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The Ups and Downs of Ivermectin

By Terry Maguire - 01st Dec 2022

Ivermectin
Treatments for Coronavirus (COVID-19): IVERMECTIN in white bottle packaging with scattered pills. Isolated on blue background. Horizontal shot. Copy space.

Terry Maguire balances the hype around ivermectin against the scientific facts and clinical investigations

I first came face-to-face with Bill Campbell where he stood outside the old stone fish-house at the top of the mall. As he was a newcomer to the Lennon riverbank, I stopped to ask my colleague Tom Murray MPSI who Bill was and why he was there. To my shame, I had to confess I had never heard of him. Since his 2015 Nobel Prize for medicine, this 92-year-old son of Ramelton, Co Donegal, has become an international celebrity, I was told, as the man who discovered ivermectin, which has largely eradicated River Blindness.

In 1975, working in his laboratory in the US for the Merck Company, Bill infected a single mouse with a parasitic worm. He then fed the mouse for two weeks with a liquid fermentation containing a Streptomycin bacterium. At the end of the experiment, the mouse was worm-free, and so began a journey that first identified the anti-parasitic agent, isolated the chemical, developed a range of related chemicals that were tested for safety and efficacy, and eventually licensed as human and veterinary medicines; the best known being ivermectin.

Ironically, I had spent the Covid-19 pandemic period with a pretty negative view of ivermectin, having to remind people that it was ineffective and potentially toxic in the treatment of Covid-19. In the early days of the pandemic, national governments and their health services were focused on preventing the spread of SARs-CoV-2 virus, developing vaccines and searching for treatments mainly from repurposed medicines. The big success in this latter category was dexamethasone, but many more medicines were promoted as Covid-19 miracle cures, later to be found ineffective. Sadly, ivermectin is one of these.

In the first months of the pandemic, a research team in Australia published a paper describing how they found that ivermectin in vitro killed the SARs-CoV-2 virus. In their paper, they suggested a plausible mode of action for the drug through blockade of Importin Nuclear Transport Proteins and in doing so, disrupting transfer of mRNA into host cells and therefore stopping viral replication. The downside was that the dose for this viral neutralisation was 50 times the normal ivermectin dose.

However, the paper spawned a race that saw numerous research teams across the globe set up and publish studies on ivermectin in the prevention and treatment of Covid-19. Some reported huge success and one even suggested that undertaking more studies would be unethical, as the effect was so large. In the UK, Dr Tess Lawrie was one of the first to claim an 83 per cent reduction in deaths in ivermectin treatment groups. On publication, using more strict criteria, this was reduced to 68 per cent but was nevertheless impressive by any standard. Other teams reported similar findings, such as Prof Pierre Kory in the US, who gave evidence to the US Senate, where he demanded the widespread use of ivermectin. He set up the action group FLCCC (Front-Line Covid Critical-Care Alliance) to promote its use. In the UK, Dr Tess Lawrie set up BIRD International (British Ivermectin Research). These became powerful lobby groups.

The studies were picked up by social media doctors and others such as Dr Jordan Petersen, Russell Brand, Joe Rogan and Dr John Campbell. The pundits enthusiastically reported and supported the emerging data and there was a significant public response requesting ivermectin, even though the drug was mostly supplied as medicines licensed for the treatment of animals.

Dr John Campbell, a well-known UK-based YouTube commentator who holds a PhD in nursing, cited two trails that in his view supported the use of ivermectin, suggesting the evidence was “powerful” and “overwhelming”. Yet a BBC investigation into his claims showed how both studies were seriously flawed. Dr John Campbell (no relation of Bill) remains unapologetic. Dr Tess Lawrie, when asked in an interview what it would take to convince her that ivermectin treatment was ineffective against Covid-19, replied: “Nothing would convince me it doesn’t work; it works.”

That small boy running the streets of Ramelton in the 1930s and ’40s who became a Fulbright Scholar to the US has made a huge impact on our world

The hype thankfully didn’t last too long. The quality of early studies was poor and easily debunked by more objective scientists. Of 26 studies included in one meta-analysis, one-third had serious errors, with potential fraud. Most of the studies were observational studies, which are of poorer quality than randomised controlled trials (RCTs). Where RCTs were done, they were poorly designed and managed and their results of little value. Supporters of ivermectin were accused of “cherry-picking” data to suit their case. In early 2022, papers published in JAMA and in NEJM showed that there is no effect on Covid-19 disease. Two trials are ongoing; one in the US and one in the UK. The UK trial under the PRINCIPLE trail group and undertaken by Oxford University was set up 16 months ago in June 2021 and is yet to report any data, but the hype around ivermectin as a cure for Covid-19 has thankfully calmed down.

For me, the takeaway is that no matter how good a scientist you might be, when you become convinced of something and you become committed, as a believer that faith is next to impossible to change. Even when the data has been shown to be flawed or fraudulent or simply wrong, you retain your original position. This is very worrying. We seem to prefer to defend a lie rather than lose face. Science is vital, but even the best scientists who seek to objectively produce science can have their thinking completely crippled by belief. Even Bill Campbell was brought maliciously into this debate. He was forced to renounce statements attributed to him supporting ivermectin’s use in Covid-19.

Ivermectin has been, and still is, a wonderful drug. It has had a huge impact on animal health, but of course its real human benefit is in treatment of River Blindness. A decision by Merck in 1987 to donate the drug to the WHO allowed worldwide use. Bill Campbell is very modest about his role in the Merck gesture, but it is clear that without his intervention, this might not have happened. Since the late 1980s, due to his discovery and his humanity, a new generation of children have grown up in Sub-Saharan Africa free of onchocerciasis. What a stunning legacy. That small boy running the streets of Ramelton in the 1930s and ’40s who became a Fulbright Scholar to the US has made a huge impact on our world and now, in gratitude, a life-size bronze statue stands in his home town. Had ivermectin been a miracle cure for Covid-19, that impact would have been even more stunning but that, it seems, is not to be. And Bill Campbell will be happy with that, as Bill Campbell is a scientist.

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