Thalidomide is a synthetic drug developed in 1954 by German pharmaceutical company, Chemie Grünenthal, for use as a sedative in the treatment of insomnia and anxiety. Because of its purported atoxic nature, the use of this “wonder drug” quickly became widespread all over Europe. It was initially used to treat conditions like colds, headaches, and depression.
Problems began to arise in 1957 after the drug was remarketed for treatment of morning sickness in pregnant women. Over the next few years, doctors noted an influx of pregnancy complications, miscarriages, and birth defects. It wasn’t until 1961 that doctor Widukind Lenz of Germany connected this to the use of thalidomide during pregnancy. However, According to BBC News, when the drug was withdrawn, over 10,000 babies had been already affected. Complications included limb malformations, heart disease, facial malformations, and delayed mental development – all irreversible defects that the victims and their families would have to live with for the remainder of their lives.
Thanks to the meticulous work that Dr. Frances Kelsey carried out at the Food and Drug Administration (FDA), the approval of thalidomide was barred in the United States, thus sparing the country the disastrous effects of thalidomide.
The Thalidomide Scandal was not only a tragic medical mishap but also an extremely relevant event in the matter of corporate social responsibility. There are a series of reasons for which the actions of Grünenthal can be considered as the quintessence of irresponsible corporate behavior:
Inadequate Testing – Though Grünenthal had carried out some research on product safety, they failed to place any focus on gestation and effects on fetal development. The company did not give adequate consideration to the predictability issue, which is a matter of crucial importance whenever a new drug is released. Luckily, specific and stringent research practices that must be carried out in order for a pharmaceutical product to enter the market are currently implemented in many countries.
Wrongful Denial – For years, Grünenthal denied claims of thalidomide’s teratogenic properties despite concerns of neuropathy and congenital defects. Rather than issuing a recall while looking into its potential dangers, the company simply dismissed any claims. It was not until 2012, fifty years after the tragedy unfolded, that the company issued a formal public apology.
Research Manipulation – Grünenthal attempted to disrupt the scientific process by threatening the individuals raising concerns about its product. Private detectives were hired to spy on doctors and scientists. It also blocked the publishing of scientific journals addressing the negative effects of thalidomide, while bribing other journalists to praise its effectiveness. The company needed published articles testifying to the utility of the drug, so it used corrupt practices to obtain them. For instance, in Spain, a doctor declared he was prepared to write a short report whereby he would leave it to the company to “revise” the final draft. In the United States in 1959, Grünenthal and the American distributor of the drug, WM. S. Merrell, “convinced” Dr. Ray O. Nulsen, a Cincinnati physician, to publish a paper promoting Thalidomide safety during late pregnancy. In reality, as it eventually emerged, the article had been written by the medical director of the drug company.
Employee Selection – Grünenthal also showed irresponsibility in its employment process. Its affiliation with the Nazi party made it somewhat of a refuge for party members post-war. Dr. Heinrich Mückter, responsible for lethal testing of vaccines on prisoners, was appointed chief of research and production at Grünenthal during the development of thalidomide. Otto Ambros, Nazi war criminal guilty of mass murder, was appointed head of the advisory board.
Insufficient Compensation –Finally, the judicial ruling allowed Grünenthal to escape responsibility for their misconduct. After a 972-page bill of indictment was brought against the organization, the case settled out-of-court under terms of recompensation to the victims and their families. Sadly, surviving Thalidomiders are now entering late middle age, and many find their physical condition deteriorating. As a result, original compensation deals made in the 1970s are no longer enough to pay all the bills. Although, legally speaking, the likelihood of a successful legal challenge against the firm – already judged once and so long ago – seems next to zero. The lack of will to offer additional economic support to the victims denotes for the umpteenth time Grünenthal’s corporate irresponsible behavior.
Thalidomide Today
Despite the heartache thalidomide has caused, it has made its way back into the pharmaceutical industry for treatment of leprosy, multiple myeloma, and other conditions. With the drug’s reinstatement, national health departments took measures to ensure history would not repeat itself. This requires collaboration between patients, physicians, regulators, manufacturers, distributors and pharmacists.
Although national health administrations must take responsibility in preventing further distress, pharmaceutical companies play a crucial role and can foster the adoption of more effective regulatory instruments. A glaring example is represented by Celgene, which followed such a direction in the United States by developing the STEPS programme to monitor the use and distribution of thalidomide. The protocol requires thorough education for all parties involved, contraceptive counseling for both men and women, frequent pregnancy testing for women of childbearing age, and the patient’s informed consent distributed to all necessary parties. Additionally, the STEPS programme implements a managed distribution system limiting the amount prescribed/dispensed at a time, and a mandatory registry to monitor patient and physician information and compliance.
