JOHN DANKOSKY, HOST:
This is SCIENCE FRIDAY. I'm John Dankosky. Ira Flatow is away. This week, a handful of scientists got the wake up call of a lifetime, a phone call from Stockholm informing them that they'd won a Nobel Prize. Here's a taste of how it felt to a few of them.
MICHAEL LEVITT: Like five double espressos. I don't know. It's like a real adrenalin hit.
JAMES ROTHMAN: Well, this is absolutely overwhelming.
RANDY SCHEKMAN: My son says, yeah, crazy. My daughter says holy bleep.
FRANCOIS ENGLERT: (Speaking a foreign language)
THOMAS SUDHOF: Are you serious?
UNIDENTIFIED MAN: I am serious.
SUDHOF: Oh, my god.
SCHEKMAN: My son says front page of the New York Times. My daughter says recognize, several exclamation points.
DANKOSKY: That was Michael Levitt, James Rothman, Randy Schekman, Francois Englert and Thomas Sudhof. Now, we have one of those scientists here with us now. He shared this year's Nobel Prize in physiology or medicine for his work on the transport systems within our cells, how things get from Point A to Point B. Randy Schekman is an investigator at the Howard Hughes Medical Institute.
He's also a professor of molecular and cell biology at the University of California Berkley. Welcome to SCIENCE FRIDAY, Dr. Schekman, and congratulations to you.
SCHEKMAN: Thank you very much. It's my privilege to be here.
DANKOSKY: And how are you feeling today?
SCHEKMAN: Well, I'm still feeling giddy, overwhelmed, and I'm drowning in a sea of email congratulatory notes, so it will take me months to get out of the flood of messages that I'm buried in.
DANKOSKY: It must be a good feeling. Now, give us a quick thumbnail sketch of what you were studying, the work that got you the Nobel.
SCHEKMAN: Sure. Well, my colleagues and I investigate how protein molecules, these are the little engines that catalyze all the chemistry of life, are organized within cells, some of which end up being shipped out of a cell by a process that's called secretion. This process is shared by all cells that have a nucleus and involves the encapsulation of some of the protein molecules that cells manufacture, into carriers that are called vesicles, which are conveyed from deep within the cell to the cell perimeter where they burst at the cell surface to discharge their content.
Many molecules that we rely on for our life are packaged this way - insulin, growth hormone, all of the blood proteins that we have - so it's a crucial element in the physiology of all animals.
DANKOSKY: Tell us a bit about some of the applications that your work has, practically speaking.
SCHEKMAN: Well, early on in my laboratory we focused on studying this process in a very simple organism, baker's yeast, because it turns out through a billion years of evolution the process that evolved long ago has been preserved over eons. And we discovered that yeast cells have not only the same process but use many of the same molecules to catalyze this pathway.
And as a result, very early in my career, the biotechnology industry was able to harness the use of yeast cells to convey human proteins through this process. For example, insulin, human insulin can be introduced into a yeast cell, the gene for human insulin, and when the yeast cell produces the protein, it packages it just as it would its normal secretory proteins and insulin can be shipped out of the cell into the culture fluid.
This is an enormously powerful tool because it allowed the industry to make huge quantities of recombitant(ph) insulin much more efficiently than had been possible before. And as a result now, one-third of the world's supply of human insulin is made by secretion in yeast. This is one of many such applications of the basic lessons that we've learned by studying how cells work.
DANKOSKY: Now, when you started this, did you have any idea that your work would have this sort of application or that you would eventually win a Nobel Prize?
SCHEKMAN: Well, no, of course one starts as a young faculty member with ideas about how to study a basic cellular process with the conviction that basic knowledge is fundamental to all technology. So of course I had no idea, and certainly hadn't planned, that yeast cells, secretion in yeast cells, could be used in this way, but this is not an isolated instance. There are many such examples of where a basic, undirected, fundamental science gives rise to breakthroughs that are useful for human health and technology.
And it's absolutely crucial that this kind of investigator-initiated basic science be continued and supported by the federal government.
DANKOSKY: And you've said in the past that you're worried that there just isn't enough emphasis on this kind of science in the country.
