QNAS
QNAS
QnAs with Jan Svoboda Brian Doctrow, Science Writer
HIV belongs to a family of viruses known as retroviruses. The ability of retroviruses to synthesize DNA using their RNA genome as a template distinguishes them from other viruses. The synthesized DNA can then integrate itself into the genome of an infected cell, becoming what is known as a provirus. Jan Svoboda, a cell and molecular biologist at the Czech Academy of Sciences, who was elected to the National Academy of Sciences in 2015, has spent over half a century studying the mechanisms of retrovirus infection. His pioneering work in the 1960s with the Rous sarcoma virus, a retrovirus that causes tumors in chickens, provided some of the first definitive evidence for provirus integration into the host cell genome. In his Nobel lecture, virologist Howard Temin of the University of Wisconsin–Madison, who proposed the existence of the provirus in 1960 and won the Nobel Prize for Medicine in 1975, acknowledged Svoboda’s independent proposal of the provirus concept (1). Svoboda recently spoke to PNAS about his scientific work, as well as his experiences as a scientist in the Czech Republic both during and after Communist Rule. PNAS: The Rous sarcoma virus has been your experimental system of choice for decades. How did you become interested in studying this virus?
Jan Svoboda. Image courtesy of Miluska Snaibergova.
Svoboda: I had been attracted to biology for many years before. I read a lot and I also had been actively engaged in experimentation, and fortunately I had been accepted to study the natural sciences. To do work in cell biology, it was required to work in tissue culture. And the only place which had been interested in tissue culture had been Dr. Keilova’s laboratory at the biological institute of the Academy [Czechoslovak Academy of Sciences]. I went there and learned how to handle the tissue cultures, especially how to handle
tumor cell growth. And in this laboratory I also first came in contact with the Rous sarcoma virus. I had been so impressed by the fact that once you infect the cell with the virus, it becomes fully changed in a few days. So this was my inspiration and start. PNAS: What, in your view, has been the biggest impact of your work? Svoboda: Because I had been so deeply concentrated on this one tumor line derived from rat tumor induced with chicken Rous sarcoma virus, it paid off very much and led to the very clear-cut conclusion that the Rous sarcoma virus, being an RNA virus, can become integrated in the cell genome, in a fixed way, as a provirus. And I think this was of the greatest importance, and this was reflected also by Howard Temin. I highly value, also, the clear-cut definition of the fact that to get maturation of the retrovirus in nonpermissive cells, for example mammalian cells infected with avian virus, you can complement it by fusion with cells, which are sensitive to the virus. This was clear-cut indication that cell factors are involved and important in the control of retrovirus infection. PNAS: How does your work inform strategies for treating retroviral infections? Svoboda: The simpleminded approach that just by chemical inhibition we can get rid of retrovirus infection is not right, as we know now, because retroviruses—HIV included—get integrated in the cell genome. And for quite a long time they can become silent. They don’t produce anything; they don’t go through rounds of replication, so chemicals can’t act on the viruses. And therefore we have to find new approaches: how to get rid of a viral genome which became a part of the cell genome. PNAS: You’ve spent most of your scientific career in the Czech Republic. What are the particular challenges to doing science in resource-limited countries? Svoboda: In the small countries, you can’t cover all topics. In a small country you have to concentrate on original-minded approaches, on people who are creative, who are highly knowledgeable, who are able to
This is a QnAs with a recently elected member of the National Academy of Sciences to accompany the member’s Inaugural Article on page 3927.
3910–3911 | PNAS | April 12, 2016 | vol. 113 | no. 15
www.pnas.org/cgi/doi/10.1073/pnas.1603145113
inspire the others, and who are fully committed to their research. I think this is a very important aspect because, especially in the small Eastern countries, you can’t import the leading scientists from the West. You can’t pay for them. It’s completely different from the United States. And therefore you have to create your basis at home. And this is how a small country can really contribute to the general knowledge: science that’s based on their roots, their experiences, their devoted people, and science that is able to recruit new scientists, young scientists, who are willing to take a risk and to really try something new. Consequently, more insight, flexibility, and responsibility in science evaluation are also required. The present scientific endeavor also demands sophisticated technologies. Therefore, establishment of the required array of wellfunctioning technical facilities is of great importance.
publish in PNAS for political reasons. How have things changed since the fall of the Communist regime?
