Scientist Stories: Susan Hockfield, Living Machines

Good evening. I'm Ruth Lehmann, and I welcome you to Director's Dialogues, a series of virtual conversations with visionary leaders of science, education, and the biotech industry. Our goal in these dialogues is to offer an inside perspective on the new opportunities and emerging challenges and trends in biomedical science and technology. I will ask our guests to share their most meaningful experiences and observations, tell us what excites and concerns them about the present and future of bioscience, and to tell us about innovations that could dramatically affect the future of human health. In a moment, I will introduce today's guest for what I'm sure will be a compelling conversation. But I'd like you to be able to participate as well, and we will reserve about 10 minutes at the end of this conversation to respond to questions that you submit. So during our conversation, I invite you to offer questions via the question and answer box at the bottom of the screen. I should also note that this talk will be recorded and distributed at a later date. We begin this series by speaking with one of the most thoughtful and dynamic of academic and scientific leaders, Susan Hockfield. Susan was the first life scientist to be president of MIT. Among her many accomplishments in that role, she oversaw the founding of the MIT Energy Initiative, the David Koch Institute for Integrative Cancer Research, the Institute for Medical Engineering and Science, and the Ragon Institute of MGH, MIT, and Harvard. Presently, she serves on the board of Pfizer and Mass General Brigham, among many other advisory roles. Susan is also an accomplished neuroscientist who has championed research and innovation emerging from the convergence of the life, engineering, and physical sciences. After stepping down from her position as MIT's president, she spent a year as a guest of the Belfer Center for Science and International Affairs at Harvard School of Government. This year at Belfer Center allowed her to reflect on her presidency and her thoughts to focus on the idea of technology convergence that led her to write a book. This book, "The Age of Living Machines: How Biology Will Build the Next Technology Revolution," is a fascinating exploration of the role that scientific convergence could play in overcoming major humanitarian, medical, and environmental challenges. Welcome, Susan. Although most of today's conversation will be future-focused, Let's start by looking back at this past tumultuous, horrendous year. There are so many lessons to be learned from the collective experience with COVID-19. What have we learned that you feel has the most relevance for the future of biomedical research and development?

Well, first, Ruth, I want to thank you for inviting me to help you launch this series with this evening's conversation. I am, as you know, such a huge fan of yours and of Whitehead Institute. And boy, as really difficult as this past year of COVID has been, in many ways, it's been one of science's brightest hours. And let me just describe a few examples. But first, I simply have to call out the simple fact that all the practical applications of science that we've seen this year including the miracles out of COVID and beyond, are only possible because of decades of fundamental discovery science that have given us the tools to understand and to combat the new coronavirus variant. This truly marvelous form of exploration which I've enjoyed, you enjoy, this process of following hints and guesses, to discover previously unknown features of the universe, in this case, biological universe, are the necessary early steps in decoding how biology works, how biology goes awry in disease, and how we might intervene. But those early steps happen invariably without any advanced insight into the possible uses to which they may apply. Let me give you two examples of things that have kind of emerged out of this terrible year and make a third observation. The first is, I think, obvious to anyone who has even dabbled in biology, that RNA has emerged as the surprising hero with RNA vaccines that were developed in months, not decades, using an entirely novel kind of biological application. I have to say, I'm on the board of Pfizer, as you mentioned, and we have one of the RNA vaccines. It has been an amazing, an amazing accomplishment to turn an idea for vaccines into real vaccines. And I hope many in the audience, as I have, have gotten at least one, the first dose of the vaccine. The second, probably to my mind at least, unexpected outcome of recent science is CRISPR-Cas9-based diagnostics. Now CRISPR itself is a crazy, really crazy bacterial immune system that protects bacteria from invading viruses. And to imagine that we could deploy it as a strategy for rapid diagnostics is simply mind-blowing. And, you know, it's for me a wonderful relief in a sense, because much of the CRISPR focus recently has been on gene editing with all of its ethical and practical complexities. And instead of having to focus on that for this year, instead, we can think about how it can be used for a rapid diagnostic. And the third observation is that equally important to my mind as the scientific achievements was a very rapid reorganization of how we do science with the shared ambition of conquering COVID, the shared goal of defeating this virus, new kinds of collaboration sprang up almost overnight. New ways of sharing data, a new pattern of distributing manuscripts before they had completed the review process. I mean, so many ways we've illustrated what and how much we can do when we lower the barriers of competition and turn competition into collaboration. So there's been lots of focus appropriately on testing and distributing vaccines, but the critical importance of longstanding investments in fundamental curiosity-driven research really has to be celebrated. And while I tend to be an optimist, I can't just reflect on the positive sides of the COVID experience because I think we've also illustrated some pretty disappointing shortcomings. This whole year has called out this country's just embarrassing diagnostics deficit. You know, a lot of other countries had rapid, accurate tests a year ago in February. And in the United States, we're not even anywhere near the kind of rapidity, the kind of accuracy, the kind of volume that we need for diagnostics. And the second is our current dilemma, delivery confusion. Can I say this? What am I— what are we supposed to call this? Along with billing confusion, and that has unfortunately highlighted how our structure of distributed heterogeneous healthcare delivery doesn't lend itself to urgent action across our entire population. So those are just 3 opening thoughts, and I'm sure everyone will have another 3, 4, 10 ideas about how this year has changed how we pursue science.

