Exclusive Episode: Working Together to Break Through

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Dr. Tyler Jacks, the President of Break Through Cancer, has dedicated his life to cancer research. He is the Founding Director of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, the David H. Koch Professor of Biology and Co-director of the Ludwig Center for Molecular Oncology. From 2001 – 2007, he served as director of the Koch Institute’s predecessor, the MIT Center for Cancer Research, and was a long-standing Investigator of the Howard Hughes Medical Institute (1994-2021). Dr. Jacks received his bachelor’s degree in Biology from Harvard College, and his doctorate from the University of California, San Francisco, where he trained with Nobel Laureate Harold Varmus. He was a postdoctoral fellow with Robert Weinberg at the Whitehead Institute before joining the MIT faculty in 1992. 

The Jacks laboratory at MIT’s Koch Institute studies the genetic events underlying the development of cancer. Dr. Jacks has pioneered the use of gene targeting technology in mice to study cancer-associated genes and to construct mouse models of many human cancer types, including cancers of the lung, pancreas, colon, thyroid, and soft tissue. These powerful, sophisticated models closely recapitulate human disease, and have led to novel insights into tumor development, as well as new strategies for cancer detection and treatment.

In recognition of his contributions to the study of cancer genetics, Dr. Jacks has received numerous awards, including the AACR Outstanding Achievement Award, the Amgen Award from the American Society of Biochemistry and Molecular Biology, the Paul Marks Prize for Cancer Research, the Sergio Lombroso Award in Cancer Research, and the AACR Princess Takamatsu Memorial Lectureship. He was a member of the Board of Directors of the American Association for Cancer Research (AACR), and served as the organization’s President in 2009.

Dr. Jacks is an elected member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and was a member of the inaugural class of Fellows of the AACR Academy. In 2015, Dr. Jacks received the Killian Faculty Achievement Award, the highest honor the MIT faculty can bestow upon one of its members. In 2016, Dr. Jacks co-chaired the Blue-Ribbon Panel for (then) Vice President Joe Biden’s Cancer Moonshot Initiative. He was also chair of the National Cancer Advisory Board of the National Cancer Institute during the Obama administration.

Dr. Jacks serves on the Board of Directors of Amgen and Thermo Fisher Scientific. He co-founded T2 Biosystems and Dragonfly Therapeutics, where he also serves as chair of the Scientific Advisory Board. He also is a member of the scientific advisory boards of Skyhawk Therapeutics, SQZ Biotech, the Lustgarten Foundation for Pancreatic Cancer Research, and the Francis Crick Institute. Dr. Jacks is a member of the Harvard University Board of Overseers.

Show Notes

• Tyler Jacks, Ph.D. 
• Koch Institute for Integrative Cancer Research at MIT
• The Jacks Lab 
• Break Through Cancer  
• National Cancer Plan 
• Cancer Moonshot  

Ad: NanCI by NCI mobile app 

Your Turn: Guest Recommendation

• Dr. Yinzhi Lin (Listener) The Sound of Waves by Yukio Mishima 

Episode Transcript

[UPBEAT MUSIC]

OLIVER BOGLER: Hello and welcome to Inside Cancer Careers, a podcast from the National Cancer Institute. I'm your host, Oliver Bogler. I work at the NCI in the Center for Cancer Training. On Inside Cancer Careers, we explore all the different ways that people join the fight against disease and hear their stories. Today, we're talking to Dr. Tyler Jacks, founding director of MIT's Koch Institute for Integrative Cancer Research, Koch Professor of Biology at MIT, Co-Director of the Ludwig Center for Molecular Oncology, and President of Break Through Cancer. Listen through to the end of the show to hear our guest make an interesting recommendation and where we invite you to take your turn.  

It's a pleasure to welcome you, Dr. Jacks, to the pod. 

TYLER JACKS: Thanks very much. It's a pleasure to be here. Looking forward to the conversation. 

OLIVER BOGLER: Dr. Jacks has many accomplishments to his name, stemming from his research, his leadership, and his engagement across the cancer research community. He has been recognized with many prizes and honors. He's a member of the National Academy of Sciences and of Medicine and the AACR Academy. He serves on boards of biotechs, including some he founded, and co-chaired the Blue Ribbon Panel for then Vice President Joe Biden's Cancer Moonshot Initiative. He was also chair of the National Cancer Advisory Board for the National Cancer Institute during the Obama administration. We will link Dr. Jacks' LinkedIn page in the show notes so you can see all the things that I missed.  

Dr. Jacks, with such a broad series of engagements and experiences, I'd like to start with asking you where we are in cancer research in 2023. 

