Joan Steitz Interview
EpiGenie: What area of research in your lab are you the most excited about these days?
Steitz: Well, that’s always a hard question because I’m excited about several things that we’re doing. But you know, my lab has always worked on non-coding RNAs, and what’s so exciting now is that there’s just been a recent explosion, and it just keeps exploding and exploding and exploding, and getting bigger and bigger. So clearly, I’m excited. I’m excited about what we’re doing on microRNAs. I’m excited about what we’re doing with respect to some viral non-coding RNAs that we’ve been working on for many, many years and haven’t really figured out their functions. And I’m excited because I think some of them might interact with the microRNA pathways, and we couldn’t have discovered that years ago because microRNAs hadn’t been discovered.
I guess the third thing that I’m excited about is that when you think about all of the information that’s come out in the last several years about blanket transcription of the genome, and only some of those transcripts are actual pre-messenger RNAs that actually make it out of the nucleus, that mammalian cells, in particular, have to have wonderful ways of surveying and then getting rid of all the crap RNA that’s made. You know, a lot of the RNA goes on to control transcription, control chromatin, et cetera, but you still have to be very fastidious in being able to sort out what you’re going to use and what you’re not going to use. I think that’s an absolutely fascinating area, so we’re doing some things on RNA decay in the nucleus.
EpiGenie: As you mentioned, the ncRNA field has exploded in the past decade. What do you think has been one of the most interesting findings of the past few years?
Steitz: I think the most interesting finding in the past decade is that the stuff that always used to run at the front of our gels turned out to be something real. And the reason that microRNAs were not discovered earlier was because back in the dark ages, we were all labeling cells with P32 and getting incorporation and then running gels that would fractionate small RNAs. There was always this big band right at the front of the gel, and we said, “Oh, that’s degradation product.” But that isn’t what it was. It was really mostly microRNAs, and some degradation products. Then people switched to indirect methods, like Northern blots, where you only find what you’re probing for, and since they weren’t probing for the stuff at the front of the gel, microRNAs went another two decades without being discovered.
So finding microRNAs, which came through genetics originally and the work by Ambros and Ruvkun, has been absolutely seminal to discovering this whole new class. And then, microRNAs do all sorts of additional things besides what we traditionally think of microRNAs as doing, for instance piRNAs and the ones that interact with chromatin, and the ones that divide up genomes to make gene-sized pieces. It’s just absolutely fabulous, all the additional things that very, very small RNAs can do.
EpiGenie: We were curious?what was it like doing your thesis research with James Watson?
Steitz: Well, again, that was back in the dark ages. At the time that I was in his lab, it was a very exciting time. It was the early time when some of the principles of protein synthesis were being figured out. Other things going on in the lab were figuring out that protein synthesis initiated with formylmethionine and figuring out how suppression worked by having a tRNA whose anticodon had been mutated to match a nonsense triplet. It was just a very, very exciting time to be there. It was a much smaller field, and everybody sort of knew what everybody else in the field was doing. You could read all of the literature.
I think the most important thing I learned was that you shouldn’t work on something unless you think it’s important. Then, of course, you have to ask the question, how do you tell whether something’s important or not important? That’s the next decision, and that of course gets a lot more detailed.
There are lots of interesting anecdotes from that period. At the time, Watson was writing The Double Helix, and chapters of it would go back and forth, and he would not be on speaking terms with various people at the Cambridge lab. Or it would appear that he wasn’t on speaking terms, and he would post these letters on the bulletin board. Since I was going from Cambridge, Massachusetts, to Cambridge, England, I started worrying, am I going to get dragged into this? Of course, it was all sort of tongue-in-cheek stuff, although some people took it a bit more seriously.
EpiGenie: You were really one of the pioneering women in the field of molecular biology. In fact, we read that you were the only woman in your graduate class in 1963.
In many regards, it seems that women in science have come a long way, yet women PIs are still very much a minority. Is there anything you think could be done to improve this situation?
