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

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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.


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.


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.


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.


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.

And those changes, in terms of MIT's development of life science here, has been matched by changes across the community and across the campus, as Susan Hockfield has discussed with you. We established, at MIT, a Department of Biological Engineering to bring biology to engineering. Chem engineering, civil, mechanical, electrical, and computer science all have life science as part of their research portfolio now. But we also have a specific department of biological engineering.

A third of all MIT engineering faculty are engaged in life science now, indicating the movement and the opportunities that life science offers in terms of innovation for society, not only in health, but in energy and other areas where life science can contribute to solutions. And as you've heard, MIT is part of a cluster of hospitals, medical schools, biotechnologies, and other devices creating part of the innovation society here in New England and across the country, bringing health care advances and other advances to society.

I will end their given that I have already exceeded my time, but basically, summarizing that the investments in the Cancer Center over the last 30 years have dramatically extended how we understand this disease of cancer. We've seen it provide the basis for others working in bringing personalized cancer care as an opportunity to patients. And we believe that this convergence between physical science, engineering, mathematics, and computational science, and life science in the Koch will lead to much further advances, and more rapid advances, and accelerating, taking our knowledge, and improving the lives of patients. Thank you.


HOPKINS: Thanks very much, Phil. Also, we have another panelist. And that is Michael Goldberg, Dr. Goldberg. He said he was going to join us on the stage. So if you'd like to come up, it would be great to have you. He is a post doc in Phil Sharp's lab. The next speaker is my colleague, Jackie Lees, who is the Associate Director of the Koch Institute and a professor of biology.

LEES: Thank you, Nancy. So what I'm going to talk to you about today is two topics. The first one is to tell you a little bit more about cancer development and how the genetic changes that occur in those tumors and the biological consequences of those changes. And then, in the second portion of my talk, I'm going to hopefully convince you why we need to bring mouse models to bear on this problem.

So Nancy's already introduced this concept that cancer is a disease of age, that it goes up with time in aging people. And the reason that it takes so long for cancers to develop is that it actually requires the stepwise process in which you acquire different characteristics of the tumor cells as the disease proceeds, going from normal tissue to hyperplasia, to a benign tumor, and then ultimately to a cancer in situ that leads to an advanced cancer that is capable of metastasizing. And as Nancy's already mentioned, it's actually the metastasis that is really the terrible portion of this disease. A metastasis is actually responsible for the death of 90% of cancer patients.

So what do these steps really correlate to? What we know is that this actually reflects a stepwise evolution in the tumor cells that disrupt a variety of core biological processes. And work from many different labs has really contributed to an understanding of what these processes are.

So I'm just going to walk you through the central players in a list. So firstly, there's this issue of growth factor dependence. So for any cell in the body, it's receiving signals from the surrounding environment that are either stimulating that cell and causing it to divide or inhibiting the cell division in that individual. And in an adult, most tissues are set. And the vast majority of cells in that tissue are really under inhibitory growth factor control. So in order for this cell to kick out and begin to undergo this hypoplasia, one of the very earliest events you see are changes in these pathways that involve growth factor signaling in a way that either up-regulates the effect, or renders you independent of these stimuli growth factors, or overrides the effect of these inhibitory growth factor pathways.

The second event that has to happen is you have to alter this process of cell cycle control, or cellular proliferation. So this is physically the event where one cell actually divides in to give two daughter cells. And this, obviously, is in large part responsible for the massive expansion of the mass that gives rise to the tumor in any of these individuals.

The third biological process we know about is this process of apoptosis, or programmed cell death. And in fact, now it's well established that cells actually have an internal suicide mechanism. So in response to certain cues, or inappropriate signals, cells will actually die. And it turns out that in cancer cells, these apoptotic mechanisms are actually up-regulated. So this actually acts as a restraining activity even in the development of normal cancer.

And we also know that many of the classic chemotherapeutic agents actually work by activating this apoptotic process within the tumor cells. So these cells are predisposed to die. The chemotherapy actually synergizes with that predisposition. And cells within the tumor undergo cell death. So in order to be a very successful tumor, particularly to evade classic chemotherapy, the tumor cells have to undergo a mutation that overrides this apoptotic response.

In addition, in the later stages of tumorigenicity, tumor cells have to undergo this process of angiogenesis. And that is that a tumor has a set size that it can reach and then cannot expand beyond unless it has a capability to bring nutrition into the center of the tumor and to remove waste products. And in order to do that, the tumor actually recruits blood vessels from the body to grow into the tumor, bringing the nutrition it needs. And this, in turn, actually creates a route where cancer cells can actually escape the primary tumor as part of the process of metastasis. So tumor cells need to activate this process of angiogenesis.

And in addition, in order to be a highly invasive or successful metastatic tumor, the cancer cells have to gain this ability to actually invade into the surrounding cell matrix and even extend beyond the borders of the tissue through the basement main brain into blood vessels to metastasize to other regions in the body. And we now know that in order to be a successful metastatic tumor, you have to acquire mutations at each step in this process.

Now, how do we change each of these biological processes? Well, as Phyllis mentioned, this actually involves the stepwise acquisition of mutations in cancer genes. So you actually altar the genetics within the tumor cell in a way that you disrupt those biological processes. And as Phil has already mentioned, cancer genes come in two flavors.