Absolutely. So this year really showed that it's possible to move biomedical development and approval process much, much faster than in the past. Do you think that that was something that will just happen in general now that there's an openness for this? You mentioned a number of the aspects which were really novel. Do you think we'll go back to as it was, or do you really think this is a change?

Well, we really did show that we can move faster. There have been unprecedented, incredibly productive collaborations among the academy, industry, and government. I mean, things that you could have wished would have happened have actually happened. And despite the embarrassing public face and stumbles of government, they really deserve a lot of credit for moving vaccine approvals faster, for adjusting their processes so industry could move at the speed of science. While preserving integrity and accuracy of the process, it is still a safe process of approving vaccines. So we've moved at pandemic speed, and there is— lots of credit should go to the individuals and small groups that launched and committed to open access data in a way we haven't seen before. Publishing changed dramatically, at least in the biological sciences, changed dramatically with preprint distribution of articles becoming the standard. I really think that this publishing, distributing pre-reviewed manuscripts is here to stay. And, you know, the physicists have been doing it for quite a while, and it hasn't had any negative impact on the quality of their work. And I think it's about time that biology joined the present, not even the future, in terms of how we communicate our findings. And the really big question is, can our regulatory agencies move faster standardly? The big question, of course, is, is it safe to move faster? And we've seen for vaccine development, it absolutely has been safe. No, no steps have been missed. They've just been done faster. And if you think about other things, parts of our system that are kind of sluggish, I mean, does it really take 9 months to review a grant proposal? I mean, it seems incredibly inefficient. But then on the other side is that, you know, we've had through COVID too many examples of rush to approve what have ended up to be ineffective treatments. So clearly, we haven't gotten it right. But I really hope we've learned that we can move faster and we can move faster safely and incorporate the kinds of methodologies that we've used now to be more standard than they've been.

Definitely. Let's turn to your book. And that's actually much of the broader future, way beyond sort of what we were just talking about. So you talk about the age of living machines and really pushing the idea that biology will build the next technology revolution. And so you bring up the, meaning of convergence. And so can you tell us how we're seeing this to manifest?

