 20 amino acids to build proteins, and those amino acids are all left-handed.

But work by people like Steve Benner and others has shown that life could be based on amino acids other than that set of 20, and it could be based on another handedness, or orientation. If we fly through the plume of Enceladus, measure amino acids and find a bunch of them that all have the same handedness, even if they are different amino acids than the ones that support life on Earth, that would be very convincing evidence of a different type of life. Not fundamentally different like silicon-based life, but different enough that we would be sure that is doesn't represent a common origin with life on Earth.

S.B.: I think Chris is on point here. Amino acids are extremely good ways of putting together functional molecules. It would surprise me to encounter a life form that works in water and is carbon-based, but that does not use the assembly of amino acids in some way. Amino acids are found all over the place, including in meteorites where they presumably originated without biology. So if Chris were to find amino acids in the plume of Enceladus, the challenge becomes determining whether they are the product of a biological process.

If he were to find that they're all the same hand, that would be convincing, because that's what makes the protein evolvable. And we happen to believe that a higher-level biosignature is the ability to use Darwinian evolution to get the function out of functionless matter.

J.D.: If you're flying through the plume on Enceladus, then amino acids are a great idea. But if you're digging in the soil of Mars, you want to look at other types of molecules like forms of lipids, or fats, that resist degradation. If you're looking at the atmosphere of exoplanets where we can't go, then you're going to have to look for different types of gases, such as oxygen. So, the question is really where are you looking and then what can you look for?

TKF: Chris, you've mentioned Enceladus and Mars. But what are the best candidates in our solar system for life and why?

C.M.: I would list them as number one, Enceladus, because of its plume. Number two, Mars and Europa. Mars because of evidence that it once had water, and it's such an Earth-like world in terms of the diversity of the surface environments. And Europa because it's clearly got a large ocean underneath the ice and tidal heating, which keeps its water liquid. Then in category three, I would put Titan, not because it has water but because it's got another liquid at the surface. And it's the only world besides Earth that has beaches where liquid comes up on shore, and that, as Steve was one of the first to point out, could be a liquid used for life. In the fourth category would be the other small worlds of the solar system like Ceres and asteroids and comets, which have tantalizing hints of water activity but no clear evidence of it yet. In the bottom category are Venus and Mercury, places that I wouldn't go to if they paid me.

TKF: Has there been a particular discovery in the past year that has raised your hopes that we'll find evidence of extraterrestrial life, past or present?

C.M.: For me, the most inspiring news was the discovery of Kepler 186f, which is the first Earth-sized planet in a habitable zone of a small star, and I think that is a benchmark in the notion that there could be life on other worlds. Jocelyne mentioned that one way to search for life is by looking for oxygen in the atmosphere of a world. That's something we can apply to this planet. We can't yet, because the telescopes aren't big enough, but we will.

J.D.: I agree that the very large number of exoplanets is very exciting. But it's a bit like having a candy that you can't eat because we can't do the follow-up experiments to look for signs of life. So that's the issue for me.

S.B.: What is Chris's excitement is our headache, because following the discovery of an Earth-like exoplanet, the problem gets kicked back to us. We get asked: What can you observe from a g-r-e-a-t distance that would be definitive evidence or even suggestive evidence of biology on this very, very interesting extrasolar planet?

C.M.: True, we don't have the technology to look at the atmosphere of Kepler 186f. It is 500 light-years away. But the astronomers know what they would like to build to do that. So I predict that in 10 years we will have detected oxygen in Earth-size planets around Sun-like stars.

S.B.: I have frequently bet against the technological capability of the astronomers. Then, usually within 12 to 18 months, they've turned around and surprised me.

Let me give you an alternative prediction, however. In the next five years, I think we will see the generation of laboratory versions of self-replicating "Darwinian" systems. These artificial "life forms" will be based on chemistry that is inspired by the Earth's biology but sufficiently different that they are recognizably not descendants of a common ancestor of you and me. It's going to be an alternative life form that is able to evolve, adapt and reproduce like natural life, but differently. It will give us a new perspective of life as a general phenomenon, independent of the one example of life that we see on Earth.

Of course people will say, "Well, as a chemical synthetic product it's not likely to be anything specifically found on Earth or on an exoplanet." But it will be a second example of life, and I think that the study of that will be most informative about life in general.

J.D.: I agree that the astronomers are making huge progress. So my question to you, Chris, is where do we have the best chance of finding life in the next 10 or 20 years: inside or outside of our solar system?

C.M.: I see a race with three horses in it: the discovery of oxygen on other planets, organics on Mars or Enceladus, and the second genesis created in the laboratory by Steve Benner and his friends. One of those three might succeed in the next 10 years. The horse I'm riding is Enceladus and Mars, but all three of them are moving ahead quickly. I think it's pretty cool.

TKF: Bringing things back to microbes, do you think that when we find life beyond the Earth, it will be microbial?

J.D.: If I have to bet, I would say microbial, absolutely. They can do pretty much anything.

S.B.: We will find microbial life. Macroscopic life will be what finds us.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Space.com.

Alan Brown, writer and editor for the Kavli Foundation, edited this roundtable for Live Science's Expert Voices: Op-Ed & Insights.

For two decades, scientists and engineers have labored to build and control nanomaterials and to understand how they interact with the world around them. Now, researchers have begun to harness that knowledge to change the world. The results of their efforts include "invisibility cloaks," nano-coated stealth antibiotics that slip past a cell's defenses to attack a disease's vulnerabilities, artificial systems that mimic photosynthesis, quantum computing, and even instant transmission of information over long distances. More prosaic advances include longer-lasting batteries and energy storage systems, more efficient water purifiers, and even improved golf clubs and bicycles. In fact, research at the nanoscale is so broad and so profound, it is often difficult to understand how its various strands fit together.

To unravel the answers, the Kavli Foundation invited the directors of three of its nanoscience institutes to discuss the future of nanoscience and nanoscale technologies:

Paul Alivisatos, director of the Kavli Energy Nanosciences Institute at University of California, Berkeley, and the Lawrence Berkeley National Laboratory, and director of the Lawrence Berkeley National Laboratory;

Paul McEuen, director of the Kavli Institute at Cornell for Nanoscale Science;

Nai-Chang Yeh, co-director of the Kavli Nanoscience Institute at the California Institute of Technology.

Below is an edited transcript of their discussion. The participants have also been provided the opportunity to amend or edit their remarks.

Kavli Foundation: Nanoscience encompasses everything from quantum computing and understanding the brain to creating targeted medicines. It also seems to make the seemingly fantastic possible, such as teleporting information and invisibility cloaks. How can all these things fall under the heading, "nanoscience?" What ties them together? Are they really that similar?

Nai-Chang Yeh: Size. The prefix "nano" is short for nanometer, and it refers to length scales in the billionths of a meter. All the topics you mentioned deal with objects and phenomena that take place at similar length scales. While nanoscience is a multidisciplinary field that branches off in many different scientific and technical directions, its methodologies and approaches to fabrication, characterization, and integration of nanostructures are similar across those fields.

Paul Alivisatos: Maybe I could jump in and add that nanometers are not a randomly chosen length scale. It's the size where our building blocks — atoms, crystals, and molecules — start to show certain types of phenomena, or they achieve sufficient complexity to demonstrate certain functions. So, control of matter on the nanoscale becomes unusually important.

Until recently, we've built nanoscale objects by carving small structures out of larger wholes. This top-down approach limited our ability to access the nanoscale realm. As we learn to build from the bottom up, we can access the type of things you mentioned in your question, like quantum phenomena and the complexity and functionality of an enzyme catalyst. The length scale is a very specifically relevant one, and that's why the applications of nanoscience can be so broad.

Paul McEuen: I'll throw in one other thought. In addition to being an important length scale, nanoscale is also defined by its difficulty. It pushes researchers from every discipline outside of our comfort zones. It's too small for solid state physicists, it's too big for chemists, and it's too interdisciplinary for biologists. We don't know how to play very well at that length scale, all the way from imaging to manipulation and control.

P.A.: Meanwhile, we can be very jealous of nature, which seems to have no trouble doing it at all.

P.M.: Correct.

TKF: Clearly, this is field with great diversity and rapid growth. That makes it hard for people to get their arms around it. Can you explain how our understanding of nanoscience is changing, and discuss its potential?

P.M.: There are many answers to that question. One is that, in many ways, we spent the past decade or two learning how to make and measure individual nanoscale objects. These are sort of nano building blocks. Now, people are putting a lot of effort into learning how to put these building blocks together to create systems with interesting properties or functions that emerge only from these more complex structures.

