Ivermectin: The wonder drug that was discovered by a Derry man
One of the most talked about medications of the pandemic has been the blockbuster anti-parasitic, ivermectin, which has been touted as a potential future treatment against COVID-19.
The drug has been shown to be potently effective against SARS-CoV-2 in test tube conditions. It has not been approved for human use, however, due to fears it could prove toxic if administered in high dosages.
The current evidence on the use of ivermectin as an anti-viral is inconclusive, according to the World Health Organisation. The health body is clear that until more data is available the drug is only recommended for clinical trials.
Suggestions ivermectin might be used to treat coronavirus have proven contentious. The controversial President of Brazil Jair Bolsonaro and US ex-President Donald Trump prematurely advocated for its use as a COVID-19 treatment without it having been deemed safe by the regulatory authorities.
Anti-vaccination networks too have seized on the medication as a potential alternative to the highly effective vaccines against SARS-COV-2. Indeed there have been widespread reports in the British and US media, in particular, of people being hospitalised after self-administering strong forms of the medication that is also sold commercially as a veterinary medicine.
Needless to say the strong advice of the health authorities is NOT to take ivermectin as a treatment against SARS-CoV-2. The European Medicines Agency (EMA) has warned that while studies have found that ivermectin could block replication of SARS-CoV-2 this is at much higher ivermectin concentrations than those achieved with the currently authorised doses. A lot more research will clearly be required before ivermectin is approved as a COVID-19 treatment, if it ever is.
What readers may not know is that Professor William C. Campbell, who discovered ivermectin and received the Nobel Prize for Medicine in 2015, was born in Derry in 1930. The acclaimed scientist grew up in Ramelton. His father Robert John Campbell hailed from the townland of Drumfad on the Mulroy side of Knockalla near Port Salon.
His mother Sarah Jane ‘Sadie’ Patterson was from Murroe on the Falcarragh side of Dunfanaghy.
“Though I had been born in County Derry (in Londonderry in 1930), I lived with my family in Ramelton throughout childhood and early adulthood. We lived on The Mall, in a terrace of houses by the estuary of the Lennon River, a short distance from where the waters flow into Lough Swilly and then onwards to the Atlantic Ocean.
"As a child, I would occasionally see boats arriving from England to disgorge their deliveries of coal. Over the years as the harbour silted up, the port traffic slowed almost to a complete stop, but the river remained the defining landmark of the town,” Prof. Campbell recalls in his memoir ‘Catching the Worm’ which was co-written with science writer Claire O’Connell and published last year.
The book is both a personal memoir and a detailed account of his storied career as a parasitologist. It is peppered with vignettes of a life that most readers will recognise including this trip to the beach as a child: “One of our favourite destinations for family outings was a secluded, and then often deserted, beach called the Kinnegar, which lay beyond Rathmullan.
"I remember my father once saying that he had lain awake at night because he was thinking of the previous day when he had been swimming with us at the Kinnegar. The tide had come in over the sandbars, placing my siblings and me out of our depth, and he had instructed us to swim immediately toward the beach. I think this must have been memorable because, seen in hindsight, it would have been my earliest insight into parenthood.”
We learn Prof. Campbell was educated at Campbell College in Belfast rather than at Foyle or Royal and Prior that might have seemed more obvious choices before he went on to study at Trinity College. Long before he met and married his wife Mary he recounts taking a girl from Derry to the Trinity Ball.
“I invited the young woman who sat next to me in my first science classes. She was extremely pretty and I developed a romance with her that was mostly wishful thinking. She was a Derry girl and had visited me briefly in Ramelton during summer vacations.
"I was to reconnect with her later in life, and invited her and her husband to a couple of functions in Dublin - at which her husband was given to teasing his wife by asking her why she had let me get away.”
We also learn how his sister-in-law - married to his brother Bert - was an Anne Mills from Derry. But it is the story of how Prof. Campbell discovered ivermectin - a triumph of old fashioned empirical research - that forms the backbone of the tale. He was working at pharma giant Merck in New Jersey when, in conjunction with Prof. Satoshi Ōmura, he made his breakthrough in 1970.
