A Cure for Euthanasia?
Science 18 Sep 2009:
Vol. 325, Issue 5947, pp. 1490-1493
(continued from page 1492)
Ja sent in his proposal, and he was one of nearly 30 scientists asked to submit a full grant application. His idea draws heavily on his work in fruit flies, for which he has designed proteins that target specific receptors involved in aging. For his Michelson project, Ja wants to target Sertoli cells and granulosa cells instead. In mammals, these gonad-specific cells foster the development of sperm and eggs, respectively. Ja hopes that by attaching a cytotoxin to his targeting proteins, he could essentially create a missile that would seek out and destroy these cells and cause permanent sterilization. “The basic idea is to treat cells that are critical for reproduction as cancerous,” he says.
The first applicant to actually receive Michelson grant money is Beverly Davidson, a neuroscientist and the associate director of a gene-therapy center at the University of Iowa in Iowa City. Davidson’s project builds on her lab’s use of RNA interference to treat neurogenetic diseases like Huntington’s. Like Ja, she’s pursuing a targeted approach—but her weapon is genetic: Davidson’s lab plans to design a virus that would deliver an RNA interference payload to regions of the brain involved in fertility, genetically silencing critical pathways. The virus would hang out in these brain cells indefinitely, resulting in permanent sterilization. “It would be like a switch we turn off,” she says.
Levy and Mayer have also applied for Michelson grants, hoping that the cash infusion will help them optimize GonaCon and ChemSpay for dogs and cats. “Our excuse for not having a product after 30 years of research into contraception is that there’s never been enough money or enough people with interest in this field,” says Levy. “All of that has now been wiped away with the stroke of a pen.”
Michelson says he hopes to see a product on the market within 10 years. But is such a product realistic?
Pitfalls in the past
Any research team embarking on the path of companion-animal sterilization would do well to heed the lessons of Neutersol. A formulation of zinc gluconate—the same compound often found in anti–cold and flu lozenges—the product was designed to be injected directly into the testicles of dogs, where it causes testicular atrophy. ACC&D’s Briggs says lack of funding slowed U.S. Food and Drug Administration approval, and veterinarians were hesitant to use the product when it finally came on the market in 2003. What’s more, Neutersol was not much cheaper than traditional spay/neuter surgery, so shelters had little incentive to adopt it. Disagreements over how to market the product forced it off U.S. shelves in 2005, although some Latin American countries still use it.
Michelson says he has designed his awards to avoid these pitfalls. To ensure that a promising technology makes it to market quickly, his foundation will “finance and support commercialization of the prizewinning product,” including funding clinical trials and helping with regulatory approval. Ja says that’s been a huge incentive for him: “As a basic researcher, it’s very appealing to think that if my work gets somewhere, I don’t have to build a team all by myself and push this out.”
Michelson also says he’ll work to make the product cheap, subsidizing its cost if necessary. “If it’s going to get widespread traction in the developing world—and even in cash-strapped U.S. shelters—it’s going to need to be a few dollars a dose,” says Levy.
Still, some question whether Michelson’s scientific criteria are too rigorous. The prizewinning product must cause permanent sterilization, for example, but Levy says even a temporary contraceptive could dramatically reduce the number of feral cats, because most don’t live more than 3 to 4 years. What’s more, Cassandra James, a viral immunologist who has researched nonsurgical sterilants at Murdoch University in Western Australia, says she doubts any single product will work in both males and females, dogs and cats: “I think it’s a Holy Grail that will probably never be achieved.” Michelson says his foundation is “willing to consider applications for grant funding that may not address all criteria but have the potential to significantly impact the problem.”
Levy and others also caution that even a perfect product will not eliminate cat and dog overpopulation. People still need to be responsible pet owners and spay/neuter their animals, for example. “There isn’t one intervention that’s going to solve this problem,” says Levy. Michelson is optimistic, however. Citing data from high-volume spay/neuter programs, he says that if the prizewinning product could lower the number of animals coming into shelters by half, the euthanasia rate would drop by more than 90%.
Ja will find out in November if he’ll be receiving Michelson funding for his cytotoxin-targeting project. Even if he doesn’t, he says he’s been so inspired by the problem that he may dedicate some of his start-up money to the idea once he heads his own fruit fly lab in a few months.
Back in Oak Hill, David Fuller is doing some anxious waiting of his own. “When I first heard about the Michelson Prize,” he says, “I said, ‘Bingo! This is just what we need.’” He’s even volunteered his feral cats for clinical trials. “If we could put a sterilant in the feed that we put out for these cats, we could control the population,” he says. “It would be a lifesaver.”