N.Y.: I completely agree with that. Today, we seeing new approaches to put those building blocks together in novel ways. We can build metamaterials with unusual properties. We can couple functionalities that don't usually go together, like microwaves and optical lenses, do innovative physics, or manipulate quantum information. All of these things are really new dimensions in our study of nano science and nanotechnology.

P.A.: Now the research is more fun, because we're not stumbling around completely anymore. We can approach these problems in a more interesting way because we've got a little bit more control.

P.M.: I could say this is a very optimistic viewpoint.

P.A.: Well, at least we're stumbling around on a different stage, let's put it that way.

P.M.: Like a child who has his fingers in the paints, and now we're going to have to make art.

P.A.: Exactly like that. At least we've got the paint.

N.Y.: I would like to bring up another point. People are realizing that we have to deal with the hazards and safety of nanosystems , and that as we develop the capability of nanoengineering biological systems, there are also issues related to ethics. We're not just scientists playing in our sandboxes. We also need to be aware of some of these societal issues.

TKF: Could you give me an example of a health, safety, or environmental issue related to nanoscience?

N.Y.: For instance, if certain types of nanoparticles get into the environment, they may not decompose. They might prove hazardous if they get into the bloodstream. Airborne nanoparticles might get into your lungs. Nanomaterials promise many benefits, but people must also pay attention to potential hazards as well.

P.A.: I agree. These are important issues, and people have been sort of grappling with them for a while, actually. We've made a lot of progress in understanding nano toxicology and availability intellectually. One of the things that's been difficult is that you can start with nanoparticles with identical compositions, and depending on how you formulate them, they will behave very differently.

For example, we can coat nanotubes so they disperses very nicely into a liquid or precipitate as an ultrafine powder. We can embed the same nanotube inside a chunk of glass and it will never come out, or make it as a powdery substance that wafts into the air. We start with the same building block, but each formulation behaves differently. That's made it more difficult to understand the toxicology. After all, how do you build a firm foundation for the science when the formulation is as important as the substance you're looking at?

The nanoscience community started working on these issues almost from its start, though maybe not as systematically it could have. Over the past five years, I think researchers have made a lot of progress in building those foundations, learning how to classify these materials and formulations in ways that allow a lot more understanding.

P.M.: Actually, the health and safety issues that we're facing are not unique to nanoscience in any way. Chemical safety issues have a long history. Take, for example, thalidomide, a drug that was introduced for morning sickness in the 1950's. No one realized that there were two chiral forms, one left-handed and one right-handed. One made you feel better if you had morning sickness, the other gave you birth defects. So we need to understand the complexities of what we're working with, and not just label it based on its atoms.

Also, there are well-defined regulatory structures designed to deal with these issues. Most nanoscience research does not present particularly unique challenges in terms of how we regulate other chemicals or biological agents or what have you. I think that's good news. It means, there's a system out there for us to plug into. Of course, nano has unique aspects, but it's not like we have to build something new from the ground up.

TKF: Is there a role for nanoscientists in dealing with health and safety?

P.A.: Different societies take very different approaches to risk. The United States and European Union take different approaches to how they deal with regulation and risk. Because our understanding of these issues has grown much stronger, we have a better basis for approaching them more systematically. I think we are actually getting close to the stage where future decisions will leave the science realm and enter the policy realm. At that point, nanoscientists could be helpers, but they are not as good as policymakers at determining regulatory outcomes.

TKF: Researchers often talk about grand challenges, big questions whose answers promise to open up new possibilities and unexpected avenues of research. What are the grand challenges in nanoscience?

P.M.: I'll throw out one. One of key problems we face is that we don't have good tools. What we want is a magic box, where we can put in a nanostructure and find the location and movement of all the atoms as they respond to external stimuli. In other words, we want to make atomic-scale movies of what's happening inside nanostructures. That would push things forward in a thousand different ways, because very often we don't know what's going on and we have to infer indirectly. This year's Nobel Prize in chemistry for super-resolved microscopy was a small step forward toward such a magic machine.

N.Y.: I completely agree with Paul on this one. Basically, we need a four-dimensional tool that can characterize properties spatially over time. There are some tools out there, but generally, if you get the spatial resolution you don't have the time-dependent information, and to do both together is not easy.

Another big challenge is the integration of a large number of nanostructures into functional devices. And the reliable mass production of those nanodevices with proper error corrections. Nanostructures are usually more prone to errors than large structures, so this is not easy.

Another grand challenge is understanding how the properties of nanoscale objects relate to the properties of larger structures built from those objects.

Those are technical challenges, and they are important. There are also other challenges that are more societally related. As our research grows more expensive, we need to find ways to fund our work at a time when our government seems to be reducing its support. Also, very multidisciplinary nature of nanoscience poses challenges to our education, training, and research.

P.A.: Maybe another way of saying that is we face both inward-looking and outward-looking challenges. Developing better instruments is an inward-looking challenge. The outward looking challenges touch on societal needs, and there are many of them.

For example, the BRAIN Initiative, which uses nanotechnology to measure how neurons function in large groups, is very, very important. There is also a slew of needs that relate to energy and the environment, such as whether we could make materials that have an intrinsic ability to be recycled easily.

I think there will be increased long-term interaction between those inward and outward-looking challenges. The field's just getting to a stage now where the outward-looking challenges feel more achievable, although they're still really hard.

P.M.: Paul and I were recently part of a panel that reviewed National Nanotechnology Initiative grand challenges. These included nano-enabled desalination of seawater to solve the emerging water crisis. This was an example of outward-looking challenges. Another was the creation of 3D nanoscale printing, which was more of an inward challenge.

I also wanted to mention a grand challenge that is both inward and outward looking, one that we have been discussing for probably two decades. This would be making self-replicating systems from simple, basic constituents. This type of system would borrow from biology, harvesting energy to manufacture copies of itself and perhaps even improving its functionality over time. I can't help but think it's the most interesting thing out there.

P.A.: In the two decades we've been thinking about it, I'm not so certain we've gotten all that much closer to achieving something like that. It is a really interesting challenge, of course, but I don't know anybody that's seriously got their sights set on being able to do this in the next 10 or 20 years, or in any other reasonably foreseeable unit of time.

But borrowing from biology opens some very interesting doors. Think, for a moment, about all the garbage people generate. Imagine having materials that, instead of making copies of themselves, would break apart into constituents that we could reuse to make other products.

That would be a big step forward. A characteristic of life on the global scale is that it unmakes what it has done. Otherwise, it creates a big, unsustainable waste problem. I think that creating reusable nanomaterials is actually pretty achievable if we work on in it more systematically.

N.Y.: We can also borrow from biology to achieve energy sustainability. For example, nanoscientists hope to learn from nature and become very efficient at artificial photosynthesis or splitting molecules. We could do this in ways that would be simpler than imitating nature's complex biological functions, and that would be a big step forward.

P.A.: That's a good example. That way, if we make carbon dioxide by burning fuel, we could turn the carbon dioxide back into fuel. That would close the cycle, and you have to close the cycle if you want to be sustainable on a planetary scale. When we learn biology in grade school, it's all about cycles — nitrogen, carbon, water, whatever. That's what nature evolves towards, because that's what's stable when you talk about really big systems.

TKF: There are many great challenges. So, should nanoscience researchers try to prioritize them? One reason physicists and astronomers can line up money for expensive experiments is that they can agree on the experiments they need to run. And really, they are interested in knowledge for its own sake, while you want to give us cheap renewable energy and safe drinking water. Is there any chance of nanoscience researchers getting behind a single research agenda and lining up the money for breakthrough experiments?

P.A.: If you aggregate all nanoscience research, it adds up to many billions of dollars. It's just done in many smaller pieces. Now, I happen to believe that, in many cases, there are enormous advantages to large organizations that bring people together to achieve a goal more efficiently through larger scale cooperation. I think the astronomers do that because, if they make a small instrument, they can't learn anything new.

Nanoscience is different. We're still at a stage where we can make a lot of progress in a laboratory with a small group of faculty, post-docs, and students.

That said, I'm so happy that astronomers get major funding. It means that society is still moved to understand what goes on around us, and that's a really good thing. But I don't look at that funding with much jealousy myself. Given our stage in understanding, I think nanoscience's scale of funding makes a lot of sense.

