Conquering Cancer: Reflections on Major Milestones in Cancer Research and Technology Development

MINDELL: Good morning. It's my pleasure to introduce the MIT150 symposium on conquering cancer through the convergence of science and engineering. My name is David Mindell. And I'm chair of the MIT150 Steering Committee. And as an engineer and a historian, I've become something of a student of MIT's history.

In 1853, William Barton Rogers came north from Virginia to pursue his dream of a new kind of technical education, an education that would mix the world of science and useful arts, theory and practice, what we have come to know as Mens et Manus, mind and hand. Fulfilling Roger's dream, the governor of Massachusetts signed MIT's charter on April 10, 1861 creating this unique and innovative educational institution. Even the name was bold and dramatic. The word technology in the title was, until then, a novel and obscure term as opposed to the more common useful or mechanical arts. So the T in MIT brought the very idea of technology to the American imagination.

The future that Rogers envisioned would belong not to those of high family, nor to those schooled in theology, but to those of the middle classes schooled in science, engineering, and what he called large general cultivation, applying their knowledge to practical problems for the betterment of society. Roger's original vision for MIT included lectures and exams, yes, but also, quote, "practice in physical and chemical manipulations and excursions for the inspection and study of machines, motors, processes of manufacturers, buildings, works of engineers, geological sections, quarries, and mines." Sounds like fun.

He imagined that MIT graduates would be both practical experts and thinkers of great breadth. It would not be easy. As Charles Eliot wrote in 1869, when he was an MIT professor of chemistry before he became president of a school down the street, "The graduates of this new Institute, with their new education, would require courage, so much would their preparation differ from those of the other leaders in their society with whom they would rub shoulders." And that is still true today.

Now we are celebrating 150 years of accomplishments in a variety of fields, of ideas and inventions that changed our world and define it today and of the courageous professors, students, graduates, and alumni who have gone forth from this place to make their contributions. The MIT150 celebrations take place over 150 days over the course of this spring. And they include many events, concerts, and other festivals.

I want to particularly highlight the next century convocation, which is on April 10, just a few weeks from now, celebrating the actual signing of the charter. I encourage you all to register online and attend. It's free. And the whole campus, plus all the alumni, are invited. It's sure to be a stupendous, historic, once in 50 year event.

Today we are here to reflect on the past and to envision the future. The core, the intellectual core, of MIT's 150th anniversary celebration is what comprises the core of MIT, thinkers, students, researchers, and professors talking about great ideas, contemplating the world, talking about their research, and hopefully even making a little bit of progress on some of the big problems. We honor our history by doing what we do best and inviting the world in. This is the essence of the six MIT150 symposia, the second of which we're opening today.

The other symposia focus on economics and finance, which occurred just a few weeks ago in January, women's leadership in science and engineering, which will be just about two weeks from now, computation and the transformation of our world in mid-April, the future of exploration of Earth, air, ocean, and space in late April, and new approaches to the problem of intelligence, brains, minds, and machines, in early May. Each of these was chosen for its leading faculty, its exciting new ideas, and the symposium's focus on more than one department and more than one school. Of course, they in no way cover the full range of what goes on research-wise at the Institute. But they all represent cutting edge work that epitomizes what's best about MIT.

My thanks to professors Tyler Jacks and to Director of the Koch Institute and to Robert Urban, Executive Director, for their willingness to step up and organize this historic gathering. And thanks also to all of the participants, and to all of you, for coming to share your time and insights. I also specifically want to mention the MIT150 staff, led by Gayle Gallagher and Ted Johnson, who have been working long hours for many weeks and will continue for many weeks, and are responsible for the beautiful and smooth logistics you'll experience today. I have literally never seen so many people receive so many lunches in such a short, efficient amount of time than at the economic symposium in January. And I'm sure you'll see that feat repeated today.

I, like so many others, have a personal interest in the topic today as my own father is battling cancer. I was walking around the Koch Institute yesterday and couldn't help but feeling that were William Barton Rogers alive today, he would understand that place. And he would be proud. The convergence of science and engineering to address one of society's critical problems, 150 years later, still captures the essence, and indeed, the special courage, of Roger's vision for MIT. I'll now turn the microphone over to President Susan Hockfield of MIT.

[APPLAUSE]

HOCKFIELD: Thank you, David. Good morning, everyone. I particularly want to thank David for his truly heroic work in shedding fresh light on MIT's sesquicentennial events. He introduces so many of the events. And every time I hear him introduce something, he pulls out some new nugget of MIT history that I did not yet know.

