Randy Schekman delivers the commencement address at the 2019 Rackham Graduate Exercises

Randy Schekman is excited about the future of basic science (and thinks you should be, too)

June 28, 2019

When Randy Schekman, Ph.D., started his independent research program in 1976, he decided to investigate a biological process he’d never studied using a model system he’d never worked with. By the end of the decade, his lab had identified how yeast cells transport molecules to various locations within and outside of the cell. The findings formed the basis for the techniques that the biotechnology industry uses to produce useful protein drugs, including insulin for diabetes patients and the hepatitis B vaccine, and they earned Schekman the Nobel Prize in Physiology or Medicine in 2013.

Since those groundbreaking discoveries, Schekman has continued to seek out and implement new approaches to push the boundaries of his field — whether in his lab at the University of California, Berkeley, as the editor-in-chief of a journal that is changing the nature of academic publishing, or as the scientific leader of a foundation that is using basic research to unearth potential cures for Parkinson’s disease.

At its 2019 Spring Commencement ceremony, the University of Michigan awarded Schekman an honorary doctorate in recognition of his “distinguished contributions as a researcher, educator, academic publisher, and champion of public universities and basic research.”

After delivering the commencement address at the U-M Rackham Graduate Exercises, Schekman, a founding member of the Life Sciences Institute’s Scientific Advisory Board, sat down with LSI faculty member and fellow cell biologist Yukiko Yamashita, Ph.D., to discuss the changing landscape of basic research, his thoughts on broadening the reach of academic publishing and his advice for aspiring scientists. Their conversation, edited for clarity and length, follows.

Yukiko Yamashita: Basic science is changing a lot. Before, I think it was really curiosity-based, which is still most important for making discoveries. But I think the connection to therapeutics has become stronger and perhaps has changed the way basic research is done. I’m curious to hear how you think basic science has changed along the course of your career.

Randy Schekman: You’re right; it has changed. It’s true that there are more opportunities to apply what we learn. The genetic tools have advanced with mammals and with cultured mammalian cells quite dramatically, and that presents itself with more opportunities. But also what’s happened is that biomedical scientists have themselves become more entrepreneurial, too. Most of my young colleagues are involved in biotech start-up companies. The culture is very different now, I think. There’s almost an expectation that people will try to patent what they’ve discovered. I have no problem with that, as long as what’s done within the university is basic science. And I feel very strongly that what scholars do in the university must be published. You must not do private work, contract work in the university that cannot be published. To me that is antithetical to the academic exercise.

YY: So with that said, do you think the future of basic science is bright?

RS: There are still many things that need to be discovered. I’m not worried about that. And there are bright, ambitious people coming along who are really doing exciting, original, creative work. It’s much more technologically driven than when I started. The nature of science is changing quite dramatically, compared to when I started. I still think that there’s a place for basic genetics and biochemistry; but, increasingly, technology is taking a big chunk of the interest.

YY: In this era of so many advanced technologies — and some are, of course, critically important — I am still seeing studies that elegantly show something completely novel, but using experiments that could have been done three decades ago in terms of materials and tools. But the idea is just so novel. And sometimes I’m totally blown away by that kind of intellectual activity.

RS: Yes, we’re not about to be replaced by robots. There’s still a role for the individual creative instinct, that’s for sure. In fact, that’s really how people are recognized — for their individual, creative initiative. So I’m not pessimistic at all. 

I’m often asked by young people if it’s much more difficult to have a career in the biomedical sciences now. And I tell them that, actually, I think it’s easier. It’s hard to get a job if your only focus is to get an academic position in a high-ranking institution. But when I started as a graduate student, the biotechnology industry didn’t exist. Graduate students in that generation had only one option: to become an academic. There were no alternative careers. And now there are many more opportunities for science that are equally attractive. It’s a different kind of science. It’s more of a team approach. But it still involves working at a bench and doing experiments. I know this is not a popular point of view, but I think it’s actually easier now to have a career in biomedical science.

There are still many things that need to be discovered. ... There’s still a role for the individual creative instinct, that’s for sure. In fact, that’s really how people are recognized — for their individual, creative initiative. So I’m not pessimistic at all.

Randy Schekman, Ph.D.

YY: That’s true. So do you have a message for younger scientists who might be feeling worried about career prospects?

RS: At an early career stage, you have to remain flexible and not be fixed on one particular career path. You have to be willing to consider alternatives. And with an advanced degree in the life sciences, there are many ways to go. There are teaching jobs. There’s a whole world of biotechnology. You can work in academic publishing, in law, in public policy. I think undergraduate or a graduate students have to be sufficiently self-aware to know where their talents are, and to optimize the application of their talents.

I also feel very strongly that people really have to focus. Everyone who’s in the creative endeavor, such as ours, has lots of ideas. It’s just as important to have a good filter and to know what’s worth working on and what’s too much of a digression. You have to really dig deeper and deeper on a single problem — and you actually can make more of a contribution to the science if you’re really digging down deeply into a problem.

Another thing I advise people is, at the outset of their career, they should train in different areas. If they do their graduate work in one area, they should do a postdoc in another area to leaven their experience with other exposures. And then when they choose to start their own career, they shouldn’t be limited to continuing to do their postdoc work. That’s too easy. If you’re not willing to change and recreate yourself at the outset of your independent career, you never will.

