Neither has the wait for Godot
CINCINNATI, Ohio––Cat rescuers and cat haters alike are jumping up and down excited over reports amplified by The Atlantic, Science, The New York Times, CNN, SciTechDaily, Science News and the Alliance for Contraception in Cats & Dogs that a single-injection chemosterilant for female cats may be at hand.
As usual, though, if something sounds too good to be true, it usually is, and reality is that the biochemistry generating the excitement is unlikely to become a product, let alone an affordable product accessible wherever needed, until after at least five more years of research and development, followed by product safety testing––as the researchers and developers acknowledge.
Nothing, in short, is a done deal, or even close to it.
Read the link to the science here
Generating the excitement are mass media readings of a scientific paper published by the online periodical Nature Communications on June 6, 2023 entitled “Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene.”
You can read the whole paper here: https://www.nature.com/articles/s41467-023-38721-0.
But the title is about as easily readable as the paper gets.
What the scientists say
The bottom-line conclusion, for the 21 authors and co-authors, is that “Herein, we report evidence that a single intramuscular treatment with an adeno-associated viral vector delivering an anti-Müllerian hormone transgene produces long-term contraception in the domestic cat.”
The evidence, in the authors’ words, is that treated female cats were “followed for over two years, during which transgene expression, anti-transgene antibodies, and reproductive hormones” were monitored, while “mating behavior and reproductive success were measured during two mating studies.”
The paper, the authors and co-authors explain, shows that “ectopic expression of anti-Müllerian hormone does not impair sex steroids nor estrous cycling, but prevents breeding-induced ovulation, resulting in safe and durable contraception in the female domestic cat.”
What in the name of Bastet the cat goddess?
Most folks can understand the last eleven words of that sentence.
Reports based on those eleven words are why people are jumping up and down.
But what in the name of Bastet, the Egyptian cat goddess, is “Anti-Müllerian hormone”?
Explain the authors and co-authors, “Anti-Müllerian hormone (AMH) (or Müllerian inhibiting substance, MIS) is a member of the transforming growth factor-beta (TGFβ) superfamily of ligands that is crucial for sex determination in fetal development.
“We show that this vectored contraceptive prevents breeding-induced ovulation, results in complete infertility, and may constitute a safe and durable strategy to control reproduction in the domestic cat.”
Got that?
No, AMH cannot be baked into cookies, even by Alex Pacheco
Most folks might understand the science.
Some might even realize that AMH, which is temperature-sensitive and must be kept refrigerated, cannot be baked into “spay and neuter cookies.”
Neither could an AMH-based product be administered to cats in ice cream, or in either vegan or mouse-flavored pie from the sky.
(See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165850/ for the science of AMH temperature sensitivity. For the nonsense, see “600 Million” reasons to toss Alex Pacheco’s alleged spay/neuter cookies, Pseudo-science & the Alex Pacheco “Spay & Neuter” Cookie, Alex Pacheco of “600 Million” says he was gunner on a boat with no guns, Steve Hindi & SHARK up the ante & call Alex Pacheco’s bluff, Alex Pacheco serves stale “Spay & Neuter Cookies” again for Christmas, and Spay/neuter popcorn? It’s as real as Alex Pacheco’s s/n cookies!)
Two separate questions
But “Does it work?” and “Why does it work?” are two separate questions, essential to answer for researchers and developers to make further progress toward developing a possible eventual cheaper, easier alternative to neuter/return, as practiced worldwide by perhaps millions of people.
The 21 authors and co-authors of “Durable contraception in the female domestic cat” go on to acknowledge that, “While we favor the interpretation that the contraception observed herein is caused by a direct effect of AMH on the ovary, by inhibiting ovarian follicles to complete maturation and ovulate in response to an LH surge, we cannot rule out an impairment of the LH surge itself. Indeed, others have shown that AMH may also directly regulate gonadotropins in the pituitary,” which could cause the same effect.
Grimm addresses the fairy tales
Science online news editor David Grimm offered the most succinct, accurate, and lucid mass media translation of the geek-speak to hit the web within 24 hours of the Nature Communications article.