TYLER JACKS: Well, we're in a very exciting point, I would say. As perhaps we'll discuss a bit later in our discussion, I've been doing this for a very long time. And I've never been more excited than I am today about what's happening in terms of the advancements of our understanding of the disease at the molecular level, our understanding of the disease in many other dimensions and then how that's led to improved ability to both diagnose the disease and intervene at earlier stages, but importantly also to bring new treatments based on those insights. I mean, I think we're in a revolution in terms of how we treat cancer today, with respect to immune targeting drugs and precision medicines. It's incredibly exciting to see the impact of the science in the clinic.  

OLIVER BOGLER: So in terms of our ability to meet, for example, the goals of the National Cancer Plan, which was recently unveiled, and also President Joe Biden and First Lady Jill Biden's reignited Cancer Moonshots, the plans call for reducing cancer mortality by at least 50% over the next 25 years, and improve  the experiences of people living with and surviving cancers, their families and their caregivers. How do you feel about those goals, that or that particular goal? 

TYLER JACKS: Yeah, I think those are actually achievable goals. They're lofty goals to be sure. I think if we are successful in bringing about that level of change, it will be impressive. But I think it is achievable. 

And I think it relates to some of the things that I just mentioned. The tools that we have now for treating cancer more effectively are in place and in use for certain cancers and they will expand, and they will have impact on those diseases. So, mortality will come down as a function of better treatments. But in addition, our ability to diagnose the disease at earlier and earlier stages, allowing us to intervene at earlier stages, where we all agree the disease is more controllable, will likewise contribute to reduced mortality. And I think related to our treatment strategies, you know, the drugs that are being developed are simply more well tolerated by patients. And so, reducing the burden of individuals who are dealing with a cancer diagnosis and undergoing treatment will improve as well. So, this is all pointing in the right direction. I'm glad that the White House and the NCI put out these, you know, bold goals and aspirations. And I think we as a community have a responsibility to try to achieve that. 

OLIVER BOGLER: One of the interesting things in my mind of the National Cancer Plan is this idea that everyone should get involved, everyone has a role. What's your perspective on that? 

TYLER JACKS: I agree with it, first of all. This is a disease that is exceptionally common, and all of us have either suffered from a diagnosis or were close to someone who did, maybe lost a friend or family member to the disease. It's a very personal disease for many people, and in that respect, we should all be compelled to try to make a difference. In addition to that a central set of individuals who should and will step up as it relates to that call for action are the patients themselves. Patient engagement, patient involvement, patient participation. 

We're finding, and we'll talk a bit later about Break Through Cancer, we're finding tremendous interest on the part of patients to participate actively in the research enterprise, a willingness to have samples shared and data shared and benefit themselves and have benefit to others through that type of interaction. So, in terms of participation, I think we want to really emphasize the role of the patient in that participation.   

OLIVER BOGLER: One of the key features of the plan and one of the key ingredients, if you will, of achieving its goals is going to be the workforce. We need a skilled workforce that can drive forward the research, that can apply the therapies you described, the cancer prevention measures, the policies, everything, and engage with the patients. What's your assessment of where we are regarding the cancer research workforce specifically? 

TYLER JACKS: Yeah, well, I'm heartened every day by the high quality of the people that I interact with who are working in cancer research labs at MIT, but really around the country and around the world. And I interact with a lot of them. These are very smart, highly motivated individuals who come, from the U.S., but also come from all over the world. And one can understand why, because this is a very exciting area of science, and the applications of what one does in the science have direct benefit to individuals with potentially life-threatening diseases. So, I'm buoyed by the workforce that we have today.  

Now having said that, there are concerns, in academia in particular about the interest level that students and postdoctoral fellows have in pursuing careers in academia. I think that's a legitimate concern and I see it myself, the trend towards seeking other career options, biopharmaceutical and other career paths, I would say is increasing, has increased over the last decade or so. That's not necessarily a bad thing in the sense that those are important jobs to do and individuals in those roles play a very important role in our ability to control the disease. But if we think about academia per se, there is a bit of a strain. And I think we as a community need to think about that and think about what can be done to improve the attractiveness of a career in academia. 

OLIVER BOGLER: I'd like to go a little deeper on that. I mean, you have led an academic center, the Koch Institute for Integrative Cancer Research, which I should mention carries an NCI designation. You've also founded some startups and worked with established biotech companies. So in terms of that competition for talent between the private and the public sector, perhaps as a rough way to describe it, how can the public academic sector compete more effectively? What changes are needed? 

TYLER JACKS: Yeah, well, some of them are fairly simple-minded. One of the reasons why individuals choose careers in industry is that they pay better. So, in a simple-minded way, we need to face that fact. And academic institutions are facing that fact. And pay scales, as you probably know, are rising, perhaps not rising as fast as they need to. But that's one gap that exists. 

I would say we in academia need to do a better job in demonstrating the value and advantages of an academic career. The freedoms that come with an academic lab position, the ability to demonstrate one's creativity every day without needing to justify to a superior or manager what direction your research is taking. That you can really pursue your own interests and develop new paths for yourself that address those interests. 