PNAS: In your Inaugural Article (2), you mention how your research was determined in part by what questions could be answered with the limited resources at your disposal.
PNAS: Based on your experiences, what is the importance of a free and open society for science?
Svoboda: Right. The vision should be realistic and should fit within the framework of your possibilities. PNAS: Your Inaugural Article (2) also discusses some of the difficulties you encountered working under the Communist regime, such as not being allowed to
Svoboda: At the beginning, things became a bit confused because people supposed that just importing something from West would save us. It is not true. You have to import, but in addition you have to build upon something. In fact, Americans helped us very much by different types of grants, which were provided to our scientists: Fogarty Grants, and, even better, NIH grants, and so on. This was very helpful at the beginning, after the fall of the Soviet empire. Of course the former Eastern countries are still in some sort of difficult position. We went through periods when the sciences had not been funded properly. Our situation now is improving at the moment. The European Union stimulated creation of some new centers, which are focused on special topics. The question is, how much support will they get in the future?
Svoboda: Open society is a prerequisite for science. Without an open society, you can’t get real progressive science. If you go to history, Bertrand Russell wrote an excellent book, A History of Western Philosophy, where he mentioned that the Greeks with the loss of their independence lost their originality of thinking. So losing democracy, losing civil society, you lose the possibility to create.
1 Temin HM (1976) The DNA provirus hypothesis. Science 192(4244):1075–1080. 2 Svoboda J (2016) On board a raft or boat in the retrovirus sea. Proc Natl Acad Sci USA 113:3927–3931.
Doctrow
PNAS | April 12, 2016 | vol. 113 | no. 15 | 3911
QNAS
QnAs with Jan Svoboda Brian Doctrow, Science Writer
HIV belongs to a family of viruses known as retroviruses. The ability of retroviruses to synthesize DNA using their RNA genome as a template distinguishes them from other viruses. The synthesized DNA can then integrate itself into the genome of an infected cell, becoming what is known as a provirus. Jan Svoboda, a cell and molecular biologist at the Czech Academy of Sciences, who was elected to the National Academy of Sciences in 2015, has spent over half a century studying the mechanisms of retrovirus infection. His pioneering work in the 1960s with the Rous sarcoma virus, a retrovirus that causes tumors in chickens, provided some of the first definitive evidence for provirus integration into the host cell genome. In his Nobel lecture, virologist Howard Temin of the University of Wisconsin–Madison, who proposed the existence of the provirus in 1960 and won the Nobel Prize for Medicine in 1975, acknowledged Svoboda’s independent proposal of the provirus concept (1). Svoboda recently spoke to PNAS about his scientific work, as well as his experiences as a scientist in the Czech Republic both during and after Communist Rule. PNAS: The Rous sarcoma virus has been your experimental system of choice for decades. How did you become interested in studying this virus?
Jan Svoboda. Image courtesy of Miluska Snaibergova.
