John Durant
My name is John Durant. I’m the director of the MIT Museum and an adjunct professor in the Science, Technology & Society Program at MIT, which feels as if it ought to be relevant to the agenda of a meeting called Science + Society. I’d like to join other moderators before me in thanking the organizers very warmly for the flair with which they’ve brought this meeting together. The quality of the talks we’ve been hearing over the last two days I think has been outstanding. The amount of new and interesting ideas, and initiatives that are coming through I think is quite unusual for a meeting of this kind.
Now, having said that I would like to take a liberty for thirty seconds of abusing my position as moderator and putting in a very brief plug for an initiative which I mentioned briefly in one of the parallel sessions yesterday. It excited enough response from members of the audience that I felt maybe I ought to say just a word about the Cambridge Science Festival, which a whole group of us here in the Boston area are organizing as a new venture in engagement of the wider public with science and technology. As you can see from this slide, the Cambridge Science Festival is launching this coming April. It’s a nine-day celebration of science and technology in one of the United States’s most distinctive science cities. I will just point to the fact that we’re expecting to hold between two and three hundred separate activities and events across the city of Cambridge in that nine-day period, all manner of things—a science carnival, a televised town meeting on science. We hope we’re going to get an entry into the Guinness Book of World Records for the world’s largest model of the human genome, which we’re going to create as a two-mile stretch of Massachusetts Avenue in Cambridge with information about contemporary molecular genetics and genomics in the form of a human genome trail that people can follow from Kendall Square T in Cambridge, for those of you who know the city, right through to Harvard Square T. Many, many, many other things. Many arts initiatives of the sort that we heard so eloquently described in the previous session. The point mainly of saying this is to alert people who live and work in this area in the audience, and I know there are many of you, to the fact that this is existing. If you haven’t already come across it, now you know. Please get in touch with us. We’d be pleased to work with you. This is a partnership initiative. We want as many scientists and science communicators as possible to be involved. So please have a word with me afterwards if you’d like to. End of advertising jingle.
So our session today—let me come back to business, "Visions of the Future—Science in the Coming Decade. " I thought it might be helpful just to put here a quotation. Sometimes people still look back to the work of the physicist and novelist C.P. Snow all those decades ago. One comment he made in his famous "The Two Cultures " lecture was that, as he put it, "The scientists have the future in their bones. " I think one of the motives for a meeting like this is surely that we know that scientific discovery and technical innovation based on scientific discovery is collectively one of the great engines of change for the better, we hope, in our culture. Today in this particular session I think in a sense we’re asking what can the scientists themselves tell us about the contents of their skeletons. In other words, how much do scientists working in active research in key areas, how much of a clear sense do they have, and how much can they tell us about what the immediate future holds? That is of such importance for those of us who are concerned about the science-society relationship.
Rita Colwell, who will be summing up this conference after this session, used a phrase which I tried to write down when she gave it. I’m not sure I’ve got it exactly right. She said I think in the opening session that she thought the future might be in the field of bio-info-nano-neuro-psy-tech or some such. We’ve got a lot of that represented here on the platform this morning, but clearly there are problems with prophecy and we have to be sensible about what we expect even of scientists by way of firm predictions of the future.
I see as a science communicator the great challenge and the great opportunity in this field of the immediate future being the extent to which new science and technology provides an opportunity to give the public a more vivid sense of the nature of the scientific enterprise itself. People have observed, and I’ve written in the past about, the contrast between so-called finished science, science that’s all essentially done and dusted, which can look very neat and tidy especially in the form of textbooks, and unfinished science, science which is in the course of active completion. Unfinished science typically looks a lot less neat and tidy precisely because the whole point of unfinished is you don’t know quite how the story is going to end. It’s also in many ways much more relevant and often much more interesting to the general public than finished science. There aren’t a tremendous number of high-profile public debates these days about Newton’s laws of motion because we pretty much seem, thanks to the work of physicists a few centuries ago, to have sorted that out. When it comes to nanoscience and technology, when it comes to the biosciences and their myriad applications in medicine and elsewhere, and so on and so on, these unfinished areas of science are the subjects of tremendous interest. I know that colleagues with me who work in the field of museums have become much more engaged in trying to communicate with our audiences about unfinished science, about science in the making, which means that we need to find ways of dealing with current and emerging science and technology because that is often what our visitors want to hear about, want to know about, want to understand, and in many ways and very often, want to be able to express points of view about, as we heard yesterday in the debate about public engagement and public consultation.
It seems to me as a moderator of this session that trying to get a grip as far as we can on what the immediate future holds is of immense importance and of immense significance for the work of communication that goes on with the wider public. It’s not easy. It’s much easier to construct an exhibition about finished science when you know how the story ended than it is to construct an exhibition about unfinished science when neither you nor anybody else knows how the story is going to end. It’s quite exhilarating to do it, in my experience, but it’s not easy. So there are big challenges here, and the excitement of this session for me is to try to improve a little bit our understanding of what lies just over the horizon. In order to help us do that we have a very eminent and distinguished panel of speakers. I’m going to introduce them all briefly now. The way that we are going to handle this session is that I’ve asked each speaker to be concise and brief as has been the tradition during this meeting. We will take a small number of immediate questions arising from each presentation in turn, and I’d ask people who are going to ask questions to abide by the general convention here—waiting until you get the microphone and telling us who you are. But we’ll take a short period with a small number of questions for each speaker in turn, which should leave us with a decent period for more general question and discussion with the whole panel at the end.
Now in the order in which our colleagues are going to speak, let me say first we welcome Bruce Cohen, who’s director of the Shervert Frazier Research Institute and the Stanley Research Center at McLean Hospital and who leads a consortium of investigators and clinicians using laboratory brain imaging and clinical-research techniques to develop new treatments of the most severe psychiatric disorders. He is a professor of psychiatry at Harvard Medical School and President and Psychiatrist in Chief Emeritus at McLean Hospital.
Secondly we welcome Andrew Dobson who’s a professor of ecology and evolutionary biology at Princeton University, where he’s taught since 1990. His main areas of interest are the application of theoretical ecology to problems in the areas of conservation biology, the control of infectious diseases, and population dynamics and life-history strategies of birds and mammals.
Mauro Ferrari is professor at the Brown Institute of Molecular Medicine and chairman of the Department of Biomedical Engineering at the University of Texas Health Science Center at Houston. He’s a founder of biomedical nano-stroke micro-technology. We’re in Rita Colwell territory here, especially pertaining to drug delivery, cell transplantation, implantable bioreactors and other innovative therapeutic modalities.
Raju Kucherlapati is scientific director of Harvard-Partners Center for Genetics and Genomics. He’s a Paul C. Cohen professor of genetics and professor of medicine at Harvard Medical School. His research includes cloning of human disease genes and the generation and characterization of mouse models for human disease.
And last but by no means least, David Charbonneau is on the faculty in the department of astronomy at Harvard University. His research focuses on the development of novel techniques for the detection and characterization of planets orbiting nearby and of Sun-like stars.
So as you can see, we have an extraordinary range of talent and expertise here, and without further ado, I want to hand over to our first speaker, Bruce Cohen.
Bruce Cohen
Thank you, John. I’d like to thank the organizers of the conference and thank the audience for being here on this beautiful, crisp morning.
I knew when I was a child, like most the people on the panel, I would guess, that I was likely to end up a scientist of some sort and the reason for that was because that seemed to offer the greatest opportunity to help change the world. I was at MIT when I recognized the brain might be one of the most fascinating things to study and in medical school before I realized I’d be a psychiatrist, after I met patients and understood that some of the most interesting problems we have as human beings, things we should solve, are around cognition, emotion, and such, those things which make us most human.
Why the brain? I just want to cite two things here on this complex slide, which indicates the complexity of the brain. One is: there are a trillion nerve cells in the brain. That’s a million for all of us, British or American, and there are 1,000 trillion or more connections between those cells. Each cell is a little computer and all of those connections are also computing devices. Anything which goes wrong with those trillions of connections can produce a disease. Worldwide, there’s a lot of it. The brain is fragile. There are over one billion people with neurological and psychiatric disorders. Twenty-eight percent of all years lived with a disability are due to neurological or psychiatric disorders, psychiatric being the more important of the two in terms of the number of years of disability, and this costs trillions of dollars however you measure it. So it’s a crucial area for us as human beings.
The good news is we’ve come a long way already in understanding these disorders, and I’d like to show you very briefly why. If you went back a hundred years, these are the disorders you would see in people in hospitals with neurological or psychiatric conditions. Look at the left-hand column, these were the majority of people; brain infections like neurosyphilis, very common nutritional deficiencies like pellagra, endocrine disorders such as myxedema madness due to low thyroid levels and so on, poisoning due to bromides. These disorders, at least in the developed world, are largely gone one hundred years later. We rarely see them. On the right-hand side, you’ll see the disorders we’re still trying to treat. The good news there is we treat them much better than we did a hundred years ago. Why? Purely technology. The advance of science and in many different categories; it’s always interdisciplinary. What solved neurosyphilis? The combination of epidemiology, microbiology, and pharmacology; understanding the origin of the disease and coming up with a specific, in this case, anti-infective, treatment. What solved nutritional disorders? Largely biochemistry did that, along with epidemiology and so on. What allows us to treat psychiatric disorders today so much better than fifty years ago when the drug revolution started? Medications. They’re not the answer but they’re extremely helpful.
