The saga began with ratification of the Eighteenth Amendment, which banned the manufacture, sale, or transportation of alcoholic beverages in the United States. High-minded crusaders and antialcohol organizations had helped push the amendment through in 1919, playing on fears of moral decay in a country just emerging from war. The Volstead Act, spelling out the rules for enforcement, passed shortly afterward, and Prohibition itself went into effect on January 1, 1920.

  But people continued to drink—and in large quantities. Alcoholism rates soared during the 1920s; insurance companies charted the increase at more than 300 percent. Speakeasies promptly opened for business. By the decade's end, some 30,000 existed in New York City alone. Street gangs grew into bootlegging empires built on smuggling, stealing, and manufacturing illegal alcohol. The country's defiant response to the new laws shocked those who sincerely (and naively) believed that the amendment would usher in a new era of upright behavior.

  Rigorous enforcement had managed to slow the smuggling of alcohol from Canada and other countries. But crime syndicates responded by stealing massive quantities of industrial alcohol—used in paints and solvents, fuels and medical supplies—and redistilling it to make it potable.

  Well, sort of. Industrial alcohol is basically grain alcohol with some unpleasant chemicals mixed in to render it undrinkable. The U.S. government started requiring this "denaturing" process in 1906 for manufacturers who wanted to avoid the taxes levied on potable spirits. The U.S. Treasury Department, charged with overseeing alcohol enforcement, estimated that by the mid-1920s, some 60 million gallons of industrial alcohol were stolen annually to supply the country's drinkers. In response, in 1926, President Calvin Coolidge's government decided to turn to chemistry as an enforcement tool. Some seventy denaturing formulas existed by the 1920s. Most simply added poisonous methyl alcohol into the mix. Others used bitter-tasting compounds that were less lethal, designed to make the alcohol taste so awful that it became undrinkable.

  To sell the stolen industrial alcohol, the liquor syndicates employed chemists to "renature" the products, returning them to a drinkable state. The bootleggers paid their chemists a lot more than the government did, and they excelled at their job. Stolen and redistilled alcohol became the primary source of liquor in the country. So federal officials ordered manufacturers to make their products far more deadly.

  By mid-1927 the new denaturing formulas included some notable poisons—kerosene and brucine (a plant alkaloid closely related to strychnine), gasoline, benzene, cadmium, iodine, zinc, mercury salts, nicotine, ether, formaldehyde, chloroform, camphor, carbolic acid, quinine, and acetone. The Treasury Department also demanded that more methyl alcohol be added—up to 10 percent of the total product. It was the last that proved most deadly.

  The results were immediate, starting with that horrific holiday body count in the closing days of 1926. Public health officials responded with shock. "The government knows it is not stopping drinking by putting poison in alcohol," the New York City medical examiner Charles Norris said at a hastily organized press conference. "Yet it continues its poisoning processes, heedless of the fact that people determined to drink are daily absorbing that poison. Knowing this to be true, the United States government must be charged with the moral responsibility for the deaths that poisoned liquor causes, although it cannot be held legally responsible."

  His department issued warnings to citizens, detailing the dangers in whiskey circulating in the city: "Practically all the liquor that is sold in New York today is toxic," read one 1928 alert. He publicized every death by alcohol poisoning. He assigned his toxicologist, Alexander Gettler, to analyze confiscated whiskey for poisons—that long list of toxic materials I cited came in part from studies done by the New York City medical examiner's office.

  Norris also condemned the federal program for its disproportionate effect on the country's poorest residents. Wealthy people, he pointed out, could afford the best whiskey available. Most of those sickened and dying were those "who cannot afford expensive protection and deal in low grade stuff."

  And the numbers were not trivial. In 1926 in New York City, 1,200 were sickened by poisonous alcohol; 400 died. The following year, deaths climbed to 700. These numbers were repeated in cities around the country as public-health officials nationwide joined in the angry clamor. Furious anti-Prohibition legislators pushed for a halt in the use of lethal chemistry. "Only one possessing the instincts of a wild beast would desire to kill or make blind the man who takes a drink of liquor, even if he purchased it from one violating the Prohibition statutes," proclaimed Senator James Reed of Missouri.

