William C. Campbell is careful to emphasize that he’s grateful for the Nobel Prize. It’s the obligations that accompany the award—articles to be written, interviews and speaking engagements in far-flung locations—that have added unexpected stress to his retirement. At 85, Campbell, the former Merck researcher who received the 2015 Nobel Prize in Medicine or Physiology for his part in the discovery of the drug ivermectin, has a playful, contemplative nature that seems to find its happiest expression in favorite pursuits like painting, ping-pong, kayaking…and studying parasitic worms.
Campbell loves worms. In fact, his passion for flatworms, roundworms, tapeworms and their ilk led to ivermectin, which effectively treats—and may well one day eradicate—one of the great scourges of mankind. River blindness, also known as onchocerciasis, afflicts the world’s poorest, largely in sub-Saharan Africa but also in South America. Caused by a parasitic nematode worm known as Onchocerca volvulus, the disease is transmitted by blackflies whose bites deposit infective larvae into the skin. In the body, the larvae mature and reproduce, and the new larvae migrate toward the skin, collecting in lumps that resemble half-marbles, and to the eyes. They provoke an immune response that generates an unbearable itch, which compels sufferers to rake at their skin; when the larvae die in the eye, they cause irreversible lesions on the cornea and, if untreated, blindness.
Before the discovery of ivermectin, a drug in the avermectin family, the only real weapon against river blindness was an insecticide sprayed over the fast-flowing rivers and streams in which blackflies breed. Aerial spraying has helped reduce blackfly populations, but it hasn’t come close to eliminating the disease. Ivermectin promises to do just that—and already has in parts of the world, including Colombia and Ecuador. None of this might have happened, however, if Campbell hadn’t been fascinated by worms.
His interest may have been kindled on a high school trip to an agricultural fair just outside Belfast, some 100 miles from County Donegal, the craggy northwest corner of Ireland where he grew up. At the fair, he chanced on a pamphlet about the treatment of cattle suffering from a parasitic worm disease. “I was fascinated by the fact that these domestic animals have worms,” he remembers, “and I was fascinated by the fact that you could treat them.” To this day, he remembers the name of the drug mentioned in the pamphlet and the company that manufactured it—his only memories of the outing.
It wasn’t until his undergraduate days at Dublin’s Trinity College that Campbell decided to pursue a degree in zoology, specializing in parasitology. The decision was sparked by his relationship with a professor, the noted parasitologist J. Desmond Smyth, who saw promise in the young scientist.
“He was interested in talking to me,” Campbell remembers, “even though I was an absolute nobody, a college kid from the sticks.” Smyth later recommended Campbell to a colleague at the University of Wisconsin, Arlie Todd, who was recruiting graduate students. After Campbell earned his PhD. at the university on a Fulbright Travel Grant, Todd recommended him to Merck, then located in Rahway. Campbell took the job, settling in New Providence, where he and his wife, Mary, raised their three children. Campbell remained at Merck for 33 years until his retirement.
At Merck, Campbell made a significant discovery: a process for deep-freezing worms without killing them. Previously, researchers working with worms affecting sheep and cattle had to keep livestock on hand, infecting them with the parasites and then extracting their eggs from feces or carcasses. The process had to be repeated multiple times with each new parasite studied.
One day, Campbell attended a lecture by a British scientist whose team had tried to freeze a guinea pig. The procedure had failed, but Campbell was intrigued. Okay, he thought, maybe you can’t freeze and reanimate something as large as a guinea pig, but people are already doing it with single-celled organisms and spermatozoa. Worms, he figured, were somewhere in the middle. And so the quest began, rooted firmly in Campbell’s sense of play.
As he experimented with different procedures, Campbell had no sense whatsoever that what he was doing might change the way parasitologists worked. The discovery, he stresses, “did not come about because it was important. It came about because I had this crazy passion to freeze worms.” Eventually, “by a tremendous bit of luck,” he says with typical modesty, he discovered that the worms were more likely to survive freezing when he removed their slender outer membrane. This counterintuitive discovery enabled parasitologists to maintain worm banks instead of stocks of cattle and sheep, saving them time, trouble and—a big factor in research—money.
Science doesn’t always advance in a straight line; in reality, the lines of progress can be as wiggly as Campbell’s worms. When he first started working on the project that would one day win him the Nobel Prize, Campbell had no idea that it might ease the suffering of millions of people. At Merck, Campbell mainly worked on the development of antiparasitics for animal populations. In 1974, his Merck colleagues received a sample of bacterial cultures from Japanese scientists led by future fellow Nobel Laureate Satoshi Omura. Merck’s hope was that they might contain an effective compound against the parasitic worms that afflicted livestock in large numbers.
