My Research Career: Lessons Learned

In these interviews, PIs talk about defining moments in their careers, including advice received and given, successes, mistakes, and challenges.

My motivation was always primarily curiosity. When I first heard about enzymes, I felt the urge to figure out how they achieved their enormous rate accelerations. That drove me for the first 30 years of my career. What motivates me now is wanting to cure Parkinson’s and Lou Gehrig’s diseases.

What was your smartest career move?

That’s easy: Asking Dagmar Ringe to join her research efforts with mine at Brandeis. We’ve run our two labs as a joint operation for 30 years; she’s the best scientist I ever worked with and the finest colleague you could ask for. Anybody who knows me will tell you she must be a saint.

Worst career move?

Staying too long at an institution (MIT) that didn’t suit my personality, character, and temperament.

Who was your best mentor, and in what ways did he or she help you?

I’m fortunate that I had several excellent ones. As a Princeton undergraduate, Bill Horrocks and Bob Langridge. As a graduate student at Oxford, Sir David Phillips. As a post-doc, Pierre Douzou. And later, Demetrius Tsernoglou, Martin Karplus, Hans Frauenfelder, and Ira Herkowitz. Each of them taught me something different, sometimes about science and sometimes about life.

I guess the biggest influence on me was Sir David Phillips. He taught me how to see what I did in the broadest possible context and to understand that science is a service performed for the public good. He believed that we have an obligation to the people who put us in the lab to use our talents and hard work to better their lives.

And, of course, I usually learn something important from Dagmar just about every day.

As a mentor yourself, what's the first piece of advice you give a new post-doc?

Have fun. This should be one of the best times of your life, so don’t forget to enjoy it. Don’t live in the lab — there’s more to life than that. And learn as much as you can, about as many different things as possible.

What are some managerial, ethical, or personal principles that helped you succeed?

Dagmar and I have always thought that, if we focused on training and established an environment that was supportive and fun, where learning was the objective, the research would take care of itself. So far, that’s worked out pretty well.

We have always believed in being generous to our collaborators and as inclusive as possible in terms of authorship, credit, etc. We’ve never suffered for that.

If you could start over, what do you wish someone had told you?

— To ignore the voice in your head that tells you “You’re not good enough” or that you don't belong here. It's in everybody’s head — and it usually lies.

— That things never get easier or less frantic, but your ability to cope with them will improve.

— And that it’s essential to know when you’ve reached "Good Enough." If you don’t learn that, you will never finish anything.

What's one mistake you wish you had avoided?

Not taking enough risks.

What's the best — and worst — advice you ever received?

The first independent job I had was as an instructor at Wayne State University School of Medicine; it was all I could get. No, it wasn’t a top-tier place, and Detroit wasn’t high on my list of where I wanted to live. Dick Hudson, a professor on the faculty there, took me aside one day and said, “Everybody in this place is constantly trying to move elsewhere, and because that’s all they think about they never do much. Don’t waste your energies trying to get out. Focus on doing good work, and let whatever happens happen.” I took that to heart and in five years had gotten enough good work done that I got an offer to move to MIT and another to move to University of California-San Francisco. I did take the MIT job (noted above), but by then I had come to love Wayne State and the people there, and I almost stayed. Funny how life works.

As for the worst advice, I think it was when someone said to me that I should try to maintain a low profile. I didn’t pay much attention. I always figured that I had to be me; it’s a lousy job, but someone has to do it…

What was your toughest funding challenge?

Finding money to support the complete change in research direction when Dagmar and I decided to tackle neurologic disorders. We had no track record in that area, so NIH wanted nothing to do with our ideas. Fortunately, a few private foundations (the McKnight Endowment for Neuroscience; the Ellison Medical Foundation; the Fidelity Biosciences Research Initiative; and the Michael J. Fox Foundation) liked what we were proposing enough to help us get started. Without them, we would never have been able to make the transition from basic enzymology to working on human disease.

Do you see any new funding trends developing?

Do you mean besides the obvious one that money is getting impossibly hard to come by? Yes, a few. I think private philanthropy is becoming more hands-on and is looking for milestones sooner. I think government funding is becoming too conservative. I also think there’s a disturbing trend, especially at NIH, toward top-down setting of directions rather than letting priorities emerge from competition among individual investigator-initiated proposals. And I think we have failed completely to find a way to terminate Big Science projects that have outlived their usefulness or were a mistake to begin with.

