Science

It’s time for parasites to get a little more respect

Irish man who made worms a defining element of his glittering career has been honoured in his native Co Donegal

A bronze statue of Nobel Prize-winner Prof Bill Campbell was unveiled in October by his daughters Jenni and Betsy in his home town of Ramelton in Donegal. Photograph: NW Newspix

Jessica Page Campbell
Thu Dec 29 2022 - 06:00

A new statue celebrates Nobel laureate Bill Campbell in his hometown of Ramelton in Co Donegal. His grandniece, Jessica Page Campbell, explores the impact his liking for worms has had on veterinary and human health.

On October 1st, 2022, a large crowd gathered in the small town of Ramelton in Co Donegal. The usual sound of the rushing river Lennon was masked by brass bands, bagpipes and people battling with umbrellas. At the centre of the commotion was a statue of a man poised in his thoughts.

That contemplative figure depicts my great-uncle Bill – the brother of my late grandfather Lexie. Bill is also known as Prof William C Campbell, Nobel Prize laureate for physiology or medicine, the seventh Irish person to be awarded a Nobel Prize, the second Irish person to receive the prize across the sciences, and Ireland’s first Nobel Prize winner for medicine. He was jointly awarded it with microbiologist Satoshi Ōmura in 2015.

The statue, the work of sculptor Paul Ferriter, is located in the place where Campbell grew up, along with my grandfather and their brother Bert and sister Marion. On the day of the unveiling, the proud townspeople gathered in the rain to celebrate the local boy’s work. Campbell, now in his 90s, joined via live-stream.

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The Nobel Prize he received was for his work in parasitology, and particularly his role in developing ivermectin, a therapy that kills the parasitic worm Onchocera volvulus and treats the disease it causes in humans, known as river blindness.

Campbell tracks his love of worms to conversations with James Desmond Smyth, a professor of parasitology at Trinity College Dublin, where Campbell graduated in 1952 with a first-class honours degree in zoology. Next, my grand-uncle attended the University of Wisconsin-Madison in the US, earning a PhD in 1957 for his work on a type of parasite called a liver fluke in sheep. He stayed in the US and went on to work at Merck Institute for Therapeutic Research, where he played important roles in the development of treatments against parasitic worms, including ivermectin.

Ivermectin’s beginnings

The story of ivermectin started when Satoshi Ōmura sent a microbe with unusual characteristics from the Kitasato Institute lab in Tokyo to Campbell and his colleagues at Merck. Upon its arrival, the microbe was cultivated in laboratory broth and fed to a roundworm-infected mouse, to see whether the microbe had any effect on the parasites. Sure enough, after being fed the broth, no roundworms could be found in the mouse. However interesting, Campbell tells me this was not a “eureka moment”, as he and the other researchers had learned not to pin their hopes on an early result.

The skin loses tone with the infection, enabling others to identify an infected individual, who may then face social exclusion

—  Prof Celia Holland

As the scientists continued to study the microbial broth, they became more enthusiastic about their findings, and identified the microbe as a previously unknown type of Streptomyces bacterium. After isolating the bacterium’s antiparasitic substance, chemically tweaking it and producing it in larger quantities, ivermectin was born.

Once Campbell and his team knew ivermectin could kill the larvae of Onchocerca in cattle and horses, questions arose surrounding its application in Onchocerca volvulus infections in humans, a cause of enormous suffering in the developing world.

A devastating disease

It wasn’t until I attended a lecture on roundworms, as a biology student in Manchester, that I learned the true debilitating extent of an Onchocerca volvulus infection.

My earlier, first impression of parasitic worms had been more pleasant, seeing the large, colourful contorting tubes in my grand-uncle’s artwork. In those paintings, the worms did not look horrifying and ugly but impressive, and sometimes pretty, as Campbell would depict them as flowers in a vase or as panels of stained-glass windows.

In real life, though, the picture is not pretty. Onchocerca volvulus is transmitted to humans by blackflies that live and breed near fast-flowing rivers and streams, giving the disease the “river” part of its name.

Upon infection, the adult worms produce larvae that migrate to the skin and across the eye, generating inflammation and a severe itch. In the worst cases, the immune system can overreact to the infection, causing damage to the eye and subsequent blindness.

At the time of Campbell’s studies on ivermectin’s use in Onchocerca volvulus, river blindness was prevalent mainly in Africa, with additional concentrations in Central and South America.

Prof Celia Holland, a recently retired professor of parasitology at Trinity College Dublin, describes wider implications of river blindness. “An infection with Onchocerca volvulus is also socially and economically devastating,” she says. “The skin loses tone with the infection, enabling others to identify an infected individual, who may then face social exclusion.”

Transforming millions of lives

The first river blindness trial took place in Dakar, Senegal, in 1981. The results were promising and led to larger trials. Eventually, in 1987, Merck & Co Inc made the pivotal decision to make ivermectin freely available for the treatment of river blindness. This decision was an important one as, for maximum eradication of the disease, the people who were suffering needed access – but they could not afford to buy the medicine.

Now, more than 30 years later, more than 3 billion ivermectin treatments have been donated, and thanks to the extraordinary efforts of the World Health Organisation and many non-governmental organisations, river blindness has been eradicated in close to all endemic regions in Central and South America. Millions of people have also benefited from ivermectin in sub-Saharan Africa, where blindness has been reduced immensely.

Parasites can enable us to uncover significant questions about biology that are important to decipher

—  Grace Mulcahy, University College Dublin

The sheer amount of suffering alleviated with this undertaking is astonishing, and this feeling is shared by Campbell, who says it was “a tremendous effort involving corporate responsibility, public-health management and above all, goodwill and care”.

Ivermectin has also had a substantial impact on veterinary medicine, as a treatment for internal and external parasites in horses, cattle, pigs, goats and sheep.

Respect for parasites

Campbell said in his Nobel Prize acceptance speech that “it is time for parasites to get a little more respect”. But why should we respect them? “Parasitism is not only a vital mode of life in nature, but the most common mode of life, and underlies all ecology,” he replies – speaking to me from his home in Massachusetts.

Grace Mulcahy, professor of veterinary microbiology and parasitology at University College Dublin, takes a similarly broad view of parasitology. She is a proponent of One Health, an approach recognising that the wellbeing of humans and animals more generally are inseparable. “These intertwined interactions are reasons for the importance of studying and celebrating parasitology,” she says. “Parasites can enable us to uncover significant questions about biology that are important to decipher.”

Fittingly, Campbell says one of his most meaningful awards is the William C Campbell One Health award, established by the American Association of Veterinary Pathologists, which recognises veterinary parasitologists who have made contributions to One Health.

Holland, who worked in the zoology department in Trinity from which Campbell got his primary degree, notes co-infection is currently a popular area of research, looking at the interplay between parasites and other factors such as microparasites (bacteria or viruses for instance) or vaccinations. “When you are studying parasitology, you are involved in many different areas of science, from molecular biology to vaccinology and sociology,“ she says. “[So it is] vital to have people involved with parasitology, as they have this useful perspective.”

And there is plenty yet to study. The field of parasitology is compiled of many layers, with branches that reach into diverging academic fields, and exploring the threads that they run through our shared ecology is important work. “Parasitology teaches us the critical lesson of complexity being built on simplicity,” says Campbell. “Worms are something you can really get your teeth into.”

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