Steitz: Well, I think that having universities with more family-friendly practices, like readily available day care that costs a reasonable amount, would probably be a huge thing. It strikes me that if it had been a little bit easier for a lot of women to get really good, really flexible child care, they would have made the decision to stay in science, and they wouldn’t feel so conflicted over how they’re spending their time. So I think that’s a really, really critical thing.
Then, you get into all of those unconscious bias issues?little things that add up to discourage women from going on in science. I don’t think we really understand how profoundly those affect people’s decisions. If you talk to virtually any woman, you’ll find out that there were little things that happened here and there that led to self-doubting.
I do think that role models are important because if you’ve never seen anybody who was doing what you thought maybe you could do, then it’s very difficult to convince yourself that you can be the first one to do it. So it’s much easier if there are some role models out there so you know that at least in some cases it’s possible.
It’s a very difficult and very interesting problem, but clearly progress is being made because we’re certainly at the point in the life sciences where as many women as men get PhDs. And that didn’t used to be the case.
EpiGenie: What advice do you have for women scientists who are trying to balance the demands of a research career with family life?
Steitz: Well, this may be too late for some, but it’s really important how you pick your spouse. You have to pick a spouse that’s supportive and is probably willing to do a little bit more sharing than on average because you have to have somebody who understands what your goals are and who’s willing to help you get there. So that’s really important, but that comes pretty early on, before you start all this juggling. I’ve gone to some conferences and sat at a Women in Science lunch where I’ve heard some pretty horrifying stories from some women about their boyfriend or their new husband, who clearly wasn’t going to be very supportive of their continuing in science.
I also think it’s important, no matter where you are, to try to establish connections with some other women. There’s a book called Every Other Thursday that was written about a group of women in San Francisco?Christine Guthrie is one of them, and Carol Gross is another, and then there are a couple from Berkeley?who’ve been getting together every 2 weeks for 25 years. They’re in different fields, and they talk about difficult decisions they have to make. For example, my chair told me to teach two courses, and none of the men are teaching more than one course, and what do I say to my chair when I go back in to try to argue with him that I shouldn’t have to do this? Or what do I do when I have a graduate student that’s a real problem? Or what do I do if I have to fire a technician? One of the members of the group, Ellen Daniell, wrote this book, and it really tells you how this sort of network functions. The reason that I mention this is that usually there aren’t enough women in the environment, so that you can automatically network. If you deliberately think about putting together something like this group, then you’ve got that sort of support.
EpiGenie: You mentioned that having a supportive spouse is very important. So what’s it like being married to another eminent scientist. Do you tend to leave the scientific talk at the lab, or do heated discussions about the spliceosome come up at the dinner table?
Steitz: Sometimes it’s about the science, but because my husband is actually in the same department that I’m in, more often it’s political issues having to do with how the department’s run, how the university’s treating the department, et cetera, et cetera. I remember when my son was 6 or 7, one night he said, “No more ‘ain’t it awful’ tonight.”
It’s almost impossible to leave things behind. I mean, I don’t think any of us does that with our spouses. And again, that feeds into having somebody who really does understand and somebody who’s willing to listen, even if they’re not in the same field or anything very closely related.
EpiGenie: Speaking of your son, did he ever have an interest in science? Or did the “ain’t it awful” talk steer him away?
Steitz: Our son insisted on going to Yale, and what he really majored in was baseball. He was a pitcher. So he did what was easy for him in terms of a major, which was to major in my department, molecular biophysics and biochemistry. Luckily, the year I would have taught him, because I teach all the undergraduate majors, I was away on sabbatical. I told him that he couldn’t major in the department unless he could arrange to take my course the year that I’m on sabbatical and not teaching it, which he did. So he then went on and actually played professional baseball for a couple of years. He hurt his shoulder, ended up going to law school, and is now doing financial consulting at McKinsey. So he did science, but he didn’t really want to be a scientist.
EpiGenie: What are your thoughts on the current state of academia, and how things have progressed in your eyes?