SCHEKMAN: Well, at two levels. One, of course, is the current paralysis in Washington has discouraged many young investigators who may be brilliant scientists, but who will do other things. We've lost faculty members who were trained in the U.S. but who are foreign born who are returning to their countries because of the difficulty in obtaining funds, so that's one level.
Another level, quite frankly, is the decisions that are made at the level of the NIH about what kind of investigations are funded. I'm very concerned that decisions are made increasingly based on application rather than on the thirst for fundamental knowledge, and this is - I think this is counterproductive. I think the NIH should rebalance its portfolio and focus even more of its effort on basic investigator-initiated science.
DANKOSKY: And that's your point really, is that you didn't know that this application was going to be something when you started out and yet through basic science you got there. It seems as though, as you say, there needs to be a balance there. Do you think that we'll ever get there in this country?
SCHEKMAN: Well, let me just emphasize that it's not just me. If you look at all the Nobel laureates this year in science, every one of us started with a fundamental interest in some basic principle, and the conviction is that in all cases there will be applications. I'll give you another example from the work of my colleagues, Jim Rothman and Thomas Sudhof, worked on proteins that are involved in mediating the transmission of a nerve impulse across a synapse.
It was discovered that a toxin made by a bacterium, botulinum toxin, degrades one of the crucial molecules in this process and through that basic understanding we now have Botox as a result of what was really fundamental undirected research. So, you know, you can go down the list. There are so many examples of this that it's just so obvious to us that this is where the emphasis should be.
And I believe if scientists, like myself, focus our efforts now in trying to convince the people in charge at the NIH that this balance needs to be restored, we can make progress.
DANKOSKY: Randy Schekman is a winner of the 2013 Nobel Prize in physiology or medicine. He's also an investigator at the Howard Hughes Medical Institute and a professor of molecular and cell biology at the University of California Berkley. Congratulations again and thanks for joining us.
SCHEKMAN: Thank you very much.
DANKOSKY: Now, next up, the Nobel Prize in physics. You're heard, of course, of the Higgs field and Higgs boson, a frequent topic here on SCIENCE FRIDAY. Well, the Noble Prize in physics this year went to two gentlemen who developed the theory of the Higgs field, Peter Higgs and Francois Englert. Now, they couldn't be with us today but my next guest has done a lot of the actual experimental work to prove their theories correct.
Last year he and his colleagues announced that they'd found evidence of the Higgs field in the form of the elusive Higgs boson. Joe Incandela is head of the CMS Experiment at CERN, the European organization for nuclear research in Geneva, Switzerland. He's also professor of physics at the University of California Santa Barbara. Welcome back to SCIENCE FRIDAY, Dr. Incandela.
JOE INCANDELA: Thanks. It's great to be here.
DANKOSKY: So what was the mood like at CERN when the news was announced?
INCANDELA: It was explosive. I mean, we had about 100 of us from the two different experiments in our five-storey atrium of our joint office building and we watched the presentation and they could not even complete the name of Francois Englert before everyone exploded into applause and cheers. We were very, very happy.
DANKOSKY: So gives us a one-minute refresher course on the Higgs field. Tell us what it is.
INCANDELA: The Higgs field in one minute is almost impossible to do, but I'll try my best. The idea is basically, we were trying - we're theorists and physicists in general for a long time were trying to find a basic framework to explain the fundamental interactions, the basic forces of nature.
And the best formulas they have, if you like, the best approach they had demanded that the force carriers, the particles that carried forces, should be massless and what happened in terms of the key contributions that were produced by Brout, Englert and Higgs was that they found a way to make it work with masses force carriers and the way they did it was by saturating the universe essentially with a field, a field made up of particles with no spin, bosons.
DANKOSKY: So why does this field have to exist? Why is it here?
INCANDELA: Well, we didn't know for sure that it had to exist per se. We knew something had to be there, let's say, because there's really no other good explanation for how you can produce masses of force carriers. And we didn't know exactly what the structure of this mechanism would be, but the most simple formulation was that given by Englert, Brout and Higgs and in some sense the reason it's so exciting is that it turned out to be right. And we didn't know that know that a priori.
DANKOSKY: Now, of course, one of the dicier questions around this is you run CMS, one of the two Higgs experiments, along with the Atlas experiment, without the experimenters, the people running these experiments, this theory couldn't have been confirmed. Do you think that the experimenters themselves should have gotten some of the recognition here?