The first flavor are oncogenes. These are genes that actually act in gain of function mutations. So you gain either point mutations within the oncogene that activate, or increase the activity of that protein, or somehow render it independent of negative factors. You can get increased levels of some of the amplifications that you see in cancer result in multiple copies of that gene, increasing the levels of that gene. Or you can get inappropriate expression, have a gene that's normally expressed off, maybe in a terminally differentiated tissue, becomes re-expressed, somehow, in that tumor.

At the same time, the second general class of cancer genes are called tumor suppressors. And as Phil mentioned, the first tumor suppressor was actually cloned when I was a post doc by Bob Weinberg in the Whitehead Institute in 1986. There's really been a major explosion in our understanding of tumor suppressors in the last 20 years. I would say that there's now more than 50 known tumor suppressors.

And these genes basically function to inhibit tumor progression. So in order to override this effect in the cancer cell, you actually need loss of function changes within the tumor, so either mutations within the gene itself that inactivate the function-- in many cases, they just completely block the function of the protein-- or you need to lose expression of these genes within the tumor. And it turns out that tumor suppressors are both hard for the cancer cell to mutate, but also particularly challenging for us in terms of targeting these mutations for treatment of cancer.

So I want to remind you that each one of us has two copies of every gene. We inherit one from mom and one from dad. So in order to inactivate these growth inhibitory genes, you actually have to inactivate both copies of these tumor suppressors. And this is actually achieved in two ways.

So there are a number of people who have family or hereditary cancer syndromes. Their family is highly predisposed to develop a particular cancer type. And it turns out that in almost all of those cases, those individuals are carrying, within their genome, a single, mutated copy of this gene.

That gene's still working because they have the wild type copy. But those patients have a very high probability that they'll acquire the mutation that deletes the second copy of that gene. And when the second copy of that gene is deleted, the tumor develops in these individuals. And that accounts for their very high predisposition to cancer.

Now, these family syndromes were very rare. And initially, there was some argument, why should we study these rare cancer families where it only affects one in 20,000, one in 50,000 individuals in the population. But what we now know is that if we look at sporadic disease-- these are patients who have no familial predisposition-- those same tumor suppressors are also mutated in the cancers that many people in the population get.

In the case of the sporadic disease, those individuals actually start out with two wild type copies of the gene. A single cell in the body will acquire a mutation of one copy. This is now an accident waiting to happen. And that cell, if they acquire a mutation of the second copy of that gene, that now gives rise to the tumor in this sporadic manner.

And I want to give you an example of one such gene family. It's actually the retinoblastoma gene, the gene that my lab works on. It was the first identified tumor suppressor. And it was identified by virtue of its association with this tumor type called retinoblastoma. It's actually a tumor that children typically develop in the retina.

And it turns out that about 2/3 of these individuals develop this tumor because they have the hereditary form of the disease. And in these individuals, the tumors arise at less than two years of age. That's because they're carrying this first mutation. They're highly predisposed. And they actually get tumors, typically, in both eyes, sometimes multiple tumors. And that's because all they have to do is lose the single copy.

The sporadic form is less common. The tumors take longer to arise. Typically, the tumors arise around five years of age. These individuals have a single tumor. And that's because they're unlucky enough to acquire both the first mutation and then in the same cell, the second mutation that goes on to give rise to this disease.

So retinoblastoma is highly treatable. But it turns out that especially the patients that carry this germ line mutation-- they go on to be predisposed to a variety of other tumor types, including osteosarcoma, or bone cancer, and also small cell lung cancer. And again, if we look at these tumor types in the sporadic population, people who happen to get osteosarcoma or small cell lung cancer with no family history of retinoblastoma disease-- again, in 90% of cases, these individuals can carry mutations in the retinoblastoma protein tumor suppressor.

So what does the RB gene do? What we know is that the RB gene plays a critical role as inhibiting this key step that I told you about earlier, this process of cell proliferation. If you lose RB, cells can now undergo this proliferation next step, allowing for expansion of cells within the tumor.

Now, since this is such a fundamental process, you might wonder why-- we wondered why mutation of RB is specifically mutate linked to these tumor types and not other tumor types. So it turns out that there are actually other genes or proteins upstream of RB that control its activity. There's a complex called cyclin D-CDK4. And that inhibits RB. It turns out that both of these proteins are actually oncogenes. A mutation of these genes is associated with breast cancer.

There's a third protein in this pathway called P16. This actually inhibits cyclin D-CDK4, restoring RB function. And again, P16, consistent with that function, works as a tumor suppressor. And P16 is mutated at very high frequency in melanoma.

So this idea of a cancer pathway-- we have a very fundamental process, the control of cellular proliferation-- what we find is that many of the proteins that exist in this pathway that control this process are either oncogenes or tumor suppressors. And in fact, with the exception of colon cancer, almost all human tumors contain a mutation at one of these three steps in this pathway, arguing that this is a critical process. And in fact, as you see other talks in the process of this session, you'll see a lot of people talking about cancer pathways or signaling networks. And this just shows you an example of one such pathway.

OK, so we can learn a lot about oncogene and tumor suppressor function by studying cells in culture. And this is actually the starting history of the Cancer Center, as Phil just mentioned. But it turns out that studying isolated cancer cells in culture is not enough to solve the problem. Instead, we really need mouse models.

