The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (18 page)

Scenes from Barentsz’s doomed voyage over the frosty top of Russia. Clockwise from top left: encounters with polar bears; the ship crushed in ice; the hut where the crew endured a grim winter in the 1590s. (Gerrit de Veer,
The Three Voyages of William Barents to the Arctic Regions
)

Understanding why that’s so awful requires taking a closer look at certain genes, genes that help immature cells in our bodies transform into specialized skin or liver or brain cells or
whatever. This was part of the process Barbara McClintock longed to comprehend, but the scientific debate actually predated her by decades.

In the late 1800s, two camps emerged to explain cell specialization, one led by German biologist August Weismann.
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Weismann studied zygotes, the fused product of a sperm and egg that formed an animal’s first cell. He argued that this first cell obviously contained a complete set of molecular instructions, but that each time the zygote and its daughter cells divided, the cells lost half of those instructions. When cells lost the instructions for all but one type of cell, that’s what they became. In contrast, other scientists maintained that cells kept the full set of instructions after each division, but ignored most of the instructions after a certain age. German biologist Hans Spemann decided the issue in 1902 with a salamander zygote. He centered one of these large, soft zygotes in his microscopic crosshairs, waited until it divided into two, then looped a blond strand of his infant daughter Margrette’s hair around the boundary between them. (Why Spemann used his daughter’s hair isn’t clear, since he wasn’t bald. Probably the baby’s hair was finer.) When he tightened this noose, the two cells split, and Spemann pulled them into different dishes, to develop separately. Weismann would have predicted two deformed half salamanders. But both of Spemann’s cells grew into full, healthy adults. In fact, they were genetically identical, which means Spemann had effectively cloned them—in 1902. Scientists had rediscovered Mendel not long before, and Spemann’s work implied that cells must retain instructions but turn genes on and off.

Still, neither Spemann nor McClintock nor anyone else could explain how cells turned genes off, the mechanism. That took decades’ more work. And it turns out that although cells don’t lose genetic information per se, cells do lose access to this information, which amounts to the same thing. We’ve already
seen that DNA must perform incredible acrobatics to fit its entire serpentine length into a tiny cell nucleus. To avoid forming knots during this process, DNA generally wraps itself like a yo-yo string around spools of protein called histones, which then get stacked together and buried inside the nucleus. (Histones were some of the proteins that scientists detected in chromosomes early on, and assumed controlled heredity instead of DNA.) In addition to keeping DNA tangle free, histone spooling prevents cellular machinery from getting at DNA to make RNA, effectively shutting the DNA off. Cells control spooling with chemicals called acetyls. Tacking an acetyl (COCH
₃
) onto a histone unwinds DNA; removing the acetyl flicks the wrist and coils DNA back up.

Cells also bar access to DNA by altering DNA itself, with molecular pushpins called methyl groups (CH
₃
). Methyls stick best to cytosine, the C in the genetic alphabet, and while methyls don’t take up much space—carbon is small, and hydrogen is the smallest element on the periodic table—even that small bump can prevent other molecules from locking onto DNA and turning a gene on. In other words, adding methyl groups mutes genes.

Each of the two hundred types of cells in our bodies has a unique pattern of coiled and methylated DNA, patterns established during our embryonic days. Cells destined to become skin cells must turn off all the genes that produce liver enzymes or neurotransmitters, and something reciprocal happens for everything else. These cells not only remember their pattern for the rest of their lives, they pass on the pattern each time they divide as adult cells. Whenever you hear scientists talking about turning genes on or off, methyls and acetyls are often the culprit. Methyl groups in particular are so important that some scientists have proposed adding a fifth official letter to the DNAlphabet
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—A, C, G, T, and now mC, for methylated cytosine.