Good morning to everyone. I am delighted to see so many of you here so early in the morning. But who would not come out for this particular topic?

Many of you know I'm a neuroscientist by training. And my very last big project in my lab, when I had a lab-- seems like a long time ago but probably not so long ago-- I studied genes that were implicated in the ability of glioma cells, brain tumor cells, to spread into normal brain tissue. And so I can tell you that I have enough background to understand that the roster of speakers today represents absolutely an extraordinary set of leaders in cancer research, and frankly, in the new frontier of cancer research that we're pioneering here at MIT.

And while you can be quite astonished and impressed by their stellar contributions as individuals, what they aim to do together is even more compelling. And that is to build interdisciplinary collaborations to find new ways to diagnose, treat, and prevent cancer. So as an introduction this morning, I want to answer just one question as we sit here, as David said, at the Massachusetts Institute of Technology, an Institution famously lacking a medical school and a hospital. What gives us the audacity to imagine that MIT should be an important player in the great biomedical struggle against cancer?

The first answer, of course, is that we believe MIT can do significant work in this field because MIT already has done. Since the MIT Center for Cancer Research was founded more than 35 years ago, MIT researchers have earned four Nobel prizes for their fundamental discoveries about the mechanisms of cancer. Yet as each of us knows, and again, David pointed out from the suffering of family members and friends, despite the very best efforts of, now, generations of clinicians and scientists, the roughly 200 or more diseases that we together call cancer have not entirely, but continue, in a major way, to defy human intervention.

So why should I believe that we can make progress against this scourge for patients today when progress has eluded us for so long? And I would assert that we believe we can make progress because we have the right team in the right place at the right moment in history. Let me explain.

We begin here at MIT with our home team, the dream team, the talent and resources of the David H. Koch Institute for Integrative Cancer Research. The Koch Building that we dedicated-- I think it was about 10 days ago-- holds 27 faculty labs. And those labs are almost evenly divided between biologists and engineers. And the Koch Institute includes another 20 affiliated labs that are spread across the MIT campus.

Inside the Koch building, MIT biologists and engineers, with their laboratories deliberately architected to be side by side, collaborate in understanding the most basic molecular mechanisms of cancer cells and in developing practical patient-ready devices. The work that goes on in the Koch stretches across the entire continuum from abstract theory to advanced applications.

Now, in my own life as a scientist, I've encountered many groups and many institutions that emphasize collaboration. Collaboration has become one of this areas buzzwords. You often see it on signs in the T, or in newspaper ads. And I always look at it and say, hah. I wonder what that means when they use collaboration.

But I can tell you that when you bring researchers from different disciplines together, they come together with different vocabularies and different approaches to problem solving. And when you actually look at what's going on, what might be called collaboration actually looks a lot more like parallel play with each investigator going down his or her own path and only occasionally peeking over the wall between disciplines to get a very superficial view of what's going on.

In contrast, the research leaders who are gathered here today, those at the Koch Institute and beyond, are reaching for something far more powerful and inspiring, the true invention of a new approach to cancer research through the truly conjoined work of scientists, engineers, and clinicians. And the creative energy of the Koch labs is markedly amplified by something we are committed to doing at MIT. And that is education. It's the intelligence, curiosity, and potential of next gen researchers.

The Koch Institute includes over 100 undergraduate students engaged through MIT's Undergraduate Research Opportunities Program, or UROP. There are over 150 graduate students at the Koch and about 150 postdoctoral scholars. You can just imagine the long-term impact of the work that's going on at the Koch when our student researchers who were educated in this extraordinary environment-- they then take the collaborative instincts, interdisciplinary skills, and hands-on problem solving that they are learning and sew these seeds in universities, hospitals, and companies around the world.

So we begin with the right team. At the same time, the Koch Institute is very much in the right place. Many of you will have seen the building, or actually visited the building. The building sits at the corner of Vassar and Main, encircled by scientific, engineering, and clinical talent. The Broad Institute, the Whitehead Institute, the McGovern and Picower Institutes surround it. MIT's own departments of biology, chemical engineering, biological engineering, computer science and electrical engineering, civil and environmental engineering, and others are next door neighbors.

We have great pharmaceutical innovators like Novartis, Genzyme, Pfizer, Sanofi-Aventis, Vertex, and Biogen Idec and dozens of start up companies, small and mid-sized companies, all within easy walking distance of where the Koch sits today. And within a T-stop, or a few T-stops, are the five top funded academic hospitals in the nation including Mass General and the Dana Farber Cancer Institute.

