The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (19 page)

Their expected heroes’ welcome never materialized. That same day another Dutch convoy returned home as well, laden with spices and delicacies from a voyage to Cathay around the southern horn of Africa. Their journey proved that merchant ships could make that long voyage, and while tales of starvation
and survival were thrilling, tales of treasure truly stirred the Dutch people’s hearts. The Dutch crown granted the Dutch East India Company a monopoly on traveling to Asia via Africa, and an epic trade route was born, a mariner’s Silk Road. Barentsz and crew were forgotten.

Perversely, the monopoly on the African route to Asia meant that other maritime entrepreneurs could seek their fortunes only via the northeast passage, so forays into the 500,000-square-mile Barents Sea continued. Finally, salivating over a possible double monopoly, the Dutch East India Company sent its own crew—captained by an Englishman, Henry Hudson—north in 1609. Once again, things got fouled up. Hudson and his ship, the
Half Moon,
crawled north past the tip of Norway as scheduled. But his crew of forty, half of them Dutch, had no doubt heard tales of starvation, exposure, and, God help them, skin peeling off people’s bodies head to toe—and mutinied. They forced Hudson to turn west.

If that’s what they wanted, Hudson gave it to them, sailing all the way west to North America. He skimmed Nova Scotia and put in at a few places lower down on the Atlantic coast, including a trip up a then-unnamed river, past a skinny swamp island. While disappointed that Hudson had not circled Russia, the Dutch made lemonade by founding a trading colony called New Amsterdam on that isle, Manhattan, within a few years. It’s sometimes said of human beings that our passion for exploration is in our genes. With the founding of New York, this was almost literally the case.

A
farmer from Long Island arrived with trepidation at the Rockefeller Institute in Manhattan in 1909, a sick chicken tucked under his arm. A seeming plague of cancer had been wiping out chicken coops across the United States that decade, and the farmer’s Plymouth Rock hen had developed a suspicious tumor in its right breast. Nervous about losing his stocks, the farmer turned the hen over to Rockefeller scientist Francis P. Rous, known as Peyton, for a diagnosis. To the farmer’s horror, instead of trying to cure the chicken, Rous slaughtered it to get a look at the tumor and run some experiments. Science, though, will be forever grateful for the pollocide.

After extracting the tumor, Rous mashed up a few tenths of an ounce, creating a wet paste. He then filtered it through very small porcelain pores, which removed tumor cells from circulation and left behind mostly just the fluid that exists between cells. Among other things, this fluid helps pass nutrients around, but it can also harbor microbes. Rous injected the fluid into
another Plymouth Rock’s breast. Soon enough, the second chicken developed a tumor. Rous repeated the experiment with other breeds, like Leghorn fowls, and within six months they developed cancerous masses, about an inch by an inch, too. What was notable, and baffling, about the setup was the filtering step. Since Rous had removed any tumor cells before making the injections, the new tumors couldn’t have sprung from old tumor cells reattaching themselves in new birds. The cancer had to have come from the fluid.

Though annoyed, the farmer couldn’t have sacrificed his hen to a better candidate to puzzle out the chicken pandemic. Rous, a medical doctor and pathologist, had a strong background with domesticated animals. Rous’s father had fled Virginia just before the Civil War and settled in Texas, where he met Peyton’s mother. The whole family eventually moved back east to Baltimore, and after high school, Rous enrolled at the Johns Hopkins University, where he supported himself in part by writing, for five dollars a pop, a column called “Wild Flowers of the Month” for the
Baltimore Sun
, about flora in Charm City. Rous gave up the column after entering Johns Hopkins medical school but soon had to suspend his studies. He cut his hand on a tubercular cadaver bone while performing an autopsy, and when he developed tuberculosis himself, school officials ordered a rest cure. But instead of a European-style cure—an actually restful stint in a mountain sanitarium—Rous took a good ol’ American cure and worked as a ranch hand in Texas. Though small and slender, Rous loved ranching and developed a keen interest in farm animals. After recovering, he decided to specialize in microbial biology instead of bedside medicine.

