DARWIN's Surprise

ANNALS OF SCIENCE Darwin’S SuRpRISE Why are evolutionary biologists bringing back extinct deadly viruses? by michael specter hierry Heidmann’s office, adjacent manity than viral diseases: yellow fever, composed of broken and disabled retro- to the laboratory he runs at the In- measles, and smallpox have been caus- viruses, which, millions of years ago, stitutT Gustave Roussy, on the southern ing epidemics for thousands of years. At managed to embed themselves in the edge of Paris, could pass for a museum of the end of the First World War, fifty DNA of our ancestors. They are called genetic catastrophe. Files devoted to the million people died of the Spanish flu; endogenous retroviruses, because once world’s most horrifying infectious dis- smallpox may have killed half a billion they infect the DNA of a species they eases fill the cabinets and line the shelves. during the twentieth century alone. become part of that species. One by one, There are thick folders for smallpox, Those viruses were highly infectious, though, after molecular battles that Ebola virus, and various forms of in- yet their impact was limited by their fe- raged for thousands of generations, they fluenza. sars is accounted for, as are rocity: a virus may destroy an entire cul- have been defeated by evolution. Like more obscure pathogens, such as feline ture, but if we die it dies, too. As a re- dinosaur bones, these viral fragments are leukemia virus, Mason-Pfizer monkey sult, not even smallpox possessed the fossils. Instead of having been buried in virus, and simian foamy virus, which is evolutionary power to influence humans sand, they reside within each of us, car- endemic in African apes. H.I.V., the as a species—to alter our genetic struc- rying a record that goes back millions of best-known and most insidious of the vi- ture. That would require an organism to years. Because they no longer seem to ruses at work today, has its own shelf of insinuate itself into the critical cells we serve a purpose or cause harm, these files. The lab’s beakers, vials, and refrig- need in order to reproduce: our germ remnants have often been referred to as erators, secured behind locked doors with cells. Only retroviruses, which reverse “junk DNA.” Many still manage to gen- double-paned windows, all teem with vi- the usual flow of genetic code from erate proteins, but scientists have never ruses. Heidmann, a meaty, middle-aged DNA to RNA, are capable of that. A found one that functions properly in human with wild eyebrows and a beard retrovirus stores its genetic information mans or that could make us sick. heavily flecked with gray, has devoted his in a single-stranded molecule of RNA, Then, last year, Thierry Heidmann career to learning what viruses might tell instead of the more common double- brought one back to life. Combining the us about aids and various forms of can- stranded DNA. When it infects a cell, tools of genomics, virology, and evolu- cer. “This knowledge will help us treat the virus deploys a special enzyme, called tionary biology, he and his colleagues terrible diseases,” he told me, nodding reverse transcriptase, that enables it to took a virus that had been extinct for briefly toward his lab. “Viruses can pro- copy itself and then paste its own genes hundreds of thousands of years, figured vide answers to questions we have never into the new cell’s DNA. It then be- out how the broken parts were originally even asked.” comes part of that cell forever; when the aligned, and then pieced them together. Viruses reproduce rapidly and often cell divides, the virus goes with it. Sci- After resurrecting the virus, the team with violent results, yet they are so ru- entists have long suspected that if a ret- placed it in human cells and found that dimentary that many scientists don’t rovirus happens to infect a human sperm their creation did indeed insert itself even consider them to be alive. A virus cell or egg, which is rare, and if that em- into the DNA of those cells. They also is nothing more than a few strands of bryo survives—which is rarer still—the mixed the virus with cells taken from genetic material wrapped in a package retrovirus could take its place in the hamsters and cats. It quickly infected of protein—a parasite, unable to func- blueprint of our species, passed from them all, offering the first evidence that tion on its own. In order to survive, it mother to child, and from one genera- the broken parts could once again be must find a cell to infect. Only then can tion to the next, much like a gene for eye made infectious. The experiment could any virus make use