A bitter pill

It destroyed blind faith in medicine but ultimately made it safer (12 minute read)

Although it was no longer a threat in New Zealand, there were still faint echoes of polio during my childhood. At school, there was a teacher who walked with a limp from polio she had contracted as a child. One of the books we read was Over My Dead Body, June Opie’s account of catching polio and being paralysed. There was an iron lung on display at the Museum of Transport and Technology, and it was an object of dread.

I can’t imagine how frightening polio must have been before the vaccine. The disease emerged in the early 20^th century, when other infectious diseases were declining. It struck the young, causing a paralysis which most often affected the legs but could affect the whole body, leaving the sufferer unable to breathe. There’s a terrifying photo, reproduced in the BBC article here, showing an American polio ward with about thirty iron lungs, from one of the epidemics in the 1950s.  

For the first half of the twentieth century, polio was a much-feared disease. In New Zealand, it killed hundreds and left many more with permanent disabilities. In the USA, tens of thousands died. Although it was known to be a virus, people weren’t sure how it spread, which amplified the fear when someone became ill.

Then, in the mid-1950s, there was hope. An American research team, led by Jonas Salk, had developed a vaccine. Within a decade, the disease would be almost eliminated from the USA, with other wealthy countries closely following. A few years after the Salk vaccine, Albert Sabin developed a different vaccine – one that was cheaper and easier to administer. It offered hope that the disease could be eradicated worldwide. Although polio is not yet eradicated, for many reasons, the vaccines have been a remarkable success.

Even today, people speak about the way parents were lining up around the block with their children, desperate to get them vaccinated against polio. It’s an example which is often brought up in discussions about vaccination. The argument I hear, time and again, is that because polio was so prevalent, people took it seriously and vaccinated their children. Today, diseases like polio and measles are no longer prevalent, due to vaccines, so people don’t take them seriously and don’t vaccinate their children.

There’s an element of truth in this. Complacency is one of three reasons identified by the World Health Organisation why people don’t get themselves or their children vaccinated. But it’s more complicated than that. In my first year of writing The Turnstone, I looked at smallpox vaccination, which first became available at the end of the 18^th century. I learned that people were remarkably wary of it, despite smallpox being prevalent and deadly in the 18^th and 19^th centuries.

What was different about the polio vaccine, I believe, was that it became available during a unique time in history, a time when people had unprecedented faith in science and medicine.

The 1940s and 1950s produced some stunning technological advances. One of the most remarkable was the use of antibiotics to treat bacterial disease. There was also DDT, which offered the hope that we could vanquish the pests which ate our crops and the mosquitoes which carried malaria.

But the 1960s saw that faith shaken. One of the reasons was the publication of Rachel Carson’s book, Silent Spring. I’ve written about this before, so I won’t repeat myself here. The short version of the story is that pesticides which we thought would solve many problems turned out to be losing their effectiveness and harming the environment at the same time.

But before Silent Spring, there was a drug called thalidomide.

I was born ten years after thalidomide was withdrawn from sale, but the word still made a chill run down my spine. People who are my age or older will probably get what I mean. In discussions about the safety of chemicals and medicines, I often hear people bring up the case of thalidomide, just as people often bring up the introduction of ferrets, stoats and weasels to control rabbits in discussions about biological control of pests. The thalidomide disaster was so horrific, and so memorable, that it still influences how people view the safety of medicines during pregnancy, even though many people today have never heard of it.

If you don’t know about thalidomide – and I realise that many younger people have never heard about it – it’s worth understanding the story. Not only did it have a powerful impact on society’s trust in science and medicine, it’s also a compelling case study in disinformation. There’s an excellent book about what happened co-written by a scientist who has studied the effects of the drug and a historian – it’s called Dark Remedy and well-worth reading if you are interested in medical history. Any information in this article which I haven’t referenced comes from this book.

In the mid-1950s, thalidomide went on the market as a sedative and as a treatment for morning sickness in pregnancy. When tested on animals, such as rats, rabbits, cats and dogs, not even extremely high doses would kill them, so it was marketed as completely safe. Because of its safe reputation, it didn’t require a prescription. The company marketing the drug in Britain claimed that it could be “given with complete safety to pregnant women and nursing mothers, without adverse effect on mother or child.” There had been no testing at all to support this claim – no pregnant women were included in any of the trials. Nor did even the animal tests include pregnant animals.

The testing of thalidomide had been slipshod, even by the standards of the day. The human trials were conducted largely by giving free samples to doctors to give to their patients, with little systematic monitoring or follow-up. Even then, there were side effects reported – side effects which the company’s executives, medical doctors themselves, ignored. About a year after the drug went on the market, there were cases of nerve damage reported to the company. The damage began with a prickling sensation in the feet and numbness in the toes. It could progress to a range of symptoms in the limbs, including numbness, cramping, severe pain and a lack of coordination. Between 5 and 20% of those who took the “completely safe” drug for several months would develop nerve damage, which was irreversible, even when people stopped taking the drug.

In Germany, where the drug was manufactured and most widely sold, doctors repeatedly wrote to the company with reports of serious side effects, particularly nerve damage. The company repeatedly replied that they’d received no such reports and that thalidomide was completely safe.

Thalidomide isn’t remembered for nerve damage, though, but for something altogether more tragic. We know now that when taken by a pregnant woman when her foetus is between 20 and 36 days old, the drug causes catastrophic damage. The most well-known symptom is a severe shortening of the limbs – some babies were born without arms or legs, just partial hands and feet attached to their torso. But other babies were born without ears, with facial damage, and with damage to internal organs and genitals. Some died in the womb, others died soon after birth, some died in childhood and some confounded medical predictions and are still alive today.