N.Y.: That's a good point. I also want to mention that when astronomers are ready to take the next big step, they often rely on a people with completely different backgrounds and strengths. For instance, some cosmology experiments rely on people who can make excellent superconducting nanoscale devices. My colleagues at the Jet Propulsion Lab team with condensed matter physicists and low temperature physicists to develop the new tools and concepts needed to further our study of the cosmos. So, while we funnel that money into astronomy programs, we are also pushing many other research fields, including nanoscience.

P.M.: I want to make two completely independent points. The first is that one thing astronomers have going for them, even more than agreeing on research goals, is that they've got great pictures.

N.Y.: In false colors.

P.M.: Yes, but they use their pictures well. They tap into wonder, and people will fund wonder. And I think we in nanoscience could do a better job of tapping into wonder.

The second point is that we really have to make sure that the type of funding matches the type of research. There's no doubt that we could do big projects, especially in areas like electron microscopy and imaging, where researchers just need a bigger, better instrument.

But many of the major advances in nanoscience over the last couple of decades have come from oddball people working in strange corners of the field. Graphene is the classic example. Everybody thought it was a complete waste of time, right up until it took over the nano research world.

My second example involves imaging, and two guys who were out of work and building an instrument in their living room. They won the Nobel Prize in chemistry this year. It just shows that it's not always big money that's needed, but also money for really creative, out-of-the-box stuff. In a field like nanoscience you really have to fund both.

P.A.: I totally agree with that, Paul, but there are also fields where we need the big push. Brain imaging is an example. People are very close to reaching the threshold of what can be achieved in individual laboratories. The complexity of the problem has reached a scale that is very, very challenging because it requires integration of detectors, materials, computing and many other types of engineering.

Brain science is at the threshold , and to cross it, we need to change how we are organized. That takes a little bit of time, but we've seen this before. Take, for example, the human genome initiative. We started with small, laboratory-based science and learned to manipulate and sequence DNA. But larger scale projects created the field of genomics that we have today. That was unachievable by individual laboratories. It required the community to come together. It was hard to do in the beginning, and I think that's where brain projects are at the moment. Much of the nanoscience we need is still in its cottage industry mode.

N.Y.: I see your point, Paul. Bigger themes, like the brain, draw people together and enable them to deal with complex issues. Under a well-designed plan, the government probably can come in and support these bigger themes.

On the other hand, we should not only fund big projects. It's also very important to nurture independent researchers with very creative ideas. But supporting high-risk research is an area where the United States is getting worse. That's something that other nations — China and others in Asia — are doing much better. They are investing a lot of money in trying to encourage creativity, and yet in this country we're seeing dwindling support for high-risk projects by creative individuals.

TKF: What do you think about what Nai-Chang is saying? Is the government spending enough on the right type of research? And what roles do you see for non-government funders, such as foundations and corporations?

P.M.: I think we are talking about two completely separate questions. The first involves the total amount of research funding, and if you ask any scientist, he or she will tell you that we always need more.

The second question is about whether we are spending our research dollars efficiently and effectively. I think a lot of us feel like we could do much, much better. I think it dovetails with what we've already discussed. Sometimes we do need grand challenges that identify important national needs or major projects. We are seeing attempts by federal funding agencies to adopt this model to some degree.

But we also need to fund the most creative and best people. University professors create science, but our real product is the people we train as we pursue that goal. And supporting our best people is the key thing that we need to do better. We need to give those people the freedom to do creative work without overburdening them with quarterly reports aimed towards an objective that is going to change every quarter, because that's the way we fund science now.

I think funding the people, not the project, is one positive step forward. We could, for example, fund a lot more National Science Foundation fellowships for graduate students, rather than supporting those students through individual and investigator grants. Having their own funding would free students to vote with their feet by moving to the most exciting topics, and enable them to explore some crazy idea. Of course, they would do this in concert with a faculty member, but there would be a lot more freedom of movement than in the current system.

For both young and senior faculty, funds that allow us to try out our craziest ideas and really take risks are very, very important. That is money that's very hard to come by.

P.A.: I think right now is a really interesting and very positive moment in funding. This is exemplified by Fred Kavli, a very practical engineer whose interest was always in really new ideas. So he dedicated his fortune to fostering new fundamental discoveries.

He is an exemplar of a whole community of scientific philanthropists that did not really exist 20 or 25 years ago. The science community has an unusually positive opportunity to engage with these people, because they can add value to our existing and very impressive federal science funding system. I think this is really going to be enabling.

You also mentioned companies. They have become more focused on the immediate term, yet they realize that they have enormous needs for longer-term research. As a result, the partnerships between companies and universities have gotten much deeper and more substantive over the past 10 years. It looks like that trend is going to continue.

I think these are good trends. The philanthropists want to promote early discovery, and the companies are asking us to focus on the technologies they really need. Both types of research enrich the science community in the United States, and create avenues to do really vital work.

N.Y.: I completely agree, and want to inject one more point. Generally, government funding comes with regulations that limit how you interact overseas. Foundations have no such limitations, and make it easier to bring people together beyond national borders. The Kavli Foundation, for example, established institutes around the world. They play a very, very important role in teaming up international talents and facilitating interactions through conferences, workshops, or even exchange programs.

TKF: Paul, earlier you said that your most important product is the researchers you train. I wanted to ask you about that. At the nanoscale, the differences between conventional disciplines begin to blur. If you want to study the mechanical properties of materials, you might need to understand quantum or electrical interactions. If you want to investigate chemistry, you may need to know about optics and electromagnetism. Do we need to train students differently to study nanoscience?

N.Y.: I'm still a strong believer that we need to train students to be very, very strong in one of the core disciplines. Then, of course, if they're moving into nanoscience or nanotechnology, we need to help them broaden their horizon beyond that core. If they're dealing with nanoscales, that's a size where quantum mechanics matters. Even biologists investigating nanoscale phenomena must be very strong in the physical sciences.

P.A.: I also believe students need to learn one core discipline really well, because otherwise they won't be able to solve new problems when they come across them. But, to make an analogy, they also need to learn to speak multiple languages better.

Here's what I mean. We live in such an interconnected world, anybody who speaks several languages can automatically do more things than somebody who speaks only one. I think nanoscience is like that. It has all these interconnections. So, while it's important to really be good at one language, like physics, all the more power to you if you can learn one or two more.

In fact, I think most students yearn to learn another language or two. So the question becomes, how can we train them up in one discipline while helping them get better in one or two others? The students want to do it, and in many cases, they're just doing it themselves. The whole way the current generation of undergraduate and graduate students learn is different than the way I might have learned because they have different and more efficient ways of accessing information. So, for universities, the challenge is to move the curriculum along so they build that strong foundation while allowing them to do more to learn that a second or third language.

P.M.: I agree. And just to follow up, what we don't need is to create and learn a new language and then not be able to talk to anybody but ourselves.

P.A.: That's right.

N.Y.: That's an excellent point.

P.A.: The languages that are out there are already quite nice.

TKF: So, final question. You're all involved in some of the most exciting nanoscience going on right now. If we were to meet again in five or 10 years, what do you think we would be talking about?

P.M.: The past 50 years has all been about miniaturization of information technologies. I think the next 50 will be about the miniaturization of what I call machines: nanoscale devices with physical parts that move and can do anything from drug delivery to disassembling themselves for recycling. Small scale machines are going to be a huge growth area, and I think that's what we will be talking about in 10 years.

P.A.: I'm hesitating here because I see our field reaching out into so many disciplines. There's progress happening in so many areas, I have a hard time choosing any one of them.

N.Y.: I think we will be talking about integrating nanoscale devices and small machines into nanosystems with special properties. Like Paul, I see many different directions where we can go. I believe that some years from now, we will see advances in information, communication technology, energy, and sustainability, as well as new materials based on nanotechnology, and new tools to better understand nanosystems. I see major things happening in nano-facilitated medicine, and, as we learn more about brain function, new types of artificial intelligence and a better understanding of complex biological systems.

P.A.: I'm hoping that people will look back on this moment as a very special one, because this was when nanoscience began to change the way we look at the world. It is like a movement, a new way of thinking and bringing things together. Instead of trying to break everything down into individual disciplines, nanoscience show us how to bring them all together. It represents an important stage of scientific development, and has many implications for technology.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Lindsay Borthwick, writer and editor for The Kavli Foundation, contributed this article to Live Science's Expert Voices: Op-Ed & Insights.

The trillions of microbes that inhabit the human body, collectively called the microbiome, are estimated to weigh two to six pounds — up to twice the weight of the average human brain. Most of them live in the gut and intestines, where they help us to digest food, synthesize vitamins and ward off infection. But recent research on the microbiome has shown that its influence extends far beyond the gut, including to the brain. During the past 10 years, studies have linked the gut microbiome to a range of complex behaviors, such as mood and emotion, appetite and satiety, and even learning and memory. Not only does the gut microbiome appear to help maintain brain function, but it may also influence the risk of psychiatric and neurological disorders, including anxiety, depression and autism. 

