In 1993, an Australian animal health company decided to withdraw all funding from its research into a revolutionary method of neutering dogs. Although a previous study had confirmed that castration could be achieved using a vaccine, the formulation at the time was not deemed commercially viable.

And that might have been the end of the story, had it not been for one determined researcher, who had already convinced the company to supply him with enough vaccine to conduct a small study in pigs. At the time, Dr David Hennessy was employed by one of Australia's State government research facilities at the Victorian Institute of Animal Science (VIAS), which had been collaborating on the development of the new technology since 1988.

With his background in pig production, Dr Hennessy had seen the potential for an alternative to physical castration for swine producers – and although he had not managed to get any backing from the private sector for the pig research, he had managed to secure a small supply of vaccine for his work.

"Fortunately, I had sufficient vaccine left to complete the pig programme that I had been funding separately, and I continued with it," he explains.

The study was successful and later that year, Dr Hennessy presented the proof-of-concept results. As a result, the company that had withdrawn funding agreed to re-start the product development programme but this time targeting pig production. It was a pivotal moment.

Sixteen years later, the vaccine has already been adopted in many swine-producing countries around the world, with more joining all the time. But, as with many revolutionary products, there were many problems to be ironed out along the way.

In fact, the vaccine did not even start with dogs: it was initially designed to prevent pregnancy in free-range heifers being fattened for export in Northern Australia. The idea being to provide an easier alternative to crush-side ovariectomy. It started as a joint venture between the Victorian State Government Department of Agriculture and private industry.

However, early setbacks meant the programme was switched to companion animals and VIAS was commissioned to run an experimental dog colony and to conduct endocrine and behaviour testing. Although similar research in cats proved unsuccessful, the canine results were good enough for registration trials to be planned. Just before the trials were due to start, problems with the formulation came to light and the project was dropped.

But the pig data saved the day, and was backed up by further studies which prompted a trial programme aimed at registering the product in 1995. But that was not the end of the story.

"At that stage, the vaccine was markedly different to the product we know today," Dr Hennessy explains.

"We were using a totally different GnRF (gonadotropin-releasing factor)-based formulation to the one we use today."

"The technology behind it was not so efficient, meaning the costs involved were higher than what was desired. As a result, the company again cancelled their total involvement in the programme, withdrawing all support and funding."

Dr Hennessy admits that, at the time, he did not believe there was another, less expensive way of coupling the GnRF to the carrier protein. But again, he refused to be beaten. He put a new team together with the aim of gaining clear guidance on the target costs of production and more information on the constraints in terms of chemistry from a manufacturing perspective.

"I got the company to agree that if I could find another way to reach the target cost of production, they would recommence the registration process."

Schematic representation of natural GnRF and the GnRF analogue in Improvac. The modification to the smaller end of the analogue prevents binding to the GnRF receptor in the pituitary.

Not only did he get that agreement but he also successfully approached VIAS management for government funding, and began studies into alternative methods of production.

"In late 1995, I presented the proof-of-concept results for an alternative chemistry method to the management. True to their word, they proceeded to quicken development and we embarked on the path to registration."

It was around this time that Professor James Pettigrew, who then worked at the University of Minnesota, visited Australia for professional research purposes and heard of the revolutionary concept.

"I spent a few months in Australia and engaged in lots of discussions with Australian scientists. This is one of the topics that generated excitement in that group. The development was vaccination to control boar taint, created by immunisation of growing boars against GnRF."

The vaccine works like any other in that it stimulates the pig's immune system to produce antibodies that, in this case, prevent boar taint. Specifically, it stimulates the pig's immune system to create antibodies to GnRF - a protein messenger produced by the brain which ultimately controls the testicular activity that leads to boar taint development.

The vaccine that is used today is based on a synthetic version of GnRF so it has no physiological effect in the pig. In other words, it is similar enough to the pig's GnRF to help trigger antibodies that neutralize GnRF; but different enough not to simulate (or act like) GnRF's role in creating boar taint.

In the final formulation, the GnRF was linked to a carrier protein, which boosted the antigenicity so that the vaccine produced a strong antibody response. This carrier protein is used in many common childhood vaccines.

Schematic representation of changes in antibody concentration, and boar taint, following IMPROVAC.
The first dose primes the immune memory cells but antibodies do not reach a protective level. The boar continues to grow as a boar. Following the second dose, close to slaughter, there is a rapid and marked rise in circulating antibodies which neutralize endogenous GnRF and thus prevent stimulation of the pituitary. As a consequence, testicular function is inhibited and boar taint is controlled

In 1996, the team started to conduct the trials for registration, and to prepare for market development. Two years later, the world's first vaccine technology for the prevention of boar taint was launched in Australia and New Zealand.

Dr Pettigrew, who now works in the Department of Animal Sciences at the University of Illinois, says the development history shows the concept has stood the test of time.

"It's been a long process, and I'm delighted that people interested in the concept and the product have persisted. In addition to the research stages, the extensive practical experience with the product in Australia (a traditionally non-castrating market) identified and solved some of the practical problems in its application. More recent experience in countries such as Mexico, where most boars are castrated, has extended the practical knowledge to those production systems."

According to Dr Hennessy, the recent launch in Switzerland is a testament to all those involved in the product's development, from its inception 20 years ago.

"Others were also instrumental in the frenzy of activity that occurred in 1996-1997 before registration. A key player was Dr John Walker, who led the transition from the test tube chemistry method to the full blown validated manufacturing process used today.

"Also pivotal was Dr Ross Henderson, who led the regulatory group that managed the registration process with our regulatory authorities," Dr Hennessy says.

In fact, the vaccine remained a little known antipodean curiosity until Pfizer acquired the product from the Australian Animal Health company, CSL, in May 2004. Having undertaken significant analysis into the safety of the product, Pfizer was satisfied in putting its name behind the revolutionary vaccine. And in realising the international potential of this new technology, Pfizer set about registering the vaccine in swine producing countries around the world.

Dr Hennessy also became part of the Pfizer team that had the vision of introducing a paradigm shift in the global pork industry.

"The success of the boar taint vaccine is firstly due to a team of true believers who saw the vision, and secondly, had the perseverance to make it real," he said.

"I wouldn't take no for an answer, and I looked under every stone. The team and I had a vision and we never gave up."

Dr Pettigrew says the vaccine holds huge potential for the swine industry.

"The worldwide pork industry is under pressure to eliminate surgical castration on grounds of animal welfare, and many people within the industry would prefer to end this practice. However, ending castration has historically required reducing the slaughter weight, and that significantly reduces production efficiency, and objectionable boar taint is often still apparent. The vaccine offers the opportunity to eliminate physical castration without these other problems."

"However, the welfare benefits from elimination of physical castration did not drive the production of intact males in countries such as Australia and the United Kingdom. Rather, those industries produced intact males because they produce substantially leaner carcasses, are more efficient in use of feed, and grow faster than castrates. The vaccine allows the industry to gain these benefits to a substantial degree without the low slaughter weights and boar taint usually associated with intact males."

Dr Hennessy suggests the product has the potential to revolutionise the swine industry across all markets, with proof of success evidenced across two decades of research and implementation.

"From cattle to dogs to pigs, it's been quite a journey. It's satisfying for our team to see the original concept for a cattle welfare product has been developed and had success in the swine industry. By the end of 2008, more than 10 million pigs worldwide have been safely vaccinated."