All the training on the ranch and in his labs, and all the evidence of the chicken case, pointed Rous to one conclusion. The chickens had a virus, and the virus was spreading cancer. But all his training also told Rous the idea was ridiculous—and his
colleagues seconded that.
Contagious cancer, Dr. Rous? How on earth could a virus cause cancer?
Some argued that Rous had misdiagnosed the tumors; perhaps the injections caused an inflammation peculiar to chickens. Rous himself later admitted, “I used to quake in the night for fear that I had made an error.” He did publish his results, but even by the circuitous standards of scientific prose, he barely admitted what he believed at some points: “It is perhaps not too much to say that [the discovery] points to the existence of a new group of entities which cause in chickens neoplasms [tumors] of diverse character.” But Rous was cagey to be circumspect. A contemporary remembered that his papers on the chicken cancers “were met with reactions ranging from indifference to skepticism and outright hostility.”

Most scientists quietly forgot about Rous’s work over the next few decades, and for good reason. Because even though a few discoveries from that time linked viruses and cancers biologically, other findings kept pushing them apart. Scientists had determined by the 1950s that cancer cells go haywire in part because their genes malfunction. Scientists had also determined that viruses have small caches of their own genetic material. (Some used DNA; others, like Rous’s, used RNA.) Though not technically alive, viruses used that genetic material to hijack cells and make copies of themselves. So viruses and cancer both reproduced uncontrollably, and both used DNA and RNA as common currency—intriguing clues. Meanwhile, however, Francis Crick had published his Central Dogma in 1958, that DNA generates RNA, which generates proteins, in that order. According to this popular understanding of the dogma, RNA viruses like Rous’s couldn’t possibly disrupt or rewrite the DNA of cells: this would run the dogma backward, which wasn’t allowed. So despite the biological overlap, there seemed no way for viral RNA to interface with cancer-causing DNA.

The matter stood at an impasse—data versus dogma—until
a few young scientists in the late 1960s and early 1970s discovered that nature cares little for dogmas. It turns out that certain viruses (HIV is the best-known example) manipulate DNA in heretical ways. Specifically, the viruses can coax an infected cell into reverse-transcribing viral RNA into DNA. Even scarier, they then trick the cell into splicing the newly minted viral DNA back into the cell’s genome. In short, these viruses fuse with a cell. They show no respect for the Maginot Line we’d prefer to draw between “their” DNA and “our” DNA.

This strategy for infecting cells might seem convoluted: why would an RNA virus like HIV bother converting itself into DNA, especially when the cell has to transcribe that DNA back into RNA later anyway? It seems even more baffling when you consider how resourceful and nimble RNA is compared to DNA. Lone RNA can build rudimentary proteins, whereas lone DNA sort of just sits there. RNA can also build copies of itself
by itself,
like that M. C. Escher drawing of two hands sketching themselves into existence. For these reasons, most scientists believe that RNA probably predated DNA in the history of life, since early life would have lacked the fancy innards-copying equipment cells have nowadays. (This is called the “RNA world” theory.
^*
)

Nevertheless, early Earth was rough-and-tumble, and RNA is pretty flimsy compared to DNA. Because it’s merely single-stranded, RNA letters are constantly exposed to assaults. RNA also has an extra oxygen atom on its ringed sugars, which stupidly cannibalizes its own vertebrae and shreds RNA if it grows too long. So to build anything lasting, anything capable of exploring, swimming, growing, fighting, mating—truly living—fragile RNA had to yield to DNA. This transition to a less corruptible medium a few billion years ago was arguably the most important step in life’s history. In a way it resembled the transition in human cultures away from, say, Homer’s oral poetry to
mute written work: with a stolid DNA text, you miss the RNA-like versatility, the nuances of voice and gesture; but we wouldn’t even have the
Iliad
and the
Odyssey
today without papyrus and ink. DNA lasts.