So why are mouse models so Important? So oncogenes and tumor suppressors affect the cancer cell itself. But we know that, in fact, cancer is a disease of the tissue. And in addition to mutations within the tumor cell itself, the progress of the disease, the progress and growth of this tumor, is influenced by a wide variety of other cells and environment within the living organism.

So firstly, the immune cells, whether the immune cells are capable of recognizing that cancer and inhibiting its development. There's an effect of stroma in normal cells providing those growth factor signals that I told you about that can influence either the tumor progressing or not progressing. There's the ability to develop new blood vessels can also greatly affect the development of the tumor.

And most importantly, this process of metastasis, invasion and transfer of cancer cells to second sites. And as I've already mentioned, metastasis is responsible for 90% of cancer deaths. We cannot study any of these events in the context of cultured cells. We really need to do it in the context of a living organism.

And to achieve that goal, we've turned to mouse models of cancer. So through the innovative work of many people in the Cancer Center, including Rudolf Jaenisch, Tyler Jacks, and many others, methods have been developed so that you can actually create, within the context of the mouse genome, point mutations that affect either activation of oncogenes in a way that mimics the mutations you see in human diseases or inactivation of tumor suppressors.

You can then take these mice carrying these oncogenic and tumor suppressive mutations. And we can study tumor development in the context of that animal. We can also analyze the progression of the disease by doing histology or imaging of the tumor, looking at the cell biology of the tumor, the biochemistry of the tumor, mapping out the signaling cancer pathways that I've just described to you. And most importantly, we can actually test chemotherapeutics, or developing agents, in the context of these mouse models.

Can we provide methods of early detection? Can we actually prevent, with chemotherapeutic drug treatment, the development or progression of the disease? And can we effectively treat end-stage developed tumors, including metastases, in this model?

So now, work from many different labs in the Cancer Center and, in fact, many institutes in the country have developed very excellent mouse models that recapitulate this whole spectrum of human tumors, carrying the right constellation of mutations that you see, typically, in the human disease and having histology that looks very similar to the human disease. So bone cancer, breast, colon, glioblastoma, leukemia, lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, lung cancer. All of these models exist and are already providing critical resources as tools for analysis.

And I just want to show you one example of lung cancer. And this is actually a model developed in Tyler Jacks' lab. So work from analysis of human tumors has identified many gene mutations that seem to influence lung cancer. So this is a list of oncogenes that can be activated in lung cancer, a long list of tumor suppressors that can be mutated in this disease, and then additional large chromosomal abnormalities.

And there are actually two genes that seem to be particularly associated with this disease. One is an oncogene, KRas. And this actually renders the cell to have up-regulation of positive growth factor signaling pathways. And P53, which is a major inducer of apoptosis and, again, a major determinant of response to chemotherapeutic treatment

So Tyler's lab created a mouse model that carries activated KRas mutations and inactivation of the P53 tumor suppressor, specifically in the lung of the animal. And I just want to show you analysis of tumor development in these mice using a process that allows animal imaging in the context of the live animal called micro-CT, exactly the same procedure you can use to monitor tumor progression in human cancer patients. So this just shows a video-- if you could play the video, please.

Here we see at zero time point of beginning detection. Here's actually two tumors that are developing with the lungs of the mice. Here, four weeks later, you can see that these tumors are developing dramatically. There's one particularly large one, eight weeks of age in this system. So you can see-- and now, 14 weeks, beautiful, large, aggressive tumors looking histologically just like the human disease.

So the other thing I want to point out is that you can see, even though these tumors were all driven by the same two mutations, activated Ras and loss of P53, you can see that the tumors are considerably different in terms of their size. And in fact, if you treat these mice with chemotherapeutic agents, some of these tumors will dissolve and go away. But the vast majority of them are incredibly difficult to treat, just like lung cancer in human cancer patients.

So why do these different tumors respond differently? So it turns out, as I've already told you, the cells have to actually acquire additional mutations in the course of development of the disease to wipe out these additional biological processes in addition to signaling and loss of apoptosis. And in fact, the relative size, and also the chemotherapeutic response of those tumors, is going to depend upon the spectrum of each one of those individual tumors acquired in the progression of this disease. There's also, obviously, an influence of the environment that can affect the development of these tumor types.

So I hope you can see that we can actually use these mouse models, interrogate these tumors to understand the additional genetic changes that correlate with progression of those disease and also their ability to respond to various chemotherapeutic agents. And we're now firmly committed to the idea that we can use these mouse models maybe as a primary testing ground of new chemotherapeutic drugs to see whether they really efficiently target the cancer cells in the context of a living organism.

So I just want to end by telling you that this is really a major component of the mission of the Koch Institute, scientists working on cancer discovery and the engineers working on cancer solution. And in fact, the engineers, as I think you'll hear about later, are using many of the mouse models that we've developed to really test their detection devices and drug delivery systems. And I'll end here. And thank you for your attention.


HOPKINS: Thanks, Jackie. That's fabulous. OK, so the next speaker is Bob Langer. And I urge you to read his bio in this book. It's quite remarkable. I don't have time to list his 180 major awards.

He was about 35 years ahead of the rest of us in being the first scientist engineer. So he's got quite a story to tell. Bob.

LANGER: Thank you, Nancy. So there have really been a number of, I think, very important engineering advances. And I just thought I'd summarize some briefly on this slide. And you'll hear more about them today.

