Prize parasites: how an Irish man won the Nobel

Hearing that you have won a Nobel Prize is a pretty special moment. But when it happened to Dr William C Campbell earlier this year, he was initially a little incredulous.

“Are you kidding?” he asked a journalist who had phoned him before the scientist himself had officially learned the news.

It wasn't a prank. Campbell had been selected to share this year's Nobel Prize in Physiology or Medicine with Satoshi Omura "for their discoveries concerning a novel therapy [ivermectin] against infections caused by roundworm parasites" and Youyou Tu "for her discoveries concerning a novel therapy against malaria".

“People keep saying, ‘Are you sure you didn’t know?’ ” says Campbell of his amazement at being called.

"People had mentioned that ivermectin was worthy of a Nobel Prize, but to me it always seemed very clear that it could not be given for the ivermectin work, because I didn't see how one could possibly pick one or two or even three people. In that sense I was surprised, yes."

The ivermectin story started decades ago when a test at the Merck Institute for Therapeutic Research in New Jersey hit the jackpot. Bacteria can sometimes produce chemicals that have activity against disease, and Merck was carrying out novel but routine screens of isolates from micro-organisms, says Campbell, who was a senior parasitologist at the institute.

Omura had sent Merck a sample of the soil-dwelling Streptomyces species found near a golf course in Japan. When it was put through its paces in the parasitology lab, it showed anti-parasitic activity.

But it was far too early to get overexcited, says Campbell: parasites are complex, as is drug discovery and development, and there were still plenty of hurdles to clear.

“Even though this was a very special and very striking degree of [anti-parasitic] activity, still the chances of it turning out to be unstable or have a stench or to be toxic in innumerable ways . . . all those pitfalls are just waiting to destroy whatever drug you are developing,” he says.

Hampering parasites

The active compound was pinpointed as avermectin, a macrocyclic lactone, and then the chemists got tweaking.

“The original [compound] was very potent but our chemists immediately started making all kinds of derivatives and getting feedback from the parasitology department about what made things better and what made things worse,” says Campbell. “They came up with something that was overall better.”

The better version was ivermectin, a compound that is thought to hamper a range of parasites by targeting tiny structures in their cell membranes called ion channels.

The ivermectin disrupts the parasite’s nervous system and it dies, reducing the burden on the host.

Ivermectin proved effective for animal health, and Campbell looked to apply it further. "I had always been interested in human parasites," he says. "[So] I wrote suggesting that it be explored for river blindness in people, because the potential was so exciting."

The idea won favour with his bosses, and human trials for river blindness turned out to be “hugely promising and very, very exciting”, he says.

But there was another hurdle. “We were very conscious of the fact that the people who would need it for river blindness would not be able to afford it at any cost,” says Campbell, who describes a remarkable move by Merck president and chief executive Roy Vagelos.

“He made this decision that [ivermectin] would be donated for river blindness for all who needed it for as long as it was needed.”

Reducing burden of disease

To date ivermectin has played an important role in reducing the global burden of river blindness and lymphatic filariasis, and Campbell describes its use as a human medicine as “the icing on the cake”.

So how has his life changed since news broke about the prize? “It has been a lot of pressure, a lot of busy-ness. Absolutely amazing,” he says. “I still try and do the ordinary everyday things but it is very difficult to juggle.”

One activity that Campbell is determined to keep up in that juggling act is his advocacy for studying parasites. “It is so often not recognised how much parasitism comes into play in the whole natural world,” he says.

Now in his mid-80s, he has no plans to go back into the lab, “mainly because I no longer have the patience or the concentration to work in a lab without endangering myself and everybody else around me”. Instead he sees his role in education. “I like to talk to students; that is one of the things that I plan to go on doing.”

And Campbell insists that the Nobel award is for the wider team involved in ivermectin. When he heard about the prize, he had two emotions right away: “One was the happiness at the news, but the other was absolutely simultaneously that so many of my colleagues could also be named, and so I have to accept it as a representative of my colleagues.”

CEREMONY NEXT WEEK

When William C Campbell receives the Nobel Prize in Physiology or Medicine at a ceremony in Sweden next week, he will join a highly select club: he is one of just two people from Ireland to win the honour for science. The other is Ernest T Walton, who in 1951 shared the Nobel Prize in physics for his role in “splitting the atom”.

Campbell was born in Derry and brought up in Ramelton, Co Donegal. He attended Campbell College in Belfast before getting a BA in zoology from Trinity College Dublin. He then did his PhD at the University of Wisconsin-Madison, before working at the Merck Institute for Therapeutic Research, where he was involved in the development of ivermectin.

Campbell is an associate fellow in the Charles A Dana Research Institute for Scientists Emeriti (Rise) at Drew University, which enables students to research with scientists who have retired from the corporate world, and he sees the need for scientists to appreciate a full spectrum of science, from the fundamental to the applied.

“I think it is very important that the people working in industry work in an atmosphere where they can do what I consider playful research as well as highly focused research,” he says.

“And similarly I think people working in academia should do their basic thing, but also be more attuned to the kinds of research going on in industry.”