November 28, 2008
NIH Podcast Episode #0072
Balintfy: Welcome to the episode 72 of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I'm your host Joe Balintfy. Thanks for tuning in - I hope you had a great Thanksgiving. Coming up in this episode, we won't talk about food. Instead, we have an interview with the former director of the NIH about the prestigious Pioneer and New Innovator Awards. But first, news stories about how the HIV virus has been spreading among humans earlier than though, and how a specific gene plays a role in drug resistance. Those stories and the interview are coming up next on NIH Research Radio.
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New Findings Indicate HIV/AIDS Pandemic Began Earlier than Previously Thought
Balintfy: Do you know how long the HIV virus has been around? Well, recent findings show that the HIV/AIDS pandemic began earlier than previously thought. New research indicates that the most pervasive global strain of HIV began spreading among humans closer to the turn of the century, not during the 1930s, as previously reported. The research, led by Dr. Michael Worobey, of the University of Arizona in Tucson, was co-sponsored by the National Institute of Allergy and Infectious Diseases.
Young: What Dr. Worobey was able to do is take samples that had been stored in a laboratory in Kinshasa and develop a technique to isolate DNA and RNA from it.
Balintfy: Dr. Janet Young, from NIAID explains that Dr. Worobey was able to compare the HIV samples.
Young: He was able to show first of all that they differed by twelve percent, showing that they were related, but that a considerable amount of evolution had taken place.
Balintfy: Roughly 40 years of evolution. Dr. Young comments that by knowing that HIV entered the human population earlier than previously thought, between 1884 and 1924, researchers will be better informed in their efforts to develop a vaccine. Dr. Rosemary McKaig, also with NIAID, concurs:
Dr. McKaig: By knowing the circumstances around that entry, we might be able to somehow evaluate better how to deal with it in the human population both through prevention and treatment, because it continues to evolve.
Balintfy: Dr. McKaig emphasizes that Dr. Worobey's HIV discovery is significant for both viral evolution, and human evolution.
McKaig: And as we attack our problems today, we need to, one, look at other viruses that might be entering into the population, that are quiescent right now; but we can also look at this virus and say, "there was a time in history when it wasn't here" and "what was it about humans that changed that made it explode into our population." And he has some great concepts that he's thinking through about those issues because they relate to our prevention techniques now and how we might be able to actually finally get this virus out of our population because that's really what we'd like to do, whether it's eradicate it, or treat it out, or where we no longer have effective transmissions.
Balintfy: For more information on this study, Dr. Worobey's paper in Nature magazine, and HIV research, visit www.niaid.nih.gov.
Gene Delivers Clues about How Cancer Cells Develop Resistance to Chemotherapy Drug
Balintfy: In this next report, we learn how researchers have shown that increased activity of a gene called SIRT-1 in cancer cells plays a significant role in the development of resistance to a chemotherapy drug. Wally Akinso has the story.
Akinso: In a National Cancer Institute study, researchers have discovered clues about how cancer cells develop resistance to chemotherapy. In the study, researchers have shown that increased gene expression in cancer cells which is the process by which inheritable information from a gene is made into a functional gene product, such as protein, plays a significant role in the development of resistance to the chemotherapy drug cisplatin. Dr. Michael Gottesman, of the NCI's Center for Cancer Research and an author of the study, discusses the findings.
Gottesman: We've been trying to understand why it is that cisplatin isn't an even more effective drug, why there are tumors that are resistant to it or become resistant. And we developed in our laboratory a model system using cancer cells and found that they became resistant cisplatinum in a way that involved the increase expression of a gene-which is called SIRT 1.
Akinso: Cisplatin, a chemotherapy drug that contains the metallic element platinum, is widely used in the treatment of many types of cancer, including bladder, lung, ovarian, and testicular cancer. It slows or stops the growth of cancer cells by binding DNA. Dr. Gottesman feels that knowing more about how cells become resistant to cisplatin will help researchers increase the effectiveness of this treatment.
Gottesman: So our goal is to improve the treatment of cancer. It's to make the drugs we currently have more effective. And to enable us to develop new drugs that we can use that won't be effected by the resistance mechanisms.
Akinso: Dr. Gottesman and colleagues are developing molecular tools to define the drug-resistance genes that are expressed in individual cancers, and, in the future hope to use this information to predict a patient's response to therapy and to design new ways to get around resistance. For more information about this study, visit www.cancer.gov. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Balintfy: Thank you Wally. Dr. Gottesman’s findings were published in the September 15 issue of Molecular Cancer Research. When we come back, an interview with Dr. Elias Zerhouni about how the NIH extended its commitment to transformative research with 138-million dollars. Stay tuned, we’ll be right back.
NIH Extends Its Commitment to Transformative Research with $138 Million for Director's Pioneer and New Innovator Awards in 2008
Balintfy: Dr. Elias Zerhouni stepped down as the director of the National Institutes of Health, at the end of October. One of the hallmarks of his tenure was the launch of new programs to encourage high-risk innovative research, such as the Director's Pioneer Awards and New Innovator Awards. Before Dr. Zerhouni left, we talked about those programs. We started with the Director’s Pioneer Award.
Dr. Zerhouni: The word “pioneer” is a very important word because when you look at science, you have very different ways of doing science. You know you have what we call settler science when somebody has found something completely new and others come behind that person and fill in the blanks, if you will. And then you have the explorer science where you know there’s a new land, a new continent, and you’re exploring it. The pioneer is the one who discovers whether there’s a continent and where to go. So I wanted to send a signal that we needed to really encourage no-boundary blue sky research from the best and brightest and not limit them, you know fund them well, give them five years of freedom and see what happens. So that’s what the Pioneer Award is all about.
