Spay-neuter surgeries can be time-consuming for veterinarians and expensive for many dog and cat owners. But what if the same outcome — permanent sterility — could be achieved with a low-cost injection? Such a discovery would be a game changer for the profession. Practitioners then could devote more time to wellness checks, sick care and managing their clinics, while their clients would save potentially hundreds of dollars.
Retired orthopedic spinal surgeon Gary Michelson, MD, believes that a permanent, nonsurgical sterilant is achievable in veterinary medicine, and in 2008, he promised a $25 million prize to the person or institution that successfully develops one. However, more than a decade later, no one has claimed the Michelson Prize. For many of the academic and biopharmaceutical researchers, the eight-figure reward isn’t the incentive. Instead, they’re chasing the science.
Feral Numbers Remain High
A nonsurgical sterilant could reduce feral populations of dogs and cats significantly. Though the Humane Society of the United States reports that 80% to 90% of owned dogs and cats are sterilized, the American Society for the Prevention of Cruelty to Animals estimates that nearly 6.3 million strays find their way into community shelters each year. The stop can be a death sentence for many animals. The ASPCA estimates that 920,000 adoptable dogs and cat are euthanized annually in the United States alone.
“Fewer lives lost is always awesome to me,” said Erik Olstad, DVM, an assistant clinical professor of community practice at the University of California, Davis, School of Veterinary Medicine. “If we can easily and effectively reduce euthanasia at community shelters through a nonsurgical sterilant, I foresee far fewer animals in cages.”
The criteria for the Michelson Prize are precise. The winning entry must be, at a minimum:
- A single-dose, nonsurgical sterilant administered in one patient encounter and without general anesthesia.
- Safe and effective in male and female cats and dogs, both pre- and post-pubertal.
- Effective at ablating sex steroids or their effects.
- Suitable for administration in a field setting.
- Viable for regulatory approval.
- Reasonable from a manufacturing and cost aspect.
- No more dangerous than surgical gonadectomy.
- Able to induce sterility for at least 10 years.
While the criteria encourage research into male and female animal reproduction, the greater focus is on females because of their ability to produce a lot of offspring over a lifetime.
“Focusing on females rather than males really has much more of an advantage as far as a long-term population control,” said Thomas Conlon, Ph.D., the chief science officer at the Los Angeles-based Michelson Found Animals Foundation.
Valuable Insight
The $25 million prize isn’t all that Dr. Michelson and his foundation put on the line. An additional $50 million in grants is available to investigators.
“They’re here to make a difference and achieve their goals,” Dr. Conlon said of the grant recipients. “For many, the incentive is not the prize by any means.”
Since the program’s inception, more than $19 million has been awarded to support 41 research projects worldwide. Though none of them has perfected a nonsurgical sterilant, the efforts shed greater light on the reproductive systems of dogs and cats and clarified which approaches to sterilization hold the greatest promise, said foundation CEO Brett Yates.
“We are seeing vectors, such as nanoparticles and viral vectors, as very promising technologies,” Dr. Conlon said. “Clinical trials that are treating human diseases with viral vectors and nanoparticles have shown longevity for years. And the animal models that went into the experiments prior to human studies have been ongoing for up to 14 years in some cases, which is well past the reproductive span of a dog or cat. Those two technologies could incorporate genetic sequences that could alter either of those signaling pathways or how certain cell types function.”
The use of viral vectors to alter or correct specific genes and protein functioning is especially intriguing and the subject of a growing body of human medical research. Gene transfer using carriers known as adeno-associated viruses (AAVs) targets specific cells to correct disease-causing improper protein function. Inside the target cell, the carrier provides copies of a gene that corrects the defective or missing protein function. Theoretically, a similar type of transfer could alter protein functions and permanently render dogs and cats incapable of reproducing.
What hasn’t worked, Dr. Conlon said, is the chemical ablation of certain cell types, such as the GnRH neurons in the brain or the GnRH receptor cells within the pituitary gland, though he pointed to an ongoing project using gene toxin in these cell types.
“When you target a certain cell type to cause sterility, in most cases you have to kill off the entire population of cells,” Dr. Conlon said. “That’s the difficult part. You can’t just get 98% or 99%. You have to get 100% of the cells because the signaling pathways involved find a way to correct themselves over a period of time.”
Input From Human Medicine
The universities and individuals receiving Michelson research grants represent a variety of clinical specialties but few of them in the veterinary space. Among the recipients are:
- Patricia K. Donahoe, MD, the director of Pediatric Surgical Research Laboratories and chief emerita of Pediatric Surgical Services at Massachusetts General Hospital and the Marshall K. Bartlett Professor of Surgery at Harvard Medical School.
- David Pepin, Ph.D., an assistant molecular biologist at Massachusetts General Hospital and an assistant professor of surgery at Harvard Medical School.
In 2015, the two researchers received just over $1 million to support a multiyear investigation of a single treatment using AAV9 Mullerian inhibiting substance (MIS) as an ideal permanent contraceptive.
Physicians who specialize in human fertility, Drs. Donahoe and Pepin are working with a protein to help women stall the development of primordial follicles during cancer treatments, Dr. Conlon said.
“Their pool of eggs is held in check so that they don’t lose them during the years of treatment they may undergo,” he said. “It was just chance that they heard about our program and said, ‘Hey, we’ve got this technology that’s working this way in humans. But we can also use it for dogs and cats with similar effects.’ They weren’t focused on veterinary diseases or treatments, but they had a technology that they could translate into a new use.”
The Michelson program has enabled relationships with research groups all over the world, Yates said.
“There are no restrictions on who can apply for a grant,” he said. “If someone in another country wants to apply, that’s fine. We could not care less where they come from as long as the research is solid and it achieves the goal. That’s what we’re after.”
