The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (23 page)

But who gave cancer to whom? Scientists had never solved this mystery before; even the McC case was ambiguous, since the fatal tumors appeared only after the pregnancy started. Doctors pulled out the blood-spot card taken from Emiko at birth and determined that the cancer had been present even then. Further genetic testing revealed that Emiko’s normal (nontumor) cells did
not
show a Philadelphia swap. So Emiko had not inherited any predisposition to this cancer—it had sprung up sometime between conception and the delivery forty weeks later. What’s more, Emiko’s normal cells also showed, as expected, DNA from both her mother and father. But her cheek tumor cells contained no DNA from Hideo; they were pure Mayumi. This proved, indisputably, that Mayumi had given cancer to Emiko, not vice versa.

Whatever sense of triumph the scientists might have felt, though, was muted. As so often happens in medical research, the most interesting cases spring from the most awful suffering. And in virtually every other historical case where a fetus and mother had cancer simultaneously, both had succumbed to it quickly, normally within a year. Mayumi was already gone, and as the doctors started the eleven-month-old Emiko on chemotherapy, they surely felt these dismal odds weighing on them.

The geneticists on the case felt something different nagging them. The spread of the cancer here was essentially a transplant of cells from one person to another. If Emiko had gotten an
organ from her mother or had tissue grafted onto her cheek, her body would have rejected it as foreign. Yet cancer, of all things, had taken root without triggering the placenta’s alarms or drawing the wrath of Emiko’s immune system. How? Scientists ultimately found the answer in a stretch of DNA far removed from the Philadelphia swap, an area called the MHC.

Biologists back to Linnaeus’s time have found it a fascinating exercise to list all the traits that make mammals
mammals.
One place to start—it’s the origin of the term, from the Latin for breast,
mamma
—is nursing. In addition to providing nutrition, breast milk activates dozens of genes in suckling infants, mostly in the intestines, but also possibly in spots like the brain. Not to throw any more panic into expectant mothers, but it seems that artificial formula, however similar in carbs, fats, proteins, vitamins, and for all I know taste, just can’t goose a baby’s DNA the same way.

Other notable traits of mammals include our hair (even whales and dolphins have a comb-over), our unique inner ear and jaw structure, and our odd habit of chewing food before swallowing (reptiles have no such manners). But on a microscopic level, one place to hunt for the origin of mammals is the MHC, the major histocompatibility complex. Nearly all vertebrates have an MHC, a set of genes that helps the immune system. But the MHC is particularly dear to mammals. It’s among the most gene-rich stretches of DNA we have, over one hundred genes packed into a small area. And similar to our intron/exon editing equipment, we have more sophisticated and more extensive MHCs than other creatures.
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Some of those hundred genes have over a thousand different varieties in humans, offering a virtually unlimited number of combinations to inherit. Even close relatives can differ substantially in their MHC, and the differences among random people are a hundred times higher
than those along most other stretches of DNA. Scientists sometimes say that humans are over 99 percent genetically identical. Not along their MHCs they aren’t.

MHC proteins basically do two things. First, some of them grab a random sampling of molecules from inside a cell and put them on display on the cellular surface. This display lets other cells, especially “executioner” immune cells, know what’s going on inside the cell. If the executioner sees the MHC mounting nothing but normal molecules, it ignores the cell. If it sees abnormal material—fragments of bacteria, cancer proteins, other signs of malfeasance—it can attack. The diversity of the MHC helps mammals here because different MHC proteins fasten on to and raise the alarm against different dangers, so the more diversity in the mammalian MHC, the more things a creature can combat. And crucially, unlike with other traits, MHC genes don’t interfere with each other. Mendel identified the first dominant traits, cases where some versions of genes “win out” over others. With the MHC, all the genes work independently, and no one gene masks another. They cooperate; they codominate.

As for its second, more philosophical function, the MHC allows our bodies to distinguish between self and nonself. While mounting protein fragments, MHC genes cause little beard hairs to sprout on the surface of every cell; and because each creature has a unique combination of MHC genes, this cellular beard hair will have a unique arrangement of colors and curls. Any nonself interlopers in the body (like cells from animals or other people) of course have their own MHC genes sprouting their own unique beards. Our immune system is so precise that it will recognize those beards as different, and—even if those cells betray no signs of diseases or parasites—marshal troops to kill the invaders.

Destroying invaders is normally good. But one side effect of the MHC’s vigilance is that our bodies reject transplanted
organs unless the recipients take drugs to suppress their immune systems. Sometimes even that doesn’t work. Transplanting organs from animals could help alleviate the world’s chronic shortage of organ donors, but animals have such bizarre (to us) MHCs that our bodies reject them instantly. We even destroy tissues and blood vessels
around
implanted animal organs, like retreating soldiers burning crops so that the enemy can’t use them for nourishment either. By absolutely paralyzing the immune system, doctors have kept people alive on baboon hearts and livers for a few weeks, but so far the MHC always wins out.