Over the next few years, there was an epidemic of birth defects – more than 10,000 cases worldwide (some sources suggest double that, and that only includes those born alive). But because there was such a diverse range of symptoms, doctors took time to make the connection between the birth defects and a drug the mothers had taken in early pregnancy. Some had taken as little as one pill. Most of the doctors assumed that the cases they saw were isolated, not knowing that other doctors were seeing the same thing. In that era, professionals were less connected to others in their field than they are today.

The company kept up a strategy of claiming that their drug was completely safe, resisting suggestions that it should require a prescription. Around 1960, one of the company representatives visited a medical clinic and was asked about the danger of nerve damage. When later asked how he responded, he said: “I did my best to foster confusion on the subject”. The company issued a report suggesting that the nerve damage was caused by other sedatives and excessive alcohol consumption.

By mid-1961, there had been multiple published reports about nerve damage in people who had taken thalidomide. Doctors at many hospitals in Germany were joining the dots, and stopped prescribing it. They could talk to their colleagues, meaning that they had more data. Doctors who worked out in the community continued to prescribe it. The company’s head of research and development admitted at a company meeting that he wouldn’t prescribe the drug. But their public strategy didn’t change. They told their sales staff to deny the link, and if that didn’t work, blame the reports on rare allergic reactions and rumours from competitors.

In late 1961, a Hamburg doctor saw a number of cases where babies were born with similar birth defects – specifically the limb shortening – and was convinced it was no coincidence. He went through the birth records for his city from 1930-1955 and found one case out of more than 200,000 births. Together with a lawyer who was the father of one of the babies, he placed advertisements in newspapers, to see if there had been any more cases. There had. By mid-November, the doctor had found fourteen cases of similar birth defects, and in all cases the mother had taken thalidomide during early pregnancy.

He contacted the company, first by phone and then by letter. By his own account, there were ten days of “intensive discussions” before the drug was withdrawn. The account in the book Dark Remedy says that the company threatened him with legal action and attacked his data. The German Ministry of the Interior told the company to withdraw it. The same executive who’d said in July he wouldn’t prescribe the drug refused to withdraw it. It was only when a German newspaper broke the story that the company withdrew the drug – from the German market. They wrote to distributors of thalidomide in other countries telling them of the withdrawal and stating that it was a response to sensational media coverage.

Then, in December, 1961, an Australian doctor published a letter in the medical journal The Lancet. He said that he had seen severe abnormalities in 20% of babies born to mothers who had taken thalidomide during pregnancy. Had others seen similar cases, he asked? The letter brought the drug to the attention of the medical community outside Germany and led to the withdrawl of the drug in most countries over the next year. However, it took Spain until 1985 to ban the drug.

Although company executives were put on trial, the trial was shut down and the executives walked free. The company was then granted immunity from further prosecution. It would be decades before the full story of political interference behind the ending of the trial would come out. The Hamburg doctor who first made the connection between the birth defects and thalidomide suffered a decade of attacks by the company on his credibility and integrity. Although many of the victims eventually received some compensation, they faced many obstacles in getting that compensation. It doesn’t necessarily provide enough to pay for their care, which can require complicated customisation of equipment to account for their specific needs.

Thalidomide changed the way pharmaceutical trials were done and how drugs were regulated. In the USA, for example, there were few regulations governing how trials were done prior to 1962. In response to thalidomide, rules came in requiring companies to submit detailed plans to the Food and Drug Administration (FDA) stating who would be testing the drugs, what qualifications they had and how they would conduct the trials. They needed to monitor the trials closely and report regularly to the FDA. Thalidomide also changed the way drugs were monitored once they were approved, with much closer scrutiny of reported side effects.

There’s a sting in the tale of the thalidomide story, though. The drug turned out to be useful in treating leprosy and some cancers. Many countries are careful when prescribing it, for example requiring women to take a medically supervised pregnancy test before being prescribed the drug and then regularly during treatment. But in some countries, most notably Brazil, there are still tragedies. Researchers estimated that from 2005-2010 there were around 100 children born with thalidomide-induced birth defects in Brazil.

Drugs (and for that matter vaccines) today are safer because of thalidomide. Nonetheless, when I look at the story of how this drug was sold to an unsuspecting public, and how unethically the manufacturer behaved when evidence of harm came to light, I have to sympathise with people who don’t trust medicine or drug companies or the organisations which regulate them. It’s far from the only example of unethical behaviour or regulatory failure. Among the most egregious recent cases was the marketing of Oxycontin, a dangerously addictive painkiller, in the USA.

Stories such as thalidomide, Oxycontin and DDT go a long way to explaining why some people don’t trust assertions of safety from medical professionals and scientists. In fact, as I write this, it strikes me as more surprising that so many do trust them. But what about the opposite, when scientists say something is dangerous? Why do some people not believe them then? Are the reasons the same?

These are crucial questions for understanding why it has been so hard for humanity to take action on climate change. At their core, they relate to how people perceive risk – what seems dangerous and what seems safe. It’s a topic which has long fascinated me – I worked in biosecurity risk assessment for 16 years, and even before that I was involved in both risk assessment and risk communication. So I’ll come back to this. I can’t promise it will be next week, as there are other disinformation topics I’d like to cover, but I will come back to it soon.

But it doesn’t seem right to end here. I can’t write about thalidomide without recognising the thalidomide survivors. Although they’ve faced a lifetime of challenges, many have lived independently, obtained degrees, had partners and children, and worked in a range of jobs. Thalidomide survivors became journalists, politicians, disability rights campaigners, entertainers and writers. However, they’ve also had many health problems and are experiencing age-related conditions prematurely. Their mothers, too, often suffered lifelong guilt. The suffering of those mothers and their children made us all safer, but it came at a terrible price.

Image credit: Melanie Newfield