The keynote remarks at the Nixon National Cancer Conference were delivered by National Cancer Institute Director, Ned Sharpless, M.D.
If you weren’t able to tune in live to watch his remarks, you can view his remarks here.
The full transcript of his remarks are listed below.
Dr. von Eschenbach: Welcome back. We hope that you’re enjoying your lunch. And I’m gonna ask you to continue to enjoy it but maybe somewhat more quietly in the sense that it’s really an opportunity for us to welcome our keynote speaker for this afternoon. It’s a personal pleasure for me to introduce Norman Sharpless, “Ned,” to all of us who respect, admire, and love him. And why it’s a particular pleasure is because he had the temerity and the courage to do what I had done, which is to be both the director of the National Cancer Institute and the commissioner of the Food and Drug Administration.
Ned started his career, of course, as a distinguished medical oncologist. He began as an undergraduate with a degree in mathematics. And I stress that because one of the important contributions that Ned made, particularly during his tenure as the director of the Cancer Center, the Lineberger Cancer Center at the University of North Carolina, was to recognize the importance of incorporating into a cancer center the infrastructure of data and informatics and the ability to extract information, acquire it, aggregate it, and analyze it.
And as you heard from some of the previous panels, this whole idea of seeing biology as a digital science and the acquisition and analysis of data is critically important to us understanding the complexity of disease. Ned Sharpless has been a pioneer in oncology as a hematologist oncologist, but he’s also been a pioneer in leading a cancer center to be transformational. He’s also a true public servant. He took on the responsibility of being the director of the National Cancer Institute, but when he was called upon to step in to be able to lead the Food and Drug Administration, he willingly and willfully did that as someone who’s devoted and loves being able to contribute to oncology. That’s not necessarily an easy transition. But for those of us who have recognized his talent in oncology, we’re pleased and grateful for the fact that he’s come back to NCI and currently leads that institute, not only in recognizing the greatness of its past but, more importantly, appreciating the potential it has for its future.
Our National Cancer Program, when President Nixon put the responsibility for the National Cancer Program into the hands of the National Cancer director who would report directly to him, I think he had Ned Sharpless in mind. We are in good hands. Ned, thank you for being willing to join us even virtually. I will tell you he was committed to be here in person, but President Biden called a session at the National Institute for him to address the emerging variant. And we have been, as public servants, we know Jim, right? That when the president says, you’re there, you’re there. So it’s a command performance. He’s in Washington, but he said, “I’ll still do it virtually.” So, Ned, thank you for that. And we recognize that we’ve been overpowered by the President, but that’s okay. Thank you.
Dr. Sharpless: Well, thank you for that introduction. Is the audio okay? Can you guys hear me? No one’s saying otherwise. So I’m gonna assume that’s yes. I wanna thank the organizers for inviting me to this. I wanna thank the Nixon Library for hosting this, Friends of Cancer Research for their support of this, and the other sponsors, and particularly Andy for being such a good friend, being such a good source of wisdom in this job. I used to say, when I went to the FDA that I had performed successfully the von Eschenbach maneuver, which is to transition from NCI to FDA. And then when I came back to NCI, I now tell people I have performed the reverse von Eschenbach maneuver, which has been… It’s really great to be back in the National Cancer Institute, what I believe is the best job in government, running this terrific organization.
Also, as Andy said, I really wanted to be there today. I’m very sad to miss this in person, this important event. But, as Andy said, when the White House calls, you have to change your plans. So I’m in DC today. Thank you. So I thought I’d make a few remarks briefly today, and then hopefully there’ll be a little time for questions, and we’ll see how that works virtually. And so I think the National Cancer Act is well known to this audience. It’s been a terrifically important piece of legislation. I think, as this group knows, it didn’t create the National Cancer Institute. You know, the NCI goes back to the ’30s, but I would argue the National Cancer Act really created the modern National Cancer Institute.
