Jon Lorsch is arguably one of the most influential scientific public leaders in the United States for the ASCB constituency. As Director of the National Institute of General Medicial Sciences (NIGMS) since 2013, he guides a multibillion dollar enterprise that funds over 10% of National Institutes of Health (NIH) grants, many of which are held by ASCB members who devote themselves to the NIGMS mission to “support basic research that increases our understanding of biological processes and lay the foundation for advances in disease diagnosis, treatment, and prevention.”

When I first met Lorsch, we were both relatively new to jobs, he as NIGMS Director and me as an ASCB Councilor. Lorsch was visiting the ASCB Council to introduc

Jodi Nunnari

e himself and to inform us on some changes he was instituting at the NIH. Those who know me know that I tend to be inherently distrustful of administrators. So I was surprised to find myself thinking that Lorsch was just “one of us”—a scientist devoted to getting good science done. Indeed, before he became NIGMS Director, Lorsch ran a successful basic research program at Johns Hopkins focused on protein translation mechanisms, which he has continued at the NIH.

At this ASCB Council meeting he stated his intention to divert NIGMS funding away from big top-down, center-based initiatives toward investigator-driven awards (R01s). As history now shows, this single decision served to significantly improve the NIGMS R01 success rate and was met with great enthusiasm in the community. Since then it has become apparent that Lorsch deeply believes that science is best served by spreading the wealth to fund a greater number of investigators. Fueled by this belief, Lorsch has initiated programs and driven changes in NIH policy. Among these, he has created the Maximizing Investigators’ Research Award (MIRA) program, championed the controversial Grant Support Index (GSI), and is overseeing the current overhaul of the NIGMS T32 program for graduate student training. Perhaps his most impactful creation is the MIRA program, in which both junior and senior investigators are enticed to abandon the prospect of multiple R01 awards in exchange for a single MIRA award that for well-funded investigators pays less, but has a five- instead of a four-year funding period, a separate investigator-focused reviewing mechanism that emphasizes past accomplishments, more flexibility to follow new directions and ideas, and a goal of more stability and funding.

As is the case for many innovative leaders, Lorsch’s agenda to fund more investigators has been met with some controversy and skepticism among our scientific community, including the worry that it may promote a shift from meritocracy toward mediocracy. Controversy can and usually does breed misinformation. Thus, I took the opportunity that the ASCB presidency affords me and sat down with Lorsch to get the straight scoop on a range of issues that greatly influence the ASCB membership. What follows here are excerpts from the full interview found at ascb.org/Lorsch_Interview.

Nunnari:
I guess the first question is what inspires you to come in every day?

Lorsch:
The main thing is to get the most out of the taxpayer’s money in terms of high-quality science. That’s what we do here. And that’s what drives me. That’s pretty much it.
What I worry about is lost talent. I worry about all the tremendous researchers who are struggling to stay funded, are struggling to get funded, who could be the person that makes the next great discovery or 10 years from now contributes in some important way to a medical breakthrough down the road. We may lose those advances if we don’t find a way to get them funded.
[G]etting the most and best science for the taxpayers’ money and ensuring that we are funding all the great ideas and all the great scientists that we can…are closely related to each other because the way we’re going to get the best science done, the way we’re going to maximize chances for breakthroughs is to ensure that we have a broad and diverse portfolio of researchers.

Nunnari:
What evidence is there that a diverse portfolio really does produce the best science? The…criticism…that I’ve heard many times in the community is that if you take that strategy of distributing the wealth to more investigators, to more grants, maybe what will result is a shift toward mediocrity.

Lorsch:
History shows that’s not true, that the big discoveries come from all sorts of unexpected places. You couldn’t have predicted them in advance. You can come up with plenty of examples of great scientists struggling to be funded….I think the key for us, one of the driving principles, is this broad and diverse portfolio.
We think in terms of success rates. What is the number of grants funded divided by the number of submitted applications. Right now we’re around 30%. I think that’s good. Really good. There are still things left on the table with a 30% success rate, but we would be starting to get into a ballpark where we feel a little more comfortable. When you get down to the 20s or below, you’re really leaving a lot of tremendous science on the table.
In the current system, people can submit lots of grants. That underestimates the true nature of the problem because there are people who have multiple grants. What we started to do is to focus on how many investigators we are funding. That’s another metric that really drives us. We want to make sure that we’re funding enough meritorious investigators—not just enough good grants—because the investigators are the ones with the ideas, they’re the ones who are going to make the big contribution of breakthroughs.

Nunnari:
Was MIRA your baby?

Lorsch:
Certainly, I guess you could say that. Others here had been thinking along similar lines. Peter Preusch certainly was one. He was the initial program director for MIRA….When I came here and started studying the problems, [it became apparent that] changing the paradigm from this project-based funding model to a program-based funding model—in other words, to a single PI to support a program of research rather than individual projects in a lab…could have really profound positive implications for the system. It was at a time where the Alberts et al. paper1 had come out and they were talking about similar problems, with some similar ideas for things that might be changed. It seemed like the time was right to try an experiment that was relatively radical and see if we could actually change the paradigm.

Nunnari:
As a corollary to the MIRA program, do you feel like your
program officers have gotten tougher about multiple R01s?

Lorsch:
Yes. And we’re headed even more so in that direction.

Nunnari:
I understand the rationale for [limiting funds for] the senior investigators based on everything you’ve said….I don’t quite understand why you’d want to limit a junior investigator right out of the blocks.

