The treatment of parasitic disease hit the media rounds in a big way lately following the announcement that the pair of scientists, William Campbell and Satoshi Omura, responsible for the discovery of avermectin, along with a Chinese scientist, Youyou Tu, for the discovery of artemisinin, were awarded the 2015 Nobel Prize for Physiology or Medicine.
Avermectin’s discovery led the development of a new class of drugs that were highly effective against nemtodes, fleas, tics and mites. Whereas artemisinin, based on tradition Chinese medicine, led to the development of new class of antimalarial drugs for the treatment of malaria.
The Nobel Assembly noted in its press release “These two discoveries have provided humankind with powerful new means to combat these debilitating diseases that affect hundreds of millions of people annually. The consequences in terms of improved human health and reduced suffering are immeasurable.” While that may be the iceberg, the tip is the more interesting story to sea lice researchers and aquatic veterinary practitioners. The discovery of avermectin in its many derivatives, the most famous of which was ivermectin, became known under the newly coined term “endectocides” as they were high effective against endoparasites, namely nematode worms, and ectoparasites, namely fleas, tics and mites - and the soon to become infamous – salmon louse.
Development of the drugs
As the story goes, in 1978 Omura, a Japanese microbiologist and world expert on bioactive compounds found in soil microbes, isolated an actinomycete, Steptomyces avermitilis, from a soil samples collected from the margin of a golf course. Although given that Omura golfs with a 5 handicap, one has to wonder what he was doing so far away from the green. Nonetheless, finding useful isolates this way was not an easy task as he worked with thousands of cultures to find those with the most promising chemical properties.
After a commercial collaborative agreement was developed with Merck Sharpe and Dohme (MSD) in the US, samples of the most promising were sent to Campbell, an Irish born parasitologist working for MSD who isolated a compound he found to be toxic to nematode worms, that he later named avermectin. Not long after, ivermectin was derived from avermectin and found to be even more effective. The rest is history, as they say, culminating in explosive scientific fame.
The initial focus for drug development was on veterinary medicine applications and by 1981 ivermectin was introduced for the control of endoparasitic nematodes and ectoparasitic arthropods in livestock. The product became so successful in these applications that it became the global veterinary pharmaceutical market leader within 2 years with annual sales of US$1Billion.
Around the same time (1982), the drug was also being developed for use in human medicine for the treatment of River Blindness, a severely debilitating disease affecting tens of millions of people in tropical regions. Clinical trials were undertaken in West Africa in collaboration with the World Health Organisation which become a model for public-private-partnerships, now used to develop and distribute pharmaceutical therapies for disease that have little return on investment. These clinical trials led to the approval for use in humans in 1987. However, shortly thereafter MSD announced that it would provide the drug for free for “as long as it is needed”. Since then ivermectin has been used effectively to combat other extremely debilitating diseases such a Lymphatic Filariasis (aka Elephantiasis) and several others.
The aquaculture link
Not surprisingly, researchers working on sea lice control strategies looked to ivermectin as a possible treatment. The first trials were carried out in Ireland (Campbell’s birthplace no less) in the mid-1980s by a team at the University College, Galway (now known as the National University of Ireland, Galway). The compound was found to be highly effective against all stages of lice as a feed additive and quickly become the compound of choice as an “extra-label” prescription. It is matter of record that MSD was not interested in completing the necessary regulatory work to get the drug licenced for use in aquaculture. As a result use in aquaculture was highly restricted where extra label drug use provisions could be applied.
It wasn’t until Schering Plough Animal Health began preliminary trials in the UK on emamectin benzoate, another derivative of avermetin, in the mid-1990s that the potential of the avermectins for sea lice control was fully realised. Emamectin benzoate was highly efficacious against all stage of lice and had a wide therapeutic margin, meaning it was also very safe for the fish being treated. Following licensure of the compound under the trade name “SLICE®”, it soon become the compound of choice for the treatment and management of sea lice infestations on salmon farms in all major salmon farming regions.
The discovery of the avermectins has been a game changer for human, animal and, as it turns out, salmon health. Interestingly there has been much debate about the use of SLICE® in aquaculture; however, I suspect that if you plotted all avermectins used around the world for human, food and companion animal uses on a pie chart, you wouldn’t even see the slice that represents use in aquaculture. While the focus of the Nobel Assembly is on the benefits of such scientific discoveries to humankind, it’s interesting to see how veterinary medicine contributed to this benefit and, more importantly for us aquaculturists, how the world of aquaculture benefited.
— Myron Roth