And from my point of view, the National Cancer Act did three kinds of things that I think are important. It provided increased funding for cancer research, and that’s really important, it granted the NCI a whole bunch of new authorities and capabilities like clinical trials infrastructure, and Frederick National Lab, and the SEER program, and really the modern Cancer Center program. And those authorities and capabilities were very, very important. And the last thing I think it did that is tremendously important is it really removed the stigma around the diagnosis of cancer. So, prior to the NCA, cancer was a disease that was spoken about in sort of hushed tones. And this act really, in this advocacy movement, really brought cancer into the limelight and made it a diagnosis one could discuss in public and thereby created the modern cancer advocacy movement, which has been so important to our progress in cancer over the last 50 years.
But as visionary as the National Cancer Act was, I think we also have to admit it was somewhat naive. Many of those involved at the time expected a cure for cancer very quickly, the same way that sepsis had been brought under control by antibiotics very quickly. So, obviously, things did not work out that way. We didn’t have the basic science understanding in 1971 of cancer biology that really, you know, it prevented predicting when we’d be able to make success against the disease. So, in other words, we didn’t know back then what we didn’t know. But I think that’s what’s changed in the last 50 years. Today we know what we don’t know, and that molecular understanding of cancer has begun to pay off for huge advances for our patients.
So, now, I think there’s this almost incredible progress in cancer research. There’s a sense of new treatments, and new ways to diagnose cancer, and new ways to prevent cancer. And in some ways, I almost feel like we’re beginning to become a victim of our own success. It’s almost a little bit like computing power. I think we just take for granted that computers are gonna be faster and more powerful every year, but really that accelerated performance is the fruit of hard-won scientific and engineering development. And it’s pretty amazing, but we’re almost in that cycle now for cancer research. I think the progress in recent years has been so good that it’s almost nearing to the public. And there’s this sense that we’ll have wonderful new approaches for cancer every year.
But for those of us who’ve been in the business for a while, we know that has not always been the case. That really the dramatic increase in FDA approvals, and new therapeutics, and new ways to diagnose, treat cancer that we’ve seen in, say, the last decade that has been a long time coming, as I said, was really built upon the decades of basic science work that was supported by the National Cancer Act. And so I’ve come to think of it that we’ll look at this period right now today, you know, the decade maybe that preceded this today and the decade that comes next as a really a golden age for cancer research, when this rapid progress fueled by our improved understanding of cancers, molecular underpinnings really allowed us to make the kind of progress against cancer that we hope for as a nation.
And there are several reasons why I believe this. We’ve seen these declines in cancer mortality. Cancer mortality has been going down since the early 1990s for several reasons, including tobacco control and screening. But that rate of decline has been accelerating significantly in recent years and for many reasons, including better treatment. And, for example, with regard to lung cancer, we’ve seen these many new drugs approved, both immuno-oncology and kinase inhibitors, and we’ve adapted whole new frameworks for testing these agents. You know, these basket trial approaches like Lung-MAP and ALCHEMIST that can really, I think, accelerate the development of novel therapeutics in a sort of precision oncology approach.
In addition to the declines in cancer mortality, we’ve seen these rapid developments in new therapies, including immuno-oncology and molecularly target approaches. We’ve seen record numbers of FDA approvals. When I was at the FDA, like a third of the business, in terms of approvals of new drugs and devices was in the cancer space. The oncology space was by far the most exciting area in terms of medical product development at the FDA when I was there. And another thing that we’ve seen but I think is not insignificant at all and really important to talk about, in fact, has been a massive increase in scientists coming to the National Cancer Institute seeking funding through new grant applications.
And we’ve done an analysis of this, and it’s really being driven by new approaches to cancer research coming to our field. So the NCI has seen a greater increase in applications since 2013 than the rest of the NIH combined. And I think that we’re seeing mathematicians, and physicists, and chemists, and health services researchers, and people from really disparate, disparate disciplines now coming into cancer research with new ideas. And I think that’s because of this somewhat sophisticated understanding of cancer biology, scientists see this is an area where they can have a real impact, and they come to the NCI seeking funding. And that is a good problem to have for the NCI. We get to choose from these best ideas which ones to support, but it is also a real problem for the extramural research community because it provides this intense competition for funding.