YY: So When very young scholars are facing this future that is completely unknown — in a good way — what might help them to really focus on the one right thing?

RS: It may be that when you start your career, you have to have a couple of different irons in the fire. And then you have to be willing to drop everything when one thing really works. You also have to know when to give up on something that’s not working.

YY: In your career, when you didn’t know you were to win the Nobel or become a National Academy member, was there a moment where you felt like you didn’t know if something was going to work out?

RS: That’s a great question. Near the end of my postdoc, I decided that I was going to work on yeast. I’d never worked with yeast. I’d never done genetics. I’d never really worked on this process of secretion. And so when I got to Berkley and my grant was rejected, I was very nervous. I remember thinking “maybe I should have just continued to explore what I was doing as a postdoctoral fellow.”

But I also knew that I had good ideas, and I knew that I had been successful before and I could certainly continue to be successful. And most importantly, I had a fantastic graduate student in my first year.  Within a year, we had the first success. And I knew from the moment that we isolated the first mutant that we would have at least 20 years of work, no problem. I could see a path. I had started other little things, but I just dropped them like a hot potato when the first mutant came up. I mobilized the lab to that effort, because we had results that were clearly novel, and they had a lot of legs for future experiments.

You have to know what to take advantage of and what to exploit when you happen on it. You have to be willing to jump, to take a leap.

At an early career stage, you have to remain flexible and not be fixed on one particular career path. … You have to be willing to jump, to take a leap.

 

Randy Schekman, Ph.D.

YY: I think that’s very important to remember: All of these people who seem like they’ve been successful forever, they had to take risks and not be afraid of doing something new or something unclear to them.

So beyond your achievements in the lab, you’ve played a big role in academic publishing. You’ve been the editor-in-chief of several journals, most recently the founding editor-in-chief of eLife. When you started eLife, what made you feel that we as the science community really have to change the publication landscape”?

RS: One of the things that troubled me most when I was the editor-in-chief for other journals was that some of the staff started to feel like we should be measuring ourselves by our Impact Factor. I don’t care what the Impact Factor is. I said that we weren’t going to be measured by some phony number. And I really started to developed a distaste for these so-called exclusive journals.

I was given the opportunity through the Howard Hughes Medical Institute to start this new journal. And it was very appealing because I could formulate my own policies. I could make sure that there was no whiff of members’ privilege. No one would get any special favors. And, most importantly, all of the decisions would be made by active scholars. 

I knew we’d have to be creative and do something different. We couldn’t just start a new journal and do the same thing. And I always want to do something different.

I knew from my experience at PNAS that there was a way for the editors and the reviewers to actually have an online chat. I thought this should be open so the reviewers should be identified to each other. I thought it wouldn’t be too difficult to adapt that system and allow reviewers to exchange messages online with each other and be identified to each other. That’s been the major innovation, I would say. And I think generally it’s been very successful. We also came out right from the start with a very strong opposition to being measured by the Impact Factor.

I’m pleased with how it has moved the field forward, but not satisfied. I’m pleased that the journal has grown in success as measured by the number of papers, by the number of prominent people who will send their best papers to the journal. But it’s a work in progress. I may have stepped down as editor but I’m not going to stop talking about it wherever I go.

YY: So what is next for you, now that you’ve stepped down from eLife?

RS: I’m working on a new initiative on Parkinson’s disease. My wife died of Parkinson’s a year and a half ago. As her illness progressed, I was in touch with the Sergey-Brin Family Foundation. Brin, the co-founder of Google, has a family history of Parkinson’s and has invested a lot in researching the disease. He has decided that what we really need is a focus on basic science and basic understanding of the disease. And so I was asked, when my wife died, to lead this new effort.

I’ve decided that the way I want to pursue this is to identify groups of collaborators who are already working in this area and encourage that kind of collaborative spirit — because collaborations can be better than the individual efforts. They are a very effective way to make discoveries that you can’t make by yourself.

I want to see if, in the 10 years of this program, we can make some basic discoveries that can then be used for more effective treatments or cures, which really don’t exist. We’ve known about Parkinson’s for over 100 years; and while there are some treatments that mitigate some of the symptoms, the progression of the disease is inexorable. It’s a death sentence, and there’s nothing that has changed that course. The same is true of Alzheimer’s. And so we need a more basic understanding of why dopaminergic neurons are dying in these patients at a greater rate than in normal people. If there were some fundamental understanding of why those neurons are dying more rapidly — and if one could then, based on that knowledge, intervene to delay that death — Parkinson’s would be a very manageable disease. But it’s not.

So that’s the aim: To understand the fundamental basis of why those cells are dying. It is easier said than done, but that is in the scope of basic science. So I feel really good about that.

Top Image: Randy Schekman delivers the commencement address at the 2019 Rackham Graduate Exercises.

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Randy Schekman, Ph.D., is a professor of molecular and cell biology at the University of California, Berkeley; an adjunct professor of biochemistry and biophysics at the University of California, San Francisco; and a Howard Hughes Medical Institute Investigator.  

Yukiko Yamashita, Ph.D., is the James Playfair McMurrich Collegiate Professor of the Life Sciences at the University of Michigan, a research professor at the U-M Life Sciences Institute, a professor of cell and developmental biology at the U-M Medical School, and a Howard Hughes Medical Institute Investigator.