"Exploring the Complexity of Life"
Life Sciences Grand Opening Convocation
May 14, 2004
Thank You So Much.
Dean Lichter, President Coleman, Dr. Saltiel, faculty, students, colleagues, friends. I thank you so much for the special privilege and opportunity of coming to this event and speaking to this extraordinary new Institute. It is one of those developments for which the word extraordinary is not just politesse. I’d like to start by providing a bit of historical perspective and let me just elude to Dr. Saltiel’s noting of the 50th anniversary of the four minute mile. If you look at the world record times for the mile from about 1900 and plot them down, you’ll find that they form a straight line such that in the 1940’s, that trajectory extrapolated would cross 4 minutes at about 1954. And then slice on down. Hardly without, I think it may be bottoming out now, Alan, but I just wanted to point that out. Because I think that this Institute is aiming for an equivalent four minute mile and with the quality of its faculty, the strength it plans in research and teaching, the collaborative efforts and partnerships it envisions is “slicing on down.”
Let me present as background first, a little bit of history of biology; of the way its disciplines were organized, have been organized since the beginning of the 17th century. For most of that time, the disciplines were divided vertically according to groups of organisms studied. A large percentage of scientist of my generation chose to specialize in disciplines organized according to these groups such as botany for plants, entomology for insects, ornithology for birds, mycology for fungi, and so on…microbiology for prokaryotes. Academic departments also followed this Linnaean arrangement for the most part. There were other more general disciplines such as genetics and physiology forming up, but by and large, we lived among a bestiary of “-ologies.” Professors and students alike were expected to know a great deal about all aspects known of the known biology of the taxonomic group they chose, from the classification and ecology on down, to other fragments of knowledge that were available on genetics and biochemistry. The expression “molecular biology” did not even exist at that time.
During the molecular revolution, following the discovery of the structure of DNA in 1953; an amazing advance that struck like a thunderbolt to those who had lived before it, I was a graduate student then, and afterward. To those who felt that probably it would be far into the 21st Century before we finally saw the decoding of the probable protein components of what had to be the most complicated code imaginable. Following that, the orientation of disciplines rotated 90 degrees. Now, biology was divided horizontally according to level of organization. And we had, from bottom to top, an array that included molecular biology and biochemistry, cell biology, organismic biology, population biology and so on. And as the age of molecular triumphalism spread across the land in the late ‘50s and ‘60s, the old taxonomically based “-ologies” shrank in prominence. There was a wide-spread sense that the cutting edge of our science would henceforth be molecular biology. And the older sub-disciplines need only be kept at substantive level, until molecular studies moved up through the successive levels of organization: to organelle, cell, organ, and then through population, rejuvenating and propelling forward the study of each of them in turn. I might mention that my own involvement in this transition and shift in balance of power, which is exacerbated shall we say, by the fact that Jim Watson and I were the only assistant professors in the department of biology at Harvard University. And by a turn of chance, I was offered a tenured position at Stanford – I was promoted and given tenure before Watson. That was one of the most tragic events of my life. They immediately caught their mistake over at University Hall and bumped him up fast too. But it was 20 or 30 years before he forgave me. I can say happily now that we are very good friends. During the 50th anniversary of the events last year, we even took the stage for a two person dog-and-pony show, on biology and conservationism and so on.
And now the pendulum has begun to rotate back. Not 90 degrees to the old vertical alignment, but 45 degrees. There are three overriding causes for this partial rotation. The first is the growing unity of biology. The sub-disciplines of ecology and biogeography and systematics, plus the original taxon-oriented “-ologies”, which have been loosely grouped under the ages of organismic and evolutionary biologies, have grown far richer and more sophisticated. Increasingly technology driven, using many of the same tools as molecular biology, down to and including genomics and computer based pattern searching. The experts on birds and fungi and snakes and other taxa are able not only to explore and classify the biology of the groups of their choice, but to work on them, according to inclination and opportunity at any level of biological organization. And for their part, coming from the opposite direction, many molecular biologists and others, focused on processes at the level of cell and tissue, have embraced evolutionary biology using genomic analysis to reconstruct phylogenies, that is evolutionary family trees, of the major groups of organisms and exploring the evolution of the genome and basic processes of the proteome, by comparisons of species. Collaborations between molecular and evolutionary biologists have become commonplace, and as I expect, they will become important at the Life Sciences Institute.
