Sperm: The Final Frontier
Joseph Tash is determined to do something that’s supposed to be impossible: stop sperm.
Tash is a biologist at the University of Kansas Medical Center. His lab, on the third floor of the new life sciences building at 39th Street and Rainbow, affords him a panoramic view to the north — tree-covered hills, downtown’s skyline.
He is one of the world’s experts on male contraception, and he’s on the verge of developing a birth-control pill for men.
He knows what you’re probably thinking. He’s heard the jokes: Dudes won’t remember to take a pill every day — they can’t even remember to take out the trash once a week. Or they’ll lie in a heated moment, whispering, “Don’t worry, baby, I took my pill.”
But Tash says people said the same things about the female pill: Women wouldn’t remember to take it, and men couldn’t be certain that women were on it. Today, the pill’s widespread use makes those doubts sound silly — nostalgic and innocent, like the whole era of sexual liberation that’s been cleaned up and repackaged in commercials to sell baby boomers retirement accounts.
The male birth-control pill is another story. It presents a monumental scientific challenge. The female pill has to stop just one egg at a time. But a normal male ejaculation — about a teaspoon of semen — contains around 100 million sperm. To do its job, a pill for men would have to stop every last one of them.
People might doubt the need for it. There’s still the female pill, and there are other contraceptive options. But for men, condoms and vasectomies seem so 20th century, given the alternatives that Tash and other scientists might be able to supply.
The effort is important enough that the National Institutes of Health is backing Tash with millions of dollars. After working on projects funded by two federal grants that totaled $7.75 million over five years, in March he banked another $7.5 million to make KU a national center for male-contraception research and drug development.
Go ahead and laugh, then. Tash has a sense of humor about this stuff. Hanging on one wall of his office is a Matt Groening cartoon depicting a handful of Homer Simpson heads, each with a tail. “Actual Homer Simpson sperm magnified many, many times,” the cartoon reads. It’s signed “Your pal, Matt Groening, 4-1-1993.” Tash loved The Simpsons episode in which Homer worries that working at a nuclear plant might hurt his fertility. (Tash’s brother Max, who is married to Groening’s sister-in-law, commissioned the cartoon for him.)
Cartoons aside, Tash is a serious scientist. His wardrobe suggests practicality — it seems to consist entirely of cargo pants and knit T-shirts (long-sleeved in the winter, short-sleeved in the summer). He’s quiet and private. But his lifelong personal mission is one that could help the planet.
And in case the planet’s doomed, he’s also helping to figure out how humans might be able to survive migration to other galaxies.
Growing up in the comfortable, older Chicago suburb of Lincolnwood, Illinois, Tash loved chemistry class and buried his head in biographies of scientists. His first moment of scientific amazement came at middle-school age, when one of his teachers lent him a telescope with a solar filter. Tash took it out to a field. He was mesmerized by sunspots 93 million miles away. Once, for a science fair, he made his brothers and sisters chew on paraffin wax so he could collect their saliva to determine whether fluoride in toothpaste affected the bacteria in their mouths.
[page]
In 1969, after his freshman year at Northwestern University, Tash got a summer internship in the obstetrics and gynecology department at Michael Reese Hospital.
He was fascinated by the high-tech equipment. He watched surgeries. He performed experiments, starting with liters of pregnant women’s urine — he used solvent to extract the hormones, then separated various hormones to see which ones were there and how much. “I didn’t appreciate it at the time,” he says, “but Michael Reese was one of the world centers of reproductive health.”
Everyone seemed to be focusing on the female system, though. What about the male?
All around him, the world was churning. The previous summer, thousands of protesters had taken to Chicago’s streets during the Democratic National Convention. The town was tense. Michael Reese Hospital was on the South Side of Chicago — the predominantly black part of town. One night, 18-year-old Tash finished the day at his internship. As he headed toward the arched entryway, he saw a policeman standing at the entrance.
“He was holding his billy club, hitting his palm in a slow, steady beat,” Tash recalls, “presenting this intimidating look.” He was struck by the message this cop was sending to the neighborhood: What does this look like if you’re trying to come inside? “There was a basic unfairness about it. Somehow, it triggered this desire to try to make things fair in some way that I could effect. Not just protesting.”
At Northwestern, his fellow undergrads were giving him an education in 1960s politics. It was two years after the Summer of Love in San Francisco. More than 33,500 U.S. troops had been killed in Vietnam. Project Apollo’s Eagle had landed on the moon. A decade after the female birth-control pill hit the market, millions of American women were taking it, but plenty of others, including Pope Paul VI, were opposing it.
