Public Funding of Biomedical Research: A Hematologist’s Education

My family tells me I have wanted to be a doctor since I was two years old. I had wonderful family role models — my grandfather and my great-aunt were pediatricians, and an uncle was an oncologist. In college, however, I was encouraged to get a PhD degree instead, reflecting both the favorable state of basic science research funding in the 1960s and the bias against women in medicine. I saw the transformation of academia as an undergraduate, being in one of the first Radcliffe classes to get Harvard degrees — arriving when there were strict curfews for women and the school functioned in loco parentis and leaving when all the rules were honored only in the breach. Two years in graduate school reinforced my commitment to medicine; inspirational teachers including Dr. Bill Zinkham at Hopkins set me on a path to academia; Dr. Jane Desforges and Dr. David Nathan were the chemoattractants to hematology; and Dr. Tom Stossel cemented my interest in nonmalignant hematology.

Moving to Cleveland, my lab at Case was the only regional facility studying neutrophils. This fortuitous situation positioned us to receive, from colleagues from a large swath of the Midwest, blood samples from patients with suspected disorders of granulocyte function. Consequently, we were able to characterize, more than 30 years ago, leukocyte adhesion deficiency as a defect in complement recognition. We described the first functional defect in the neutrophil oxidase causing chronic granulomatous disease, confirming NADPH as the preferred electron donor, and eventually characterizing the defect in 47pHox. Most recently, working with Dr. Ed Plow, we described a defect in Kindlin-3 as a severe form of leukocyte adhesion deficiency. As my administrative responsibilities increased, I moved out of the lab and on to clinical research on sickle cell disease, hemophilia, and pediatric oncology. Teaching, taking care of patients, and interacting with my outstanding team was an endless pleasure.

Working in the changing world of academic medicine, however, became increasingly unpleasant. The extent to which managed care prevented rather than facilitated the good practice of medicine, the limited vision of hospital leaders, and the lack of institutional commitment to academic pursuits all made day-to-day work less fun. Serving on NIH study sections felt like an exercise in futility — no matter how we scored the applications, only a fraction of those deserving would be funded. I thought it was bad in the 1980s and 1990s; it is infinitely worse today.

So after a quarter of a century on the faculty of a fine medical school, hospital, and cancer center, I decided there must be more to life than having tenure. It was also clear that the ability of dedicated faculty to fulfill their teaching, research, and service missions was being undermined by institutional pathologies. So I took a deep breath and went over to the dark side of administration. I spent three years as a university vice president, dealing with governance and financial issues. It was there that I received experience on a larger scale so that I could appreciate how complex institutions work; grasp the importance of clarity of purpose and accurate, meaningful data; and understand the crucial role that honest, committed leaders with integrity play in the success (and failure) of large enterprises.

I arrived at NIH not knowing that it was my destination, only that there were important things going on. I knew that the $3 billion annual budget at the National Heart, Lung, and Blood Institute (NHLBI) could accomplish much, if not enough; that while my immediate impact might be small, the sphere of influence would be much larger than I had experienced previously; and that it would be fun and a privilege to work with Dr. Betsy Nabel. All those things proved to be true. We embarked on modernizing and updating multiple aspects of how the institute was organized and doing business. We put in place actionable reviews of what we were doing and adjusted resource investments to ensure relevant outcomes. We also worked to increase the breadth and depth of our network of advisors so that we were skating to where the puck was going. As an example, this strategy led us to take advantage of opportunities that our large, well-phenotyped cohort of colleagues offered during the rapid expansion of research in genomic science. All of these initiatives were difficult, took a long time to accomplish, and had winners and losers. Some remain as ongoing projects now under the stewardship of Dr. Gary Gibbons.

NIH is a wonderful place to work. The majority of the nearly 1,000 staff members at the NHLBI are mission-driven and committed to the science they support or conduct. The accomplished intramural scientists and the amazing work done by the extramural scientists that the Institute supports are sources of immense pride and enthusiasm.