Let me sort of present a brief image, which you may find slightly jarring, of where molecular biology is at the present time, relative to the other groups of biologies. And this is said with a tone of praise and not of pejoratives of any sense. As we saw so brilliantly illustrated by the seminar talk yesterday, molecular biology is what you might call the natural history phase of biology at that level of biological organization. The scientists have entered, shall I use the word, the rainforest of the cell to explore its biogeography. And they are in the process of discovering and classifying the species therein, of which it turns out, there are probably many hundreds of thousands, and particularly proteins. They are describing the anatomy, the function and the inter-relations among them. And what makes the whole effort so spectacular is of course the technology that has to be developed and the long armament of devices that are brought to bear just to see these creatures and watch them shift and rotate and move angstroms in distances, and so on. This is truly spectacular and requires ingenuity of the highest kind ever seen in the history of science. But I would just call your attention to a certain parallel there in appreciating, here at the Life Sciences. There are Humboldt’s and Darwin’s and Agassi’s that you are providing endowed professorships to. And then to give a kind of parallel orientation to organismic biology and population biology and ecosystems studies, in which the beasts were easier to find and identify, but about which we will know very soon, I will have to say.
The second reason for the emerging reorientation that I just mentioned is that we have now entered the age of synthesis and the analysis of complex systems. And I promise you that I will not use the word “Consilience.” Reduction of complex systems to their elements and basic processes remains at the cutting of biology as just suggested, but now we have reached a sufficiency of understanding through this reductionist phase to proceed more deliberately to the grand program of synthesis. Contrary to the common opinion, science is primarily, if not entirely, a reductionist process and therefore a one sided, dehumanizing, simplistic, even brutalizing enterprise. All science grows to maturity by repetitive cycles of reduction and synthesis. The best biology is accomplished by addressing a complex system such as a molecule, organelle, and organ or an ecosystem. Like a diamond cutter seeking that perfect plane to drive the wedge, finding a point of entry and cleaving it into its elements and most basic processes. Then either literally, or by mathematical models, resynthesizing it, that is putting it back together again. Synthesis is much slower. The era of biology in which synthesis will dominate has only begun and it will last for a very long time. As long a time, in fact, as biology remains a creative and growing science. And you can almost measure the magnitude of the synthesis along with the difficulty of the technology required to advance biology; measure it by counting the number of co-authors on the important papers. And as it goes up, you know you can plot as a measure of the magnitude and sophistication of synthesis. But all of those collaborations are needed and all of those forms of expertise have to be put together.
In this new age of unification and synthesis, it will be wise to cultivate two styles of research and talents of the scientists who choose one of the styles or the other. The first style is defined by the dictum that “For every problem in biology, there exists an organism, a species ideally suited for its solution.” Thus E. Coli for molecular genetics, the squid with its giant neurons for neuron transmission, the nematodes C. Elegans for the total mapping of the nervous circuitry and much more as well. And so on through a short list of model elite organism and species. Those attracted to this strategy are problem solvers. This is the strategy that we saw, again, so brilliantly, illustrated in yesterday’s symposium. These people like puzzles, they like mysteries, they like to get into the unknown and solve a difficult problem. The other rule of successful biological research is the inverse of the first. And that is, “That for every organism, there exists a problem to the solution of which, it is ideally suited.” This is a strategy of the scientific naturalist and the taxonomic-ologist, the tribe, so to speak, to which I belong. You fall in love with a group of organisms, birds, fungi, ants in my case. You dedicate your career to learning all about them, every single thing you can find out about them. You are encyclopedic in your approach. And then you ask, “What are the qualities of my organism that can be exploited to yield discoveries of general importance in science?"
I like to tell starting graduate students at Harvard, I get the chance to talk to them the beginning of every year, that there are four ways to be a very successful scientist. Now I don’t need to address or pass this on to the senior members of this group, but for the students back there, I am going to pass it on to you. The first method is to explore or begin a scientific exploration of a previously overlooked phenomenon or series of phenomena. People thought, well we couldn’t examine that scientifically, or maybe it’s not interesting enough. But go after it. The second strategy is to become the world expert on some group of organisms or phenomenon, whether it is for example birds, or chaperonins, or whatever. You become thee expert and you know it from start to finish and you work it out creatively with others as you go along. The third method is to invent a new technology or be the first to apply that technology to an important biological problem. And the fourth is, in some ways in the more difficult and challenging, and that is to solve an attractable problem. I think it is obvious that the strategies that I just described and all kinds of scientists, including problem solvers and diversity lovers, are necessary for the progress of biology as we move on into the synthesis phase of its history.
