The Extraordinary Challenges and Opportunities Facing Cancer Research
The following is an abridged version of the remarks delivered by NCI Director Dr. John E. Niederhuber on Monday, April 20, at the 100th Annual Meeting of the American Association for Cancer Research in Denver.
We come together at a time that is truly like no other. The United States, and in fact the world, is struggling to right a financial system in turmoil, and far, far too many of our fellow citizens are unemployed or underemployed. The number of those around us who lack health insurance may now have reached 50 million. Even comparatively wealthy communities in the United States are struggling to support those in need. In Montgomery County, MD, for example, the home of NIH, food stamp requests have grown 16 percent since last year. All of the family shelter beds are full, and more than 50 additional families are currently housed in motels.
All of us gathered here are more than aware that science has not been immune to these economic hard times. Scientists everywhere have felt the strain of NCI budgets that, for 4 years, have received no increase. You have felt the strain of the upfront downward negotiation of your grants, on average 17 to 21 percent. As a result, I regularly hear from investigators who have had to decrease the scope of their studies, let a lab technician go, or were unable to add or replace a post-doctoral student. We have all worried that the pace of cancer research will suffer and that biomedical research will no longer attract the best and the brightest. These deep concerns have echoed from university laboratories to the offices of deans and university presidents to my office and to those of our elected officials, as well.
But, as surely as we live in an economically troubled time, we also come here today at a moment of extraordinary scientific opportunity.
On February 17, just over 2 months ago and right here in Denver, President Obama signed into law a sweeping economic recovery plan. The $787 billion bill is called the American Recovery and Reinvestment Act. This legislation is about employment; about creating and preserving jobs and righting the American economy. But it is about more than just that. When he signed the stimulus act into law, President Obama said: “I hope this investment will ignite our imagination once more, spurring new discoveries and breakthroughs in science, in medicine, in energy, to make our economy stronger and our nation more secure and our planet safer for our children.” The President clearly recognizes that the future of our country and the stability of its economy will depend on the creation of new knowledge, of new technologies, of imaginations unleashed.
This is no small challenge. Yet, it strikes at the very heart of what we do as scientists. We are fortunate to work every day toward a collective goal that cancer will not be the feared diagnosis it is today. We are, I believe, on the threshold of altering the course of this disease for millions of patients, young and old alike. And I believe that in this hall, on this day, at this hour, we have the opportunity to tell President Obama that we are listening, and that we will wholeheartedly take up his call.
Yesterday, we heard from another stalwart supporter of cancer research, Senator Arlen Specter. Senator Specter believes deeply in the power of biomedical science, with a passion grounded in personal experience. His efforts helped make certain that the economic stimulus legislation included funds for research dedicated to curing human diseases. As a result, the stimulus package provides $10.4 billion to the National Institutes of Health, of which $1.3 billion goes to the National Cancer Institute during the 2-year span of 2009 and 2010.
During hearings and other meetings on Capitol Hill, Senator Specter and many of his colleagues often ask questions that begin with: “What will it take…” What will it take, they ask, to accelerate the downward curve of cancer death rates? What will it take to make certain that today’s laboratory progress will become tomorrow’s clinical successes?
The questions posed to us by Senator Specter and his colleagues are the same questions we see in the eyes of our patients. These are questions we at NCI have not taken lightly, and the answers are far from easy. The bottom line is that NCI is committed to the core belief that how we spend all of the resources we are granted, how we strive for comprehensive plans and strategies must, by their boldness and vision, provide answers that ultimately change the course of the diseases we call cancer; not one disease, but hundreds of diseases. The people rightfully expect us to do no less.
So today I want to share with you the ways the National Cancer Institute—your National Cancer Institute—is taking up the call: how we have more than just a vision; how we have developed a coordinated action plan to move cancer research forward in innovative ways.
When it became clear that economic stimulus funds would be coming to NCI, we began to carefully consider where $1.3 billion in new resources could do the most good; where the demand was greatest; where our knowledge of the biology of cancer and new technology were leading us. Given that the American Recovery and Reinvestment Act is a once-in-a-lifetime opportunity, we also thought long and hard about what Americans want from all of us. We came back repeatedly in these discussions to the conclusion that they want better ways to prevent cancer; they want the earliest diagnosis; and they want new therapies with fewer side effects that turn cancer into a condition you can live with and not die from.
