Authors: James Essinger and Sandra Koutzenko
The authors of this book with a reverential tone paint the portrait of a woman who doesn’t fit the popular imagination of a heroine but yet took one of the most consequential decisions in the history of medicine. The book chronicles the firm determination and clear-headedness demonstrated by Frances Kelsey as she faced up to the mighty onslaught of a giant pharmaceutical company equally determined to get official sanction for thalidomide, the villain of the story that was developed and marketed as a sedative but with catastrophic teratogenic adverse effects. The biography specifically illustrated how heroism, in this case, ‘consisted simply of saying ‘no’ when confronted with an enormous pressure to say ‘yes”. Appropriately portraying her as ‘one of the most eminent women in the history of medicine’, the book reveals how her background prepared her to be sceptical about the drug that turned out to be the most nightmarish toxin to ever grace the medical pharmacopoeia. Absolutely committed to the safety of the general public, and going by her training and gut instincts, the book revealed Kelsey to be a model for every healthcare worker at whatever level of the healthcare system they work. The book also conveys the story of the thalidomide disaster as ‘a painful example of corporate greed at its worst’ – both in terms of its underhand pursuit of profit, and in its subsequent reluctance to pay victims appropriate compensation (pages 2, 6 and 14)
The book sought to convey the underlying personal qualities that enabled Kelsey to do what no other person across the world did – to simply but insistently ask for clear evidence that thalidomide was a safe drug. In explaining why ‘Frances was the only public servant, the only drug assessment official in the world, who had an instinctive feeling that thalidomide was not to be trusted’, the authors argued that she was acting as much on her training, as on her sentiment. The authors acknowledged that at the outset there was no particular reason for her to doubt the safety of thalidomide, but ‘almost from the start she was wary of the application’ for its approval, particularly concerned that thalidomide might ‘represent a threat to the unborn’. But beyond her initial instinctive reaction to thalidomide, the book clearly showed how her experience and familiarity with drugs further entrenched her negative opinion of thalidomide. For example, the author said ‘the more she scrutinized the application…the more unsatisfactory she found it’. Indeed many of the objections the book said Kelsey had were based on the poor quality of the application which contained ‘insufficient data about chronic toxicity, incomplete detail about both the animal and clinical studies that had been performed, and limited information about the drug’s stability‘. Kelsey was also helped by her habit of reading the medical literature, and was aware as soon as reports started emerging of the occurrence of peripheral neuritis with thalidomide in the British Medical Journal. All these, the authors showed, fed into her decision to delay her approval ‘for as long as she could, until more information became available about the drug’ (pages 7, 9, 111, 118-119 and 126-129).
The most unnerving theme depicted in the book was its account of the tense encounters between Kelsey and Dr Joseph Murray, the pushy representative of Merrel – the company marketing thalidomide in the United States. Kelsey, the book noted, was a 46-year-old pharmacologist at the Food and Drugs Administration (FDA) when she handled the application submitted by Merrell in 1961 to licence thalidomide under the brand name of Kevadon, touted then as ‘a miracle sedative, without side effects’. The authors detailed how Murray ‘initiated over fifty contacts with Frankie’ and how he ‘engaged in a sustained and determined campaign to truncate review’ of its application. Despite the aggravation, the authors lauded Kelsey who ‘always kept her cool, even under considerable provocation‘, and how she faced down the ‘increasingly annoyed and frustrated‘ Murray who they said was making ‘insidious and in many ways unethical‘ attempts to get thalidomide licensed. What the authors depicted was indeed a dramatic and perilous standoff, the culmination of which was vindication for Kelsey whose caution the authors attributed to ‘professional conscientiousness‘. Her achievement was even the more remarkable when the authors pointed out that the thalidomide application was only the second such application she had ever handled, and that she has had no training for the tense saga that unfolded as she pitched her relative inexperience against Murray’s assertive onslaught (pages 29, 119, 123-124, 153 and 107).