For similar reasons, the MHC made things difficult for mammal evolution. By all rights, a mammal mother should attack the fetus inside her as a foreign growth, since half its DNA, MHC and otherwise, isn’t hers. Thankfully, the placenta mediates this conflict by restricting access to the fetus. Blood pools in the placenta, but no blood actually crosses through to the fetus, just nutrients. As a result, a baby like Emiko should remain perfectly, parasitically invisible to Mayumi’s immune cells, and Mayumi’s cells should never cross over into Emiko. Even if a few do slip through the placental gate, Emiko’s own immune system should recognize the foreign MHC and destroy them.

But when scientists scrutinized the MHC of Mayumi’s cancerous blood cells, they discovered something that would be almost admirable in its cleverness, if it weren’t so sinister. In humans, the MHC is located on the shorter arm of chromosome six. The scientists noticed that this short arm in Mayumi’s cancer cells was even shorter than it should be—because the cells had deleted their MHC. Some unknown mutation had simply wiped it from their genes. This left them functionally invisible on the outside, so neither the placenta nor Emiko’s immune cells could classify or recognize them. She had no way to scrutinize them for evidence that they were foreign, much less that they harbored cancer.

Overall, then, scientists could trace the invasion of Mayumi’s cancer to two causes: the Philadelphia swap that made them malignant, and the MHC mutation that made them invisible and allowed them to trespass and burrow into Emiko’s cheek. The odds of either thing happening were low; the odds of them happening in the same cells, at the same time, in a woman who happened to be pregnant, were astronomically low. But not zero. In fact, scientists now suspect that in most historical cases where mothers gave cancer to their fetuses, something similar disabled or compromised the MHC.

If we follow the thread far enough, the MHC can help illuminate one more aspect of Hideo and Mayumi and Emiko’s story, a thread that runs back to our earliest days as mammals. A developing fetus has to conduct a whole orchestra of genes inside every cell, encouraging some DNA to play louder and hushing other sections up. Early on in the pregnancy, the most active genes are the ones that mammals inherited from our egg-laying, lizardlike ancestors. It’s a humbling experience to flip through a biology textbook and see how uncannily similar bird, lizard, fish, human, and other embryos appear during their early lives. We humans even have rudimentary gill slits and tails—honest-to-god atavisms from our animal past.

After a few weeks, the fetus mutes the reptilian genes and turns on a coterie of genes unique to mammals, and pretty soon the fetus starts to resemble something you could imagine naming after your grandmother. Even at this stage, though, if the right genes are silenced or tweaked, atavisms (i.e., genetic throwbacks) can appear. Some people are born with the same extra nipples that barnyard sows have.
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Most of these extra nipples poke through the “milk line” running vertically down the torso, but they can appear as far away as the sole of the foot. Other
atavistic genes leave people with coats of hair sprouting all over their bodies, including their cheeks and foreheads. Scientists can even distinguish (if you’ll forgive the pejoratives) between “dog-faced” and “monkey-faced” coats, depending on the coarseness, color, and other qualities of the hair. Infants missing a snippet at the end of chromosome five develop
cri-du-chat,
or “cry of the cat” syndrome, so named for their caterwauling chirps and howls. Some children are also born with tails. These tails—usually centered above their buttocks—contain muscles and nerves and run to five inches long and an inch thick. Sometimes tails appear as side effects of recessive genetic disorders that
cause widespread anatomical problems, but tails can appear idiosyncratically as well, in otherwise normal children. Pediatricians have reported that these boys and girls can curl their tails up like an elephant’s trunk, and that the tails contract involuntarily when children cough or sneeze.
^*
Again, all fetuses have tails at six weeks old, but they usually retract after eight weeks as tail cells die and the body absorbs the excess tissue. Tails that persist probably arise from spontaneous mutations, but some children with tails do have betailed relatives. Most get the harmless appendage removed just after birth, but some don’t bother until adulthood.

A hale and healthy baby boy born with a tail—a genetic throwback from our primate past. (Jan Bondeson,
A Cabinet of Medical Curiosities
, reproduced by permission)

All of us have other atavisms dormant within us as well, just waiting for the right genetic signals to awaken them. In fact, there’s one genetic atavism that none of us escapes. About forty days after conception, inside the nasal cavity, humans develop a tube about 0.01 inches long, with a slit on either side. This incipient structure, the vomeronasal organ, is common among mammals, who use it to help map the world around them. It acts like an auxiliary nose, except that instead of smelling things that any sentient creature can sniff out (smoke, rotten food), the vomeronasal organ detects pheromones. Pheromones are veiled scents vaguely similar to hormones; but whereas hormones give our bodies internal instructions, pheromones give instructions (or at least winks and significant glances) to other members of our species.