The academic pursuit is unusual in that way. The level of creativity that one can express by being an academic researcher is, to me, incredibly invigorating. And there are other aspects of the academic lifestyle that I think are very attractive, at least for me. The ability to work with these young people, these trainees, and help contribute to their education and career development is incredibly exciting. I teach, for example, at MIT.  So I interact with undergraduate students. I'm teaching a class right now on the hallmarks of cancer. We've got a group of, I don't know, 90 or so students in the room. And they're there to learn and to grow. And some fraction of them will become cancer researchers themselves. And that, for me, is incredibly exciting and incredibly rewarding. And I think all of that together makes the academic experience very, very attractive. 

OLIVER BOGLER: I'd like to pivot a little bit to one of your other roles. So just a couple of years ago, a new organization, Break Through Cancer, was started. You serve as its president. And if I may quote you from the website, quote, “when we act together, we have the potential to be an unstoppable force. There’s nothing that will build momentum and progress faster”, end quote. So please tell us about Break Through Cancer. How does it work and what is it doing? 

TYLER JACKS: Yeah, so Break Through Cancer is a new foundation, as you mentioned. We opened our doors about two and a half years ago. We are an organization that was formed to facilitate, promote, and fund inter-institutional team-based cancer research to tackle very difficult problems, historically difficult problems in cancer. Initially focused on four cancer types, and that will grow over time, but glioblastoma, pancreas cancer, ovarian cancer, and AML are our first four target areas. 

OLIVER BOGLER: Acute myelo…  

TYLER JACKS: Acute myelogenous leukemia, sorry. And so, we were formed to promote and support inter-institutional teams. What does that mean? Well, first of all, we have five key partners, five outstanding cancer centers in the country, all with an NCI designation. MIT's Koch Institute, the Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, the Kimmel Cancer Center at Johns Hopkins, and the MD Anderson Cancer Center, all are founding partners of Break Through Cancer. And importantly, for all of those organizations, we have members of their leadership serving on the board of Break Through Cancer, which is a demonstration of their investment in this activity. They've sort of all pledged to work together to, in part, bring the resources of their institutions, including, importantly, investigators from their institutions to this activity.  

The research that we fund is team-based, and we are trying to instill an approach wherein members of those teams, even though they might come from multiple institutions, and in our case they do, behave and treat each other as though they were members of the same laboratory. And we have a term for that called the team lab. So these teams form a team lab, and there is a degree of interaction and information sharing and data sharing and sample sharing that occurs across this group of investigators within the team lab in much the same way might happen in an individual laboratory at a particular institution. Our role is to help form those teams and help them think through exactly what they want to pursue together. 

And this is a distinguishing feature of Break Through Cancer, I would say. The active role that we play with our staff and with our scientific advisory board to help the teams themselves refine their ideas, improve their ideas, shape their ideas to become the most effective team they can be. 

And then when that process is completed and the team is funded, we don't walk away. Break Through Cancer stays involved and helps them continue to effectively engage as a community of researchers, and also helps work through problems that they might encounter, including at the level of their institutions. In order for this to work well, the institutions have to work together well. And these institutions sometimes have policies that are not harmonious, and we need to work through those. Sometimes we need to work with industry partners. That's actually an important feature of Break Through Cancer. And that can be challenging, even with a single institution, let alone five institutions. And so in all of these ways, Break Through Cancer is trying to enable a form of research which we call radical collaboration. It's collaboration across many investigators, across many institutions, between academic institutions and industry, between researchers in an institution and administrators within an institution, everybody pulling together to try to achieve a common goal.  

That's beginning to work, I'm pleased to say. We're now at two and a half years into the organization, about a year and a half into our first funded teams. And that new culture of collaboration and genuine teamwork is beginning to take hold. And it's incredibly satisfying to all of us here at Break Through Cancer to see that happening. And I think our team members likewise are excited to be participating. 

OLIVER BOGLER: So that sounds really amazing what you're doing there and incredibly interesting. The incentives in academia or in the private sector aren't always aligned with radical collaboration. How are you overcoming that barrier? 