Steitz: What the NIH budget crunch is doing, which everybody is extremely upset about, is it’s pushing off the age at which people get positions, get their first grants, and become independent. It’s really changing the face of science in a not very good and not very encouraging way. If you look at the fraction of the GNP that’s going towards research and development in this country, it’s at pretty much an all-time low, if you go way back to 1950. So there are really serious problems there, and hopefully the country’s going to get its act together and be able to do something about that. What’s so strange about it is that it’s happening at a time when the science is so exciting, and when the science is becoming so much more relevant. Now we really see all these crossovers between the basic science and the clinical applications. It’s absolutely remarkable what’s happened.
Now, the universities I don’t think are blameless, either, because what they’ve done is they’ve built new buildings at medical schools and expected the NIH to pay the salaries of everybody that’s in them, as well as support the research. The universities should really be paying more for the professors that they have on their faculty. I think it’s unreasonable to expect the government to completely foot the bill, as happens at so many private universities and medical schools. So we’re at a very, very interesting and very difficult juncture, but something’s going to have to happen.
EpiGenie: In your observations, what’s been the largest impact of the budget crunch?
Steitz: Even though you see fantastically innovative research being done, I think it is impacting the quality of the research that people are doing because to get funded in this very tight budget crunch, you have to do more conservative research. Now the NIH has tried to do things about that by setting up, for instance, the Pioneer Awards, but there are a very limited number of these available, and they don’t really fill the gap. And I think it’s feeding back on how adventurous people are willing to be in their experiments. Now, it’s always been the case that there are certain types of research that you can do in Europe that you can’t do in this country because they have a system of institutes that are funded long-term, big equipment and technicians and things like that, making it possible to do certain things that you just can’t do here. But on the other hand, I do think that the budget crunch is making all scientists more conservative.
EpiGenie: Do you see a fluctuation in the amount of dollars that are allocated towards the traditional RO1s versus the more exploratory R21s?
Steitz: Well, I wouldn’t make the contrast between those two particular grants, but for instance, one of the things that was puzzling and not good about the doubling of the NIH budget that we had 7 or 8 years ago was that if you actually look at the numbers and look at the line, it wasn’t that the budget doubled. It was that the budget had been leveling off relative to how it had grown for four decades, and all that the doubling did was get it back up on the line. But what it also did is that because they had to expend the money within a certain length of time, and that’s just the way the federal budget works, what they did was establish some large programs, so that now we’ve got back up to the line. But in the process, we lost RO1s and have more large ongoing programs that aren’t necessarily, in my opinion, the best investment of those dollars. So there was actually a shift from RO1s, which are the grants that can be innovative, and the R21s and other things like that to larger projects, of which I’m not a great fan. And many of those don’t have sunset clauses, and they go on and on, even if they’re not being terribly productive. Especially when money is tight, it’s not the best way for the NIH to be spending its money. But once they’ve committed to it, they’ve committed.
EpiGenie: So do you think those larger endeavors create mini-bureaucracies?
Steitz: They create bureaucracies, and they cost more money and produce less science. That’s not true of all of them, but it’s true of some of the genomics type of things that have been invested in.
EpiGenie: Some people might argue that on the other side, this budget crunch is forcing the research community to approach things more innovatively or to collaborate.
Steitz: Well, collaboration isn’t necessarily a bad thing. I know that because I’m on the advisory committee for one of the EU grants in Europe, and the European Union has put some money into scientific research, and it does this demanding that there be big collaborative networks and demanding that a large fraction of the budget that they give goes for meetings and trading people back and forth between labs. This is actually a good thing, even though there’s a lot of paperwork and bureaucracy involved. Often when I go to Europe to a meeting, I think, oh my God, they’re collaborating, and they’re way ahead of us, whereas we’re back here competing with each other instead of collaborating. It’s partly the structure of how they’re giving the money that’s making those demands.
I’m on the board of something called EURASNET, which is an alternative splicing network. The problem is that there’s too much direction, in my opinion, coming from Brussels into the actual science and what’s prioritized rather than letting it come from the scientists. There’s stuff coming from bureaucrats, who have scientific backgrounds but who should not be the people, in my opinion, who make the decisions about what projects are undertaken. But it’s done wonderful things for collaboration within Europe, and it’s scary because they’re taking off. That plus our budget crunch is making things here much, much, much more difficult.