Yeah, so convergence of, in this case for our generation, biology with engineering, I see as without question the technology story of the 21st century. I've got to give you a little history, and simply what it means is using biological bits, the parts list of biology, to build new technologies. And I came upon this because As a president of a university like MIT, obviously I've got responsibility for how buildings get built and how things go this week and next week and next year. But a president's real responsibility is to set the stage for the next 25, 50 years. And I don't know about you, Ruth, but my crystal ball goes pretty fuzzy after about 5 years. And I needed a way to think about the future, to help MIT in planning for that future. And I figured that one way to think about it was to think about the future that we're living today. And if we think about the technologies that most profoundly transformed our lives in the 20th century, there is no competition. It's clearly been the digital technologies. First, there was the electronics industry in the middle of the early to mid-20th century, and then its successors, the computer and information industries, have transformed our lives. But where did these transformational industries come from? And if you dissect it back, I'm, I'm an anatomist, so I like to dissect things. But if you dissect back this current of research and this current of industry and look at physics around the turn of the 20th century, in late 19th century, early 20th century, physicists at that time decoded the parts list of the physical world. J.J. Thomson discovered the electron in 1897. The Curies were describing X-rays. All of this incredibly important and breathtaking work in physics gave us a parts list of the physical world. Well, my dear friends, the engineers, love a parts list. And once you present a parts list, they'll pick them up and turn them into interesting new ways to solve technological problems. And indeed, the product of the parts list of physics, first of all, was the electronics industry. Transformed lives, absolutely transformed lives, a new kind of industry, a new way of using the facts of the world around us, that is the physics parts list, to build televisions and radios and movies and all kinds of interesting technologies. And then, as I mentioned, the successors of the electronics industry, the computer and information industries, all those industries based on the fundamental parts list physics. So What will the new parts list be for the 21st century? Well, as biologists, we all know that we didn't have much of a parts list before the 1950s. Biology was a productive science, but mostly a descriptive science, the way physics was in the beginning of the 19th century. But with the discovery of DNA as the heritable material, the structure of DNA, and then the understanding that the intermediary between DNA and protein was this new molecule called RNA, and a deeper way of understanding proteins and how they work, ways to do experiments based on the tools of molecular biology— DNA, RNA, and proteins. Biology presented a parts list, and one of the things I discovered when I came to MIT— I knew about biomedical engineering. We had put together a new department of biomedical engineering when I was dean and then provost at Yale, but I didn't understand just how broad this new way of building things was until I came to MIT. But the idea is that with a parts list, engineers are picking up those parts and using biological parts to solve some incredibly daunting technological problems. And it's happening all around us already. And I see no reason to believe that it's not gonna continue to accelerate. And so the convergence of biology with engineering, that convergence, convergence 2.0, if the convergence of physics with engineering we consider to be convergence 1.0, convergence 2.0 will be the technology story of the 21st century. And I can tell you, we need it because we have a lot of just staggeringly daunting problems facing us. When we think about our current world population of about 7.5 billion rising to 10 billion by 2050, and think about all of the technologies we need to address the needs of 10 billion people on planet Earth, So that's kind of the story of convergence 2.0. And, you know, I can give you some examples if you're interested. But, you know, to my mind, this is the technology story of the 21st century. It's already happening all around us. And the reason I wrote the book was I was so intrigued by this new way of thinking about where our future is going to come from. That I wanted to describe it in a way that would be understandable to a lay audience, to a general audience, because what could be more fun than having a front seat on the ride to the future?

Yes. What I thought was so fascinating about your book is how you start with the biology, right, and sort of this complicated issue. And so you're sort of proposing almost a a biorevolution, where there could be a significant role in transforming how we address major challenges such as disease, energy supply, water, food, starting with learning from biology and then going to engineering. So almost the other way around than you were describing to us. Could you talk to us and tell us a few examples from your book, from some of your chapters that— I'm actually curious which one of those you may find The most intriguing, I would have a hard time picking.

