The Best American Science and Nature Writing 2013

by Siddhartha Mukherjee

  Fouchier spent much of his career working on the structure of the AIDS virus. In 1997 he abruptly turned to bird flu, both because he was fascinated by its molecular structure and because he quickly grasped its pandemic potential. He has published scores of scientific articles on how influenza viruses move between species. Since December, however, when the advisory board recommended postponing publication of the bird-flu research, and some of his colleagues called for stopping it entirely, he has felt, he says, like the focus of “an international witch hunt.” He was incensed. “To attempt to prevent this research from reaching the largest number of scientists is bullshit,” he told me. “The more people who have access to it, the more likely we are to get answers to the many questions we still need to ask. Everyone who knows anything about virology can get hold of the recipe.” There were nearly a thousand people at the Malta meeting where he first announced his findings. “This moratorium serves some fake sense of security,” he said. “It does not serve the public health.”

  Fouchier, as well as Kawaoka and other researchers, had been trying for years to learn whether H5N1 could trigger a worldwide pandemic. He wondered why the virus has destroyed so many poultry flocks in the United States, Europe, and Asia but infected so few people. Fouchier hoped to characterize the properties that make the virus so much deadlier than others. The only way to answer these questions was to create a variant that would cling to human cells in the nose and throat. Fouchier’s research was hardly the work of a furtive renegade. Several international review committees oversaw his experiments, and he received funding from the National Institutes of Health. Despite the risks, most people in his field believed that the experiments were necessary. Moreover, they were not without precedent. In 2002 Eckard Wimmer, at Stony Brook University, stitched together hundreds of DNA fragments, mostly acquired via the Internet, then used them to create a fully functional polio virus. In the fall of 2005, several published academic papers described the genomic sequence of the 1918 Spanish flu, which caused the world’s deadliest influenza pandemic. In each case, the publications were initially denounced but were eventually accepted as valuable.

  “In this profession, you always do it wrong,” Ab Osterhaus, a leading infectious-disease expert who runs the virology department at Erasmus, said. “Either you give too much warning or not enough. Either you take things too seriously or not seriously enough. Fouchier’s work is essential, and the questions it raises must be addressed.”

  There have been many hypotheses about how bird flu could become epidemic. Most researchers had believed that the avian virus would have to combine with human genes in pigs. Pigs usually serve as a mixing vessel for influenza viruses that make the transition from poultry to humans. (This is how the global pandemic starts in Steven Soderbergh’s recent film Contagion: Gwyneth Paltrow is exposed to a pig that’s been infected by a bat, and soon much of the world is dead or dying.) Other scientists believed that the H5 protein, because of its molecular structure, could not easily infect human cells. (Strains of influenza are named for two proteins on their surface that latch on to respiratory cells and make it possible for them to invade our lungs.) “There has been a lot of speculation that this virus cannot be transmitted easily or through the air,” Fouchier told me. “That speculation has been wrong.”

  Although no animal study can predict with certainty what will happen in humans, ferrets get flu pretty much the way we do. Their lung physiology is similar to humans’, and avian-influenza viruses bind to the same receptor cells in their respiratory tracts. Still, there has been sharp debate among scientists about whether results in ferrets can predict how humans will react to similar infections, with some researchers discounting the data entirely.

  “The mutations . . . could cause the viruses to be more transmissible between humans,” Peter Palese, a prominent microbiologist at Mount Sinai School of Medicine, wrote recently. “But this is simply unknowable from available data.” Palese argues that the virus may be better adapted to ferrets than to other mammals.

  “You cannot say, ‘Just forget about it, because it happened in a ferret,’” Fouchier said. “This is our best model. But you also can’t say, ‘Because it happened in a ferret, it will happen in a human.’ So it becomes a question of whether it’s worth the risk of finding out. This is one of the most dangerous viruses you can imagine. It’s not my virus—it’s our virus. And it’s out there. We need to deal with that. And if we focus on what matters, we can.”

  Once you create a virus that could kill millions of people, what should you do with it? And how should you handle the knowledge that made it possible?

  There have been angry calls for Fouchier’s virus to be destroyed, for it to be transferred to a military-level bioweapons facility, and for research to be stopped entirely. “It’s just a bad idea for scientists to turn a lethal virus into a lethal and highly contagious virus,” Dr. Thomas Inglesby, a bioterrorism expert and the director of the Center for Biosecurity at the University of Pittsburgh Medical Center, said. “And it’s a second bad idea for them to publish how they did it, so others can copy it.”

  Still, most scientists who work with viruses insist that the value of this research outweighs the risks. Anthony S. Fauci, the longtime chief of the Institute of Allergy and Infectious Diseases, told me, “Those data could help scientists determine rapidly whether existing vaccines or drugs are effective against such a virus, as well as help in the development of new medications. It’s hard to stop something if you don’t know what it’s made of. Naturally, if epidemiologists in countries where pandemics most often arise know what they are looking for, they will be able to move with greater urgency to contain the spread.”