And this is not just theory. We already enjoy robust collaborations among our neighbors. And we believe there will be more to come.

So we've got the right place, the right people. And finally, this is the right time. We're riding a crest of a powerful wave in the history of science. Simply put, the story of the 21st century will be written in the language of the life sciences melded with physical and engineering sciences. Uniting the strengths of these formerly separate fields gives us extraordinary, extraordinary power in the struggle against cancer. You're going to hear more about this convergence of disciplines today. We often call it the third revolution in biology.

So what do we hope to accomplish by the power of this convergence? Our student newspaper, The Tech, captured it beautifully a few months ago. They had a comic strip. And I believe most, if not all, the comics in The Tech are actually done by MIT students or members of the MIT community. This comic strip showed the grand opening of the Koch Institute. And then it was followed by newspaper headline that read, Cure for Cancer Found. The very next frame showed a sign in front of our beautiful new building, The Future Home for Hair Loss Research Institute.

And ultimately, that's our goal, not to do research on hair loss, but to put ourselves out of business. With that very modest goal, I would say, distinctly immodest goal, I want to now introduce the director of the Koch Institute, Tyler Jacks. Tyler is the David H. Koch Professor of Biology. He's been a member of the MIT faculty since 1992. And any way you measure Tyler's accomplishments, he comes up counting as a star.

As a scientist, he has been celebrated for his absolutely pioneering studies using path-breaking mouse models to understand the genetic events that contribute to the development of cancer. Tyler grew up in the heart of cancer research, in the trailblazing tradition of cancer research at MIT. In another sense, he really did grow up at MIT because his father was on the MIT faculty. Now, when I went to the web to put together the few details of Tyler's career that I could brag about him today, I find that Tyler has, in a very modest way, put very little on the web that allows you to actually list all of his awards and honors. And I thought that was marvelous and quite remarkable. And then I discovered the video.

So if you want to know more about Tyler, I urge you to watch his excellent interview on the MIT Infinite History website in which he tells all, or almost all. Let me just give you a few highlights in terms of Tyler's celebrations and honors. He is a Howard Hughes investigator. He's the past president of the American Association of Cancer Research, the major cancer research organization. He's been elected to both the Institute of Medicine and the National Academy of Sciences. And importantly for this event today, I credit him with the vision to recognize that MIT's dual expertise in technology and biology created an opportunity for an incredibly powerful, multi-disciplinary attack on cancer, in very much the same way as MIT's legendary Rad Lab called on cross-disciplinary strengths to develop radar during World War II. Tyler has provided extraordinary leadership for MIT and for the field of cancer research. So please join me in welcoming the leader of our dream team, Tyler Jacks.

[APPLAUSE]

JACKS: Well, thanks very much, Susan. I have to say that when Susan mentioned-- watched the video, I was a little concerned. But I do know the video she's referring to. I will keep my remarks quite brief because the hour is upon us. And my colleagues are anxious to get started. And they have much to tell you. And I, for one, am extremely excited about this program.

This program is actually a bit different from ones that we have organized in the past. We will be featuring experts in various areas of cancer research and technology development, engineering approaches to cancer emphasizing, as Susan described, this convergence of approaches that help us understand the disease better and are already helping us treat the disease more effectively, monitor it more accurately and more sensitively, and I believe, one day, give us the tools to prevent it altogether. So this is an exciting day for us. And it will be a wide ranging day featuring many speakers from our faculty, but also outside guests. And I want to welcome them and thank them for coming.

Joe DeSimone, Lee Hood, Dan Haber, and David Livingston will be joining us from other institutions to participate in the fun. And I want to emphasize the fact that we do expect this to be fun and engaging. It's not just educational. Part of the distinctive feature of today's program is that, in addition to the research presentations that you'll hear and the perspectives that our speakers will impart from the podium, they'll also be sitting here in the living room entertaining questions from each other and from you. Some of you have already given in questions that are represented on three by five cards. If you haven't done that already-- you may have-- and if you don't, get a three by five card and fill out a question, hand it in to one of our runners. And that will be put to the stage for review and discussion. That part of each of our sessions will last perhaps 25, 30 minutes. And we hope that it's very interactive and very enjoyable and informative, as well.