But these are all, I think, important milestones, new imaging methods, drug delivery, which I will talk about, bioprocessing, bioinstrumentation like PCR sequencers, and FACS machines. And again, Lee Hood, I'm sure, will talk a lot about this since he pioneered it. And systems biology, which I'm sure Lee, and also Doug Lauffenburger of MIT will talk about. And actually, there'll be a book coming out by David Lee of the Koch Institute on some of these and other aspects, as well, in the future.

But I think the reason people ask me to speak, as Nancy mentioned-- I'm an early example of somebody that was and still is an engineer, but that is doing the type of convergence work that Phil and Tyler talked about. And so you might ask, how does an MIT engineer-- and you look at all the terrific engineering that MIT's done for many years-- how does an engineer even get into cancer research. So I thought I'd tell you a little bit about my personal story.

I got my doctorate in MIT in chemical engineering in 1974. For those of you that are old enough to remember, in 1974, there was a gas shortage, like a couple years ago, but much worse, because not only did the prices keep going up, but if you had a car, you had to wait in line at the gas station for over two hours to get your gas. But the consequence of that is that if you were a young chemical engineer, there were just tons of job offers.

And so myself-- pretty much all my classmates and I got lots of job offers from oil companies. For example, I got four job offers from Exxon alone. And it wasn't like I was at the top of my class or anything. And I got offers from Shell, from Chevron. I think every oil company except British Petroleum offered me a position. And they just didn't interview at MIT.

But I wasn't very excited about that. I just felt that the kind of work that was going on there wasn't that exciting. And so I was interested in education. I'd helped start a school for poor kids in Cambridge. And so I started looking for jobs, because I had developed new ways of, I thought, teaching chemistry and math. And I was looking for teaching jobs that would help in developing education like that.

And one day I saw an ad, actually, at a college in New York City to do that. And I wrote them. But they didn't write me back.

But I liked that idea. So I wrote to about 40 other schools for being an assistant professor of chemistry education. And I think maybe one wrote me back. And that wasn't a very positive letter.

So the next thing I started thinking about is I really wanted to use my engineering education to help people. And I started thinking about health. And so I wrote to a lot of hospitals and medical schools for jobs. And they didn't write back, either.

But one of the post docs in my lab said to me, he said, Bob, he said, there's a surgeon at Boston Children's Hospital named Judah Folkman. And he says, sometimes he hires unusual people. He actually thought very highly of Dr. Folkman. I won't say what he thought of me.

Let me start by showing you a picture from the New York Times-- and Jackie mentioned this a little bit. I'll show you my New York Times version. But this is from 1971.

And it was Dr. Folkman's idea of how tumors grew in relation to their blood vessels, which Jackie mentioned. And the point was is that if tumors didn't get blood vessels, as she pointed out-- that was her fourth point was that they couldn't grow beyond a millimeter in size. And that's a nutrition problem.

Cells in the center will die. They can't get nutrition. They can't get rid of waste. Cells on the outside will proliferate because they can get oxygen and can get rid of waste. But what the tumour is able to do, he said, is create a substance called tumor angiogenesis factor.

Later on, he and others would show that there are various growth factors, as she mentioned. And that would trigger the blood vessels, which are normally quiescent. They don't do much of anything. It would trigger them to grow and proliferate towards the tumor. And that would enable the second phase of growth, where the tumors would get bigger and bigger because they could get nutrition. And they would also, as she pointed out, metastasize.

Dr. Folkman's thought was that if you could stop angiogenesis, maybe you'd have a new strategy to stop the tumor. But nobody'd ever done this before. So my post-doctoral project was to see if we could isolate the first angiogenesis inhibitor.

The substance we thought about using, just to get this started, was cartilage. And so this is a bone from a meat packing place in South Boston. And here you see the cartilage, which is this white glistening part and has no blood vessels. And so what I did is I would get thousands of these bones. I would scrape the meat off of them. There's no meat on this. This is one I worked hard on. And then I would put it through various purification procedures. And at the end, I'd have all kinds of different isolates that I wanted to test.

But one of the biggest things that's always made, I think, medical discoveries very hard, going from penicillin and many other things, is how do you have a bio assay to test these things. And there was no bio assay to test substances that could stop blood vessels from growing. And so the bio assay that Dr. Folkman and I talked about was could we use the eye of a rabbit.

And the idea is that normally there are no blood vessels in the eye, either. But if you put a tumor in, over a several month period, blood vessels will grow, as I'll show you, from the edge of the cornea to the tumor, mimicking what happens in the patient. But the problem was all the things we were isolating were fairly big molecules.

And we couldn't get them into the cornea. We couldn't make them last very long. So we felt if we're ever going to solve this problem and develop an assay, we would need to develop a polymer system that was A, very, very bio-compatible, even in the eye, and B, could release molecules of any size for at least several months.

But when we started this work, the conventional wisdom was that you could not do this. So if you look in the literature in the 1970s, you often see quotes like this. I'll read this to you. It says, "The agent to be released is a small molecule with a molecular weight no larger than a few hundred. One would not expect that macromolecules, for example proteins, could be released because of their extremely small permeation rates through polymers."

Now really, the only thing that I had going for me is that I just didn't know that. So I spent several years in a laboratory experimenting with different techniques. I actually found over 200 different ways to get this to not work.

But eventually-- and engineers do that. You keep plugging. Eventually, I found a way where I could make little microspheres like this. Later on I'll mention nanospheres. Here's what one looks like. And here's one cut in half.