So what about the future? The topic now is: can we take all of the technologies that have been mentioned by Rita and John and others and turn them into use to make better treatments for neurologic and psychiatric disorders.
Here’s some more good news: there are so many approaches that are helpful. Biologically, we’ve got advanced genetics. Raju will talk about this. I will barely stray except to say that with the sequencing of the human genome and modern technology, we are in a position to find genes that put us at risk for neurological and psychiatric disorders just as they do for all other medical conditions or any human conditions. Yes, we are finding such genes. There are some early leads in both cases. Brain imaging is showing us structural, chemical, and functional abnormalities in the brain, not only in neurological disorders but in psychiatric disorders. Molecular-cell and-systems biology will give us the tools to address the problems that we see by the other technologies.
Then there are the non-biological technologies, and other speakers will say more about these too, but it is because of computing and information technology that we can do advanced genetics and brain imaging. Without the computers and information handling we could not. Also, computing and device technology will give us interfaces between us and machines that will replace brain functions, whether by prosthetics or by devices that will help repair brains. So what kind of new understandings and treatments will arise from these new technologies? And here we’re speculating, so I will certainly partly be wrong. I just hope to partly be right.
One should acknowledge—I think of all us would agree—there will be new medications. I hope some of them will look different than the ones we already have. There will be new psycho-therapies. There will be new rehabilitative therapies. There will be new surgeries. But some of the most exciting opportunities should be in what’s on the bottom of the slide. Prevention will probably only come when we know more about the cause of these disorders. Neuro-prosthetics are already underway. People are designing systems that can replace sight, that can replace hearing when it’s damaged, that can reconnect the signals in our brain to devices, to our own muscles, by getting around damaged pathways that connect our brains to muscles, for example, or to a computer cursor for people who are paralyzed. You can take brain waves; you can connect them through an interface and run a computer. I’m not going to talk further about those. I would like to give you two examples of neuro-repair, which is one of the topics on which the laboratories I oversee work rather extensively right now.
First, it’s important to recognize that not just for neurological conditions where the lesions tend to be fairly obvious, but also for psychiatric conditions, there are specific if subtle reductions of cells and cell connections or their functions in the brain. This is true for all the major psychiatric disorders. Things are not just physical or mental; they’re both. The question is: Can we replace those or repair those functions? Now, for us as human beings, and it’s probably necessary, the brain has a limited capacity to repair itself under normal circumstances by growing out new nerve cells or new support cells. It does it a bit. This slide is not from a human brain. It’s from a mouse brain, but the big green thing is a new blood vessel growing out to repair tissue that’s been damaged in a stroke. The red dots are new nerve cells, brand new, and the purple cells are brand new support cells, so-called glia, for the nerve cells. This happens in human beings too, although to a more limited extent than in other animals. So the question is: How can we achieve better cell replacement and repair?
Again, the very good news is: We have lots of technologies for approaching this problem. It doesn’t have to be one answer--it’s going to be a combination of these answers. There is gene alteration. If the defect is due to a gene that can be replaced, some day we’ll be able to replace it. However, sometimes that’s too late. Once the damage occurs, replacing whatever the genetic factors were that put you at risk aren’t going to help anymore. Still, altering genes in your remaining cells may get them to grow out better or otherwise repair the damage.
Nanomedicine, very powerful. We will probably have little machines that clear out strokes. We will probably have the ability to reconnect in part a nervous system that becomes disconnected through mechanical means at some point in the foreseeable future.
Organelles refer to little parts of cells, the third item down. It means "little organ, " obviously. Cells have many different parts. We’re working on a part of the cell which is crucial for the brain, which takes, by the way, ten times as much energy to run as the rest of the body on average. They’re called the mitochondria. They’re the energy factories of the cells. They get damaged with aging. They’re probably damaged in bipolar disorder. They seem to be damaged in Parkinson’s disease. They are replaceable, and we are learning to replace them. I want to show you one example of cell replacement and one example of biofeedback just to tweak your interest, but I won’t talk more about the other options.
In cell replacement, we can provide new cells to the brain. These cells might either directly replace lost cells or defective cells, or may just go in and provide factors that support the existing cells to help them be healthier or to grow out appropriately. These cells, by the way, do not have to come from embryonic sources, although that may be necessary for some purposes. There are many different sources of stem cells. This particular example, again, is in a mouse brain. The cells were given up through the nose. They actually go through the top of the nasal cavity into the brain where there are openings. You can see at seven days post-treatment they’ve wandered into the brain. At fourteen days, they’ve wandered further. This is a march. This is a war I think we could possibly all support because these cells will go to the site of a lesion in the brain. There they are where there has been damage. They glow green because they’re stained with green fluorescent protein by the way. They are developing into new nerve and support cells. That’s shown by the dye in the middle figure. On the left are the cells glowing. In the center it shows you that they’re not stem cells anymore. They’re developing into cells of the brain.
What about biofeedback? Very briefly, can the brain be trained to repair itself? Well, actually, we do that all the time. Current treatments repair the brain. Here’s an anti-depressant treatment and a psycho-therapy. If you look at the right in each (the anti-depressants, on the left) the same part of the brain has become activated. This is blood flow. It’s in the right basal ganglia. Whether you give someone a drug or you talk to them (works for men as well as women, by the way), they actually will listen to talk and can get better. We’re already changing the brain and its activity. The issue is, can we change this structure and activity more efficiently? Can the brain train itself to change its own structure and activity? The Buddha would tell you yes; knew that 2,500 years ago, but it took him a lifetime to learn. This was done in three sessions in an MR scanner—three sessions. What you do is you put someone in the scanner and you give them live real-time feedback on an activity of a part of their brain and say, "Can you change it? " The answer is: just as you can learn to change your blood pressure with feedback or you can learn to change your pulse with feedback, you can learn to change the regional activity of your brain. This was done to control pain; but if you can control pain and it worked, why can you not learn to control, depression, anxiety, hallucinations? It’s entirely possible.
Lastly, what does the future hold for treating our brains? Here again, I’m speculating, but it seems obvious that as these new technologies develop, they will change the way we look at ourselves, and we will have to make choices about how to use our new power. The hopeful thought is: As with other conditions (HIV, cancer, Alzheimer’s disease), we will not only get improved care, we will reduce stigma. As we understand what’s actually causing these disorders, we’ll tolerate our illnesses better and those who have them. We’ll want to help more.
The substantial issue is this: with the increased ability to change the brain, we’ll have ethical and financial issues. In particular, will the technologies be applied only for illness or also for personal improvement and, of course, is there a clear distinction between the two? Lots of people may want this, and any technology can be used poorly or even for harm. With wise use, my hope is we’re on the threshold of doing unprecedented good for the many people who suffer from brain disorders. I thank you for listening.
John Durant
Well, thank you very much for a very rapid but very, very instructive review of some extraordinary developments going on. Now, if the lights could be put up as far as it’s practical, I’d like to take one or two questions about specific things here. I see a hand right in the middle. Could you wait for the microphone, please? And Emlyn, you should tell us who you are.
Audience
Emlyn Koster from Liberty Science Center. I wonder with respect to this presentation whether the next ten years are going to rebalance the understanding we have between environmental causes, lifestyle-choice stimuli, or whether what you’re researching is just naturally inevitably part of being a Homo sapien?
Bruce Cohen
I hope we’re studying what it is to be a Homo sapien. I have to give John his due, by the way too, which is he wisely advised me to keep the slides to a limit, and I apologize in my enthusiasm for sharing so many. I think the crucial question that you asked, if I understand it, is, Can we use these technologies to understand the whole of who we are?, which is to say we are not obviously just biological creatures in the sense we understand and we have mental and spiritual life? I don’t personally draw much distinction between those. I think they integrate. I’ve always felt that the evidence, by the way, in psychiatric disorders is absolutely overwhelming that as much as for any medical conditions, all the severe psychiatric disorders have substantial inherited risk factors which determine whether we get the illness or not.
The second part of it is that illnesses all have some kind of environmental or life component. It’s hard to study either of those components until you get a foothold in one of them. I think the foothold in the biological side is going to tell us who’s at risk and, therefore, will allow us to do good studies of what triggers illness. Stress is clear but there may be environmental toxins of other kinds. Those answers will come to us over the next few decades, I believe, as this is iteratively pieced together from side to side.
John Durant
Thank you. I’m going to take just one more at this stage, bearing in mind there will be some discussion at the end. There’s a person here, please.