So the last thing I'll say before I turn the program over to Nancy Hopkins is to emphasize something that Susan stressed in her remarks, as well, that the Koch Institute's efforts in cancer research, and I would say MIT's efforts in cancer research, more generally, are all about partnership, partnership in the Koch Institute between scientists and engineers, but also partnerships between the Koch Institute and the many entities on the MIT campus that contribute to cancer research, the departments of biology, the Whitehead Institute, the Broad Institute, chemistry, physics, biological engineering, so many of the engineering departments that are contributing. And this is absolutely critical to our efforts. It's not just about the Koch Institute. It's about MIT's commitment to solve the big problems in cancer.

And these partnerships also extend beyond MIT, as Susan mentioned, very importantly, interactions with our clinical colleagues locally, throughout the country, and internationally, and importantly, interactions with our colleagues in industry who can take our discoveries and our new technology developments and turn them into products that can benefit individuals in the very near term. And so with that, I will turn things over and introduce my colleague, Nancy Hopkins, the Amgen Professor of Biology, a long-time member of the Center for Cancer Research and now the Koch Institute, and an office mate neighbor of mine. And Nancy will introduce the first session. Thanks very much.

[APPLAUSE]

HOPKINS: OK, well thank you very much, Tyler and Susan. You can't see a thing. I assume you're out there still.

OK, so this session is called Reflections on Major Milestones in Cancer Research and Technology Development. And we have three fantastic speakers. And I'm going to be brief in my comments.

These three speakers are going to talk particularly about milestones from the 38 year history of MIT's Center for Cancer Research. But of course, they couldn't resist, as well, talking about the exciting research that they're involved in today. And I was asked to use my few minutes to talk about prehistory. I've reached the stage of life where I'm the person who reflects on the ancient history.

Specifically, I'm going to talk a few basic facts that were known at the time that the war on cancer was declared in 1971 and that led up to the building of the MIT Cancer Center in 1972 and '73.

So these three facts about cancer have been known for a very long time. And they really motivated people's thinking about the problem in those very early days. One fact, if I-- tell me this works. Let's see. OK, three long-known facts.

The first fact that's been known for a very long time is that most cancers occur in older people. So the incidence and the mortality from most common cancers, for example, colon cancer, as shown on this slide, rises very sharply with age. So on the one hand, it's good news that most cancers occur in older people. On the other hand, the bad news is there are a lot more old people in the United States. And that's illustrated on this really amazing slide, to me amazing. I think people my age find this to be one of the remarkable changes in our lifetime.

This is a slide that shows the change in lifespan of people. And what it is is you take a hypothetical cohort of 100,000 people. So imagine 100,000 people born in 1900 who live through their lives at the age-specific death rates that prevailed in 1900. And you get the curve that's closest to me, the green one at the bottom. And you ask, well how many of those people are still alive after one year, two years, 10 years, 20 years, et cetera. And what you see is that quite a few people back then died as infants, and infant mortality. And then they continued to die. So by the time you reach 60 years of age, fewer than half the people who were still alive.

But 50 years later, in 1950, infant death had decreased enormously. And the death rate was lower in midlife, as well. As a result, by the age of 60, 3/4 of those people were still alive.

50 years after that, 56 years, 2006, people are living longer, and in part due to advances of preventing early deaths from heart disease. So now, by the time you're 60 years old, 88% of those people are still alive. It's very hard to die these days.

OK, so the bottom line, there are a lot of old people. And they're still getting more cancer, not because the rate has increased, really, but just because there are more old people.

So in an ideal world, this curve would be rectangular. That is to say, nobody would die before the age of about 90. So the curve would go out straight. And then you'd get sick and you'd die within a few days. So it would drop vertically. Not impossible.

OK, to get to that ideal world, you first have to cure cancer. OK, so a second fact about cancer that also has been known for a very long time is that the incidence of specific cancers is different in different parts of the world. And a related fact is that the incidence of specific cancers can change quite rapidly, even within a single country. What this slide shows is death rates from stomach cancer on the left and prostate cancer on the right in men in 50 different countries. And the number is adjusted to what's called the age-adjusted rate so that these differences do not reflect differences in the age distribution of the population, but truly differences in the rate.

And what you see is that stomach cancer, for example, is very common in Japan, but not in the United States. Other hand, United States has more prostate cancer than Japan. So interestingly, if you move to a different country with a different rate, you acquire the rate of the country that you move to if you'd move in time. If you're too late, then you have to wait for the next generation. Your children will acquire. So that suggests that there's something about the way we live that explains these very striking differences in rates of cancer around the world.