Well, it's hard to have a favorite child. But it was hard actually to choose the examples. Let me describe two. One is related to the diagnostics deficit that I've described. To me, it's frustrating and crazy that we don't have diagnostics as our primary tool in facing health issues. The example I give in the book on diagnostics uses nanoparticles, very, very tiny particles that are equipped with biological signals to move diagnostics earlier. And I could, you know, use the example from any number of diseases, but let's talk about cancer. Cancer is a terrible disease and we've made some progress. There are some cancers we can treat, most we still can't. But the problem with cancer, frankly, is we have a way to treat it. The problem is diagnosing it early enough. Cancer, as most of you know, is a disease that originates as a single cell, a single cell whose rate of division goes out of control because of cancer genes. And one cell becomes two, becomes four, becomes eight, it continues. And, you know, eventually you have a very reasonably large tumor mass. Our current state-of-the-art techniques for diagnosing cancer are better than they used to be, But they're still pretty late. Obviously, if you have a growing cell mass, which at some point is going to escape the organ in which it first develops and moves someplace else through the process of metastasis, the best strategy for cancer— obviously, the best strategy for cancer is not to get it. And so if everyone stopped smoking, which has reduced the rate of lung cancer by a huge fraction since smoking reduction became a popular thing, or if we all wore sunscreen when we went in the sun— I'm as guilty as the next person of not doing that enough— if we received vaccinations against the viruses that we know to cause cancer, I know together we could reduce the cancer incidence by prevention. But frankly, if we did everything we now know to prevent cancer, we would still get cancer. So the second Best strategy for cancer is early diagnosis. Catch it when it's small, very small cell mass that can easily be removed before it's moved to other tissues when it becomes very difficult to treat. So where are we with diagnostics? We're late. Even the best diagnostics, mammography, colonoscopy, PSA for prostate cancer, you know, these are late and not particularly accurate. So my colleague Sangeeta Bhatia, who's an MD-PhD— she's an engineer-clinician and who has a lab at the Koch Institute for Integrative Cancer Research, where my office is— has developed a different approach to diagnostics that is more sensitive and promises to be able to diagnose cancers when they are 1/10 the size of current cancer detection techniques. And she uses nanoparticles, fabulously interesting part of engineering science, nanotechnology. What she's done is paired nanoparticles with a very basic biological process. Every tissue has its particular kind of characteristics because of particular genes that are expressed. And one kind of gene that's expressed in different kinds of cells are enzymes. Cancer cells have particular enzymes, and those enzymes are part of the reason why cancer is able to move and invade through spaces that normal cells can't. Cancer cells have enzymes that cut the material that is between cells that inhibit cell movement. What Sangeeta reasoned was that if she could detect cancer not by looking for the cell mass themselves, But looking at the enzymes for the presence of an enzyme that a cancer expresses, that would give her a much more sensitive way for detecting the presence of cancer. What she's done is decorate nanoparticles with little protein segments that are the target site of enzymes. At the end of that little tether of a protein, she puts a marker, a marker that she can detect. If it's released from the nanoparticle. In the standard practice, you would inject these labeled nanoparticles into the bloodstream, and if you don't have cancer, they stay intact and pass out of the body the way waste products pass out of the body. However, if you do have cancer, the enzymes of that cancer will clip off the end of these tethered molecules, releasing a signal protein. She's designed that signal protein to be so small that it finds its way back into the bloodstream, and so small that the kidney recognizes it as a waste product and takes it out of the bloodstream into the urine. What she has is a urine-based diagnostic test for cancer. She can, in experimental animals, and they're now in clinical trials, detect cancers that are 1/10 the size of standard state-of-the-art cancer detection technologies. And often when I give this talk, people say, detect something in urine? Is that possible? And I simply remind people that there's an over-the-counter pregnancy test that detects a protein in urine that is inexpensive, highly accurate, and is sold in huge quantity to the regular population. So Sangeeta's method is based somewhat loosely on that kind of urine detection. She's also now broadened this technology so that she can detect, discriminate between different kinds of pneumonia with a strategy like this where the nanoparticle is not injected into the bloodstream but is inhaled into the lung, and depending on what kind of pneumonia you have, each pneumonia expresses a different kind of enzyme, and those enzymes will similarly cleave the marker molecule from these nanoparticles, and then the individual who has pneumonia will exhale that marker and then use a breathalyzer approach to detect the presence or absence of the marker protein. This way she's combined an engineering technology with a biological technology and lets biology do the work. Enzymes are nature's amplifiers. And she uses those amplifiers to amplify the signal for her cancer diagnostic. Hugely powerful and would be a real game changer in terms of accelerating diagnostics. The other example I'll offer is hugely important in terms of 10 billion people. And the real problem we've had, we've had it for thousands and thousands of years, is how to purify water. Since a couple thousand years BC, we have been purifying water by the same technologies. Distillation, you boil contaminated water and collect the water that evaporates. That water is then pure. You can use that to drink safely. Or filtration. There's a drawing that was found in an Egyptian tomb from about 1500 BC showing water purification through filtration through sand. These are the main techniques. We now filter through chemically designed filters, but filtering water is very expensive. It's very energy intensive. Frankly, already we don't have enough clean water for people around the world to drink, to cook with, and it is a very pressing problem. Certainly with climate change, the problem is getting even worse. So the question is, how do you build a better water filter? This is a marvelous story that begins with a Nobel Prize-winning series of science experiments. These are experiments done by Peter Augre, who's a hematologist at Johns Hopkins University. And, you know, one of the things that is fun in the book is that so many of the great discoveries that changed our lives were accidents. So this is an accident. Peter Oudtgrave wanted to study the Rh protein. As a hematologist, he was interested in what the Rh protein actually is, and this is the protein that can provoke an immune response by a mother against her fetus. We now know how to mitigate that, but we don't know a lot about the Rh protein itself, so Peter went through a big purification process. He took a lot of red blood cells and went through the purification to get down to the single protein that he was certain was the Rh protein. And then in analyzing it, he realized that, oops, not the Rh protein at all. And very odd distribution, didn't understand what it was. He scratched his head, puzzled over it, was wrong. So he went back and repurified it. He got the same wrong protein again. He was quite puzzled by what this protein was. Well, long story short, Our cells, every cell in our body, every cell in every plant and every animal is a genius at purifying water. And they do it through a channel which Peter had discovered. People sought this water channel for decades and decades, couldn't find it, gave up, and they decided that water crossed into and out of cells simply by diffusion, end of story. And Peter, without meaning to, finally identified the water channel. He named it aquaporin, beautiful name, a water pore, and was busy studying it, doing all kinds of beautiful analyses of the thermodynamics of this protein. It's a little protein that kind of looks like a barrel without a top and a bottom, and it sits in the membrane of every cell. And the beautiful thing about aquaporin aquaporin is the only molecule that it allows to pass is water. There are variants of aquaporin that will pass other things, but most aquaporin molecules will only pass water. Beautiful series of studies. A biophysicist in Chicago was reading these papers, a guy named Piholm Jensen, and he was reading them and he had the most amazing thought. He thought, huh, if our cells use this protein to filter water, maybe we could use that protein to build water filters. And he's a great example of an academic turned entrepreneur. And he started a company which is called Aquaporin. And I visited the company when I was writing the book. It's outside of Copenhagen. And he— the company now builds very effective water filters. Using the aquaporin protein as the filtering mechanism. Quite amazing. They have filters that are on the market for home water filtration, and their goal is to build industrial-scale water filters that could desalinate water and clean water from any number of sources. An absolutely fascinating story of serendipity, but also a fascinating story of the power of biology. When I visited Aquaporin and the company, Peter said to me, he said, you know, we could bust our brains trying to figure out a better way to filter water, but why don't we just use nature's genius? And that really is the theme of the book, is that nature's genius is full of wonderful solutions to our technological problems. If we can be smart enough to figure out how nature solves technological problems, we could use nature's genius to solve them ourselves.