And that brings me to the third reason for the present reorientation of biology which I find happening and I believe inevitable. Let me recapitulate that the first two are the emerging unity of biology and the shift in emphasis toward the synthesis and understanding of complex systems. The third reason is the recognition that science has only begun to explore the biosphere, and it needs urgently to get on with this job. I think the status of life on Eearth, at the present time, can be put in a nutshell as follows. Research, particularly during the last several decades, by biologists has revealed the biosphere to be vastly richer in diversity than ever before imagined. That diversity is disappearing through human activity at an accelerating rate. We do not know what most of the species are, or even of their existence, that are disappearing. The great loss of species and ecosystems that is occurring, or will occur unless it is abated in this Century, will exact a severe cost for future generations in security, environmental security particularly, in economic opportunity and, a slight allusion to the art programs that you are ingeniously including here, to Spirit. How many species are there on Earth? That question ought to be on every biology exam. But incredibly we do not know the answer, even to the nearest order of magnitude. Somewhere between 1.5 and 1.8 million species of plants and animals and microorganisms have been discovered and given a scientific name. Remarkably, we haven’t even done a proper counting of what is known at the present time. But estimates of the true number vary widely according to method. They have ranged from an improbably low 3.6 million, to a mind-boggling high of a 100 million or more.
Let me give you a quick picture of how little we know about life on the planet Earth. About 60,000 species of fungi are now diagnosed and classified but the true total number believed to exist, classified, or discovered and undiscovered by methods of extrapolation, has been estimated by the leading expert as 1.6 million: 60,000 out of 1.6 million out there. Consider the nematode worms, the most abundant animals on the planet making up 4 out of every 5 animals. So dominant that it has been said that if all solid matter were removed from the surface of the Earth, you could still see its ghostly outline in nematode worms. These tiny animals are undoubtedly essential for the maintenance of healthy environments. Nematodes are known from about 16,000 species, but the real number could easily be in the millions. So we know a great deal know of one species, Caenorhabditis Elegans, but what will we discover when we study the unknown millions still out there? Realizing that the average lifespan of the species, at least for the known eukaryotes for which we have a fossil record, the average life species for the species and its daughter species before natural extinction, separate from human activity, is about a million years. And knowing that the genome and the proteome are exquisitely adapted species by species for the particular environment in which the species lives. What will we learn when we move from Caenorhabditis and out into the full diversity of the nematode, especially with the methodologies of molecular and genetic biology? Consider bacteria, the dark matter of the biological universe, on which our existence certainly depends. As of late 2002, 6,288 species were known and classified, but about 5,000-6,000 exist, we now know from quick DNA sequence scans, occur in a single gram of fertile soil: 5,000-6000, virtually all unknown to science. And it has been estimated recently in the proceedings of the National Academy that in one ton of soil are found four million species. Even the largest and best known study of organisms, are far from fully known. The global number of frog and other amphibian species, and the global number of mammal species, has grown in the past 20 year by ¼, from around 4,000-5,000 described species. Each year about 2,000 new species of flower and plant are added. And the total number could easily rise from the present 275,000 known to over 300,000. Flower and plants, I daresay, rival birds as the best known of all organisms on the planet.
Let me stress then a fundamental fact about biology that should concern us all. Earth is a little known planet. We don’t know what we are doing as we continue wiping out our ecosystems, our natural ecosystems, and drive species into extinction. We are flying blind. If life were discovered on Mars and biologists were to report that they had identified 10% of the species on Mars, I am sure Congress would be pleased to increase the budget of NASA by billions in order to explore the remaining 90%. The total amount spent each year on the exploration and the classification of biodiversity on planet Earth, from all sources, government and private, is between $150-200 million. Let me repeats that. All of the support, from all sources in this country, to explore the biological diversity on Earth is between 150 and 200 million dollars. That is why I like to think sometimes, and again not with any pejorative tone, that that is approximately the amount lost in broken glassware in the laboratories of molecular biologists.