And that’s why some viruses convert RNA into DNA after infecting cells: DNA is sturdier, more enduring. Once these
retro
viruses—so named because they run the DNA → RNA → protein dogma backward—weave themselves into a cell’s DNA, the cell will faithfully copy the virus genes so long as they both shall live.

The discovery of viral DNA manipulation explained Rous’s poor chickens. After the injection, the viruses found their way through the intercellular fluid into the muscle cells. They then ingratiated themselves with the chicken DNA and turned the machinery of each infected muscle cell toward making as many copies of themselves as possible. And it turns out—here’s the key—one great strategy for the viruses to spread like mad was to convince the cells harboring viral DNA to spread like mad, too. The viruses did this by disrupting the genetic governors that prevent cells from dividing rapidly. A runaway tumor (and a lot of dead birds) was the result. Transmissible cancers like this are atypical—most cancers have other genetic causes—but for many animals, virus-borne cancers are significant hazards.

This new theory of genetic intrusions was certainly unorthodox. (Even Rous doubted aspects of it.) But if anything, scientists of the time actually underestimated the ability of viruses and other microbes to invade DNA. You can’t really attach degrees to the word
ubiquitous;
like being unique, something either is or isn’t ubiquitous. But indulge me for a moment in marveling over the complete, total, and utter ubiquity of microbes on a microscopic scale. The little buggers have colonized every
known living thing—humans have ten times more microorganisms feasting inside us than we do cells—and saturated every possible ecological niche. There’s even a class of viruses that infect only other parasites,
^*
which are scarcely larger than the viruses themselves. For reasons of stability, many of these microbes invade DNA, and they’re often nimble enough about changing or masking their DNA to evade and outflank our bodies’ defenses. (One biologist calculated that HIV alone has swapped more A’s, C’s, G’s, and T’s into and out of its genes in the past few decades than primates have in fifty million years.)

Not until the completion of the Human Genome Project around 2000 did biologists grasp how extensively microbes can infiltrate even higher animals. The name
Human
Genome Project even became something of a misnomer, because it turned out that 8 percent of our genome isn’t human at all: a quarter billion of our base pairs are old virus genes. Human genes actually make up less than 2 percent of our total DNA, so by this measure, we’re four times more virus than human. One pioneer in studying viral DNA, Robin Weiss, put this evolutionary relationship in stark terms: “If Charles Darwin reappeared today,” Weiss mused, “he might be surprised to learn that humans are descended from viruses as well as from apes.”

How could this happen? From a virus’s point of view, colonizing animal DNA makes sense. For all their deviousness and duplicity, retroviruses that cause cancer or diseases like AIDS are pretty stupid in one respect: they kill their hosts too quickly and die with them. But not all viruses rip through their hosts like microscopic locusts. Less ambitious viruses learn to not disrupt too much, and by showing some restraint they can trick a cell into quietly making copies of themselves for decades. Even better, if viruses infiltrate sperm or egg cells, they can trick their host into passing on viral genes to a new generation, allowing a virus to “live” indefinitely in the host’s descendants. (This is
happening right now in koalas, as scientists have caught retroviral DNA spreading through koala sperm.) That these viruses have adulterated so much DNA in so many animals hints that this infiltration happens all the time, on scales a little frightening to think about.

Of all the extinct retrovirus genes loaded into human DNA, the vast majority have accumulated a few fatal mutations and no longer function. But otherwise these genes sit intact in our cells and provide enough detail to study the original virus. In fact, in 2006 a virologist in France named Thierry Heidmann used human DNA to resurrect an extinct virus—
Jurassic Park
in a petri dish. It proved startlingly easy. Strings of some ancient viruses appear multiple times in the human genome (the number of copies ranges from dozens to tens of thousands). But the fatal mutations appear, by chance, at different points in each copy. So by comparing many strings, Heidmann could deduce what the original, healthy string must have been simply by counting which DNA letter was most common at each spot. The virus was benign, Heidmann says, but when he reconstituted it and injected it into various mammalian cells—cat, hamster, human—it infected them all.