The big question is how?

Recently, The Kavli Foundation brought together three researchers at the forefront of this emerging field to discuss the microbiome-brain connection and whether we can treat disorders of the brain through the gut.

The participants were:

Tracy Bale, a professor of neuroscience at the University of Pennsylvania School of Veterinary Medicine and Perelman School of Medicine. She is studying the effects of early prenatal stress on fetal brain development and has shown that this is partly mediated by the microbiome.

Christopher Lowry, is an associate professor in the Department of Integrative Physiology and Center for Neuroscience at the University of Colorado Boulder and director of the Behavioral Neuroendocrinology Laboratory. Lowry is developing new strategies to prevent and treat anxiety and depression, including the use of beneficial microbes that live in the gut.

Sarkis Mazmanian, is a professor of Microbiology at the California Institute of Technology and a 2012 MacArthur Fellow. A microbiologist and immunologist by training, Mazmanian studies how the brain, the immune system and the microbiome interact in health and disease, including its affects on autism spectrum disorder.

On January 15, 2015, at 3:00 p.m. ET, join The Kavli Foundation for a live webcast with Christopher Lowry and Sarkis Mazmanian, in which they discuss new discoveries about the gut-microbiome-brain connection and answer your question. Submit your questions via e-mail at any time to info@kavlifoundation.org or via Twitter using the hashtag #KavliLive.

The following is an edited transcript of a roundtable discussion that took place via teleconference in December 2014. The participants have been provided the opportunity to amend or edit their remarks.

The Kavli Foundation: The idea that the microbes living in our gut have an effect on the brain is a relatively new one. What set you down the path to studying this relationship? And how has your thinking evolved since then?

Sarkis Mazmanian: For more than a decade, my laboratory has been studying the interaction between microbes and the immune system. I took this path in the last five years because, through conversations with neuroscientists here at Caltech, I realized there are many parallels between the immune and nervous systems. For example, immune cells and neurons produce and sense many of the same chemicals. Since microbes were having such a profound effect on the immune system, I wondered whether they were having an effect on the brain, too. I thought that we would find that microbes interact with the brain via the immune system. But the data we've generated so far have shown that microbes interact with the brain by producing molecules that impact behavior without altering the immune system. Though we haven't ruled out an immune link, we have discovered mechanisms by which microbial molecules may directly interact with the nervous system. 

Christopher Lowry: My lab has been studying interactions between bacteria, the nervous system and emotional behavior for about 15 years. We've found, for example, that mice exposed to an inactivated soil bacterium called Mycobacterium vaccae increase production of the neurotransmitter serotonin in the brain, which has antidepressant-like effects. 

The turning point for looking at gut-microbiome-brain interactions in my lab really came with our first collaboration with Rob Knight, who leads the American Gut Project here at CU-Boulder. Together, we've been investigating ways of modulating the immune system to prevent stress-related psychiatric disorders, such as anxiety and mood disorders. Although this work is still in progress, it's clear that the microbiota plays an important role in stress-induced chronic anxiety, at least in animal models. [5 Ways Gut Bacteria Are Good for More Than Just Your Gut  ]

Tracy Bale: My lab works on the impact of stress during pregnancy on the developing brain using a mouse model of early maternal stress. There was a Radiolab episode on NPR that provoked a conversation in the lab about the vaginal microbiome, which is the main source of the bacteria that first populate a newborn baby's gut. We started thinking about the environmental factors, such as stress, that could change the vaginal microbiome and wondering if that would have an impact on our model of brain development. It blossomed from there because the relationship between a newborn's gut microbiome and his or her mother's vaginal microbiome is almost one-to-one, with a newborn's microbiome changing in direct response to its mother's. We wondered, how does this interaction alter the way a baby's brain develops in our mouse model of early prenatal stress? [The Truth About How Mom's Stress Affects Baby's Brain ]

It turns out that stress changes the levels of Lactobacillus, a gut-dwelling lactic acid-producing bacteria that affects the brain's chemistry, in both mothers and their offspring.

TKF: What are the big questions about the gut-microbiome-brain connection that researchers are trying to answer right now?

T.B.: Now that we know the microbiome changes in response to stress, I think the field is trying to understand the processes by which the gut microbiome alters the brain.

C.L.: I totally agree. The big question right now is how the microbiome exerts its effects on the brain. Some questions we're all still trying to answer include the composition of the gut microbiota, its effects on the permeability of the lining of the gastrointestinal tract, its effects on whole-body inflammation, and its effects on neuronal signaling from the gut to the brain.

S.M.: Another big question is whether we can treat brain disorders, such as autism, by aiming therapies at the gut. One of the barriers to treating psychiatric and neurological disorders is that we often don't understand the underlying disease mechanisms; in other words not only what to target but where those targets are in the body. If the therapeutic targets are in the brain then it becomes particularly challenging because of the blood-brain barrier, a network of blood vessels that protects the brain from harmful substances. But if a neurological condition actually originates in the gut, which we believe is the case for some individuals with autism, then delivering therapeutics is much easier. In my lab, we've been able to alter some of the symptoms associated with autism, such as repetitive behaviors, in mice by feeding them specific bacterial species. These bacteria modulate molecules in the gut and in the blood that affect the nervous system. 

TKF: That leads me to my next question. Sarkis, how do you think the microbes in the gut are communicating with the brain and driving behavior? Have your experiments using mice with autism-like symptoms offered any clues?

S.M.: There are at least three ways gut microbes are communicating with the brain: the first is directly through the vagal nerve, which connects the network of nerves in the gut to the brain; the second is through circulating immune cells that are primed, or educated, in the gut and then travel to the brain; and the third may be metabolites, molecules that are produced by microbes in the gut that enter the blood and circulate to regions of the brain where they affect behavior. We've shown, for example, that a metabolite produced by gut bacteria is sufficient to cause behavioral abnormalities associated with autism and with anxiety when it is injected into otherwise healthy mice. This suggests that microbial molecules may connect the gut to the brain via the circulatory system. [Autism's Rise: Researchers Look at Why Cases Are Increasing ]

T.B.: Sarkis covered most of what people currently understand about what's happening in the gut. But keep in mind that there's a developmental window that is also important. We've shown in our mouse model of early maternal stress, for example, that short-term changes to the microbiome during a critical period of development can result in brain changes.

TKF: Has anyone actually traced changes in the human brain back to the microbiome?

S.M.: Emeran Mayer and his colleagues at the University of California, Los Angeles, used functional magnetic resonance imaging, or fMRI, to look at the effects of specific microorganisms on brain activity. He showed that treating healthy people with fermented milk products containing probiotics, or healthy bacteria, altered brain activity in regions linked to emotion.

T.B.: Developmentally, that's a harder question, because you can't do controlled experiments in newborns. But there are plenty of studies ongoing in Europe and in Canada where researchers are giving vaginal lavages to the newborns delivered by C-section to ensure that they are getting a nice dose of their mother's microbiome.

TKF: Tracy, you've talked about the close connection between a mother's vaginal microbiome, which a baby encounters as it passes through the birth canal, and her newborn baby's. Can you expand on how this natural form of inoculation helps lay the foundation for brain development?

T.B.: There are key developmental windows when the brain is more vulnerable because it's setting itself up to respond to the world around it. At the same time, as Sarkis pointed out, the gut microbiome is helping to prepare the baby's immune system. So, if mom's microbial ecosystem changes – due to infection, stress or diet, for example – her newborn's gut microbiome will change too, and that can have a lifetime effect. It could alter how the gut, and the immune system within the gut, develops and how the brain develops. 

What's interesting, from our experiments on the effects of exposure to early maternal stress in mice, is that if you look at those babies in adulthood, their microbiome may be completely normalized, but if you then stress them or give them an immune challenge, you see big differences again in the way their bodies respond. So even acute exposure to prenatal stress seems to alter how an organism responds to changes in its environment in the long term.

TKF: I find that a little scary. Pregnant women already have so much to worry about.

S.M.: I can understand that reaction. Just the very concept that microbes can have profound effects on the brain may be hard for a lot of people to believe. But I tend to think that by understanding these effects, one can do something about the epidemics of anxiety, autism and attention deficit and hyperactivity disorder, also known as ADHD, that we're seeing in today's society. We're learning that society may be doing things that are not in the best interest of a child's health and by understanding those things we can change practices and prevent, for a lack of a better term, mistakes during critical periods of development. So my take is a little bit more positive.

