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Thalidomide: a debt of honour

Half a century after one of the world's worst medical disasters, hundreds of victims of the thalidomide scandal have reportedly now been given an apology from the government - and they are also being given £20m compensation …

In January 2010, Minister of Health Mike O'Brien announced a major new funding scheme that will help survivors cope with the changing needs of age. In a public statement made in the House of Commons, Mr O'Brien said:

"The government wishes to express its sincere regret and deep sympathy for the injury and suffering endured by all those affected when expectant mothers took the drug thalidomide between 1958 and 1961.We acknowledge both the physical hardship and the emotional difficulties that have faced both the children affected and their families as a result of this drug, and the challenges that many continue to endure, often on a daily basis."

Today, in Britain, there are around 460 "thalidomiders", now in middle age, all born some 50 years ago. Their mothers each took the drug thalidomide for morning sickness in early pregnancy. The result was a startling range of birth defects, most noticeably undeveloped limbs. But how did thalidomide ever get to be licensed? And was the British government really so negligent that it owes victims an apology?

Origins of thalidomide
In the 1950s the German pharmaceutical company Chemie Grunenthal took over responsibility for the continuing development of a new chemical compound synthesised by Ciba, a Swiss-based company. Ciba had found no use for the product, which had been named after its source, phthalic acid. That new compound was named thalidomide.

Chemie Grunenthal tried thalidomide out as an anticonvulsant for epilepsy treatment: it was of little use. It was also found to be equally ineffective as a treatment for allergies. The allergy trial, however, did reveal that the new drug was a useful sedative. It was as a sedative that the drug was found to be particularly helpful in combating morning sickness in pregnant women.

Thalidomide's biggest selling point was that it was completely safe, with no known side-effects. The drug was so safe that Chemie Grunenthal could not even establish what a fatal dose might be: large overdoses simply caused prolonged sleep. What no one suspected was the adverse effect that thalidomide might have on foetal development.

Retrospective enquiries would reveal that the first thalidomide baby was born, with damaged ears, in December 1956, but the event passed unnoticed at the time. Five more years would elapse before the dreadful truth emerged.

Marketed in the UK from April 1958, thalidomide was sold under a variety of names: Distaval, Tensival, Asmaval, Valgis and Valgraine.

The following years would see an increasing number of birth defects. In addition to babies born with missing and deformed limbs, doctors, nurses and midwives would see others suffering from deafness, blindness, cleft palates and malformed internal organs. Britain was hardly alone. Nearly 50 countries would eventually report the birth of thalidomide babies. The true number of thalidomide-affected pregnancies will never be known, as many thousands ended in miscarriage or stillbirths.
Worldwide, however, approximately 12,000 thalidomide babies were born, around a third of whom died before their first birthdays.

There would remain some 8,000 thalidomide victims across the globe; the largest single group, around 2,000, in Germany; in Britain there would be 456 long-term "thalidomiders".

Why there should be a surge in the incidence of birth defects was at, first, a puzzle. Some blamed the radiation from recent nuclear bomb testing. Of course, not all women who gave birth to babies with undeveloped limbs had taken thalidomide - and many women who had taken thalidomide during pregnancy gave birth to perfectly healthy babies.

It would only emerge later that thalidomide was relatively safe during pregnancy if taken only before the 34th day after the last menstruation, or after the 50th day.

There were just 16 dangerous days. If thalidomide was taken between the 35th and 37th days of pregnancy the result would be deafness and an absence of ears; between the 39th and 41st days an absence of arms; between the 43rd and 44th days phocomelia with three fingers; and between the 46th and 48th days thumbs with three joints. If taken throughout all the critical 16-day period, the consequence was likely to be all of these problems, as well as fatal internal problems.

It was an Australian gynaecologist and obstetrician, Dr William McBride of Sydney, who put all the clues together. He linked thalidomide with limb and bowel malformations in three children he had recently seen.

In December 1961, a letter from McBride was published in The Lancet expressing his fears. In Germany belated experiments on pregnant monkeys were simultaneously about to confirm Dr McBride's theory.

Thalidomide was withdrawn in the UK in a matter of weeks. The drug would, however, continue to be prescribed for several more months in Belgium, Brazil, Canada, Italy and Japan. Despite the British ban in late 1961, the last affected baby was not born until May 1963, a result of old drugs being retained by patients.

Internationally, the thalidomide tragedy would have been much more serious, had the drug been licensed in the USA. One woman was to be thanked for that. Dr Frances Oldham Kelsey, the newest medical officer with the US Food and Drug Administration (FDA), had persistently refused to licence thalidomide despite intense pressure to do so. Kelsey had previously worked in animal toxicity research (including work on drug effects in pregnancy). She steadfastly refused to approve thalidomide for use until she obtained better documentation of its effects.

It would later emerge that thalidomide had only "passed" safety tests performed on animals because full tests - particularly those involving pregnant animals - had not been done. German court hearings revealed that some tests were either conducted inadequately, or that the results were falsified.

Subsequent tests demonstrated that giving the drug to rabbits and mice reproduced thalidomide's characteristic deformities in their offspring, although it had no effect on rats.
In future, throughout the world's pharmaceutical industry, animal testing would become an increasingly important part of research whenever a new drug was being developed.

In the UK the Yellow Card scheme was set up in 1964 to provide a system for the early detection of emerging drug safety hazards, now the joint responsibility of the Medicines and Healthcare products Regulatory Agency (MHRA) and the Committee on Safety of Medicines (CSM), which are jointly responsible for running the scheme.

Since the Yellow Card scheme was set up, over half a million reports of suspected side-effects ("adverse drug reactions") have been reported, enabling the authorities to identify and take action on a wide range of medicines safety issues. Pharmaceutical companies have a legal obligation to report suspected serious side-effects to the MHRA.

Surprisingly, despite a worldwide ban on the drug in 1962, that was not the end of the thalidomide story, nor of the tragedy. In 1965, Israeli doctors discovered that thalidomide was useful in treating skin lesions caused by leprosy.

In 1998, thalidomide was licensed by the FDA for use in treating the symptoms of leprosy. The drug has been tested in the USA for its effectiveness in a number of other diseases, including AIDS and cancer. In Britain, patients suffering from leprosy and genital ulcers, as well as some kinds of skin disorders, rheumatoid arthritis, glaucoma, lupus, transplant rejection, cancer and AIDS, have found themselves being prescribed thalidomide as part of ongoing research projects.
Thalidomide has even been used experimentally to treat children with brain tumours. Ironically, just as the drug can prevent proper foetal growth, it can also inhibit tumour growth.

Given thalidomide's terrible reputation it is sad to report that the tragedy did not end in the 1960s. During the 1970s, 80s and 90s a fresh generation of more than 60 thalidomide victims were born to mothers in Brazil, women who took the drug in the early stages of pregnancy in the mistaken belief that it would ward off leprosy and thus benefit their unborn children. Three more Brazilian cases have been reported since 2005.

British victims of thalidomide did eventually receive begrudging compensation from Distillers, the UK distributors of the drug. Most recently, the company (now part of Diageo) has earmarked an extra £150m over three decades to be given to survivors.

As for the government's recent "apology" and "compensation", anyone who reads all of Minister of Health Mike O'Brien's carefully chosen words will quickly realise that his expression of "sorrow" does not amount to an apology, let alone any admission of liability. Nor, despite reports to the contrary, is the £20m being handed over by the Thalidomide Trust over the next three years to meet victims' health needs identified anywhere as compensation.

Perhaps, in law, the government does owe no compensation. But there is certainly a debt owed: the price of the safeguards we all enjoy today was paid by those who were not able to benefit from them.