Economic stimulus funds give us the chance to be visionary; to make strides today toward realizing the promise of personalized medicine; to enhance the process of drug development from target identification to translation into viable therapies; to move cancer research from the accumulation of scientifically exciting genomic data to a new way of approaching prevention, diagnosis, and therapy and to ensure access to our latest science for all.
My friends, this is not a time to be timid in our vision. By our vision and our creative actions, we must demonstrate that NCI is worthy of sustained, increased support for years to come. NCI needs to lead with a clear direction that will hasten the pace of cancer research.
The groundswell of interest in what we are doing with our Institute’s share of economic stimulus funds comes in concert with an increase in our appropriated budget of about 3 percent. It is extremely important that I clarify how stimulus funds and appropriated funds must not be mixed. Each must be accounted for separately. NCI must maintain separate account numbers and accounting procedures, and there are different rules in many cases for what can be funded from which pot of money. We sometimes joke that some of these dollars are green and others purple, so that they cannot be comingled. We must optimally use the purple stimulus dollars to maximize the use of our green appropriated dollars. Above all, we must always strive to fund our best science.
President Obama also made it eminently clear that the economic stimulus plan “will be implemented with an unprecedented level of transparency and accountability.” On the day he signed it, the president also said: “And we expect you, the American people, to hold us accountable for the results.” That is an admonition all of us take most seriously. Indeed, recipients of the stimulus funds will also have some stringent requirements, particularly around reporting on your stewardship of these dollars.
A week ago, our first package of stimulus grant funding plans moved out of NCI, to go through a final administrative approval process. As the availability of funds nears, I am now able to offer you some broad highlights.
NCI’s planning is grounded in the respect of the individual investigators who are at the very heart of scientific discovery and who embody a tradition that dates back many years, before there was an NCI or an AACR; of investigator-initiated scientific excellence and groundbreaking discovery. For you, NCI’s support will not waver.
Because of that commitment, NCI is taking a series of steps to increase our support for Research Project Grants (RPG), particularly the investigator-initiated R01. I am well aware of the importance, both practically and symbolically, of the NCI payline—the line of demarcation between grants that are funded and not funded, based solely on peer review. For the 2009 fiscal year, I am proud to tell you the RPG payline will be rising considerably.
Using our increased fiscal 2009 appropriation, NCI has raised the payline from last year’s 12th percentile to the 16th percentile. Funding grants that were meritoriously reviewed but fell outside of last year’s payline is an important first step. As you well know, these are not simply science projects. They are laboratories that employ technicians and other highly skilled workers. They are places where experienced investigators work to develop doctoral students and fellows into the next generation of laboratory and clinical scientists.
In fact, a 2008 NIH study indicated that on average, every NIH grant supports six to seven full-time or part-time scientific jobs. And those jobs are estimated to be magnified threefold in their economic effect on local communities, thanks to the goods and services purchased by scientists and technicians.
But NCI’s payline increases do not end at the 16th percentile. Through coordinated but separate administrations of stimulus and appropriated funds, NCI will, like many of its fellow NIH institutes and centers, raise the payline to the 25th percentile. We will utilize a combination of 2-year and 4-year grants, with concurrent increases in the grant payline for young, first-time investigators. While the numbers are not yet firm, it is clear that there will be a marked increase in the number of principal investigators studying cancer.
The economic stimulus package conveys 2 years of funding, which in laboratory science is a relatively short amount of time. For just that reason, it falls to NCI to carefully calculate and thoughtfully assume the risks of initially funding some 4-year grants with economic stimulus money, knowing that we will need to find additional resources for the out years. I believe it falls, as well, to our grantees to come forward with only their strongest science.
