The search goes on for a single-dose non-surgical way to sterilize dogs & cats

[Guest guest]

From ANIMAL PEOPLE, April 2010:

 

 

The search goes on for a single-dose non-surgical way to sterilize dogs & cats

 

DALLAS--More than 50 contenders for the

$25 million Michelson Prize for the invention of

a successful non-surgical method of sterilizing

dogs and cats registered for an intensive

briefing about how to win the money at the April

8-10, 2010 Alliance for Contra-ception of Dogs &

Cats conference in Dallas.

The first step, for most, will be

winning some of the $50 million research and

development funding offered by Found Animals

Foundation founder Gary K. Michelson, M.D., to

help the contenders approach the jackpot.

To do that, the contenders must present

ideas that clear rigorous screening for

feasibility, practicality, and safety by the

Found Animals Foundation scientific advisors.

As holder of more than 900 patents issued

or pending worldwide for medical instruments,

procedures, and other medical devices, mostly

used to treat back pain, Michelson has a clear

idea what he wants to see: a single-dose

treatment that will quickly, inexpensively

sterilize dogs and cats for life, and can win

regulatory approval for widespread use.

If the money was equally distributed

among the applicants, Found Animals Foundation

executive director Aimee Gilbreath told ANIMAL

PEOPLE, it would soon be gone, not necessarily

with anything to show for it. Millions of

dollars have already been invested during the

past 50-plus years to develop animal

contraceptives, but no product has come close to

meeting the Michelson criteria, simple as they

are.

The Michelson Prize may go to the

inventors of an immunocontraceptive, a

chemosterilant, or some other method as yet

unknown, but it is not likely to go to anyone

soon, cautions Gilbreath.

" To our knowledge, there isn't any

product at nearly a stage of development that is

worth getting excited about, " Gilbreath said.

" Our presentations will focus on work in the

research pipeline and discussion of what has been

tried in the past, why it hasn't worked, and

promising new avenues for exploration. "

 

Why not pet food?

 

Animal advocates may be disappointed that

the Michelson Prize criteria do not include the

further stipulation that the winning method be

potentially accessable for unsupervised use by

individual rescuers. For more than 30 years dog

and cat rescuers have yearned for a product that

could live up to the promises that accompanied

the introductions of several different " birth

control pet foods " between 1963 and 1978.

At that time there was still relatively

little concern about the longterm effects of

birth control drugs on human health, almost no

consideration of the use of pharmaceuticals as

biological weapons, and was not yet any

regulatory attention to the effects of drug

residues in in the environment.

The " birth control pet foods " included

progestin-based hormonal contraceptives.

Repeated dosing was required, and sustained use

led often to pyometra. Two products from this

generation of animal contraceptives are still

available--Ovaban, for dogs, and Feral-Stat,

for cats. But neither is actually a sterilant.

The " birth control pet food " introduced with the

greatest fanfare, Mibolerone, was a progestin

product closely related to the post-coital human

contraceptive RU-486. It had the same issues as

the rest, however, and the active ingredient

was banned in the U.S. as an abortificant from

1988 to 2000.

" I'm not sure that we'll ever get to

something that could be distributed by lay

people, but I bet we could get to something that

a vet tech can do--perhaps under indirect

veterinary supervision, " Gilbreath told ANIMAL

PEOPLE. " Our goal is for it to be at least as

easy as vaccinations are now, " Gilbreath added,

anticipating that the Michelson Prize will

probably be won by an injectible product.

Procter & Gamble toxicologist Mark

Lafranconi, manager of the $300 million P & G

program to develop alternatives to animal

testing, surveyed the P & G regulatory experts on

behalf of ANIMAL PEOPLE as to whether a " birth

control pet food " could gain regulatory approval

today, even if it worked perfectly in laboratory

settings.

" I have polled across our organization

and the unanimous conclusion is this type of

initiative would never receive approval, "

Lafranconi reported, " no matter what the

jurisdiction, for the reasons you have already

identified. Inability to control access and

exposure is the major limiting factor. "

Agreed Linda Rhodes, vice president for

clinical development at AlcheraBio LLC, of

Metuchen, New Jersey, a division of Argenta

Inc., " I would say that there is no chance that

the government will approve a substance to be

given to feral animals using a bait, flavored

substance or food, by lay people, given what we

know about the science today. In order to not

impact people, especially children, or other

wildlife, such a substance would have to be

completely species-specific. For example, a

drug that could only be effective in cats and no

other birds or mammals. Given today's science,

there is no drug or substance that I can think of

that has that level of species specificity. "

The oral rabies vaccine Raboral has been

used successfully since 1969 in foxes, raccoons,

and coyotes, but only in pellets that can only

be dissolved by the stomach enzymes of the

specific target species.

