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Going the Distance: Setbacks and a Meaningful Career in Science

Allison Webel, PhD

On July 4th, me and 60,000 of my closest friends ran in the 50th Peachtree Road Race in Atlanta, Georgia. This was my first 10K run and as a relatively new runner, my inclination for training for this race was to go hard and go fast – a manta not just for running but possibly for my entire generation. But as I would eventually learn, distance running is not about just getting it done. It is about being patient, listening to (and adjusting) my body, and having a long-term mindset focused on the process as much as the goal.

nih rejectionsThroughout my training, I was struck by how similar distance running is to a career in science and to grant writing in particular. When I finished my PhD 10 years ago, I was confident in my ability to write manuscripts and proposals, secure funding, and ultimately do and disseminate the science that would leave a lasting impact on the health of vulnerable populations. This confidence continued even when, during the last few years of my K award, I submitted grant after grant to the NIH only to have them be not discussed repeatedly.  I understood that NIH success rates were low, with institutes reporting a range of success rates from ~10% to 35% in 2018. Mentors reminded me that failure was part of the process and that everyone has a string of not discussed grants in the early phase of their career. I just needed to keep listening to the reviewers, getting more preliminary data, refining my ideas, developing great teams, and above all writing, and eventually my ideas would hit. However, when my string of not discussed/not funded grants grew to 15 (Figure 1), each set of pink sheets more soul crushing than the last, I knew that statistically I was failing more than I should. And I questioned if I should even be in science or if these past few years were just wasted time.

These setbacks can be devastating – causing approximately 10-15% of early career scientists to leave the field. But what about those who stick it out? What happens to them and, more importantly, what is their long-term impact on science? These are the questions explored in a recent article by Yang Wang, Benjamin Joes, and Dashun Wang, “Early-Career Setbacks and Future Career Impact”. Through a series of pretty cool analyses they examined if early success in obtaining an R01 award from the National Institutes of Health led to more success and a higher impact (measured as highly-cited manuscripts) compared to those who almost, but just missed the funding threshold. Essentially, they wanted to figure out among early career health scientists which perspective is true: Do the “the rich get richer” or will “what doesn’t kill you makes you stronger”?

Unsurprisingly, the results were somewhat mixed but encouraging for an early career scientist who has had many misses. While those with near misses had approximately a 10% chance of leaving the NIH funding system entirely over the next 10 years; of the scientists remaining, those who had an early career funding failure wrote higher impact manuscripts, compared to those who had early funding success. This is a striking finding which needs to be carefully considered (specifically that junior scientists do not need additional roadblocks in their path in order to become “stronger scientists”). Yet, the authors do suggest that for those scientists who persevere, “early failure should not be taken as a negative signal” rather viewed as a chance for refining and improving their program of research.

Wang and colleagues start their manuscript with a quote by Robert Lefkowitz, winner of the 2012 Nobel Prize in Chemistry, “Science is 99 percent failure, and that’s an optimist view.”  While he many have been referring to failed experiments, what Wang’s  new analysis reveals is that even the process of obtaining the funding to support research is likely to be fraught with heartbreaking setbacks. But if you’re in science because you believe in its power to answer important questions which will help us to better understand and improve the human condition, perseverance is necessary.

I finished my first 10K in under 60 minutes. Not a medal-winning time but I preserved through the heat, sun, fatigue, and even a bit of pain to cross the finish line. Similarly, late last year I received the Notice of Award for my first R01 from the NIH- leading a research study that I believe in with a team that inspires me every day.  So whether you are submitting your first or 15th research grant, know that setbacks are common and despite the outcome on any one application, with a long-term mindset you can have a lasting impact on science.
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The First Funded R01 Ever

Daniel Tyrrell, PhD

The first two extramural grants for a research project (the precursor to today’s R01) were given on March 21, 1938 to Dr. John Bittner at Jackson Laboratory (then, the Roscoe B. Jackson Memorial Laboratory) in Bar Harbor, Maine for his work on breast cancer1,2.

