Medical research must change culture to support innovation, young physicians, NIH director says

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American medical research needs a culture change that offers more opportunity for young researchers to explore new ideas without fear of failure, said the leader of the U.S. National Institutes of Health (NIH).

Jay Bhattacharya, MD, PhD, presented “New Researchers, New Ideas,” a keynote address for Sustaining the Biomedical Workforce: Innovative Pathways for Retaining and Supporting Physician-Scientists. It was a daylong workshop hosted in person and online by the National Academy of Medicine (NAM) and the American Junior Investigator Association. With data, anecdotes and comparisons with other sectors, Bhattacharya evaluated the research system that leads to advances in medicine and health care, and what needs to be better.

Jay Bhattacharya, MD, PhD
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“The point is, we need a culture shift that benefits early-stage investigators, for MD, PhDs, of course, but also just generally, and we're considering many innovative approaches,” Bhattacharya said. “I really do want the feedback of the community for how to fix this problem. Because it's going to take a, embrace of the entire scientific community to say, look, we really do need a problem here. We need to figure out a way so that early career investigators can get their ideas tested. We need to punish failure less, and we need to empower — because, you know, once upon a time, actually we used to do that, not that long ago, in living memory.”

The state of research

From 1980 to now, NIH data show the average age of first-time NIH grant recipients generally has been climbing, with physician grantees now well into their 40s, instead of getting funding in their 30s. “MD-PhDs, you’re talking about late 40s. That’s a long time to wait, it’s a long time to wait before you have a chance at trying your new ideas out,” Bhattacharya said.

Meanwhile, NIH recipients are having shorter career spans, Bhattacharya said. In the 1970s, between 10% and 20% of fellowship recipients stopped pursuing funding, but by the 2010s, more than half dropped out almost immediately after NIH fellowship support, he said.

“More than half — this is a problem again that goes back decades and decades and nothing we've done seems to have worked,” Bhattacharya said.

‘One obituary at a time’

The German physicist Max Planck, a Nobel Prize winner and a giant of 20^th century science, once said: “Science advances one obituary at a time.”

“That is a very depressing thought, right?” Bhattacharya said. Planck meant that in physics, for scientists to change their thinking, “the old guard has to, like, give up,” he said.

“You look at this statement, and you think to yourself, is that really true?” Bhattacharya said. “And the answer is … we really need to make it not true. We need a culture that allows our scientific ideas to change with over time before the old guard dies. Let the old guard come along with us, right?”

Bhattacharya and co-author Mikko Packalen, PhD, an economist at Stanford University, have studied trends in grants and research, accounting for the ages of researchers and the ages of ideas. They found early career researchers are a primary source for new ideas in biomedicine, and older researchers try out older and older ideas.

“So, you can tell Nobel Prize winners are trying valiantly to combat the problems of age. But I think it's just … completely natural that the ideas that you have as a young, early career researcher, if you're creative, they're going to be different than other folks, and you're going to spend a lot of time wanting to try them out, to test them out,” Bhattacharya said. “We need a scientific infrastructure that allows early career researchers to try out their new ideas, or else we will end up in a situation where science advances one obituary at a time.”

Permission or punishment?

Bhattacharya emphasized the importance of mentorship and pairing early career researchers and mid- to late career guides. Older experts must be critical — “because, you know, that’s who we are” — but early career researchers need permission to experiment with new ideas.

“That kind of encouragement plays a big role in giving permission to early care researchers to try their ideas out,” Bhattacharya said. “Maybe they won't work out. I'm going to come back to that theme about, they maybe don't work out, because I think one major problem we have is in biomedicine, we punish failure too much. We punish failure too much, especially early on.”

Other studies have posited that productivity per researcher is going down. In the United States, from 1950 to 2010, there has been a decline in the number of drugs per billion dollars spent in research and development. There are a lot of factors affecting that, not least that drugs in the 1950s likely were regulated too little, Bhattacharya said. There also has been tremendous progress, he added, using the example of advances in preventing and treating breast cancer.