  How likely is it that publishing the genetic sequence could help a terrorist, a rogue, or a legitimate researcher who might develop a novel vaccine or drug? “Most of us are unequivocal about the value of the research,” Fauci said. “But deciding what to do with these types of studies is complicated. At the moment, there are no official governing bodies to regulate such decisions. They rely on the goodwill of researchers.” Fauci and others have noted that precisely because flu is so hard to control, the virus would be difficult to use as a weapon.

  In this case, as in most other cases, the work was supported heavily by the National Institutes of Health, and it seems unlikely to proceed without U.S. government support. Scientists bicker as vigorously as any other group, but rarely about the right to share and publish the data on which their research depends. Even the National Science Advisory Board for Biosecurity has made clear its general support for open investigation and full publication. The scientific method and the entire edifice of institutional research depend on such openness; without it, progress would slow dramatically. As biology has become more accessible, the balance between freedom and protection has become harder to maintain. This is certainly not the last time that preventing wide dissemination of information may seem necessary. But who should make those decisions, and how? Scientists fear that any regulatory body will stifle research. In 1975, when biologists met at Asilomar, California, to discuss the potential hazards of the new field of recombinant DNA technology, the group drew up voluntary guidelines to govern their research. Those guidelines have worked well, and that meeting is often regarded as a model of cooperative regulation.

  We live in a very different world now. Secretary of State Hillary Clinton recently gave a speech at a biological-weapons conference in Geneva in which she stressed that the threat of biological terror can no longer be ignored. “There are warning signs,” Clinton said, including “evidence in Afghanistan that . . . Al Qaeda in the Arabian Peninsula made a call to arms for—and I quote—‘brothers with degrees in microbiology or chemistry to develop a weapon of mass destruction.’”

  While scientists disagree sharply about whether it would be easy to replicate such a virus in a laboratory, and whether it would be worth the effort, there is no question that we are moving toward a time when work like this, and even more com
plex biology, will be accessible to anyone with the will to use it, a few basic chemicals, and a relatively small amount of money.

  Those realities have compelled many scientists to reconsider their unilateral support of the principle of open research. “I can tell you that when I began this journey I was certainly of the view that everything should be out and science should not be interfered with,” Arturo Casadevall, the chief of infectious disease at the Albert Einstein College of Medicine and a member of the advisory board, said at a recent forum on the issue sponsored by the New York Academy of Sciences. “And as the result of hundreds of hours of the deliberative process I changed my mind.” Others are even more emphatic, arguing that although the information is bound to become available, any delay is better than none. Many countries lack proper surveillance capacities, and existing vaccines are not good enough to stop influenza viruses from taking hold in the human population. By the time that public-health officials were fully aware of the swine-flu virus that originated in Mexico in 2009, for instance, it had spread across the globe.

  In January, a few days before we met in Rotterdam, Fouchier had agreed to a sixty-day moratorium on the project, but only after he received a long, late-night phone call from Fauci, who convinced him that a worldwide timeout—the first since the beginning of the era of molecular biology—would allow people to cool off and enable them to explain the value of such research to the public. In mid-February, a committee of specialists, including Fouchier, met in Geneva at the WHO headquarters and announced that the papers would eventually be published in full, but that a sixty-day moratorium was probably not long enough. It is not clear when or where the research will continue.

  Attempts to control information or to prohibit research rarely succeed for long. As the physicist and synthetic biologist Rob Carlson has written, most notably in his 2010 book, Biology Is Technology, in the case of crystal methamphetamine both prohibition and efforts by the federal government to shut down production labs have failed, and in similar ways. In each case, success in cracking down on small-time dealers led to failure on a larger scale. Carlson believes that cutting the flow of H5N1 data will have the same effect. “Any attempt to secure the data would have to start with an assessment of how widely it is already distributed,” he wrote recently on his blog, Synthesis. “I have yet to meet an academic who regularly encrypts e-mail, and my suspicion is that few avail themselves of the built-in encryption on their laptops.” Carlson noted that in addition to university computers and e-mail servers in facilities where the science originated, the information is probably stored in the computers of reviewers, on servers at Nature and Science, at the advisory board, and, depending on how the papers were distributed and discussed by the board’s members, possibly on their various e-mail servers and individual computers as well. “And,” Carlson wrote, “let’s not forget the various unencrypted phones and tablets all of those reviewers now carry around.”

  Carlson and others argue that restricting publication would retard the progress of the research without increasing safety. With influenza viruses, speed matters. Vaccine production methods have not changed substantially in sixty years, and it was months before a useful vaccine was widely available for the H1N1 pandemic of 2009. That virus infected more than a billion people. Future bird-flu research could help scientists learn how it is transmitted through the air, why it makes the leap from animal to man, and how specifically it binds to human cell receptors. By placing the virus into tissue culture, scientists could discover more about how it destroys cells and make a better assessment of whether current vaccines would protect us—and if they wouldn’t, the research could guide us toward making more effective vaccines. None of these experiments are without risk, but one must also consider the risk of not carrying them out.