“In 2009,” Grimm recalled, “to accelerate efforts to find nonsurgical alternatives [to conventional spay/neuter surgery], a nonprofit called the Michelson Found Animals Foundation,” begun by surgical inventor Gary Michelson, “announced $50 million in funding and a $25 million prize. The program has since given out 41 grants, supporting everything from toxicants that target reproductive cells to RNA-based drugs that attempt to silence the genetic machinery that leads to conception.”
No previous approach seemed especially promising, Grimm recounted.
It’s all happening at the zoo
But “David Pépin, a reproductive biologist at Massachusetts General Hospital, spent his early career researching antimüllerian hormone (AMH), which is produced by follicles in the ovary that give rise to eggs,” Grimm wrote. “In one experiment, he amped up the expression of the hormone in female mice. Their ovaries stopped forming follicles, sterilizing the animals.”
Pépin submitted his findings to the Found Animals Foundation. One of the Found Animals Foundation grant proposal reviewers, Cincinnati Zoo conservation biologist William F. Swanson, teamed with Pépin to take his approach further.
“In the new study,” Grimm explained, “Pépin, Swanson, and colleagues inserted the cat version of the AMH gene into a harmless virus widely used in gene therapy to ferry replacement genes into cells. The team then injected the virus into the thigh muscle of six young female domestic cats living in a colony at the Cincinnati Zoo.
How long does it last?
“The strategy worked,” Grimm summarized. “Other than having low levels of progesterone—a hormone produced after ovulation—the cats’ sex hormones remained normal. But the treated cats did not ovulate. And when they were placed in a room with a male for several hours a day over a four-month period—an experiment repeated both eight months and 20 months after the gene therapy—none became pregnant.
“One open question,” Grimm acknowledged, “is how long the extra AMH will stick around. The introduced gene doesn’t become part of the cat’s muscle cell DNA, so it’s possible that it will disappear over time as muscle cells regenerate. Pépin notes that AMH levels did decrease over the course of the study, but that they remained elevated in all of the treated cats, including one followed for five years.”
Will AMH work in dogs?
Added Grimm, “The Michelson foundation will be meeting with the U.S. Food and Drug Administration next month to map out larger safety and efficacy studies.
“Swanson says it will be at least five years,” Grimm cautioned, “before a commercial product is available. To be a viable solution for developing countries, a dose would have to be cheap.
“For the product to qualify for the $25 million Michelson prize,” Grimm finished, “it would need to work in dogs as well. It would also need to work in males, which seems beyond the reach of the current approach.”
“This research is a huge leap”
Proclaimed Joyce Briggs, soon to retire after 18 years heading the 23-year-old Alliance for Contraception in Cats & Dogs, “This research is a huge leap—we’re really excited about it.”
(See Waiting for Godot & a good, cheap non-surgical alternative to s/n surgery.)
Briggs mentioned that the Cincinnati Zoo veterinary research team “also included lead author Lindsey Vansandt, with whom ACC&D previously worked to study the GonaCon vaccine as a contraceptive for cats,” but did not mention that GonaCon––a product already approved for use in horses and many other species––may be significantly closer to introduction for widespread, low-cost use in both dogs and cats.
AMH vs. GonaCon
Ruth Steinberger, executive director and founder of Spay FIRST!, the Oklahoma City-based nonprofit that has taken the lead in developing GonaCon for dog and cat use, told ANIMALS 24-7 that, “Any news regarding the actual successful completion of research on a product that will increase the number of at risk animals who are sterilized is good news.
“But therein lies the caveat,” Steinberger warned. “Factors affecting animals who are not altered in the U.S., namely poverty and a lack of access to spay/neuter services, or a combination of both, means that simply replacing spay/neuter with an injectable product at the cost equal to a spay in a full’service clinic, will not likely reduce the number of unwanted litters who suffer homelessness.
“Our research on a contraceptive vaccine for cats is very promising at this point,” Steinberger said, “but to us a product is only promising once we know it truly works and that it will hit the ground at a fraction of the cost of a feline spay.
“If it’s about profit, or if it’s an early call to investors,” Steinberger finished, “Spay FIRST! has a different mission.”
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