The next slide shows the other factor I mentioned about how the cancer death rates can change within a single country, going either up or down without any deliberate intervention, again suggesting that something in behavior is responsible. So this is the famous case that everybody knows about. People took up smoking. 20 years later, they began to get lung cancer.

In the case of stomach cancer-- so lung cancer went up. People discovered it caused cancer. There was a Surgeon General report. It began to come down again. People quit smoking.

Stomach cancer is the yellow line. And what you see there is the incidence of stomach cancer in the United States has been dropping. Nobody did a thing. It just went down. And people now believe that that was due to better refrigeration, actually, and preservatives in food that prevented a bacteria that is thought to cause stomach cancer. So in summary, the second fact, then, is that a lot of cancer is caused by the lifestyle, where you live and how you live.

Now, the third important fact, the one that particularly interests us, is this cartoon, which I got from my colleague Bob Weinberg, that shows what cancer looks like at the cellular level. So we've known for a long time that cancer occurs when a single cell-- I don't seem to have a pointer-- but you can see the orange cell over here, which sits in an epithelial layer, has begun to divide when it shouldn't. So you get a group of cells that are going to become the tumor.

Ultimately, they grow. They change their properties. They invade and, ultimately, escape into the bloodstream. They go and they seed at a distant site. And they become a metastasis. And that's the problem. This person now has serious cancer that's metastatic.

Thanks, Tyler. You stole my pointer. Thank you, my leader.

OK, back. [INAUDIBLE]. Green, thanks. OK, got it. Thank you.

OK, so many years ago, these three very important facts suggested three approaches to the cancer problem. And they were these. OK, first of all, if cancer incidence varies depending on where and how you live, then it would seem obvious, the easiest thing to do, figure out what those things are and get rid of them. Stop doing them. That was the first approach that was imagined to be a good idea. And that seemed like it would probably be not that hard.

The second approach was early detection. And that came from the idea if cancer is something that develops late in life, maybe you could find it earlier on before its full fledged and get rid of it by early detection. And I think that people really thought these two wouldn't be-- maybe that was the best way to go because the third one is really quite hard. At that time-- remember back-- it's hard to remember back. Some of you weren't probably born.

But in 1971, at the time the war on cancer was declared, we really knew nothing about human cells and what controls their division. We knew that something in their genes went wrong when they became cancer cells. But we could not literally imagine what those genes were, and what had happened to them, and so forth.

But we did know that if the first two approaches failed, we'd better have the third one going strong, because that was really the only hope. If the first two didn't work, what were you going to do? So it was necessary to really try to understand the molecular basis of cancer and hope to be able to ultimately develop drugs that would specifically kill cancer cells. And what made us be courageous enough, if you like, or crazy enough to think we could do this, was that the molecular biology revolution had kicked in about 15 years earlier. And that's what opened the possibility.

So it turns out that all three of these approaches, to my mind, have been remarkably successful, actually, in terms of discoveries. And all of them are having an impact on reducing cancer death. The problem is that, as you know, while enormously impressive, somehow, the outcome, to my mind-- this is a personal opinion. I hope we discuss it during the day-- has not been as spectacular as the discoveries themselves.

So let's look at these. Because they're really pretty amazing. From the attempt to discover what are these things that we have around us, or that we do, that kill us, or cause cancer, tobacco is number one, causes about 30% of all cancer deaths. It turned out, remarkably, that about 15% of cancers-- this would be on a worldwide basis-- are caused by viruses cause cancer. Bacteria, as I said, cause cancer. And unfortunately, on the rise, obesity causes cancer.

Meanwhile, also highly successful from early detection, colonoscopy. Now I have to say, several years ago I was seeing my primary doctor at MIT. And he said to me, we almost never see fatal colon cancer at MIT anymore. I said, what? I really couldn't believe it.

He said, fatal colon cancer is more than 90% preventable by colonoscopy. So that's astonishing. The PAP test, as you know, is gradually, essentially eliminating cervical cancer in this country, although gradually. In both cases, it works because you can see the surface on which the cancer is arising. And you can screen for it. Therefore-- and you don't have to do it that often-- and that allows people to be tested. And you catch the cancer in time. And of course, vaccines are now coming along that are going to be able to prevent about 80% to 90% of cervical cancer and might replace the PAP test. And then, of course, we have these screening things.

