Thalidomide: Nine things you didn’t know about the ‘poisonous pill’

Thalidomide was marketed to pregnant women as an antidote for morning sickness in the late 1950s, but the results were calamitous. An epidemic of babies born with various disabilities including limb, organ and neural damage led to its withdrawal from sale in November 1961. There were over 5000 known thalidomide survivors living worldwide in 2003, including 500 in the UK.

As a healthcare researcher, I had come to understand the thalidomide catastrophe as a systems failure: the disastrous outcome of an inadequate medications approval process. My dad, Dr Martin Johnson, was Director of the UK Thalidomide Trust between 2000 and 2014, and through him I had come to learn about its terrible impacts upon individuals and their families. I also understood that many survivors were still awaiting justice. However, in 2018, together with his co-authors Professor Ray Stokes and Tobias Arndt, dad published ‘The Thalidomide Catastrophe’, the first and only comprehensive history of thalidomide. Reading it led me to realise I had been seeing through a glass darkly. When laid bare, the thalidomide story is stunning, shocking and almost unbelievable. Here I share with you nine things I learned from the book:

Ed, aged 3

Ed, aged 3

  1. The full number of people affected by the drug reached tens of thousands. It is well known that thalidomide caused babies to be born with disabilities. However, it is highly likely that many other children died in the days and months after birth and that even more were miscarried or stillborn because of thalidomide. Johnson, Stokes and Arndt estimate that altogether, between 87,600 and 275,500 babies were affected.
  2. A single tablet had disastrous effects. Researchers have been able to link the days on which tablets were taken with specific forms of damage. For example, a tablet on days 21-22 after conception could cause damage to, or loss of the eyes. A tablet on day 24 could cause loss of the arms and a tablet on day 29 could cause loss of the legs. The key message from this is that the babies who survived thalidomide were those whose mothers took a tiny amount of the ‘poisonous pill’.
  3. Key players in the development of thalidomide are linked with the Nazi regime. The book explores this issue in meticulous depth and it is hard to summarise the evidence briefly. However, two things are clear. The first is that the Chief Scientist of Chemie Grunenthal, the Germany company who patented the drug, was Dr Heinrich Muckter. Muckter spent World War 2 (WW2) at an institution which tested drugs on Buchenwald concentration camp prisoners. The second is that Otto Ambros was a consultant for the Distillers Company, the British organisation which distributed Thalidomide in the UK. Ambros was sentenced to 8 years for his war crimes during WW2, which included using slave labour from the Auschwitz III-Monowitz concentration camp.
  4. Thalidomide seriously harmed adults too. When taken for more than 2 weeks, thalidomide could cause adults to contract ‘polyneuritis’, nerve damage involving symptoms such as tingling, numbness, excruciating muscle cramping and even partial paralysis. It could affect coordination, balance and the ability to walk. Altogether, around half a million adults were probably affected. “The Thalidomide Catatrophe” provides the response from Chemie Grunenthal to one affected surgeon who used the drug. “Thank you for your letter of 8th March 1960 in which you tell us you are increasingly suffering from paraesthesia and… probable polyneuritis… We wish to advise you that we have received no such reports to date” (p110). This letter was a lie: the company had received several reports and their false reassurance may have caused the surgeon to keep taking the harmful drug. As Johnson, Arndt and Stokes comment, these effects probably cost this surgeon his career.
    TIna Gallagher