T.B.: I agree. I think that it's an awareness more than a fear factor.

TKF: Christopher, you've suggested that a lack of exposure to the many bacteria we evolved with may be contributing to our ills, including psychiatric disorders such as depression and anxiety. If that's the case, can we make up for the past?

C.L.: There are certain psychiatric disorders like post-traumatic stress disorder, or PTSD, and depression that seem to be associated with increased inflammation, a ramped-up immune response in the body and in the brain. So microbes that can modulate the immune system and limit inflammation may have some benefit, either by alleviating the symptoms of certain types of psychiatric disorders or, in the best possible scenario, preventing them. So yes, I think taking or being exposed to these types of bacteria during adulthood can be beneficial, although clearly their major influences are during development, as Tracy and Sarkis have pointed out. [Gut Feeling? Probiotics May Ease Anxiety and Depression ]

TKF: Are you testing any probiotics for stress or depression?

C.L.: Our current studies use heat-killed bacteria rather than probiotics, which the World Health Organization defines as live microorganisms that confer a health benefit to the host when administered in adequate amounts. We have a series of studies that we're getting ready to publish that suggest that certain types of heat-killed microbes can prevent syndromes that you would expect following chronic stress. We're hoping to conduct similar studies using probiotics in animals and humans.

TKF: Have you changed your behavior as a result of your research into the connection between the microbiome and a healthy body and brain?

C.L.: I've certainly altered mine. I eat more fresh vegetables, and we have a small garden at our house. It's becoming clear from the American Gut Project that an important source of gut microbial diversity is the number of different plants we eat. Fresh vegetables are a significant source of bacteria. For example, the leaves of a spinach plant are estimated to harbor more than 800 different species of microbes. These are microbes that you can't sterilize from the plant because they're actually inside of it. And so having access to this kind of microbial diversity through the things that we eat is probably very important. I've also added sand from ocean beaches to my children's sandbox, I let my kids swim in lakes, and we take probiotics.

S.M.: As we all know, it's still the very early days in terms of trying to understand the effects of the microbiome, even for inflammatory bowel disease or obesity, which have been studied much more than any neurological condition. That being said, as Chris mentioned, diet is a major driver of microbiome configuration and so I think that there is enough reason to believe that specific foods “are better” for the microbiome than others: eating a high fiber diet with lots of fruits and vegetables, resistant starches such as those from seeds and nuts, and, in general, a diet that is closer to the one we evolved to eat, including foods that were available before agriculture and fast food restaurants came along. So what I've done is nothing really dramatic.

T.B.: As a parent, I would also say I've spent a lot more time thinking before allowing my child to take antibiotics. There's no disputing their utility or efficacy but we shouldn't just throw antibiotics at every illness.

TKF: Sarkis, you've called recent discoveries “harbingers of extensive, currently undescribed, links between gut bacteria and the nervous system.” Can you speculate on what other links between the gut microbiome and the brain might emerge? Are we going to find that the microbiome also plays a role in cognition or neurodegenerative diseases, for example?

S.M.: It's already been shown that cognition in germ-free mice is reduced in comparison to normal mice. While the microbiome has not yet been implicated in neurodegeneration, there's a lot of speculation about this issue because there are data showing that a Mediterranean diet protects against Alzheimer's, a neurodegenerative disease. And because we know diet helps shape the microbiome, one can imagine that eating a Mediterranean diet could affect the microbiome in a way that protects against neurodegeneration. We have a program in the lab that's very, very early looking at Alzheimer's and Parkinson's diseases in mouse models, but there's nothing solid to report yet.

There are other anecdotal reasons to believe that neurodegeneration may have some connection to the microbiome, or vice versa, because the three major neurodegenerative disorders – Alzheimer's, Parkinson's and amyotrophic lateral sclerosis, or ALS – all have a GI component to them. In fact, many patients who are ultimately diagnosed with Parkinson's are known to have had GI disturbances decades before they develop motor symptoms. And a recent study showed that patients with Parkinson's disease have different microbiomes than matched controls. While this is an exciting finding, this kind of study needs to be interpreted with caution as it is an association and does not prove a causative link. So there are flash bulbs going off in the dark, suggesting that very complex neurodegenerative disorders may be linked to the microbiome. But once again this is very speculative. These seminal findings, the flash bulbs, are only just beginning to illuminate our vision of the gut-microbiome-brain connection.

TKF: In addition to more funding, what would help accelerate progress in the field?

C.L.: There are regulatory issues related to giving live or dead bacteria for treatment of psychiatric and neurological disorders, and those are significant issues that will have to be dealt with.

T.B.: Another is that not all neuroscientists have embraced this idea. It's definitely getting better: I just spoke at the American College of Neuropsychopharmacology meeting; it's quite surprising that they had a session on microbiome this year. But I can tell you that there are still vast numbers of people, especially in psychiatry, who don't believe this is real. And I think that is a hurdle.

S.M.: I have a similar story. We had a session on the microbiome at the annual meeting of the Society for Neuroscience this year but it was our third year submitting it. I think that's a sign there is a sea change taking place in the field. With that being said, if you talk to most neuroscientists, they have a hard time finding any credibility in the link between the microbiome and neurobiology. It's still a very, very new concept with much more experimental validation necessary, and honestly I have no issue with that.

T.B.: I agree. I think the field is now at the point where we've established the validity of our models and are beginning to show how the microbiome affects the brain. That is when the big change in attitude will happen. But it's going to require some hard-core studies of the mechanisms involved.

S.M.: I think the skepticism is healthy. It keeps us honest and makes sure that the science remains rigorous. At the same time, I've been surprised and gratified by the fact that our work hasn't received widespread rejection by the neuroscience community. It certainly hasn't received widespread acceptance either, but when I discuss my research with card-carrying neuroscientists they seem to be quite open-minded about the possibility. It's not that they believe it, but they're intrigued to see more.

T.B.: Right. The fecal transplant jokes have subsided!

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.

Kelen Tuttle, writer and editor for the Kavli Foundation, contributed this article to Space.com's Expert Voices: Op-Ed & Insights.

For decades, theorists have speculated that in its earliest moments, our universe underwent a mind-bogglingly fast expansion that took it from the diminutive size of a proton to a vast expanse. Earlier this year, scientists announced a stunning development: what may be the first "smoking gun" evidence in support of that theory.

How certain is this result and, if it's corroborated, what does it mean for our theories of how the universe works? Three leading theorists spoke recently with The Kavli Foundation about the evidence, the implications and the next steps. Joining the conversation were: 

• Daniel Baumann, a lecturer in theoretical physics at Cambridge University whose research focuses on inflation and string theory. He has also held positions at the Institute for Advanced Study in Princeton and at Harvard University.  
• Paul Steinhardt, the Albert Einstein Professor in Science and director of the Princeton Center for Theoretical Science at Princeton University. His research spans particle physics, astrophysics, condensed matter physics and cosmology, and he shared the 2002 P.A.M. Dirac Medal for his role as one of the architects of the inflationary model of the universe.  
• Michael S. Turner, a theoretical cosmologist known for his work on inflationary cosmology, the characteristics of dark energy and the nature of dark matter. He is the Director of the Kavli Institute for Cosmological Physics as well as the Bruce V. and Diana M. Rauner Distinguished Service Professor at the University of Chicago.

Below is an edited transcript of their discussion. The participants have also been provided the opportunity to amend or edit their remarks.

THE KAVLI FOUNDATION: When this result was announced, there seemed to be two widespread reactions within the scientific community: First, excitement that the theory of cosmic inflation finally seemed proven, and second, surprise that not only had the BICEP2 collaboration found anything all, but that the signal was so strong. As theorists not involved in the BICEP2 announcement, were the three of you taken off guard? Did you expect proof of cosmic inflation to come so soon, if at all?

MICHAEL S. TURNER: For me, it was pure shock and awe. There was no really good theoretical prediction before this detection. Highbrow theorists, who were looking for theories that satisfied some very strong theoretical principles, more or less said that we would never detect it. And the lowbrow theorists — and I put myself in this category — said, you know, we're pretty ignorant about physics at these scales and why don't we just look at a variety of models, some of them so simplistic that they couldn't possibly describe nature, but that might produce a detectable signal and guide our thinking.

So to have the signal come in basically as big as it could be — bigger even — was just amazing. We're used to cosmology awing us, but this time it shocked us as well.