TYLER JACKS: Yeah, it's a really important question and I think we've thought a lot, really since the beginnings of the organization, about how credit and incentives will be handled in order to continue to motivate people to participate in these joint activities. Because you're right, there is a fear that in the context of team-based science, people might not get adequate recognition. What I can tell you is that there's a lot of enthusiasm from our participating researchers. We've got 360 or so investigators participating across eight teams that we've funded so far. And these indivudals range from the most senior faculty members down to graduate students and post-docs. I would say my observation is that the younger people are even more excited about participating in these team-based activities. I think they recognize the value of joining forces with others and thus achieving more than they can do themselves. Now, having said that, we do have to pay attention to credit and incentives. And so when we think about authorship, we need to be careful that people get recognized for what they do. And frankly, we're still working through exactly how we will do that in a formal sense, but we know that it's important. In terms of other forms of recognition, we've talked openly about the fact that when it's time to discuss the work at public meetings and other fora, we don't just pick the senior most individual. We pick an individual from the team who may be the best to represent a particular aspect of that work. And that person might be a graduate student or a postdoc or a research scientist or somebody else on the team. And so we're very thoughtful about how we see the inner workings of the team and how we recognize the contributions. And I think the final thing I would say, and I think this is maybe has a larger scope to it: when we think about career progression, at least in academia, we know that promotions and promotion packages and letters of support in promotion packages are very important. And so we've made a commitment as an organization to go deep and if it's important that an individual on one of the teams gets special, recognition because of the role they played on that team, even if they weren't necessarily the first author or last author on the paper, but they played a really important role. We've committed and I personally have committed to writing a letter that makes it clear that this person did these important things. And I think I'm sensing now that promotion committees are very open and receptive to this notion that that you shouldn't just look at the first author and the last author, but really try to attribute properly the credit and individual plays in a team-based science project. 

OLIVER BOGLER: Interesting. I mean, you have eight teams, so this is a more general question. But one thing we are very interested in on this podcast is all the different kinds of science and expertise and minds that are required to tackle cancer. Right. It's no longer a cottage industry. It's now a team based industry. I wonder if you could comment on these teams that you have formed through Break Through Cancer, what kinds of scientists are on those teams? 

TYLER JACKS: Yeah, well we have a full range, and I could really take that question in two different directions. Let me start with the members of the teams and then I'll switch to the sort of disciplines that they represent. But as I said earlier, we have very senior faculty, we have very junior trainees participating. We have research scientists and non-tenure track faculty on these teams. In fact, we've created a position that we call the Break Through Cancer Scientist. This is an individual who's non-tenure track, but full-time researcher. At MIT, we would call that a research scientist. They have different designations at different universities. We have four of these individuals today across those eight teams, and we will grow that number. And these are individuals who are sort of dedicated to a particular team on the one hand, but also dedicated to carrying the culture of Break Through Cancer across teams. They are integrators of this activity more broadly. So that’s another category of individuals whom I think are critically important, and I’m really pleased by how well our first four Break Through Cancer Scientists are doing.  

So we have a range of individuals at different career stages participating, but we also have a range of activities and disciplines participating. From molecular biology, molecular genetics on the one hand, all the way through to the clinic. So many of our investigators are clinicians carrying out clinical trials. This is an activity that spans from the research and discovery realm through to the clinic. Importantly, breakthrough cancer is really built to bring the best of science to the clinic. And so many of our investigators are clinically oriented as well. But we also have a very serious commitment to data science and computation. One of our eight teams is actually the data science team. And we’re building within Break Through Cancer a data science hub that will support the network of individuals across all that we fund. So data science is a key component of the Break Through Cancer activity. 

We also have, beyond biological disciplines and cancer biology, cancer-oriented engineering. And that might not surprise you, given my role at MIT and the Koch Institute, which features exactly that. But not just at MIT, but from other institutions as well. We have engineers who bring their skills and their approach and their perspective, sometimes their devices and technologies, to these problems. And that really speaks to the value of the team-based approach, and I think it was really at the heart of your question.  

By being on a team that is composed of people from different backgrounds, different disciplines, different perspectives, you can take advantage of that breadth of activity and expertise to advance the project faster and more effectively. That's certainly what we believe here, and we're seeing it play out in real time. 

OLIVER BOGLER: Given the broad view of cancer that you have and these many different kinds of engagements, I wonder if I could entice you to make a prediction as to where we might be in five or 10 years. 

TYLER JACKS: Yeah, well, in our world, as you know, five or 10 years is an eye blink, but I'll try. Maybe it's more fair to talk about 10 years than five, but in 10 years' time, we will see if I think about cancer treatment, we can talk about cancer research and prevention and early diagnosis as well. But if I think about cancer treatment, I think for many of the major cancers and many cancers more broadly, we will be in an era in which targeted therapies and immunotherapies will have replaced traditional chemotherapy in the front line. 

That's obviously already happening for some cancers, and I predict it will happen for most. And deep genetic testing will be available and implemented for all patients. And molecular diagnostic techniques will be used to properly evaluate the state of the individual's disease and apply the right technology. So the whole realm of precision medicine will come into play more broadly across cancers and be more available for all cancer patients. I think that is a realistic expectation.  

Will it lead to the curing of cancer in 10 years? No, it will not. Cancer will remain a formidable foe. Resistance is a problem and will remain a problem. But our ability to manage that resistance and as we talk about converting cancer from an acute disease to a chronic disease will take shape, has taken shape and will continue to take shape. So that's where I see where we'll be and even in 10 years time. That's from the perspective of cancer treatment.  