Audience
Thank you very much for that presentation. My name is Lisa Libowitz, and I’m a writer from Baltimore. I was wondering if you could comment a little bit more on your last slide. I happen to have particular personal interest in this, in that I have a brother who suffers from bipolar disease who has currently been in jail in Florida for quite some time while awaiting a nonexistent bed in a psychiatric facility. I’m wondering how you feel from what you’ve already experienced professionally, how you feel these new technologies are going to be used, if at all, to help the poorest members of our society?
Bruce Cohen
That’s perhaps the most crucial question. It’s important to recognize that many, many years ago in this country, McLean Hospital was one of the first ones, we established asylums for people who were in trouble because of psychiatric disorders. I think we did that out of great compassion. Now, if you ask, "Where’s the largest concentration of people with psychiatric disorders? " The answer is "in prison. " That’s because society has not made the commitment to help these people that it could. So I think the simple answer to your question is, I hope that as we learn more about these conditions and we’re able to diagnose them and treat them better, we can much more practically help people and say, "Yes, you have a condition we can do something about other than locking you up. " I hope society will put the money both behind the research that will lead to those advances and behind the treatment that will help people. However, that won’t happen unless all of us speak up and say, "It really matters and we want politicians and insurance companies and all to be behind them. "
John Durant
Thank you. Well, for now we’ll leave those issues for the final discussion and we’ll turn next to Andrew Dobson.
Andrew Dobson
Thank you so much for inviting me here. What I’m going to talk about is a little bit of what I do. A very sort of broad-brush view of how different sciences might be coupled together or how we can perceive them to get some perspective on the scale of difficulty on the scientific challenges of the next twenty to fifty years.
I thought would start off by showing you a picture of my lab. This is one of my labs. I’m actually a sort of Luddite, I couldn’t stand going into lab every day. I’m one of the old-fashioned type of people who feels that what you do as a biologist is you go into the field. This is one of the places I go. This is the Serengeti in Tanzania, one of the most beautiful places in the world. One of the huge challenges we have is, for the Serengeti and many other existences, trying to work out how they work.
What I’m going to make an argument for is that actually understanding how natural ecosystems work is the biggest and the hardest scientific problem for the next twenty or fifty years. And that’s about the amount of time we have before we don’t have any really pristine interesting ecosystems to look at. It’s a beautiful place to go and work. It’s full of charismatic and beautiful animals. These are bat-eared foxes. Unbelievably charismatic.
Now, whenever I go to the Serengeti (I go about every six months), most mornings I get up at five and go for a drive around, taking photographs, looking at things, thinking about what I’m going to write on and work on that day. It’s strange. When I went in December I suddenly started seeing bat-eared foxes, and I hadn’t seen them for six or eight years. When I went and looked at the night transits that we drive—we have ten sets of forty-kilometer night transits that get driven every month recording what’s on them—I noticed there had been a huge increase in bat-eared foxes. Now, one of the reasons for that may be that for the last six years what we’ve been doing is vaccinating domestic dogs around the park against rabies, distemper, and pavovirus, three of the major diseases of domestic dogs that spill over into the wildlife of the park. And so by vaccinating these dogs outside the park, other dogs or canine species of the park seemed to have suddenly increased. And that, in many ways, is the history of the Serengeti at large. The wildebeest I showed you in the previous slide—once we had a vaccine for rinderpest, which was applied to the cattle—the wildebeest population increased from about a quarter of a million to the one and a half million that are there now. And that illustrates partly why ecosystems are complicated. They have hidden connections in them. Why should something we do outside the park have an impact on what’s going on inside it? And, of course, getting at those connections requires us to know something about the scale of which those connections work.
Let’s think about scale. Physical scale is what defines in many ways the different scientists. Here’s a big scale. It goes from ten to the minus eighteen on the far left up to ten to the eighteenth. So you could plot all the sciences on this. Well, you could plot what I do. There’s me at about a scale of a meter, there’s this room on a scale of about a hundred meters, there’s the Serengeti, which is about of the order of ten to the six, ten to the eight meters. There’s the Earth. There’s the galaxy. And we can go the other way. The cells, molecules, atoms, electrons, and down to bosuns. And essentially different sciences work at different scales. And one of the things we are seeing as scientists is a revolution that says, "Can we begin to predict what happens at slightly higher scales by using the technological ways we’ve got at looking at either huge scales or, more usually, very, very small scales? " So a major challenge of the next twenty to fifty years is, How are we going to be able to extrapolate from processes at scales in which we are putting a lot of investment looking at things up to processes that are actually relevant to us? And that’s a big challenge. Mathematically it’s a huge challenge.
So you can plot the different disciplines on there. Quite happily, plotting them out, and then there is a slight irony. You could see where the Nobel prizers lie. So there’s an intriguing thing from a science and society. We are most interested in things that either are at huge scales or tiny scales, but not a lot of interest or not a lot of reverence given… I mean, at Princeton there’s a huge amount of testosterone around the end of October; probably the same at MIT and Harvard. Who’s going to get the Nobel prizes at the big ends of the spectrum each year? You could plot utility to humans on there and ironically, that’s more in the middle. We deeply revere the things that have done very little for the quality of human life. Massive things for the quality of a few egos but not much for everybody else.
No, if we really wanted to understand complexities of how science evolves, the other thing we need to put on that axis is the number of interacting particles. Because the thing that makes the problem hard is how many different types of particles are there and how many different speeds that they interact with and how non-linear are those interactions. And again, you see an irony. Nuclear physics—very, very tiny particles, but not many of them and relatively inert. Astronomy, lots of big chunky things but relatively inert. Once we go into the realms of ecology and medicine in the brain—as we saw from the previous talk—many, many particles in the brain. I think the ecology and environmental sciences end up getting into the nightmare area. We have individuals, populations, communities, ecosystems—all of which are interesting at different time scales and different rates with many different particles, including us. And how we are affected by those particles is a huge challenge and one we much more urgently have to address.
You could also look at the funding which we should hope would be a sort of hump-shaped curve, but actually it’s more a u-shaped curve. And again, that’s a curious facet of science and society. That the "all we feel " for the huge scales I think diminishes the "all we should feel " for the scales that are relevant to the quality of human life.
Now, how do we look at this? This is where I was yesterday. I was intrigued in the previous session—the people from England were complaining about being jet lagged but waking up early. I was actually here early yesterday morning—Santa Barbara, Carpinteria Salt Marsh at Santa Barbara—so it’s still very early in the morning for me and it’s much colder. This is a salt marsh that is just south of Santa Barbara, which is actually an even more civilized city than Boston. It’s work I’ve been doing, jointly sponsored by NIH and NSF with Kevin Lafferty and Armand Kuris. What we are trying to do is say, "What’s the food web in this salt marsh? " I mean, that is one of the things that you do as the first thing you learn in kindergarten, What does a food web look like? But what if we did it properly? Well, we do it properly by using very high-tech methods. We go out on our hands and knees and quantify the abundance of everything in that marsh with two huge field crews. Two crews of twenty people, vertebrate specialists, invertebrate specialists, no two people from the same ethnic background, everybody has to surf. Those are the ground rules. And we’ve been doing this for salt marshes from San Francisco all the way down into the middle of Baja. We’ve very subtle ways of analyzing the data. We intentionally, particularly for some species, just hit them with a hammer and open them up. That gives you a different perspective on what’s going on in this marsh. This is what happens when you hit a snail. You crack its shell open and take out something that part of it’s a snail, but part of it is a parasitic trematode. We’re back to the cestodes, but like the cestodes we mentioned earlier, these are trematodes, so the back end of that snail has been taken over by another organism that’s causing it to produce more path parasites. And in fact, that has quite a beautiful life cycle. It goes off into the water column, infects the fish, gets into the brain—it’s those little red dots, a whole new addition to the brain of that fish, which causes changes in the behavior of that fish. That makes it easier for a bird to eat, so the parasite completes its life cycle in the bird and then goes from the feces of the bird back into the water. And that’s interesting because when we look at food webs, everybody who has looked in the past has ignored parasites. That’s a bit strange: you would think with the worries we have about human disease, we would be much more worried about diseases in other organisms.
But what it means is if we were to go to this challenging study of how does a food web work, this is what a food web looks like. Six different trophic levels from the sort of base or sludgy species on the bottom up to the birds at the top. If you just made up a food web by connecting together the free-living species that eat each other, it would be like this. Quite a complicated pattern, as complicated as the sort of forces pulling a galaxy together or different galaxies together. What happens if you put the parasites in? If you do that, you find it is massively more complicated. And indeed, in some ways—what I’m going to suggest is the parasites are like the dark matter, they are the hidden forces that pull the structure together. But that’s mathematically a very, very hard problem. But to just give you an image of what we’ve missed, if we were to make a traditional food web of consumers, predators eating prey, then mathematically it has the straightforward problem that every element above the diagonal is positive—I gain from eating this species. Every element below it is negative; I lose because I’ve been eaten.