    Tina Gallagher in 2002

  5. Warnings the drug was dangerous were ignored. To this date, Chemie Grunenthal claim that they could not have known about the harmful potential of Thalidomide. The evidence presented by Johnson, Stokes and Arndt makes this almost impossible to believe. For example, there is clear evidence Grunenthal’s Chief Scientist, Heinrich Muckter, received warnings a year before thalidomide even went to market from Dr Piacenza, an Italian doctor who undertook trials of the drug. Writing in 1956, Piacenza reported that the drug was unsuitable due to its toxicity. He described side effects in adult patients which included a whole-body rash and peripheral nerve damage. Reports from concerned physicians continued to be sent to Grunenthal, but the drug was not removed from market. Concerns were also raised about the potential harmful effects of thalidomide on unborn babies. For example, in 1959, scientist Dr Randolph Riemschneider raised concerns that thalidomide was causing birth defects in tadpoles he was experimenting with. As he later recorded, “we sent this information with photos to Chemie Grunenthal… Unfortunately, no answer was forthcoming” (p115).
  6. Even when its impact was known, Chemie Grunenthal continued to sell thalidomide. There were warnings that thalidomide was harmful before it even went to market. However, Chemie Grunenthal did not publicly acknowledge its harmful potential until 1961. In a speech on 14th July that year, Heinrich Muckter, Grunenthal’s Chief Scientist told his staff, “if I were a doctor, I would not prescribe Contergan [trade name for thalidomide] any more. Gentleman, I warn you… I see great dangers” (p41). Yet he didn’t withdraw the drug from sale until November that year. If he had pulled it immediately after his speech, more than 25% of the babies who were affected would have been saved.
  7. The impacts of thalidomide are sometimes invisible. Not all survivors were affected by the limb damage which is characteristic of thalidomide. As a toxic nerve agent, it also caused devastating hidden damage. Johnson, Stokes and Arndt report the situation of Julie Lane, whose mother had been supplied with the drug. Outwardly, Julie only had minor hand damage. However, at a young age, she developed epileptic fits. In her teens, she lost the use of her legs and later on, her arms. She also gradually lost her hearing and her sight. As her epileptic brain activity was not typical, her symptoms were misdiagnosed as being psychosomatic, and not of physical origin. This caused her problems to be stigmatised. However, a post-mortem conducted after she died aged 44 showed evidence of major internal damage which had been there since birth.
  8. Survivors still wait for justice. Chemie Grunenthal, the company which patented thalidomide, has never been held to account. A trial was called in 1968 but later suspended, apparently on the basis that “public interest in a continuation of the criminal prosecution no longer exists” (p.131). In the UK, Distillers, the company which distributed the drug paid out some compensation following a lengthy legal battle. However, survivors in some other countries have never received compensation, and all survivors are still waiting for an apology from Chemie Grunenthal.
  9. Some countries protected their populations from thalidomide. Several countries which considered licensing thalidomide denied or significantly restricted the sale of the drug. These included Turkey, East Germany, the USA and France. In Turkey, Dr Aygun undertook tests involving tissue cultures and concluded the drug was unsafe in 1960. In East Germany, the relevant officials had concerns based simply on the information supplied in the patent. They noted that due to the structure of the molecule, an “embryo-toxic effect” (p124) was possible. They refused a license. In the USA, Dr Frances Kelsey resisted significant pressure from the prospective American licensee company (Richardson Merrell) and managed to delay the approval of the drug until it was removed from sale in 1961. Her delay meant that only around 160 babies are estimated to have been affected by thalidomide in the USA. What these countries show is that the toxic properties of thalidomide were possible to identify using the technologies and processes of the time. Those governments which failed to prevent the distribution of thalidomide are partly to blame for the disaster, and should also be held to account.

 

In 2019, the generation of thalidomide survivors is turning 60. What “The Thalidomide Catastrophe” makes clear is this: the international sale of the drug was preventable. Its risks should have been identified by the company which patented the drug, those which distributed it and by the governments which allowed its sale. The damage which was initially caused has been extended over six decades by a failure to acknowledge and apologise for the harm that was caused. The need for an apology remains.

How to start a journal and beat the academic publishing racket

Academic publishing is a multi-billion pound industry, with profit margins reportedly higher than those of Apple, Google and Amazon. It has always struck me as a racket: academics sign over their work to private businesses for free, and then their universities pay the same businesses hefty fees in order to read what they publish. Academics are also responsible for editing these journals and providing the peer-reviews, usually for free.

It hasn’t always been this way. In a remarkable brief history of the academic publishing industry, Stephen Buranyi highlights the key role of Robert Maxwell, a brash business tycoon whose greatest desire was to “be a millionaire”. Maxwell arrived on the scene just after the Second World War, which was a key turning point in academic history. The post-war years saw a huge growth in the number of people attending higher education and also in the academic publishing trade. In 1950, there were 10,000 journals published worldwide, but by 1980, this was had reached 62,000. Robert Maxwell and other businessmen capitalised on this growth and took the opportunity to privatise what had previously been a largely non-profit sector. There is now growing awareness that this industry is both ludicrous and detrimental, unwieldily costly and harmful to the progression of science. However, solutions are slow in coming. While open-access journals are growing, the majority of these charge fees for publication that far outstrip real costs. For these reasons, I have been intrigued and encouraged to see the development of peer-reviewed open access journals which do not charge authors to publish with them. These include Musicology Research Journal (MRJ), whose Chief Editor is Dr James Williams, Senior Lecturer at the University of Derby, and Psychreg Journal of Psychology (PJP), whose Chief Editor is Dennis Relojo-Howell, founder of leading psychology blog Psychreg. These journals offer a solution that previously would have been regarded as impossible: they are both free to the authors and free to readers. I spoke to Williams and Relojo-Howell to understand more about their journals.

Why start a peer-reviewed academic journal?

As both Williams and Relojo-Howell attested, self-publishing an academic journal is a significant amount of work. So why do it? Williams said his motivation arose from his experience as a PhD Student and early career researcher. “Acceptance of manuscripts in current musicology-based journals can sometimes feel a little elitist. Editors and traditional publishers prefer to go with already-known academics, and are less likely to take on manuscripts from early-career scholars”. Williams also described his dissatisfaction with the traditional academic publishing industry, and its money-oriented focus. MRJ meets this gap by focusing on publishing the work of early career researchers, and by managing all copy-editing and manuscript management in-house. Relojo-Howell’s motivation was different. As a psychology blog editor, he had begun to receive blog post submissions that were overly long and technical. These posts weren’t suitable for publication as blog posts, but he could see their importance and academic merit. He created the journal to provide an outlet for these articles, and to broaden the overall scope of Psychreg. 

