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      The Science of Artificial Testicles

      April 5, 2015

      Photo by Flickr user Iqbal Osman

      Someday, in the not-so-distant future, we won't need sex or even sperm to make babies. All it will take to reproduce is a swab of the cheek, or a scrape of the skin, or some other way to collect a live cell carrying your DNA, and voila: a bouncing baby, without all that mess and fuss. The technology to do so is almost within reach, in part because of a research team that has been working to develop an artificial human testicle.

      California urologist Dr. Paul Turek is the man leading this group, which includes doctors and scientists from Stanford University, Montana State University, and the San Francisco biotech company MandalMed. The model they're developing now—an unassuming piece of lab equipment made out of bottles and tubes—is designed to mimic the complex inner structure of a man's testicle, and, ideally, turn stem cells into sperm.

      Turek says a working artificial testicle could let men who struggle with infertility due to cancer treatments or other conditions or injuries make babies with the aid of in vitro fertilization. It could also be used in the safety testing of pharmaceuticals in place of animals.

      "I get driven by this every day," Turek says. "I know the need is there."

      Stem cells are treasured by researchers for their ability to proliferate and, in the right conditions, develop or "differentiate" into other types of tissue cells or organ cells. And in recent years, research has shown that stem cell biology can be useful in the study of infertility. In 2011, a group in Japan made a major breakthrough, announcing that they were able to make mouse sperm in a lab by seeding a piece of gelatinous material with stem cells drawn from the testicular tissue of baby mice. Last May, another team of scientists took things even further, publishing a report in the journal Cell Reports that documented how they used skin cells taken from infertile men to make primitive sperm precursor cells inside mice testes.

      Turek, who was a co-author of the latter study, says the trick with the artificial testicle is to create an environment in which stem cells become convinced that they're living in a real-life testicle. With the right combination of cells and hormones, the stem cells—whether testicular stem cells, embryonic ones made in a lab, or adult stem cells derived from a man's skin—could be nurtured enough that they might transform into full-blown sperm.

      "You gotta figure out the recipe, and you gotta figure out what you're going to put into the recipe," Turek says. "There are all these variables, but it's just a matter of good science. It's all good science. It's taking your time, paying attention to details, watching what happens, and tweaking it and tweaking it until you get it."

      Of course, there's no guarantee that an ersatz testicle will actually be capable of making a baby. Even if it did get up and running, it'd be a complicated piece of equipment requiring careful use in a lab—not something you could implant or put on the nightstand.

      Whatever the case, it's exciting to think that humanity might one day have access to a bona fide sperm-making machine. After all, men have been plagued with the specter of infertility probably for as long as they've been walking the earth.

      Over the years, plenty of patients have turned to dubious solutions. In the early 1900s, gents flocked to the American doctor John R. Brinkley to seek a highly unorthodox treatment in which he transplanted their testicles with goat glands. The procedure, which cost nearly $9,000 in today's dollars, was supposedly meant to cure infertility as well as a range of other ailments. Not surprisingly, though, the goat balls proved disastrous for many patients, leading to infection and even death.

      These days, the standards of medical science are improved, and men have plenty of options if they're worried about not being able to make babies. Though chemotherapy for testicular cancer can potentially render men infertile, they can have their sperm frozen in a sperm bank before treatments begin. As for men who suffer from extremely low sperm counts, they can resort to a highly specialized procedure in which a surgeon will literally open up their family jewels to hunt for trace sperm.

      Peter Schlegel, a surgeon and professor of urology at the Weill Medical College of Cornell University, explains that a man's sperm cells are made inside an intricate network of seminiferous tubules found inside the testicles. "The tubes that are larger and thicker are basically the tubes that have more cells in them—and therefore [those are] the tubules that are most likely to have sperm present," he says.

      When asked about the artificial testicle, Schlegel says replicating this complex structural system in a lab situation might prove to be the biggest challenge for Turek and his team.

      "An artificial testicle sort of assumes that you can take those hundreds of thousands of complex interactions that occur and simplify them to kind of a soup that you put around the sperm-making cells," he says. It might be more effective, he suggests, to use testicles from an animal as a way to grow human sperm, instead of a device built in a lab. Yes, that's right—get a mouse or rat to make your sperm for you.

      "The testicle itself, in terms of function, is pretty complex," he says. "There's a lot of cell-to-cell interaction, and so the concept of generating an artificial testicle may be best done in a mouse or a rat or some other animal that has all of those other growth factors and hormones and materials that could support the development of the testicle."

      It's a curious notion, having our sperm made outside of our bodies. But we're still a ways away from that future. Right now, Turek's team is focused on getting funding to continue its research. One goal is to develop an assay for pharmaceutical toxicology testing purposes. That wouldn't be as complicated as making personalized sperm, and it could also serve as a source of revenue to keep the greater mission going.

      "We are interested in developing this whole area as a business," says Constance John, the president of MandalMed, who started working with Turek on the artificial testicle idea in 2009. "One of the strategies here is to develop this assay, which we think would be commercializable and could be profitable and therefore would make the company not a losing proposition."

      To raise cash for the project, Dr. Turek has also thought about using more populist means—a.k.a. a Kickstarter campaign. The only question is what prizes he'd give to donors.

      "You can't give them sperm, because that costs a fortune," he says.

      Sperm-shaped pillows, maybe?

      "Yeah, we can do sperm pillows," he says. "Good one. Let's do that."

      Follow Peter Holslin on Twitter.

      Topics: testicles, balls, transplant, sperm, artifical, stem cells, health, research, men, science

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