Is there anything a scientist can do to enhance his/her creativity?

Yes, I think there is. Get outside your comfort zone. Go to talks and meetings in areas you know nothing about. Read as widely as you can. And take more chances.

Can creativity be forced or hastened?

Not in my experience.

On the lighter side, what's the most embarrassing thing you ever saw or heard of in a research lab?

I once wandered into the lab and saw a cord hanging on the wall I had never seen before. (It had been installed the previous week, but I had been out of town). So I tugged on it. It was the pull-cord for the safety shower, and I was standing right under the showerhead.

Is a research lab a likely place for romance to blossom?

Sometimes. Among peers, it can work: I’ve certainly seen that happen a few times in our lab. As for why, who else but another scientist is likely to understand our passion for what we do and the insane lifestyle it can drive us to?

Where did you grow up?

Washington, D.C.

Where did you earn your undergraduate degree?

Princeton University.

Is there a moment from that time that stands out?

Yes. In 1970, when I was a senior, the all-male university decided, after over 200 years, to admit women. I was the DJ on the campus radio station when the news came in. I played the Hallelujah Chorus from Handel’s Messiah continuously for an hour over the air.

Are you married? Have children?

My wife is Dr. Laurie Glimcher, a physician/scientist who is the Irene Heinz Given Professor of Immunology at Harvard School of Public Health and Professor of Medicine at Harvard Medical School.

I am stepfather to Laurie’s three children: Kalah (attorney in Washington, D.C.); Hugh (surgical resident at Massachusetts General Hospital); Jake (just graduated from Harvard, now a second lieutenant in the Marine Corps).

Pets?

Two dogs, Mink (a large, chocolate Labrador Retriever) and Clifford (a small Spaniel/Poodle mixed breed). They are very smart and have occasionally appeared as guest columnists in my science and society column in Genome Biology (e.g., http://genomebiology.com/content/10/10/112).

What do you read — to stay informed in your field and for pleasure?

Staying informed in any field is increasingly difficult. Important papers can be found almost anywhere, and review articles often have a particular agenda and are not sufficiently critical. Increasingly, I depend on meetings, large and small, to keep me up to date — so I travel a lot.

For pleasure, mostly history these days. I go through periods of years when I tend to read mostly one type of thing. And I never miss either The Economist or Sports Illustrated.

Any other thoughts, advice, or philosophy you'd like to share?

Yes. Use all, part or none of this, as you wish:

Dagmar and I often are asked if the principles of the lab ever got written down somewhere. They have; a few years ago we made a list of 20. Some are our own words; others are borrowed from things we heard somewhere, sometimes long ago, that seemed to make sense. We’ve never tried to find out who might have said them first. For those of you who are interested, here they are:

1) If you think you know the answer, you will get that answer, even if it's the wrong answer. (More succinctly: The desired result tends to be observed.)
2) Never confuse an assumption with a fact.
3) One good experiment is worth 1,000 expert opinions.
4) The strong shall take from the weak, but the smart shall take from the strong.
5) Take nothing on faith. Things are frequently not what they seem to be or what people tell you they are. Check everything.
6) Excellence is the result of preparation, planning, imagination, and tenacity. Neglect any one of these and the result is mediocrity.
7) It's often not that hard to handle a crisis, because usually your course of action is obvious. It's how you deal with day-to-day living that really proves what you're made of.
8) Adversity doesn't build character; it reveals it.
9) You are what you do.
10) Luck is the residue of design.
11) The odds of success are never improved by excessive caution.
12) Never let your sense of morality prevent you from doing what's right.
13) When you fully understand the simpler alternative, it will usually turn out to be as complicated as the complex alternative. Occam’s Razor is usually a poor reason for making a choice, especially in biology.
14) Only a fool is never afraid, but never let fear make the decisions for you. Do right, and risk the consequences.
15) It's nice to be first, but it's better to be right.
16) Create an environment where people can learn and have fun learning, and the work will take care of itself. The results are just the report card.
17) Be your own toughest referee. Whenever you get a result that you expected or that you think you understand, always ask: "How might nature be trying to fool me?"
18) Be generous to your lab staff, colleagues, and collaborators. Give more credit rather than less, and err on the side of inclusiveness. It won't cost you a thing, and it will gain you a lot.
19) Under-promise and over-deliver.
20) Fame is a bubble, popularity an accident, and money takes wings. The one thing that endures is character.

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