Within the hopeful and helpful news of greater funding of grants, we must also note the President’s call to “ignite our imagination.” We must not simply see the economic stimulus package as more dollars toward “business as usual.” We must look to new ideas, new methods, new areas of cooperation and collaboration, none more important, I suggest to you, than fostering the next generation of cancer science and cancer scientists. NCI has a plan to fund early stage investigators who are physician scientists and Ph.D.s, who are committed to careers in translational cancer research. These start-up packages will assist young faculty members in establishing laboratories; in creating a foundation for a career of excellence. A parallel program will be available to investigators at the NCI-designated cancer centers and at institutions funded through the Minority Institution/Cancer Center Partnership program.
We are surrounded today by transforming technologies that are changing the nature of diagnosis, of prevention, of early detection. As Eric Lander so eloquently reminded us yesterday, the day of the $1,000 genome is no longer a futurist’s provocative prediction. Dr. Lander predicted that complete cancer genome analysis could be routine in laboratory research in 5 years and in patient care in 10 years.
And that will necessitate some changes; a rebalancing, if you will, in the way we at our respective universities conduct the science of the future and translate that science to our patients.
NCI has outlined signature projects—areas of investigation that are uniquely positioned to accelerate discovery in a short number of years. Among NCI’s signature projects, I am proud to announce here today three key initiatives that hold important promise to unlocking cancer’s genetically driven pathways and move them forward to first-in-man-studies. The nature of much of this work will be focused, team science.
In 2006, NCI and the National Human Genome Research Institute initiated a pilot project designed to accelerate our understanding of the molecular basis of cancer through the application of high-throughput genome analysis technologies. Three years later, The Cancer Genome Atlas, or TCGA, as it is better known, has established characterization and sequencing centers, along with programs in data management, bioinformatics, and computational analysis. To date, TCGA has sequenced more than 200 tumors in glioblastoma, along with lung and ovarian cancers. Already in glioblastoma TCGA has identified three genes not previously associated with this deadly cancer and delineated as many as four subtypes of glioblastoma. With that foundation of success, we plan to move TCGA forward with a goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types.
In addition, during the past year, NCI has also begun a program in pediatric cancer genomics. TARGET, which stands for Therapeutically Applicable Research to Generate Effective Treatments, will apply next-generation sequencing to at least 100 tumor specimens per childhood cancer.
Programs like TCGA and TARGET, along with numerous other whole-genome association studies using large population cohorts to assess germline risk, are generating a mountain of data and revealing potential genetic defects that occur within cancer. While scientifically fascinating and intellectually groundbreaking, these data primarily remain raw information that must be developed into knowledge of causal pathways and functional biology. Based on an intimate understanding of these pathways through the development of new probes and new assays of biologic function, we will convert what is today considered “un-druggable” into functional pathways with clearly defined targets for manipulating those pathways.
Moving from data to function to target to therapy will not be simple, nor will it be easy or inexpensive. But NCI is firmly committed to using today’s opportunities to design and construct a personalized cancer care drug development platform, which is the second of NCI’s signature initiatives.
At the beginning of the platform will be functional biology centers: A virtual network of investigators who will take promising genetic alterations identified in TCGA and answer specific questions about biologic function and potential druggable targets. High-throughput screening will follow, using appropriate assays that compare vast libraries of compounds to newly defined targets.
Another network, the Chemical Biology Consortium, will provide the necessary chemistry and chemists to accelerate the discovery and development of new anticancer agents, which NCI will be able to have produced and moved into preclinical testing and toxicology.
In addition, NCI is taking steps to create the first of a small national network of patient characterization centers. Always employing the latest technologies, these facilities will serve wide geographic areas, bringing together genomics and genetics, proteins and proteomics, all in the interest of matching a genetically characterized patient and his or her characterized tumor to appropriate and optimal therapeutic solutions.
Creating an integrated, 21st-century translational science program will require data integration and a reinvigorated push for the cancer electronic health record, managed through NCI’s cancer Biomedical Informatics Grid, better known as caBIG, and its companion BIG Health consortium. This will create, for translational research, a national cohort of highly defined cancer patients to match to experimental protocols.
To accomplish both the scale-up of TCGA and the genetic characterization of our patients, we will require state-of-the-art biospecimens collected using standardized protocols, tissue characterization, cataloging, and analysis, through NCI’s caHUB program.