Unfortunately, we’ve missed lots of other species. That would be the free-living web. As we add in the parasites—and these are just parasites we see—you can get an increase in the diversity of species out there of about fifty percent. That is just things we can see. If you look at the additional linkages, where the webs coupled together, if we’ve ignored them we’ve only seen twenty-one percent of the links. So there is another eighty percent of couplings in that thing that we’ve got to turn into a mathematical equation if we are to understand how that works. And those are often very strong couplings and may make a huge impact on how that salt marsh works. And there is an irony there, because we received benefits from that salt marsh but we have no idea of how to put it together. That’s a tragedy. How would you make a salt marsh just starting off? Do you throw a bunch of organisms in? Do you put the parasites in? And indeed, is a healthy salt marsh one that’s full of parasites?
Ironically, the more we go and look at more pristine salt marshes, they have a much higher diversity of parasites in them. So losing those things may be the thing that gets rid of the dark forces that are holding the food web together. But mathematically that’s a hard problem even though it initially involved going out in your surfing gear and cracking open the snails. It also sort of shows a couple of basic patterns. If you are at the bottom of the food web, you get eaten from the outside. If you are at the top of the food web you are much more likely to be eaten from the inside out than the outside in. And guess who’s at the top of most food webs?
So we have to find ways of breaking that up. We could make it even more complicated if we go down into the mud and we can use sort of shot-gun genomics to show that if we go into the mud, into the non-visible area, there may be as many as another thousand, maybe two thousand, species—Half of which are phage-eating-bacteria, eating viruses. So there’s even more complexity there than we can see. Which again, just going back to the old point—that makes understanding the structure of that food web one of the biggest challenges out there.
There’s a fantastic group of people that I’ve just spent some time with at Santa Barbara who have great a Web site called "Webs on the Web " and who are putting together different machinery to start looking at how food webs work. What causes them to persist? And we’ve been berating them that you are not going to be able to solve that unless you put in those missing links, like the parasite species.
There are lots of food webs we would like to do that for. What I was doing in Santa Barbara this week was writing a grant (that’s in fact what we do when I go to my lab is write grants) hopefully that provides the money to go into the field. We’ve been writing a grant to put together data for parasites in a diversity of other food webs, because collecting data on food webs is an urgent thing.
Here’s a web we would love to do. This is where I was over Christmas and New Years. This is just north of Alta Floresta in Brazil. It is what is now the southern edge of the Amazon. It’s the most deeply beautiful forest. I took my kids there because they had not been to the Amazon and I thought it would be great to take the children there. When I got up at five o’clock last Sunday morning to fly to Santa Barbara there was an email from the guy I’d met, the guy in the middle, saying, "Oh, guess what happened over Christmas? " People in Alta Floresta managed to sign a surreptitious deal while everybody was away celebrating Christmas and New Years, to clear-cut the forest we spent Christmas in. So it will be gone. We will never get that web. And that’s a tragedy for my kids and your kids. Thank you.
John Durant
Andrew, thank you very much. Again, the same format please. If you would like to ask a question, a point of information at this stage, please do. Do I see a hand? Yeah, I’m going to take one right at the back, because people at the back are discriminated against in this auditorium.
Audience
How much do you utilize statistical researchers or other quantitative analysts in your work?
Andrew Dobson
To repeat the question. How much do we rely on statistics and mathematics in our work?
Audience
Right and do you have collaborators within your team that actually help you to do any of the quantitative analysis?
Andrew Dobson
Well, I’m actually the person who does quite a lot of the quantitative analysis. Princeton has a focus on what we call theoretical ecology, which is essentially using mathematics to understand the ecology of natural systems. So a lot of the people that we try and train, ironically, we’re trying to train to be more like me, Simon Levin, or Steve Pacala—my colleagues—using mathematics to understand the properties of complex non-linear systems such as ecosystems, the brain, etcetera. So, almost half of the people on each team use mathematics as a sort of way of communicating.
Audience
Can I ask a quick follow up?
John Durant
Sure.
Andrew Dobson
Please.
Audience
Are you familiar with the Mathematical Biosciences Institute at Ohio State?
Andrew Dobson
No, I’m not. But I’d love to know more about it
Audience
I’ll be up later.
John Durant
Sounds like an information gathering afterwards. One more, I think, at this stage, and then we will move on. Yes, right down in the front this time.
Audience
You’ve demonstrated a lot of study of connections and describing the systems in terms of what’s there and what’s linked to what. Are you also studying the dynamics? You talk about non-linearities, for instance, and it’s not just a matter of knowing what’s there and how they are connected but understanding it as a system and how you preterb it leading to complex behaviors.
Andrew Dobson
Yeah. The question is—the figures I presented suggest we’ve made a focus looking at connections between different species in a web. Have we looked at its dynamics, its trajectory through time with a different species? And to a greater or lesser extent, the answer to that is yes. Certainly, for the Serengeti we have both collected long-term empirical data and begun to look at how as the abundance of some species changes, some go up, and the others go down. So we’ve looked at the dynamics of interaction. The people I’ve mentioned, the Webs on the Web people—Neo Martinez, based at Berkeley—they are beginning to put together models that look at what happens if you have fifty to eighty species interacting and what are the trajectories of those interacting species through time. How can we use ways that come out of scaling laws—that the fact that species have different body sizes, have different birth and death rates, and are required to eat different amounts of things—can you use those underlying scaling laws of biology to paramatize models for very complicated numbers of species? So, yes, we are getting there. But that’s why I say it’s a big challenge. People are making massive progress over the last ten to fifteen years and there is a very good book by Mercedes Pascual and Jennifer Dunne that came out from the Santa Fe Institute last year that summarizes a lot of where we are on that. It’s an SFI book but it’s published by Oxford University Press. It’s called Ecological Networks: Linking Structure to Dynamics in Food Webs.
John Durant
Thank you. Well, for now, we will move on to our third speaker, Mauro Ferrari.
Mauro Ferrari
Good morning and thank you for the invitation to this wonderful event. Now, let me start with the bad news. At the end of World War II, the likelihood of someone having cancer, and surviving that cancer was about forty-five percent. Sixty years later, about one trillion dollars later of research money worldwide, now the same number has been pushed up to about fifty-five percent which is a tremendous improvement. A very remarkable improvement by the community. But obviously, nowhere near where we need to be. Now, the question could be why?
We have clearly made spectacular strides in the understanding of the fundamental science of cancer—how cancer begins, originates, develops, and what are the key mechanisms of cancer. Since 1971, you may remember President Nixon then declared war on cancer, we have discovered many great things. One, we know that it is a genetic disease that is very unique in the sense that it requires multiple evolutions of a cell to go from normal into a cancer cell. And these multiple transformations can take as many as ten or fifteen years. We don’t really know exactly. Typically, it will take ten to fifteen years and involve at least two, perhaps as many as ten, fifteen, or twenty, successive evolutions. So, the good news with that is that it would give us a big window of opportunity to catch the disease before it manifests itself in its most damaging forms. Now, we know that the earlier we catch the disease, the easier it is to treat. So, there is a great call for early detection. Unfortunately, if you look at clinical reality, by the time we pick up cancer in a patient today, the lesion has been there—or has been a precancerous lesion evolving into a true cancer lesion—for many years.
Why can we not catch it earlier? That is one of the questions that perhaps we can help solve with a new set of technologies and relationships. Why does it become harder to treat a cancer as it evolves? You know, the big transition that makes it untreatable in many cases, is from the single lesion stage of primary cancer, which we have been able to treat with a knife for many years in many, many cases, to the situation where there is the evolution of different distant lesions, at least in the deposits of the disease which we call metastasis. The unfortunate reality is that if you have one, you have many—ten, one hundred, more—and it becomes essentially impossible to remove them all. It’s certainly impossible to do so with a knife in the vast majority of cases. But even by treatment, the sad new is all of the metastasis are different.
Well, now we know that no two cancers are alike. Like malignant snowflakes. And we also know that a single cancer can evolve into different metastases, which are heterogeneous in themselves. But to make matters worse, they are really different from one another. So the question is, what drugs are we going to be using? Because in reality any drug that we work with, even if it hits one set of metastases, it probably would not hit many others. So, we have a heck of a problem. What we do in the clinic is, of course, to make recourse to the strategy of carpet bombing the patient with drugs that have been proven to have some degree of efficiency against the various strains in which we put the biggest manifestation of the diseases that we call cancer. But it becomes very, very difficult to actually pinpoint and identify a direct therapy in the proper fashion.
Now, having said that, that’s where nano comes in. What is nano? There are a number of different definitions. For many, nano is a four-letter word. The prefix, nano, comes from a Greek word that means, "Apt to bring in research dollars from Washington, D.C. " Remarkably, nanotechnology is the one field of science where people can confront each other by saying, "Hey. Mine is smaller than yours. " Which is a welcome change. But perhaps an operational definition that you can use in your mind—you remember the game of LEGO building blocks. So, nano is about building synthetic functional devices starting with building blocks that are essentially atoms, classes of atoms, or molecules. It is remarkable how much progress has been recorded in the last ten or fifteen years in nanotech for multiple applications, including medicine.