Balintfy: Is that why the Pioneer Awards were created?
Dr. Zerhouni: You know when you get into the routine of something, sciences repeats itself and then you do things and then you forget that at the end of the day, scientists are discoverers. And often what you hear when you keep doing things in a certain way is that you may be missing things, that maybe you’re too conservative, that maybe you’re too tradition bound, that perhaps what you’re doing is not as innovative as you think it is. So how do you prove a point like this? Because my experience is that when you have a situation like this, you know half the people say things are going very well, you don’t need to change anything. And then the other half say things are going very badly, you need to change everything. So how do you go about doing that?
So my strategy was look, I’m a scientist; let’s do the experiment. So we launched the Pioneer Award so that we would see who comes in to apply for a Pioneer grant and then we’ll compare these scientists who applied for that to the scientist who applied to our regular grant program, and then we’ll do over five years we’ll do a real scientific study. And see, okay, did the people who come to the regular program didn’t get funded and then they got funded through the Pioneer Award? Were there ideas that only came through this pathway and not the other? And that was the idea behind the Pioneer Award is not only to encourage bold research, but to truly understand for the first time whether or not we were doing a good job at identifying outstanding research.
Balintfy: Can you share some impacts or give examples of outstanding research that is being recognized?
Dr. Zerhouni: I can give you examples, other examples. I’m fascinated by there’s a young fellow his name is Carl Deisseroth from Stanford and he came up with an idea, which I think is revolutionary and that is that he can excite neurons through very specific wavelengths of light and he can do it to specific neurons so that this is the first time we’re going to be able to study complex neural science and how neurons are interacting in life, in vivo. It is done in a mouse. And this is something that if you had asked me three years ago was this possible? You ask any neuroscientist is it possible? The answer was no. In fact, he applied for grants, couldn’t get it. People thought it was real blue sky, so he was funded through the Pioneer Award.
And we have examples after examples. Dr. Eric Jarvis is trying to understand how hearing and voice interact and found that in fact in the brain those are intertwined. So the way we’ve learned how to speak came from our ability to hear, but more importantly to find that these nerve fibers were integrated with our voice fibers, if you will, that’s a simple way to explain it for the general public. But what it meant is that genes were turned on or off depending on what you heard. That’s why when you can’t hear, you can’t speak. And he showed the genetic basis in the molecular, genetic and neural basis of that. I thought that was fascinating, that’s fantastic. So case after case you realize that you can truly stimulate new ideas by programs like this.
Balintfy: How does the Pioneer Award compare to the New Innovator Award?
Dr. Zerhouni: So once we did the Pioneer Awards as an experiment, as I said. We wanted to learn from it. And then what we realized is that we had obviously committed dollars to that and then what I realize is that you really needed to go one step further in terms of number of people you could fund. But the independence of a scientist early in their career is also a condition for them to be creative. In other words, I as a scientist myself, I was very fortunate to make contributions when I was young at 30, 31 years old.
But here’s the thing, the thing that I thought was important was to encourage risk taking early in the career. Pioneers can be pioneers at any time in their careers. The Pioneer Award is open everywhere, but I wanted to really fund and support about 30 grants, which we do about 30, 31 grants a year because that’s the money we had. I requested the money from Congress and I said, “Listen, what’s really important here is not so much that you have great ideas, but you encourage risk taking, because the greatest risk in science is to stop taking risks.” And I was concerned that because of the tight budgets and restrictions and, you know the more established scientists are more competitive, they have a track record. I said what we need to do is give a chance to those who are within ten years of their degree and to really tell them we welcome risk taking. We don’t want you to be very conservative in your science. If you have good ideas and you’re creative, come with them right now we want to support you. And that’s why we did the Innovator Award so that we would really focus on that early career scientist.
Because I believe that indeed -- you know, in Biology we tend to make our contributions between the ages of 35, 40. If you look at Nobel Prizes in Biology, that’s when they tend to occur. David Baltimore was less than 35 when he received his prize and our own Marshal Nierenberg here at the NIH who uncovered the genetic code was less than 35 years old. So you always worry about stifling innovation by telling people, “Oh wait a minute. You’re going to have to work 10, 15 years with your mentor, your boss before I can let you fly.” And I always have this saying. I said you know you don’t become a racehorse by longevity. You have to be given a chance early in life and that’s what the new Innovator Award is all about.
That’s one of the things I wanted to create, which we did through the Roadmap for Medical Research, because we were able to convince Congress that the Pioneer Awards, the New Innovator Awards, you know, there’s a new award called the Eureka Award, which is Eureka a great idea, the transformative R01s. I wanted to push as much resources to that sort of blue-sky research for innovators as early as possible in their career, but also throughout their careers because you never know when a breakthrough is going to come. It could come at any time.
But do it. Do it as a matter of discipline and try new things. Try flexible things and that’s where we -- that’s what I believe in. That’s what science is all about. You know you can’t just, you know, manage science; you have to let it go and let it happen. That’s what these programs are about, especially when budgets are tight. That’s when you want to take chances.
Balintfy: Thanks very much to Dr. Elias Zerhouni, the former director of the National Institutes of Health. For more information on the Director’s Pioneer Awards and New Innovator Awards, visit website nihroadmap.nih.gov. Also, be sure to tune into our upcoming vodcast, “I on NIH” we’ll have a report on more of those awardees Dr. Zerhouni mentioned.
Balintfy: For now, that's it for this episode of NIH Research Radio. Please join us again on Friday, December 12th when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening. NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.