And that has created the very low paylines at the NCI that I think are a real threat to our field and something I’ve worked very hard in my time as NCI director to try and increase paylines to support extramural research, particularly junior investigators. I think we’ll come to see that this value, this investment in cancer research has been a terrific value per tax dollar spent. And there are many ways to look at this. There was a recent analysis that I, like, conducted through one of NCI’s major networks that documented 14 million life-years saved as a result of NCTN, National Clinical Trials Network’s research since just 1980. And I think that’s really astounding. And I think we’ve also seen the important role that, you know, basic science supported by the NCI has played in the approval of many modern and important therapies that have impacts beyond just cancer research for many disease areas.
So I think it’s really a fair question to ask, given the expense of cancer for our society. It costs the United States hundreds of billions of dollars a year in terms of treatment costs, as well as loss of productivity, and also the demonstrated strong return on investment of cancer research. I think it’s incumbent on us to ask, “Are we as a society spending enough on cancer research to address this problem?” And it’s really a good time, I think, now, 50 years after the National Cancer Act to be asking these kinds of questions and to think about what comes next in the future. So I propose that we should build on this momentum of the last 50 years that has developed a sophisticated, fundamental understanding of cancer and really stand on the shoulders of those giants who’ve helped us get here and talk about where to go now.
And that’s what I’d like to do in the next few minutes. So next slide, please. To begin with, I think it’s really galvanizing to have a president in the White House who has this intimate connection to cancer research. And the President and the First Lady have spoken in many times about their deep personal connections to cancer, and how they understand the tragedy of cancer, and how they’re firm believers in the power of cancer research. And many of us will remember the then Vice President Biden’s very critical leadership in the Cancer Moonshot, which the NCI has now been directing for the last five years. And the current administration has vocally said several times to the cancer research community that, “We would like to end cancer as we know it.” And the National Cancer Institute has sort of been tasked with thinking through how that would work and what that means.
And, you know, we really have spent a lot of time thinking about how we know cancer today and what it would mean to change that. And I think that’s a somewhat nuanced and sophisticated statement. You know, we’re not talking to be clear about eradicating all cancer. We don’t think that’s likely to occur anytime soon because of the biological, you know, strong relationship between cancer and aging. We think some amount of cancer mortality is just a fact of human biology, at least for some time to come. But we think the experience of cancer, the way we know cancer, the way we know the tragedy of cancer, that is something where we can have tremendous impact for the American public. And to really talk about this, I think we have to be upfront about some uncomfortable realities of how we know cancer today.
So while we made a lot of progress that I mentioned since the National Cancer Act, we still have 600,000 Americans dying from cancer every year. Cancer is still the leading cause of death from disease in children, young adults, and even middle-aged adults. Cancer costs the nation hundreds of billions of dollars a year in terms of lost productivity and healthcare costs. And even when we cure patients today, too often this comes at the cost of severe treatment with significant long-term toxicities. And cancer for many patients is still a devastating diagnosis and a family tragedy. And so, if we want to end cancer as we know it, we have to end those ways of how we know cancer. And I think that’s possible, and that’s what the President is asking us to do.
So, one of the ways I’ve talked about this in the past is around mortality. Cancer mortality is a very clear metric. We measure it every year at the NCI with the help of CDC, and the American Cancer Society, and others, publishing the Annual Report to the Nation, and we can see progress. And the peak at age-adjusted cancer mortality in this country occurred in the early 1990s at around 215 deaths per 100,000. And right now, it’s down to about 150 deaths per 100,000. That represents about a 30% decline in cancer mortality over the last three decades, which has really good news. That’s been good progress reflecting advances in prevention, diagnosis, and treatment. Many important things like tobacco control, and cancer screening, etc. But this number that we have today is still way too high, and that rate of decline, for my taste, is way too slow.
I believe we can continue to cut mortality significantly. I think we can reduce it from that peak in 1990. We can cut that in half, and we can do this soon. But to do that, reaching a halfway point from the 1990’s peak will require a considerable acceleration of what we’ve been able to achieve in the past few decades. To cut cancer mortality from its peak in 1990 in half at the historical decline rate, which was about 1.5% per year, would take well beyond 2040, and that’s just too long. At a rate of about 2.4% decline per year, which is what we’ve done the last few years, that would still take too long, 2034, which is not good enough.
But I think if we could continue to accelerate this rate of decline using all our mini tools of prevention, screening, therapy, then I think we can get there much sooner, perhaps as early as 2027. Substantially reducing annual cancer mortality would be one really important and highly visible step in ending cancer as we know it, and cutting it in half and mortality in half from its peak would be such a visible step. But mortality is just one way to think about cancer and how we know it, but there are many other ways that we know cancer. And I think we have to work on those as well.
