Interview with Professor Phillip Sharp by Joanna Rose, science writer, 4 December 2001.
Professor Sharp talks about pleasant places in his life; how curiosity has directed his life (1:55); the Nobel Prize and the work behind it (4:23); the Human Genome Project and split genes (5:10); the next big challenge in biology (8:05); the work with his company Biogen (10:34); and his thoughts about genomics research (13:45).
Professor Phillip Sharp, welcome to Stockholm and to this Nobel interview and I think that we will start from the beginning.
Phillip Sharp: It’s always a good place to start.
You start your autobiography writing these words “A sense of place was and remains an important part of my life” and I wanted just to ask you what did you mean by this sentence.
Phillip Sharp: I mean by the sentence that I have always found that I am comfortable in identifying myself with certain special places. I grew up on a farm in Kentucky, a family farm, a small farm, and I identify with that place. I go back every year and it’s always relaxing and home. I worked at MIT for 30 years almost and it’s an outstanding institution, does tremendous research and education and I’ve been in the same office all that time. It’s a place, I go there, it’s one of those pleasant places that I have. So, I tend to identify with certain places and enjoy working there.
But MIT’s very far away from a farm.
Phillip Sharp: Very far away from the farm and very different backgrounds, very different places and histories, but both special in the sense that one place it’s special, that was my place and then at MIT it’s a special place to do science and engineering. It’s a spectacular research institute.
So how come you did this big step from the farm to this institute?
Phillip Sharp: It was a step driven by curiosity. I clearly did not want to spend my life being a farmer. I enjoyed the time when I was young, but it wasn’t intellectually stimulating and the world was very confined and as I looked out on the world and thought about what I would like to do, I would like to continue learning and science gave me the opportunity to continue learning, even today. As I flew across the Atlantic Ocean I was taking research papers written by colleagues in the field and learning from them and it’s just terribly enjoyable being able to understand in detail how other people think and how problems unfold and adding your own little bit to it and creating something new and that’s a wonderful life. It’s just an enjoyable way to spend one’s time.
When you look backwards can you see when one could, for the first time, see a Nobel Prize winner in the future in you?
Phillip Sharp: Oh, I had no idea about a Nobel Prize. When I was about 10 or 11, I started getting fascinated about science and mathematics and the area of study that I excelled at, other people admired my ability to do it and then as I rose through science and at each stage did well and moved to MIT I knew I was in a research community that was absolutely at the forefront of what was going on in the world and I had great colleagues in my environment to talk to about, you know, cutting edge research and there I began to do research that I knew was important. Now, there’s many, many great scientists out there who cannot be blessed by a Nobel Prize; there just aren’t enough around and never did I think I was going to necessarily see a Nobel Prize but I knew I was doing very good science and enjoyed that and that’s what life is about, it’s doing good science. If you’re a scientist that’s what you want to do and have people appreciate it. It’s wonderful when people appreciate it.
Yes, and this was genetics that you were in? You were two that got the prize, Richard Roberts.
Phillip Sharp: Rich Roberts and his group worked at Cold Spring Harbor and my group worked at MIT and in parallel we made this discovery of the split gene structure.
So you worked day and night? Was it the big race there?
Phillip Sharp: We worked day and night. We didn’t actually know at the time we were both on the same thing. It was at the end when we started to talk to people about this new discovery that we realised that there was another lab who was talking about a new discovery too and as we got together and compared our results it was clear that we had come to similar conclusions at about the same time.
The last announcement about HUGO, the human genome project, also revealed that we have much less genes that you were hoping for?
Phillip Sharp: I mean from a biologist’s point of view the fewer the better because we would like to understand how those genes function in the physiology of what makes us work as a human being and the estimate at the end of the day was that there are 35,000 genes.
Instead of 100?
Phillip Sharp: I use the term estimate because of this mosaic gene split structure, this split gene structure, it’s very difficult to identify those little bits of information that are genes.
Hidden in the garbage?
Phillip Sharp: They may be hidden in the garbage. There could be many other genes but even with the genes we know, because of this split gene structure, that a gene is split up into 10 or 20 different pieces, we now know that as the gene is expressed, different pieces of that gene can be joined together to make the protein, and this gives you the ability to use combinations in different cells in the body. For example, there’s been recently described the gene in the brain of a fruit fly, a simple fruit fly, one gene, and that gene has the ability to be expressed in 38,000 different proteins.
Because of the split genes?
Phillip Sharp: The split genes and alternative splicing, 38,000. There’s more variations in the way that gene can be expressed than there are genes in the whole genome. When we look at 35,000 genes we know more than half of them are alternatively spliced. We look at a complexity that’s much larger than 35,000. We’re looking at complexities of hundreds of thousands of possible variations in gene expression that could give rise to the complexity that you see in the different cells and different functions of our bodies. So, though we have what is thought to be 35,000 genes, we know that those 35,000 genes can generate a great deal more complexity than just 35,000 genes. But, even with 35,000 genes, if you take one here and one there and one there and one there and mix them in different combinations at different times you can make an enormously complex machine. So, we have a lot to understand yet in biology. The genome is not the end of biology. The genome is actually just the beginning of biology. It is going to set us on a whole new plane or rate of discovery that will make it fascinating for decades to come.
So what is the next challenge in biology do you think?
