The Role of the Life Sciences in Transforming America's Future

Wednesday, December 3, 2008
The 2008 National Academies Biology Summit Washington, DC

We come together at a time of acute contradictions: a time of deep concern about the global economic scene, but also a moment full of the hopeful energy of a new administration.

Those of us involved with the life sciences and their federal funding are experiencing a parallel contradiction: We have, and we should have, grave concerns about future funding after years of stagnant research budgets. However, two conditions counterbalance those concerns: first, the incredible excitement of seeing a field exploding with new possibilities, and second, the hope that our appeal for federal funding for life science research may soon encounter more receptive ears in government.

I will not pretend to guess how the broader national story will play out. I do believe, however, that those of us who understand the extraordinary importance of funding for the life sciences can seize this unusual moment and transform it into a tremendous opportunity. We must argue boldly for the value of investments in research and development, investments that will pay off in at least three very important ways: by furthering our understanding of some of the most fascinating systems in the universe; by generating striking new approaches to medical care and other great technical challenges; and by fostering a set of industries that will help fuel America’s innovation economy.

The life sciences in transition: a personal perspective
Before I expand on these opportunities, I first want to set out a context for why we should anticipate incredible return-on-investment from life science research. Let me start by offering my own somewhat personal perspective on the rate of change in the life sciences. Over the last roughly 50 years, a time frame that embraces the lives of many in this room today, the life sciences have rapidly accelerated as a modern discipline. To offer one example: I am a neuroscientist, and today many students on many campuses major in the field. When I started college, however, neuroscience did not yet exist as an independent area of study. When I began my graduate work, in a department of anatomy here in Washington, D.C., only a couple of programs in the country offered graduate degrees in neuroscience. Today, almost every university or academic medical center grants degrees in the field.

The cloning of the first genes for a neural protein, the four subunits of the acetylcholine receptor, was reported in 1980, the year I began my first academic job, at the Cold Spring Harbor Laboratory. At the time, as my neuroscience colleagues may recall, we believed that six neurotransmitters accounted for all of the chemical transmission in the nervous system; since we believed we were only dealing with six neurotransmitters, and that the single receptor anticipated for each might have on the order of four subunits, there was no need for sophisticated computational approaches.

Today, of course, we know that in addition to the steadily growing number of neurotransmitters, already numbering in the dozens, even a single neurotransmitter, such as GABA, can exert its effects through potentially hundreds of different receptors. It turns out that a few orders of magnitude change everything; without advanced computational strategies, today’s biology would come to a standstill.

Let me offer one more relevant personal fact: As you may know, I am the first woman to head MIT. When I became president four years ago, that was somewhat surprising and a bit newsworthy. From a science and engineering perspective, however, the more interesting story is that I am the first life scientist to serve as MIT’s president. I joined an Institute that, even then, received more funding from the National Institutes of Health (NIH) than from any other single federal source, an Institute renowned for engineering, yet where roughly one third of our almost 400 engineering faculty engaged the life sciences in their work. Simply put, the MIT I joined in 2004 was not our grandparents’ MIT, and biology today is not the biology they knew, either.

The defining intellectual convergence of our time
In half a century, the life sciences have swiftly evolved into a quantitative, experimental discipline that delivers critically important applications, from medical treatments that save lives to environmental strategies that will help save the planet. Engineering and computational breakthroughs have propelled huge progress in the life sciences, and life science now supplies intriguing new tools for engineers. In short, the maturation of the life sciences and its applications has given rise to what I believe will become the defining intellectual movement of our time, and which I take as my topic today: the opportunities emerging from the historic convergence of the life sciences with the physical sciences and engineering.

I’ll begin by giving a quick history of how these forces came together, describing how far this convergence has progressed and sketching out what this convergence promises for the future. I’ll then conclude by suggesting how we as leaders in the scientific community should respond to today’s opportunities.

Building on an earlier convergence: the physical sciences and engineering
As background, let’s consider a previous intellectual convergence – the convergence that spawned the most transformational forces of the 20th century. In the course of our lifetimes, the technological forces that most dramatically changed the texture of human life are the continuing revolutions in electronics, in computers and in information technologies. These technological revolutions sprang from basic research in the physical sciences, carried out as the 19th century turned into the 20th. That research produced a depth of understanding of the physical world that held, and still holds, enormous scientific and philosophical significance. It revealed the fundamental structure and relationships of the universe. It gave us a new sense of our place in the cosmic scheme. It was a triumph of knowledge for the sake of knowledge, a crucial value for any advanced society.

At the same time, early 20th-century physics also gave us a “parts list” of the physical world. Seizing on this “parts list,” engineers incorporated the insights of physics into an array of new practical applications. Ultimately, this convergence of the physical sciences with engineering spawned the electronics industry, the computer industry and the information industry. If you contrast daily life today with life a century ago, you would be hard pressed to name a set of technologies and industries that has had a more transformative impact on how we live and how we do our work.

