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Q&A With Scientific Director Dr. Larry Norton

By BCRF | July 8, 2014

BCRF sat down with Dr. Larry Norton to discuss his current work and interest in breast cancer research. Read on to learn more.


Q: Tell us about yourself as a scientist and how you became interested in breast cancer research.

A: What attracted me to science in the first place was that it seemed capable of attacking big problems, the kinds that affected a lot of people. Among these, cancer seemed a good place on which to focus my life and energies. But once I made this decision I had to make another choice: Would I focus on a narrow topic (which the academic reward system favors) or a broad approach, which engenders considerable risk regarding an academic career? I wanted to try to cure cancer any way I could, so I took the riskier path.

Accordingly, for graduate school I chose to earn a medical degree rather than a PhD in science. This was not easy for me because I regarded (and still regard) the accumulation of knowledge through unfettered scientific discovery one of humanity’s most commendable goals. But I also felt compelled to try to help people through hands-on medicine. A combined degree, an MD-PhD, would have been optimal, but my local draft board precluded that – they would not have given me a draft exemption during the Vietnam War had I pursued a PhD after I had finished my medical training.

In the 1970s, in the second year of my fellowship in medical oncology at the National Cancer Institute, I had the opportunity to do laboratory work in viruses and cancer, which was then and remains a hot topic. However, with my colleague Richard Simon I had already made some interesting observations about the mathematics of cancer growth, observations with clinical implications that just begged for testing in clinical trials. I knew that to get these ideas tested I would have to earn the trust of the cancer clinical trials community, largely hands-on physicians, which means I would have to pursue that path even though laboratory-based science offered more academic rewards. For example, very few clinical trialists or theoretical biomathematicians get elected to the National Academies! Nevertheless, I was compelled to try to test our ideas in the clinic.

The very first implication of our work was that for cancer-killing drugs to work optimally they should be given often at a “right” moderate dose level rather than at a high “maximum tolerated dosage.” This new approach, using moderate dose levels frequently, was later termed “dose density.” It is an approach designed mathematically to maximize the killing of cancer cells while minimizing side effects. It took about two decades to get the idea into a clinical trial and another five years thereafter to show that the idea worked! But now it is widely applied, in breast cancer and many other cancer types.

Over the years I have been involved in many research topics, including the identification of inherited genetic abnormalities that predispose people to cancer, the development of new drugs such as monoclonal antibodies that target growth factor receptors, vaccines, and most recently, with my colleague Joan Massague, a self-seeding concept of how tumors grow and spread. This latter work actually explains the mathematical basis for dose-dense anti-cancer therapy and has many other implications for further research and, we hope, clinical applications.

My decision to “cure cancer anyway I could” has guided all of my career decisions. It has led me to become a physician, a mathematical scientist, a research administrator, a teacher, a mentor, a fundraiser, and now the medical director of a wonderful health facility. I wake up every morning and ask the question, “How can I make further progress today?” and pray that some good will come from it.

Q: Did you ever seriously consider another kind of career than that of the sciences?

A: I think that biomedical science was always in picture, even when it was obscured by other loves. For example, I love music and think the making of music with other musicians, especially before a live audience, is one of life’s greatest pleasures. Frankly there is no substitute for that experience on an emotional level. But I made the decision early on follow my current path, and I am not sorry (most of the time).

Q: What advice would you give to young physician-researchers?

A: It depends on how young they are. I would say to the youngest students that they should think about studying neuroscience rather than cancer because cancer will be licked by the time they are ready to do their mature work. Neurodegenerative diseases will be the next big problem to solve after infectious diseases and cancer are controlled. And in all of these areas, prevention is the name of the game, although therapeutic advances are a step in that direction. To medical students interested in clinical work I say that they should spend some time doing formal laboratory research to enhance their personal development and professional growth. Still, we need great clinicians and clinical trialists as well as great laboratory-based researchers, and I hope the academic system will learn to reward such career choices.

Q: How close are we to preventing and curing all forms of breast cancer?

A: That is a question that is on every person’s mind. We have made massive strides in curing cancer, and have realized many improvements in the areas of diagnostics (such as the use of MRI) and breast conservation surgery. When The Breast Cancer Research Foundation began 16 years ago, we started our sentences with “If we cure cancer…” Today it is not “if” but “When we cure cancer…” Everyone knows breast cancer will be eliminated and our goal is to make it happen as rapidly as possible.

Q: You have directed BCRF’s activities since its beginnings. How has the BCRF grant program expanded over the years?