Yeah, that's very nicely said. And, you know, I recommend everybody to read the other stories in the book, like how to, you know, transform how we breed plants, controlling brain activity for The movement and making batteries from viruses, all amazingly amazing stories. And I think what I like so much is how you explain the work and how you explain the— how you talk about the people behind the work. And I think talking about the scientists and in particular, as we're sort of considering sort of how, you know, this emerging age of convergence and where, you know, translation and application is sort of the key, what you're talking about. When I think about Peter Agger's sort of chance discovery of aquaporin that you just raised and told us about, I wonder how do we balance these bioapplications that you are talking about with, you know, scientists exploring new biology so we get more applications, right? And so there is a lot that we haven't discovered yet that could be used. So how do you think we can kind of balance those?

Yeah, Ruth, I mean, it's as if the more success we have, the more vulnerable the seed corn is, right? So the only way to, aquaporin, the only way to— Angie Belcher's virus-enabled batteries is having, as I said, the toolkit, the parts list in hand, and the parts list does not come from purpose-driven discovery. It's just some crazy person like you or like me, you know, people who love doing this stuff, just being puzzled about how things work and figuring out place to basically place the lever so you can open up the mystery. It's the reason why I'm so just in awe of these RNA vaccines. These vaccines are going to absolutely change our lives. They're going to— actually, the use of RNA as a medical tool will change medicine. Will change medicine. And I can promise you that back in the 1950s, when our colleagues were studying RNA, I cannot, you know, it's hard to imagine they were doing that with a medical purpose in mind. Perhaps in the abstract, you know, when you write your grant proposal to the NIH, you know, the last sentence of the abstract has to have the clinical application and I remember my friends, my colleagues, and I sitting around at the Banbury Bar at Cold Spring Harbor and talking about that last sentence of our abstracts and just laughing uproariously, knowing that whatever we imagined we would do for clinical applications, the story wasn't going to turn out that way, but what's absolutely critical is the commitment to fundamental research and the commitment to funding fundamental research, discovery research, funding it well and funding it continuously. One of the things that I talk about in the book, because I just think it's such an important part of the story, is the, you know, obviously, it is the impact of World War II on America's 20th century economic and industrial progress. So war is the great accelerator of technology, and the nation with the best technology wins wars is, you know, commonplace. And the investments that the United States made in developing the science and the technology to prosecute World War II is the reason that the Allies won the war. You can think about what many people consider to be the war-winning technology, which is the development of radar that happened at MIT. Or the war-ending technology, the atomic bomb. These were technological, scientific and technological marvels. So as the war was drawing to a close, FDR, the president, asked the man who had led this scientific effort, Vannevar Bush, who had been Dean of Engineering at MIT and then president of the newly established Carnegie Institute, who was recruited by FDR to lead the effort. And FDR turned to Bush and said, well, now that we've done these amazing technological things for war, what should we do now? Can these principles of investing in technologies to win wars, can it be productively applied in peace? And Bush delivered in response one of the most amazing future views, treatises on the future of the world that I've certainly ever read. It's called Science: The Endless Frontier. And most scientists have heard about it, perhaps read parts of it. I finally sat myself down and read the whole thing, and it is breathtaking. In wisdom and ambition and in farsightedness. And Bush said to FDR, look, we can make the same kinds of investments now because investments in fundamental research— in fundamental research— that's the way to build the technologies of the future. It will fuel industrial growth, economic growth. Nothing could be more important to the nation. And the health and livelihood of the nation and safety of the nation than making these investments. And of course, in retrospect, it has all proved to be true. Unfortunately, FDR died and his successors were not as enthusiastic about the model. So that transformation of the United States into an ongoing engine of creativity, an ongoing engine of invention, got started a little bit slowly, but it was, let's just say, reinvigorated by the Russians getting Sputnik up into space before the United States got a satellite up into space. And that renewed the enthusiasm for making these kinds of investments. And out of Sputnik was born truly the biggest World War II post-World War II investment, now sustained investments in fundamental research, basically following the plan that Bush had laid out. So it's really a very powerful model, and you know, it hasn't been a secret that the United States has pursued this model, and I can tell you while I was president, hardly a week would go by when there wasn't a visit from some emissary from some country who would come to my office and say, we understand how the United States invested in research and developed technology. And we also understand that having a university like MIT is a critical part of that recipe. And will you please help us build our MIT? So it's open access stuff. And what's very important is the United States continues to make these massive investments in early research and discovery research because it is the seed corn for next year's harvest and next decade's harvest. And it's always debated. Happily, we've been able to maintain a high level of investment, but we reached our peak nationally relative to GDP in the mid-1960s. When it was about 2% of GDP, and it's fallen off quite a bit now. Today it's 0.7, 0.8% of GDP. And I spent a lot of time when I was president going to Washington and arguing for the importance of these kinds of investments to build our technological capabilities, also to fuel our educational enterprise.