I am among the biologists now proposing that it would be an enormous benefit to science and humanity to get on with the exploration of biodiversity. The prospect of the initiative has now been accelerated greatly by new technology, in particular high resolution digital photography, Internet publication and rapid DNA sequencing. With the high resolution photography and the method of slicing the specimen, that is not literally, but in different focal lengths so that extremely minute organisms can be photographed with perfect focus and then rotated and panned. With this new method we get images that we can now put up on a screen that are better than what you can see using ordinary light microscopy, or at least on a stage microscope which is what we use to look at larger organisms. And then we can create and are creating, what were are calling e-types, which is a series of such photographs in standard form that can be taken, in any museum the world and put up for immediate single access, on-command viewing. What this does is to free the type specimens from the museum, the type specimen on which the classification of the entire species is based, and have it immediately available. So we no longer have to visit the museum or to borrow specimens. Now, this not to say that museums are going to be obsolete, quite the opposite, because they will be, of course, the centers of future exploration of life on Earth. But what I am saying is the information generated in them and these exploratory missions through planet Earth will be vastly increased in efficiency and speed by the use of these techniques and of course other methods, such as bar coding with the selected genome sequencing. That in time, as we get to know groups better and better, we can identify very swiftly, species from any fragments of tissue or any life stage, identify swiftly to species.
With these new methods, we expect, and we held a conference 2 years ago at Harvard to examine all these methods and to estimate what needs to be done to complete the exploration of life on earth. And we agreed, leaders on biodiversity studies on a continental and global basis, that we could do this within 25 years. The quantum leap implicit is made clear when it is realized, whereas roughly 10% of earth’s species, to pick a reasonable guess, have been researched and classified within the past 250 years. Thus made available the science of the whole and public information system, beginning with the binomial system of Linnaeus in the mid-1700. Now is seems possible to complete the 90% remaining of the species in 1/10 that time. The total cost spread, over the 25 years and many countries, would be comparable, I believe, to that of the Human Genome Project, say around $3 billion. And I might add that we are already, threadbare though we are, and minutely budgeted though we suffer, have already completed 10% of the million or so species that I believe can be e-typed and put on the web. This through the 90,000 species of plants, by the pioneering project of the New York Botanical Garden, and we are doing this now by the insect collections of the Museum of Comparative Zoology, which will add another 10,000. So you can say 10% species have been done already.
We can do this rapidly with the right kind of impetus. Upon this effort, then can be built an Encyclopedia of Life, where on each electronic page for which species known, from virus to whale, is available anywhere by single access, on command. The page would contain its scientific, and if available common name of the species, a pictorial, a genomic presentation, the primary type specimen on which the name was based so that we will have stability in nomenclature and reference systems, and a summary of the species diagnostic traits. The page will open out directly or by links to other databases to a summary of everything known about the specie’s biology and its perceived practical importance to the environment and humanity. And a note that would make it crystal clear about what we don’t know about the particular species or particular major groups of species. And from what we do know, it will present a picture for biologist, coming in from different levels of biological organization or with different goals in mind, to see what species are the most promising in accordance with that first principle of successful biological research, alluded to a while ago. The electronic encyclopedia will be built and we are calling it now, semi-officially (we just had a conference at the Smithsonian Intuition at which we agreed on this term). The Encyclopedia of Life will be built sooner or later, and I hope sooner, to unite biology to the rest of science. Its knowledge will serve human welfare in diverse ways quickly and upfront. It will democratize biological knowledge. The discovery of wild plant species adapted for agriculture; or new gene enhancements for crop productivity; and new classes of pharmaceuticals that will be speeded. The outbreak of pathogens and other harmful plant and animal invasives will be better anticipated and halted. Never again will we over look so many golden opportunities in the living world, or be so surprised by the sudden appearance of destructive aliens springing from that world.
"The Life Sciences Institute will be a force for the inevitable unification of biology that will be ongoing in this century."
Knowledge is what we need to save as much as possible as much of life for future generations, by building strength in the disciplines of ecology and conservation biology. The initial focus of the Life Sciences Institute is of course on the cell, and the molecular machinery of life, as appropriate. But its aim is very clearly boarder, to serve as the intellectual hub of multi-disciplinary interactions around the new life sciences. In short, the Life Sciences Institute will be a force for the inevitable unification of biology that will be ongoing in this Century. And it will succeed not just by the depth of penetration into the workings of the cell, but by the partnerships it creates across disciplines that address higher levels of organization. And I hope I have added something, Ms. President, something however small to that conception. And again, I thank you for the privilege of joining you here on this occasion.