Phillip Sharp: The next challenge in biology. Well, there’s so many challenges, and so little time. The challenges of how we are formed. We’re making great progress on how development of a complex organism such as ourselves, with skin and hair and all these other different tissues develop from the 35,000 genes. We’re going to understand that and that’s going to underwrite a lot of development of new drugs and treatment for diseases but then we look at the real challenge and ultimate challenge. There’s nothing that a human biologist would like to study more than the brain, the human brain. It’s a fascinating organ.
So this is a new field you’re moving into?
Phillip Sharp: It’s a new field I’m moving into and I’m leading the development of institute at MIT but if you think about that as an area of science first you’ve got the biology and physiology and how the brain works. I mean that’s a fascinating substance unto itself but then as we understand more about how the brain functions and what’s the physiology and part of emotion and intuition and all these other things. It has implications for culture, it has implications for communication, it has implication for education, it has implications for economics. It’s just a wonderful interface between biology and the rest of society and culture. So I see, as one of the great challenges of the future, developing a more complete understanding of how the brain functions and how we modify it by our educational cultural experiences and use that to do creativity and that’s a fascinating field and I think young people are going to flock to it, it’s going to change us, the way we view ourselves, it’s going to change the way we view culture and history. It’s a wonderful field and I’m hoping by taking the responsibility of being director of a new institute at MIT to expand that field at MIT and get a lot of bright young people working on it and enthusiastically making progress.
You’re also involved in a biotech firm since very long time ago. Biogen.
Phillip Sharp: Biogen. I was very fortunate early on. I entered science just at the time of recombinant DNA so the early stages of my career recombinant DNA developed that I assume in my research programme the manipulation of DNA and this was a new tool and frequently when a new tool arrives in science it changes science and it certainly was the case for recombinant DNA. It gave us the ability to take DNA from different species and put them together.
When was it?
Phillip Sharp: It was in the 1975-76-77 period in which that technology really became quite widely spread. I’d learned about it in the early 1970s and participated in it but then in 1976-77 we knew we had this technology, we knew we could make new pharmaceuticals and that they would benefit man and a group of scientists, myself and Wally Gilbert out of the US, Charles Weissmann and Bernard Mach out of Switzerland, Heinz Schaller and Peter Hofschneider out of Germany and Ken Murray and Brian Hartley out of England all got together and stared a company with a bunch of capitalists who gave us money to do it and the company’s called Biogen and it’s still a very significant biotech company. It’s located in Boston and there are some remarkable things that Biogen’s done. It holds the intellectual property patents for hepatitis B vaccine and most of the people in Europe and in the US and many parts of the world have been vaccinated with that vaccine. It holds the patent for alpha interferon and it’s one of the major treatments for hepatic infections from hepatitis B and C and it’s really changed a lot of people’s lives and it now is selling the major drug for multiple sclerosis called avonex. The first type of drug made interferon and several companies have it and Biogen’s the market leader, but it’s changed people’s lives because it gives a significant fraction of people better control of that disease, which is a horrible disease. I’ve been fortunate to being able to touch many people’s lives by having participated in developing a technology and then helping translate it into the private sector and then have it used to improve the quality of people’s lives around the world. So that’s been a great experience and I’ve learned a lot from that experience and how business works, how societies work and all those sorts of things and it was a tremendous time in science.
In the context of genomic research there has been quite large criticism against commercialisation of science. What do you think about that?
Phillip Sharp: In the genomics research there’s been this specific issue that we have human genome sequence and do we patent it and do we patent specific parts of it, how assessable to the scientific community around the world is this sequence going to be and I think the scientific community has come down on the side strongly that it will be available and that people will be able to do research with it. The other side is that to develop a pharmaceutical requires easily between $400 and $800 million.
From the basic research to the product?
Phillip Sharp: From the basic research to the approval for sales. Now those two numbers just appeared in the press in the US from a news study and it’s not important to go through the details; they’re both very large numbers and to be able to husband those resources, apply them and get new drugs requires the ability to use patents to recover those investments because you make the investments long before you actually sale. Now, I’m not justifying the industry. It’s a very profitable industry, there’s no question about, highly profitable industry but in addition it does deliver drugs, right, and most of the drugs that we use today, almost all of them without exception, they have been developed through that mechanism and I’m confident people will not make those types of investments without being able to patent and recover their investment with some profit after they make it. Now, societies are going to debate just what the amount of profits reasonable and how long those patents should be used for creating a monopoly but there have to be some mechanism to allow recovery of those costs.
So this will be the future of biotechnology?
Phillip Sharp: I mean that’s the way pharmaceuticals have been structured for the last decades and in biotechnology it will also be the case. Biotechnology is predicated on new science, new things happening so fast that large organisations find it difficult to incorporate those new things and I think the addition of the genome sequence and our abilities to use new ways of studying cells and physiology is going to mean that there’s going to be a continual rapid advance in biological science creating many opportunities and therefore biotech will continue to be a thriving subpart of the pharmaceutical world for at least a decade or more and will bring us new treatments for diseases and infections and other things.
So we can be optimistic about that?
Phillip Sharp: We can be optimistic. I’m the eternal optimist.
Thank you very much for this interview Professor Phillip Sharp.
Phillip Sharp: Thank you.
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