However, due to the presence of regulatory double standard around the globe, some pharmaceutical companies may tend to consider in an irresponsible way the profit versus safety tradeoff. Such a risk is particularly relevant in developing countries. Where domestic regulations are inadequate, corporations should take it upon themselves to limit the distribution of drugs because they are aware of the potentially tragic consequences arising from the absence of safety guidelines. Although these steps may result in loss of revenue, it will ultimately benefit the company as it avoids legal liabilities that may arise, as well as builds a strong reputation in both the regulators and consumers’ eyes for making morally and ethically sound decisions.
Brazil’s current situation is a prime example of the necessity for stricter health regulations. Thalidomide was removed from the Brazilian market in 1965 for a brief period, but was never fully out of circulation. It was rapidly reinstated later that decade following the revelation of its effectiveness in treating leprosy.
For many years, there was no adequate legislation in place in the country. It wasn’t until 2011 that Claudia Marques Maximino, in association with the Brazilian Association of Thalidomide Syndrome Victims, sought and achieved approval of four main stipulations to thalidomide regulation: education; no administration to women of childbearing age; national register of physicians and patients; criminal charges for misuse.
Though these standards have been successful in reducing Brazil’s overall risk to the fetus, there’s still roughly four million thalidomide tablets being administered yearly, meaning the risk is still very present. As a matter of fact, today, Brazil is still highly susceptible to the negative effects of thalidomide because of its high prevalence of leprosy and its poverty crisis. There is a large population in need of treatment, but a great percentage cannot afford it. As a result, restrictions and costs encourage consumers to obtain the drug through other means. So it is not surprising that a scientific study has recently indicated that thalidomide is still causing congenital disabilities in Brazil.
India is the only country that surpasses Brazil in number of leprosy cases, with Indonesia falling in third. However, it’s been many years since India has reported any new victims of Thalidomide. While Brazil’s new regulation has made a great difference, a few more measures can be adopted from India’s healthcare system. First, it would be beneficial for the Brazilian Ministry of Health to make thalidomide analogs and safer drug alternatives available for its patients. Secondly, India utilizes a hospital administration system for thalidomide. To combat illegal dealing and drug sharing, Brazil may consider implementing this method of administration to ensure the correct patient is receiving the correct dosage, thus eliminating risk of unintended users.
The thalidomide scandal has taught us important lessons we must not forget. The existence and implementation of sound legislation are vital in medicine. This requires collaboration between patients, physicians, pharmacists, manufacturers, regulators, and non-government organizations. But, most importantly, in the absence of adequate regulations, pharmaceutical companies must exercise a greater level of corporate social responsibility because of the inherent nature of their business operations, which directly impact the lives of millions.
Dear Kellisha,
Thank you very much for this extremely interesting post.
I completely agree with you, like the Enron collapse for Corporate Governance, the actions of Chemie Grünenthal related to the Thalidomide scandal can be considered as the quintessence of irresponsible corporate behavior. It is always important to stress the lessons learned from the past, especially taking into consideration that, as you have rightly highlighted, some issues (e.g., insufficient compensation) are still unresolved today.
It is also crucial to raise public awareness about the risks that the commercialization of Thalidomide currently poses. This is particularly true in relation to developing countries where a lax attitude to health and safety regulations might be present. The danger is serious and you are no alarmist. For instance, South African medical scientists have recently hailed thalidomide as a possible “wonder drug” in treating children with TB meningitis (see https://www.iol.co.za/news/south-africa/western-cape/dreaded-drug-saves-tb-kids-1880504).
In our globalized world, which is plagued by the chronic issue of double standard, the development of pharmacovigilance (see http://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/) and the adoption of a more socially responsible corporate behavior within the pharmaceutical industry are without a shadow of doubt of paramount importance.
Hello Costa,
Thank you for your comment.
Pharmacovigilance is exactly the type of protocol that needs to be established internationally. Though all drugs will have their side effects and some of these negative effects will inevitably slip through the cracks, pharmacovigilance programs accelerate the time to detection and correction of these adverse effects. Drug surveillance does not stop after the trial and development period, but must continue to be observed after the drug is released into the market to evaluate its true effect on the population as a whole.
The balance between profitability and safety is a really important issue especially for developing countries. Identifying the current situation and exploring the future development is very interesting.
Thank you for your comment.
I agree. Developing countries are so susceptible to such medical events because of their lack of regulation and knowledge. It is critical that pharmaceutical companies act responsibly alongside the national health departments to educate the population and minimize risk of adverse effects. While profitability is of great importance in any business, patient safety must always be the heart of every organisation in the medical field.
Kellisha,
You have posted a thoughtful retrospective of thalidomide, including some of the ethical and moral issues that are involved with its past use as well as its present circumstances.
Health authorities are indeed right to be circumspect about prescribing or using thalidomide, based on what has occurred in the not-too-distant past with it.
