The Flight of the Spermatozoon

in THe first of a seRies of in-DePTH rcports on THe science of maLe sexuauTy, me TRacK a speRm cei_L anD its DeLicaTe payLoaD, THe unDeRRaTeD y CHRomosome, on THeiR FanTasTic uoyaGe to maKe a man. you'LL neueR look aT youR BaLLS THe same way aGain

n the time it takes to read this sentence, your testicles will have produced 5.000 sperm. By the end of this page, another 100,000. A bil­lion more wait in reserve. They hope to be released inside a vagina, but if no woman is

--------------• available, they will find a way out. Your brain

will help by providing a fantasy in which the female doesn't say no. Your brain is generous with these fantasies. You cant walk down a runway of breeders like Fifth Avenue in Manhat­tan without judging every woman in an instant as doable or, in more polite terms, as a means to push your genes into the next generation. If you could have a quickie with every five or better without expending any effort besides catching up with her. and she would bear your child without asking you to stick around (with the exception of a few playdates: you're not heartless) or pay for anything, how many kids would you create? Moulay Ismail the Bloodthirsty, ruler of Morocco from 1672 to 1727, is the official record holder, with

at least 867. Because with as much grief as men get for our seemingly boundless sexual appetites, it's not about getting off. We can do that on our own. At the most basic level it's about ego: There can never be too many versions of you.

That biological truth drives the conveyor belt in your testicles. It also drives this article, the first of a series that will examine what scientists know about male sexual­ity. The sperm factory is a natural place to start because the tenacity of a single spermatozoon produced by your father's factory is (along with his seduction skills) the rea­son you exist. A man's sperm factory operates 24 hours a day, seven days a week, from about the third grade to as long as 48 hours after death. The genetic material packed into the head of the first sperm to penetrate an egg—the lone survivor in a sprint that resembles either the Bos­ton Marathon or Death Race 2000— determines whether an infant will be born with a penis or without (with a few notable and fascinating exceptions).

The spermatozoon that created you, the quadrillions you will produce and those made by your sons constitute a broth­erhood. Each contains a nearly identical Y chromosome, the trigger that makes the man. We will ride these sperm for the first part of our journey. Saddle up.

speRm HuriTeRS

Not until the 17th century did anyone realize there are crit­ters swimming around in semen. According to one account, in 1677 a Dutch medical student named Johan Ham thought he had seen something in the discharge of a patient with gonorrhea. He took a sample to Antoni van Leeuwenhoek, a businessman who spent much of his free time peering through microscopes he had built. Leeuwenhoek continued the investigation with semen from healthy males, including his own. In a report to the Royal Society of London, he is careful to note that he gathered these specimens not by "sinfully defiling myself" but from the "residue of conjugal coitus." In 1679, after dissecting a hare. Leeuwenhoek con­cluded that sperm originate in the testicles.

Each sperm takes 10 weeks to make. The process starts with a group of stem cells created during the first few weeks of your existence. Numbering only in the tens of thou­sands—fewer than you'd find in a drop of blood—the cells march through your gut and pitch camp in your testes (which have yet to descend). These starter cells will always remain outsiders. If your body didn't set up a barrier between your blood and sperm, white blood cells would attack them as they would a common infection. As scientists are discover­ing, sperm stem cells, also known as the germ line, have amazing properties. First, they are essentially ageless. When other cells divide, the chromosomes inside them that carry your DNA fray a little. But in the germ line, enzymes repair these wounds. Second, experiments with mice have found that when stem cells from the testicles are placed with cells from the heart, brain or skin, they grow to become matching cells. This suggests that doctors may someday be able to harvest your germ line to cure you of diabetes, spinal-cord injuries or any number of other maladies.