“I just felt that I could do something beyond just voicing an opinion,” Tash says. “Since I had an interest in science and saw possibilities, it opened my eyes in that area.”
Tash gravitated toward a professor named Larry Gilbert, who was studying insect hormones. It was Tash’s first chance to do real research.
The science of birth control at the time was all about hormones — the female pill uses hormones to prevent a woman from producing an egg. But in men, blocking the hormones that produce sperm has too many unhappy side effects — mainly, decreased testosterone. No man wants less testosterone. Having less testosterone kills the sex drive and shrivels muscles, among other disturbing consequences.
His junior year, in 1971, Tash got another life-changing summer internship. This one was at the University of Cambridge in England. He studied with Michael Berridge, a pioneer in discovering the ways that cells communicate with one another.
Berridge’s title is now “professor sir” because he was knighted in 1997 for his contributions to science. In an e-mail to the Pitch, Berridge writes of the young Tash, “He stood head and shoulders above the other students at Cambridge both for his intelligence and for his grasp of the literature.” Also, “He had that special quality, which is so lacking in most scientists, of knowing exactly what he wanted to do. He had the maturity to identify an outstanding problem and was able to formulate how he was going to tackle it.”
In the afternoons at Cambridge that summer, Tash would join his colleagues at the Eagle Pub. The tavern was a famous hangout of James Watson and Francis Crick, who had won a Nobel Prize in 1962 for discovering the structure of DNA. Tash grew fond of the bar’s thin-shaved corned-beef sandwiches, Greene King ale and 25-pence slot machines.
[page]
“A lot of Cambridge profs would go down late in the afternoon for drinks,” Tash says. “They’d talk about science and everything else.”
It was a thrilling summer for a Yankee undergrad, and Tash fell in love with the place. After his senior year at Northwestern, he went back to Cambridge in 1972 for a doctorate in reproductive biology.
Just outside Cambridge was the Animal Research Station. The sprawling farm had been set up by the British government specifically for Thaddeus Mann, a world-renowned expert in the physiology of sperm and semen. Scientists came from all over the world to study the reproductive systems of sheep, pigs, cattle, horses, rabbits and rodents.
He had gone there to be mentored by Mann but ended up surrounded by experts. “I never knew there could be so many people working on male reproduction,” Tash says.
He began to focus on the questions that he would spend a career answering: “How does sperm function? What makes it move? How does it find, penetrate and survive the journey through the female reproductive system for several days? What is it about sperm and all of its components that allows it to do its little job?”
When he wasn’t in the lab, Tash rode horses, including the queen’s mare, which had been sent to Mann with reproductive problems. And he competed with the University of Cambridge equestrian team in a pastoral sport that afforded him fresh air and relief from the rigors of research.
Tash wore his hair long and spent late nights working as a roadie for a band called Public Foot the Roman. On its only album, recorded in 1973, the band sounds like a blend of Yes, the Who and the Allman Brothers.
A Cambridge local named Lorraine Stutzman caught his attention. They were married in 1977.
Just before Tash accepted a postdoctoral position at the Baylor College of Medicine in Houston, he cut his long hair.
These days, Tash wears the stylish buzz for men who don’t have so much hair anymore. His drinking establishment is the LattéLand on the Plaza, the one with the Ben Franklin statue out front. He’s such a regular that when some of the coffee shop’s employees organized a trip to rebuild houses in New Orleans, he went along. He gets a lot of good writing done at LattéLand.
It took him awhile to get to Kansas City, though.
Tash arrived at Baylor just after marrying Lorraine. In Texas, he began studying sperm in a new way. This line of research would lead him closer to the male pill.
Tash had been looking at the ways in which sperm functions. But his mentor at Baylor, a professor named Tony Means, wanted him to study the testes. Specifically, Tash’s new research would target the crucial Sertoli cell, the cell that responds to male hormones and generates the cell-division process that creates sperm.
Tash explains the Sertoli cell’s role like this: If you think of sperm as a litter of puppies, the Sertoli cell is like the mother. The least mature puppies nurse at the teats closest to the mother’s head; farther down are the more mature puppies, which are eventually able to leave her care. As a junior faculty member looking for a niche, Tash decided to take everything he’d learned and concentrate on how that process could be interrupted.