As you know, I mean, the Whitehead is founded on this idea that scientists want to conduct curiosity-driven and discovery research and really push that forward. And so for us, it is obviously really important to think what the science policies are to go forward, because it always seems like, oh, we've done this. Now we can move to this next— it's all translation. It's all application. And as we were just discussing, that is certainly not so, because where are the discovery is coming from. In a way, you could say with your, you know, proposal to say, you know, let's take the biology for the next discoveries, is also finding in new biology the next applications. And we're not going to find the new biology if we don't have this curiosity-driven science. So I want to kind of— we're almost at the end, so I want to just sort of shift a little bit, sort of give— just hear a little bit about what your thoughts are on science policy. So President Biden has done a lot already in the first couple of weeks now. He's trying to help the pandemic and to undo all the economic economic damage it's caused. But he also tapped a biologist, Eric Lander, former Whitehead Fellow and faculty member, and then the founding director of the Broad Institute of MIT and Harvard, as the president's science advisor. Actually, the first time that a life scientist is in that position. So before there were physicists. So I think really echoing what you're saying in your book. And then also MIT's Maria Zuber and Caltech's Arnes Frankel as the co-chairs of the President's Council of Advisors in Science and Technology. So really putting science in as a really, really important part. So what do you feel, and I'm sure you could go on for quite a while, but what do you feel are the top priorities for federal science policymaking in the next year or two. So what would be your advice?

Yeah, so I think obviously task one is to maintain and raise the kind of resources that are available for discovery research, for curiosity-driven research. That's absolutely essential. We've got to keep that going. I think MIT's NASA is an unusual place because we do both discovery and translational research. And, you know, got to get the balance right. And, you know, frankly, when federal funds drop, so it's just too hard to get grants and just too hard to do your research, it discourages the next generation. I, you know, can't tell you how much time I spent in Washington when I was president trying to explain that if you cut NASA's budget, you're going to lose not just the research of today but the research of tomorrow because the graduate students aren't going to stay in the where they can't do their work. So, you know, this consistency of funding is key. You know, one of the problems that comes out of understanding this convergent style of research, it is very hard to cross disciplines. I speak about it as though it was a trivial problem. It's not. It's a really, really hard problem. And in terms of federal funding, the problem we have to solve right now and fast is that we have silos in terms of federal support. So the NIH funds biological and biomedical research. The Department of Energy funds physics research. NSF funds engineering and a little bit of biology research. But once in a while, we get it together to have initiatives across disciplines. The Human Genome Project was one. The National Nanotechnology Initiative was another. The New Brain Initiative— not so new— Brain Initiative. On another where, you know, it's actually set up so the agencies all participate in a particular cross-disciplinary effort. But those are the exceptions rather than the rule. And I think we've got to figure out how to make that happen more easily. And, you know, a lot of the responsibility is on us as universities to figure out how to make it possible for people to work across disciplines. So that's part of it. I'm delighted that, you know, the people that the Obama team has put in place because it's clear that they understand the power of biology. I'm sure they understand the power of biology to solve our medical problems. I don't know that they understand it as profoundly as a solution to many of our technological problems. But I do think they believe they understand the importance of curiosity research, and certainly Eric Lander and Maria Zuber and Francis Arnold get it. I have a lot of confidence in what that group is going to bring forward in terms of changes in— or adjustments, I would say, to national policies. You know, I think, again, you know, the more successful we are, the harder it is to do what we need to do. Biology moves much faster now than it used to, and it's not uncommon for a discovery in biology to lead to a clinical application or industrial application. And so our faculty and our students either live a dual life or have to decide which path to pursue. And for me, the most critical side of this dilemma is making sure that it's possible for those who are crazy enough to love the exploration of discovery research, as you As I said, Ruth, you are and I was. We want to be sure that that's an attractive and possible path to pursue, and that requires consistent, reasonable levels of federal funding for that kind of just exploratory experience, adventure into the unknown.

