The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (52 page)

the three times he owned up to crying
:
Because you’re dying to know, the first time Rossini cried was when his first opera flopped. The bawling with Paganini was the second. The third and final time, Rossini, a bona fide glutton, was boating with friends when—horror of horrors—his picnic lunch, a delectable truffled turkey, fell overboard.

the church finally forgave him and permitted burial
:
Biographies of Paganini are surprisingly scarce in English. One short and lively introduction to his life—with lots of details about his illnesses and postmortem travails—is
Paganini,
by John Sugden.

throbbing-red baboon derrieres
:
For whatever reason, some classic American writers paid close attention to debates in the early 1900s about sexual selection and its role in human society. F. Scott Fitzgerald, Ernest Hemingway, Gertrude Stein, and Sherwood Anderson all addressed the animal aspects of courtship, male passion and jealousy, sexual ornamentation, and so on. In a similar way, genetics itself shook some of these writers. In his fascinating
Evolution and the “Sex Problem,”
Bert Bender writes that “although Mendelian genetics was a welcome discovery for Jack London, who heartily embraced it as a rancher who practiced selective breeding, others, such as Anderson, Stein, and Fitzgerald, were deeply disturbed.” Fitzgerald especially seemed obsessed with evolution, eugenics, and heredity. Bender points out that he makes constant references to eggs in his work (West Egg and East Egg are but two examples), and Fitzgerald once wrote about “the cut-in system at dances, which favors
the survival of the fittest.” Even Gatsby’s “old sport,” his nickname for Nick Carraway, the narrator of
The Great Gatsby
, probably has its roots in the early habit among geneticists of calling mutants “sports.”

bone deformities and seizure disorders
:
Armand Leroi’s
Mutants
explores in more detail what specific disease Toulouse-Lautrec might have had, and also the effect on his art. In fact I highly recommend the book overall for its many fascinating tales, like the anecdote about the lobster claw–like birth defects mentioned in
chapter 1
.

looking rather apish
:
The lip was more obvious in pictures of men, but women didn’t escape these genes. Reportedly, Marie Antoinette, part of another branch of the family, had strong traces of the Hapsburg lip.

Lincoln, fifty-six when assassinated
:
Funnily enough, Lincoln’s assassin got caught up in a genetic contretemps of his own in the 1990s. Two historians at the time were peddling a theory that it wasn’t John Wilkes Booth but an innocent bystander whom Union soldiers tracked, captured, and killed in Bowling Green, Virginia, in 1865, twelve days after the assassination. Instead, the duo argued, Booth gave the troops the slip, fled west, and lived thirty-eight increasingly wretched years in Enid, Oklahoma, before committing suicide in 1903. The only way to know was to exhume the body in Booth’s grave, extract DNA, and test it against his living relatives. The caretakers of the cemetery refused, however, so Booth’s family (spurred on by the historians) sued. A judge denied their petition, partly because the technology at the time probably couldn’t have resolved the matter; but the case could in theory be reopened now.

For more details on Booth’s and Lincoln’s DNA see, well,
Abraham Lincoln’s DNA and Other Adventures in Genetics,
by Philip R. Reilly, who sat on the original committee that studied the feasibility of testing Lincoln.

Jewish tradition bungled this story
:
Overall, though, Jewish people were acute observers of hereditary phenomena. By AD 200, the Talmud included an exemption to not circumcise a young boy if two older brothers had bled to death after their circumcisions. What’s more, Jewish law later exempted half brothers of the deceased as well—but only if they had the same mother. If the half brother shared a father, then the circumcision should proceed. The children of women whose sisters’ babies had bled to death also received exemptions, but not the children of men whose brothers’ babies had. Clearly Jewish people understood a long time ago that the disease in question—probably hemophilia, an inability of blood to clot—is a sex-linked disease that affects mostly males but gets passed down through the mother.

severe lactose intolerance
:
If the world were just, we would call the condition not “lactose intolerance” but “lactose tolerance,” since the ability to digest milk is the oddity and only came about because of a recent mutation. Actually, two recent mutations, one in Europe, one in Africa. In both cases the mutation disabled a region on chromosome two that, in adults, should halt production of the enzyme that digests lactose, a sugar in milk. And while the European one came first historically (about 7,000 BC), one scientist said the African gene spread especially quickly: “It is basically the strongest signal of selection ever observed in any genome, in any study, in any population in the world.” Lactose tolerance is also a wonderful example of gene-culture coevolution, since the ability to digest milk would not have benefited anyone before the domestication of cattle and other beasts, which gave a steady supply of milk.

