$75 million offered to further non-surgical sterilization

From ANIMAL PEOPLE, October 2008:
(Actual publication date 11-5-08.)
CHICAGO For $75 million, can someone invent a vaccine against canine and feline pregnancy? Or a chemosterilant that will be widely accepted by the humane and veterinary communities?
If an effective immunocontraceptive or chemosterilant for dogs and cats existed, would it be used where most needed?
Might the money be more productively used in extending high volume, low cost, best practice dog and cat sterilization surgery to all parts of the world and in keeping existing low-cost sterilization programs operating, at a time of plummeting donations?
The headline item at the mid-October 2008 Spay USA national conference was the $75 million incentive package offered by Found Animal Foundation founder Gary K. Michelson, M.D., to encourage the development of nonsurgical dog and cat contraception.

Representatives of the Found Animal Foundation at an October 16 pre-Spay USA conference reception announced that Michelson is offering a prize of $25 million to the inventor of a successful single-injection sterilization method for dogs and cats. The claimant may be either an individual or an organization. Of more immediate help to researchers who have promising ideas but lack financial backing, Michelson is also offering up to $50 million in grant funding for nonsurgical sterilization research.
Researchers have been on the verge of discovering pet contraceptives and non-surgical steriliants for years, said Found Animals director of communications Michael Gilman, but a lack of funding has kept these ideas stalled in the early stages of research. New scientific breakthroughs in other health care fields may offer promise when applied to this goal.
Michelson, 59, has put comparable money into promoting medical breakthroughs on behalf of human beings. A practicing orthopedic surgeon for more than 25 years, Michelson eventually turned to surgical invention, chiefly associated with treating back pain. According to the Found Animal Foundation web site, Michelson has over 900 issued or pending patents worldwide related to instruments, operative procedures, and medical devices. In 2005 Michelson assigned ownership of much of his spine-related intellectual property to Medtronic for a price in excess of $1 billion, catapulting him onto the Forbes 400 where he has since remained.
Medtronic announced in April 2005 that it would pay Michelson $550 million to settle five years of litigation between Michelson and Medtronic, as directed in 2004 by a federal grand jury, and would pay Michelson $800 million for the rights to over 100 issued U.S. patents, over 110 pending U.S. applications and approximately 500 foreign counterparts.
The Medtronic settlement was actually Michelson s second big payday through litigation. In 1995, recounts his Forbes 400 profile, he sued a subsidiary of U.S. Surgical (now Covidien) for infringing his patents on a fusion technology. The case won a large settlement that he is not allowed to talk about, although he confirms it was nine figures. His licensing revenue grew to $40 million annually. In 2001, when his dispute with Medtronic began, Michelson had a net worth, he says, of $300 million.
The Michelson initative is without doubt the biggest thing to happen in our field, said Alliance for Contraception in Cats and Dogs executive director Joyce Briggs. ACC&D has long seen the need for an infusion of funding to attract researchers. Dr. Michelson has risen to that challenge, and we are delighted to be working closely with the Found Animal Foundation on this initiative.
We re completely agnostic regarding the approach, said Found Animals Foundation executive director Aimee Gilbreath, who was hired in March 2008 from a background in business consulting and animal shelter volunteer work. We ll consider anything. We really believe if cutting-edge technologies are applied we can solve this.
But the idea is actually to replace cutting-edge technologies, which involve invasive surgery and are as old in concept as castrating male animals or human slaves and sewing shut the vaginas of females, practiced in some parts of the world since early Biblical times.
The basic methods of sterilizing dogs and cats remain castration of males and ovariohysterectomy of females, 75 years afer the American Veterinary Medical Association first formally endorsed the procedures. The surgical techniques have been expedited and refined, enabling top sterilization surgeons to operate on more than twice as many animals per hour with hundreds of times less risk to the animals than when sterilization surgery became commonplace, in the 1970s.
Yet despire the improvements, sterilizing animals remains markedly more costly and complicated than vaccinating them. The prevailing belief in the animal advocacy, veterinary, and animal care and control communities has for decades been that sterilizing animals must become almost as easy and inexpensive as vaccination, in order for the procedures to become universal enough to prevent dog and cat overpopulation.
The need for a cheap, quick, safe and effective non-surgical sterilization method is believed to be especially acute in the developing world, where the veterinary shortage afflicting the U.S. since the early 1990s is much more intense, and pressure to reduce the numbers of street dogs and feral cats is omnipresent, especially in regions where rabies remains endemic.