Your germ line divides about 30 times before you hit puberty, when the testicles begin to pump out so much sperm that the stem cells must split every 16 days to keep up. It's a wonder smoke doesn't rise from your snorts. By the time you hit the age of 30 your germ line has divided 380 times; by 50 it has divided 840 times. (By contrast, the germ line that creates a woman's eggs divides only two dozen times, all before she is born.) The problem is, these hundreds of splits create more opportunities for mutations: At least 20 disorders, including dwarfism and schizophrenia, have been associated with older fathers, leading the American Society for Reproductive Medicine to recommend that anonymous sperm donors be younger than 40. Not that mutations are all bad. "Men are the source of most of the errors that provide the raw material of genetic change." says biologist Steve Jones, author of Y: The Descent of Men. "Some are harmful, but others do good and are soon picked up by natural selec­tion. A lot of evolution takes place in the male line."

Before it is ready to be ejaculated, a sperm must go through a IE-day training camp. This occurs in the epididy-mis, a tightly coiled tube clumped along the back of each testicle. Stretched out. it can measure as long as 20 feet. Here the eager young bucks—hungry for adventure but so naive—learn to swim and are briefed on how to penetrate an egg. The assembly line continues outside the testes in the 16-inch-long vas deferens. which is more of a straightaway and is what a doctor snips if you have a vasectomy. It loops

over the bladder and continues as the ejaculatory duct, which empties onto the flight deck of the urethra.

As a guy becomes aroused, hundreds of millions of sperm are pushed through this double set of tubes. As they leave the vas deferens. the sperm are mixed with semen produced by the prostate gland and seminal vesicles. This versa­tile substance will carry them toward the light, keep them from being burned alive in vaginal acid and fit each with the equivalent of a hooded sweatshirt so they can slip past the woman's immune system. At the same time, glands release two or three drops of mucus that lubri­cate the inside of the urethra. Although this precome has been used to explain an untold number of pregnancies ("But I pulled out"], several studies suggest it doesn't contain sperm. The pressure builds to the point of what scientists call ejaculatory inevitability—the moment, often verbalized, when you know you're about to come. The mixture leaves at the speed of a city bus. propelled by what one study recorded as eight to 33 rapid-fire shivers, the pattern of which appears to be unique in every man—an orgasmic fingerprint. The amount of fluid ejaculated, on average, would fill most of a teaspoon, if you had that sort of aim. If not collected in a condom, the globs splat against the woman's cervix, then puddle on the floor of her vagina. Thanks to the adventurous producers of The Human Animal, a BBC series, this event has been videotaped—the most penetrating porno ever made. The Brits attached a flexible, pen-size cam­era to the underside of a man's erec­tion before he had intercourse with his wife. The footage revealed that as a man thrusts, the cervix stretches so that it's in position to dip into the pool of semen. Biologist Robin Baker compares this to an elephant lowering its trunk into a watering hole. Once contact is made, the sperm swim into mucus channels toward the uterus, a rope climb that is taking place inside millions of women at this very moment. After a few minutes the cervix pulls up. leaving behind a pool that becomes part of what researchers refer to as flow back, a.k.a. the wet spot.

Those sperm that make it inside still face almost impossible odds, especially if the woman's reproductive tract isn't accepting visitors, which is most of the time. Yet the journey is essential: if you mix freshly ejaculated sperm with an egg. they will ignore each other. Those sperm that manage to negotiate the cervix and traverse the uterus arrive at one of the two oviducts, or fallopian tubes, where they receive a burst of energy and a

stamp on the hand that allow them a shot at life. In 1963 sci­entists figured out how to mimic these chemical changes well enough to combine the egg and sperm of a hamster in a petri dish. This discovery led 15 years later to the first test-tube baby. Louise Brown, and since then more than 3 million children have been conceived through in vitro fertilization.

The success of IVF has had interesting consequences. One is the phenomenon of inherited infertility, in which a sterile man passes along his damaged Y chromosome to his sons, who are born sterile. Another is much older mothers. In 1996 scientists combined the sperm of a 57-year-old California man with a donor egg to impregnate his 63-year-old wife. In 2005 a 66-year-old Romanian woman, after nine years of hormone treatments, broke that record. However, both the sperm and egg came from anonymous donors, leading sticklers to consider her only the oldest surrogate. A more recent development in baby making without sex is intracytoplasnrric sperm injection, in which scien­tists select a sperm from the testes and shoot it into the center of an egg. The technique has been controversial because no one knows if that particular sperm would have made it to the egg on its own. It may be the village idiot. But the oldest ICSI children are now 16, and so far scientists haven't found any mutants.

