This story was updated at 11 a.m. on Dec. 13
NORTH ANDOVER, Mass. — William Campbell had no idea what was in the vial labeled MA-4680. It was just one among thousands of freeze-dried bacterial cultures sent from Spain and Japan to be tested by the Merck Institute for Therapeutic Research, a lab at the New Jersey drug company where Campbell worked as a senior researcher.
He couldn’t have predicted that the brownish, sand-like stuff at the bottom of that test tube would end up saving millions of lives — or that it would win him the 2015 Nobel Prize in physiology or medicine. Campbell accepted his Nobel medal on Dec. 10 at a ceremony in Stockholm.
Vial MA-4680 contained a new species of bacteria isolated from Japanese soil, and that microbe produced a compound that would become ivermectin — the Superman of anti-parasitic drugs, capable of killing off the roundworms that cause river blindness and lymphatic filariasis, two of the world’s most debilitating tropical diseases.
But when Campbell describes the initial discovery, he doesn’t talk about pinpointing molecules or tracing biochemical pathways. He doesn’t even talk about identifying the bacteria. All that would come later. Right then, in 1975, his team infected mice with worms, added the mystery microbe to their feed, and waited to see whether the parasites disappeared from their gut.
“You’re treating mice with an unknown quantity of an unknown substance,” Campbell said. “It seems, superficially, totally non-scientific, but the proof was in the pudding. It worked.”
That kind of playful experiment is harder to find today, but for Campbell, it was nothing out of the ordinary. He spent five decades tinkering with vials and following his curiosity, publishing papers and books on parasitology, drug discovery, the history of medicine — and even Antarctic exploration.
At night, he would slip into the lab to conduct oddball experiments — “playing,” as he called it. He was inspired rather than discouraged by unexpected results. Even now, at 85, exhausted from all the attention that comes with winning a Nobel, he can’t help but get carried away when talking about his favorite lab maneuvers. He mimes the delicate motion of extracting tapeworms from a host. He squeezes his fingers together to show how to squirt worm-eggs into the gullet of a mouse.
And at the heart of all that research was a perverse relationship. He loved worms, wrote poems about them, painted their mouthparts as if they were flowers in a vase — but he spent most of his life figuring out how to kill them.
Campbell grew up in a small Irish town in County Donegal, and his love affair with parasites began in 1946, when his boarding school took a field trip to an agricultural fair near Belfast. Afterwards, all he could remember was a pamphlet he’d picked up on how to rid livestock of worms. He was 16, and it was his first exposure to parasites. His father had kept sheep and cows, but Campbell had never known that inside of them lurked a whole other herd of animals.
His interest resurfaced four years later, when he met a professor named J. Desmond Smyth, at Trinity College, Dublin. On a particularly dreary day, Smyth invited Campbell into the lab to watch worms being extracted from the body of a fish. “This small fish, its belly was absolutely bloated with tapeworms,” Campbell recalled, an Irish lilt still audible after more than 60 years in the United States. “That was such a nice thing he did to invite me in.”
Campbell was hooked, and began to do research with Smyth. That led to graduate school studying liver flukes, a type of sheep parasite, on a Fulbright Scholarship at the University of Wisconsin, Madison, which in turn led straight to Merck, where his playful streak really emerged. At night, after he’d put his kids to bed, he would walk back to the lab and try to freeze worms.
He knew that mammalian sperm cells could survive freezing temperatures: The whole industry of artificially inseminating livestock counted on it. Other researchers had found a way to freeze a tiny, free-living roundworm without killing it, so they could use it for genetics research. But no one had ever successfully frozen and thawed parasitic worms.
“I tried freezing every worm I could get my hands on,” Campbell said. To see if the worms were still alive, he’d dunk the frozen vials into warm water. But because improperly sealed vials could explode at the sudden change in temperature, he would place the thawing bucket across the room and lob the test tubes into it.
For years, every last vial yielded dead worms. But then, in the early 1970s, he noticed that some hookworms started to move after he thawed them. “There’s a huge element of chance in this,” he said. “Instead of having 100 percent of my worms die, I only had about 99.9 percent of my worms die.” That was enough to get Campbell excited. Noticing that the surviving worms lacked a membrane that most others had, he began to remove that tissue manually, and was able to coax a larger percentage into surviving a deep freeze.
“For me, it was just doing fun, crazy experiments,” he said. But to other parasitologists, it was a lifesaver. Until then, the only way they could keep live samples of these parasites was to keep livestock as hosts. Now, they could just put hookworm larvae in the freezer, and get it out when they wanted to do an experiment.
“It was another fundamentally important contribution he made to the science of parasitology,” said Tim Geary, a parasitologist at McGill University. And unlike the discovery of ivermectin, or the decision to give the drug away in order to make it accessible across the developing world, both of which involved huge teams at Merck, this idea began with Campbell alone in a lab after dark, tinkering with worms.
I wonder what would happen if …
Campbell lives with his wife in a newly built farmhouse 30 miles north of Boston, down the road from a horse field. After retiring from Merck, in 1990, Campbell kept playing in the lab and mentoring undergraduates at Drew University, a small liberal arts college in Madison, N.J. But he gave up lab work six years ago to move closer to a daughter who lives in New Hampshire.
When I visited Campbell twice this fall, he perfectly embodied the role of an old-school professor: white beard, dark sweater, and a boundless enthusiasm for the life cycle of worms. He’d long ago stopped worrying that he’d be lost without vials to play with. The only lab equipment in sight was Campbell’s collection of historic microscopes, and those gleaming instruments made a fitting backdrop for a discussion about his work.
Campbell taught courses at Drew on the history of science, and he knows that every major medical discovery can be chalked up to serendipity, but that doesn’t mean the findings are accidental. Rather, they are the result of meticulous trial and error, of testing even those ideas that couldn’t be explained by the current way of thinking.
“The students got banged into their heads that you need to formulate a scientific question that you want to be testing,” he said. “But I’ve always maintained that a perfectly legitimate question is ‘I wonder what would happen if?’”
Working with Campbell as an undergrad in the 1990s was what led Dr. Heidi Smith to become an infectious disease researcher at the University of Massachusetts Medical School. “There was this popular idea that infectious diseases had been conquered,” she said. But then she met Campbell.
She sat in his office looking at the spaghetti-like tangles of worms in jars. She borrowed his books. And she absorbed his open-mindedness as they did research that would become her first scientific paper: a study of how worms ingest ivermectin.
Even without his own lab, Campbell still has three papers in the works. Two are the kinds of publications you might expect from a retired parasitologist: long retrospectives on the drugs he helped develop. But one is a little quirkier. That one focuses on a drawing from the Middle Ages, of a medical quack selling potions by the side of the road, with a flag to illustrate the effects of one of his remedies.
Past historians have claimed that the illustration shows a man who has just taken a laxative, but Campbell disagrees. “He just passed some worms,” said Campbell, chuckling. “There’s no way to describe it. You’ve got to see it to believe it.”