My eight-and-a-half years as Deputy Director of NHLBI included nearly three years as Acting Director and a two-month stint as Acting Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. During this time, I had abundant opportunity to observe the difficulties and challenges of managing large bureaucratic institutions. Chief among these are leading any kind of change; communicating across organizational boundaries (and often within them); addressing complex political issues, made more difficult by contemporary US politics; and trying to make wise investments with both too few resources and highly imperfect mechanisms for setting priorities in rapidly moving fields of science. Creativity requires the time to think and the opportunity to take risks and fail — never easy, but increasingly difficult for all of us.

Many of the structures at the NIH originated early in the careers of people who have spent their professional lives there, and they persist with relatively few adaptive changes. The end of the draft in 1973 dramatically affected recruitment and retention in the intramural program — no one now comes to NIH as a military obligation. The NIH Clinical Center, an amazing 220-bed research hospital, is unique in the world but has grown without adapting fiscally or organizationally to a U.S. health-care system that has been radically transformed. The end of mandatory retirement in higher education in 1994 has affected both the NIH intramural and extramural programs. As older investigators continue to work, we no longer have the zero-sum game in which retirement of one generation created opportunities for the next. Peer review today is not the peer review of 30 years ago; even if the system were perfect (which it is not), it is a very blunt instrument for establishing priorities among projects that are often quite different. It is inadequate as a sole or even primary tool for funding decisions, but we have not yet determined what other tools to use or how to use them. The impact of these trends is greatly increased by the unpredictable and declining resources available. The 30-percent decrease in spending power of the NIH appropriation over the past decade follows the NIH doubling, which subsequently led to unsustainable demand. The chronic failure of Congress to consistently pass a budget means that NIH institutes do not know how much will be available in any given year, forcing administrators to run almost continuously on a contingency treadmill, with the associated uncertainty leading to anxiety at best and mistrust at worst among grantees and grant applicants.

Several things were different at NIH compared with academic medicine. In academia, most of my ability to accomplish things derived from using influence and garnering outside resources. Although effective, the provincial nature of such institutions limits one’s sphere of influence. At NIH, I had authority, but all of it was delegated. Every time I went to Capitol Hill, I thought of the Tom Lehrer song about Hubert Humphrey: “Once a fiery liberal spirit, now when he speaks, he must clear it.” I wasn’t there as myself, but as a representative of NHLBI and NIH. But having the imprimatur of NIH and NHLBI also meant that decisions that were well-thought-out and justified could be implemented. Compared with academic medicine, at NIH both status and quality of life for many staff depend more on where you sit in the hierarchy of the institution. Priorities and institutional identity were clearer and more focused at NIH. Everyone there had a sense that the successes and failures of each reflected on all. This ethos was less common within the loosely coupled system of an academic medical center in which different components valued different things.

Several things are similar in the two settings. All of us tend to put more weight on input (how we expend energy and resources) than output (what we have actually accomplished). This myopic view of purpose obscures real achievement. In both settings, human beings tend to resist change and respond to the same incentives (money, power, status, praise) and disincentives (criticism, unreasonable or ill-conceived demands, and lack of respect). The most important decisions you will make in a leadership roles have to do with how you hire and manage your staff. Honesty, integrity, trust, and treating people with respect and decency are essential for long-term success. Even when this philosophy seems counterproductive for achieving short-term goals, applying it liberally makes it much easier to live with one’s self, and in the end, the good will that accrues will make the collaborative effort more productive and rewarding for all involved. In both settings, I dealt with many people who were suffering, sometimes because of and sometimes in spite of things I had done. There is no substitute for empathy.

What did I learn that members of ASH should know? The NIH manages the public investment in biomedical research. Democracy doesn’t mean that you always get what you want individually, but rather that your voice should be, and is, heard. Speak up, make your thoughts known to both the NIH and political leaders, and you will certainly have an impact. Submit the best applications you can. Talk to the NIH staff; they are honestly there to serve, and they get both personal satisfaction and reward from their leaders when they build strong relationships with investigators. Winston Churchill made two very wise observations to keep us going in difficult times:

“Democracy is the worst form of government, except for all those other forms that have been tried from time to time.”

“You can always count on Americans to do the right thing — after they've tried everything else.”