"me PLunGe

Once the most robust sperm have gathered at the oviducts, they apparently wait to be called to the egg—or eggs, in the case of fraternal twins or triplets—which at a hulking .004 inches wide is the largest cell in the female body. Studies sug­gest that only a small percentage of the sperm are capable of receiving this beacon, which sends their tails into overdrive; one group is called forward, then the next, then the next, like a graduation ceremony. These overachievers surround the egg like a crowd of suitors on ladies' night, looking for an opening, while the egg asks a few basic questions, such as "Are you human?" If the egg arrives and no sperm are there, it sits tight for a day or so before disintegrating. But it's never happy about being made to wart. Research suggests that a woman is more likely to get pregnant if the sperm arrive first.

If the timing is right (or wrong, depending on your perspec­tive], a single sperm breaks through the egg's membrane. Instantly the egg shuts down. Nature has no plans for a tie. The loser sperm continue to jockey for position, too drunk on egg juice to realize the party is over. Inside, the alpha male is having the best sex of its life, despite having had its tail snapped off (it can be seen floating around in the egg), its head melted and its tightly packed payload unraveled. This is necessary so the 23 chromosomes containing your father's genes can combine with the nucleus of the egg and its 23 chromosomes containing your mother's genes. The DNA provided by your parents differs by a tenth of a percent, which becomes the gap between you and any other human. At the moment they fuse, which occurs within about 20 hours after the sperm breaks through, the genetic data that make you the son of your parents—your height, skin, eye color, nose, personality, penis size and whether you will lose your hair—is set. You are now one cell old and unlike any other being who has ever existed or ever will.

THe y

The answer to the question of man is the Y. If the head of the first sperm to reach the egg contains a Y chromo­some, it joins an X supplied by the mother to create a male: XY. If it has an X. the fetus will be (continued on page 130]

mai_e

(continued from page 54)

female: XX. One of the scientists who dis­covered this simple mechanism, in 1905, was a Stanford grad named Nettie Maria Stevens, whom biologist Steve Jones calls "the Albert Einstein of manhood." It would take another 85 years for scien­tists to nail down the specific part of the Y that makes the man, and they learned this (as they usually do) through muta­tions. In the mid-1960s scientists found two women who had, rather than a sec­ond X chromosome, a partial Y. Since the women did not have testicles, scientists could rule out a good portion of the Y as the source of genes that lead to maleness. Through a series of similar deletion map­pings, including those from XXY men, a team of British geneticists pinpointed the male trigger, a gene they called SRY, for sex-determining region of the Y. The gene takes up just 3,000 spaces on a DNA string 55 million spaces long. To confirm the finding, they injected a female mouse embryo with a tiny sliver of Y that con­tained only the SRY gene. As expected, the embryo developed into an XXY male. The discovery was announced in Nature, which paid tribute by putting the big-balled rodent on its cover. By show­ing that only this tiny fragment is needed to make a male, scientists seemed to con­firm a long-held belief that 95 percent of the Y is useless.

After nailing down SRY, scientists turned their attention to the rest of the chromosome. Beginning in 1999 a team of 40 geneticists spent five years ana­lyzing a Y provided by an anonymous donor recruited through a classified ad in The Buffalo News. The good news is the team discovered many more genes than expected. The bad news is there are only about 76. The X, by comparison, has 1,098. What's worse, the Y appears to have lost so much genetic material since its origin as a mutated X. about 300 mil­lion years ago, that tearjerkers such as Adam's Curse: A Future Without Men, by geneticist Bryan Sykes, began appear­ing in bookstores. Given the apparent rate of decay, Sykes gave the Y as little as 125,000 years to live.