But finally, we come to this approach here. And this is the one that has been pursued so successfully here at MIT. I think it's fair to say that progress in understanding the genetic cellular basis of cancer has been breathtaking. That's not an exaggeration. I think it's a serious understatement.

And this approach is finally leading to development of very remarkable drugs called smart drugs, or targeted drugs, a few of which seriously extend the life span of cancer patients and don't have such side effects as past therapies have had. And it's this progress that we're going to hear a lot about today.

So where does that bring us in all of this? So to my way of thinking, if indeed, worldwide, about 2/3 of cancer deaths are preventable theoretically, and a significant percentage today are manageable or curable, I think you have to say that those people 50 years ago, 40 years ago, 30 years ago, were on the right track. All three of these have been very successful. And they're very real successes that are leading to fewer cancer deaths, lung cancer-- people quit smoking, cervical cancer, liver cancer, a vaccine against hepatitis B, which hopefully is going to cause many hundreds of thousands of fewer deaths, and so forth, and these various things.

There's no question it's working. There's no question lives are being saved. This is a estimate of some number of lives.

But it also is true that the number being saved is not nearly as great as it should be. For example, there are about 40,000 avoidable colon cancer deaths a year in the United States. And this leaves us with the final slide here, which is this sobering picture, also that I got from my colleague, Dr. Weinberg. And we had a great debate about is the glass half full or half empty. I'm the half full. He's a bit more half empty.

Here is the decline in deaths from heart disease. And here is cancer, coming down but not coming down fast enough. So why is it? And I think that the discoveries are great. It's true. We haven't got enough discoveries in basic science on certain cancers, pancreatic, brain, ovarian, lung, and colon.

But it's also true that the methods we have got, the discoveries we have made, to my mind, are not being exploited as effectively as they could be. And that's what really excites me about this Koch Integrative Cancer Center, because I think we need the engineers. I hate to admit it. But I think we do.

They are the problem solvers. And I think there are many discoveries that have been made that can be exploited more rapidly with their help. So I think I have to agree with the previous speakers, President Hockfield, that we could be on the verge of something truly unique by this combination. And I hope there are a lot of students here. I can't see, so I don't know. But I think that that generation of people with these tools, coming together, can really do something extraordinary.

So with that, I would like to introduce the first speaker. And that is my colleague, Professor Phil Sharp, who's in the biology department and is an Institute professor of many accomplishments. Where do I start? With the Nobel Prize, I suppose, somewhere at the top of the list. Many others, no end to them. Phil, take it away. OK.

[APPLAUSE]

SHARP: Thanks, Nancy. It's a pleasure to have the opportunity to address you this morning. The table has been set by Nancy, and by Susan, and Tyler in terms of my job. And my job is to talk about the history of cancer research at MIT.

And I will talk about the history of the Cancer Center and how it's contributed. Nancy has commented on the effect of the Cancer Center, or the goal of the Cancer Center to understand the molecular and cellular bases of cancer. I will relate that to the third revolution, which is something that's happening across MIT. And I'll try to explain a little bit of that. But it's a major effort across the campus.

And then, if I have time, I'll turn to the fact of why we have not cured cancer, as Nancy has set the table for. And part of the answer to that question is we still know very little-- or we know a lot about how our cells function. But there's still major things we don't know about when we think about human cancer and how the process occurs.

But let's go back and think a little bit about the genetic understanding of how cancer develops. You'll see here on this timeline that, as the century opened, we understood that chromosomes were rearranged in cancer cells and suggested the idea that there was a relationship between chromosomes and cancer developing. And then there's other progressions.

And I've inserted in here a very interesting little tidbit because in the early '40s, MIT was already involved in cancer research in a collaboration with Saul Hurst over at Mass General. And through the reactors here, and the physicists here at MIT, we were involved in generating iodine to treat thyroid cancer and thyroid conditions. So MIT's had a long history of integrating advances in science and in technology with cancer research.

And then if you look on into the '60s, the Philadelphia chromosome, which we'll talk about in a few moments of being the basis of CML, chronic myelogenous leukemia, was discovered. And then in the '70s, Dave Baltimore and others at MIT, which I'll come back and mention, identified the protein that's mutated by that rearrangement as a tyrosine kinase. And then we look in the '70s, we identified that human genomes contain genes that, when activated, would cause cancer, oncogenes. And then we isolated, here at MIT-- this is green-- Bob Weinberg isolated one of the first mutated oncogenes from a human cancer cell and showed conclusively that mutations in human genes cause cancer.