Now the two challenges. I have written the program in nanotechnology for the National Cancer Nanotechnology Institute, and that remains the largest program in the world on nanotechnology applied to medicine. In the process of doing that, I had the privilege of working with any number of great people. Nobel laureates, clinicians, community advocates, bioethicists, entrepreneurs, and investors for about two years all over the country and all over the world. So I’m comfortable telling you about the two areas where nanotechnology can really make epochal differences if properly integrated with the fundamental biological sciences in the clinical disciplines.
Number one, the field of early detection. Now, I’ve made the case for cancer, but similar arguments can be made for other pathologies, starting, for instance, with cardiovascular disease. One is early detection and the other one is the direction of therapy moving from the carpet bomb to the "smart " bombs, if you will. I usually don’t like military analogies, but it gets the point across. You know, make sure we hit the enemy and that we don’t hit the civilian population that is there, the innocent bystanders if you will.
So let’s talk about early detection. It is also true that all of us have developed cancer many, many times during our lifetimes but our immune system is able to keep that in check. So how are we going to be able to find out—if you want to do early detection, if you want to screen everybody—when and where a cancer develops that is going to escape immuno-surveillance. How can we learn where it is quickly enough, early enough, inexpensively enough, and non-invasively enough. No way can we do that with imaging, if you ask me. Certainly there is no way we can do that with taking biopsies, chopping pieces out of people to find out if they have cancer or not, multiple times a year. There’s an untenable thought.
So, I think there is a lot of hope that perhaps we can develop screening strategies based on biological fluids (taking blood samples, or maybe sputum samples, or other fluids that come from the body). Now, the problem with that is that what kind of a signature are we going to be looking at? It probably is going to be a molecular biological type of signature. Let’s think about proteins for a moment. How many proteins do we have in the bloodstream? Different species, I mean. Well, nobody really knows. But a number—about a million—has been cited. Several hundreds of thousands for sure, proteins and proteolytic fragments—how the proteins break down in the process of disease and health, actually.
Now, which ones of these are important to diagnose in the early stage of cancer? The old thought that it could be a magic molecule painted red that we can take out and say, "Huh. We got cancer. " Nobody believes that anymore. So it’s probably a combination of ten, fifteen, twenty, who knows how many different molecules that are also there in health, but happen to be slightly overly expressed or under expressed in the course of disease. So it’s quantitative. You have to get a set of perhaps ten or twenty out of one million. And now let me make it very difficult for you. The concentration ranges in differences that we need to pick up for these things are six, eight, ten, twelve orders of magnitude. Smaller than the concentrations—the noise, if you will—the concentrations of the most abundant proteins in the bloodstream like albumin, and immunoglobulins, and all these things. So, it is a needle in the haystack of truly astronomical proportions to the extent that I’m jealous of the astronomers—they can use the word astronomical. This is a problem of biological complexity that should scare you even more or perhaps just as much as the astronomical complexities. It is unbelievable.
So the question is, why nano? Nano is a natural tool to use for this because the nano objects we use to pick up these molecules are of the size of these molecules. Now the question is to make sure that we can pick up many molecular signatures in real time, in an inexpensive fashion, quantitative, replicable, reliable, and all those things. There are many nanotechs that you’ve probably heard about that are actually very useful. Nano things such as nanowires and carbon, nanotubes—the first thing for which anybody won a Nobel Prize in the very small domain, and that was Rick Smalley and a couple of other great people, Bob Curl and Professor Kroto in England. And there are things that you have heard about, perhaps, that nano can deliver beam technologies in this fair city but in other places as well, such as Berkeley, California. You have nanochips to use together with mass spectrometry that you can use for picking up this molecular signature and profiles. So, there is a lot of nano. To me, by definition, if any major breakthrough is going to be taking place in this field of early detection from biological fluids, it will have to necessarily go, at least in part, through nanotechnology. The second big piece for early detection is won. The other is making sure that the drugs—that the therapeutic principles that we used, that the therapeutic agents get to the lesion. Very difficult.
One piece of that in which we have thirty years of history is the notion of targeting through recognition capabilities. That’s putting on the drugs some sort of a way to find out whether the environment around it is an environment of cancer or not. Through antibodies, for instance, or other recognition modalities. That’s great, but it doesn’t even start to solve the real problem. The real problem is that the bodies sit up to make sure that all the foreign stuff that could get in there doesn’t get to important places. There’s a tremendous bnumberof booby traps and traps for foreign substances such as drugs. What we call biological barriers. So the real problem is making sure that not only do we have recognition but also the capability to address these biological barriers like the walls of your blood vessels. There are all sorts of liners and surfaces that you have in the body. As well as physical conditions, such the fact that as the tumor grows there is an added pressure that squeezes stuff out as opposed to bringing it in from the bloodstream. I can go on and on for a long time talking biological barriers. So it’s a very complex problem of vectoring your drugs to a place, and when it is in the right places to recognize the targets.
That, I think, is the other place were nanotech can actually be of great help. Some technologies that I will mention on that is this notion of multi-stage. They are actual silicon-based nanoporous particles somewhat akin to the notion that if you want to get to the—you remember we are in Houston, Texas, so we talk about space travel analogies a lot. When people started thinking about getting a man to the moon, they probably thought about a big cannon ball and shooting it up high. That doesn’t work. So what you do, you put in a multiple-stages type of system. The first stage is atom five. It takes you out to some place high enough. Then you have a way to get across, then you would circle the moon, and then there is a landing module that gets in the right location on the moon. What people are doing in nano right now is developing multiple-stage particles into which we can address one of the sequential biological barriers. And the last element of the landing module actually has biological recognition capabilities. These are very, very innovative thoughts and some of the stages that comprise this are words that you heard about that by themselves are not capable of solving the problem; but together, I think, really give great innovation to the fight against cancer. Again, buckyballs, nanoshells, nanoshuttles, and including some of the things that actually were already made, play the significant role in the fight against cancer. Lipisomes for breast cancer or ovarian cancer, they are part of standard care. Abraxane, or Paclitaxel—a nanoparticulate formulation of albumin—is now used, so nanotech is already in the works to these examples, but there is so much more that we can do.
In closing, I think the vision that can be brought about for our future—and it is the immediate future that we are talking about—is the idea that everybody be screened in a non-invasive fashion so they pick up early signals of occurrence of disease. That is something that is happening, I think, in the rather immediate future. Now, on a longer time scale, there is this notion of developing vectoring technologies that are personalized and are made specific for the pathology of the case that can actually intervene in the early stages before the cancer develops into something that is very hard to treat.
The net result of A and B is the notion of keeping cancer, transforming cancer, from a disease which is a death sentence or a sentence of suffering, to a disease which can be kept below the threshold level of pain and suffering. So that it can become a chronic condition that we can all live with for a long, long time without an unacceptable level of loss of quality of life. That would be true for cancer but transferable to other diseases. I just talked about cancer because of the time limitations.
Nanotech is not the solution. It is not the way to get to these things, but it is, I think, an important component of this development. The two necessary conditions in my mind that can help nanotech bring what nanotech can to this fight is number one, a very close integration with the fundamental biological sciences. And number two, a very close integration and acceptance within the clinical community. These are important and difficult issues, but the only concern that I have is the question of integration and the embracing of the powers of nanotech by the community at large. In that sense, I think that events such as this play a tremendously important role, and I wish to thank the organizers for putting this together. Thank you very much.
Raju Kucherlapati
Thank you very much. It is a privilege for me to be part of this meeting. So, I wanted to try to first talk about genetics and genomics in clinical medicine. Let me pose a problem to you. Today, the amount of money that we are spending on health care is increasing at an enormous rate. Whether you think about this in absolute dollars or in terms of the proportion of the GDP, it is increasing tremendously and it is anticipated that within the next ten years we’ll be consuming more of the GDP in health-care costs. Despite the amounts of money we are spending on health care, everybody complains about the cost of medicines, and part of the reason is that the cost of developing drugs is increasing at a tremendous rate. Today, the cost of developing a drug is considered to be about eight hundred million dollars, and it’s increasing.
Despite this increase in cost and the amount of money that we are spending, the drug-related adverse events are very high. And it turns out, if you consider what is the most important cause of people visiting the emergency rooms and hospitals, it is because of drug-related adverse events. That cost is not only for the patients, but it also turns out to be important for drug companies. Many of you here in Boston, I’m sure, have heard about what happened to Vioxx, a drug from Merck, which had to be withdrawn from the market. That is costing several billion dollars a year.
So, there is a possible solution for this, and I want to argue that genetics and genomics research is going to change this landscape. How is it going to change the landscape? This is really because of three revolutions that have occurred over the last forty years or so. The first of these revolutions is the recognition that occurred during the part of the last century, that virtually all aspects of human health and disease have a genetic basis for it. I think for many of you this may be obvious because the fact of genetics plays a very important role is immediately recognizable. If we look at our children or our other family members, we immediately see reflections of ourselves. Not only in the way that they look, but also in the way that they behave. But most importantly, in terms of the kinds of susceptibility that they have for disease. So, if genes indeed play a very important role in health and disease, wouldn’t it be wonderful to actually try to identify what those genes are and to try to obtain knowledge about how those genes function and how they cause health and disease? Then we would be able to utilize it for health care. It is with this view that there is a public and a private effort in the last century to sequence the human genome, and that was the second revolution. The third revolution that is currently underway is the revolution in which we are actually using the knowledge from genetics and genomics to actually take care of people. That is referred to as personalized medicine.