  “We can learn a great deal about transmission of influenza virus through the air from this work, and it’s something we know very little about,” Ab Osterhaus, the leader of the Erasmus team, said. “Nobody was going to make this virus in his garage. There are so many better ways to create terror. You have to compare the risk posed by nature with the theoretical risk that a human might use this virus for harm. I take the bioterror threat very seriously. But we have to address the problems logically. And nature is much more sophisticated than anyone in any lab. Nature is going to manufacture this virus or something like it. We know that. Bioterrorists might, but nature will. Look at the past century: the 1918 flu, HIV, Ebola, and H1N1. The Spanish flu took months. SARS, maybe a couple of weeks. This is happening all the time, and we have ways to fight it. So where is the greatest risk? Is it in someone’s garage or in nature? Because you cannot prevent scientists from getting the information they need to address that risk. I understand politics and publicity. But I also understand that viruses do not care about any of that.”

  ALAN LIGHTMAN

  Our Place in the Universe

  FROM Harper’s Magazine

  MY MOST VIVID encounter with the vastness of nature occurred years ago on the Aegean Sea. My wife and I had chartered a sailboat for a two-week holiday in the Greek islands. After setting out from Piraeus, we headed south and hugged the coast, which we held three or four miles to our port. In the thick summer air, the distant shore appeared as a hazy beige ribbon—not entirely solid, but a reassuring line of reference. With binoculars, we could just make out the glinting of houses, fragments of buildings.

  Then we passed the tip of Cape Sounion and turned west toward Hydra. Within a couple of hours, both the land and all other boats had disappeared. Looking around in a full circle, we could see only water, extending out and out in all directions until it joined with the sky. I felt insignificant, misplaced, a tiny odd trinket in a cavern of ocean and air.

  Naturalists, biologists, philosophers, painters, and poets have labored to express the qualities of this strange world that we find ourselves in. Some things are prickly, others are smooth. Some are round, some jagged. Luminescent or dim. Mauve-colored. Pitter-patter in rhythm. Of all these aspects of things, none seems more immediate or vital than size. Large versus small. Consciously and unconsciously, we measure our physical size against the dimensions of other people, against animals, trees, oceans, mountains. As brainy as we think ourselves to be, our bodily size, our bigness, our simple volume and bulk are what we first present to the world. Somewhere in our fathoming of the cosmos, we must keep a mental inventory of plain size and scale, going from atoms to microbes to humans to oceans to planets to stars. And some of the most impressive additions to that inventory have occurred at the high end. Simply put, the cosmos has gotten larger and larger. At each new level of distance and scale, we have had to contend with a different conception of the world that we live in.

  The prize for exploring the greatest distance in space goes to a man named Garth Illingworth, who works in a ten-by-fifteen-foot office at the University of California, Santa Cruz. Illingworth studies galaxies so distant that their light has traveled through space for more than 13 billion years to get here. His office is packed with tables and chairs, bookshelves, computers, scattered papers, issues of Nature, and a small refrigerator and a microwave to fuel research that can extend into the wee hours of the morning.

  Like most professional astronomers these days, Illingworth does not look directly through a telescope. He gets his images by remote control—in his case, quite remote. He uses the Hubble Space Telescope, which orbits Earth once every ninety-seven minutes, high above the distorting effects of Earth’s atmosphere. Hubble takes digital photographs of galaxies and sends the images to other orbiting satellites, which relay them to a network of earthbound antennae; these, in turn, pass the signals on to the Goddard Space Flight Center in Greenbelt, Maryland. From there the data is uploaded to a secure website that Illingworth can access from a computer in his office.

  The most distant galaxy Illingworth has seen so far goes by the name UDFj-39546284 and was documented in early 2011. This galaxy is about 100,000,000,000,000,000,000,000 miles away from
Earth, give or take. It appears as a faint red blob against the speckled night of the distant universe—red because the light has been stretched to longer and longer wavelengths as the galaxy has made its lonely journey through space for billions of years. The actual color of the galaxy is blue, the color of young, hot stars, and it is twenty times smaller than our galaxy, the Milky Way. UDFj-39546284 was one of the first galaxies to form in the universe.

  “That little red dot is hellishly far away,” Illingworth told me recently. At sixty-five, he is a friendly bear of a man, with a ruddy complexion, thick strawberry-blond hair, wire-rimmed glasses, and a broad smile. “I sometimes think to myself: What would it be like to be out there, looking around?”

  One measure of the progress of human civilization is the increasing scale of our maps. A clay tablet dating from about the twenty-fifth centuryB.C., found near what is now the Iraqi city of Kirkuk, depicts a river valley with a plot of land labeled as being 354 iku (about 30 acres) in size. In the earliest recorded cosmologies, such as the Babylonian Enuma Elish, from around 1500 B.C., the oceans, the continents, and the heavens were considered finite, but there were no scientific estimates of their dimensions. The early Greeks, including Homer, viewed Earth as a circular plane with the ocean enveloping it and Greece at the center, but there was no understanding of scale. In the early sixth century B.C., the Greek philosopher Anaximander, whom historians consider the first mapmaker, and his student Anaximenes proposed that the stars were attached to a giant crystalline sphere. But again there was no estimate of its size.