The NIH Clinical Center, NCI’s SPORE program, the NCI Community Cancer Centers Program, Cooperative Groups, CCOPs, and NCI-designated Cancer Centers network will all be key players in establishing a highly characterized national cohort of patients who can be easily matched with potential new agents.
This wide-ranging plan will require the contributions of biologists, chemists, informaticians, and clinical scientists who are devoted to a clear path from discovery to patient. That is not only the nature of translation; I believe it will be a model for the study of many diseases and, ultimately, a model of 21st-century health care, when we are able to match pharmacogenomically characterized patients and molecularly profiled tumor types to highly-specific, molecularly-targeted therapies.
This platform is a vision for a new way of thinking. But it is not an unrealistic concept. It is an action plan, a blueprint for what we are beginning to assemble this year, making the optimal use of every new resource. It is a blueprint for 21st-century translation.
Hand in hand with the effort to develop a platform for personalized medicine, we need to develop an improved clinical trials system, to better accommodate the validation of highly targeted therapies and to accurately assess the targeting of those therapies in patients in real time. The challenge in translation is optimally matching the tumor and therapeutic recipe. As we move forward this will be the pattern of treatment for all malignancies.
NCI’s third signature initiative is one that is personally extremely exciting and I daresay another bold answer to the President’s challenge to expand the boundaries of science. Over a year ago now, NCI commenced a series of workshops that began to bring aspects of the physical sciences to the problem of cancer. We discussed how physical laws governing short-range and other forces, energy flows, gradients, mechanics, and thermodynamics affect cancer, and how the theories of Darwinian and somatic evolution can better help us understand and control cancer.
From those meetings has come an idea that is soon to become a network of NCI-supported physical sciences-oncology centers. Working closely with the cancer research community, these centers will foster a team science environment that incubates and tests novel cancer concepts by studying and sometimes challenging accepted scientific dogma. These centers will, I believe, be proof yet again that approaching a difficult scientific problem from a new perspective can advance all research. These new centers will interface exceptionally well with our very successful centers in nanobiology, proteomics, and systems biology.
Cancer is, after all, an old problem, and it is the nature of science to move judiciously and incrementally. Today’s pace of discovery regarding the genetic basis of disease is unfolding at a rate never before envisioned. Even so, we must be mindful that our task is far from complete. Patients still need answers. Patients still need better treatments, better prevention, and better early detection. We must recommit ourselves to answering that call.
We have many challenges ahead, many discoveries still to be made. We would be wise to follow George Bernard Shaw’s admonition that “science becomes dangerous only when it imagines that it has reached its goal.” My friends, cancer will long be with us. We are undoubtedly moving toward the day when cancers will be diagnosed early and controlled. We will not rest until we have constructed molecular and genetic methods of cancer prevention. We will not rest until we have well and thoroughly prepared those who will take up the fight after we are done.
One of the great Americans to whom all of the National Institutes of Health owe many great debts is Mary Lasker.
Mrs. Lasker was a steadfast friend of cancer research and research funding; she was a prime advocate of the National Cancer Act of 1971. Several NIH institutes exist today because of her efforts. But consider, if you will, one of Mary Lasker’s simplest yet stunning achievements: In the years after World War II, she convinced broadcasting pioneer David Sarnoff that his powerhouse company, the Radio Company of America, RCA, could allow the utterance of a single word: cancer.
Although now the word cancer is part of everyday conversation, can any of us say cancer causes less fear today than it did 50 or 100 years ago? Our collective foe remains a frightful one. I would venture that everyone in this room knows in some very personal way the heartache cancer brings. Losing my wife and best friend to breast cancer 7 years ago certainly brought it home to me, and it does so every day.
Because cancer remains such a feared condition, I believe the demand from the leaders of our country and the American people will intensify in the years ahead; a demand for there to be changes in the way we approach the conduct of science; changes in the way the outstanding science that springs from our laboratories is translated, rapidly and safely, into improved health for our patients.
The American Reinvestment and Recovery Act is a chance to enhance and to change cancer science. The world is watching, waiting to see what we make of it. I know that you will firmly grasp its every opportunity. Thank you for being here this morning and for listening to my thoughts on our exciting future.
Dr. John E. Niederhuber
Director, National Cancer Institute