Svoboda: I had been attracted to biology for many years before. I read a lot and I also had been actively engaged in experimentation, and fortunately I had been accepted to study the natural sciences. To do work in cell biology, it was required to work in tissue culture. And the only place which had been interested in tissue culture had been Dr. Keilova’s laboratory at the biological institute of the Academy [Czechoslovak Academy of Sciences]. I went there and learned how to handle the tissue cultures, especially how to handle
tumor cell growth. And in this laboratory I also first came in contact with the Rous sarcoma virus. I had been so impressed by the fact that once you infect the cell with the virus, it becomes fully changed in a few days. So this was my inspiration and start. PNAS: What, in your view, has been the biggest impact of your work? Svoboda: Because I had been so deeply concentrated on this one tumor line derived from rat tumor induced with chicken Rous sarcoma virus, it paid off very much and led to the very clear-cut conclusion that the Rous sarcoma virus, being an RNA virus, can become integrated in the cell genome, in a fixed way, as a provirus. And I think this was of the greatest importance, and this was reflected also by Howard Temin. I highly value, also, the clear-cut definition of the fact that to get maturation of the retrovirus in nonpermissive cells, for example mammalian cells infected with avian virus, you can complement it by fusion with cells, which are sensitive to the virus. This was clear-cut indication that cell factors are involved and important in the control of retrovirus infection. PNAS: How does your work inform strategies for treating retroviral infections? Svoboda: The simpleminded approach that just by chemical inhibition we can get rid of retrovirus infection is not right, as we know now, because retroviruses—HIV included—get integrated in the cell genome. And for quite a long time they can become silent. They don’t produce anything; they don’t go through rounds of replication, so chemicals can’t act on the viruses. And therefore we have to find new approaches: how to get rid of a viral genome which became a part of the cell genome. PNAS: You’ve spent most of your scientific career in the Czech Republic. What are the particular challenges to doing science in resource-limited countries? Svoboda: In the small countries, you can’t cover all topics. In a small country you have to concentrate on original-minded approaches, on people who are creative, who are highly knowledgeable, who are able to
This is a QnAs with a recently elected member of the National Academy of Sciences to accompany the member’s Inaugural Article on page 3927.
3910–3911 | PNAS | April 12, 2016 | vol. 113 | no. 15
www.pnas.org/cgi/doi/10.1073/pnas.1603145113
inspire the others, and who are fully committed to their research. I think this is a very important aspect because, especially in the small Eastern countries, you can’t import the leading scientists from the West. You can’t pay for them. It’s completely different from the United States. And therefore you have to create your basis at home. And this is how a small country can really contribute to the general knowledge: science that’s based on their roots, their experiences, their devoted people, and science that is able to recruit new scientists, young scientists, who are willing to take a risk and to really try something new. Consequently, more insight, flexibility, and responsibility in science evaluation are also required. The present scientific endeavor also demands sophisticated technologies. Therefore, establishment of the required array of wellfunctioning technical facilities is of great importance.
publish in PNAS for political reasons. How have things changed since the fall of the Communist regime?
PNAS: In your Inaugural Article (2), you mention how your research was determined in part by what questions could be answered with the limited resources at your disposal.
PNAS: Based on your experiences, what is the importance of a free and open society for science?
Svoboda: Right. The vision should be realistic and should fit within the framework of your possibilities. PNAS: Your Inaugural Article (2) also discusses some of the difficulties you encountered working under the Communist regime, such as not being allowed to
Svoboda: At the beginning, things became a bit confused because people supposed that just importing something from West would save us. It is not true. You have to import, but in addition you have to build upon something. In fact, Americans helped us very much by different types of grants, which were provided to our scientists: Fogarty Grants, and, even better, NIH grants, and so on. This was very helpful at the beginning, after the fall of the Soviet empire. Of course the former Eastern countries are still in some sort of difficult position. We went through periods when the sciences had not been funded properly. Our situation now is improving at the moment. The European Union stimulated creation of some new centers, which are focused on special topics. The question is, how much support will they get in the future?
Svoboda: Open society is a prerequisite for science. Without an open society, you can’t get real progressive science. If you go to history, Bertrand Russell wrote an excellent book, A History of Western Philosophy, where he mentioned that the Greeks with the loss of their independence lost their originality of thinking. So losing democracy, losing civil society, you lose the possibility to create.
1 Temin HM (1976) The DNA provirus hypothesis. Science 192(4244):1075–1080. 2 Svoboda J (2016) On board a raft or boat in the retrovirus sea. Proc Natl Acad Sci USA 113:3927–3931.
Doctrow
PNAS | April 12, 2016 | vol. 113 | no. 15 | 3911