The emergence of modern biology
In a parallel way, and building on the gains of this convergence of the physical sciences with engineering, in the middle of the 20th century a similarly fundamental group of discoveries set the world of biology ablaze. When Watson and Crick reported their elucidation of the structure of DNA in 1953, it triggered a massive new experimental direction that assembled a “parts list” for the life sciences. The discovery of the structure of DNA laid the groundwork for two great revolutions in biology: first, the remarkable unfolding of molecular genetics, which led to, second, an explosion of information through genomics.

For those of us who get excited by new scientific knowledge for its own sake, these developments were, and are, incredibly exciting. They also produced many practical outcomes, from the unification of the many branches of biology through a common set of core building blocks, to remarkable medical advances, such as targeted cancer therapies and the use of statins to lower cholesterol. What’s more, in addition to saving lives, the biotech industry now contributes billions of dollars to the nation’s economy. In the health care biotech sector alone, revenues from publicly traded companies soared from $8 billion in 1992 to almost $60 billion in 2006.

Life science and engineering: a growing relationship
Since World War II, the evolution of the life sciences has drawn increasingly on engineering and the physical sciences. The relationship grew from seizing technological opportunities, and it was accelerated as physicists turned their attention to biology, vastly speeding up biology’s ability to commandeer new technologies. The electron microscope and a range of powerful imaging technologies offered insights at higher and higher resolutions. Clinicians adopted these tools to diagnose and treat patients, with technologies including CT, MRI, ultrasound and PET scans, among others. Life scientists adopted new analytic tools, from centrifuges to chromatographic technologies, and these technologies, too, found their way into clinical uses. This pattern of adopting and developing technologies from the physical sciences and engineering has led to stunning advances, in biomedicine and far beyond.

Physical sciences-based engineering also offered strategies for working with the avalanche of data spilling out of the genomics revolution. Archiving and manipulating large data sets – a common problem in the physical sciences and engineering – is endemic to modern biology; now, the tools that engineers and physicists developed for their own work have a new life in the biology lab. The Human Genome Project drew on mathematics and computational science as much as it drew on powerful new gene sequencing technologies. Many disorders are believed to stem from multiple genes that vary between individuals and can respond to triggering factors in the environment. That complexity requires the analysis of many DNA samples to detect complex genetic signatures: perhaps as many as 10,000 samples must be examined for each disease, analyzed side-by-side with samples from 10,000 people without the disease. The DNA then must be scanned comprehensively for genes with disease correlation. Fortunately, ever-faster and more economical computational methods for genomic analysis now permit a sample to be scanned for nearly a million genetic variations, a level of complexity that earlier generations of biologists could not have contemplated.

In the life sciences, the birth of a third revolution
More recently, these two revolutions in the life sciences have sown the seeds of a third revolution. Initially, the connection between life scientists, and engineers and physical scientists, revolved around borrowing tools. It started very much as an arms’ length engagement that often cast engineers as service providers to biologists. However, what began as a relationship of proximity and convenience has today progressed into an incredibly strong and fruitful new synthesis – a relationship of equal partners, working together to push the frontiers of research, a powerful fusion in which both realms gain from the connection. We see this new fusion growing up across the MIT campus and across the country; the seeds of the third revolution in the life sciences have certainly been sown, and in some cases they are already bearing fruit.

At MIT, faculty in our School of Science and our School of Engineering are working closely together on projects in the biomedical sciences and many other fields. Let me offer a few examples by way of illustration.

The third revolution: examples from cancer research
As we saw the overwhelming evidence of this revolution, it inspired us to create a new organization and to design a new building to capitalize on its vast potential in the fight against cancer. The Koch Institute for Integrative Cancer Research at MIT grew out of our Center for Cancer Research, which was established in 1974 during the War on Cancer. Salvador Luria, a Nobel laureate at the time, brought together a dozen biologists to investigate the biological basis of cancer. That group, among others around the world, turned cancer research into a science-based endeavor. Along the way, they cracked the code of the so-called Central Dogma, demonstrating many key steps in the translation of the information stored in DNA into the protein machinery of living organisms. Much of modern molecular genetics emerged from that work, as well as our contemporary approaches to targeted cancer therapy.

We now see the frontier of cancer research populated with biologists and engineers, computational experts and chemists. They bring together a mix of disciplines and perspectives that is driving new strategies to diagnose, treat and prevent cancer. MIT’s Koch Institute will house about a dozen cancer scientists and about a dozen engineers and their research groups. It will offer core facilities to the Koch investigators and to others on the MIT campus working at the interface of the life sciences with engineering.