Next slide. So we’ve been working with the White House, the Office of Science and Technology Policy to think about how we know cancer today and ways we like to change it. And here are just some of those kinds of statements, things that are true today that we would like to make untrue. So on the bottom left, we see that cancer, you know, kills too many people, and I’ve talked about the mortality piece of this. But I think we also have the fact that we have too few methods to prevent cancer, and we have serious inequities in diagnosis, treatment, and trial access that leads to different outcomes based on race, wealth, and access. We have curative therapies that come at these serious costs of long-term side effects. And we have really limited success in some of the toughest-to-treat cancers.
And there are many other statements about cancer that are true today that are not on this list. But these are the kinds of things we’re thinking through. And so for each one of these, the NCI has given a lot of thought about how we make progress against these problems and how we accelerate our goals in these areas. And I don’t have time, because of our short time today, to really go into depth on all of these, but I think, you know, if you just pick out a few of them, say, you know, we lack effective early detection approaches to diagnose many types of cancer, that’s an area where we could really make some progress.
Lung cancer screening, for example, could be very powerful, but it’s tremendously underused in our society. And by encouraging adoption of lung cancer screening, appropriate populations, we could substantially reduce cancer mortality at the population level. Similarly, multi-cancer early detection tests, these blood-based tests that can diagnose cancer in healthy individuals, multiple different cancers are very exciting and promising technology that could really have an impact on cancer mortality at the population level. But, of course, they also bring up the issues of overdiagnosis and overtreatment. And therefore we have to be very careful about how we develop such tests and how we test them and make sure they’re ready for use in the general public.
You know, cancer health disparities is an area where the NCI has funded work for many years, but, frankly, that work has been reinvigorated and really accelerated by recent events, including the murder of George Floyd. And, you know, we need to ask… And the disproportionate impact of the pandemic on certain populations. And so we need to ask ourselves, “Why do these disparities in care exist in the United States, and what can we do about it?” And it’s really the business of the National Cancer Institute to try and study the causes of healthcare disparities and to try and address them. And that is a complicated set of questions that involves things like race, and ethnicity, and wealth, and rurality.
And one thing that we’ve really come to appreciate at the NCI is that these things cannot really be studied as single variables. We have to treat the entire patient and think about the entire set of social determinants of health that lead to their outcomes and really take this problem on as a whole. And rare cancers is a really interesting area where I think we have the possibility to do more. I think we’ve been surprised at the National Cancer Institute how our MATCH trial, the NCI-MATCH trial, that enrolled 6,000 patients at 1,100 sites in a little over 2 years, one of the fastest accruing trials in the history of the NCI. But how many of those patients that enrolled in those trials had rare and unusual cancers? It was, you know, a population that hasn’t had access to sophisticated clinical trials in many cases in the past.
And so, with the appropriate NIMBLe framework and clinical trials framework, we can really do more to study disease in patients with rare cancers. So I think that’s an opportunity where new, very exciting agents can be rapidly brought to test in rare populations using appropriate, innovative clinical trials design. So these are a few examples of areas where I think the NCI has a big role to play in promoting progress against these statements.
Next slide. And so here are some of the ways we’re thinking about how to get there. You know, these are the things that we think it will take to end cancer as we know it. So we have to build on 50 years of progress. We have to keep health equity as a sort of North Star in everything we do in our work in cancer research. We have to really, I think, embrace this precision oncology, this personalized cancer care that has been, I think, a successful new paradigm for cancer research over the last decade. We have to embrace technology and innovation so that we can learn from every patient. We’re particularly interested in doing this through novel approaches of data aggregation and using our traditional cancer registries like SEER and new and innovative ways.
We have to inspire the next generation of cancer researchers. I believe training the next generation of cancer scientists is perhaps the most important thing the National Cancer Institute does. And all of these things done together will help us prepare for the future, the challenges of the future so that we can meet the President’s goal of ending cancer as we know it.