[page]
This meant also thinking back to his undergraduate days at Northwestern. There, a scientist named Erwin Goldberg had theorized that there might be a unique enzyme in sperm, an enzyme critical to sperm’s ability to move. Goldberg’s idea was that you could inject an antibody that would stop this enzyme from helping sperm move. One reality stood in the way: A biological firewall protects all the cells in the testes, and antibodies can’t break through.
“I was able to make discoveries and gain insights into how things work,” Tash says. But the purely academic pursuit of knowledge wasn’t enough. Tash wanted to find something people could use.
By then, other scientists were beginning to look for the same thing.
The Population Council, an international organization based in New York, has been working on male contraceptives for 20 years. It has tested inconvenient-sounding combinations of hormones and testosterone replacements and in recent years has trademarked an implanted contraceptive, but it’s only 85 percent effective — not good enough.
In his Houston lab, Tash was growing frustrated. Research money was hard to get — it was the ’80s, and the National Institutes of Health was suffering the Reagan administration’s budget cuts. He began to think about doing his work at another institution.
At the end of the decade, Tash heard about a faculty opening in the physiology department at the University of Kansas Medical Center. Impressed by Kansas City and the people he met at the medical center, he took the job.
“We packed up an 18-wheeler and a half worth of lab equipment,” he says. The family settled into a house surrounded by big trees in the older section of Leawood.
He continued the work he’d started in Houston, but he still hadn’t found a practical male contraceptive. And he still had trouble getting his grants renewed.
Tash was reluctant to admit that what he’d been doing wasn’t the best approach. Maybe, he thought, everything his critics were saying was right.
That’s when NASA called.
It was 1996, and the space agency wanted to study reproductive systems in space.
Tash had submitted a proposal. He was on a faculty retreat when he got a message to call NASA. On a pay phone in the hallway, a flight manager for a series of experiments wanted to know whether he could be in Washington, D.C., within a week, all expenses paid.
Tash met with representatives from NASA, the European Space Agency and the Russian Space Agency.
He hoped to do an experiment that might answer two simple questions: Does sperm swim differently in a weightless environment than it does on Earth? If so, why? But when he told NASA that the tests were impossible without hauling a microscope aboard the space shuttle Atlantis, the agency rejected his idea.
He was crushed. But he learned a lesson: He needed to be flexible.
Soon, NASA solicited proposals for the shuttle’s next two flights. Tash created a different experiment, one that would work with equipment he knew would fly. NASA approved his experiment — for two flights just six months apart.
In 1997, Tash went to the Kennedy Space Center in Florida. His team re-created his med center lab in a set of offices next to Hangar L, a tall bay on Cape Canaveral that was set up with a mini mission-control area.
When the shuttle launched at night, Tash watched from a parking lot. The rockets lit up the place as if it were day. Huge, bright smoke billowed from the launch pad, and sound waves rippled across the water before slamming through his body. He could still see the light of the rocket when it was almost over Africa.
[page]
More than 127 miles above the Earth, astronauts on Atlantis performed Tash’s experiments by turning screws on a hand-sized cassette with tiny wells containing sea-urchin sperm. When seawater rushed in, the sea-urchin sperm began swimming. The astronauts measured distances after 30 seconds and after a minute.
Tash’s ground team had all of the same equipment. They watched what the astronauts were doing on a video feed delayed by two hours — that gave the ground team time to adjust for any unexpected temperature changes or other anomalies in space. It was critical that the experiments on the ground matched the space experiments precisely.
On the second flight, Atlantis approached an area over Australia where the shuttle would temporarily lose radio contact. Thirty seconds before losing the signal, Houston’s controller called Tash to see what he wanted to do: Tash needed to tell astronaut Edward Lu whether to keep going with the precisely timed experiment, but Tash was too focused on his own work. Atlantis headed toward the dead zone.
The voice from Houston began counting down — 10, nine. Tash froze. He was worried that, without audio and video feeds, his team wouldn’t be able to replicate Lu’s work two hours later.
“Wait,” he told Houston’s controller. But it was too late. He heard only crackling. Eight minutes passed, then 10. Then Tash heard Lu’s voice: “Atlantis.”
Lu had waited. The experiment was still on track. And it occurred to Tash that he’d just experienced something that happens to few men: NASA had asked him what an astronaut should do.
For the NASA experiments, Tash had designed a way to study how a series of proteins and enzymes regulated sperm’s movements. When they first start to swim, reactions occur faster, he found. But then they respond more slowly to influences from the egg. The experiment led to startling results that suggested fertilization in space might be difficult.
