Rabbit Contraception

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In the mid-1800s, English rabbits, Oryctolagus caniculus, were imported to Australia as a convenient source of meat, but some of these mammals escaped from their hutches, multiplied like rabbits, and their populations ran wild. More than 600 million rabbits soon overpopulated the continent, devastating croplands, pastures, and forests with their voracious appetites and penchant for digging burrows.

The problem became so great that Australians fought back with every available tool. Early pictures show thousands upon thousands of rabbit pelts, often set out to dry in long racks, from animals that had been shot, trapped, or poisoned. Another approach was to erect rabbit-proof fences. Some of these surrounded single farms, but others stretched for hundreds of miles in attempts to thwart expansions of the exploding rabbit populations from one Australian region to another. None of these pest-control methods worked particularly well.

The desperate situation called for drastic action, and in 1950 a bold approach was initiated. The myxoma pox virus, a natural disease agent of rabbits, was intentionally introduced into Australia from Brazil, the purpose being to create a myxomatosis epidemic. This oft-fatal sickness of rabbits and hares (family Leporidae) is spread primarily by fleas and mosquitoes, and this illness can be devastating to naive leporid populations not previously exposed to the virus.

The experiment worked, initially: Rabbit populations plummeted as the pox virus spread across Australia. However, the most virulent strains of the virus died with the rabbits they infected, leaving only the temperate forms in the rabbits that survived. Concurrently, rabbit populations naturally were selected for increased viral resistance. What emerged was an evolutionary standoff in which the surviving rabbits and the pox virus came to coexist in quasibalance. Rabbit numbers in Australia are far lower than in the pre-pox era, but the feisty mammals still thrive and make nuisances of themselves.

For pest species like rabbits that proliferate rapidly and occupy large geographic areas, control strategies that focus on mortality factors alone are usually less than fully effective. In Australia, this has led to calls for alternative approaches that might impact rabbit fertility rather than survival. The result has been considerable scientific experimentation on rabbit contraception, and this is where genetic engineering has entered the picture.

In female mammals, eggs and early embryos are surrounded by a glycoprotein layer known as the zona pellucida (ZP). This extracellular coat plays a key role in reproduction by acting as a gatekeeper for the passage of fertilizing sperm and by influencing embryo implantation in the womb. It has long been known that if the immune system of a female develops antibodies against one or another glycoprotein in the ZP, her fertility can be diminished or blocked. Called "immunocontraception," this phenomenon has been exploited to develop injectible antifertility vaccines for more than 90 mammalian species. These dart-delivered vaccines have been effective in controlling the proliferation of large mammals, such as elephants, that may overpopulate zoos or natural landscapes, such as some parks in southern Africa. However, for logistical reasons, injected vaccines are of little use against abundant small mammals in the wild. Recently, however, Australian scientists conceived of a new way to deliver immunocontraceptives to wild rabbits: via genetically engineered viruses.

In one such procedure, a ZP-coding gene was inserted into a strain of myxoma virus. When the virus was allowed to infect experimental rabbits, the ZP glycoprotein not only was expressed, but it also elicited an immune reaction that significantly reduced the rabbits' fertility. Other viruses that specifically infect rodents have been engineered to confer partial sterility in house mice. Analogous kinds of genetic engineering can be envisioned that in effect might cause partial or complete male sterility, for example by eliciting female antigens against sperm or by altering sperm-expressed proteins that interact with the ZP or egg during fertilization.

Conceptually, genetic engineering for immunocontraception provides an interesting departure from conventional experimentation with most other GM traits in nonpest species. Normally, transgenes are engineered with the goal of improving an organism's performance (e.g., in growth rate or in resistance to diseases). The hope is that progeny of the initial GM generation will inherit the transgene and also benefit from it. In contrast, individuals engineered for sterility cannot transmit transgenes "vertically" because, by definition, they have no offspring. Thus the need arises for a delivery system that can spread sterility genes "horizontally" in the pest population. In the Australian case, the recombinant myxoma virus provides the infectious delivery vehicle intended to drive the rabbit population down.

In principle, genetically engineered sterility has some key advantages over traditional methods of mammalian pest control. To animal rights advocates, immunocontraception promises a humane alternative to overt killing by guns or poisons. To farmers and ranchers, the procedure might afford control over devastating feral pests that otherwise have proved impossible to eradicate. To ecologists, immunocontraception might offer an environmentally friendly alternative to chemical agents for eliminating pests.

However, some salient issues must be resolved before any mammalian contraceptive transgenes are released widely into the environment (by viruses or via other delivery systems such as transgenic plants). First and foremost, there must be strong assurances that a live vector does not reach and sterilize nontarget species. The myxoma pox virus is thought to be specific to Leporidae, but the possibility of dangerous transgene movement to unintended hosts cannot be neglected. A related concern is that the live myxoma virus might escape from Australia and harm rabbits elsewhere. Finally, the entire approach could fail if rabbit populations in Australia evolve genetic resistance to these contraceptive tactics.

To circumvent the first two problems mentioned above, alternative means to lower fertility have been contemplated. For example, contraceptive compounds could be delivered to rabbits via darts, baited foods, or by attenuated (dead or debilitated) virus. But at best, such halfway contraception would yield halfway success, because the sterility would be noninfectious and would impact merely the relatively few animals that could be reached by such methods of direct application.

Feral rabbits, rats, cats, goats, and other small mammal species are often devastating to the native lands and biotas they invade. Furthermore, no easy way exists to eliminate such pests once they have been unleashed into a natural ecosystem. Thus, in the future, far more effort should go toward blocking introductions of alien species, rather than dealing with the consequences after the fact. With respect to eliminating exotic pests, a few ounces of prevention can outweigh many pounds of attempted cure.

On balance, due to the exceptional dangers entailed, relative to the potential gain of lowering rabbit numbers in Australia, I gauge this project as a current boondoggle.

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