Hormones

The oldest approach to non-surgical dog and cat population control involves regulating hormone levels, as in human birth control, and has been researched without a breakthrough to finding a safe, practical, single-shot method for approximately 50 years.
Among the first researchers in the field was Wolfgang Jochle, originally from Germany, now a senior advisor to ACC&D. Jochle began his studies when street dogs were re-emerging as a problem in western Europe, then recovering from World War II. While colleagues developed birth control pills for humans, Jochle anticipated a future when dogs and cats would no longer be killed to control their numbers. Several times he thought he was close to finding the magic elixir that would make this possible. Eventually much of western Europe, including Germany, reduced dog and cat overpopulation to the point of becoming almost no-kill nations. But Jochle by then had emigrated to the U.S. His discoveries, while achieving limited use with pets in Europe, never proved practical for use with street dogs or feral cats, except in some closely supervised colonies, and never gained popularity in the U.S.
Several hormone-based contraceptive products have been marketed in the U.S. for use by prescription, primarily in show animals. One of them, Ovaban, reached the U.S. market in 1975, and is still sold, but has not become popular because of the severity of the side effects frequently associated with it.
The Connecticut sterilization service provider Tait s Every Animal Matters, headed by John Caltibiano, DVM, in mid-2008 began marketing a similar product for feral cats, called FeralStat. The two TEAM mobile units have performed conventional sterilization surgery on more than 117,000 cats since 1997, but noting that it is difficult for those who are managing feral cat colonies or feeding homeless cats to trap each cat for sterilization before they reproduce, Caltibiano began prescribing this oral contraceptive to feral cat caretakers in Connecticut, Oregon, Texas, California, Florida, and Canada seven years ago, according to the TEAM advertisements.
By all accounts, the ads claim, FeralStat is safe, effective, convenient it works.  The active ingredient, a synthetic progestin, was patented and approved by the U.S. Food & Drug Administration in the early 1950s. It is used extensively in human medicine, and has been prescribed by veterinarians for over 30 years for cats with skin, urinary tract, and behavioral disorders. It also has FDA approval for off-label use as a feline oral contraceptive to postpone estrus in cats.
According to the ads, FeralStat can be mixed with food once per week and fed to all of the cats in a feral colony, without harmful effects on male cats, pregnant females, and kittens who share the meals.
The recommended daily dosage for treating cancer in humans, the FeralStat ads say, will prevent 20,000 cats from coming into heat.
But FeralStat is unlikely to share in the Michelson prize, because it does not actually sterilize the cats who ingest it, and is not a single-shot method.
The Alliance for Contraception in Cats & Dogs is also skeptical of Caltibiano s safety cliams. The active ingredient in FeralStat is megestrol acetate, points out Joyce Briggs. This is the same active ingredient which is in Ovaban.  In numerous studies over three decades, this drug, like other progestins, has been found to pose serious health risks in cats, including diabetes mellitus, mammary swelling and tumors, uterine disease, pyometra, and skin disorders. Megestrol acetate is not now, nor has it ever been, approved by the FDA for use in cats, Briggs asserts, though it is approved for contraceptive use in dogs.
There do not appear to be any controlled studies of FeralStat that show that it is either safe or fully effective at the dose used, Briggs continued in a July 24, 2008 media statement. We have no information that FeralStat has gone through any formal review process. Because FeralStat is given as a food additive for outdoor cat colonies, there is no way to control the amount of the drug each cat ingests, or to prevent wildlife or owned pets from consuming the drug. While we continue our thorough review, Briggs said, ACC&D cannot recommend the use of FeralStat.