  Officially, the special denaturing program ended only when the Eighteenth Amendment was repealed in December 1933. But the chemist's war itself faded away before then. Slowly, government officials quit talking about it. And when Prohibition ended and good grain whiskey reappeared, it was almost as if the craziness of Prohibition—and the poisonous measures taken to enforce it—had never quite happened.

  Fertility Rites

  Jon Cohen

  FROM The Atlantic

  PASCAL GAGNEUX, one of the few laboratory scientists who has studied wild chimpanzees, is a walking encyclopedia of chimpanzee/human differences. Ever since scientists began studying chimpanzees, they have emphasized our similarities, which are striking. But today neither Darwinists nor conservationists need such similarities to further their respective causes: abundant genomic evidence supports Darwinian evolution, and laws and regulations are in place to protect all endangered species, regardless of whether they are cute enough to excite human sympathy. This has paved the way for chimp researchers like Gagneux to focus on what separates us from chimps. Their goal is to sharpen our understanding of what makes a human human.

  In Gagneux's case, he and his colleagues are hoping to use their analysis of the differences between human and chimp sperm—especially the sugars that adorn the sperms' surfaces and let them bind to cells in the walls of the uterus or a fallopian tube—to unlock one of the riddles of human infertility: does sperm sometimes have components that undermine its ability to fertilize an egg? Perhaps the differences between chimp and human sperm can help explain why humans miscarry nearly 50 percent of all conceptions, while chimps seem rarely to lose an embryo or fetus.

  To get at such questions, Gagneux has spent many hours fashioning devices to coax sperm from chimpanzees. He began by sculpting a silicone version of a female chimp's rear end. But the male chimpanzees at the Primate Foundation of Arizona that were recruited to help with the project did not see it that way, and the model sat unmolested on a counter. "It's a nice chimp butt, but I thought it was a bonobo butt when I first saw it," Jim Murphy, the foundation's colony manager at the time, admitted to me when I visited a few years ago. "Maybe that's why they don't like it."

  Gagneux's next attempt relied more on medical science than on art. He modified a piece of PVC pipe to create a variation on what's known as a Penrose drain, which is used to remove pus and other liquid discharge from wounds. For the chimps the pipe was rigged with a compartment that holds warm water; latex coated with K-Y Jelly lined the interior.

  On this day Rachel Borman, who had worked at the foundation for ten years as an animal handler, was given the job of selecting a sperm donor and encouraging him to produce a sample. Borman first "gowned up" to protect her clothes. The target donor today was a sixteen-year-old named Shahee. Borman asked me not to follow her into the space that held the caged chimps, as the presence of a stranger might break the mood. So I peered through the glass portal in a door. "I'm just going to go in there with these other guys to make him jealous," Borman told me as she entered the chimp space. She did a quick pass by Shahee's rivals and returned to the supply room for the modified Penrose drain. With it in one hand and a training clicker in the other, Borman walked toward Shahee. (Trainers use clickers in tandem with positive reinforcement, usually food, to condition animals to perform a specific behavior—in this case, masturbation.) After a few
clicks, Shahee stuck his erect penis through the bars. Borman held up the PVC pipe and said, "Good boy! Good boy!" She then gave him an M&M and walked back to the lab. "He did it," Borman said proudly.

  Borman cracked open the tube. Lying on the tan latex was a chunk of chimp sperm about the size of a small wine cork. I say "chunk" because most of it had coagulated into what is known as a plug, about one-quarter of which usually melts in the warm vaginal vault. Using a Popsicle stick, Borman transferred the ejaculate into three vials. "It's fun for the chimps to do this," Borman explained as she capped the vials. "They love it."

  My job was to shuttle the vials to San Diego when I flew home that night and then drive them to Gagneux's lab at the University of California at San Diego so he could study them while the sperm were still alive. As we exited the enclosure, we passed Shahee. He spat on me.