" Oral rabies vaccine scattered as bait

for raccoons, fox, and other wildlife, has

been successful, " Rhodes acknowledged, " but

only because it is administered as part of

government programs, and because human or

multi-species ingestion has only beneficial

results, i.e. vaccination against rabies. "

Rhodes was previously director of

clinical development projects for production

animals at Merial Ltd., the maker of Raboral.

She now chairs the Alliance for Contraception in

Dogs & Cats board of directors.

Whether a new " birth control pet food "

could be marketed today " really will depend on

the country, " said Humane Society of the U.S.

chief of staff Andrew Rowan, an ACC & D board

member who has professionally followed

developments in toxicology and birth control for

more than 30 years.

" You can buy all sorts of medications

over the counter in many developing countries

without much in the way of regulatory oversight, "

Rowan pointed out, " so if one could develop a

chemosterilant that was not too toxic, it could

find its way to the market in some countries for

use by the general public. In the U.S., "

Rowan suggested, " it would depend how it was

classified. If it was viewed as an animal

health product, then the veterinary profession

would be loath to cede control over

distribution. If it was classed as a pesticide,

the situation would be different. You can look

at Ovocontrol as an example. It is available in

the U.S. for use by non-medical people because it

is classed as a pesticide. Of course,

something targeted rather narrowly at bird

reproduction is likely to be treated rather

differently from a chemical that interferes with

mammalian reproduction. "

Offered David M. Petrick, who is both a

veterinarian and a lawyer, and heads Delta

Consortium Regulatory Consulting Inc. in

Princeton, New Jersey, " If the issue is whether

a product will be offered for sale

over-the-counter, at which point all

professional judgment is lost, I don't think so,

but it will certainly depend very specifically on

the product itself, how it is administered, the

margin of safety, and safety to the

environment. But even if the product is a

prescription veterinary drug, the regulations

state they can only be used 'by or on the order

of a licensed veterinarian.' In this case, 'on

the order' could certainly mean a group of

volunteers designated and trained by a

veterinarian, who would be supplying the product

and who would be responsible in the Food & Drug

Administration's eyes. Likewise, if the

Environmental Protection Agency were involved,

EPA may require a certified pesticide applicator

to use the material, in which case it would not

be a vet, but a licensed pesticide professional. "

Petrick previously worked in regulatory

affairs and product development for both American

Cyanamid and Schering-Plough Animal Health. He

is also vice president of regulatory affairs for

Velcera Pharmaceuticals.

USDA Animal & Plant Health Inspection

Service regulatory specialist John Eisemann,

identified by Janet Raloff of Science News as

" the go-to guy for identifying what permissions,

waivers or requests are required before wildlife

managers can apply poisons or anti-fertility

drugs, " told the spring 2010 national meeting

of the American Chemical Society about " legal

tactics by which wildlife officials can thwart

invasive vertebrate species with off-the-shelf

chemicals, " Raloff wrote in the March 22, 2010

edition of Science News.

" He noted, for instance, " Raloff

continued, " how scientists have used a

contraceptive vaccine, " called Gonacon,

" designed to control white-tail deer populations,

on rodents. It offered a nonlethal approach to

reining in a population explosion of non-native

fox squirrels on a University of California

campus. In another instance, " Raloff said,

" wildlife managers employed a cholesterol

inhibiting drug to reduce sex hormone levels--and

the urge to reproduce--among monk parakeets. "

So some openings may remain for

introducing a " birth control pet food, " if such

a product is developed, even if it does not meet

the Michelson criteria.

 

SenesTech

 

Despite expert skepticism, a June 2008

report by Arizona Biosciences News rekindled hope

that a " birth control pet food " might be just

around the corner.

The report focused on the work of a

company called SenesTech to develop a rodent

birth control product called ContraPest.

" Until recently, " said Arizona

Biosciences News, " 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. "

Partnering with the Australian

government's Invasive Animals Cooperative

Research Centre, SenesTech has tested VCD as a

possible way to sterilize rats and wallabies.

SenesTech has also experimented with a VCD

product for dogs called ChemSpay.

Concluded Arizona Biosciences News, " One

of SenesTech's first tests of ChemSpay occurred

on the Navajo Nation. " SenesTech founder Loretta

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. "

Rowan was unable to identify any

involvement by the Humane Society of the U.S.,

but HSUS is a major funder of the Alliance for

Contraception in Cats & Dogs, and ACC & D did fund

one early study of ChemSpay.