And the way these work-- I'll just show you a cross section of one of these. And what you see is a very intricate, porous network. And when you look at this-- and we did all kinds of studies-- what you'd find is these pores are large enough so that molecules even millions of molecular weight can get through.

But the pores are interconnected. There's actually tight constrictions between them. And the pores are very, very winding and torturous. So it takes a really long time for the molecules to get through.

One analogy I sometimes use is it's like driving a car through Boston. Chemical engineers have a term for this. And we call that high tortuosity. Boston has a very high tortuosity. And so do these.

And what we could do is we could put almost anything in these materials, now, and release them for-- this is over 100 days for different proteins. Here's constant release of a protein. And so now we were really in a position to study this angiogenesis problem. And here is the assay, as I mentioned before.

But now we actually could put all the different things in them to see if we could even find anything at all that would stop blood vessels. And I should point out, in the 1970s, when we did this, a lot of people didn't agree with Dr. Folkman's theories. They didn't think things existed that would stop blood vessels that were chemicals.

But what we published in Science in 1976-- this was the first inhibitor that was ever isolated-- and I apologize if people don't like the sight of blood. But I just want to show you the rabbit eyes about seven weeks after the start of the experiment.

Here's a typical control without an inhibitor. You see a sheet of blood vessels growing from the edge of it over the little polymer towards the tumor. Two or three weeks after this, that would be huge, three dimensional tumor. And so we'd sacrifice the animals before then.

On contrast, if you put the inhibitor in, you can see what happens. The blood vessels avoid the polymer. And the tumors don't grow. So this showed that you could do this.

And research moves slowly. It took another 28 years from this paper that we wrote in Science in 1976 before the first angiogenesis inhibitor was approved by the FDA. And really, it took the great work at many companies like Genentech to do this, and billions of dollars. But today, over the last, now, seven years or so, we see all kinds of new treatments of angiogenesis inhibitors for all different types of cancer.

And the FDA has now called this the fourth-- there's three main ways, up till then, that people had used to treat cancer, chemotherapy, surgery, and radiation. This is now considered the fourth possibility. And many times, you'd do these in combinations. And again, it's still an early field. People are trying to learn how to use these better and better.

Also, it occurred to us that if we could deliver these things in animal models, there are a lot of cancer drugs and other drugs that are very, very difficult, if not impossible, to deliver. For example, there's a lot of drugs, peptides and things like, that people have tried to give by mouth, or by trans-dermal patch. And they just don't get in. They have a bioavailability-- that's the amount that gets into the blood-- of say, less than 0.01%. It's impractical.

So what this has enabled is to take drugs that you'd have to inject that would normally be destroyed right away, in seconds, and now make them last for times that make the therapies possible. And there are many treatments based on this now. Just to show you a few that you can use them for anywhere from mental health diseases to drug eluding stents.

But in the cancer area, for example, there are drugs like luteinizing hormone, releasing hormone analogues that people couldn't get into the body by any means other than injection. And then where they were injected, they were destroyed right away. So now, there are many of these systems-- here's one. Here's another. Here's another-- where you can actually put the drug in. And instead of having to inject the person every few seconds, which you'd have to do normally if you [INAUDIBLE] work. But now you can inject them once every four months. And this has actually been one of the most common ways, now, of treating advanced prostate cancer and some other diseases.

To give you a more recent example that we're very excited about, and moving to the Koch Institute, a few years ago, Phil and Tyler asked if I would help head up a project to see if we could get funding to start a nanotechnology program at MIT. And we were very fortunate to get some wonderful biologists and some wonderful engineers to work on this. And the National Cancer Institute picked us as one of the places to do this. In fact, Joe DeSimone, who's speaking later, is at another one at UNC which is also doing this.

There were a number of strategies that we looked at. And in particular, with Omid Farokhzad, who was a fellow of mine and now a professor at Harvard Medical School, we looked at could we target chemotherapy right to the tumor cell. And Omid and [INAUDIBLE] before him-- this was another paper we had published in Science-- worked out a way to decorate a nanoparticle, shown here, with different molecules that could-- and it's very challenging-- that could both avoid cells that will normally eat nanoparticles and still, at the same time, target it to a tumor cell.

Now, it's very hard for me to explain this sometimes. But about two weeks ago, I turned on the TV. And there was Nova, the TV show on PBS-- they actually had come to our lab and interviewed me. And then they, actually, did a much better job than what I just did. So I thought I'd actually steal a clip from Nova and show you this. And I hope it works. Let's just see.


-He starts with a nanoparticle of anti-cancer drug. That gets encased in a plastic that releases the drug over time. That, in turn, gets a special [INAUDIBLE] that disguises the package as a water molecule to fool the body's immune system. And last but not least, the address where it should be delivered, a key that will only fit the lock of cancer cells.



Now, I should say that I've been informed by some of my biology colleagues that it doesn't really blow up the tumor cell like that. But actually, I thought they did a much better-- like you could see, they certainly explained it a lot better than I did. And we're very excited about that.

Omid and others-- this is from a paper we published-- showed that you could actually direct it to a tumor cell. And here, what we did is-- this is just a experiment in mice where we basically did a control nanoparticle. The tumor grows. Docetaxel, a drug, the tumor grows. But if you target it to the tumor, you can shrink it to zero. You can also see that in the pictures.