INCANDELA: I think we're all very happy with how things went. I mean, for us, I said before, the real reward is the discovery and given the rules of the Nobel Prize being restricted to three people, it would be very hard to pick amongst the thousands of us involved here who should get the reward. And frankly I think we were all just very happy to see that it went to Englert and Higgs. It's unfortunate the Brout passed away a couple years ago.
I'm sure he would have been the third name. And the citation directly references CMS and Atlas and what we've done and, you know, we're all thrilled about it.
DANKOSKY: So what do you think is the next big physics puzzle that's out there that might get someone a Nobel Prize?
INCANDELA: Well, in our field, what's interesting is that we have this great, great model now, standard model, which explains pretty much in great precision and accuracy everything we can see, but as you know well, 95 percent of the universe is dark to us and we're not sure what it's made of.
And in particular, dark matter is really something we're going after. Could be related to something called super symmetry, could have relations to the Higgs, and it's something we're hoping to chase down here at CERN when we go back into operation in a couple of years at higher energy, and it's really our biggest target.
And that would be, in some sense, a much bigger discovery if we can see that we're making dark matter.
DANKOSKY: Well, here's to another big discovery. Joe Incandela is head of the CMS experiment at CERN, the European organization for nuclear research in Geneva. He's also professor of physics at the University of California Santa Barbara. Thank you so much for joining us.
INCANDELA: It's been a pleasure.
DANKOSKY: Now we have to take a break. When we come back, the Nobel Prize in chemistry. Stay with us.
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DANKOSKY: This is SCIENCE FRIDAY and I'm John Dankosky. We're talking this hour about this year's Nobel Prizes. Next up, the Nobel Prize in chemistry, awarded to three scientists who pioneered the field of computational biology, modeling things like proteins and chemical reactions on the computer. Now keep in mind, they were doing this back in the 1960s and '70s so your cell phone probably has more memory and processing power than the computers they were using this to do Nobel Prize-winning work.
Now my next guest is one of the recipients of this prize, the gentleman you heard earlier in the program saying that getting the phone call from Sweden felt like five double espressos. Michael Levitt is winner of the 2013 Nobel Prize in chemistry and a professor of structure biology at Stanford University in California. Welcome to SCIENCE FRIDAY and congratulations.
LEVITT: Good morning, John. Thank you so much. It's great to be on SCIENCE FRIDAY. I'm a super fan. I'm not going to say that I recognize Ira's voice much more than yours, but I checked you on the Internet and your qualifications, so it's great to be interviewed by you. I just want to congratulate Randy because Randy Schekman and I have gone back a long way and we interact in many, many ways and I'm not sure if he's still listening, but congratulate him and the other prizewinners.
And yeah, it's a great feeling.
DANKOSKY: And have you come down from this espresso high?
LEVITT: Yeah, I mean, there's probably espresso adrenalin. The interview that I gave 13 or 14 hours later fortunately was in Hebrew and it will not be seen by people, but there were comments in there that I'd rather not repeat on the radio. Very nice ones, but I think at one point I said I feel like I'm 16 years old so I have no ego. Just kind of (unintelligible).
DANKOSKY: What I've been asking people to do so far is explain to our audience what exactly it was that you've done to win the Nobel Prize, so give us a little primer on this, laying the foundations for computational chemistry and biology. Tell us a bit more.
LEVITT: Okay. So basically (unintelligible) people are pretty used to simulating things. We simulate the weather, weather predictioners, you know, you simulate the weather system, you see whether it's going to be in 24 hours, and you (unintelligible) in California the best predictor is tomorrow's weather will be like today's weather, and (unintelligible) actually heard that on the radio once.
But the other systems are not quite as predictable. We predict how airplanes will behave in wind tunnels. We don't need to have wind tunnels anymore. We predict how nuclear bombs explode, we don't actually have to do testing, so basically the idea of simulation has become very, very commonplace, principally because computers have become so cheap.
When we started doing this in the, I guess, I started in '67, I should say that I was 28 years old and had just finished a BS degree in physics. I didn't have my PhD yet. I took like a year between my BS degree and my PhD degree. At that time people were starting to think that small molecules could actually be simulated, so small molecules probably let's say up to 50 atoms.