It appears the United States has reached the flat of the curve, so to speak, for research. There are systematic problems in how researchers support new ideas, but that does not mean there are not new ideas out there, Bhattacharya said.

“I don't think that we are at the end of history, as far as science goes. There are tremendous ideas out there,” he said. “The science that we will have, if we do things right, 20 years from now, will look nothing like the science we have now, because we'll revolutionize how we think about things.”

To do that, there must be incentives and structures so the system works correctly to support research, Bhattacharya said.

Killing new ideas, or nurturing them

Bhattacharya cited his own experience as an NIH panel reviewer, and it appeared those in the audience also had.

“How easy is it to kill a new idea by saying it won't work? I've sat through that. And then, how hard is it for some panels to say, you know, I don't know if it'll work, but it's worth trying. It's difficult, isn't it?” Bhattacharya said. “Ask yourself that question, right? You have to stick your neck out. We've become much, much more conservative than we kind of ought to be.”

In funding research, new ideas require investment. Some ideas, no matter how much effort, will go never go anywhere, while others could lead to a Nobel Prize. Current research funding — and not just at NIH — punishes people at the bottom.

“You know, if your postdoc doesn't work out, you're done,” Bhattacharya said. “I want to contrast that with Silicon Valley, where an early career entrepreneur establishes some company, it fails, and that's a steppingstone to future success, because the infrastructure, the structure of how support happens for entrepreneurs, is such is that people are looking for constructive failures. We don't allow for constructive failures as much as we ought to in biomedicine.”

He cited the work of Max Perutz, the German molecular biologist at the University of Cambridge. Searching for the structure of myoglobin, his advisers told him it was impossible because tools did not exist to find it, but Perutz persisted for a decade.

“He figures out the structure of myoglobin, revolutionizes our understanding of protein structure, and wins the Nobel Prize in 1962,” Bhattacharya said. “The question I have is, could someone like Max Perutz survive in our infrastructure?

“He would have failed out, I think, a long time before he got to a success,” Bhattacharya said. “It's very, very difficult to be someone like him. This is what a healthy research ecosystem ought to look like. But we're very, very far from this.”

New measures of success

The author Bill James revolutionized thinking about baseball by thinking beyond home runs and runs batted in. Those are two important measures of player success, but they also are a narrow set of statistics to evaluate baseball player productivity. James’ ideas spread in baseball and became the foundation of the book and movie, “Moneyball,” which detailed how the Oakland Athletics integrated those elements into their team.

American science is in the pre-“Moneyball” stage, Bhattacharya said, and needs a broader set of metrics to evaluate its physician scientists.

“The metrics fundamentally changed baseball so that you can identify what's valuable in a baseball player much more effectively,” he said. “Right now, the metrics we use to evaluate the sign of the productivity of scientists are basically two. It's how many papers you published, and how much influence you have. Volume and influence. But we know that there's so much more to a great scientist than just those two metrics.

“We are not measuring the things we want to measure, and so we're not rewarding the things we want to reward for scientists,” Bhattacharya said.

Evaluating proposals

At NIH, evaluation is changing firstly by centralizing its Center for Scientific Review, and secondly reducing five criteria to three. The prior criteria often overemphasized methods at the expense of innovation, and overemphasized the quality of the investigator, which is important, but which also hurt early career investigators, Bhattacharya said.

The new criteria will be:

• Importance of research, including innovation.
• Rigor and feasibility of methods.
• Expertise and resources, scored as either present or not.

Paying for it

There have been commentaries and projections with gloom and doom and naysaying about NIH’s future. The House of Representatives and the Senate have approved a budget that essentially keeps NIH at the same as the last year, Bhattacharya said.

“There's no cut proposed by the House or the Senate,” he said. “There's bipartisan support in this country for continued investment in biomedical research, and I'm absolutely heartened by that. Go back and tell your early career researchers, the future is bright.”