Needless to say, at 180,000 square feet, the building is large. Yet its location speaks even more vividly to its ambition: it stands at the center of a circle of buildings that house biologists, chemical engineers, biological engineers, neuroscientists, electrical engineers, computer scientists and environmental engineers, along with the Whitehead Institute for Biomedical Research and the Broad Institute for genomic medicine.

One example of the kind of progress that comes from this kind of interaction addresses a long-time search by cancer researchers for a technology that could deliver therapy directly to tumor cells. Now, labs at MIT and elsewhere have engineered nanoparticles that can transport anti-cancer drugs straight to cancer cells. Designed to be internalized only by cancer cells, such particles can deliver strong doses of chemotherapy, perhaps inhibitory RNAs, with minimal injury to normal cells. Several laboratories have demonstrated the engineering of a nanoparticle that acts as a homing device, or a “smart bomb,” with encouraging evidence of their efficacy.

That is one promising example. Yet the question remains: why should we think this kind of biology-plus-engineering approach will work more broadly? Why would MIT invest more than $300M in such an experiment? The answer is that the experiment has already succeeded: This kind of approach has already made enormous headway in combating another group of stubborn diseases. Over the last 30 years, the NIH invested four dollars per American per year in cardiovascular research. According to former NIH director, Dr. Elias Zerhouni, that investment has reduced the rate of death from heart disease and stroke by 63 percent. The innovations that produced this extraordinary success came out of biology and out of engineering: we now have new drugs and new devices; statins (to lower cholesterol) and stents (to open occluded vessels). That is our proof of principle, and our daily experience in practice is equally encouraging. At MIT we have already seen that early integration of engineering and science approaches can produce even more revolutionary strategies and technologies.

The logical extension: Biological Engineering
Let me offer one final example of the power of this convergence, this third revolution. In the last decade, we have witnessed the birth of a new field, biological engineering. Derived from cellular and molecular biology, it parallels the birth of chemical engineering from the scientific discipline of chemistry. At MIT, our new department of Biological Engineering has established the intellectual framework of a new discipline, with sophisticated undergraduate and graduate curricula. It does more than put biologists and engineers in proximity; it produces individuals fluent in the language of engineering, in the language of the life sciences, and in the distinctive new language of biological engineering. With a very deep understanding of biology, biological engineers do what engineers do best: analyze complex systems, describe predictive mathematical models, derive fundamental design principles, and then design entirely new solutions.

The promise of the third revolution for biomedicine is simply immense. Yet, its significance does not stop at the doors of the hospital. For instance, advances from this great convergence also present tempting new strategies for tackling challenges in energy and the environment. Second-generation biofuels, for instance, are emerging from genetically engineered fuel crops that produce more material with less water on less land, and that bioengineered microbes can more readily convert into biofuels.

One of the more astonishing products of the third revolution is a new kind of battery, fabricated by viruses that are selected to incorporate battery materials and that then self-assemble into sheets of anode or cathode. These batteries, engineered by MIT professors Angela Belcher and Paula Hammond, look like sheets of plastic wrap – clear, flexible, lightweight and with equivalent power and recharging cycles of conventional batteries. Meanwhile, civil and environmental engineers Ed DeLong and Penny Chisholm use genomics technology to decipher the microbial ecosystem of the oceans and its response to climate changes.

A third revolution that will transform our lives
Let me sum up the potential of this third revolution in a simple way: In the early part of the 20th century, no one could have named the industries that would come from the convergence of the physical sciences and engineering, yet the electronics, computer and information industries have transformed life on earth. And today, we do not yet know the names of the industries that will come from this century’s great convergence of the life sciences with engineering, but we can have confidence that those new industries will transform our lives as powerfully as last century’s new industries.

Seizing the potential of the moment: vital next steps
The promise is so great that progress seems inevitable. But candidly, given the problems we face, from pandemic disease to a stumbling world economy, “inevitable” isn’t good enough. We need progress that is certain and soon, and that kind of progress demands immediate action. Let me suggest a few specific steps.

1. Encouraging young people to pursue fields at the convergence
We must encourage young people to take up this next challenge, to get them as excited by the possibilities of science and engineering as we all were in the Sputnik generation. I have to tell you how easy this seems, from my perspective at MIT. Every year in late August, I walk around campus, meeting the newly arrived freshmen. When I ask them what they think they might want to study, many talk about areas emerging at the convergence. Whether they have interests in mechanical engineering, or biology, or computer science, they talk about the promise of work that crosses the disciplinary boundaries of science and engineering.

2. Educating students to be bi-lingual across disciplines
So, once we have captured their enthusiasm, what then? We need to offer a broad education for biologists and engineers, computer scientists and mathematicians, so that the material they study has common elements, equipping them to talk and work across disciplines. At MIT, we offer this kind of dual disciplinary study in the biological engineering curriculum, but also in variants of chemical engineering and mechanical engineering. There is also much activity around other ways to link science with engineering.