DANIEL BAUMANN: Like Michael, my initial reaction was also shock and awe. I was intellectually prepared for these experiments, because of course I knew about them and I knew they had the sensitivity to see things, but somehow in my gut I wasn't prepared to have a signal that was as big as it actually was. At the beginning I was literally shocked. For two days I couldn't even comment on it because I didn't know what to say.

PAUL STEINHARDT: My reaction was rather different, I think, than most theorists. I immediately set to reading the paper, and so my first reaction — and continued reaction — has been one of concern about whether or not these results are really correct. The observation is really important. My concern at the moment is that it's not yet clear whether or not they got it right. So others are now looking to confirm the results. If the BICEP result has to be retracted, these competing experiments will start the race again, to really nail whether or not these primordial gravitational waves are there.

TKF: Paul, where does your concern come from? Are you worried that it's not necessarily what they think they've seen, or is it that there might be a flaw in the analysis?

PAUL STEINHARDT: They've definitely seen something; they've detected this twisty pattern in the cosmic microwave background. But deciding whether it's due to gravitational waves produced in the early universe or due to some source in the foreground that's between us and where the microwave background was emitted, that's a key issue. There are lots of things in the foreground that could produce a similar twisty pattern. And many of those effects are larger than the gravitational wave effect they're trying to detect. So it's important that they understand those foregrounds very thoroughly. It's an exciting time in the sense that we now have instruments that can make this measurement. But whether the measurement has really been made, whether one can really claim victory at this point, is still uncertain in my view.

MICHAEL TURNER: I think they've done a really good job and many of the criticisms have been asked and answered. The big issue is dust, and another experiment, the Planck satellite, will have better dust maps. So far, it looks very good. I think they were pretty careful. But as we all know, an extraordinary result requires extraordinary proof. Maybe this will turn out to not be a real detection, but they've put a very good case forward.

DANIEL BAUMANN: Over the past couple of months, I've become a skeptical optimist. I share some of Paul's concerns about whether we really have seen a signal that is cosmological. One of the tests to decide whether it really is cosmological is to see if the signal has the expected frequency dependence. Unfortunately, out of no fault of their own, the BICEP2 collaboration could only provide us with a detection at a single frequency, and a little bit of cross correlation with a second, very noisy frequency. In order to reject dust as an alternative explanation, we're waiting to see multiple frequencies and crosschecks with other experiments and in other parts of the sky. I'm still waiting for these other things to come in before deciding if this signal is actually of primordial origin and if its amplitude is as big as BICEP2 claims it to be.

PAUL STEINHARDT: One of the problems that we all have is that normally when a group presents results on the cosmic microwave background, they also present a so-called systematics paper that explains how they got the results that appear in their main conclusions. That paper has not yet been presented by the BICEP team. So it makes it very hard for anyone who's on the outside looking in to try to resolve some of the questions that are raised by the main paper. The Planck dust maps will be helpful, but even after that, we still need to understand exactly how they got to their conclusions.

TKF: If we assume that all of the systematics are correct and that the BICEP2 results will be confirmed, what are the theoretical implications? Which inflationary models does the data seem to support?

PAUL STEINHARDT: I would say that it depends upon what data you want to trust. It's not easy to put the BICEP2 results together with the earlier Planck and WMAP results and make everything fit — they don't line up all that well. If you try, you end up with rather strange and contorted models. These ugly models don't give you a lot of confidence in inflation at all. Other theorists are leaning toward simpler models, but that requires not taking all of the experimental results seriously. Depending on which results you ignore, you're driven toward different models.

My own view is a little bit different still. One of the problems with inflation is that it really doesn't make predictions; it is so flexible that it is not falsifiable. You're always going to be able to change parameters and add degrees of freedom such that it can fit any combination of data no matter what is observed. This is a fundamental problem. A theory that is not falsifiable is not scientifically meaningful.

PAUL STEINHARDT: I would say that it depends upon what data you want to trust. It's not easy to put the BICEP2 results together with the earlier Planck and WMAP results and make everything fit—they don't line up all that well. If you try, you end up with rather strange and contorted models. These ugly models don't give you a lot of confidence in inflation at all. Other theorists are leaning toward simpler models, but that requires not taking all of the experimental results seriously. Depending on which results you ignore, you're driven toward different models.

MICHAEL TURNER: I think it's fair to say that nature is a still a lot smarter than we are on inflation. Our models are naïve, I agree with Paul on that point. But I wouldn't go quite as far as saying they're not predictive. We really haven't sharpened them up. This result could help us sharpen them up.

I would also say that the level of proof in cosmology is a little bit complicated. To really prove things in cosmology, you need to close the circle. That means to do a laboratory experiment that tests things. It's going to be a long time before we close the circle on inflation. If you believe that there's some field of nature akin to the Higgs that caused inflation, then I think closing the circle would mean producing a related particle in the laboratory. That's a long way off. So I don't think the BICEP2 announcement proves inflation. But I think it has given us some hints on how to define our very simple ideas about inflation, on how to take them to the next level.

TKF: Where do we go from here? If other experiments confirm the BICEP2 results but we can't do laboratory tests anytime in the foreseeable future, how do we proceed?

PAUL STEINHARDT: There are eight different experiments that I know of that are chasing after these cosmic gravitational wave signals. If they find them, they're going to want to map them and measure other properties that will help us better understand the source of those gravitational waves and what kind of physics produced them—whether it's something like inflation or not. So I think the next few years are going to be a very exciting period.

DANIEL BAUMANN: Because the level of the signal seems to be so large, it gives us the opportunity to measure the signal very accurately and really prove that it has the shape that we expect it to have from inflation. Maybe we could even see some subtle deviations from that shape that would lead to the discovery of new physics. In that regard, we're very lucky that the signal is so big.

TKF: One of the great quests in physics is to unite the fundamental forces (gravity, electromagnetism and the strong and weak nuclear forces). Does the strength of the signal—and the associated high energy scale in the early universe—mean we might have a chance to understand how the forces unite?

DANIEL BAUMANN: Maybe. If BICEP2 is correct, then the inflationary energy scale sits not far below the Planck scale. In theories that unify quantum mechanics and gravity, we believe that there are additional scales between those energy scales. If the energy scale of inflation had been lower, it would be hard to see imprints of those kinds of effects. However, if inflation really happened at such a high energy scale, then these effects are around the corner and one might hope to be able to see subtle signatures of them.

MICHAEL TURNER: As Daniel says, this was very lucky, if indeed it is correct. With such a high energy level, we may be able to measure how the gravity waves change with frequency. That would provide kind of a consistency test on all of this. If we got extraordinarily lucky, maybe we would be able to directly detect these gravity waves. But it's going to take a while for us to get our heads around this. This was such a big leap; it's going to take us a while to catch up.

PAUL STEINHARDT: One of the interesting things about the energy scale of the so-called theory of everything or string theory is that it's at the scale at which, when you go backward in time, you can no longer think of the universe as just having three space dimensions and one time dimension. Instead, string theory says that there are extra additional dimensions that are wrapped up and small, but which can no longer be thought of as small when you go back to this time scale. They would have a profound impact on the nature of gravity. It's interesting that it's rather difficult to fit together string theory and this very large energy scale. It's something that a lot of people have been thinking about and will become a sharper issue if it becomes clearer that BICEP2 really has made this detection and there really is this very large energy scale of inflation.

DANIEL BAUMANN: I agree that there is a slight tension between interpreting the signal as a simple inflationary model and taking into account the additional fields and extra dimensions required by string theory. How is it that the data seems to be pointing to such a simple picture of inflation and the early universe, while our fundamental theories at face value look a bit more complicated? I am optimistic that we will understand this better in the future.

PAUL STEINHARDT: Daniel, when you say it fits this very simple model of inflation, that's an example where you're changing something, either BICEP2's measurement or WMAP and Planck's measurements, in order to say that those fit a simple model.

DANIEL BAUMANN: I might not be as concerned as other people about the tension between BICEP2 and Planck. That's because, even with my limited experience, I've seen these kinds of tensions appear in first detections and then disappear upon further scrutiny. For example, the early WMAP measurements had an anomalously large value for the optical depth of reionization that later went away. So although I can believe that there's a signal, I think that the details of that signal are still subject to change.

PAUL STEINHARDT: I think that's fine as long as one makes clear that that's what one's doing. In other words, it's not true that those simple models fit the current data as presented. They fit the current data only assuming that you allow some significant flex in the reported results that have been presented by the combination of WMAP, Planck and BICEP2. That is, only if you assume the results of at least one of those experiments is significantly off. 