The flights were productive for Tash: Five published papers came out of the research, as well as a book chapter, nine published abstracts, formal seminars at national and international scientific meetings, and a patent.
Sitting in LattéLand, Tash reveals that his work with NASA changed him.
“I was crossing the line between science and a spiritual experience,” he says.
At night at Cape Canaveral, he would look up at the stars and realize that somewhere up in space were his fingerprints.
“I just felt,” he says, “part of something so big.”
On the NASA project, Tash learned other personal lessons. He had to rely on everyone from the astronauts who performed his experiments to the earthbound techs who fueled the space shuttle’s tanks. It gave him a new appreciation for the fact that he couldn’t do his work alone.
That was his frame of mind when, in May 2000, the National Institutes of Health offered a $3 million grant for work on male contraceptives. There was a catch: The lead researcher would have to be a medicinal chemist, not a reproductive biologist like Tash. “Previous approaches weren’t even going to be considered,” he says.
As it happened, there was a noted medicinal chemist on the KU campus in Lawrence. Gunda Georg is one of the country’s most prominent pharmaceutical researchers. She’s renowned — and well-funded by the NIH — for her work on cancer-treating drugs.
[page]
When Georg got the NIH’s letter announcing its request for proposals, she asked around and discovered Tash in Kansas City. “Since he had been involved in the biology of male reproduction for such a long time,” she says, “he made very good suggestions about things we could work on together.”
But Georg recalls that Tash was skeptical. “It’s very tough to get money from the NIH,” she says in a German accent. “From day one, I said to him, ‘There is nobody who can beat us as a team.’ Because it’s very unique: someone like myself, who has a really good track record in the field of medicinal chemistry, and then someone who is a reproductive biologist specializing in the male reproductive system. That was exactly what the NIH wanted.”
Tash was on board. They got the contract in March 2001.
Georg knew about the cancer-fighting drug lonidamine, which has a side effect of blocking sperm production. The problem was other side effects: muscle pain and damage to the liver and kidneys. That might be acceptable for a cancer patient who faces death without treatment, but not for a healthy male. The Population Council, in its 20-year effort to find a male contraceptive, had developed a couple of lonidamine variations that had fewer side effects but weren’t very potent contraceptives. Researching the Population Council’s patent, Georg discovered a part of lonidamine that no one had researched. She and Tash believed they could play with that molecule to create a drug that blocked the sperm production but didn’t cause damaging side effects.
A year and a half later, in November 2002, they’d synthesized more than 150 chemical variations of the compound. One looked especially promising. They called it simply RC-MC-110 and began testing it on male rats.
It worked better than they had imagined. Microscopic cross-sections of the rats’ testes showed no sperm.
Thrilled by their discovery, the NIH asked Tash and Georg to supply enough doses to send to independent researchers, who would try to confirm the results.
As the next year passed, Tash and Georg realized that the feds were conducting wide-ranging experiments that went way beyond their own — testing the potency of various oral doses and percentages of reversibility. And the NIH’s contractors went on to the next step: giving doses to male rats and putting them in cages with females to see what would happen.
In June 2004, Tash’s fax machine began spitting out spreadsheets from the NIH. Tash saw only zeros. None of the rats had produced a litter. Every few weeks, Tash would get new faxes. More zeros.
Three years later, Tash recalls no adrenaline rush during this drawn-out moment of discovery. No congratulatory phone call from the National Institutes of Health. No lighting of a rare cigar. Just faxes with zeros.
“It was like, ‘Wow,” he says calmly. “We knew it was potent.”
It’s a cold spring evening on the first dry, clear day after an awful winter. At Settlers Acres Stables in Greenwood, Tash wears a black helmet, a black sweater, black riding pants, black boots and gloves.
This is one of Tash’s favorite places. About 45 minutes east of his office, past Lee’s Summit, the city fades away and the air begins to smell like cut grass, clean mud and sweet manure.
Tash’s horse is Jabberwocky — named by his breeder because the horse’s attitude reminded him of the Lewis Carroll nonsense poem. “The look in his eye is a combination of love and impishness,” Tash says. He calls the horse Jabber for short. Gray with brown speckles that will fade to white in the next year or so, Jabber is a 7-year-old Lippizan — the most elite breed of horse.
[page]
In the center of the ring are fake stone walls and trick hurdles. Three other riders are practicing with a trainer. In the crisp air, their voices seem far away.