But for additional and sometimes finer control of DNA, cells
turn to “transcription factors” like vitamin A. Vitamin A and other transcription factors bind to DNA and recruit other molecules to start transcribing it. Most important for our purposes, vitamin A stimulates growth and helps convert immature cells into full-fledged bone or muscle or whatever at a fast clip. Vitamin A is especially potent in the various layers of skin. In adults, for instance, vitamin A forces certain skin cells to crawl upward from inside the body to the surface, where they die and become the protective outer layer of skin. High doses of vitamin A can also damage skin through “programmed cell death.” This genetic program, a sort of forced suicide, helps the body eliminate sickly cells, so it’s not always bad. But for unknown reasons, vitamin A also seems to hijack the system in certain skin cells—as Barentsz’s men discovered the hard way.

After the crew tucked into their polar bear stew, rich with burgundy liver chunks, they became more ill than they ever had in their lives. It was a sweaty, fervid, dizzying, bowels-in-a-vice sickness, a real biblical bitch of a plague. In his delirium, the diarist Garrit de Veer remembered the female bear he’d helped butcher, and moaned, “Her death did vs more hurt than her life.” Even more distressing, a few days later de Veer realized that many men’s skin had begun to peel near their lips or mouths, whatever body parts had touched the liver. De Veer noted with panic that three men fell especially “sicke,” and “we verily thought that we should haue lost them, for all their skin came of[f] from the foote to the head.”

Only in the mid–twentieth century did scientists determine why polar bear livers contain such astronomical amounts of vitamin A. Polar bears survive mostly by preying on ringed and bearded seals, and these seals raise their young in about the most demanding environment possible, with the 35°F Arctic seas wicking
away their body heat relentlessly. Vitamin A enables the seals to survive in this cold: it works like a growth hormone, stimulating cells and allowing seal pups to add thick layers of skin and blubber, and do so quickly. To this end, seal mothers store up whole crates of vitamin A in their livers and draw on this store the whole time they’re nursing, to make sure pups ingest enough.

Polar bears also need lots of vitamin A to pack on blubber. But even more important, their bodies tolerate toxic levels of vitamin A because they couldn’t eat seals—about the only food source in the Arctic—otherwise. One law of ecology says that poisons accumulate as you move up a food chain, and carnivores at the top ingest the most concentrated doses. This is true of any toxin or any nutrient that becomes toxic at high levels. But unlike many other nutrients, vitamin A doesn’t dissolve in water, so when a king predator overdoses, it can’t expel the excess through urine. Polar bears either have to deal with all the vitamin A they swallow, or starve. Polar bears adapted by turning their livers into high-tech biohazard containment facilities, to filter vitamin A and keep it away from the rest of the body. (And even with those livers, polar bears have to be careful about intake. They can dine on animals lower on the food chain, with lesser concentrations. But some biologists have wryly noted that if polar bears cannibalized their own livers, they would almost certainly croak.)

Polar bears began evolving their impressive vitamin A–fighting capabilities around 150,000 years ago, when small groups of Alaskan brown bears split off and migrated north to the ice caps. But scientists always suspected that the important genetic changes that made polar bears
polar bears
happened almost right away, instead of gradually over that span. Their reasoning was this. After any two groups of animals split geographically, they begin to acquire different DNA mutations. As the mutations accumulate, the groups develop into different species with different bodies, metabolisms, and behaviors. But not all DNA
changes at the same rate in a population. Highly conserved genes like
hox
change grudgingly slowly, at geological paces. Changes in other genes can spread quickly, especially if creatures face environmental stress. For instance, when those brown bears wandered onto the bleak ice sheets atop the Arctic Circle, any beneficial mutations to fight the cold—say, the ability to digest vitamin A–rich seals—would have given some of those bears a substantial boost, and allowed them to have more cubs and take better care of them. And the greater the environmental pressure, the faster such genes can and will spread through a population.

Another way to put this is that DNA clocks—which look at the number and rate of mutations in DNA—tick at different speeds in different parts of the genome. So scientists have to be careful when comparing two species’ DNA and dating how long ago they split. If scientists don’t take conserved genes or accelerated changes into account, their estimates can be wildly off. With these caveats in mind, scientists determined in 2010 that polar bears had armed themselves with enough cold-weather defenses to become a separate species in as few as twenty thousand years after wandering away from ancestral brown bears—an evolutionary wink.