Ten steps for starting a journal

Whatever the focus of your journal, the steps for setting one up are similar.

  1. Identify the gap. What is the need your journal will meet? How will it improve information sharing in your field? Once you’ve identified this gap, you need to set the scope of your journal. Decide which types of articles you will include, and those you won’t.journal website
  2. Build a website that will home your journal. A full description of this process is beyond the capacity of this article (and my expertise!) but the key parts of this are to buy a domain name, find a web hosting company and then prepare the content within this. Popular web-creation platforms are wordpress.com, wix.com and weebly.com. Relojo-Howell suggested that it’s also worth looking into the Public Knowledge Project: this provides Open Journal Systems (OJS), federally funded software designed to support the set up and management of open access journals.
  3. Set up an editorial board. Both Williams and Relojo-Howell highlighted the importance of this. First, this group can provide the strategic direction and support that can get your journal started and help it grow. Second, this group can provide credibility to the project. As Relojo-Howell said, “When I started, potential contributors were only interested in who was on the editorial board. I have never been asked about the journal’s impact factor”.
  4. Involve associate editors who can provide support. Williams described the importance of including a multi-skilled team. “We have editors with different areas of expertise and varying skillsets, including people who are familiar with copy-editing and academic publishing”.
  5. Call for papers. You can spread the word about your new journal via social media, personal networks and by contacting other relevant university departments. Neither Williams nor Relojo-Howell had found this aspect challenging. As Williams said, “We have only ever advertised the journal in the UK, but we have received submissions from Australia, Canada, the USA and Asia”.academic publishing
  6. Manage your submissions. Traditional journals use manuscript-management software, but this comes with a steep price tag. “I contacted Emerald about their systems”, Relojo-Howell said, “but they asked for £38k”. Open Journal Systems (OJS) provides an alternative, free-to-use alternative, but this isn’t necessary. “I use a spread-sheet to keep on top of submissions”, Williams said. “It works fine”.
  7. Copy-edit and type-set your articles. While this may feel like a challenge, both Williams and Relojo-Howell said it was possible to do using widely available software. Williams said that he uses Word and Adobe programs to provide a professional-looking finish to his articles. Relojo-Howell commented on the fonts he uses: “I use a combination of paid-for fonts and some free Google fonts”.
  8. Apply for an International Standard Serial Number (ISSN). For us in the UK, this involves submitting an application to the British Library. Williams suggested that the British Library will expect to see evidence of around 3-4 previous publications and a commitment to continue publishing on a regular basis.
  9. Plan how to give your articles a Digital Object Identifier (DOI). DOIs are a string of numbers, letters and symbols used to permanently identify an article of document and link it to the web. Relojo-Howell recommends using Zenodo for this purpose. Initially funded by EU project funding, Zenodo is now open to all research outputs and offers its services free of charge for open access publishers.
  10. Wider registration. There are a variety of international platforms with which to register journals, including Web of Science, PubMed and SCOPUS. This type of registration seems to be a longer term process, however. Relojo-Howell said he had contacted both the Directory of Open Access Journals (DOAJ) and Thomson-Reuters, but they indicated that they would expect journals to be up and running for closer to five years before they would register them.

Other considerations

  • Finding peer-reviewers. My colleagues who edit traditional journals have described to me the challenges of finding peer-reviewers. While Williams and Relojo-Howell suggested this could also be challenging with new, open access journals, Williams suggested a personal touch could help support a positive response rate. “We approach academics who are working closely in the field of the article, and send personal requests. 60 or 70 per cent of the time, they agree”.
  • Clarify that you are a genuine academic ground-roots initiative. Unfortunately, at the same time that the genuine open-access field is growing, the number of predatory journals is proliferating at great speed. In a previous post, I clarify the warning signs of academic spam emails. However, if your potential contributors are concerned, let them know that the first clear distinction is that predatory journals ask for large sums of money and usually offer to rush through submissions at great speed. The second clear distinction is your academic board. You can signpost potential contributors to contact your board members for reassurances, if they are concerned.

Is it worth it?

Both Williams and Relojo-Howell admitted that their journals were time consuming and offered no financial benefits. However, what is clear is that starting these journals offers significant job satisfaction. As Williams said, “I saw it as a real problem – I wanted to help other graduating PhD music students… I don’t think I have reaped any rewards for myself, but I do know a lot of people now. It’s great for networking”. Similarly, for Relojo-Howell, the reward lies in contributing towards open science: “I wanted to demonstrate that dissemination of science can be reconstructed to become more democratic – a science that is shared for wider consumption”.