Here's a control. Here's the drug. These are big, highly vascularized tumors. But with a nanoparticle, the tumor essentially goes away. And what's happened is-- one of the other things MIT's been very good about, and aggressive about, is starting companies that can really bring these to patients. And as I mentioned, in the angiogenesis thing, that held things up for a long, long time.

Here, locally, BIND is a local company that's actually developed these and brought them through manufacturing and now into clinical trials. And what we're very excited about is that they've now developed a nanoparticle called BIND-014, which is in human clinical trials just starting this January. And so we're looking forward to seeing how that goes.

My final slide is just a brief summary of pictures just to give you a very, very high level overview of some of the things now going on at the Koch Institute. And you'll hear more about these today. But I think it's incredibly exciting, now, the interface of engineering and biology as Phil and Tyler mentioned. You have not only the targeted nanoparticles, but through work that Tyler Jacks and Angie Belcher are doing, new imaging agents that can be used with the type of mouse models that Tyler and Jackie are developing, new, tiny nanosensors that Michael Cima's been developing. This is a nanosensor that can detect all kinds of aspects of cancer in an animal, maybe someday a person, next to a coin.

These are new cancer vaccines developed by Darrell Irvine, who's trying to come up with vaccination methods of killing cancer, new mathematical modeling approaches that are being developed to help predict what's going on. And finally, here is a new what I'll call a femtomolar scale that is being developed by Scott Manalis, one of our colleagues at the Koch Institute. And I was mentioning nanotechnology. This scale measures a change in cells. And it does it at, actually, one one millionth the weight of a nanogram. So it's unbelievably sensitive. It's the most sensitive scale in the world. Probably wouldn't be helpful in measuring our weight. But it can measure cells very, very accurately.

So these are a few examples of, I think, what's going on that I hope will change our future and give examples of the interface of the type of convergence you've heard about and how engineers and biologists working together will hopefully come up with the new types of solutions that Jackie and Nancy mentioned. Thank you very much.


HOPKINS: Terrific. Well, thank you so much. That was marvelous. Michael, you're going to lead the questioning. [INTERPOSING VOICES] This is the top duty for the audience.

GOLDBERG: So as Tyler mentioned in the beginning, you guys had the opportunity to submit questions during registration. Many of you submitted very poignant ones. Becky is actually, now, complementing that with the collection of cue cards. You guys will have the opportunity, if you don't already have one, to go collect them outside by the registration desk. Please just pass them to the end of the aisle. And Becky can collect them. Thank you very much.

OK, so here's one that was actually spoken to briefly during the course of the talks. And that has to do with metastasis. So the question reads as follows.

Despite several tremendous advances in the treatment of cancer, some of which you have described, death rates owing to metastatic disease have not improved. What are some promising approaches that might change this?

LEES: Boy, I think that's tough. I think that the metastatic cancers are the ones, often, that have acquired mutations in all of those pathways and processes that I've talked about already. So they've often acquired resistance to many of the classic chemotherapeutic agents and some of the smart drugs. So I think the challenge firstly is hopefully treating the disease before metastasis happens. So all the advances that occur in terms of detecting disease early so we can avoid metastatic spread are already going to be critical in cutting down the number of metastasis deaths.

There's also a number of labs, in fact, a group of us in the Koch Institute working very hard to understand the biological processes that actually are involved in metastasis itself. And we're starting to really figure out the players and proteins that are actually involved in the process of metastasis, and also in the ability of those cells to survive in the second site. So we're hopeful, as we move forward with those discovery of pathways in proteins, that we can actually get smart drugs that will specifically target the events that are the events involved in metastasis.

But I think that's really the tough problem. It's been a tough problem for many years. I think, really, in the last 5 or 10 years, we're starting to get a handle on what metastasis involves. And I think we're very optimistic that we'll move that frontier forward in the next few years.

GOLDBERG: You mention the word prevention in that answer. And one of things that Bob actually alluded to, towards the end of his talk, was this notion of cancer vaccine. So is that going to be prophylactic? What does that look like? It's a term that's often used now along with cancer stem cells. So how might those affect cancer intervention strategies?

LANGER: Do you want me to-- well, I think people are looking at various ways of using them. But I think they could possibly be used either way. People are trying to develop vaccines.

It's still early. I think there's just now been one cancer vaccine that just actually got approved for the first time earlier this year. I think it's called PROVENGE. But so I think it's very early. But I think, depending on how they're designed, they might be able to be used in different ways, either prophylactically or-- there's just different strategies the way people have used them or are trying to use them.

SHARP: There is just an-- enormous advances have been made in understanding how the immune system accommodates and doesn't attack tumor cells and suppresses the activity of the immune system in the vicinity of the tumor. And that knowledge has led to some new approaches. I was just at a meeting where they were talking about treatments of prostate cancer where they combined activation of the immune system in the conjunction with local radiation of a tumor mass. And apparently, we're seeing activation of the immune response.

So there is clinical work going on. And in fact, there's a lot more excitement today in ways of advancing the activation of the immune system in cancer than there has been for the last 20 years. And as Bob mentioned and commented, Darrell Irvine in the Koch Institute has really got some very imaginative ways of directing the immune system and using it to attack cancer cells. So I think, maybe, we are going to see the whole immunology of cancer actually turn a corner and become much more a viable therapy.

GOLDBERG: And what of these cancer stem cells? So that was a point that came up repeatedly in the questions.