So the first of these, as we’ve talked about, is the sequencing of the entire human genome, which is a monumental effort. This was started in 1990 and it culminated in the sequence in 2003 by both public and private efforts. This sequence cost about two billion dollars, but this is indeed historical and monumental for a variety of different reasons. The three billion base pairs of DNA that each of us carries actually contain a history of all of the living things on Earth in all of history. It also contains all of the information that we are going to utilize to become whatever we are going to be in the future. And it also contains all of the individual information about what diseases we are susceptible to, how we react to drugs, and many other types of features. This discovery culminated in 2003, just in time for the fiftieth anniversary of the celebration of the discovery of the structure of DNA by Watson and Crick.
So what’s happening after we discovered this sequence? The first of these things that is happening is that now we are beginning to understand the architecture of the human genome. How all of these three billion base pairs of DNA are put together and whether there is any rhyme or reason for why these things are put together. The other thing that is happening is we are really beginning to understand what it is that the genome encodes. It is really very interesting that when we were trying to sequence the human genome—and I was privileged to be a part of that—there was a competition in the scientific community about the number of genes that we would have. And since we are all considered, by ourselves, to be the most advanced and the most evolved human species on Earth, one would consider that we would have the most number of genes. There are estimates that some people said that we have fifty thousand genes and other people said that we have about a hundred thousand genes. Some people said that maybe we have as many as two hundred thousand genes. However, it turned out when we examined it that we actually contain only twenty-five thousand human genes. Interestingly, wheat, which we eat every day in the form of bread, has forty thousand genes. Clearly, we human beings are much more than wheat, don’t we think? And yet, we have fewer genes.
So the question is, How is it that we turn out to be so advanced that we could utilize so few genes? It turns out that one of the interesting ways that all of nature works is that these gene products work in common accord and we use the same genes over and over again in many, many, different ways throughout our life history. And trying to understand these natural works is turning out to be a great challenge and a tremendous opportunity to really understand how we are really put together.
The next thing that is happening is that we are also understanding how each of us is unique. So, first of all, clearly all of us contain the three billion base pairs of DNA. All of the people here in this room, we all grew up to be normal. Maybe some more normal that others, right? And yet, you know, we are different. We’re different in trivial ways and we are different in profound ways. I’ll show you one simple illustration in how we are different in a simple way. I would like all of you to clasp your hands like you are praying, look at the clasped hands, and look and see which thumb is on the top. I want to have all of the people who have the right thumb on top, to raise their hands. All right. I want all of the people who have their left thumb on top to raise their hands. Here is a simple genetic variation which is present in approximately fifty percent of the population. In terms of genetic variation—because if you try to arrange it in any other way, you’d feel absolutely uncomfortable.
This is a simple way that humans are different from each other. We also differ from each other in very profound ways. In the way that we would be able to think about, you know, whether we are susceptible to particular types of disease, and how we might be able to respond to drugs, or how we might behave. People talk about, you know, when we go to a sad movie and some people are actually crying, there are tears streaming down their faces, and other people are absolutely unaffected by that. People believe that these types of behavioral features also have a genetic basis for them. But not only that, we are now beginning to understand these new technologies that I’ve talked about that are enabling us to understand how genes are important for health and disease. And many complex diseases that were considered to be non-genetic are now turning out to be genetic. That includes all of the common disorders that we think about.
We are also beginning to understand how we would be able to identify people who would be able to respond to drugs. Here’s an example of a couple of drugs that have become available about three years ago. These are drugs for lung cancer, and interestingly, it turns out that only about ten percent of the people who have lung cancer are capable of responding to these drugs. But the way that they are responding to these drugs is shown in the bottom of the figure. On the left-hand side you’d be able to see that this is a sixty-five-year-old woman who had lung cancer. You are able to see this very white structure that’s completely filling one lobe. When she took this drug, within two months, as you can see, the cancer has completely cleared. We know now that the reason for this is that there are genetic changes in the tumor and we know now how to look for these genetic changes. And we can identify the particular types of patients with nearly ninety-five to ninety-seven percent accuracy—to identify which patients are going to respond. That in turn, changes dramatically the way that you would be able to treat patients.
It’s also turning out that the pharmaceutical industry is recognizing the importance and the knowledge of this, and they are developing new types of drugs that are linked to diagnoses. Here are a couple of different drugs. One drug called Herceptin that was developed by Genentech. This is given to women with breast cancer. It turns out that a particular type of test predicts which women with breast cancer are going to respond to this drug and which women do not. Similarly, a different type of drug called Gleevec that is developed by Novartis; it’s also a genetically based kind of drug. So there is a recognition by many, many, pharmaceutical companies that this is the way to go. And indeed, developing such drugs is really going to change the face and bring personalized medicine into possibility.
So, all of this is going to depend upon the sequencing of the human genome to be able to recognize that. And as I’ve indicated to you, the cost of sequencing sorted out at about two billion dollars, and today, even within the last few years, this cost has tremendously changed and there is a challenge now to sequence the entire human genome for a thousand dollars within the next ten years. Indeed, there are technologies that are emerging that are going to make this possible. It also turns out that there is a challenge by the X PRIZE Foundation to sequence one hundred genomes in ten days, and the first group that is successfully able to do that would receive a prize of ten million dollars. There are a number of people who are lining up to be able to compete in this.
Once all of this information really becomes available, it’s also important to think about how we would be able to utilize all of this information in actually making and taking care of health-care decisions. Currently, one of the most important challenges is to be able to have the health-care information portable. There is a national effort to try to have all of the medical records, be electronic so that all that information would be present at one location and is immediately portable. And indeed, we feel that if it is possible for us to be able to get this type of information and recognize all of the kinds of things that I’ve talked about, we would truly be able to accomplish this goal of providing the right drug or treatment at the right time, for the right patient, and at the right cost. Indeed, if we are capable of accomplishing that, that is going to truly be a transformation in the practice of medicine. Thank you very much.
John Durant
Well, thank you very much. A startling image of a potential future for genomic-based individualized healthcare. We’ll just take one or possibly two brief questions from the audience at this stage before we move to our final presenter. If I could have the lights raised slightly. Who’d like to ask a question, please? I see a hand back there on the aisle.
Audience
I just wonder to what extent the insurance companies know about these possibilities, because certainly with HMOs they limit the kind of individuation that can happen in the practice of medicine.
Raju Kucherlapati
The insurance companies are beginning to think about this very carefully. Our conversations with the insurance companies tell us that if we could demonstrate that using genetics and genomics in making clinical decisions indeed is going to resolve in better outcomes, they would be willing to consider reimbursements for those. Such experiments are currently underway.
John Durant
Thank you. One more brief question and again, I see a hand quite near the back and then we’ll move on.
Audience
The title of your talk was personalized medicine. What is it going to do for public medicine? The irony is this huge amount of data you have on people can be taken to the population level and yet how we fund and how we ask questions about public health is different than personalized medicine. Can you comment on the power of this stuff for public health?
Raju Kucherlapati
I believe that, they’re not different from each other. In the case of lung cancer, for example, instead of taking all of the patients which lung cancer and treating them with a drug that is going to be effective only in ten percent of the patients, if you could truly identify those ten percent of the patients up front and treat them, these are two things that you’d be able to do. One is that for those people you know that the drug is going to be effective and two is that you benefit society and the public medicine that you’re talking about. Indeed, that would be the right thing to do because if those ninety percent of the patients are not going to respond to the drug, they shouldn’t be receiving the drug. So I think that personalized medicine and public medicine are not separate but they’re integral parts of each other.
John Durant
Thank you. Well, in the interest of time we’ll move finally to our last speaker. We’re shooting back and forth along Andrew Dobson’s scale of the modeling of everything, and having spent a bit of time down at the fairly small scale, nano and molecular, we’re now going up to the astronomical with David Charbonneau.
David Charbonneau
Well, this is a great opportunity over the next ten minutes to share with you this incredible enthusiasm I have for the topic I’m going to discuss, which is indeed I think arguably the most exciting topic in all of astronomy and cosmology; not in all of science but in astronomy and cosmology and I think that really is the conclusion of many of our surveys of the field. There are some very deep and abiding questions that have faced humanity, certainly we can trace back through written records for hundreds of years, possibly for thousands of years. We’re extremely fortunate. You’re extremely fortunate, because we’re all alive at a time when we will be the first generation in which we have the technological ability to actually look for life elsewhere in the universe and actually answer that question. I think that’s fascinating and I think we have to get ready when we teach our students and when we educate the general public for that possibility. So what I’d like to do is to start first of all by setting the scale as Andrew did. This is a photograph taken with the Hubble Space Telescope of a very, very tiny part of the sky. And indeed, what we’re doing is we’re looking at a part of the Milky Way, the galaxy in which we live, and, of course, you can see some very bright stars. I think I’ll work off of the slide to your left. You can see some very bright stars but, of course, the point is that everything in this image is a star: it’s stars all the way down. You can’t see dark sky because simply your line of sight eventually intersects with the point of the light. So we are but one of two hundred billion stars in the galaxy. You know, are we really alone or is it in fact a biological universe in which we inhabit?