And a simulation of any system depends on how many degrees of freedom, and you can think about each atom as being a degree of freedom. Maybe 30 atoms would be a fairly big molecule. I was actually working with Arieh Warshel, who is a co-winner with me, and we were both working under a man called (unintelligible) who was the guy who had the idea about doing this, and his idea was is that there should be a mathematical way to treat molecules.
Now, this had been done before but what (unintelligible) idea was was that if you had a carbon atom and two different molecules, there should be some commonality in the properties of those carbon atoms, so it shouldn't be, like, carbon in one molecule is different from carbon in another molecule and they're both the same elements they should be similar.
And he called this a consistent force field. Force fields are a way in which you describe the forces between atoms. And he went on to develop this on small molecules, and also was very, very - his PhD was how you would actually derive the parameters that would give you a consistent force field, and I sort of went there as their programmer.
I'd never been programming, but they handed me the idea and (unintelligible) handbook and said go and punch cards and I guess I did and I was probably quite good at it, so that ended up being useful. But then about four or five months into this project I realize that if the program could do 30 atoms, it would probably be possible to do 1,000 atoms, and at that time the three dimensional structures of two proteins, myoglobin and lipozine(ph) had both been determined in England, one in Cambridge and one at Oxford.
And myoglobin was the first protein structure that was determined in (unintelligible) prize in 1962 for doing so. And after my year in Israel was going to go to that same lab in Cambridge, so I go the coordinates and a couple of boxes of punch cards and had use of the computer and then decided to do very similar calculations that we were doing on small molecules on these large molecules.
And to our surprise, the calculations actually were possible. They were relatively quick. The thing you said before about the power of the computer, I would say that today's cell phone is probably a million times more powerful than the computers we were using back then. And in terms of memory, we were measuring memory in kilobytes, which is a thousandth of a megabyte and most phones have a gigabyte at least, of memory.
My laptop currently has 16 gigabytes of memory, so we're talking about (unintelligible) memory and memory's important. We have lots of atoms, need lots of memory. Anyway, we did these calculations and then things looked very interesting and this - why the program I wrote ended up being important. Martin Karplus actually did it at the same lab in Israel a couple of years after I left to go to Cambridge and then I came back.
And it was sort of a period probably from 1967 to 1975 that we sort of laid the framework of how to do simulations on large molecules and even the smallest protein has at least 1,000 atoms, so this is a huge size for a chemical. Organic chemists, it's heroic to deal with something that's 100 atoms. This then laid the whole framework and I guess in the same way that simulating airplanes is really good if you want to fly in them, simulating molecules is really good if you want to design drugs and bind things to them and correct things, etcetera.
Essentially, as Randy said, inside a cell everything is highly structured and highly organized. A cell is much, much more like New York City than it is like a bag of blood. I mean, it's a very highly organized object. Everything has a shape, everything has a time, everything has a position, and all of these things interacting in a very, very precise way, which is computable.
This is what makes the whole thing so exciting.
DANKOSKY: One of the things that we actually talked with Randy about before was this idea that our ability to fund basic science and experimentation of this sort is something that seems to be going away, that indeed we're more interested in funding the applications that come out of the type of work that you do as opposed to funding basic research.
Give me your take on that and whether or not you think we're heading in the wrong direction.
LEVITT: Well, let me first say that I am super, super grateful to the NIH. I have been funded entirely by the NIH since I got to the USA 25 years ago, almost entirely. I also had some money from the Hughes funded science program. Hughes actually wasn't interested in me when I applied about ten years ago and Hughes was a wonderful choice of funding to the lucky few who have it.
So NIH has been phenomenally good for funding. I think at NIH there's a balance between multidisciplinary science programs and individual grants to people. And ten years ago when almost of the grants were in individual grants called RO1s, nowadays there are fewer RO1s and more center grants. I think you can see pros and cons in both things.
The center grants are quite good because, in sense, you can have a few good senior scientists and a few junior scientists in some way in which junior scientists can get funded. One of the things that's happened is that since scientists no longer have to retire, because of various anti-age discrimination acts, if you look back, in 1980, almost nobody over 65 had NIH funding, but a lot of people below 40 had NIH funding.