LEES: Yes, so the broadest definition of a cancer stem cells are basically cells within a tumor, often a subset of cells within a tumor, that if they're placed back into an animal, are actually capable of re-growing that tumor again. So they can undergo all of the cell divisions to basically recreate the tumor. And those are really the bad players in terms of treatment of this disease.

So you can imagine in many cases, there are very low percentages in the context of the tumor. And you can imagine having very successful treatment of a tumor, the vast majority of cells die. But if you leave even a small number of these cancer stem cells, maybe 1 in 1,000, 1 in 10,000, or even rarer, they can actually re-grow that tumor. So I think the challenge for us is really to understand what is a cancer stem cell, what distinguishes it from the cells in the bulk of the tumor, and to really design therapeutic treatments that will target those rare guys.

So I think for a long time, we felt we were very successful if we could get the vast majority of the tumor to go away. And that is a clear advance. But what we need to do is target those rare cancer stem cells that are the ones that recur, give rise to the recurrent disease.

GOLDBERG: That's actually a great segue to the next question, which has to do with potentially using outside the box strategies, and instead of killing, rather having differentiation strategies. So it reads as follows. "Current anticancer drugs extend patient lives for months and sometimes years. But it appears that they generally do not cure the disease. Why is this so? And might therapies that induce cancer cells to differentiate-- perhaps cancer stem cells-- into normal cells be more effective than cytotoxic drugs and radiation, which select for resistant populations?"

HOPKINS: Well, maybe I'll say something about that. One of the problems about cancer that I think has been not focused on that much is the variation within a single tumor. If you look at the genome of the cells within, say, a solid tumor, the genome is different within each cell within one tumor. Not every cell is different, but astonishing variation. So it's like a population which is evolving.

And so it's very difficult to-- there's usually somebody in there who's got a mutation that will allow that particular cell to do something abnormal. And you kill most of them. But there's some cell that can escape. And it's this huge genomic variation, which is one of the problems, we think. That's why that model that Jackie showed us is so amazing, where you can watch them evolve, check out which ones are resistant, and follow the genetic changes that correlate with these different biological properties. But that variability is a big problem.

LEES: Maybe I can speak to the notion of activating differentiation. I actually really like this idea. We have some experiments in my own lab which are arguing that for certain tumor suppressor drivers, and certain tumor types, that is actually a very successful strategy, being able to drive those tumors to actually terminally differentiate. It's clearly going to be cancer specific.

There are actually some known examples of lymphomas and leukemias that are treated by drugs that do enable them to reacquire the ability to terminally differentiate. So I think for some tumor types, that's going to be a successful strategy. We're going to have to worry about the heterogeneity problem, and escaping cells which can bypass that and gain additional mutations. And I think for other tumor types, it's not going to be a viable strategy. And we have to think broadly about bringing multiple approaches to the problem.

SHARP: It's really difficult to know what happens after you treat a patient and put him in remission. How many cells survive in the body, where the niches are that they might be latent, not growing, may not grow for five years, then become activated due to local immune activation or stimulation. This whole field of seed of cancer cells around the body-- we tend to think of every cancer cell will grow and will develop a tumor. And it's a irreversible, one-way path to cancer. But there's evidence that in many tissues, you can have cells that have mutations that would be tumor cells, and active tumor cells, that aren't developing tumors at that moment, and aren't growing, aren't spreading. So it's a field in which we know little.

But the really exciting thing, due to advances in mouse genetics and everything else, and imaging, and biopsies, and way to recover cells from the circulation system, is that we can now begin to move the human patient more central to the research program, and be able to recover cells from patients, and analyze the nature of those cells. So I think that that is where a forefront is going. And having direct relationships with hospitals and people who are managing patients and treating patients will be a big advantage in what the Koch Institute is going to be doing over the next decades.

GOLDBERG: So we have a symposium here at the Koch Institute every June. And I hope some of you will join us. This year's focus is on cancer cell metabolism. And we actually have an expert here in the Koch Institute, Matt Vander Heiden. I wonder if one of you might be able to describe to the audience what this whole field is all about.

SHARP: Do you want to try it?

HOPKINS: I don't.

SHARP: But we have a wonderful scientist called Matt Vander Heiden who would be able to answer that question much better than I, even though he's 30 years younger than I am. And in fact, he's been a major player since it emerged as a field. It's really striking.

Back at the turn of the century, Warburg described that the metabolism of cancer cells frequently is different than normal cells, and that it is using energy in a different way than normal cells. And we worked out, over many decades, we collectively, as a community, the metabolism of bacteria, and the metabolism of animal cells, animals. And we thought we understood all that.

And now that we're beginning to investigate exactly what changes in the metabolism of cancer occurs, we realize that those pathways aren't as simple as we thought they were, and that they're being modulated in more interesting ways. And they're being changed by the oncogenes and activities we're talking about. And it's presenting a whole host of new targets for treating cancer with maybe even drugs we now use to treat diabetes and other things that we could use in conjunction with other treatments to control the development and curing cancer.

So that whole field's exploded. It's really one of the most exciting areas. One of the major symposiums in biological science this year, the Cold Spring Harbor Symposium, was focused on it. The Koch is in a very strong position in leadership, as well as other research programs around the country. And I think it will be an absolutely fascinating, fascinating day of new ideas on how you can possibly treat cancer and understand the disease.