The big questions that are facing us, I think, are the following. First of all, are there planets orbiting other stars and if so, do they look like the solar system or is our system of planets somehow unique? Secondly, what about Earth-like planets? There’s something very special about the Earth in the solar system that’s obvious from a distance. The atmosphere and the abundance of life on Earth is incredible. The rest of the solar system appears to be quite inhospitable, although we haven’t yet precluded the possibility of life. Are there planets orbiting other stars, and if so, do they look like the solar system or is our system of planets somehow unique? Or indeed is our world a cosmic rarity? And then finally, is there life elsewhere in the galaxy, and if so, does it resemble life on Earth? Might it be DNA- or RNA-based or might it be completely different?
The excitement is that actually we’re just about ready to get at these questions. We actually know the answer to the first question. That’s an ongoing study. That’s what has preoccupied many astronomers for the last ten years. I think in the next few years we will have the detection of a planet like the Earth around another Sun-like star. That is a fascinating development. And then we will have the technological ability in the next decade to actually look for life on other planets. I’m not talking about radio beacons from another intelligent civilization. I think that’s for Hollywood to explore. I’m talking about just simply studying other planets, looking at their atmospheres, and looking for clear evidence of biological activity.
The image that really sets the scale to explain why, you know, when I teach my students in my introductory astronomy course most of them express shock that it’s only recently we found the first planet around another star. Most of them and perhaps many of you feel that this is something astronomers must have been doing for centuries, right? Isn’t this what astronomy is about? This image tells you why that’s so difficult. This is an image of the Sun. It was taken in November a few years ago, in 2003, and it was taken at a very special time because it’s not just an image of the Sun. It’s also an image of a planet. Can you see the planet? Right, there it is. Oh, wait. I’m going to work off the left here. Maybe you thought it was this. No, unfortunately, that’s just a star spot. That’s just a little blemish due to a darker patch of the Sun. That’s the planet. That’s Mercury. So that sets the scale for how tiny and precious planets are compared to their stars and why it’s so difficult to distinguish the light from the planet from that of the star. The Earth is a little bit bigger than Mercury, but not by much. It’s about twice as big, so if the Earth was viewed in front of the Sun it wouldn’t be much different than that tiny speck, and yet that’s everything. I mean, all of what these gentlemen have discussed takes place there. So yeah, that’s not to be disparaging, but how fascinating would it be if there were other systems out there just like that? What if, you know, let’s explore that. So the point is we can’t take pictures, right? We can’t take photographs of planets from other stars. I need to shake you free of that notion because many of you probably feel—you’ve read articles in newspapers about the first photograph of a planet around another star. It’s never been done. There are no pictures of planets orbiting other stars, at least systems of planets like our own, stars like the Sun. But we know about dozens of these, and how are we doing that? The point is that we’re coming up with clever techniques that allow us to infer the presence of these planets, to actually learn a great deal about them without having ever taken their photograph. And so if we’re going to educate students and the general public about these discoveries, we can’t lie to them. We can’t misrepresent how we’re doing this. There are simple geometric explanations, just simple pictures you must put in their minds for how those discoveries are taking place, because otherwise they’re just going to have take it as on some authority, "A planet was found today. Oh, scientists found a planet. Oh, that’s interesting. " No, what we want to do is we want to make it clear that all of these subjects are—that the deep questions are unanswered, right? That we’re all going to be part of the exploration, that it’s worthy of funding if indeed it is, and that together we’re going to explore this really deep question about, you know, "Are we alone? "
So the way that most astronomers have found these planets is through a couple of indirect techniques. This is the one I just want to make sure you’re clear on. Many of you have heard of this. This is the wobble. When I talk to people about what they know about astronomy and whether they know about the fact that astronomers have found planets around other stars, many of them do know about the wobble and that’s remarkable that they’ve actually heard about a technique; not a discovery but a technique. The basic idea behind the wobble is simply that the picture you probably have of this is the star, then planets orbit the star, and the star just remains fixed in space. But the truth is actually that both the planet, this little pipsqueak guy, and the star wobble in sort of a dance around each other. And so if we can’t see the planet because it’s so small, remember that previous picture, we can see the star, and we can see the star wobble back and forth. So what astronomers do is they measure very, very carefully, the speed of the star, and they can see that some stars appear to be coming towards us and away from us, towards us and away from us. So they say, "Ah, okay, there’s got to be a planet. There’s got to be something pulling that around. Let’s go and study that planet. " Okay?
Well, it was only ten years ago, I guess eleven years ago now, that the first planet orbiting another Sun-like star was discovered. And so here are the actual data. Those are the actual data and so what you can see is this wobble in time, these data points, they’re actually seeing the star being pulled to and fro, to and fro by this orbiting planet. You can see these two astronomers are really excited about the data, right? They’re two Swiss guys, Michel Mayor and Didier Queloz, and indeed that discovery transformed this from sort of a cute little curious topic of astronomy—you know, this was not the principal focus of astronomy ten years ago because we did not appreciate how close at hand we were to finding these planets. I think that’s an important lesson when we try to look ahead and predict what’s going to matter in the next ten years.
In 1994 people didn’t talk about how we were about to find dozens of planets around other stars. We didn’t know how close we were. We didn’t know that a combination of technology and the fact that actually many planets are different and easier to detect than we had assumed would lead to this revolution one year later. Moreover, we’ve actually studied the atmospheres of these planets. So we’ve never taken a picture. There’s never been a picture of a bright star and a little faint planet next to it, but we have studied the atmospheres, and this is something I do in my research, by again coming up with these clever techniques. These are techniques we can explain to non-scientists so that they don’t just take it on authority that an atmosphere was studied but that they can understand, "Oh, yeah. That’s how the scientist did it. I can visualize that. Maybe I’d like to get involved in that as well. "
And just to show you how that’s done, the idea is that if you have this planet and it’s orbiting a star and you happen to catch one system where your line of sight is exactly aligned with the orbit of the planet, then each time the planet swings around it’s going to pass in front of the star and then it’s going to swing around again and then one orbit later it will go in front of the star. When it goes in front of the star some of the light from the star will pass through the atmosphere of the planet and then we detect that light on Earth and we can study it. When we study it we can see the fingerprints of atoms, of molecules, in that atmosphere. So if we could do that for Earth-like planets we would see—you know, if you did that for Venus and you did that for the Earth, you would see the Earth is very different. There’s all the oxygen. Fortunately, there’s not a lot of C02, although that’s changing. You would see that there’s real evidence of biological activity. Just to show you how rapid the discovery has been, it’s really just been in the last eleven years. So in 1995, the first planet was found. By 1999 we knew about systems of planets. We can now find systems which have three or four planets, possibly more, but at least that many. Those are the ones we can actually detect and study. In 2001 there was the first detection of an atmosphere around one of these worlds and the study of that atmosphere. That was done with the Hubble Space Telescope.
Just last year, several groups, I was leading one of them, for the first time measured the light emitted by these planets, and so we can actually see the thermal radiation. If I took an infra-red camera and I took a picture of this audience and we turned off the house lights, we would see all of you glowing in the darkness, and that’s because you’re hotter than the room. We can do that for planets. We can understand their temperatures. Temperature, well, gee, that’s an important factor in life for sure. Just recently, the two-hundredth planet has been found. So from one to two hundred planets in only eleven years, you can image how steep that discovery curve is at the current time. So what’s the hang-up? Well, what we’re finding are the big guys like Jupiter. What we want to find are the little guys like Earth. And you can see why it’s so much easier to find things like Jupiter.
So what we’re going to do is the following. I think this is our best bet for finding a planet like the Earth. It uses the transit method, so it’s that eclipse I discussed. If the planet goes in front of the star, it blocks a little bit of the light, and so you just see a little miniature eclipse. So we don’t take a picture. We don’t see that black spot like that image I showed you, but we will see that the star appears to get dimmer. So there’s a little animation of that. You can see the planet goes in front of the star, blocks some of the light, and then it moves out and again the star gets brighter and the star’s happy.
Next fall, NASA will launch a mission called the Kepler Mission. It will look at a hundred thousand stars in a dense star field like I showed you at the beginning of the talk. It will find the Earth-like planets that pass in front of those stars. If Earth-like planets are common, it will find hundreds. If it finds none, we won’t know that there are no Earth-like planets elsewhere in the galaxy; but we’ll know that less than one percent of stars have a planet like the Earth in what we call the habitable zone, the right distance where it would permit life or at least life based on water. That would be a fascinating discovery. We’re going to know that in a few years, provided there are no technical glitches in the Kepler Mission.
