War and Peace of Viruses Deliberated at Nobel Conference

Photo: Steve Waldhauser SCIENCE IN PUBLIC: Almost 6,000 people attended the Nobel Conference, showing a high degree of public interest in science. When a group of leading virus researchers and scholars presented their reports on "Virus: The Human Connection" at the annual Nobel Conference in St. Peter, Minn., last month, the story that emerged was one of war and peace. The primary themes emanating from these talks--which were open to the public--outlined a heavy viral volume of battles won and lost. Viruses still mystify humans in many ways. Where do they originate? When and where will the next viral threat emerge, and how will it be transmitted? Research science, however, has delivered humans into a new era of virology and medicinal biology--uncovering ever more sophisticated means to thwart deadly invasions as well as the technology to harness viral power to extend lives. Nevertheless, the absolute unpredictability of viruses, coupled with the continual globalization of Earth and its peoples, points to the war being waged forever, with intermittent eras of peace as scientists solve bits and pieces of the puzzle along the way. Nearly 6,000 people packed into a transformed hockey arena and two overflow auditoriums at Gustavus Adolphus College during the two-day conference, October 6-7, to hear scientific details as presented by research virologists W.K. Joklik, John J. Holland, Robert C. Gallo, virus hunter C.J. Peters, physician-researchers Gary J. Nabel and Elizabeth G. Nabel, historian Alfred W. Crosby, and theologian Ted Peters. Even before the presentations got under way, it was obvious that this was not your conventional scientific symposium. The Nobel Conference is the only public educational research science conference to have the official authorization of the Nobel Foundation, Stockholm, Sweden. Its mission is "to show the public what is happening in scientific research and to encourage our own children to consider the research sciences and not to lose them to other distractions," conference director Richard Q. Elvee told The Scientist. "Often we find in the biographies of scientists that somewhere early on they get turned on by some experience; this conference has done that for many students, and each year some 150 high schools and dozens of colleges in the Midwest are represented here." Because the conference is essentially for the public, it is designed to cover the scope and breadth of the given topic, and although some of the jargon and technological specifics are no doubt lost on some of those in attendance, "we never cheat on the research science," Elvee says. It's the conference's infusion of theology into the mix, however, that raises the eyebrows of most Darwinians. Intriguingly, Gustavus Adolphus is a Swedish Lutheran college, and Elvee, who has served as Nobel Conference director since 1981, is the chaplain. Strange? "Science is one of the ways that God creates the world," says Elvee, in explanation, adding that " Max Planck, Niels Bohr, Erwin Schrodinger, and Werner Heisenberg were all Lutherans." Still, how can you mix research science and theology? "You can't," he says with a chuckle. "They are really two different languages. But, we think we should consider what we ought to do with what we think we know." And so, to that end, a theologian has always been included in the lineup of presenters. Ted Peters Elizabeth Nabel Every year, the Nobel Conference addresses a different contemporary topic. Organizers chose viruses for this year, because as conference chair John Lammert, associate professor of biology, put it: "They're hot, and because virtually everyone of us has been affected--and infected--by them." W.K. Joklik, James B. Duke Professor Emeritus, Duke University Medical Center, a pioneer in promoting research on interactions between viruses and hosts and on the biochemistry of virus replication and multiplication, offered up a concentrated and animated review of the first "spectacularly successful" 100 years of virology. The field, he said, "has proved the key to many fundamental concepts concerning the nature, structure, and expression of genetic information." Along the way, its scientists have earned 12 Nobel Prizes. While many achievements--including "the eradication of the most deadly of human viruses, smallpox"--have been made, there is much more to learn about protein structures, virus replication cycles, the components of antiviral defense mechanisms, and the genes involved in the viral functions to overcome components of host defense mechanisms, Joklik said. He made the case for the preservation of the remaining stockpiles of smallpox virus, stressing that we still do not know why it is "so successful in overcoming human defense mechanisms, and why it is such a uniquely human pathogen." The latest experiments concerning a human protein that appears to cause tumor regression, and appears also to have antiviral properties, highlighted the Nobel Conference. Robert Gallo, codiscoverer of the AIDS virus and director of Institute of Human Virology (IHV) at the University of Maryland, Baltimore, described the protein, tentatively known as human chorionic gonadotropin associated factor (HAF), as "the most exciting thing" with which he has been involved. "We don't know what the heck it is," he said, quickly adding that his lab is now close to purifying the protein, and will then begin to determine its mechanism. The HAF protein, first described last spring after its discovery by IVH's Animal Model Division head, Joseph L. Bryant, is found in women's urine during early term