“[Ivermectin’s] saga as a therapeutic agent started with a microbe and a mouse. The microbe was from a soil sample that has been collected and examined at the Kitasato Institute in Japan. Soil teems with microbes, tiny bacteria, fungi and other organisms that are invisible to the naked eye.
"Many of these microbes produce substances that can be useful in some way for humans, such as killing agents that cause disease. At the Kitasato Institute lab in Tokyo, biochemist Satoshi Ōmura, who shared the 2015 Nobel prize, collected samples of soil from various locations.
"He and his colleagues then isolated microbes from the samples and looked to see if the microbes had any interesting anti-bacterial activity under ‘test-tube’ conditions in the laboratory.
“They also had an arrangement that if microbes were isolated that looked different or had unusual characteristics but were not of direct interest to them, they would send these microbes to Merck Research. Professor Ōmura, who kept a plastic bag with him in case he spotted interesting places to collect soil had scooped this particular soil sample from close to a golf course near the institute where he worked.
“That is how a particular kind of microbe, one of many, came from Professor Ōmura’s lab to the Merck Research labs in New Jersey, where I worked,” Prof.Campbell relates.
In the US the Derry-born scientist used the Japanese bugs - a previously unknown type of Streptomyces bacterium - to create a microbial broth that was fed to mice infected with worms. It worked. Merck’s chemists and biologists set about isolating and synthesizing its active compounds and a wonder drug was born.
“We called it ‘avermectin’. The name was a nod to the drug’s biological action. So often, drugs are named according to their chemical attributes, and I wanted to plant a flag, so to speak, for biology. So I made up a mongrel word to be distinctive and that incorporated the drug’s biological attributes: the ‘a’ refers to ‘not’, the ‘verm’ draws on the Latin for worm, and the ‘ectin’ refers to ectoparasites, because ivermectin is active against external parasites, such as lice and mites, as well as parasitic worms.”
After this initial discovery tweaks were made by Merck’s chemists to make the drug even more effective. This resulted in the name of the medication being changed.
“The result of this process was a molecule with a chemical structure that was similar to that of avermectin but with added hydrogens. At first it was thought the most suitable name for such a thing might be ‘hyvermectin’, until it was pointed out that in some languages the word ‘hyver’ means testicle. Change of plan, it was named ivermectin!”
Ivermectin first went on the market in 1981. By 1985 it was the world’s top animal pharmaceutical. This would have been achievement enough but it was when Dr. Mohammed Aziz, a colleague of Prof. Campbell’s at Merck, successfully trialled it as a treatment against the onchocerca volvulus parasite which causes river blindness in humans that its true worth was realised. Remarkably, Merck’s former CEO Roy Vagelos agreed to donate millions of courses to countries in the Global South afflicted by the illness.
This has made an incalculable difference to the lives of millions. The fact it is effective against lymphatic filariasis, a disease that can cause elephantiasis, has only served to extend the benefit.
“More than 30 years later, and taking into account the distribution of ivermectin for the prevention of filariasis (elephantiasis) and other diseases, more than three billion ivermectin treatments have been donated. River blindness has been certified as eradicated in almost all endemic regions of South and Central America.
"In Sub-Saharan Africa the burden of suffering blindness has been vastly reduced for millions of people, and in some regions the transmission cycle of the parasite has been halted.”
Is another chapter to be written in the ivermectin story? Clinical trials continue to determine whether or not it can be used safely as a SARS-CoV-2 anti-viral.
Speaking last year after studies showed the drug was effective against COVID-19 in vitro Prof. Campbell cautioned: “The concentration of drug needed to kill the virus in the lab was many times higher than the concentration of ivermectin found in the blood of people in the normal use of ivermectin to control parasitic disease. So the probability of ivermectin being used safely to kill the virus in people must be considered low.
“On the other hand, there is, as the authors of the report point out, the possibility that a safe dosage of ivermectin might reduce the rate of viral replication in the mammalian body, or affect the virus in other ways that might be revealed by further research. That is a more positive prospect.”
‘Catching the Worm’ by William C. Campbell with Claire O’Connell was published in 2020. Visit https://www.ria.ie/catchingtheworm