How will we know eventually that some of these support life? Well, what we can do is study their atmospheres. So again we’re not going to take photographs. We’re not going to see city lights; but by studying their atmospheres we can actually look for biologically driven activity just like all of the oxygen on the Earth, right? That’s all driven by photosynthesis. That’s not geologically produced. It you look at the Earth’s geological record, there wasn’t oxygen. Oxygen had to be created so that then later we could come along and use it. Then, finally, just to look ahead about ten years. We are considering architectures from missions that will not just find these planets, but actually study their atmospheres. So we will look for the biological activity and we might actually be able to detect life on these planets. That really is only ten years out and I believe, if we’re clever about using other ground-based techniques, perhaps even sooner. And such a discovery, I mean, maybe to lead into the discussion, clearly such a discovery—it’s very different what I study than what these gentlemen study, right? What’s the relevance of astronomy? I don’t pretend to offer therapies. I understand how critical it is that we study the environment and the ecology of the Earth, but still there’s this deep relevance to our sense of cosmic scale and this question about whether or not we’re unique in the universe. We have to capitalize on that. Many non-scientists’ first tug, for many of our students, their first interest in science comes through astronomy. We have to convey to them this incredible excitement and the fact that we do live at this very precious time for these questions. Well, thank you.
John Durant
Thank you very much and thank you to all the speakers for doing such a heroic job with ridiculous time constraints. If we could have the lights gently lifted again, we’re going to take questions for the remainder of this session. Perhaps people would like to concentrate their questions initially on David’s talk and also perhaps on Mauro’s since we didn’t have an opportunity to take questions then, but increasingly questions to any of our speakers. Yes, in the center please.
Audience
Hi. My question is actually for the entire panel. My name is Karen McNulty Walsh. I’m a science writer and public- affairs representative at Brookhaven National Laboratory. One of our greatest challenges, of course, is getting information about our research out to the public and I work very closely with our scientists and with journalists. I’m wondering if there is a way to work within the framework of—one of the tenets of scientific research is the peer-review process and many of our scientists are sometimes hesitant to talk with reporters, especially, but I think also the general public about their research before it is published in a reputable journal and has gone through the peer-review process. I understand their concerns. I just wonder if that somehow helps or causes the problem of the public not understanding science as a process and if there are ways to help scientists talk to the public without feeling like they’re giving up their scientific integrity? So anyone who feels like commenting on that.
John Durant
A question to any panelist. How do you talk about science that isn’t yet peer-reviewed?
Raju Kucherlapati
I think, you know, for many of these large-scale projects such as the human genome effort, for example, all of the people who participated in that effort said that all the data would be released to the public within forty-eight hours. So the information was available for everybody to utilize it and many of those types of large-scale projects today that is more the rule, you know, rather than the exception. I think the other thing about not talking to the public prior to publication that is partly dependent upon the journals. You know, Nature explicitly tells you that you cannot talk to the press until the paper is published. So you’re in jeopardy of not being able to publish in a prestigious journal if you say that I’m going to flaunt it and I’m going to talk before publication. But on the other hand, I don’t think that difference of the two or three months is going to make a very significant difference in terms of the public’s understanding or knowledge of what’s happening in science.
John Durant
Other comments, please? Yes, Bruce?
Bruce Cohen
I don’t know if this is going to be helpful but I totally agree, of course, with what Raju has said. A lot of it is out of our hands if we want to publish, but from the media side it’s been pointed out frequently that the media are interested mostly in breakthroughs. The truth of the matter is, there almost never are breakthroughs. Rare events come along that are, but what you heard a lot of people talk about this morning is processes. I don’t think that it’s anybody’s fault that people are interested in breakthroughs, but perhaps there’s a way to make the process more exciting and to use the news media to educate people more about how science is done so that all of us can evaluate better what the rare breakthroughs mean. It will cut this kind of problem out as being the important matter.
John Durant
Okay. Yes, please, Andrew?
Andrew Dobson
I think we’ve come along a way, that we’re heading back towards the sort of era when the best way to keep something secret was actually to publish it. The key step is, I mean, there are all these constraints on major breakthroughs that you cannot talk to the media about them until they’re published. On the other hand, setting it up with the person at your university who does press releases so the when it is published the press is aware of it. It takes as much effort as the work you actually put into the paper, but if you don’t put that effort in, in many cases you just wasted your time entirely. So that paper that came out in Nature in December on the decline of ecosystem services provided by the world’s oceans and loss of the world’s fish species by fifty years out, had a tremendous amount of press work done beforehand. So the people who did it were actually getting calls in from every news agency in the world. Putting that effort in makes a big difference.
John Durant
Thank you. There are a couple of hands over in the block right over there. I’d like to make sure not to neglect people on the wings.
Audience
Thank you. Laura Shigemitsu. I work with Sage Publications, an academic publisher. My question is actually for Dr. Charbonneau about looking for non-oxygen-based life forms when we’re looking at other planets, and do you think that’s on the horizon or is that something that we may not be able to broach for another ten years?
David Charbonneau
I think that we have convinced ourselves that there are all sorts of reasons why life has to be based on water. It’s true that water has some very beneficial properties that we don’t find in any other substance that would be expected to be abundant in liquid form, that oxygen-based life is likely an outcome of that. All of that simply reflects a deep and abiding prejudice. We have just convinced ourselves that since it worked here, it must be the natural outcome elsewhere. So we start by looking for life as we know it because we would know how to recognize the chemical signatures of that life when we see it. We admit that we will probably miss, unless we become adept at thinking more broadly, we will probably miss life because we will think that it is not biological activity, when in fact it is. So one of the great opportunities afforded by this field which is about to be born, which is astrobiology, is that the search for planets around other stars is a feat for astronomers and engineers. However, the understanding of life on those planets is really something where we want planetary scientists and prebiotic chemists, and biologists to work together. So there is this opportunity for this immense fundamental interaction between all these different scientific disciplines to understand, you know, "Yeah, how would you recognize life that was significantly different than that on earth if it was staring you in the face? "
John Durant
I think maybe I’m not wrong in thinking that quite a lot of the big problems and challenges scientists face in the coming decade are interdisciplinary problems of that kind. We’ve heard that from several of our speakers. We have time for one more question only, I’m afraid, and the person I saw was also over there so I’m going to ask if the microphone could go to her and then I’m afraid we’ll have to sum up.
Audience
This is also a question to David. My name is Molly Bentley and I work with BBC Science Radio but I also have an interest in SETI and I’m wondering, given what we’re coming to suspect about the prevalence of life in the universe, microbial, why it is that you consign the hunt for intelligent life to Hollywood?
David Charbonneau
The search for extra-terrestrial intelligence is actually one of the scientific endeavors that many of you have participated in, or perhaps many of your children have, and that’s because through—how many of you have the SETI web—right. I can see some hands going up. So this is a screensaver where you’re actually doing research. You didn’t know it but you’re downloading data and your desktop processors are being used to analyze that data. The idea with the search for extra-terrestrial intelligence is that we’re going to listen for radio beacons and it just involves so many assumptions that there are aliens that are interested in communicating, that they build radio telescopes which have already fallen out of fashion on Earth. I mean, you have cell phones, right? We communicate differently now than we did even thirty years ago. It seems as we just watch technology sweep by us over time scales of ten or twenty years, when the light- travel time to these closest stars is 500 years, just to time it just right so then in that same twenty-year window they’re using that same technology and trying to flag us down seems awfully presumptuous. Whereas the chemical signatures of life in an atmosphere are robust, you know, there are deep and abiding processes, we don’t know exactly what they are—I mean life on Earth has completely changed. The defining property of the Earth is that it is alive. So if you look at its atmosphere you wouldn’t miss that. So I think it’s a much safer approach. However, I’m so glad that some scientists are doing SETI and by God how fascinating it will be if indeed they do find a beacon from another galactic civilization.
John Durant
Well, many apologies to all of the others here who want to ask questions. Perhaps you can take up comments with the speakers after the session. I have two final things that I must do. The first is to inform everybody that the final plenary session, the closing perspective by Rita Colwell, will follow immediately after this panel. So please don’t get up and leave and then try to come back. You will waste your and everyone’s time. Please stay here if you will for the final summative session of this extraordinary conference. That’s the first thing.
The second thing I want to say is by way of a compliment to all our speakers. We’ve looked at some enormous challenges between science and society in this conference and they are big challenges and some big opportunities. It seems to me that one of the most encouraging things is just how many practicing scientists at the leading edge in their respective areas are actually able and willing to get up and talk very clearly and very convincingly and very compellingly about what they do. The scientific community in that sense is the single biggest asset we have in making sure that the gap between science and society is not too wide. I think you’ll agree with me, we’ve been fantastically well-served by our five speakers this morning in their different fields who demonstrate that it is possible to talk sensibly and intelligently and concisely about big questions in science to big audiences. Thank you all very much.