Next slide. So, with that, I will wrap up, and I will just say that this all got started in 1971 with the National Cancer Act and the vision of President Nixon to, you know, task the nation to work collectively in this so-called War on Cancer. And we really have the work of very important advocates like Mary Lasker and a number of very visionary politicians, and doctors, and caregivers of the time who came together to lead to the successful passing of this act that has had such an impact on our field, creating such great progress today. And now the challenge is to see where we can go next, how we can build on the work of the National Cancer Act to achieve the President’s goals for the benefit of the American public. So, with that, I’ll wrap up and take questions if there are any. And, again, I apologize for not being there in person. I very much wanted to be there, but it’s delightful seeing you all at least on camera today.
Dr. von Eschenbach: Dr. Sharpless, thank you very much for your time. Let’s give him a round of applause. I know you are pressed for time. You have a meeting with the President of the United States. We will take one quick question. That will be from Dr. Ellen Siegel. Dr. Ellen Siegel?
Dr. Siegel: Hey, Ned. Thank you for all you’re doing. You talked about the next generation or inspiring young people to come to science. We heard from three Nobel laureates today who’ve spent their entire career in academics, science, and government. Today, young people have choices. They can go into technology, they can go to work for Apple, they can go to Google, and they don’t have to deal with the indentured servitude that we have and the complexity of a career in science. What can we do to keep these young people inspired and get them to commit to science, and what can we do to make it easier for them?
Dr. Sharpless: Yeah. Ellen, thank you for the question. This is a really tough problem and, as I said, something we think about a lot at the NCI. I think training is really the future of our field. And you’re right. You know, I think that the talented researchers, the people that could be great cancer researchers, they have a lot of options today. Data scientists, in particular, are really hunted to extinction. I mean, they’re so valuable to industry in so many different fields that, you know, retaining them in academia to work on cancer research can be quite hard. And, you know, we see things like the average age of the first R01 for an academic scientist is increasing, increasing, and people see that, and they say, “Why would I wanna go into this field?”
And so the NCI has been thinking, and thinking, and thinking, “What can we do to try and make a career in cancer science appealing?” And there’s some good news here. So, first off, cancer research is tremendously rewarding and inspiring, and it’s frankly fun. And so, I think, there are a lot of people that go into our field because they want to, because they’re passionate about it, and it’s this great mission. It’s just a lot more exciting than helping people find hotel rooms or, you know, a quicker Uber ride or something. So I think the appeal of cancer research is very strong.
Secondly, we have, you know, a bunch of innovative mechanisms to try and get to people at that stage in their career when they need support to the NCI. And so these are sort of awards that we often implement before their first sort of R01 large grant. And so these are sort of these K awards that are K12, and K99, and other forms of awards that have been quite successful. We’ve recently, for example, reduced the percent of effort that surgeons need to take on these kinds of awards so that we can continue to attract surgeons to our field and certain other specialties. We’ve created a new award to try and bring in postdocs with a little less experience because that’s what data scientists and health services researchers tend to do, short of postdocs. And so we wanna have an award for those types of individuals. But, most importantly, I really think a real key to this is paylines, that if an 8% success rate for an R01 is very, very negative for a junior scientist, and they will see that, and they will decide to go elsewhere.
And so supporting paylines and increasing paylines, which in 2021 were all the way up to 11%. So we were very pleased to get them up from a nadir of 8 to 11, but we still have more to go. The goal of the NCI, as I’ve said many times, is the 15th percentile by 2025, and I think this audience will know why we have to do it so gradually because they out your cost of grants. But, you know, at that kind of number, remember, we also give a bonus to early-stage investigators. So ESIs get 5% on top of that. So I’d say, 11th percentile last year, they would be at 16th percentile, which is a much more somewhat easier-to-look-at payline and gives one more enthusiasm.
As you know, we do not have a budget for 2022. The appropriation from this year’s Congress to support the NCI will be critical to how well we can continue to support the external research community, and it will allow us to set those paylines. But I think that that’s a really critical issue, is that as long as this is a rewarding field, people will come to it as long as it looks like it’s possible. And to do that, we need to make the path, the independent research career as easy and as smooth as possible. With that, I will wrap up and thank you all for allowing me to speak. And, again, good to see you all at least virtually.
Dr. von Eschenbach: Thank you, Dr. Sharpless.