MICHAEL TURNER: Let me put a positive spin on what Paul is saying. We've been on a roll here since almost 1998, where every new measurement confirmed our very simple picture of the universe, called Lambda-CDM. Now we may be seeing what I like to call a crack in the cosmic egg; maybe everything doesn't quite fit together. It could be that when we put everything together two years from now, when we have a confirmation and Planck has reported more results, that we find out that the simplest possible model isn't working, and that there's something else that's needed. It could be that these tensions that Paul is talking about—although I would agree with Daniel that it's a little early to call them tensions—that they point to something else, some other exciting discovery that will help us move forward.

TKF: A good number of inflationary models suggest that, once started, inflation should continue forever. This leads to the idea of the "multiverse"—that there are different regions of the universe that act differently. In some regions, inflation continues today and in others, like our own, it settled down to a relatively slow expansion. What do the BICEP2 results have to say about the validity of this multiverse theory? How does it fit into the simple models we've been discussing?

PAUL STEINHARDT: The fact that the inflationary scenario leads to this multiverse is another reason why I have issues with it. We heard some people after the BICEP announcement say that this proves the multiverse . But the multiverse predicts a range of cosmological properties—in fact, literally every conceivable physically possible option will occur and will occur an infinite number of times in the multiverse. This is another sense in which the theory is totally unpredictive. Anything you might observe would be possible in a multiverse. To my mind, this makes the theory scientifically untestable and therefore meaningless. Once we accept one scientifically meaningless idea, I think we open the door to many other meaningless ideas and it quickly becomes a danger to normal science generally. I consider this to be a very serious issue for the entire scientific community.

MICHAEL TURNER: In science, theories have to make testable predictions. On the other hand, I think science is a self-regulating process. We have to hold theories to the high, rigorous standards that scientists have been using since before the time of Galileo. But at the same time, you wouldn't want to throw out a really good idea just because it's immature and isn't yet testable. So I'm kind of in between here. The multiverse gives many of us a headache because it could be one of the most important ideas in the last 500 years, yet the way it's formulated, it's not quite science.

I think that science will be able to deal with it. We're able to hold high standards and also allow ourselves to look at new, radical ideas. I put my faith in the younger generation, like Daniel. Paul, they're a lot smarter than we are and they're going to be able to figure this out. They'll keep us on track.

TKF: Daniel, that puts a lot of pressure on you.

DANIEL BAUMANN: That's true. But I agree with what both Paul and Michael said here. The way that I view inflation is that it's fulfilling two different types of roles. There's the conservative role, where we think of inflation as a mechanism to produce the initial seeds for the early universe, and we can make conditional predictions. Then there are also deeper questions about how inflation started, whether it is globally eternal, how we assign probabilities to the vast possibilities of the multiverse, and so on. Those are valid questions, I think, but they're not necessarily in conflict with the success of inflation as a mechanism for explaining the seeds of structure in the universe.

PAUL STEINHARDT: I certainly think so. I think we're absolutely at the edge of our seats. Even though we have different points of view about where we are at the moment, I think we all would agree that it's extremely exciting. And it's not like the situation is going to stay unresolved for a long period of time. There's this race going on with eight different groups going after the same science in different ways. The race is going to be intense, we're going to learn a lot, and the science will be clarified within a few years. That's going to be a historic moment that sets the agenda for what needs to be done next in cosmology and fundamental physics.

TKF: Whatever is determined about the BICEP2 results, it seems like this is a very exciting time for this field.

MICHAEL TURNER: I completely agree with that. It is really exciting. We know a lot and we're learning even more, yet we understand less. We have to put the pieces together. I'm here in Paris right now with Planck collaborators. They just released some dust maps two days ago, maps that actually excised the BICEP field. So they're not saying anything yet. In fact, they have this thing called the BICEP face. Whenever you say "BICEP," they go to a poker face.

So if I'm trying to be a fortune teller, I think they haven't disproven it. Planck has a shot at saying something one way or another; my colleague John Carlstrom at the South Pole Telescope has a shot at saying one thing or another; if you look at some of our other colleagues, all of a sudden people are excited about what's the next experiment to mount. Is it a satellite, is it another experiment from the Atacama Desert in South America, is it an experiment from Greenland, is it a balloon experiment? This is quite simply an extraordinary time to be around. We have a lot of puzzle pieces on the table and our hope is that we can put the puzzle together.

DANIEL BAUMANN: As a member of the younger generation, this right now is the most exciting time that I've experienced. I narrowly missed the discovery of dark energy, so this is really the first time that I'm experiencing first-hand what might be one of the major discoveries in my lifetime. And as a theorist, it's been incredibly exciting. I've gotten very little sleep for about a month now as I've worked to understand both the data and the theoretical implications. It really did revitalize the field, in the sense that it brought everyone together to try to understand what the data mean, how we can interpret them, and what kind of theoretical models to build to understand them better.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google +. The views expressed are those of the author and do not necessarily reflect the views of the publisher.  This version of the article was originally published on Space.com.

Bruce Lieberman is a freelance science writer based in San Diego, Calif. He frequently writes about astrophysics for The Kavli Foundation and has also written for Air & Space Magazine, Sky & Telescope, Scientific American and other media outlets. He contributed this article to Space.com's Expert Voices: Op-Ed & Insights

In late February, on behalf of The Kavli Foundation, I attended an annual conference of dark matter hunters — men and women on a common quest to identify the unknown stuff that makes up more than a quarter of the universe.

At Dark Matter 2014, held at UCLA, more than 160 physicists from around the world discussed their latest findings and technologies, and they shared their hopes and frustrations in solving one of cosmology's biggest mysteries. So where does the hunt stand?

As part of a series of discussions about the universe conducted by The Kavli Foundation, I had the opportunity to speak with three leading physicists at the conference about its biggest highlights and prospects for future progress.

Joining the conversation were Blas Cabrera, professor of physics at Stanford University, Member of the Kavli Institute for Particle Astrophysics and Cosmology (KIPAC) at Stanford, and spokesperson for the SuperCDMS dark matter experiment; Dan Hooper, scientist in the Theoretical Astrophysics Group at the Fermi National Accelerator Laboratory, associate professor in the Department of Astronomy and Astrophysics at the University of Chicago, and senior member of the Kavli Institute for Cosmological Physics (KICP) at Uchicago; and Tim Tait, professor of physics and astronomy at the University of California, Irvine, and Member of the university's Theoretical Particle Physics Group.

The following is an edited transcript of the discussion.

THE KAVLI FOUNDATION: Almost everyone at the conference seems to think we're finally on the path toward figuring out what dark matter is. After 80 years of being in the "dark," what are we hearing at this meeting to explain the optimism?

BLAS CABRERA: This conference has highlighted the progression of larger and larger experiments with remarkable advances in sensitivity. What we're looking for is evidence of a dark matter particle, and the leading idea for what it might be is something called a weakly interacting massive particle, or WIMP. We believe the WIMP interacts with ordinary matter only very rarely, but we have hints from a few experiments that might be evidence for WIMPs.

Separately at this conference, we heard about improved calibrations of last fall's results from LUX, the Large Underground Xenon detector that now leads the world in sensitivity for WIMPs above the mass of six protons — a proton being the nucleus of a single hydrogen atom. Under a standard interpretation of the data, the LUX team has ruled out a range of low-end masses for the dark matter particle, another major advance because it does not see potential detections reported by other experiments and further narrows the possibilities for how massive the WIMP might be.

Finally, Dan [Hooper] also gave a remarkable presentation here about another effort: to indirectly detect dark matter by studying radiation coming from the center of the Milky Way galaxy. He reported the possibility of a strong dark matter signal, and I would say that was also one of the highlights of the conference because it provides us with some of the strongest evidence so far of a dark matter detection in space. Dan can explain.

DAN HOOPER: Four and a half years ago, I wrote my first paper on searching for evidence of dark matter at the center of the Milky Way galaxy. And now we think we have the most compelling results to date. What we're looking at is actually gamma rays — the most energetic form of light — radiating from the center of the galaxy. I think that this is very likely a signal of annihilating dark matter particles. As Blas explained, we believe dark matter is made of particles, and these particles, by themselves, are expected to be stable — meaning that they don't readily decay into other particles or forms of radiation. But at the dense core of the Milky Way galaxy , we think they collide and annihilate one another, in the process releasing huge amounts of energy in the form of gamma rays.

TIM TAIT: We expect that the density of dark matter particles, and therefore the intensity of the gamma-ray radiation released when they collide, should both fall as you move away from the galactic center. So, you sort of know what the profile of the signal should be, moving from the center of the galaxy outward.