tally the sequence
:
If you like to get your fingernails dirty, you can visit
http://samkean.com/thumb-notes
for the gritty details of Sanger’s work.

giving Venter an F
:
Not a biology teacher but an English teacher inspired this devotion from Venter. And what an English teacher! It was Gordon Lish, later famous as the editor of Raymond Carver.

Einstein’s brain, to see if someone could sequence its DNA after all
:
Celera people had a thing about celebrity DNA kitsch. According to James Shreeve’s riveting book,
The Genome War,
the lead architect of Celera’s ingenious supercomputer program kept on his office bookshelf a “pus-stained Band-Aid” in a test tube—an homage to Friedrich Miescher. By the way, if you’re interested in a long insider’s account of the HGP, Shreeve’s book is the best written and most entertaining I know of.

in early 2003
:
Actually this declaration of being “done” was arbitrary as well. Work on some parts of the human genome—like the hypervariable MHC region—continued for years, and cleanup work continues even today as scientists tidy up small mistakes and sequence segments that, for technical reasons, can’t be sequenced by conventional means. (For instance, scientists usually use bacteria for the photocopying step. But some stretches of human DNA happen to poison bacteria, so bacteria delete them instead of copying, and they disappear.) Finally, scientists have not yet tackled telomeres and centromeres, segments that, respectively, make up the ends and central girdles of chromosomes, because those regions are too repetitive for conventional sequencers to make sense of.

So why did scientists declare the work done in 2003? The sequence did meet at that point a sensible definition of done: fewer than one error per 10,000 bases over 95 percent of the DNA regions that contain genes. Just
as important, though, PR-wise, early 2003 was the fiftieth anniversary of Watson and Crick’s discovery of the double helix.

Venter can claim he won the genome war after all
:
On the other hand, it might actually
bolster
Venter’s reputation in a topsy-turvy way if he lost out on the Nobel. The loss would confirm his status as an outsider (which endeared him to many people) and would give historians something to argue about for generations, making Venter the central (and perhaps tragic) figure in the HGP story.

Watson’s name doesn’t come up often in discussions about the Nobel, but he arguably deserves one for compelling Congress—not to mention the majority of geneticists in the country—to give sequencing a chance. That said, Watson’s recent gaffes, especially his disparaging comments about the intelligence of Africans (more on this later), may have killed his chances. It sounds crude for me to say, but the Nobel committee might wait for Watson to croak before giving out any HGP-related prizes.

If either Watson or Sulston won, it would be his second Nobel, matching Sanger as the only double winner in medicine/physiology. (Sulston won his prize for worm work in 2002.) Like Watson, though, Sulston has entangled himself in some controversial politics. When WikiLeaks founder Julian Assange got arrested in 2010—charged with sexual assault in Sweden, the Nobel homeland—Sulston offered many thousands of pounds for bail. It seems Sulston’s commitment to the free and unimpeded flow of information doesn’t stop at the laboratory door.

to conceal these results didn’t succeed
:
An amateur scientist named Mike Cariaso outed Watson’s
apoE
status by taking advantage of genetic hitchhiking. Again, because of hitchhiking, each different version of a gene will have, purely by chance, certain versions of other genes associated with it—genes that travel with it down the generations. (Or if there aren’t genes nearby, each version of the gene will at least have certain junk DNA associated with it.) So if you wanted to know which version of
apoE
someone had, you could look at
apoE
itself or, just as good, look at the genes flanking it. The scientists in charge of scrubbing this information from Watson’s genome of course knew this, and they erased the information near
apoE.
But they didn’t erase enough. Cariaso realized this mistake and, simply by looking up Watson’s publicly available DNA, figured out his
apoE
status.