pregnancy (Y. Lunardi-Iskandar et al., Nature Medicine, 4:428-34, April 1998). In animal trials, the small protein caused cancerous tumors to regress. In AIDS patients with virtually no T-cell counts, it caused T cells to increase and the virus to retreat, as well as killing Kaposi's sarcoma cells. In addition, Gallo told the crowd, "We learned that it kills every prostate cancer we've looked at, and at the same time, we found it's a powerful drug factor for all the lineages of our blood cells." In one experiment, "We were able to radiate animals with 800 rads--to their death essentially--and all the rats injected with HAF lived, and their bone marrow is completely restored." He added, "It has an antiviral effect, an antitumor effect, and [it] promotes blood cell formation." To date, it has been without toxicity "in concentrations five-fold higher than we're using." He cautioned, "There is still a lot of work to be done," but he said he hopes to begin clinical trials in two to three years. Keynote speaker at the conference was C.J. Peters, chief of the Special Pathogens Branch, Centers for Disease Control and Prevention (CDC), and author of Virus Hunter: Thirty Years of Battling Hot Viruses Around the World (New York, Anchor Books, 1997). Peters chronicled his work tracking a hantavirus that broke out in the Four Corners region of the United States in the spring of 1993 to its natural host, the deer mouse (K. Kreeger, The Scientist, 8[14]:14, July 11, 1994). He drove home the point that "new" viruses are found all the time, saying that various new strains of hantavirus have emerged in small epidemics in the Americas during the last few years. He noted that one strain, the Andes, in South America, was transmitted human-to-human, something not seen before with hantaviruses. Peters said that "the single biggest danger" for emerging new viruses are the megacities. "These are really tinder boxes for all kinds of other viruses that might want to make the leap," he warned. "But, having said that, a friend of mine who was studying monkey diseases in Kenya went to Sayonara Park, where they served a buffet outside. She was eating her salad when she saw this little African green monkey walk up and pee in the salad dressing. The point is," Peters concluded, "viruses are out there looking for evolutionary opportunities anywhere they can find them." John Holland, a biology professor emeritus at the University of California, San Diego, offered up a crash course on RNA viruses. Holland, who was among the first to show that the presence of cell surface receptors determines the susceptibility of animal and human cells to virus infection and disease, has spent the last 25 years documenting the significance of the extremely high mutation frequencies of RNA viruses. He dazzled the audience with his descriptions of the mutant swarms they produce to not only infect hosts, but to evolve, and with his elaborations on their perpetual presence and unpredictability. What virus will emerge next or when it will break out cannot be predicted, Holland explained, because of the vastness of sequence space. He said, "The number of possibilities that have to be tested to find all viable viruses, all viruses that might break out in the future, are beyond the size of the universe, a thousand universes, a trillion universes." The only thing that is certain, he concluded, is that "new epidemics are absolutely inevitable. They will occur." Alfred Crosby, professor of American Studies, University of Texas, Austin, and author of America's Forgotten Epidemic: The Influenza Epidemic of 1918 (New York, Cambridge University Press, 1990), lectured on humanity's relationship to infectious diseases through four stages. During the hunter-gatherer stage, he said, "Humanity was, by unintentional Darwinian processes, protected against many infections by their small numbers and movements." But the agricultural stage that followed, "cost a lot, in terms of human discomfort and misery," as increased trading and the domestication of various animals led to increased infections. The Eastern Hemisphere's Neolithic revolution, the stage of world integration that started around the end of the 15th century, improved transportation and created transoceanic empires that "guaranteed epidemics and the migration of diseases," Crosby maintained. Beginning in the last half of the 18th century, technological and scientific revolutions catalyzed a period of "great acceleration," leading to the current global transmission of viruses and the production through evolution of "the fittest microbes," some of which, like tuberculosis, have developed resistance to formerly effective medications. "Humanity was not genetically prepared for the environment it started creating 10,000 or so years ago," Crosby said, "and it isn't yet." Photo: Steve Waldhauser LARGER THAN LIFE: Keynote speaker C.J. Peters, the person, almost gets lost in C.J. Peters, the image, in the background. Explanations of gene therapy and various investigations now under way to forge a peaceful alliance with viruses to treat all kinds of diseases were provided by Gary Nabel, a Howard Hughes Medical Institute investigator and the Henry A. Sewall professor of internal medicine and biological chemistry at the University of Michigan Medical Center, and his wife, Elizabeth G. Nabel, professor of internal medicine and physiology, and chief of cardiology at the University of Michigan Medical Center. "Any virus you look at becomes a potential vector," Gary Nabel said. He pointed out that most viruses are now under investigation, including retroviruses for use in treating a variety