  On the way to the airport, I realized that the chimp sperm created something of a dilemma. I had the vials in my day pack, the only bag I had brought for my short trip to Arizona. If I wanted to carry the bag with me onto the plane, I would have to pass it through security, and surely the screeners would question the liquid in my vials. What would I say? It was hair conditioner? Packed in laboratory vials? If I told the truth, would they think I was a modern Ilya Ivanovich Ivanov, the Russian scientist who tried to breed a "humanzee"? But if I checked my small day pack as luggage, would they suspect that I was a drug smuggler or some such and escalate to a search and a humiliating outing?

  I gambled that the security checkpoint was a higher risk, and I checked my day pack at the ticket counter. My bet paid off. Before I knew it, I was back in San Diego, sperm in hand, at a late-night rendezvous with Gagneux.

  People tend to think of sperm as cylindrical, but they are actually paddle-shaped, Gagneux told me. "When they move around, they resemble a surfboard tumbling around in the waves," he said. He prepared some of the sperm I'd flown in, placing it on a microscope slide. The microscope was connected to a computer screen, so I could watch in real time. The sperm did not resemble surfboards rumbling in the waves so much as bugs flittering about on the top of a pond. "Wow, look at that," said Gagneux. "It's pretty sweet, huh? There's nowhere near that many in humans."

  Gagneux's lab space was adjacent to that of his collaborator Ajit Varki, who had helped uncover the functioning of the sugars, known as sialic acids, on cell surfaces. The sialic acids on the surfaces of human and chimp sperm have become the focus of Gagneux's work, too. Humans, as Varki discovered, have lost the ability to make one sialic acid, Neu5Gc, and Gagneux suspected that Neu5Gc played a role in fertilization. He hypothesized that Neu5Gc helped female chimpanzees, in a process called "cryptic female choice," get the benefit of the most compatible, highest-quality sperm. The sugar acted like the fuzzy part of Velcro and attached to barbs formed by sugar-binding proteins on the surface of the cells in the uterus or fallopian tubes. Neu5Gc, as Gagneux imagined it, might "sweet-talk" the female reproductive system.

  Gagneux's Neu5Gc ideas had a critical implication for human fertility. Although we have lost the ability to synthesize Neu5Gc, we ingest the sugar when we eat meat and dairy products, and it, in turn, can then be incorporated into our cells. Does Neu5Gc coat the surface of human sperm? Is it found more readily on the sperm of men who eat lots of animal products? Does the extremely foreign Neu5Gc then trigger in women an immune response that selects against the survival of the sperm? "It could be that men who eat loads of meat pass a threshold and become infertile," suggested Gagneux.

  I left Gagneux shortly after midnight, and he was cranking away on the fresh chimp- and human-sperm samples he had received during the day. Science has few "Eureka!" moments, and Gagneux did not solve any great mysteries that night. But profound insights time and again come from asking simple questions that, once raised, seem abundantly obvious. Do the different sugars on the surfaces of chimp and human sperm impact fertility? is one of those obvious, beautiful questions. And it may just lead to an unobvious explanation for one of the more vexing problems that modern humans face.

  The Brain That Changed Everything

  Luke Dittrich

  FROM Esquire

  THE LABORATORY AT NIGHT, the lights down low. An iMac streams a Pat Metheny version of an Ennio Morricone tune while Dr. Jacopo Annese, sitting in front of his ventilated biosafety cabinet, a small paintbrush in his hand, teases apart a crumpled slice of brain. The slice floats in saline solution in a shallow black plastic tray, and at first it looks exactly like a piece of ginger at a good sushi restaurant, one where they don't dye the ginger but leave it pale. Then Annese's brush, with its practiced dabs and tugs, gently unfurls it. The slice becomes a curlicued silhouette, recognizable for what it is, the organ it comes from, even if you are not, as Annese is, a neuroanatomist.

  He loves quiet nights like these, when his lab assistants set him up with everything he needs—the numbered twist-off specimen containers, the paintbrushes, the empty glass slides—and then leave him alone with his music and his work.