TKF: So Dan, in this case the gamma rays that we observe radiating from the center of the Milky Way match our predictions for the mass of dark matter particles?

HOOPER: That's right. We predicted what the energy

level of the gamma rays should be, based on established theories for how massive the WIMP should be, and what we've seen matches the simplest theoretical model for the WIMP. Our paper is based on more data, and we found more sophisticated ways of analyzing that data. We threw every test we could think of at it. We found that not only is the signal there and very statistically significant, its characteristics really look like what we would expect dark matter to produce — in the way that the gamma-ray radiation maps on the sky, in its general brightness, and in other features.

TKF: Tell me a bit more about this prediction.

HOOPER: We think that all the particles that make up dark matter were all produced in the Big Bang nearly 14 billion years ago, and eventually as the universe cooled a small fraction survived to make up the dark matter we have today. The amount that has survived depends on how much the dark matter particles have interacted with one other over cosmic time. The more they collided and became annihilated, the less dark matter survives today. So, I can basically calculate the rate at which dark matter particles have collided over cosmic history — based on how much dark matter we estimate exists in the universe today. And once I have the rate of dark matter annihilation today, I can estimate how bright the gamma-ray signal from the galactic center should be — if it's made of WIMPS of a certain mass. And lo and behold, the observed gamma-ray signal is as bright as we predict it should be.

TKF: What else caught everyone's attention at the conference?

TAIT: A really striking result was from Super Cryogenic Dark Matter Search, or SuperCDMS, the direct detection experiment that Blas works on. They didn't find any evidence for dark matter, and that contradicts several other direct detection experiments that have claimed a detection in the same mass range.

CABRERA: What we're looking for is an exceedingly rare collision between an incoming WIMP and the nucleus of a single atom in our detector, which in SuperCDMS is made from germanium crystal. The collision causes the nucleus of a germanium atom to recoil, and that recoil generates a small amount of energy that we can measure.

Direct detection experiments are situated underground to minimize background noise from a variety of known sources of radiation, from space and on Earth. The new detectors that we built in SuperCDMS have allowed us to reject the dominant background noise that in the past clouded our ability to detect a dark matter signal. This noise was from electrons hitting the surface of the germanium crystal in the detector. The new design allows us to clearly identify and throw out these surface events.

So, rather than saying, "Okay, maybe this background could be partly a signal," we can say with confidence now, "There is no background" and you have a very clean result. What this means is we have much more confidence in our data if we do make a potential detection. And if we don't, we're more confident that we're coming up empty. Eliminating background noise vastly reduces uncertainties in our analysis — whether we find something or not.

TKF: What caught everyone's attention on the theoretical side?

CABRERA: What struck me at this meeting is that nuclear physicists have recently written papers describing a generalized framework for all possible interactions between a dark matter particle and the nucleus of a single atom of the material that researchers use in their detectors; in the case of SuperCDMS, as I've explained, it's germanium and silicon crystals. These nuclear physicists have pointed out that roughly half of all possible interactions are not even being considered now. We are trying to digest what that means, but it suggests there are many more possibilities and a lot we still don't know.

TKF: Tim, with accelerators like the Large Hadron Collider in Europe, researchers are looking for evidence of supersymmetry, which could reveal the nature of dark matter. Tell me about this idea. Also, was anything new discussed at the meeting?

TIM TAIT: Supersymmetry proposes there are mirror particles that shadow all the known fundamental particles, and in this shadow world may lurk the dark matter particle. So, by smashing together protons in the LHC, we've tried to reveal these theoretical supersymmetric particles. So far, though, the LHC hasn't found any evidence for supersymmetry. It may be that our vision of supersymmetry isn't the only vision for physics beyond the Standard Model. Or maybe our vision for supersymmetry isn't a complete one.

TKF: The LHC is going to collide protons at much higher energy levels next year, so could that reveal something we just can't see right now?

TAIT: We hope so. We have very good reason to think that the lightest of the mirror particles in this shadow family is probably stable, so higher energy collisions could very well reveal them. If dark matter was formed early in the universe as a supersymmetric particle and it's still around — which we think it is — it could show up in the next round of LHC experiments.

TKF: When you think about the different approaches to identifying dark matter, has anything discussed at this meeting convinced you that one of them will be first?

TAIT: When you look at all the different ways of looking for dark matter, what you find is that they all have incredible strengths and they all have blind spots. And so you can't really say one is doing better than the other. You can say, though, they are answering different questions and doing very important things. Because even if you end up discovering dark matter in one place — let's say in the direct detection search — the fact that you do not see it at the LHC, for example, is already telling you something amazing about the theory. A negative result is actually just as important as a positive result.

HOOPER: The same goes with the direct detection experiments. I'm remarkably surprised that they haven't seen anything. We have this idea of where these supersymmetric particles and WIMP particles should show up in these experiments — at the LHC and in direct detection experiments — and yet lo and behold we got there and they are not there. But that doesn't mean they're not right around the corner, or maybe several corners away.

CABRERA: Given the remarkable progress over the past few years with many direct detection experiments, we would not have been surprised to have something rear its head that looks like a true WIMP.

HOOPER: Similarly, I think if you had done a survey of particle physicists five years ago, I don't think many of them would have said that in 2014 we've only discovered the Higgs — the fundamental particle that imparts mass to fundamental particles — and not anything else.

CABRERA: Now that the Higgs has been pretty convincingly seen, the next big questions for the accelerator community are: "What is dark matter? What is it telling us that we do not see dark matter at the LHC? What does that leave open?" These questions are being asked broadly, which wasn't the case in past years.

TKF: Was finding the Higgs, in a sense, an easier quest than identifying dark matter?

HOOPER: We knew what the Higgs should look like, and we knew what we would have to do to observe it. Although we didn't know exactly how heavy it would be.

CABRERA: We knew it had to be there.

HOOPER: If it weren't there it would have been weird. Now, with dark matter, there are hundreds and hundreds of different WIMP candidates that people have written down, and they all behave differently. So the Higgs is a singular idea, more or less, while the WIMP is a whole class of ideas.

TKF: What would a confirmed detection of dark matter really mean for what we know about the universe? And where would we go from there?

CABRERA: A discovery of dark matter with direct detection experiments would not be the end of the journey, but rather the beginning of a very exciting set of follow-up experiments. We would want to determine the mass and other properties of the particle with more precision, and we'd also want to better understand how dark matter is distributed in and around our galaxy. Follow-up experiments with detectors would use different materials, and we'd also try to map which direction the WIMPs are coming from through our detectors, which would help us better understand the nature of dark matter that surrounds the Earth.

Overall, a discovery would be huge for astrophysics and cosmology, and for elementary particle physics. For astrophysics we would have identified the dominant form of matter in the universe that seeded structure and led to galaxies, solar systems and planets, and ultimately to our Earth with intelligent life. On the particle physics side, this new particle would require physics beyond the Standard Model such as supersymmetry, and would allow us to probe this new sector with particle accelerators like the LHC.

TAIT: I think there's a lot of different ways you could look at it. From a particle physicist's point of view, we would now have a new particle that we'd have to put into our fundamental table of particles. We know that we see lots of structure in this table, but we don't really understand where the structure comes from.

From a practical point of view, and this is very speculative, dark matter is a frozen form of energy, right? Its mass is energy, and it's all around us. Personally, if I understood how dark matter interacts with ordinary matter, I would try to figure out how to build a reactor. And I'm sure that such a thing is not at all practical today, but someday we might be able to do it. Right now, dark matter just goes right through us, and we don't know how to stop it and communicate with it.

HOOPER: That was awesome, Tim. You blow my mind. I'm picturing a 25th century culture in which we harness dark matter to make an entirely new form of energy.

TAIT: By the way, Dan, I'm toying with the idea of writing a paper so we should keep talking.

HOOPER: I would love to hear more about it. That sounds great. So, to kind of echo some of what Tim said, the dark matter particle, once we identify it, has to fit into a bigger theory that connects it to the Standard Model. We don't really have any idea what that might look like. We have a lot of guesses, but we really don't know so there's a lot of work to do. Maybe this will help us build a grand unified theory — a single mathematical explanation for the universe — and help us, for example, understand things like gravity, which frankly we don't understand at all in a particle physics context. Maybe it will just open our eyes to entirely new possibilities that we just never considered until now. The history of science is full of discoveries opening up whole new avenues for exploration that were not foreseen. And I have every reason to think that that's not unlikely in this case.

Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google +. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Space.com.