As scientists discovered endogenous retroviruses in other species, they naturally wondered about
our own DNA. After all, we suffer infections from many retroviruses. Virologists tried coaxing
endogenous retroviruses out of human cells without any luck. But when they scanned the human
genome, they found many segments of DNA that bore a striking resemblance to retroviruses. Many of
those segments resembled retrovirus-like segments in apes and monkeys, suggesting that they had
infected our ancestors thirty million years ago or more. But some of the retrovirus-like segments in
the human genome had no counterparts in any other species. It was possible that the segments unique
to humans started out as retroviruses that infected our ancestors a million years ago.
To test this idea, Thierry Heidmann, a researcher at the Gustave Roussy Institute in Villejuif,
France, tried to bring a human endogenous retrovirus back to life. Searching through the genomes of
different people, he and his colleagues found slightly different versions of one retrovirus-like
segment. These differences presumably arose after a retrovirus became trapped in the genomes of
ancient humans. In their descendants, mutations struck different parts of the virus’s DNA.
Heidmann and his colleagues compared the variants of the virus-like sequence. It was as if they
found four copies of a play by Shakespeare, each transcribed by a slightly careless clerk. Each clerk
might make his own set of mistakes. Each copy might have a different version of the same word—say,
wheregore, sherefore, whorefore, wherefrom. By comparing all four versions, an historian could
figure out that the original word was wherefore.
Using this method, Heidmann and his fellow scientists were able to use the mutated versions in
living humans to determine the original sequence of the DNA. They then synthesized a piece of DNA
with a matching sequence and insert it into human cells they reared in a culture dish. Some of the cells
produced new viruses that could infect other cells. In other words, the original sequence of the DNA
had been a living, functioning virus. In 2006, Heidmann named the virus Phoenix, for the mythical
bird that rose from its own ashes.
Retroviruses are a major threat to human health when they’re free-living, but even after they
become endogenous they remain dangerous. Mutations can give them back the ability to make full-
blown viruses that can escape and cause new infections and even cause cancer. Endogenous
retroviruses that can only insert new copies of their DNA into their host genome are dangerous as
well, because they can cause genes that are shut down to switch on at the wrong times. The threat
from endogenous retroviruses is so great, in fact, that our ancestors evolved weapons that exist only
to keep these viruses from spreading.
Paul Bieniasz, a virologist at Rockefeller University, discovered two of these weapons in 2007 by
reviving an endogenous retrovirus, as Hiedmann’s team had revived Phoenix the year before.
Bieniasz dubbed his resurrected virus HERV-K[con]. When he infected human cells with it, he found
that the cells could fight the virus using two proteins called APOBEC 3. Bieniasz’s experiments
suggest that APOBEC 3 homes in on endogenous retroviruses as they are making new copies of
themselves destined to be inserted back into the host’s genome. The protein upsets the gene-copying
process so that the new copies of the viruses pick up extra mutations. The extra mutations act like a
hail of bullets. Some of them don’t cause any harm, but if one of them hits a vital spot in the virus’s
DNA, it can cripple the virus so that it can no longer reproduce.