As described in
Here Is a Human Being
, by Misha Angrist, Cariaso’s revelation was a shock, not least because he was something of an expat bum: “The facts were inescapable: The Nobel Prize–winning [Watson] had asked that of his 20,000+ genes… just one lousy gene—one!—not be made public. This task was left to the molecular brain trust at Baylor University, one of the top genome centers in the world…. But the Baylor team was outfoxed by a thirty-year-old autodidact with a bachelor’s degree who
preferred to spend most of his time on the Thai-Burmese border distributing laptops and teaching kids how to program and perform searches in Google.”

banish from their field forever
:
History has a funny sense of humor. Darwin’s grandfather Erasmus Darwin, a physician, actually published an independent and fairly outlandish theory of evolution (in verse, no less) that resembled Lamarck’s. Samuel Taylor Coleridge even coined the word “Darwining” to pooh-pooh such speculation. Erasmus also started the family tradition of raising the hackles of religious folk, as his work appeared on the papal index of banned books.

In another irony, just after Cuvier died, he himself got smeared in the same way he’d smeared Lamarck. Based on his views, Cuvier became indelibly linked to catastrophism and an antievolutionary outlook on natural history. So when Charles Darwin’s generation needed a foil to represent stodgy old thinking, the pumpkin-headed Frenchman was perfect, and Cuvier’s reputation suffers even today for their lancing. Payback’s a bitch.

the tempestuous ex-wife of (among others) composer Gustav Mahler
:
Alma Mahler also had the good taste to marry painter Gustav Klimt and Bauhaus designer Walter Gropius, among others. She became such a notorious jezebel in Vienna that Tom Lehrer wrote a song about her. The refrain goes: “Alma, tell us! / All modern women are jealous. / Which of your magical wands / Got you Gustav and Walter and Franz?” I have a link to the full lyrics on my website.

before she was ever born
:
Since Dolly, scientists have cloned cats, dogs, water buffalo, camels, horses, and rats, among other mammals. In 2007 scientists created embryonic clones from adult monkey cells and let them develop enough to see different tissues. But the scientists snuffed the embryos before they came to term, so it’s unclear whether the monkey clones would have developed normally. Primates are harder to clone than other species because removing the nucleus of the donor egg (to make way for the clone’s chromosomes) tears out some of the special apparatus that primate cells need to divide properly. Other species have more copies of this apparatus, called spindle fibers, than primates do. This remains a major technical obstacle to human cloning.

letting politics color their science
:
Psychoanalyze this how you will, but both James Watson and Francis Crick have stuck their size tens into their mouths with impolitic public comments about race, DNA, and intelligence. Crick lent support to research in the 1970s on why some
racial groups had—or, more truthfully, were tested to have—higher or lower IQs than others. Crick thought we could form better social policies if we knew that certain groups had lower intellectual ceilings. He also said, more bluntly, “I think it likely that more than half the difference between the average IQ of American whites and Negroes is due to genetic reasons.”

Watson’s gaffe came in 2007 while on tour to promote his charmingly titled autobiography,
Avoid Stupid People
. At one point he proclaimed, “I’m inherently gloomy about the prospect of Africa,” since “social policies are based on the fact that their intelligence is the same as ours. Whereas all the testing says, not really.” After the media flagellated him, Watson lost his job (as head of Cold Spring Harbor Laboratory, Barbara McClintock’s old lab) and more or less retired in semidisgrace.

It’s hard to know how seriously to take Watson here, given his history of saying crude and inflammatory things—about skin color and sex drive, about women (“People say it would be terrible if we made all girls pretty. I think it would be great”), about abortion and sexuality (“If you could find the gene which determines sexuality and a woman decides she doesn’t want a homosexual child, well, let her”), about obese people (“Whenever you interview fat people, you feel bad, because you know you’re not going to hire them”), et cetera. The Harvard black studies scholar Henry Louis Gates Jr. later probed Watson about the Africa comments in a private meeting and concluded that Watson wasn’t so much racist as “racialist”—someone who sees the world in racial terms and believes that genetic gaps may exist between racial groups. Gates also noted, though, that Watson believes that if such gaps do exist, the
group
differences shouldn’t bias our views toward talented
individuals.
(It’s analogous to saying that black people may be better at basketball, but the occasional Larry Bird can still thrive.) You can read Gates’s thoughts at
http://www.washingtonpost.com/wp-dyn/content/article/2008/07/10/AR2008071002265.html
.