OLIVER BOGLER: What about research? 

TYLER JACKS: Yeah, so I think in research, we are again living through this amazing time related to the technologies that are available to us today. Our ability to do profiling at depth and at scale in ways that one could not have imagined, using single cell methods and spatial omics methods and various integrations of molecular techniques of various types to give a more fulsome picture of what's happening in cancer, bolstered importantly by more and more powerful computational methods to help us understand and organize all of those data. So cancer research is at an important turning point as it relates to that. And then, of course, our ability to manipulate genomes with greater and greater precision. CRISPR and all the follow-on technologies related to CRISPR, our ability to manipulate genomes by the nucleotide, make our ability to model cancer much more powerful. And this is, of course, the work that we do in my own laboratory. And when I think about where it was when we started compared to where it is today, it's really breathtaking. 

So the power of technology as it applies to cancer biology is really changing the way we even think about what's possible And in ten years, I can't even imagine where we'll be but it will be in an even more powerful place. 

OLIVER BOGLER: Well, that's a great teaser for the second part of our conversation. So we're going to take a quick break. And when we come back, we will talk to Dr. Jacks about the research in his lab, how he mentors scientists and ask him to give you some advice. You, our listeners. 

[music] 

OLIVER BOGLER: PubMed lists over 270,000 cancer papers published in 2022 – that is a staggering 750 papers every day. It’s great that cancer research is such an active field, but it makes finding the pubs that are critical to your work a challenge. What if you had an AI that paid attention to the papers you read and suggested others as they appear in PubMed? That is exactly what the NCI is building with an app called NanCI. With me to discuss NanCI are two members of the team that are creating NanCI: Chris Perrien of Blue Pane Studios and Duncan Anderson of Humanise.ai. 

Chris, you’ve been building apps for NCI for over a decade. What is new about NanCI? 

CHRIS PERRIEN: Fundamentally NanCI represents a shift in the scientists user experience – in the prior generation of apps people had to know where to look to find things. Now, they can find the information using AI agents. I think of NanCI as a friendly research assistant who makes suggestions and answers questions. Of course, it is early days, and NanCI is still learning from their users, but they will get better and better over time.  

OLIVER BOGLER: Duncan, you bring AI expertise to the project. Can you tell us what capabilities that brings to NanCI? 

DUNCAN ANDERSON: Yes. NanCI is all about connecting scientists. Right now the focus is on connecting them to papers relevant to their interests, which NanCI does by matching vector representations of abstracts and looking at co-citations. If you tell NanCI that you find a group of papers interesting, by bookmarking them, the app will keep an eye on PubMed for you and suggest related publications. You can also share these folders with colleagues and export them to your reference manager. You can read the paper right there in NanCI, and follow any author to see when they publish preprints. Down the road we intend to help people network based on shared scientific and career interests. And much more – these are just some of the features of the app.  

OLIVER BOGLER: Thanks, Chris and Duncan. Right now NanCI is available in the Apple app store, and it will be coming to android later this year. Download it and give it a try! Your feedback on NanCI is very welcome – you can send that to us here at NCIICC@nih.gov.   

[music] 

OLIVER BOGLER: And we're back. Dr. Jacks, I'd like to pivot to your own science. Your lab's web page says that your group is interested in the genetic events contributing to the development of cancer with a focus on mouse models. How did you come to focus on this? How did you get into science in the first place? 

TYLER JACKS: Yeah, my story goes back to college. Entering college, I don't think I knew for sure what I wanted to do. Science was on the list but it certainly wasn't at the top of the list. And I was lucky enough, like many people are, to take a course that really changed my interest level dramatically. It was a course in molecular biology taught by a professor named David Dressler. And he brought to life this young field of molecular biology. This was in the early 1980s. And I got captivated by what we could know and what we could do. 

He fortunately offered me an opportunity to work in his laboratory, which I did, and began to do firsthand cancer research at the bench, which was very exciting to me. I then had another pivotal moment in college where I was taking a cancer biology class, not unlike the one that I teach myself today. And along the way, this was back in 1982, by the way, a young Bob Weinberg wandered up the road from MIT and gave a special lecture on work that he had done, and his laboratory had done just in the last several months, which was the cloning of the first human oncogene, HRAS. That was unpublished work that he was presenting to us at that time. And I remember well sitting there in that class thinking, this is the future. This is how we will understand the cancer problem. And this information will give us ways to treat the disease better and diagnose the disease better. I decided at that time that this is what I really wanted to do in my life. So, I applied to graduate school, went off to UCSF, and was fortunate enough to join the laboratory of Harold Varmus, who, as you know, became one day the NIH Director and then the NCI Director. 

OLIVER BOGLER: Indeed. 