“The first thing I gotta do is walk him around, take the sightseeing tour, make sure everything’s as it should be,” Tash says from his place in Jabber’s black saddle. He notes that a horse’s eyes are on the sides of his head, not in front. They walk around the ring in one direction, then in the other, so Jabber can survey his surroundings from each eye.
After a dozen or so times around, Jabber picks up the pace from a walk to a trot. Later, Tash and the horse will speed up to a canter. The point of their training is for Jabber to understand Tash’s commands solely from the movements of his leg or seat, not from any pressure in the reins.
When they stop and stand perfectly still, Tash’s face is dripping with sweat.
It looks as if they’ve just been riding in circles, Jabber’s footsteps a steady pish-pish-pish in the arena’s pea gravel, but they’re training hard. They will likely ride in dressage competitions four or five times between now and October.
“With a young horse like this, it’s a constant conversation,” Tash says after another few times around. “The whole idea is for the horse and rider to work together as a team, the rider with as little effort as possible and the horse with as much willingness.”
Ever since his Cambridge days, when he competed on the equestrian team, Tash has wanted a horse with which he could do classic dressage. His son, Matt, who is now 26, and his daughter, Rose, 27, grew up riding.
“Winning the ribbons used to be the goal,” he says. Now, however, he just works on getting better.
That change in attitude parallels the way he has thought about his research over the years. “Now my goal is progress, not perfection,” he says. “Each goal is a stepping stone to the next.”
Mostly, though, he rides for the beauty of it. Their training becomes a meditation. “You have this 1,100- or 1,200-pound being that you’re working with that requires your total attention,” Tash says. “It’s a way to focus on something outside of work.”
Which is probably a good thing. Because back at the med center, Tash’s work recently got a lot more intense.
The patent for their original chemical compound — now renamed Gamendazole — is pending. Going back to the analogy about the mother dog and her puppies, Tash says the drug cuts off the mother’s milk supply (the Sertoli cell) where the most mature puppies (sperm) are suckling. Without any milk, they stop suckling, but they’re not mature enough to survive on their own.
In March, KU Medical Center announced that the NIH had given Tash $9.5 million to lead a new Interdisciplinary Center for Male Contraceptive Research and Drug Development. Georg, who left Lawrence last year and now heads the department of medicinal chemistry at the University of Minnesota’s College of Pharmacy, is associate director. Out of a new administrative office on the same floor as Tash’s lab, they’ll work with researchers at seven universities, including Duke University and the University of California-San Francisco.
[page]
“It’s nice to be part of this elite group,” Tash says of his colleagues at KU. “We’re among the big boys.”
Besides their brain power, it’s the university’s investment in high-tech equipment that helps them compete. One of those high-tech machines is housed in a strip-mall cluster of university-owned buildings called the Life Sciences Research Lab at 15th Street and Wakarusa, a couple of miles west of the Lawrence campus. There, robotic equipment called high throughput screening lets scientists test as many as 100,000 chemical compounds in a day. Without it, testing prospective drugs could take years. At KU, it takes just weeks.
Ernst Schönbrunn, a KU professor of medicinal chemistry, is part of Tash’s new team. An expert on cloning proteins, he can produce huge quantities of a single protein to test how it reacts to thousands of different chemicals. Schönbrunn can also use X-rays to see proteins in three dimensions to determine how each binds with a chemical compound.
When he got into this line of work, Schönbrunn admits, he never thought about a male birth-control pill. “If you’re in drug discovery, you think more in terms of disease,” he says. The search for a male contraceptive, he says, is “very, very challenging because you do not want to have any side effects, and it has to be reversible.”
Despite Tash’s success and the recent elevation of KU to a center for male-contraception research and drug development, the male pill is still years away.
Gamendazole hasn’t gone into human trials yet. Schönbrunn estimates it could be 10 years before it, or a drug like it, hits the market.
Tash is cautious with his optimism. “The most difficult hurdle is toxicology testing, where most drugs fail,” he says. But if such a drug survives the rigorous trials, he envisions a once-a-week pill. “It wouldn’t be a night-before contraceptive,” Tash says. “It would require that a person be willing to plan their life.”
Schönbrunn is philosophical about the prospects. “Personally, I think it will be quite interesting to see if men in general are ready for the male contraceptive.”
In the meantime, on Friday afternoons, Schönbrunn and the other Germans in his lab are the ones playing foosball at Harbor Lights in downtown Lawrence.
And that picture of a schnauzer up on the wall of the Ben Franklin LattéLand? That’s Joe Tash’s dog, Ruby. The quiet guy with his laptop? Try not to bother him too much. He’s working.