All of these features of the drug, its use, its treatment outcomes, as well as all of its known adverse events fall within the net of the discipline of ‘pharmacovigilance’, which Costa has mentioned above. Every drug product for any indication has known treatment effects (demonstrated in clinical trials), but these don’t occur in a vacuum (in isolation from additional physiological effects). For this reason, during clinical trials for drug products, a list of side effects, adverse events, and outcome measures are collected relative to placebo. In some cases, instead of placebo, a drug comparator is used – this allows head-to-head comparison against a ‘within-class’ treatment to determine which drug, if either, is superior. Sometimes superiority in outcomes needs to be weighed against inferiority with respect to heightened risks of side effects or adverse events.
What’s important to stress with this is that no drug targets a disease or condition with 100% specificity. So, for example: If we were to dose a patient with pseudoephedrine for use as a nasal decongestant, there are ‘side effects’ listed which include nervousness, restlessness, tremor, among others. However, these are not so much ‘bad’ effects, but are a result of how the drug functions physiologically in the body – by affecting vasoconstriction through α-adrenergic receptor activation in the muscles lining the blood vessels. So by trying to manipulate the constriction of blood vessels (which helps to reduce swelling in the nasal passages and improves the sensation of congestion), there are other effects in the body which occur holistically.
Thus, like anything being scrutinized by the fields of ethics, bioethics, morality, etc., there are no ‘bad’ drugs (or ‘bad’ chemicals, for that matter); they are each agnostic, arranged in three dimensions according to the rules of quantum mechanics, and perfectly do what it is that they do. In the world of toxicology, to paraphrase Paracelsus, ‘the dose makes the toxin.’ Even water has a lethal dose (typically measured with LD50) – and there are several examples of people with a psychiatric condition called “psychogenic polydipsia” consuming lethal quantities of water. The water itself is neither ‘good’ nor ‘bad’, but it is the manner in which it is used. We’ve seen several examples of certain drug products being banned for use for particular indications, when it’s become apparent that they’ve contributed to more potential (or realized) harm than benefit. And also, sometimes these drugs are found to be useful later for other (initially unintended) diseases or disorders. And other drug therapies have been found to produce profound risks, and seem to offer very little benefit, and therefore are withdrawn never to be used again (hopefully).
It’s indeed apparent that with great power comes great responsibility – where ‘power’ in this case is the power to influence, improve, or negatively affect lives – and the ‘responsibility’ can come from the pharmaceutical companies’ application of CSR. Their inherent information and knowledge asymmetry (knowing much more about the drugs’ molecular function, the public distribution, and behavioral patterns of use than the general public does) puts an ethical imperative upon them to do the right thing. Interestingly, this is also the same moral and ethical underpinnings of the pain management opioid crisis currently afflicting many industrialized nations. The Centers for Disease Control and Prevention (CDC) have suggested a number in excess of 66,000 overdose-related deaths in the U.S. alone in the year 2017. This is more than 150 people per day (on average). Because of this, of course, there are many who are working on stemming this problem, and the issue directly involves the pharma companies (creating the molecules), physicians (deciding to write the prescriptions), patients requesting pain medication (there are many more direct-from-patient requests for these treatments than ever before in the past), social media (for providing the psychological triggers through priming), and many other agents within a multifactorial scenario.
Importantly, what we have seen more in the past 20 years than ever before in the history of consumerism is that corporate social responsibility begets corporate financial performance — companies that do ‘good’ tend to do ‘well’.
And again, it’s not about trying to apply bioethics to a molecule, but balancing the overall calculus of the “risk to benefit” both for individuals as well as at population levels.
Thank you for your comment.
You have mentioned some great points. It is very true that there are no ‘bad’ drugs out there. They each serve a purpose, whether its their intended purpose or not. Here is where the specificity of the scientific process comes into play in the development of new drugs and assessing whether its benefits outweigh its risks.
Thalidomide as such has proven itself effective time and again for a vast array of conditions, so in no manner can be deemed a ‘bad’ drug. Rather, fault surely lies with the corporation who failed to explore all risks, and the regulatory agencies who lacked legislation stringent enough to avoid the disaster.
As mentioned, in pharmaceutics, with responsibility comes trust. The average consumer has very limited knowledge of the drug’s physiological properties, and therefore are entrusting the manufacturer to understand and communicate all relevant information concerning composition, dosage, and risks. This relationship is just as meaningful (if not more, concerning the health aspect) as one’s day to day relationship with friends and loved ones: there must be shared values (safety over profit), clear communication (adverse effects), and time spent nurturing the relationship (pharmacovigilance). Achieving each of these will earn the corporation a favorable reputation, thus influencing its customer retention, new customer acquisition, and financial gain. Full transparency will go a long way for the pharmaceutical company.
The opioid crisis in itself is a form of trust and dependency on the pharmaceutical industry and here the consumer will find themselves turning to the very same companies to provide yet another drug to correct the epidemic. Much effort has been placed into interventions to curb the crisis including education, monitoring and distribution programs, reversal drugs, and non-addictive alternatives. It is just a matter of following through with the implementation of these programs to improve the situation and fall back in line with the mission and values set forth by these corporations.