For some feminists, the idea that men may someday disappear has a certain romance. It has become a calling card for geneticist Jennifer A. Marshall Graves of Australian National University, who dismisses the Y as a wimp because most of its genes, including those responsible for sperm production, originate with the X. She has noted that several mammals, including the Armenian mole vole and the Scandinavian wood lemming, have shown a species can survive without a

male chromosome. "The rodents are leading us into the new era of Y-less exis­tence," Graves declares, and in fact a few fully functional men have been discov­ered who are XX with no apparent SRY. The notion that humankind can survive without the Y has also inspired colum­nist Maureen Dowd, who makes it the centerpiece of her book Are Men Neces­sary? "Now that we don't need men to reproduce and refinance, the question is, Will we keep you around?" Dowd asked during an appearance on CNN. The answer is yes, she said, but "you'll be more ornamental."

Dr. David Page, a professor of genet­ics at MIT, has been studying the Y for more than 25 years. It has never been a popular area of genomics—decoding the repetitive DNA inside the chromosome is complicated and time-consuming. (Page likens the process to comparing two aer­ial views of Manhattan that vary only in the placement of a few fire hydrants and mailboxes.) A slim, gregarious 50-year-old, Page says he is at peace with the fact that his own Y will not survive—he has three teenage daughters—but admits he recently brought home a male puppy. Only later does one of the scientists in his lab at the Whitehead Institute for Bio-medical Research reveal that the dog will be neutered the following week and that Page had assigned her to retrieve its tes­ticles in the event he decides to decode the canine Y.

When Jennifer Graves's name comes up in conversation. Page seems more bemused than impatient with her con­viction that the Y is doomed, although in the past he has dismissed many of her assertions on the topic as "rheto­ric and theory unburdened by experi­mental data." To summarize her view that the Y began millions of years ago with as many genes as the X but will eventually die off, he draws a graph on the board in his office at White-head, with the line representing the Y continuing downward like a crippled fighter plane crashing into the sea. "But what if," he asks, "the line goes this way"—he curves his marker gently to the right so the line levels out—"and stabilizes?" That is precisely what his research indicates is happening. After comparing Buffalo Man's Y with that of a chimp, Page and his team found that four genes on the chimp Y have mutations that make them inactive, while the same genes in the human Y are going strong. This suggests that our Y has held steady for at least the past 6 million years, ever since chimp

and man diverged. In other words. Page says, the Y is not falling.

Even so. no one debates the fact that the chromosome has suffered a stun­ning decline. It has decayed so rapidly that big-screen televisions, football and cigars should probably not exist. Much of its shrinkage can be attributed to how the V exchanges DNA with the X during the making of a sperm cell. In a complex process called meiosis, the 23 pairs of chromosomes inside each germ cell exchange DNA with their partners and then are rather violently separated, giving you a newly minted sperm car­rying 23 individual chromosomes and a unique mix of paternal and maternal genes. The problem is that when (he X and Y come together during their initial meetings, they can swap genes only at their tips. Otherwise the testicle-making SRY gene would jump to the X, mak­ing everyone male. (Fun for a weekend, yes, but we'd get lonely.) Over hun­dreds of millions of years, this limited exchange has caused most of the Y's genes to disappear. So what has slowed the process? Faced with annihilation, the Y learned to fuck itself. Within each Y is a DNA strand that consists of eight palindromes—sequences that are identi­cal whether read forward or backward. By folding into the shape of a hairpin, the strand can replace damaged genes in one section with healthy genes from another, without involving the X.

This clever adaptation has kept men around, but it hasn't solved every prob­lem. For instance, 60 genes that control sperm production are inconveniently located on the tips that recombine with the X. meaning they are sometimes lost, which is a major cause of male infertil­ity. And the fact that the Y largely keeps to itself means it can't serve as a backup. The only way a woman suffers an X-related genetic disorder is if she inherits the same bad gene from both parents. But if a gene on a man's X is broken, he's screwed. This is why more males suffer from such X-linked disorders as color blindness, hemophilia, Duchenne muscular dystrophy and fragile-X retar­dation. There are at least 307 X-linked disorders, and each occurs more often in men. On the bright side, the male X provides a gold mine of genetic data for researchers hoping to eradicate disease.