Explained ACC & D president Joyce Briggs,

" ChemSpay, initially developed to model human

menopause in mice, was a novel approach to

non-surgical sterilization which piqued our

interest early on. ACC & D funded a small study in

2006 to evaluate whether the ChemSpay approach

may be effective in dogs. That study was not

able to demonstrate effectiveness. SenesTech's

subsequent work has focused on mice and rats,

though representatives of the company have said

that they plan to return to work on formulations

for cats and dogs in the future. ACC & D recognizes

that this approach is in very early stages in

terms of applications in cats and dogs. We have

asked SenesTech to keep us apprised of progress ,

and will share any relevant, non-proprietary

information that becomes available. "

SenesTech did not respond to repeated

inquiries from ANIMAL PEOPLE in 2009 and early

2010. According to the SenesTech web site,

" Consumption of ContraPest will cause female rat

sterility within one month of ingestion.

ContraPest is being formulated in a rat

attractant specific bait minimizing consumption

by non-target species. Our product is

environmentally neutral. It is rapidly

inactivated in dosed rats and the excreted

metabolite is inactive. ContraPest will not

bioaccumulate nor enter the food chain.

Therefore predators of the rats will not be

accidentally dosed. The rats who consume the

ContraPest bait have no physiologic changes other

than elimination of all eggs in the ovary,

resulting in permanent sterility. It is expected

to be marketed within two years to the 13

Southeast Asian countries that are responsible

for the vast majority of world rice production. "

Confirmed Australian Commonwealth

Scientific and Industrial Research Organisation

vertebrate pest stream leader Lyn Hinds, " I have

been undertaking trials on this chemical product

here in Australia and in Indonesia. However, "

she said, " due to the commercial-in-confidence

nature of the research, no specific publications

or details of the results are available at this

stage. "

VCD studies

But scientific journals have reported

about the contraceptive effects of VCD.

Headlined Toxicology and Applied

Pharmacology in August 1999, " A Single Dose of

the Ovotoxicant 4-Vinylcyclohexene Diepoxide Is

Protective in Rat Primary Ovarian Follicles. "

Though longterm exposure to VCD can produce

sterility, the five co-authors concluded that

" These data provide evidence for a 'protective'

response against the normal rate of atresia in

primary ovarian follicles following exposure. "

Since the Michelson Prize requires that

the winning substance be effective after a single

dose, this finding would appear to exclude

ChemSpay.

Summarized a 2001 report in Biology of

Reproduction, " Following 30 days of daily

dosing, the majority of small preantral

follicles in immature as well as in adult rats

are destroyed. Previous studies have shown that

15 daily doses of VCD (80 mg/kg, i.p.) destroy

about 50% of oocytes contained in small preantral

ovarian follicles in rats. "

In other words, a VCD product might have

to be administered every day for two weeks to a

month to be effective.

 

VCD is carcinogen

 

VCD can have other effects. The

International Agency for Research on Cancer found

in 1994 that " Skin application of VCD produced

benign and malignant skin tumours in all studies

in mice and in a study in rats. In one study in

mice, it also increased incidences of ovarian

and lung tumours in females. "

National Institute of Environmental

Health Sciences researcher James Huff confirmed

in Toxicological Sciences in 2001 that VCD

" induced both squamous cell and basal cell

neoplasms of the skin " of most male and female

rats and mice. " Both benign and malignant tumors

of the ovaries were caused by dermal exposure in

female mice, " Huff added, also noting a

possible association of VCD exposure with lung

cancer in mice.

The production of squamous cell tumors is

of particular concern in considering VCD

applications for use in dogs and cats. Explains

University of Illinois veterinarian Sandra Manfra

Marretta in Recognition and Treatment of Oral

Tumors, " Squamous cell carcinoma is the most

common oral tumor in the cat and is the second

most common oral tumor in the dogŠThe prognosis

in dogs with oral squamous cell carcinomas if

therapy is timely and correct is fair with

approximately 50% of treated dogs living one

year. The prognosis in cats with oral squamous

cell carcinoma is very poor because of the rapid

growth of this tumor in cats. "

Pharmaceutical developers often thread

their way through a maze of potential obstacles

to perfecting and marketing new products,

including the possibility that an ingredient may

cause cancer at particular dose levels. Thus the

published studies indicate not impossibility so

much as the potential degree of difficulty

involved in perfecting ChemSpay and winning

regulatory approval for it.

 

600 Million

 

But almost a year and a half after the

Arizona Biosciences News appeared, ANIMAL PEOPLE

heard from five different animal advocacy donors

and fundraisers, just a few weeks apart, that

ChemSpay or an unnamed similar product will, as

one put it, " Change the world! " One of them

specifically cited SenesTech as the developer.

