Bioscience

Flagstaff firm inks deal with Australia for rodent-control test

June 18, 2008

By Flinn Foundation

For a biotech company with only a handful of employees tucked among the pines of Flagstaff, SenesTech Inc. has some ambitious goals. Here’s one: revolutionize how researchers study menopause. Here’s another: completely overhaul one of the most common procedures in veterinary medicine. And here’s one more: Overcome one of the great scourges of the world’s food supply, boosting the production of rice enough to feed half a billion people.

SenesTech took a big step toward realizing that third goal Tuesday, announcing at the annual Biotechnology Industry Organization (BIO) convention in San Diego that it had nailed down an agreement with the government of Australia to test ContraPest, SenesTech’s rodent-control product, at a small, experimental farm in the Indonesian province of West Java.

Rice is the primary food source for nearly half the world’s population, and nowhere is it more essential than in Southeast Asia, the most densely populated region of the world. But a huge portion of the rice that farmers plant never reaches hungry people, thanks to the damage that rice-field rats inflict on the staple crop. A pair of rats and their offspring can produce over 600 individuals in just three months, and they are capable of rapidly destroying both farmers’ livelihoods and the food supply. Losing 20-30 percent of crops to the rodents is typical, and forsaking an entire crop to the pests is common in some areas.

“With the food shortages that are starting to erupt, this is huge,” said Cheryl Dyer, SenesTech’s chief scientific officer and a physiology professor at Northern Arizona University, in the Arizona Daily Sun.

Loretta Mayer, the NAU research professor who founded SenesTech in 2002, explained, “Research shows that just a 10-percent reduction in the rice-rat population could feed over 380 million people. The numbers are simply staggering.”

SenesTech has developed what might be the most-promising challenge yet to the rats’ voracity and fecundity: a bait-distributed means to chemically sterilize them that won’t harm non-target animals or humans and doesn’t foul the environment. If ContraPest works as well in the field as it has worked in the lab, Dr. Mayer anticipates that the product could rapidly replace the problematic rat poisons that farmers around the world currently use. And cornering the market on agricultural rodent-control would mean big bucks–SenesTech estimates a potential for $1 billion in revenue from ContraPest within three years of commercial introduction.

Until recently, the active ingredient in ContraPest was known in the scientific community mainly as a menace. The industrial chemical 4-vinylcyclohexene diepoxide, or VCD, is widely used in manufacturing products such as tires, polyesters, and epoxy resins. Women working in industrial settings who have received high-dosage exposure to VCD have suffered serious reproductive damage. Dr. Mayer was in fact studying VCD’s harmful effects as a post-doctoral researcher in Patricia Hoyer’s physiology laboratory at the University of Arizona when she struck upon VCD’s potential usefulness.

Dr. Mayer was working on one of Dr. Hoyer’s long-term studies of VCD’s effects on mice and rats, investigating the dosage levels that would deplete the female rodents’ ovarian follicles enough to induce sterility. Dr. Mayer and Dr. Hoyer found that VCD-induced sterility essentially mimicked menopause, and that led Dr. Mayer to believe that VCD-sterilized rodents could be an important scientific resource.

One of the persistent challenges in conducting effective research on menopause and the conditions that it impacts has been that preclinical animal models for such research have been imperfect: A mouse that has been surgically sterilized shares some physiological characteristics with humans undergoing menopause, but lacks others, particularly in regard to peri- and post-menopausal hormone production, making difficult research on menopause’s relationship to conditions such as osteoporosis, heart disease, and diabetes.

Dr. Dyer, confirmed with Dr. Mayer that VCD-sterilized mice provided much better models for menopause than surgically sterilized mice, since VCD allowed for relevant hormone production to continue and didn’t involve an invasive, relatively time-intensive procedure. Dr. Mayer and Dr. Hoyer began to pursue patent rights for the VCD-sterilized mouse model, recognizing the potential for great demand among researchers, and SenesTech–the company’s name comes from the word “senescence,” which refers to reaching old age–was soon launched.

Applications for VCD sterilization beyond the research-lab setting soon became evident to SenesTech’s small team of entrepreneurs. What about for domestic-animal sterilizing? Almost all cats and dogs that are sterilized undergo surgical procedures that usually cost about $75. A VCD-based chemical spay would accomplish the same task at a lower cost–there’s hardly likely to be a shortage of VCD, considering its prevalence in industrial settings–without the risk of infection from surgery.