Men and women both inherit an X from their mother, the Y doesn't do much besides make testicles, and wom­en's second X is thought to be largely inactive, so biologists have long insisted that the genders are not very different. However, in 2005 two scientists discov­ered as many as 300 active genes on the "dormant" female X. Combined with the fact that the Y has more genes than thought, this means men differ more from women genetically than humans do from chimps. It also means men and women are hundreds of times

further apart than any two races. Thus a white man is closer genetically to a black man than to his wife. Finally, it suggests that gender differences thought to be hormonal—how we see the world, how we behave, how we look, our susceptibility to disease—may be influenced more by genetics.

TRACING THK V

The fact that the Y chromosome remains largely unchanged when passed from father to son interests geneticists and genealogists. Doug Mumma, a retired physicist from Livermore, California, has traced his family tree the traditional way, by collecting names and dates, and, as a technological pioneer, by collecting cheek swabs from 76 men (so far) who share his surname. After having the samples ana­lyzed, he was able to assign most of the

contributors to one of three immigrants who came to the U.S. between 1731 and 1748. and he also learned that these three were closely related but probably not brothers. This is an important dis­covery if you are a Mumma. In a more formal study, Oxford geneticist Bryan Sykes collected samples from 48 British men also named Sykes. Most shared his Y, revealing that the same man who had taken the name Sykes centuries before had begotten each of them. The variation in the rest of the samples derived from different Sykes ancestors or a known or unrealized adoption of another man's son, which Sykes estimates to occur in 1.3 percent of cases in each generation. Sykes has since repeated his experiment with hundreds of other British families and found that most men who share a surname also share a Y.

Scientists have mapped other, more notorious lineages. In 2002 geneticists completed a 10-year study that involved analyzing the Y chromosomes ol"2.123 men from 16 diverse populations now living in the former stomping grounds of "Genghis Khan. They concluded that about eight percent of the men in Asia— and a total of 16 million men world­wide—are likely descendents of the Khan, who lived in the 12th and 13th centuries and was known for conquer­ing an area, killing the males and rap­ing the most desirable females. Genghis Khan's eldest son had at least 40 sons of his own; a grandson in China (Kublai Khan) had at least 22. "My guess is the Y of most living men has spent at least one generation inside the testes of a warlord." says Sykes.

On a broader scale, a team led by Michael Hammer of the University of Arizona has organized the world's Ys into 18 types, known as haplogroups, based on mutations that have remained stable for tens of thousands of years. Theoretically, all these assorted Ys originate with a genetic Adam—not the first male but the one whose Y survived. Hammer believes that this Adam lived in Africa about 100.000 years ago and that his closest relations reside today in southern Africa, as well as Sudan and Ethiopia, suggesting the earliest humans moved north along the eastern rift of the continent.

Companies such as Family Tree DNA, where Hammer consults, and Oxford Ancestors, founded by Sykes, have made a business of mapping Ys for modern men. The test results, which reveal the haplogroup you belong to and document 10 to 67 more precise DNA markers, can be entered into online databases to locate cousins. Because relatively few Ys have been mapped, a match is a long shot unless others with your surname have started a DNA project. Neverthe­less, in 2004 an American teenager used a genetic genealogy service and a bit of detective work to locate the anony­mous sperm donor who became his father. The boy paid S289 to have his Y mapped and entered into Family Free DNA's database of the mapped Ys of 20,000 other men. Within nine months he was contacted by two men with Ys that closely matched his. The two men did not know each other, but their Ys suggested a 50 percent chance that they had a common father, grandfather or great-grandfather. More important, the men shared the same last name, with slightly different spellings. The boy also knew the donor's date and place of birth, so he used another database to get a list of every male born in the right place at the right time. Only one man on the list had the surname, and 10 days later the boy tracked him down.

"My guess is the Y chromosome of most living men has spent at least one generation inside the testes of a warlord."