TYLER JACKS: He was a tremendous mentor. I was interested in cancer, as I mentioned. It happens that the project that I worked on in Harold's lab was one that was deeply in the field of retrovirology and the retroviral life cycle. I'll just say parenthetically to the audience that the reason I worked on that project is that my first project, which was on the cloning of the retinoblastoma tumor suppressor gene, failed miserably. So, I had to go to my backup plan, which was to study ribosomal frame shifting in retroviral gene expression. But I always maintained an interest in cancer research, and so when it came time to choose a postdoc, I returned to my interest, actually in the retinoblastoma tumor suppressor gene, which by then had been cloned by Bob Weinberg's lab. He comes into the story again. And I decided that if you can't beat him, join him. So, I joined Bob Weinberg's lab. The gene had been cloned, and fortunately, the techniques for generating knockouts in mice using genetic engineering and embryonic stem cells had just begun to become available. And I decided to use that set of techniques to create mouse models of familial retinoblastoma and eventually other familial cancer syndromes. And that's the work that I did in Bob's lab. So, I became interested in using the mouse as a model system and using genetic engineering as a postdoc. 

I will also say parenthetically to our audience that for the first three and a half years in Bob's lab, nothing worked. It was a series of failures. I couldn't get any of what I was trying to do to work. Bob fortunately was very supportive and allowed me to continue and eventually after three and a half years things began to work, and I was able to make those knockout strains and they really did form the foundation of the research that I do today.  

So, we continue to use the mouse as a model system. We continue to use genetic engineering. But of course, it's become so much more powerful. What we can do today with more precise targeting technologies, including importantly with CRISPR, allows us to make any mutation in any gene, in any cell of interest. And we've also been able to push the biology beyond, not just studying the cancer cells, but studying the cells that interact with the cancer cells. So a large fraction of my lab today works on how the immune system sees and fails to see cancer, and ultimately what we can do about that. 

OLIVER BOGLER: So I would like to challenge you, perhaps you know what's coming, but Dr. Richard Klausner, former Director of the NCI, has been quoted in the LA Times as saying, quote, “The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades and it simply didn't work in humans”, end quote. So, I'm curious, how do you feel about that statement and what is your perspective on mouse models? 

TYLER JACKS: I'm extremely disappointed in my friend Rick. [laughs] Others have said that, but I actually didn't know that he said that. In any event, if he were sitting here, I would challenge him to get the facts right. On one level, it's true. Using certain types of mouse models, one can quote unquote “cure the disease”. And those models typically are xenograft models where human cancers are placed under the skin of an immunocompromised mouse, maybe they're mouse tumors grown under the skin of an immunocompetent mouse but still in an ectopic site. They are not endogenously arising tumors like the ones that we create and many, many other labs create, which arise from otherwise normal cells in their normal context where they're surrounded by the proper microenvironment and interact with the immune system in particular ways. Those models are much, much, much harder to treat. 

I used to show a slide actually in my talks when I talked about these models taking on this question. I would say I would show these models that we've built of lung cancer or pancreas cancer, and I would say you know people say that these types of models in mice are easy to treat, easy to cure, and I would flash up a notice that said ‘cure this’, and I actually would offer money, never my own money, I would offer other people's money. Maybe today I'll offer Rick Klausner's money. 

OLIVER BOGLER: [laughs]   

TYLER JACKS: $10,000 if you can cure this mouse. I would put that challenge out there. I give you 10 lung adenocarcinoma bearing mice from the models that we create, cure them. I can tell you all the way to today, that was probably 15 years ago, no one has succeeded. We haven't, no one else has. So there are models and there are models.  

Now having said that, I do not, and my colleagues in this field do not pretend that the cancers that we have developed in these so-called autochthonous models, genetically engineered models, are perfect mimics of human cancer. They are not. There are many differences in the genetics and the biology, and they are, in fact, simpler. They grow, they develop more rapidly, their genomes are less complex. They are not perfect mimics of the human disease. But Rick is wrong that it's easy to cure cancer in the appropriate mouse model of the disease. 

OLIVER BOGLER: Thank you. So, your work has involved many different types of cancers, some of the common genetic drivers like p53, retinoblastoma you mentioned, and then more disease-specific molecular changes. I think one of the hardest things for any scientist is to identify the most important questions that are tractable to study. How have you achieved that? You've had many successes. 

TYLER JACKS: Yeah, I think that both how I've approached problems like that and how members of my laboratory over time have approached problems like that, I personally think it best comes together when there are two important elements that are synergistic. Important element number one is the interest level of the individual graduate student or postdoc. They have to be, passionate about what they're studying. They have to find it exciting and interesting. It's the sort of thing that keeps them up at night and wakes them up in the morning. That sort of drive from within to understand the nature of the problem and whether it's a cancer genetics problem or a cancer immunology problem or what it might be. So that sort of inherent interest and passion from the investigator is one.  