GOLDBERG: Excellent. So you mention diabetes. And one of the questions asked whether we should be thinking about cancer as a chronic disease and treating it as such rather than one where we can definitively cure it.

HOPKINS: I think we already are, don't you? I think that's the answer I give. I think-- this is the thing that's really changed. And maybe we'll talk about it more today. But you just didn't talk about cancer when I was a child. I don't even know which relatives died, because you just didn't say the word.

Now, I don't think it's such a scary thing, really. I don't know about how you feel about this. Maybe there's disagreement here. But I actually had cancer two years ago. I thought it was a fascinating experience. I was really, absolutely impressed by the whole experience. Had a marvelous time.

It was very-- I wouldn't recommend it. But it was extremely interesting. And I was-- I think that's why I feel so optimistic about it. I think that everyone is.

We could all have a story. We'd all have stories. I think that is absolutely part of what the future is going to look like. I think we all hope there'd be a drug for cancer. That's not going to happen. There could, but not soon.

We're chipping away at it. We're chipping away at it incredibly effectively. And so there are lots of-- we have to treat each issue as a separate disease. We all know that. The causes are different. The treatments are different. But they're really working in amazing numbers of cases if you have access to the phenomenal care we happen to have here in Boston.

GOLDBERG: In terms of the advice you would give to a young scientist-- as President Hockfield mentioned, we have many UROPs who work in the laboratories at the Koch Institute. If one were to come to you, what advice would you give to him or her in terms of new approaches towards cancer research? What's something that's very exciting to you?

HOPKINS: I think it's doable. I really do. And I hope we're not recording this. But I suppose we are. But I really think cancer is really within reach now. I do.

It may be manageable for some people for the rest of their lives, fixable by some, early detection. All of these things are going to get keep getting better and better. There are some things on the horizon.

There's a peculiar, interesting discovery many of you may be aware of. There's amazing research on aging, so extending lifespan. And we're seeing lifespan extending. It's an interesting thing.

But when you extend lifespan, you delay the onset of cancer. We think of aging as being associated with cancer. But actually, aging itself is not associated with cancer, as far as we know, at all. So all you have to do is push out that curve. And you keep pushing cancer away.

And it's remarkable. But there are actually, possibly, drugs that could actually mimic that process, which is done genetically, very simply now. There are a few mutations that cause this to happen. So it's possible that such a thing could have a broad spectrum effect on cancer. So there's still that hope of a miracle drug that could affect many cancers.

But I think it's going to come from the incredible discoveries that we've seen a fraction of today. I'm going to see many more of that are going to just continue to extend the number of people living longer. So it's not just whether you die, but how long do you live a healthy life before you die. So I'd say this is the time.

SHARP: One of the things I would say to any young person who's entering the field of cancer research is that this idea of convergence, of the physical science, computational, and biological science, and being able to come at understanding this disease and its treatment with bringing data, and physical techniques, and nanoparticle fabrication, and understanding imaging technology, is just going to-- it's in that mix that I think we will see our most significant advances. And to have that tool set is just very important for a young person entering this field.

LANGER: I would second that. I think one of the things that we're all excited about at the Koch Institute is that we have great biologists and great engineers. And already, even though we've only been in it a couple of months, I know some of my students are just so excited because they are engineers and chemists. And they go talk to some of their counterparts in biology labs. And what they're doing is exactly what Phil mentioned.

They're thinking about how they could apply nanotechnology to, say, some of the things that Phil's been doing on-- Michael is actually a good example. He was a graduate student in my lab and a post doc in Phil's. But basically, he can apply-- there's some wonderful new possible drugs that can interfere with RNA that Phil mentioned. But one of the big challenges is how can you get them into the cells, and how can you do that safely.

And so by using nanotechnology, that may be one of the ways to do it. So I just think there's so many examples like that in diagnostics, and imaging, and therapeutics that this whole convergence idea really opens up new opportunities for young scientists to do things they probably never could have done before.

GOLDBERG: I think we have a few more questions, actually.


GOLDBERG: In the meantime, I'll ask one of the ones that was already here. So this is actually a great segue for the next session. And it has to do with technology. So the question is do you foresee one game changing technology developing to improve cancer treatment as a whole. Or will there be a barrage of different therapeutics that address cancer as several related diseases?

LANGER: I would love to hope for the first. But right now, I expect more the second. I think that that's certainly what we've seen, a barrage of different kinds of approaches. And I think we've been making them better and better.

I think there are the possibility, as I mentioned before, of new kinds of drugs that, like SRNA, that may be much more powerful someday. And there may be other advances like that, too. We just don't know. But I think right now it's-- you want to attack it on as many fronts as you can, because we don't have a cure. We have ways, as Nancy mentioned, of prolonging it and treating it better.

But I think, right now, I personally would think you want to go down as-- one of the things that David Koch actually said when he gave his speech last week was that he didn't know what would be the right thing to bet on. But when he was a young man, he went to the Kentucky Derby. And he said, he really wanted to win his bet. And so he bet on every horse. And he won. And so I think again, if one can find the funding, that's not a bad approach.

HOPKINS: So I think maybe-- we'd love to go on, continue on. But we have other wonderful sessions coming, too. So I think we should probably stop now. Michael, is that right?

GOLDBERG: We would like to thank you very much for coming to attend this. There will be a 15 minute break. Please help yourself to refreshments. And please join me in thanking our wonderful panelists.