of its single talent, color or asthma. provide vital clues about how viruses like which is to take control of a host’s cel- When the sequence of the human H.I.V. work. Inevitably, though, it also lular machinery and use it to churn out genome was fully mapped, in 2003, re- conjures images of Frankenstein’s mon- thousands of copies of itself. These vi- searchers also discovered something ster and Jurassic Park. ruses then move from one cell to the they had not anticipated: our bodies are “If you think about this for five min- next, transforming each new host into a littered with the shards of such retrovi- utes, it is wild stuff,” John Coffin told me factory that makes even more virus. In ruses, fragments of the chemical code when I visited him in his laboratory at this way, one infected cell soon be- from which all genetic material is made. Tufts University, where he is the Amer- comes billions. It takes less than two per cent of our ge- ican Cancer Society Research Professor. Nothing—not even the Plague—has nome to create all the proteins necessary Coffin is one of the country’s most dis- posed a more persistent threat to hu- for us to live. Eight per cent, however, is tinguished molecular biologists, and was swarte joost 64 THE NEW YORKER, DECEMBER 3, 2007 tNY—2007_12_03—PaGe 64—133sC. Disabled retroviruses—fossils of molecular battles that raged for generations—make up eight per cent of the human genome. tNY—2007_12_03—PaGe 65—133sC.—live art r16858_rD one of the first to explore the role of endogenous retroviruses in human evolution. “I understand that the idea of bring- lorca ing something dead back to life is funda- mentally frightening,” he went on. “It’s a The fact that no one had ever seen Lorca run power that science has come to possess had only to do with the legend of his clumsiness, and it makes us queasy, and it should. for one foot was shorter than the other and he was But there are many viruses that are more terrified to cross the street by himself, dangerous than these—more infectious, though dogs barking in the mountains above him far riskier to work with, and less poten- brought him back to his senses and caused him tially useful.’’ when he was alone to try leaping and skipping Thanks to steady advances in com- the way you did and he tried the hop, skip, and jump puting power and DNA technology, a he learned from the 1932 Olympics talented undergraduate with a decent and loaded the left side of his mouth with green tobacco laptop and access to any university biol- when he was only eleven, for he took comfort ogy lab can assemble a virus with ease. in every form of degradation; and it was Five years ago, as if to prove that point, in John Jay Hall in 1949 researchers from the State University of that Geraldo from Pittsburgh made a personal connection, New York at Stony Brook “built” a polio for they were both housed in Room 1231 virus, using widely available information twenty years apart not counting the months and DNA they bought through the and only one of them heard Eisenhower give his maiden speech mail. To test their “polio recipe,” they in- outside the courtyard entrance, and there were bitter jected the virus into mice. The animals oranges enough for them both and you can imagine first became paralyzed and then died. one of our poets in the hands of our own bastards, (“The reason we did it was to prove that but what is the use of comparing, only the hats it can be done,’’ Eckard Wimmer, who are different, though I’m not too sure, the roses led the team, said at the time. “Progress maybe they stuffed in our mouths—the Granadas. in biomedical research has its bene- fits and it has its downside.’’) The effort —Gerald Stern was widely seen as pointless and the justification absurd. “Proof of principle for bioterrorism,’’ Coffin called it. “Noth- One team, at the Aaron Diamond aids genes and viruses. And those viruses ing more.” Then, two years ago, after re- Research Center, in New York, recently helped make us who we are today just as searchers had sequenced the genetic created an almost identical virus. In the surely as other genes did. I am not certain code of the 1918 flu virus, federal scien- past few months, groups at Oxford Uni- that we would have survived as a species tists reconstructed it, too. In that case, versity and at the Fred Hutchinson Can- without them.” there was a well-understood and highly cer Research Center, in Seattle, have also He continued, “The Phoenix virus desired goal: to develop a vaccine that produced results that provide startling sheds light on how H.I.V.

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