Bittner J. Mammary Tumors In Mice In Relation to Nursing. Cancer Research. 1937;30(3).

Bittner J. Mammary Tumors In Mice In Relation to Nursing. Cancer Research. 1937;30.

One grant for $3,200 was awarded directly to Dr. Bittner, and the other for $9,900 was awarded to the Roscoe B. Jackson Memorial Laboratory by the National Cancer Institute. These first “R01-type” awards were given by the NCI from 1938-1943, and in that time, 65 grants-in-aid were paid2.

Marshino O. Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943. JNCI: Journal of the National Cancer Institute. 1944:429-43.

Marshino O. Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943. JNCI: Journal of the National Cancer Institute. 1944:429-43.

In the early days of extramural grants in the USA through the 1970’s, most awards were Program Projects, Centers, and Development grants. The NIH preferred to grant awards for multidisciplinary centers to carry out a range of projects in a certain area of interest. It wasn’t until after Watergate and Nixon’s resignation that Investigator-Initiated Research Projects (R01) began to dominate large Program-Project grants (P01)3.

To understand the path from these first grants to today’s R01’s, it is important to understand the history of the NIH. The Hygienic Laboratory became the NIH in 1930 with the passage of the Ransdell Act, and the NCI began with the National Cancer Institute Act in 1937. The NCI could administer extramural grants for research on cancer, but the NIH at large could not3.

The federal government greatly increased research spending in medical research during World War II, and when the war was over, both the government and scientists wanted to continue federally funded research. The NIH couldn’t legally administer extramural grants until the passage of the Public Health Service Act in 1944 which consolidated the NCI and NIH under one roof under the Surgeon General.

In 1946 the Research Grants Office was created to administer extramural research grants and fellowships awards. Congressional funding of the NIH increased steadily, and all the while the NIH was adapting its branding by renaming institutions (i.e. changing “National Microbiological Institute” and “Experimental Biology and Medicine Institute” to flashier names like “National Institute of Arthritis and Metabolic Diseases” and “National Institute of Allergy and Infectious Diseases,” which further enticed congressional funding). From 1946 to 1953, the number of funded projects increased from 80 to 2,000 and the funds increased from $780,000 to over $20,500,0003.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

In 1946, the NIH Syphilis Study Section had its inaugural meeting. This was the first study section meeting at the NIH4. From this point, more and more study sections met to discuss the state of science and to review grant applications. In 1950, the standardization of study sections began with the assignment of priority scores from 1 to 5. This made it possible to rank grants based on merit for funding.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

These changes lessened the workload of study sections initially, but as research design became more sophisticated, more and more of the meeting time was devoted to project discussions3. Eventually, some within the research community became dissatisfied with the closed-door process of grant review. In 1973, the Office of Management and Budget called for the abolishment of study sections, but the acting NIH Director, Dr. John Sherman, defended peer review as the highest priority.

Political events at the time caused turmoil within the NIH. A combination of budget constraints due to the war in Vietnam along with Watergate and procedural confusion and secrecy regarding the peer review process led to a reorganization at NIH. A familiar name, Ruth Kirschstein, director of the NIGMS in 1974, stated, “How can a system, devised in an era of elitism, of secrecy, and of economic growth…be adopted to an era in which stress in on equal opportunity, openness, and limited availability of funds?”3.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.

There was rampant favoritism and bias in the review process, and over the next decade, the NIH worked to standardize peer review practices. This included extending project length beyond 3 years in 1984, scoring grants by percentiles in 1987. In the late 1980’s and through the 1990’s, grant applications could be submitted on discs rather than paper and a centralized database of applications was developed.

While the first grant application wasn’t submitted electronically using the PHS-398 form, it was the first time an NIH institute, the NCI, funded an extramural grant for an individual research project, which we now refer to as an R01.