Indeed, after working with the bacteria—which Omura and his team had isolated from soil troweled up near a golf course in Japan—they were able to identify a previously unknown group of molecules called avermectins, which, when chemically modified, turned out to be an effective broad-spectrum antiparasitic in dogs and a variety of livestock. Campbell’s area of ivermectin research was on canine heartworm disease. As a result of his research at Merck, many dog owners now give ivermectin to their pets monthly to prevent heartworms. But Campbell, who’d long been interested in river blindness, realized that some of the parasites that ivermectin was killing in animals were similar to the roundworm that caused river blindness in humans. He and his supervisor, Dr. Jerome Birnbaum, approached Dr. Roy Vagelos, then Merck’s president of the research laboratories and later chairman, and urged him to begin human studies. The subsequent studies revealed that, while the drug didn’t kill the adult stage of O. volvulus, it was highly effective at destroying its larvae.
It was clear that ivermectin, marketed as Mectizan, could be a game changer, with the potential to cure or even wipe out river blindness. There was just one problem: Given that the population that suffered from the disease lacked the wherewithal to pay for the cure, there appeared to be no way for Merck to monetize the drug.
Instead, in 1987, Merck decided to give the drug away to anyone who couldn’t afford it, for as long as it was needed. At the news conference announcing the Mectizan Donation Program (MDP), the public/private partnership formed by Merck to produce and distribute ivermectin, Massachusetts senator Ted Kennedy called the plan “a triumph of the human spirit” and lauded the discovery as “an answered prayer for the third world.”
Today, the MDP—the world’s longest-running drug-donation program—has given away more than a billion treatments for river blindness. As of 2011, the program had approved more than 140 million tablets annually. The regimen is surprisingly simple: a single tablet taken once a year over the course of 16 to 18 years. (Ivermectin kills only the worms’ larvae, and it can take up to 18 years for all the adult worms in a body to die.) Though it can’t restore lost sight, a course of ivermectin will effectively halt the progression of the disease and end the agony of itching that has degraded the quality of life for millions in the developing world.
“It’s a wonderful program,” says Vagelos, now chairman of the board of Regeneron Pharmaceuticals, headquartered in Tarrytown, New York. “It’s doing a huge amount of good for people, and none of it would be possible if not for Bill Campbell, who was the intellectual leader of the project at Merck.”
Campbell continued to work at Merck until his retirement in 1990, after which he became a research fellow at the Research Institute for Scientists Emeriti (RISE) at Drew University in Madison. The program, which Campbell calls “a miracle,” is staffed with eminent retired researchers from a variety of industries, who conduct cutting-edge research with undergraduate biology, chemistry, physics and mathematics students. RISE gave Campbell a hands-on opportunity to share his knowledge of—and perhaps more important, his enthusiasm for—parasitology with students, some of whom have found the experience life changing.
Dr. Heidi Smith, director of clinical affairs at MassBiologics of the University of Massachusetts Medical School, a nonprofit whose mission is to develop and manufacture new drugs for unmet medical needs, worked with Campbell in the RISE program, an experience that had a significant impact on her career path.
“Working with Dr. Campbell,” she says, “helped open my eyes to the tremendous impact that infectious diseases have on the world, then showed me the tremendous impact that scientific research can have on these diseases.” Campbell allowed her to borrow from his extensive library on parasites and global health, which helped her home in on her medical specialty. Perhaps equally important, “he managed to really help us see the possibility and the fun in the science.”
In 2010, Campbell became an associate fellow, which allowed him to continue his affiliation with RISE in a more limited fashion. His enthusiasm for the program, however, is undiminished. RISE, he says, “was especially wonderful because the students are undergraduates, and you get to see the change in a young person as they discover the excitement of actually doing research, not just classroom exercises.”
It’s hard to imagine a person better suited for conveying the excitement of parasitology. For years, Campbell has written poetry about parasitic worms, often from the worms’ point of view. Worms are also the inspiration for—and the subject of—his vibrantly colorful paintings, in which the parasites might form the panels of a stained-glass window or bloom, flowerlike, from a vase. “They really are like flowers,” he notes, “in the sense that they seem to display an endless morphological variation—the biodiversity is so incredible.”
He also admires their cleverness, most notably in often being able to foil their hosts’ immune attacks against them. “Animals have a way to get rid of worms, and the worms have ways of trying not to be got rid of,” he says. “It’s sort of an arms race.”
Campbell hasn’t allowed his respect and affection for worms to stop him from trying to eradicate the harmful ones—an effort that has changed the lives of millions of people around the world.
Leslie Garisto Pfaff is a frequent contributor. An avid gardener, she’s particularly fond of earthworms.Click here to leave a comment