And then the second is the ability to pursue that question, ideally in an interesting and powerful new way. So this is the bringing together of emerging technologies and technological opportunities that might not have existed a year before or six months before. And the application of that technology or set of technologies to the problem. And that allows not just iterative, incremental advance, but rather more transformative advance. And so, I encourage my people to think about their problems in that way. Don't just take the next step. Try to take the next leap. And that next leap might be enabled by the application of a new technology. And that might take time. It might take you months. It might take you years to bring together the biology and the technology in this powerful new way. But to the extent that you can do that, I think you bring valuable new insights on the one hand, and you position yourself as an investigator to have a special skill set that, if you will, is quite sellable as it relates to your career advancement. 

OLIVER BOGLER: So I want to look at the other side of that. You already mentioned your own time in the Weinberg lab and the challenges you faced where you had a dry period. How do you mentor the members of your team through those times that come to almost all scientists, I would say? 

TYLER JACKS: I think they come to all scientists certainly at some point or other in their careers, but typically they occur every day. And it's not always easy, and I don't know that there's a simple right answer to how to manage through that, because the fact of the matter is that sometimes it is important to stay the course and to continue to push, because eventually the problem will yield, the technique will get refined and the hurdles will be overcome and you and the field will benefit from the fact that you persisted.  

But sometime it doesn't happen that way and things don't yield. You were wrong about how you thought things worked and there was just no way that project was ever going to get there. 

Or the technology simply wasn't mature enough to be used in the way that you tried to use it. And therefore, at some point, one has to pull the plug and go to plan B. And I think for all mentors and probably for all trainees, there's a realization that there need to be a series of projects that somebody is working on, especially in these sort of high-risk, technology-oriented projects, where if things don't work there's an escape hatch that allows the individual to pick up another project and pursue it. 

OLIVER BOGLER: So you have a truly impressive publication record. It starts in the 1980s. You've seen a huge change in our field and you've already alluded to some of the technological advances. But I wonder if there are things that you feel we may have lost in the course of this, these successive revolutions that the cancer research field has undergone. Is there anything you miss from the early days, the old days? 

TYLER JACKS:  From the old days? The good old days. Yeah, I think there are some things that we've missed through the ways in which data is generated, collected, and analyzed leads the investigator sometimes to be a bit removed from the work that they've done. 

Samples are processed by others, data is generated by others, data is sometimes analyzed by others, and a summary of the data is supplied. Now, those are all good things because they speak to efficiency. If you had to do all those things with your own two hands, it would take you multiples of time to get things done, and we don't want to do that. 

But at the same time, it creates a distance between the investigator and the investigator's brain perhaps, and the problem at hand, and the data at hand. And so I think to overcome that one can't be lazy and one needs to really dig in, understand exactly what's happening with your sample and understand exactly what the data are and what they are teaching you and don't rely on shortcuts that one could actually in this environment take. And sometimes that would be fine, but sometimes I think important things would be missed and would fall through the cracks. 

OLIVER BOGLER: So the co-authors of your early publications read like a who's who of cancer biology. You already mentioned Dr. Varmus, Dr. Baltimore, just to mention the two Nobel laureates, many others, Dr. Weinberg and so on. What was it like to launch your career in that kind of a community at MIT and in Boston at that time? 

TYLER JACKS:  Yeah. I've been very fortunate to have outstanding mentors throughout my career. I mentioned Harold and Bob, but I've had many mentors even since I've been a faculty member. And one thing that struck me at the institutions where I've worked is despite the fact that I've been surrounded by really smart and experienced and accomplished individuals, the willingness of those individuals to take the time to help their junior colleagues and their trainees, to mentor them, to advance their careers has been extremely heartening. 

I've always felt like I was part of the community, even when I was a graduate student. I was not a junior member of the team, I was a member of the team. And that's been true interacting with people all the way through. MIT, in particular, is an amazing place to work. It's full of incredibly accomplished people, Nobel laureates, as you mentioned, but a remarkable lack of ego and a remarkable openness and access. And to me, that environment, and it doesn't just exist at MIT, of course, I think it exists throughout our community, makes the doing of what we do so much more fun, and so much more enjoyable. That opportunity to interact with people as people, and not as revered scientists, really makes the day to day of it so much more enjoyable. 

OLIVER BOGLER: So Dr. Jacks, I don't know if you remember, but I remember meeting you when you came to visit the lab of my postdoc mentor, Dr. Web Cavanee, back in the mid 1990s in San Diego. You took the time to meet with all the junior scientists at the Ludwig Institute there. And I wonder in that context, I remember enjoying your advice. What has the advice been that you have given to the many scientists you've mentored? And what would you say to people listening today who are early in their careers? 

TYLER JACKS: Yeah, I think the most important advice that I can give to a junior person is to find their passion within the field. And that's not always easy. It's particularly challenging as you're entering the field and you know less. 