A: I think “directed” is too strong a word. The key concept of BCRF is collaboration, involving leadership, supporters, scientists, physicians… indeed the whole community. We have grown because we are all part of the whole great mission that is greater than the sum of its parts. When, in 1992, Evelyn Lauder initially helped raise funds for the construction of the Evelyn H. Lauder Breast Center at Memorial Sloan- Kettering Cancer Center we knew we were developing an idea, not just a physical space. We wanted to put the patient in the middle of a circle of specialists rather than have the patient shuttle between specialists. This was a novel idea at the time. But what was missing was putting all the specialists together in their academic time – which we have fixed in our new Evelyn H. Lauder Breast Center, by the way. By extension, we realized that to make progress faster we needed to connect many great researchers together in a “virtual” space. That is where the idea for BCRF was born.

Back then, there was some – never enough – money available to support basic science and clinical trials, but very little to support the connection between laboratory science and clinical research. There was no organization dedicated primarily to fostering the development of creative ideas and collaborations that would help translate what we learned in the laboratory into the better management of breast diseases in the clinic.

For these reasons The Breast Cancer Research Foundation began in 1993 with the goal of serving two basic needs: translational science and networking among researchers. What started as Evelyn hosting an intimate dinner in her home to raise money to support these goals has evolved into an organization that not only realizes grants for like-minded investigators all over the country and the world, but one that influences other grant-giving philanthropic organizations to do the same.

Q: How has BCRF impacted breast cancer research?

A: The Breast Cancer Research Foundation has already had a significant impact, in ways specific and more general. Specifically, the research it has supported has improved all aspects of breast cancer management, from prevention to diagnosis to prognostication to therapy to wellness after therapy is completed. These achievements are documented, in part, on the BCRF website. In addition – and in the long run maybe more significant – is the fact that we have reinvented how biomedical research should be supported. We do not solicit competitive grant applications – although we applaud those other institutions that do, since this is a very important part of the mix. Instead, we search out great scientists, relative beginners and established ones as well, who are accomplished and creative and want to help solve the cancer problem. We support people, not projects, although – of course – we assess and monitor progress as these researchers work in imaginative directions. Once preliminary data are accumulated these same researchers are encouraged to attract further financial support from more conventional sources. We have had great success employing this method.

In addition, we encourage collaboration, cooperation, and networking, all aspects of creating a community of scholars interested in making progress faster by working together. Scientists do want to work together, but they need a structure within which to accomplish this most efficiently. To this end we have pioneered a Web portal to encourage the exchange of ideas, materials, and information. We also host a think tank every year with focus groups from which we expect action items to arise. The creativity of this activity has been amazing.

Great science is a creative art. So the most important characteristic of BCRF is the priority it puts on creative thinking and on giving investigators the freedom they need to explore new ideas. One way we accomplish the latter task is by funding cooperative groups and hospital consortia working together to carry out translational research.

For example, in 2005 BCRF founded the Translational Breast Cancer Research Consortium (TBCRC), which is now supported in partnership with other organizations. The TBCRC unites the efforts of fourteen leading breast cancer research centers in the United States. This group designs and conducts high-technology, usually multidisciplinary clinical trials that incorporate sophisticated laboratory investigations. The focus is on making progress against breast cancer, using the tools of modern biological science as its weapon.

BCRF also partners with other organizations such as the American Society for Clinical Oncology (ASCO) Foundation and the American Association of Cancer Research (AACR) to give grants to investigators to conduct promising translational breast cancer research.

Following the core principles of BCRF, we do not limit our support to the borders of the United States. By 2009 the BCRF had expanded its research funding to 28 countries on six continents. Just as breast cancer is a global problem, so must the solution involve global cooperation and collaboration.

Q: What challenges lay ahead for BCRF?

A: I am confident that we are moving in the right direction, but I am never happy with the speed of progress. We have an ethical obligation to move forward faster. One thing we need to do to maximize our rate of progress is to keep identifying the new ideas and new people who offer great promise. This takes a lot of work, a lot of time, a lot of travel, but the rewards are great too. And we have to continue, indeed expand, our ability to support not just the development of the new ideas, but the connections between them. If you want to hear the sound of a ringing bell, you need not just the bell and a hammer, but the means to have the hammer strike the bell: The goal is the interac- tion between the elements.

Q: Much has been accomplished but more needs to be done to eradicate and ultimately prevent breast cancer altogether. What is stopping us from reaching that goal?

A: Most people do not really know how underfunded we are in cancer research and education. We are talking about a set of diseases that will afflict up to a half of all Americans, and affect 100% of us indirectly if not directly. Yet if one puts together all sources of support for making progress – everything spent by government and industry and private donors put together – it accounts for less than 69 cents per American per week. As a nation, this is less than one-sixth of what we spend on soft drinks! Hence, to make progress faster, to save our own lives as well as the lives of our loved ones, what we need is not massive sacrifice but mass commitment. By connecting that commitment with high quality creative research we can eradicate breast cancer and all cancers in real time. We see the light at the end of the tunnel, which means it is a straight shot: Let us get there as fast as our commitment allows.

Read more about Dr. Norton’s current research project funded by BCRF.