And then, in the '70s, the retinoblastoma, another gene that's important in terms of suppressing the growth of cells, was isolated here at MIT from the work earlier on in the '70s by Knutson identified the retinoblastoma protein as being mutated in retinoblastoma of familial retinoblastoma. And then as we move through the '80s and '90s, we identified other mutations that give rise to cancer, and colon cancer, and other cancers. And then at the end of the century, or the beginning of this century, we got the sequence to the human genome and could then move at an more accelerated rate at understanding the genetic bases of cancer.

Here at MIT, after the war on cancer was declared by Richard Nixon, MIT responded with the objective of understanding the molecular and cellular basis of cancer and was led to that by Salvador Luria's vision of the future impact of molecular and cell biology. Luria was recruited to MIT in the mid '50s. But if you look at the records of his announcement of his appointment here at MIT, he was already thinking about the impact of our understanding of genetics on virology and on cancer. And he established, then, as a founding director in the '70s, the Center for Cancer Research here at MIT. And it has been a NCI cancer center ever since.

This Center has contributed enormously to our understanding of the molecular and cellular basis of cancer. And there's many ways to judge that. But one of the more striking events in the Cancer Center was its success in terms of acknowledgements of the research that went on in the Center. I show you here five photographs of individuals who were associated with the Center, or worked in the Center, who received Nobel Prizes for their insight in the study of molecular and cellular processes.

It starts with Luria himself, which identified the nature of genes in bacteria and launched molecular biology. Dave Baltimore on a reverse transcriptase, Susumu Tonegawa in terms of immunoglobulin rearrangements in the basis of genetic changes in our immune system, split genes, and Bob Horwitz here on programmed cell death. But beyond these theoretical advances, there were actually advances in the labs at MIT that led to practical treatments of cancer. These were contributions of discoveries that, then, lead to development of others to treatments of specific cancers, what we now know as personalized cancer care.

And I'll mention but two of them. And one is the discovery of the gene by Bob Weinberg that, ultimately, was the target for Herceptin, which is a antibody-based treatment for breast cancer in patients that have amplified genes of HER2, which, with this antibody, gives you much more dramatic response to therapy and a much longer life. The second one is the one I've mentioned before. And that is the treatment of chronic myelogenous leukemia, CML, by this drug Gleevec. It actually had its origins in the rearrangements of chromosomes that were recognized in the '50s and '60s. And I'll mention that in a moment and show you that timeline to make another point. But the gene that was mutated in that rearrangement is a gene that encodes a tyrosine kinase that Dave Baltimore identified here in the Cancer Center at MIT.

But let's look at the timeline for this wonder drug, Gleevec, for treatment of CML, and one of the first examples of personalized cancer care, meaning analysis of the nature of the mutation that occurs in the cancer that drives the development of cancer, and then targeting that specific mutation for therapy. And that seems to drive much more dramatic responses to the therapy than other approaches, such as general chemotherapy.

But let's look back here. I show a timeline of the science that contributed to our understanding of this target for CML. Peter Nowell and Janet Rowley discovered the chromosome rearrangements in the '50s and '60s that were hallmarks of CML. Then in the '70s, Owen Witte and Dave Baltimore, in the Center for Cancer Research, identified that this rearrangement mutated a gene that was called Abelson. It was contained in a virus. And then analysis of the protein that that gene encoded showed that the protein was a tyrosine kinase.

This means it transferred a phosphate group to a protein at a specific site, and therefore created a biochemical target for possibly developing a drug. But it took 20 years from that time until the '90s when Nicholas [? Lyons ?] from Novartis, developed a specific drug, or a reasonably specific drug to tyrosine kinase, this particular kinase in Abelson. And then Brian Druker, between 1990 and 2000, a clinician in Oregon, showed that it had dramatic responses in CML. And then in 2001, Gleevec was approved as a therapy for CML.

So from the '50s to the end of the century, the first science was done before the drug was actually approved. In the '70s, the biochemistry was done. 20 years later, the drug development was done, and then approval for clinical trials. If we're going to have an impact on that curve that Nancy discussed in terms of turning down the rate of death due to cancer, we're going to have to accelerate our understanding and ability to take fundamental discoveries and move them into therapy.

But in this particular case, and in several cases now, we have found that this personalized therapy has an enormous impact on survival of the patient. It is not the total solution. But it is a very significant advance in the treatment of these cancers where you can actually identify the nature of the mutation in the cancer cell. And you have a drug that attacks that mutation.