Many Challenges Await
Numerous challenges complicate the search for a nonsurgical sterilant in veterinary medicine. One of the biggest is maintaining sterilization over an animal’s reproductive period.
“We’re looking for permanent sterility because when we go out into feral populations and perform trap and release, we’re not going to see the same cat or dog twice,” Dr. Conlon said. “We have to make sure that these treatments will last for many years.”
Another riddle is determining which genes or proteins, if altered, could have a permanent sterilizing effect on cats and dogs.
“One would imagine that if, say, an estrogen signal is required, altering the estrogen gene would have an effect,” Dr. Conlon said. “The body finds ways to continue the reproductive cycle, so we need to find the specific genes and proteins that will lead to a permanent effect without the body finding a way around it.”
A third hurdle is ensuring that the sterilant is near 100% effective.
“Very few drugs are,” Dr. Conlon said. “And while we may not need to prove that for regulatory approval, we, of course, want a rate of 95% or higher.”
An effective nonsurgical sterilant would greatly impact animal welfare, veterinary medicine and pet ownership. Populations of unwanted dogs and cats would gradually decrease, as would the census at most animal shelters. Fewer feral animals would mean fewer cases of bites and rabies, an especially dire threat in nations such as India, where rabies claims 10,000 lives a year, Dr. Conlon said.
For veterinarians, a nonsurgical sterilant could be transformative. The cost of sterilization would be less compared with surgery, so a clinic would generate less revenue from the pet owner. However, the process would take less time — just minutes instead of up to an hour or more.
“Sterilization is not a five-minute procedure; it’s a significant investment in a veterinarian’s time,” Yates said. “If we can give patients a shot instead, it would save hours of time and allow veterinarians to see more clients. And that’s exactly what we need in this space. So many places right now are service deserts, and we would love to help those communities get the veterinary services they need.”
In addition, a nonsurgical sterilant could have broad appeal among pet owners, who might feel more comfortable with a one-time shot that poses fewer health risks to their dogs and cats than surgery.
Surgery Is Likely to Stay
A nonsurgical sterilant would hold other significant advantages, said UC Davis’ Dr. Olstad, who has performed hundreds of spay-neuters over the years and is not involved in the Michelson Prize competition.
“Think of the hurdles that our clients have to jump through to get a surgical appointment,” he said. “In addition, the practice must have the staff, the infrastructure and the funding to perform spay-neuters. Imagine a system where you could simply inject a dog or cat fairly painlessly and eliminate the overpopulation issue.”
Dr. Olstad predicted that even with the development of a nonsurgical sterilant, surgical sterilizations will never go away. One reason, he said, is the behaviors commonly associated with reproductive hormones.
“When we perform a spay or neuter, it has a multifold effect on the animal,” he said. “It’s not just to prevent pregnancy but also to prevent the behaviors associated with the hormonal signaling of that process. Intact male dogs, for example, will roam if they catch the scent of a dog in heat. They also engage in marking behaviors. That’s one of the challenges with chemical sterilization: [Will it manage] the behaviors associated with those hormonal aspects?”
Dr. Olstad also noted that surgical sterilization can reduce the risk of certain diseases.
“Female dogs, if left intact, have a higher incidence of mammary cancer,” he said. “That’s a driver for why people want to have their pets spayed.
“I don’t see surgery going away soon, though I do see huge advantages to a nonsurgical sterilant in terms of herd health.”
Research into animal medicine often benefits humans. Could the search for a nonsurgical sterilant for companion animals have human applications? Yates and Dr. Conlon are reluctant to ponder the question.
“There’s no taking it back, especially when you’re using viral or nanoparticle vectors that are introducing new DNA,” Dr. Conlon said.
A human product isn’t part of the discussion at the Michelson Found Animals Foundation.
“At the moment, we have no intention of going beyond dogs and cats,” Yates said. “That’s 100% our focus right now.”
LEARN MORE
Investigators who discover a permanent, nonsurgical sterilant for cats and dogs can claim the $25 million Michelson Prize with or without a research grant from the Michelson Found Animals Foundation. Details are at michelsonprizeandgrants.org.
THE MAN BEHIND THE MICHELSON PRIZE
Gary Michelson, MD, is a philanthropist, inventor and innovator who sees a problem and seeks solutions. The 73-year-old is an animal lover who found comfort in his family’s pets during a tumultuous childhood.
In medical school, according to his online biography, Dr. Michelson refused to participate in a lab that required him to remove the organs from a healthy dog without pain medication. He was threatened with expulsion, but the school balked after he developed a surgical procedure that saved a young human patient from amputation by transplanting a rib bone into her leg.
In 2005, moved by the large number of dogs and cats left stranded and homeless by Hurricane Katrina, Dr. Michelson established the Michelson Found Animals Foundation to provide inexpensive microchips to Los Angeles-area pet shelters. Next came a free registry where the owners of microchipped pets could register their contact information.
He followed those initiatives with grants to bring subsidized spay-neuter veterinary services to low-income families and community cat caregivers.
Another foundation initiative, now closed, was a pet retail and adoption boutique called Adopt and Shop, which rescued at-risk dogs and cats from shelters, gave them a spay or neuter, vaccines and microchips, and put them up for adoption.
In 2008, Dr. Michelson hired Aimee Gilbreath, MBA, as the foundation’s executive director, and together they turned their attention to the pressing issue of dog and cat overpopulation. The result was the Michelson Prize and Grants in Reproductive Biology, an effort to create a nonsurgical sterilant for dogs and cats.
“Dr. Michelson realized that one of the best ways to reduce the number of shelter animals being euthanized was spay-neuter,” foundation CEO Brett Yates said. “However, the number of procedures done each year is far less than the number of animals in need of spay or neuter. That was the genesis of the Michelson Prize and grants.”