Four of the five, including the one who

mentioned SenesTech, turned out to have

associations with a new nonprofit organization

called 600 Million Stray Dogs Need You, headed by

Alex Pacheco, who cofounded PETA in 1981 and in

1998, after leaving PETA, briefly headed the

New England Anti-Vivisection Society.

Wrote Pacheco in a December 13, 2009 web

posting, " We are talking with scientists about

teaming up to develop animal birth control

pellets that will allow us to end a vast amount

of suffering around the world. It's a long,

expensive and complex process that involves

everything from getting FDA and EPA approval to

negotiating with the governments of impoverished

nations, where we plan to distribute the birth

control pellets for free. "

The 600 Million rhetoric escalated in

connection with a February 28, 2010 dinner

hosted by Animal Rescue Resource Found-ation

cofounders Craig and Pam Neilson, of Vista,

California, to promote investment in developing

a " Super Birth Control Pill for Dogs. " The

Animal Rescue Resource Foundation, formerly

called the Give Some Life Foundation, has funded

surgical sterilization of more than 10,000 dogs

in northern Mexico during the past seven years.

Elaborated a 600 Million appeal mailing,

sent in mid-March, " We are in the process of

developing specialized, long-term 'super' birth

control pills (in the form of food pellets) for

dogs... formulas that will provide years of

contraception, from just one doseŠIt must be a

pill. Injections will not solve the problem

because they are too difficult to administer to

millions of dogs running loose. Pills on the

other hand can easily be mixed with food. We are

in the process of hiring scientists to fast-track

this. We are building a network to enable

distribution of the pill in more than 60

countries. "

Asked for specifics, Pacheco told ANIMAL

PEOPLE only, " I have access to data and

documents which you do not. " Pacheco said he was

" preparing a list of additional documents and

statements for publication, " and would " release

the documents when they are ready to be

released, " but the only new item he released in

the next three weeks was a letter similar to his

own appeals, signed by Jeff Young, DVM, of

Planned Pethood Plus in Denver, who also cited

no specifics about the birth control product.

Noted ACC & D director of outreach Karen

Green, " Alex has not publicly named the

technology he's referring to or the partner he's

working with. SenesTech would make some sense,

since that technology most closely matches Alex's

claims about a permanent sterilant delivered

orally. However, the SenesTech approach is

still in very early stage research in terms of

proving efficacy and safety in dogs and cats,

and beyond that stage, there are years of

hurdles to getting regulatory approval. While we

would love to see something available that

matches Alex's description, I'm afraid

we--including our network of directors,

scientific advisors, and colleagues in the

field--have seen no evidence that such technology

is anywhere near. "

Added Green and Briggs in a written

statement, " We are pleased to see other

organizations working on new ways of controlling

pet populations. We hope that 600 Million Stray

Dogs Need You will help raise awareness about the

need for new ways to control reproduction in

animals.

" Until the recent announcement about the

near-ready 'super birth control pill,' " the

statement said, " the stated goal of 600 Million

Stray Dogs Need You was to create a birth control

pill for animals--focusing on dogs--which

provides contraception for at least six months

and can be mixed into food for easy delivery.

ACC & D has long believed that cat and dog

contraceptives must be long-lasting--a minimum of

three years, but ideally permanent--in order to

have significant impact. Particularly for the

stray and free-roaming dogs in developing

countries, a product requiring semi-annual

treatment is impractical. While we do believe

there may be niche use for a product lasting six

months, we believe such a product is unlikely to

be effective for large-scale population control. "

ANIMAL PEOPLE president Kim Barltett

disagrees. " Since true street dogs-- not

'community dogs'-- in the developing world have

an average lifespan of around three years, with

possibly five breeding cycles for each female who

survives that long, an oral birth control

formula lasting six months would have the

potential to cut breeding by about 20%. This

would be a huge reduction in the birth rate by

itself, and if the product were effectively

administered twice a year to all the female dogs

in an area, the birth rate in the treatment area

would plummet. There are a lot of variables and

plenty of opportunities for improper dosing, but

I disagree with the conclusions of ACC & D that a

contraceptive lasting only six months would have

an insignificant impact on a street dog

population. "

--Merritt Clifton

--

Merritt Clifton

Editor, ANIMAL PEOPLE

P.O. Box 960

Clinton, WA 98236

 

Telephones: 360-579-2505, 360-678-1057

Cell: 360-969-0450

Fax: 360-579-2575

E-mail: anmlpepl

Web: www.animalpeoplenews.org

 

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