We certainly need it, right? If you think about like when you say, you know, where the various funding agencies and also philanthropy and any support we can get for questions like the environment and climate change, right, that requires sort of a similar effort.

You know, Ruth, you mentioned philanthropy, and I just, I have to just say a word about it. All of the initiatives that we launched while I was president, frankly, all of the initiatives that I experienced, I had the benefit of participating in as a scientist, It really is private philanthropy that gets that stuff going. Another difficulty with our grant process is it's very hard to do something entirely new. And Vannevar Bush knew that, and he recommended that these great funds that the federal government would distribute should be distributed through the process of peer review, which is frankly a lot more— has a lot more alacrity than having, you know, a small group of people deciding what kind of money goes where. However, that process is necessarily a little bit slow in coming to consensus around brand new ideas. And private philanthropy always fills the gap. And it is simply miraculous and wonderful that there are people who get excited about other people who are discovering the secrets of the universe. And, you know, for me, you know, among the most really miraculous partnerships are these partnerships that bring great philanthropy to use in helping our great scientists discover unknown things about our world.

Yeah, it's that connection that is wonderful. So Susan, I cannot thank you enough for joining me tonight for this also inaugural Director's Dialogue series meeting, and I so much enjoyed our conversation. I know we could talk about many other topics that came up. And now I do want to— I hope everyone else enjoyed this conversation, and I would like to open up for some of the questions that we got. Let me see. So we have a couple of questions. So here is, if the first question from Tina Kui, and the question is, excellent comment on RNA-based vaccine as 2020 hero and CRISPR-based diagnostic. COVID-19 has taught us enough about inflammation cytokine storm. Repurposed drug became the key of fighting COVID-19 therapeutics. Only 1% drugs match with COVID-19 viral structure. COVID-19 certainly accelerated modern medicine development from vaccine to gene therapy and big blockbuster drug making. What do you think of big data on medicine innovation?

Oh, you know, that's a great question, and in the book I, I only use big data as an example in the chapter on, on food and how we get better plants so that we'll be able to feed our growing population. But I am, I am fascinated by the application of big data, AI, machine learning on medical innovation. I've seen a couple of just astonishing examples, two from MIT. One has to do with digital mammography, which is a collaboration between Regina Barzilay in our computer science department and Connie Lehman, the head of breast imaging at MGH, and Truth be told, mammography is not that accurate because the signals are a little obscure. Regina, this is not a secret, it's well-known, was diagnosed with breast cancer herself and was meeting with her doctors. She said, as a machine learning, one of the world leaders in machine learning, she said, You know, Amazon knows more about what shoes I want to wear than you know about the chemotherapy I should get. So she took a 180-degree turn and pivoted all of her research to using machine learning to get better at diagnosing cancer, be able to diagnose cancer, breast cancer earlier. It's been a fantastic study. And, you know, she's published it and just has had wonderful success in being able— making mammography that can recognize potential cancerous lesions earlier than has been possible, a really fantastic result. And then she partnered with Jim Collins to use machine learning to find new kinds of antibiotics. And they discovered an entirely new class of antibiotics through machine learning. So I think the opportunities are vast. Some of them will be, I would say, straightforward and others will be quite surprising. All of them depend on our power to compute. I'm not sure that the universities and hospitals are as well-equipped as we should be. This is a frontier that is exploding and expanding. And it's in a tough territory because when you get into clinical care, let's just say the risks are very high when you're talking about human life. And so it's a new kind of world for most people who do AI and machine learning, but I think the potential is enormous. So thank you for asking the question.