As we’ll see later, humans are Johnny-come-latelies to the meat-eating scene, so it’s not surprising that we lack the polar bear’s defenses—or that when we cheat up the food chain and eat polar bear livers, we suffer. Different people have different genetic susceptibility to vitamin A poisoning (called hypervitaminosis A), but as little as one ounce of polar bear liver can kill an adult human, and in a ghastly way.

Our bodies metabolize vitamin A to produce retinol, which special enzymes should then break down further. (These enzymes also break down the most common poison we humans ingest, the alcohol in beers, rums, wines, whiskeys, and other booze.)
But polar bear livers overwhelm our poor enzymes with vitamin A, and before they can break it all down, free retinol begins circulating in the blood. That’s bad. Cells are surrounded by oil-based membranes, and retinol acts as a detergent and breaks the membranes down. The guts of cells start leaking out incontinently, and inside the skull, this translates to a buildup of fluids that causes headaches, fogginess, and irritability. Retinol damages other tissues as well (it can even crimp straight hair, turning it kinky), but again the skin really suffers. Vitamin A already flips tons of genetic switches in skin cells, causing some to commit suicide, pushing others to the surface prematurely. The burn of more vitamin A kills whole additional swaths, and pretty soon the skin starts coming off in sheets.

We hominids have been learning (and relearning) this same hard lesson about eating carnivore livers for an awfully long time. In the 1980s, anthropologists discovered a 1.6-million-year-old
Homo erectus
skeleton with lesions on his bones characteristic of vitamin A poisoning, from eating that era’s top carnivores. After polar bears arose—and after untold centuries of casualties among their people—Eskimos, Siberians, and other northern tribes (not to mention scavenging birds) learned to shun polar bear livers, but European explorers had no such wisdom when they stormed into the Arctic. Many in fact regarded the prohibition on eating livers as “vulgar prejudice,” a superstition about on par with worshipping trees. As late as 1900 the English explorer Reginald Koettlitz relished the prospect of digging into polar bear liver, but he quickly discovered that there’s sometimes wisdom in taboos. Over a few hours, Koettlitz felt pressure building up inside his skull, until his whole head felt crushed from the inside. Vertigo overtook him, and he vomited repeatedly. Most cruelly, he couldn’t sleep it off; lying down made things worse. Another explorer around that time, Dr. Jens Lindhard, fed polar bear liver to nineteen men under his care as
an experiment. All became wretchedly ill, so much so that some showed signs of insanity. Meanwhile other starved explorers learned that not just polar bears and seals have toxically elevated levels of vitamin A: the livers of reindeer, sharks, swordfish, foxes, and Arctic huskies
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can make excellent last meals as well.

For their part, after being blasted by polar bear liver in 1597, Barentsz’s men got wise. As the diarist de Veer had it, after their meal, “there hung a pot still ouer the fire with some of the liuer in it. But the master tooke it and cast it out of the dore, for we had enough of the sawce thereof.”

The men soon recovered their strength, but their cabin, clothes, and morale continued to disintegrate in the cold. At last, in June, the ice started melting, and they salvaged rowboats from their ship and headed to sea. They could only dart between small icebergs at first, and they took heavy flak from pursuing polar bears. But on June 20, 1597, the polar ice broke, making real sailing possible. Alas, June 20 also marked the last day on earth of the long-ailing Willem Barentsz, who died at age fifty. The loss of their navigator sapped the courage of the remaining twelve crew members, who still had to cross hundreds of miles of ocean in open boats. But they managed to reach northern Russia, where the locals pitied them with food. A month later they washed ashore on the coast of Lapland, where they ran into, of all people, Captain Jan Corneliszoon Rijp, commander of the very ship that Barentsz had ditched the winter before. Overjoyed—he’d assumed them dead—Rijp carried the men home to the Netherlands
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in his ship, where they arrived in threadbare clothes and stunning white fox fur hats.