Nowadays about 20 percent of the funds go to people over 65 and nobody below 40 has funding. So I think there's a lot of different concerns here. I think that one thing I certainly agree with Randy about is that it's very, very hard to predict what's going to be important. I was asked many, many times if there was a eureka moment, and there are lots of little eureka moments when you solve a little problem that you couldn't even tell somebody about because they're so uninteresting.
You know, a program doesn't have a (unintelligible) that's a eureka moment. Suddenly your solution's clean; that's a eureka moment. The long-term payoffs, I think there's a very simple rule and that is if something takes a long time, the potential payoff is going to be much, much higher. But if you spoke to an investment banker, they would tell you that a long-term investment is likely to have a much bigger payoff than a short-term investment.
I think unfortunately we got used to instantaneous gratification. We're not prepared to do maybe as much long-term investment as we used to. We're very involved in how popular we are today, but I actually don't see it as a really big symptomatic problem. I think, you know, and I'm not saying that everything is wonderful in this country. But when (unintelligible) see things in context, and I think that there are many really, really good things about U.S. funding, I think the federal government funding is managed in an extremely fair, balanced way (unintelligible) reviewed incredibly carefully by the community.
The program office at the NIH are incredibly dedicated. I think they are the ones who are suffering most because of the closure because they have - they know that all their customers there, their grantees are suffering. And they're really suffering. They can't even use their emails. So I think that, you know, we also have to see this in the context of the world. And the U.S. system is still the envy of the entire world. I guess we're sort of lucky that Europe hasn't got its act together as well as they should yet.
(LAUGHTER)
LEVITT: So, you know, I think the other thing that is enormously important, if you just look, for example, all three Nobel Prize winners in chemistry weren't born in this country. Martin Karplus is from Austria, Arieh Warshel is born in Israel, I was born in South Africa. And I think U.S.A. has had and still has a very liberal immigration policy, certainly compared to the rest of the world. And this is something which is an enormous bonus. I'm not complaining.
DANKOSKY: Yeah.
LEVITT: I'm somewhat allergic to the fact that Nobel Prize winners feel they can tell people what to do...
(LAUGHTER)
LEVITT: ...in any area. These are really, really hard problems. And, you know, I think if I wanted to sit down and say be worried about the future of funding, the only way I could (unintelligible) do it full time, to discuss it with politicians, to do all the maneuvering you have to do. And quite frankly, I'm still too excited about my science. I don't want to do this full time.
DANKOSKY: And because we just have a moment left, what is the science you're doing right now? Tell us what's next for you, quickly.
LEVITT: OK. So we are doing - I joke with my friends - last week was a phenomenal week in my science. We found a way to compare the genomes of all organisms. We can build family trees and genomics (unintelligible) in months. We have found a way to speed up very important calculations in X-ray crystallography. It used to take two hours, and it now takes 10 milliseconds. That's almost a million-fold increase, it's a 700,000 increase.
And finally, we are finding a way to simulate motion on very large systems in (unintelligible) your laptop. And the reason I'm stressing computer time is, is that you can do something very quickly, then the whole paradigm of how you do it changes. So I sort of joke and say that, you know, what I want to do with the next year is actually earn the Nobel Prize that I have.
(LAUGHTER)
LEVITT: So I'm working for that, and having enormously good time. And I don't want to become a celebrity. My family loves being celebrities. My 10-year-old grandson is really excited. He's also called Barack and he's really excited that I'm going to be meeting the president in...
(LAUGHTER)
LEVITT: ...early in December. But, you know...
DANKOSKY: But, so this is a bigger deal for them as far as the celebrity than for you. But I'll tell you, Michael Levitt, it sounds in your voice as though you are very excited. And we're thrilled to be talking with you today.
LEVITT: Thank you so much.
DANKOSKY: Thank you very much. Michael Levitt is...
LEVITT: Alright, John. Thank you...
DANKOSKY: ...winner of the 2013 Nobel Prize in chemistry, a professor of structural biology at Stanford University in California. I'm John Dankosky, and this is SCIENCE FRIDAY from NPR. Transcript provided by NPR, Copyright NPR.