Valerie Khan is asking, how can philanthropists incentivize scientists to cross over silos to stimulate and accelerate interdisciplinary convergence research?

Yeah, that is a great question, Valerie. Thank you for asking it. I'm not surprised you've asked the question. You know, there are so many disincentives to cross boundaries. One of them, of course, is the funding difficulty. But also, the way our universities are structured is not so— makes it not so easy. Easy to talk to the person down the hall, not so easy to talk to someone across campus. And the way we organize our lab spaces, our teaching programs, really follows disciplinary boundaries. One of the things that was very powerful at MIT, and I've seen it happen again and again, and it happened in the context of COVID is having a shared ambition, a shared goal, a shared problem that you want to address that brings people together from different disciplines, each with his or her tool or perspective, and then being engaged in conversation. We had the great joy and privilege of having George Shultz chair the external advisory board for MIT's Energy Initiative. And as you all know, he was just a master statesman and just a spectacular organizer of human endeavor. And one of my favorite Shultzisms, which he would remind us often, is that if you want to land together, you need to take off together. And so I think that one of the things that we find is that Engineers view scientists as widget providers, and scientists view engineers as service providers that you wait till you've kind of worked your way into a corner, and then you call an engineer to write some code to get you out of it. That's just not the way. I mean, that's kind of task-oriented, but to be purpose-oriented, so to start thinking about a problem together and evolve a path to a solution is really the way to go. And so we've had incredibly visionary philanthropists who have allowed us, given us funds to do, you know, seed funds for experiments to pose a question, a problem, and then to fund heterogeneous groups to come together and actually work on solving it. So I think philanthropy is a very powerful a powerful tool in catalyzing cross-disciplinary work. And you know what they say, fund it and they will come. So we've used that tool a lot. And, you know, probably it's not that people don't want to solve problems, but if you pose it as a distant ambition and not the task of today, you can be much more effective at fostering cross-disciplinary work.

There's one more question that I have to ask you because it's so, so wonderful and so important for the future, and that is from David McEffish, and he has asked, what advice would you give to a young scientist just entering the field of biological engineering? What other breakthroughs can we expect to see even within the next decade?

Oh boy, if you're entering the field of biological engineering, you will, you will, um, you know, I, I wish, I wish I was farsighted enough or had a good enough imagination to know what's coming next. One of the delights of being in this environment is the surprises. You know, people do things that, you know, I could never have dreamed of. It's incredibly exciting, and I think, um, One of the things that I've been really impressed by is that when I arrived at MIT in 2004, and when the freshmen arrived, I would walk around campus and talk to them and their parents and ask them what they were interested in. I was surprised at the number of students who said they were interested in bioengineering of some kind because it seemed pretty sophisticated. I was interested in a little bit, but I didn't know what its power was going to be. And I teach a course, a freshman advising seminar on my book. And when I first started, it was when I first started writing the book, and I had a group of 8 students, and I said, well, why did you choose this seminar? And I think 7 of the 8 said, well, I didn't get into the seminar I wanted to get in, and it seemed okay. And this year I have 12 students in my freshman advising seminar, and I said, well, why are you in this? Why are you taking the seminar? And they all said, are you kidding me? I'm doing this. This is, this is the future, and I want to be part of it. So, um, The times have changed already in a very, very short time. I think the one thing that I'd advise is that fields form very fast and they very rapidly tell you what you can and you can't do. While you have to take the courses that are required and you have to pass the exams that are required, No one makes you not think out of the box. And so I would simply look for new opportunities to apply the tools of your trade. It's going to be remarkable and fantastic. And I hope I can see a lot of the new stuff evolve, but I can't imagine what it's going to be.

Just do it, right?

Exactly.

So Susan, I cannot thank you enough. This is really a wonderful conversation. I really greatly enjoyed it, and I'm sure our guests here did as well. I want to also thank all our guests. We had a lot of people watching. Unfortunately, we couldn't do this in person, but I still hope you enjoyed your time this evening. The Whitehead Institute is an extraordinary place to me and the scientists who work here, And I hope you will take some time, if you don't know yet, to learn a bit more about the discoveries made at our institute. So please go online to our actually brand new website to learn more about our research, sign up for Pulse, our monthly newsletter, and consider making a gift to support the Whitehead Institute to support exactly this kind of science we were talking about today. The next Director's Dialogue will take place on March 22nd and will feature Noubar Afeyan, founder and CEO of Flagship Pioneering and chairman of Moderna. So thank you again for participating, and until next time, March 22nd, be well and safe.