Chemosterilants

Chemosterilants use chemical substances to reduce fecundity. No effective chemosterilant for female animals has been developed. Several chemosterilants for male dogs and cats have been experimentally introduced. Most notably, a chemosterilant called Talsur failed in field trials in India in 1991. A similar product called Neutersol has long been used successfully in Mexico, a comparable product is used in Thailand, and another is reportedly close to introduction in Brazil, but Neutersol was rejected in India after a field trial initially appeared to be producing some of the same problems as Talsur. Limited use by nonprofit organizations in eastern Europe was thwarted by veterinary opposition.
Efforts to market Neuterol in the U.S. were not commercially successful.
Neutersol was originally introduced in the U.S. in 2003, and was available until the patent holder and the original distributor severed ties in early 2005, ACC&D executive director Joyce Briggs recounted in introducing Michelson s incentive package. A reintroduction plan was introduced in 2005, Briggs added. ACC&D worked in partnership with the new marketing company to develop plans for a shelter advisory board and programs to aid the reintroduction.
However, Briggs said, ACC&D recently learned that the reintroduction of Neutersol into the U.S. has been cancelled, with the termination of a contract between the company that was going to distribute the product and the patent holder. ACC&D will shift our focus to the use of this product internationally, Briggs said, where the largest potential for saving lives exists, and where, in developing nations, veterinary surgery is a scarce commodity.
Briggs mentioned that the product called Neutersol in the U.S. is now sold in Mexico as Esterilsol.

Immunocontraception

Immunocontraception attempts to trick a female animal s body into rejecting the male animal s sperm and destroying it just as the immune system destroys viruses and bacteria. Immunocontraceptives have been developed for many mammal species, and are now widely used to control reproduction of hooved animals. The first immunocontraceptive for horses, for example, was tested by ZooMontana director Jay Kirkpatrick in 1990, and has recently been used with some success among wild horses.
Leading researchers in July 2000 told a Spay USA conference in Waltham, Massachusetts that they expected to have one or more immunocontraceptives for dogs and cats ready for general use within just a few years, based on porcine zona pellucida, the same byproduct of pork production that worked in horses. By 2004, however, when the first ACC&D conference was held in Breckenridge, Colorado, the pZP researchers optimism had waned. Cat and dog reproductive systems were not tricked by pZP.
A second immunocontraceptive approach, using anti-gonadotropin-releasing hormones, has been researched here and there for at least 18 years, but several major pharmaceutical manufacturers have abandoned work on anti-GnRH methods.
That leaves several other possibilities. One idea, still completely untested, would be to use gene therapy to modify the fecundity of animals. The idea would be to introduce altered genes into the animals, which would take over control of their reproductive systems. Similar techniques are now experimentally used in fighting many severe human illnesses with a genetic component.
The gene therapy approach might be used in dogs and cats to restrict litter sizes or reduce the frequency of ovulation cycles, so as to reduce fecundity to the level needed to replace pets, or to maintain the population of street dogs and feral cats needed in a developing world situation to control rodents and prevent monkey invasions.
Whether this could be accomplished with a single-shot injectible product, or could be done at all, is as yet not known because no one is known to have researched it. But cats and dogs are known to have relatively recently evolved greater fecundity in response to the pressures of living in proximity to humans, where more food is available but there is also risk of persecution much more intense than the risk of predation in the wild.
The fecundity of feral and domestic cats today is roughly four times greater than that of their closest wild relative, the African desert cat, and is about double the fecundity of pregnant cats who were mummified thousands of years ago by the ancient Egyptians. The fecundity of dogs is also believed to have markedly increased since domestication.
This means, in theory, that genetic selection for smaller and less frequent litters could be done by switching on recessive genes that were dominant among cat and dog ancestors just a blink ago in evolutionary time.