One of SenesTech’s first tests of what it calls ChemSpay occurred on the Navajo Nation, where thousands of stray dogs–often disease-carrying and underfed–have plagued livestock owners for decades. Mayer’s team treated 170 dogs with VCD; all are sterile, and none have died. With funding support from the U.S. Humane Society, SenesTech is continuing research toward a single-injection treatment that veterinarians and public-health officials could use to control overpopulation of both domesticated and feral dogs and cats.

VCD’s potential to help manage animal overpopulation brought SenesTech to the attention of the Australian government’s Invasive Animals Cooperative Research Centre (IACRC), an agency charged with addressing Australia’s numerous animal-overpopulation challenges. Rabbits are the most widely acknowledged pest animal, causing an estimated $200 million damage annually. Feral pigs, cats, and dogs are also rampant, as are the highly poisonous cane toads and foxes, which only arrived in Australia in 1871 but have spread over the entire continent and are responsible for the decline of many native species and the taking of up to 30 percent of lambs in some ranching areas. In some parts of Australia even kangaroos have reached untenable numbers.

Most options for controlling animal overpopulation have failed to achieve satisfactory results. Introducing new predators brings the risk of further upsetting natural balances. Poisons are typically difficult to target specifically and often have dangerous consequences for the environment. What the IACRC has described as the “holy grail” for pest control would be to design a virally transmitted immuno-contraceptive that would work its way through a population, rendering the pests unable to reproduce. The agency conducted extensive research toward such a sterilization virus for rats and mice, which cause significant losses in Australia’s sugarcane and rice crops, but could not successfully induce widespread transmission.

“The government of Australia came to us two years ago and said you are developing a product that we believe has a more wide-reaching impact,” Dr. Mayer said in the Daily Sun.

SenesTech’s first project for the IACRC was a VCD-based chemical spay for kangaroos, which was successfully tested in wallabies. Next up is the rice-rat experiment in West Java. A similar project is on tap for the Philippines.

Where ContraPest most obviously differs from the typical poisons that are used to control rats and other pests is that it does not kill its target–it only prevents reproduction. One of Dr. Mayer’s collaborators, Timothy Vail, an NAU biochemist and SenesTech’s vice president for manufacturing and regulation, has designed the bait containing the chemical so that it will not attract a non-target animal. And because VCD breaks down into inert components when the rat metabolizes it, predators will not be affected, and it does not collect in the environment.

“I am dedicated to addressing starvation with this technology and changing the livelihoods of the rural poor,” said Everett Hale, SenesTech’s CEO, whom Mayer recruited from San Diego to the lead the company last year to build its international efforts. “I never knew the extent to which governments had to use poison to prevent famine. A percentage of poison in any food supply is not acceptable. We are losing lives and the environment. Through our technology, we can now change the world and help feed its people.”

For a chemical that has had a bad reputation for its potential to injure humans, VCD as SenesTech is using it does indeed appear remarkably unproblematic. And Dr. Mayer said that means the company has a major upside. SenesTech has raised $2 million in funding and is closing in on another $9 million in support, and the research-supply company Jackson Laboratory has begun marketing Mouseopause, the VCD-sterilized mouse model. SenesTech is one of the anchor tenants for the new Northern Arizona Center for Emerging Technologies (NACET), Flagstaff’s high-tech business incubator, and the company is hiring a half dozen new scientists, though some of those will be working in Australia and Indonesia on the ContraPest project with IACRC.

Meanwhile, further characterization of the mouse model is continuing at Arizona State University, and UA can look forward to a revenue stream from the licensing of Mouseopause. Gov. Janet Napolitano said that she was impressed by the statewide collaboration and noted the importance of strengthening the research-performing institutions that can launch the next SenesTech.

“These advances–which potentially have a significant impact on the planet–are possible when we create the infrastructure for and foster science-based projects and discoveries,” Napolitano said.


For more information:

Flagstaff startup to test rodent-control technology on rice-field rats for Australian government,” Arizona Republic, 06/18/2008

SenesTech lands contract with Australian govt,” Arizona Daily Sun, 06/17/2008

Rats facing NAU spay chemical,” Arizona Daily Sun, 04/23/2008

The Big Fix: Of Mice and Women,” Northern Arizona University Horizons, 2008

SenesTech news release, 06/19/2008