I think it's important for younger people to, in effect, pay close attention. That is to say, read a lot, go to meetings, go to seminars, integrate all that you're hearing, pay attention to the trends that are developing in the field, the important questions that are emerging, the opportunities that exist because of new technologies, and sort of to bring all that together with your own inherent interests in a scientific problem that you wish to participate in. I think that... when it works well, it is a combination of those two things. The passion that exists within the individual to do science on the one hand and to pursue a set of questions more specifically, and then to integrate the opportunities that exist within the field most effectively through their own hands and through their own minds and through the colleagues and collaborators that they will have the opportunity to interact with over time. 

OLIVER BOGLER: Well, thank you very much, Dr. Jacks, for sharing your views and your experience and your advice here on our podcast. 

TYLER JACKS:  My pleasure. 

[music]   

OLIVER BOGLER: But before we go, it's time for a segment we call Your Turn, because it's a chance for our listeners to send in a recommendation that they would like to share. If you're listening, then you're invited to take your turn. Send us a tip for a book, a video, a podcast, or something you found interesting and send it to us at NCIICC@nih.gov. You can record a voice memo and send it along. We may just play it in an upcoming episode. I'd like to turn to our guest, Dr. Jacks. Please take your turn. 

TYLER JACKS: Well, thanks. I think I'm going to take your question in a slightly different direction. We've talked a lot about science and sort of the rigors of science and sometimes the disappointments associated with science. It's hard work. It's serious work. And we are serious in what we do. But for me in my career and frankly in my life, I think it's really important to also focus on the lighter side. The humor. And incorporate that as much as possible in what we do, even day by day.  

Cancer research, science in general, is hard. And frankly, we face more challenges than we do rewards. And to kind of complement that, I think it's important to focus on the lighter side.  

When I was a graduate student at UCSF, I spent a lot of time in comedy clubs, as a matter of fact, not performing but listening to comedians. And that was sort of the highlight of my week. Likewise, in my lab, I like to keep things light and to interact with people with a joke and just sort of with the balance of what's happening in their lives. And a feature of our calendar every year is to have the lab go out on a lab outing, Jack's lab outing every year, which has now become quite famous after 20-plus years of doing this. The Jack's lab summer outing typically involves a scavenger hunt, where the members of the lab, and there might be 30 or so in the summer, are divided up into teams. The teams can choose their own team themes, and they will dress accordingly. And they will wear extravagant dress, very extravagant, embarrassingly extravagant. 

OLIVER BOGLER: [laughs] 

And these teams will then be tasked to go out into the cities of Boston or Cambridge or somewhere and carry out various activities. They might have to apply for a job. They might have to slide down a fireman's pole. They might have to perform and raise money through their performance on the streets of Boston. 

OLIVER BOGLER: Serious challenges!

TYLER JACKS: These are serious challenges, and in doing that, they have a tremendous amount of fun. And they interact with people out in the world, and those people have a tremendous amount of fun. And in addition, they, as team members, and then of course as the lab as a whole, begin to interact with each other in a slightly different way. They let their hair down. They embarrass themselves, and they kind of revel in the fact that they've embarrassed themselves. And so, taking the time to have some fun, every day, even in the course of your cancer research, I think just makes life more enjoyable. So, if I had to leave your audience with a message, don't always focus on the hard things, focus on the lighter side as well. 

OLIVER BOGLER: I think that's fantastic advice. Thank you very much. 

And I'd like to share a listener recommendation, our first here on Inside Cancer Careers. It comes from Dr. Yinzhi Lin, a research fellow in the Department of Microbiology and Immunology at Aichi Medical University in Japan. Dr. Lin recommends The Sound of Waves, written by Yukio Mishima. Dr. Lin says the book is a romance between two teenagers in a seaside village and found the description of the lives of the local fishermen and pearl divers 70 years ago, particularly interesting and touching. 

Dr. Lin recommends the book because reading beautiful sentences can cool down a hot brain after a concentrated working day. We'll put links in the show notes as always. 

[music] 

That’s all we have time for on today’s episode of Inside Cancer Careers! Thank you for joining us and thank you to our guests.  

We want to hear from you – your stories, your ideas and your feedback are always welcome. And you are invited to take your turn to make a recommendation we can share with our listeners. You can reach us at NCIICC@nih.gov.  

Inside Cancer Careers is a collaboration between NCI’s Office of Communications and Public Liaison and the Center for Cancer Training.  

It is produced by Angela Jones and Astrid Masfar. 

Join us every first and third Thursday of the month when new episodes can be found wherever you listen – subscribe so you won’t miss an episode. I'm your host Oliver Bogler from the National Cancer Institute and I look forward to sharing your stories here on Inside Cancer Careers.  

If you have questions about cancer or comments about this podcast, email us at NCIinfo@nih.gov or call us at 800-422-6237. And please be sure to mention Inside Cancer Careers in your query. 

We are a production of the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Thanks for listening.