And here's an example of the early clinical trials in CML with Gleevec. And what you see here, the current treatment that was tested in parallel to this targeted treatment. And you see that they have 78% responses with a targeted treatment. The best concurrent treatment gave a 14% response. This is a cytological response in the patient. But it translates into survival.

You see here over a five year time period, death due to CML in chronic CML treatment with this drug is 5% over a five year period, a dramatic response to a therapy that has significantly changed the way we view, and raised our hopes that by further understanding of target genes, we can begin to develop more and more therapy. And right now, the translation of our science into personalized therapy is a major effort in the country.

But this has raised the issue of where do we go from here. We understand much about the molecular and cellular nature of cancer. How does MIT move forward in terms of having an impact on cancer? And we've heard about the Koch Institute and its hopes, and wishes, and design. And for my last few moments, I want to talk about that issue.

And this is the third revolution. It's the convergence of life science, physical science, and engineering that, I think, will change medical care as well as changing how we look at and treat cancer. And over the next moments, I'm going to comment on that. You've seen a timeline of what we call convergence, or the third revolution, within the '50s when Watson and Crick discovered the structure of DNA and molecular biology was launched, through the '70s when the Cancer Center at MIT was launched to understand the molecular and cellular basis of cancer, through the '70s and '80s when biotech was launched out of the discoveries of molecular biology and a new way of translating our science into therapies, on into the '90s when the genomics revolution was launched that, then, cultivated in 2003 with the sequencing of the human genome with a major contribution from the Broad Institute in this completion of the sequence.

The first revolution was this revolution in molecular biology we've been talking about. The next revolution is the genomic revolution. And the third revolution, we believe, is this convergence of life science, and engineering, and physical science, and computational sciences. And why do we need that convergence?

We need that convergence because, as Nancy has outlined, we are facing a major demographic challenge, both in cancer as well in a number of other diseases such Alzheimer's, chronic mental degeneration, and other chronic diseases. And as Nancy has already stressed, we have seen benefits of innovation in our understanding of molecular and cellular biology in terms of improvements in the lives of citizens of this country. And as the head of NIH, a couple years ago, commented that the investment, over the past 30 years, of $44 a year have gained us approximately six years in life expectancy and a much higher quality life in addition to just the longevity.

But if we're going to keep this record going, we're going to need to do it in a more innovative way, an innovative way that combines cost control and new innovation. The only way we can actually maintain increase in quality of health care is that type of innovation in health care. And that will lead us to new diagnostics and imaging methods for new therapeutic agents. And that will come out of the emergence of science and engineering, personalized treatment of diseases. And I've illustrated that for CML where, if you know the nature of the genetic change, you know what drug to use, and you know what patients to put on that drug and what patients not to put on that drug. And therefore, you don't waste resources and actual complications of treatment on people who can't benefit.

But in addition to this molecular and cellular approach, the innovations of merging science and engineering will have much broader approaches, both in terms of accessibility of information technology and quality control to the clinical treatment of patients, bringing more information to the bedside to better control treatment, specifically of cancers and others, and to actually inform patients more readily of what they can expect and benefit from in current treatments. And that will give us a more affordable health care, because we'll have more affordable and participating consumers and more patient participation in the system.

So how has MIT responded to this and contributed to our understanding of this convergence revolution that we think we're on the edge of and the Koch Institute represents? And I just want to briefly go back through this history. In the '50s, MIT created the modern department of biology by bringing in Luria and a number of other internationally known scientists to lead the department in a molecular and cellular approach. Note that this was only three years after the discovery that genetic information was transmitted in the form of DNA from one generation to another with the discovery of Watson and Crick.

In the '70s, the Cancer Center was established, which I've commented on and the nature of its contributions. In the '80s, the Whitehead Institute was developed to understand developmental biology, how the genetic information is transmitted, and decoded into three dimensional organisms, and how cancer occurs. In the '90s, MIT made the decision, as a faculty, that all students at MIT need to learn biology. And biology then joined chemistry, physics, and mathematics as one of the four pillars of knowledge in which educated people need to know to be able to move and participate in this innovative society.

In 2000, the neuroscience complex and neuroscience was dramatically expanded here at MIT. In 2003, the Broad Institute was established, focused on genomics and high throughput science. And in 2010, the Koch Institute was established, integrating cancer, fundamental cell biology, molecular understanding of cancer with engineering and approaches to translation of that knowledge into new understanding of the disease and treatment of the disease.