of blood diseases as well as AIDS; lentiviruses to treat central nervous system disorders, dementia, Parkinson's, blood clotting disorder, and AIDS; adenoviruses to treat pulmonary diseases, cancer, heart disease, and muscular dystrophy; and adeno-associated viruses to investigate neurologic diseases. Beyond that, Nabel said, "Simple, naked DNA derived from bacteria that caused infections is now being used in a number of cancer models, DNA vaccine models, and also to treat arthritis." Photo: Steve Waldhauser PANEL DISCUSSION: Assembled for questions are, from left, Ted Peters, C.J. Peters, Conference Director Richard Q. Alvee (in background), Alfred Crosby, Bill Joklik, 1998 Conference Chair John Lammert, Robert Gallo, and Gary Nabel. To the right, not pictured, John Holland and Elizabeth Nabel. He stirred the audience with a description of his and Elizabeth Nabel's work on the development of an ebola vaccine that was successful in a trial experiment on guinea pigs last year (L. Xu et al., Nature Medicine, 4:37-42, Jan. 1998). Elizabeth Nabel explained how crippled viruses are serving as delivery vectors to send genes or DNA into targeted cells, so that new or recombinant protein can be made to treat various forms of cancer and cardiovascular disease. She said viruses have been used in concert with gene therapy to stimulate angiogenesis, as well as to curb the cell proliferation process that often occurs after angioplasty, and to kill cancerous tumors (P. Smaglik, The Scientist, 12[10]:4, May 11, 1998). "We now know that we need to take the information that we learned from these early Phase I clinical studies and bring it back to the basic science laboratory in order to improve our understanding of disease pathogenesis, how the disease evolves, as well as to develop better genes and gene vectors," she said. She also pointed out the importance of public support and funding to the future of this technology. Rounding out the conference, theologian Ted Peters, professor of systematic theology, Pacific Lutheran Theological Seminary, and Graduate Theological Union research professor, Center for Theology and Natural Sciences, Berkeley, Calif., suggested that humans should exert Promethean freedom, calling upon laboratory science and medical research to relieve suffering and to hopefully influence the evolutionary future of Homo sapiens. In the end, however, in the individual sense of pain and anguish, it's humans' spiritual freedom, the ability to "act out of the centered self" that brings hope. "The concept of co-evolution may be intellectually satisfying and it may even lead to a holistic picture of mutual symbiosis between the human and the virus, but it has a limit I think," opined Peters, who is the author of 12 books and currently principal investigator for Theological Implications of the Human Genome Initiative, funded by the National Institutes of Health. "It is only through spiritual freedom that we gain the courage to affirm our true selves even in the face of the worst adversity." For the audience, the Nobel Conference offered the rare opportunity to get to know the people behind the lab coats, while for the presenters, it was the chance to leave the confines of their workspace and interact with an enthusiastic and interested public. The Nobel Conference may also be the only conference these scientists and scholars have attended where they're treated like, well ... stars. It wasn't just the darkened arena and standing atop a special stage before two oversize screens with bright lights shining in their faces. More than anything, what seemed to catch most of these scientists somewhat by surprise were the huddles of people who seemed to constantly appear around them seeking autographs. In the end, the Nobel Conference proved to be less a conference and more an experience. As Bill Joklik reviewed it: "This was the most pleasant conference of all my life--the music, the meals, the interaction, even the squirrel in the transformer (see sidebar), it was all extremely well done." When a tornado ripped through this small Minnesota town last spring, taking out every window and every tree on campus, not to mention an array of rooftops and homes in half the city, there had been some concern about whether the Nobel Conference would be held this year. But the campus was restored in time to continue the tradition on schedule. However, nature showed its "power" once again during the conference, when, during Gary Nabel's presentation, ¨ boomf! ¨science came to a screeching halt. The lights clicked off, and the look of shock on Nabel's face faded into darkness. It wasn't a mutant swarm as some in the audience hypothesized--just an errant rodent. As it turned out, a squirrel jumping the electrical lines near a major transformer on the other end of town became, however unintentionally, the conduit for connection and suddenly half of St. Peter was out of power. As the squirrel's fried and lifeless body lay at the bottom of the pole, city workers scrambled to make the necessary repairs. In the meantime, the audience calmly exited the arena and took a break outside, completely unfazed. Within an hour, the lights came on and the conference resumed. Apparently, kamikaze squirrels are not all that uncommon in Minnesota, and the accident--certainly after the feat of repairing the tornado damage--was not nearly enough to derail the conference. --A.J.S.R. A.J.S. Rayl is a freelance writer based in Malibu, Calif. She can be reached online at ajsrayl@loop.com.

War and Peace of Viruses Deliberated at Nobel Conference

Nov 22, 1998

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