  Annese coaxes the slice into position above the glass slide that lies half submerged in the tray, cocking his head, peering at it from different angles, checking to see that he has the orientation right. The left hemisphere must, when you're looking directly at the slide, be on the right side of your field of view, just as it would be were you staring into the eyes of the brain's owner. Although brains are roughly symmetrical, they are not entirely so, and Annese has become familiar with the individual topography of this one, all its subtly asymmetric sulci.

  For additional reference, Annese occasionally glances at a digital photograph on the screen of the computer. The photograph, two months old, was taken during another late night at the lab. It shows a bladed machine, a cryomicrotome, similar to a meat slicer in a deli. The machine holds a block of frozen gelatin, and the block of frozen gelatin holds a brain. Annese had sheared the whole brain into 2,401 70-micron-thin slices, the camera snapping once before each pass of the blade, and this particular image captures the moment before he sheared off the slice that now floats before him. The picture provides a useful comparison for Annese now, showing the slice as it looked in situ.

  That night of slicing had not been as solitary as this one. Not only had all his lab assistants been here, but thousands of other people had been present in another sense, since Annese had streamed the event live online. A colleague of Annese's later confessed that he had watched the Web stream with anxiety, hoping that Annese wouldn't become famous as the second doctor to screw up this particular brain.

  A few more gentle prods, and then Annese begins to slowly pull the glass out of the tray. Before he trained as a scientist, he worked as a cook, and he often uses cooking analogies to explain his work. The art of histology is a lot like baking, he says, since everything from the samples to the temperature to the tools must be finely calibrated, with little room for improvisation. And he is proud, justifiably so, of his skills. Soon the slide, with its burden perfectly positioned, is resting safely on the tepid surface of a warmer, where it will be left to dry overnight.

  Annese reaches for another cryogenic vial, number 451, and screws off the lid. Just before he tips the next slice into the tray, he smiles and turns to me.

  "See," he says, "how much work I have to do to clean up the mess your grandfather made?"

  There were things Henry loved to do.

  He loved to pet the animals. The Bickford Health Care Center was one of the first Eden Alternative elder-care facilities in Connecticut, which means that along with its forty-eight or so patients, the center housed three cats, four or five birds, a bunch of fish, a rabbit, and a dog named Sadie. Henry would spend hours sitting in his wheelchair in the courtyard with the rabbit on his lap and Sadie by his side.

  Another thing he loved was to watch the trains go by. His old room, 133, is on the far side of the center, and its window looks out on the tracks, where several times a day the Amtrak roars past. The canal for which the town of Windsor Locks was named
runs parallel to and just beyond the tracks, and beyond the canal looms the abandoned red-brick husk of an old paper mill.

  He loved word games. Many of the scientific papers that have been written about Henry describe his avidity for crossword puzzles, though in his later years, according to a nurse at the center, Henry found crossword puzzles too great a challenge and started doing simple find-a-word puzzles instead.

  He loved old movies. Bogart and Bacall, that era. The classics, we would call them, though of course they were not really classics to him. He'd ask to see one of these old movies, and one of the nurses or attendants would pop in a videocassette and press play on the remote control. Television sets were no shock to him, TV being a technology that developed during his time. But he never figured out how to operate a remote control.

  There was one TV series he loved to watch, too. A sitcom. All in the Family. It is a show, essentially, about a man who is mystified by a world and culture and family that change all around him while he remains the same, a man who digs in his heels, who holds on to the past, refusing to be dragged into the present.

  Henry was an extremely nice guy. Courteous, cheerful, compliant. He almost always took his meds when the nurses asked him to. On the rare occasions that he was stubborn and refused to take them, the nurses knew of an easy way to get him to cooperate. It was a trick passed down over the decades, from one nurse to another.

  Henry, a nurse would say, Dr. Scoville insists that you take your meds right now!

  And then, invariably, he would comply.

  This strategy worked right through till the end, until Henry died, two years ago. The fact that Dr. William Beecher Scoville had died long before then made no difference. Dr. Scoville remained an undying authority figure in Henry's life because Henry's life never really progressed beyond the day in 1953 when Dr. Scoville, my grandfather, removed some small but important pieces of Henry's brain.