Lorsch:
[O]ne of the things we did when we started the ESI [Early Stage Investigator] program was to split the review off for the early stage investigators from the established investigators so they were reviewed in separate study sections and the early stage investigators have their own review criteria.

Nunnari:
That’s wonderful.

Lorsch:
I think that is a great thing that we’re now comparing apples to apples, oranges to oranges. In terms of the funding, this is another kind of misinterpretation or myth. The maximum they can request as an early stage investigator is $250,000. Almost all of them that we funded got $250,000 in direct costs. That is almost $60,000 more than they would’ve gotten if they had gotten an R01 as an early stage investigator from NIGMS. They’re getting more money. Now when they come in for renewal, they’re not locked into $250,000 anymore. If they did spectacularly well, they can request an increase in the budget and we can give it to them.
The other thing I was going to mention is when we look at the people awarded MIRA, ESI MIRAs, they are about a year and a half, almost two years younger than the people awarded ESI R01s from NIGMS. Somehow, we are funding people earlier, which I think is really neat. It’s only two years of data. Let’s see if the trend continues. We’ve got to study it, but I’m optimistic. I think that’s a pretty great thing because one of the things we’re concerned about that we didn’t discuss is how long people are taking before they get their first grant. Thirty-nine is the average age at NIGMS.

Nunnari:
Good unintended consequence perhaps. I understand that there are some pretty big changes coming down the pipeline for training grants.

Lorsch:
From NIGMS. We have a whole new training grant funding opportunity announcement.

Nunnari:
It’s causing a lot of anxiety in the community. It’s viewed like another hurdle to jump over. Is that related to the workforce issues?

Lorsch:
There are elements of it that certainly are. Things such as reporting outcomes of graduate training programs are something that Shirley Tilghman, for instance, has called for repeatedly and is now codified in the FOA [Funding Opportunity Announcement]. Programs are expected to report their outcomes on a publicly available website so that students—both applicants and current trainees—can make reasonable judgments on whether they should go to a certain program and what they can expect as an outcome. Similarly, training in a career development program or programs within training grants is another area of emphasis that we’ve put into this new FOA.
[We are interested in] changing the focus of the didactic portion of the curriculum away from a kind of fact-based teaching model to one in which we are focusing on the range of skills that are needed to be an outstanding scientist. These could be technical skills; they can be operational skills like experimental design, strong interpretation of data, things of that nature. And then there are the professional skills: communication, education, teamwork.
…[W]e’re looking for transformation here, not just adding new bumps in the road. We are looking for a new road….We’re not asking programs to just tack new stuff on….We want them to relook at everything they’re doing and rework it. If someone wants to teach skills instead of facts, don’t just put a skills course in. Get rid of your facts course and replace it with a skills course or get rid of most of the facts courses….These are the kinds of things we’re really hoping to see. Big changes.
We’re talking about how we can improve the distribution of training support so that we reach more outstanding potential researchers in the country and potentially outstanding institutions. We actually have a new area that institutions can apply for a training grant in Transdisciplinary Basic Biomedical Research. It’s only open to institutions that don’t have one of our basic science training grants already or institutions that have multiple ones and want to merge some of their programs.
This idea came from community input….[M]ultiple
times deans or program directors asked if they could
merge two or three of their programs. This is a mechanism to allow them to do it and we’ll see if they take us up on it or not.

Nunnari:
What projects are you currently working on? Which one really excites you the most?

Lorsch:
Certainly I would have to mention data science. I’m the co-chair of the NIH Scientific Data Council, 2 which is an NIH-wide body that’s responsible for overseeing, organizing, and making recommendations to NIH leadership on issues related to data science on behalf of the ICs [NIH Institutes and Centers] and the Office of the Director. We were charged with developing a data science strategic plan to help guide NIH’s efforts in enhancing the ability of the scientific community and other stakeholders to engage modern data science approaches in advancing biomedical discovery. We’ve been working on that for several months now…and we’re about to put out a draft version of the plan, which I’m actually pretty excited about, for public comment in the next couple of weeks. You should see an RFI [Request for Information] out—26 pages—soon. [The RFI was released on March 5. The draft plan is available at https://bit.ly/2LiWM7A.]I think it really focuses NIH and hopefully the rest of the ecosystem, the rest of the community, on what we need to do to really make use of the opportunities that data science and big data are presenting us to overcome the challenges that we’re going to need to overcome. It’s something that’s overdue.
That’s one [thing]. Certainly another area that we’re working on internally at NIGMS has to do with diversity. If you look at the diversity of PhDs being produced in the biomedical sciences, the number of underrepresented minority students getting PhDs has actually increased about nine-fold in the last 25 years. It’s quite impressive. But if you look at the diversity of the professoriate, at least at academic medical schools, it hasn’t changed at all in the same period; it’s flat. That plus some other analyses that have come out recently have really indicated that a failure point is the transition from postdoc to faculty. People just aren’t making that transition for whatever reason.
We don’t know if they’re choosing not to or if they’re trying and not being successful or some combination. We’re working on interventions, a new program that would help bridge that gap and allow a more diverse population of postdocs to become successful academic faculty members running their own independent labs. That’s another thing we’re excited about.


References and Footnotes
1Alberts B, Kirschner MW, Tilghman S, Varmus H (2014). Rescuing US biomedical research from its systemic flaws. PNAS 111, 5773–5777.

2https://datascience.nih.gov/bd2k/about/org/SDC.

Jodi Nunnari

2018 ASCB President