 

References:

  1. Bittner J. Mammary Tumors In Mice In Relation to Nursing. Cancer Research. 1937;30(3).
  2. Marshino O. Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943. JNCI: Journal of the National Cancer Institute. 1944:429-43.
  3. Mandel R. A Half Century of Peer Review, 1946-1996: Division of Research Grants, National Institutes of Health. Division of Research Grants, National Institutes of Health; 1996.
  4. Pederson T. The “study” role of past National Institutes of Health study sections. Mol Biol Cell. 2012;23(17):3281-4.

 
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Funding the Business of Science: Strategies for Early Career Scientists

Allison Webel, PhD

During my graduate training, I learned how to write research proposals and manuscript, battle with the IRB, collect and analyze data, present my research in various settings, and handle regular (sometimes daily) rejection like a champ. I received excellent training from mentors who will always be my giants. However, as I have progressed through the early stages of my academic career, I have come to realize there are so many things about being an academic scientist that I never learned in graduate school.

The first thing is that, while science is (sometimes) a noble pursuit of generating new knowledge that will advance the human condition, it is also a business. I’ve never started a business nor have I considered myself entrepreneurial, but I believe in order to have a viable business model, one needs money to turn a great idea into something someone will pay for. It turns out that entrepreneurs and scientists have that common – this is why I was excited to attend the early career session on Sunday morning humorously titled, “WTF: Where’s the Funding?”

Even before we graduate with what we all hope is our terminal degree, we are primed by the academic enterprise to fund our work, and ultimately ourselves. For most of us it’s written into our first contracts. But after the glow of actually having a paying job wears off, we are left to agonize over the question, “How do we break into a system that is seemingly impenetrable to newcomers?” This was the very question this session addressed in an early career panel covering governmental, foundation, and industry-supported funding for early career scientists.

The panel started out acknowledging that the goal of every early stage investigator is R-level NIH funding, with its generous indirects and fabled prestige; however, it can be difficult for most of us to achieve this goal soon after completing our training. Against that backdrop this frank panel discussed how to  navigate two alternative funding sources industry funding and foundation funding. Jarett Barry, MD of UT Southwestern summarized these opportunities as “I think of industry, and even American Heart Association [foundation] funding as a pop off valve– a strategy used to complement traditional funding.” For many of us, a pop off valve is exactly what we need to keep our science going during the early, lean years. Further, these types of funding streams can help establish us as experts in our field and provide data needed to publish good papers and serve as preliminary data in future grants.

However, industry and foundation grants are not without their downsides. The panel agreed with Majken Jensen, PhD of the Harvard T.H. Chan School of Public Health, who said these grants are often smaller than federal grants, tend to favor academic celebrities, have low/no indirect rates and can be more heavily taxed by academic institutions, and (in the case of industry funding) can open us up to potential conflicts of interest. But science is a business and early career scientists need money to do their work, so with the limitations acknowledged the panel started to share strategies for obtaining foundation and industry funding.

  1. Develop a wide network and deftly use it. In addition to academic celebrities, science peers, and mentors, this needs to include industry and grant officials. The panel’s suggestions on how to accomplish this were fundamental: present at meetings and engage with people at the posters; strategically serve on panels and committees; and ask your mentors to introduce you to key people in funding organizations.
  2. Build a team of people at your institution who are supportive of your success. This team can include those academic celebrities who can open new opportunities for you. The committee acknowledged that while it can be intimidating to approach seasoned investigators and seek out their advice and mentorship, you need to do it. They will not come to you. You need to be prepared and persistent when asking for assistance, but it is worth it as having these allies can open amazing new doors.
  3. Write. Potential funders will look at your previous publications when determining whether or not to fund you. You need to have enough of a track record of high quality papers that will give them confidence that you will use their funding to do good science and improve the human condition.

In the end, all panelists had a common theme: if we boldly and strategically pursue all relevant funding opportunities, we can be successful.

This session left me optimistic about the future of not just funding my own research, but much of the incredible research of early career scientists. While securing funding is an exercise in endurance and humility, we don’t have to bang our head against the wall forever. If we learn from each critique, persevere, revise and repackage our ideas, and surround ourselves with an amazing team of our own choosing, eventually we will prevail.