3. Funding young investigators and bold, cross-cutting ideas
In addition, and vitally important, we need to fund young investigators. When I talk with our youngest faculty, I am struck by how often their research engages more than a single area. They are really good at what they do, and in a reasonable funding climate they get funded even though their work does not fit tidily into pre-determined interest areas. However, when funds grow short, work that crosses areas, and particularly the work of young faculty with a shorter history of achievement, often falls off the funding list. In 1990, young researchers received 29 percent of NIH’s RO-1 grants. By 2007, that had dropped to 25 percent. The average age of first-time NIH RO-1 grantees is now 43. NIH has programs designed to address the aging of the investigator population, but we must continue efforts to make research open to young researchers.

4. Designing new strategies to assess and fund cross-disciplinary ideas
We must also find ways to fund the kind of research I have described here, not simply with engineers as “service providers” to biologists, but as true partners in the evolution of research programs, side by side at the lab bench or computer desktop. We need better systems for funding projects that include investigators in different departments, schools and institutions. This will require funding structures that cut across internal NIH divisions and across federal agencies. How do we bring together a research environment historically funded by the National Science Foundation, the Department of Energy and the Department of Defense, with one funded primarily by the NIH? Our funding agencies, not just our scientists, need to be collaborators.

As part of this effort, we must also figure out how to maintain the principles of peer review, which has served us extraordinarily well, with its important commitment to being meritocratic, to the principle of “propose and not tell,” and to the idea that “everyone can play.” In this new world, our peer review system will need grant review committees with multi-disciplinary membership, and because tough economic times tend to make grant-giving agencies even more cautious, our funding practices must also include monies set aside for bold, cross-cutting ideas.

5. Accelerating the flow of ideas to market

In addition, as I have already said, as wonderful, as important and as intoxicating as pure discovery is, we must develop ever-better mechanisms to move discoveries from the mind to the marketplace. That means understanding what kind of work progresses best in the context of an academic institution and what kind progresses fastest in an industrial setting. It also means having clear-eyed, and clearly spelled out, conflict of interest policies, policies that facilitate research but that do not compromise the validity or the integrity of the outcome.

6. Making the case for the value of investing in research and innovation
Finally, let me add a note of caution, one born of the optimism inherent in the 21st century. During World War II, the U.S. developed a new kind of three-way, government-industry-academy collaboration that produced a huge number of remarkable technological accomplishments. After the war, we turned that three-way collaboration into the engine of a new kind of economy, one based on innovation. Economists now generally agree that in the decades following the war, more than half of America’s economic growth came from technology. And, because the war had not been fought on U.S. soil, for many years we had the field more or less to ourselves.

Needless to say, things have changed. Thanks to the 20th century’s new technologies and to the extraordinary global progress that has propelled more people out of poverty more rapidly than at any other time in human history, we no longer have sole access to the economic benefits of innovation. Many countries all over the world have built the foundation for their own innovation economies.

I like competition; it makes everyone better. But we need to play if we want to compete. Investments in basic research are investments in that competition; they are not costs. Many analyses have demonstrated the remarkable return on investment that stems from funding basic research. It is now up to us – those of us who know the science, who know the engineering, who appreciate the nature of the challenges and their solutions – to make the case for those investments.

For the life science community, a call to action
Garnering investment in basic research will not be easy, especially in this very tough economic climate. I believe our best chance to help lead the country to the full potential of this third revolution is to give the public a sense of the results that sit only just beyond our reach today. Unless we draw a compelling picture of how research investments will deliver new gains in health and offer new answers to today’s energy and environment challenges, research funding will continue to stagnate.

One way to understand the potential impact is by a parallel with that previous convergence I spoke of earlier – the convergence of the physical sciences with engineering that defined so much of the 20th century. In 1937, MIT’s then-President, Karl Taylor Compton, gave a speech called “The Electron: Its Intellectual and Social Significance.” Now, remember, that was 70 years ago, only two years after the invention of FM radio and still four years before the first commercial television station was licensed in New York. It was fully four decades before the personal computer reached our desks. Yet Compton saw the potential. As he put it:

“No instance in the history of science is so dramatic as the discovery of the electron, which, within one generation, has transformed a stagnant science of physics, a descriptive science of chemistry and a conventionalized science of astronomy into dynamically developing sciences fraught with intellectual adventure, interrelating interpretations, and practical values.”

In effect, with the discovery of the electron, the physical sciences moved from the perpetual, vast questions of, “What, Why and How?” to take up, in the company of engineering, the potently practical question, “Why Not?” Today, we stand at the beginning of a parallel revolution. And I hope we can help accelerate its potential: for human health, for national prosperity, and for the survival of the planet.