In its comprehensive biographical account of Kelsey, the book extracted the factors that moulded Kelsey’s character which stood her well in the thalidomide epic. For example, the book documented her diverse genealogy and upbringing by a Scottish mother who was ‘born and raised in Edinburgh‘, a father who came from Australia, and her own birth and childhood in Canada. In chronicling her early education, the book noted that her school reports depicted her as ‘an intellectually gifted young woman who was by no means always inclined to be obedient‘. Equally pertinent to her later concerns about the safety of thalidomide were her subsequent studies in zoology, human biology, and embryology, and her research work on the adverse kidney effects of the antimicrobial sulfanilamide – an experience which the authors said ‘gave Frankie a good understanding of the principle that animal tests can be highly effective in predicting likely toxicity of new drugs’. And from her personal life, the authors pointed out that she was herself ‘very cautious‘ about taking drugs during her own pregnancies, and the authors felt this indicated that she ‘had no doubt whatsoever that substances such as prescription drugs and alcohol could cross the placental barrier‘. It is gratifying that, on account of her remarkable work, ‘honors came to her regularly, thick and fast’, throughout her life – including a presidential recognition by John F. Kennedy (pages 19, 65, 74-75-98 and 205-206).
The book provided a most revealing history of thalidomide which followed a path from promising birth to fateful notoriety. The book noted that it was manufactured in the 1950’s by Chemie Grunenthal, ‘the first German pharmaceutical company to supply penicillin to the German market’, but which later attained disrepute ‘for bringing drugs to market without sufficient testing’. The book narrated how former Nazis, Heinrich Muckter, Herbert Keller, and Wilhelm Kunz, inadvertently discovered the drug when they were attempting to produce inexpensive antibiotics from peptides. The book explained that it was thalidomide’s structural similarity to barbiturates, and its lack of toxicity in rats, that inspired Grunenthal to develop and market it as a sedative that ‘could not be used in a suicidal or accidental overdose‘. The book related how the company outrageously set out, without any human trials, to ‘simply distribute free samples of thalidomide for doctors to give their patients’, and to market it under multiple over-the-counter brands names such as Contergan and Distaval. The book charted the rapid rise, and the slow but eventual decline into infamy, of thalidomide as its adverse effects became widely recognised, all the while its parent company denying the facts and resisting all attempts to withdraw the drug from the market (pages 53-61 and 165-169).
The horrors of thalidomide stood out throughout the book, and in narrating this sad aspect of the story, the authors explored why it had such a devastating effect, and how these were eventually linked to the drug. The authors graphically described how thalidomide impacted more than 100,000 babies, half dying before birth, and the others developing a range of teratogenic effects – particularly phocomelia and neuropathy. The authors explained that thalidomide damages the brain when taken between the 20th and 42nd day of pregnancy, and that it took more than five years to link thalidomide to its disastrous side effects; the book attributed this delay to its 89 different brand names around the world, and to the fact that ‘no one really imagined that a drug could cause such disastrous effects on babies’. The authors also extolled the heroism of the doctors who recognised the dangers of the drug; Widukind Lenz, who painstakingly investigated the risks of the drug in Hamburg and vociferously raised his concerns, and William McBride, who reported on the ‘large number of birth defects’ in Australia in The Lancet. The book also featured the stories of remarkable victims of thalidomide such as Kev Donnellon, ‘one of the highest-profile casualties of thalidomide in the UK’ who was born with underdeveloped limb bones such that his two feet grew ‘directly out of his trunk’, and his few fingers attached directly to his shoulders (page 11-12, 15, 20, 118 and 158-166).
Kelsey’s story is one that teaches how sheer determination and commitment prevented what was an almost inevitable catastrophe from engulfing the United States. It is also an object lesson in the value of the strict regulation of pharmaceutical agents, and in the hazards of the temptation for profit to blind everyone to the risks of new drugs. This biography is also an inspiring lesson for all doctors in how to maintain their ethical stance when under pressure to bend the rules. The book is slightly marred by a distracting and uninformative prologue, and perhaps an excessively fawning hagiographic prose. A few chapters also suffered from rather disjointed and repetitious storytelling, irrelevant anecdotal fillers, and poor prose. The research is however detailed, and the authors created the right atmosphere of horror and escape that the thalidomide story evokes. Their heroine merited the praise the authors showered on her, and the narrative explores the traits that made her able to repel the tactics of the advocates of thalidomide.
The story of Kelsey and of thalidomide conveys several lessons for doctors and healthcare, and these permeate the clinical, research, and pharmacological spheres. Kelsey reflects the qualities of thoroughness, and the importance of the ethical character and moral courage required to keep people safe – the fundamental objective of healthcare. In her life story is inspiration for all doctors, no matter their hierarchical status, to hold to higher principles even when the stakes are not obvious. Her story contains profound lessons, and I recommend the book to all doctors.
Publisher, Place, Year: The History Press, Cheltenham, 2019
Number of chapters: 16
Number of pages: 266
Star rating: 4