Thalidomide – it’s not over yet – FT.com
By Andrew Jack
Published: September 22 2007 03:00 | Last updated: September 22 2007 03:00
Lorraine Mercer describes a letter she received recently from her local job centre urging her to return to work, and throws back her head as she chuckles. “How can I work? Just look at me,” she says. Laughing and talking are almost the only things she can do unaided.
She sits in an electric wheelchair that she controls with the three functioning fingers on her left hand. The four fingers on her right hand hang limp and useless. She has no legs, just tiny feet below her hips.
Mercer was rejected by her parents after her birth in 1961, and grew up in hospitals and residential homes. “I used to cry when they visited me because they weren’t dressed in uniforms like the doctors and nurses I was used to,” she says. She was put through several painful operations including an adjustment to her shoulders, and a metal rod was put into her back to support her twisted spine.
Mercer was a thalidomide child, one of an estimated 10,000 worldwide born between 1956 and 1963 whose mothers took a supposed wonder drug heavily marketed for stress and morning sickness in pregnancy. The drug had never been tested on pregnant animals – let alone women – and families and supporters of thalidomide children fought high-profile battles in the late 1960s and early 1970s to win compensation from the drug’s makers and licensees. In the UK, £20m went into trust for the 457 thalidomiders who survive. The case seemed closed.
But it’s now 50 years since thalidomide was launched, available without prescription across Europe. Thalidomiders are entering late middle age, and many find their physical condition deteriorating. Original compensation deals made in the 1970s are no longer enough to pay all the bills.
Mercer gets the highest level of support – £30,000 a year – from the Thalidomide Trust, which holds the compensation money. Apart from normal living costs, this compensation has to pay for a share of the salary of her three carers who look after her in shifts, modifications to her flat and equipment such as her new £18,000 wheelchair. She has to operate like a small business: filing forms to seek local authority assistance, and time logs for the helpers she hires. Every evening, she takes half a dozen medicines: painkillers, sleeping pills, anti-depressants and sedatives. “I get stressed just bloody living,” she says. “It’s financially and physically frustrating.”
Mercer’s hopes for a more financially stable future could rest with her friend, Guy Tweedy, who is sitting just across from us in her small living room. He interrupts to express his anger at Mercer’s problems: “Thalidomiders should not have to worry about these things,” he says firmly, in a Yorkshire accent. “They should be able to have fun.” Tweedy pulls up his sleeve to show me the surgical scars from his own three operations as a child to strengthen his weak limbs with metal and bone inserts, but smiles as he remembers one advantage to the five painful years he spent with his arm in plaster. “I was bullied at school a bit, but I was always able to stand my ground and hit back with the splint,” he says, jerking his arm to the left to illustrate the point.
He scarcely discussed thalidomide with his parents when he was young. It was only in 1991, when he was made redundant from a billboard company, that he decided to seek compensation. It took five years of doctors’ reports and legal battles for him to win a stipend from the UK’s Thalidomide Trust. His fight turned him into a campaigner, and now Tweedy is one of a small group of professional, articulate thalidomiders who are ready to fight a fresh and more ambitious battle over the drug itself.
It’s not just about the money. It’s a fight for control of the story of the drug, and an attempt to grasp the bigger moral issues. The resulting skirmishes are pitting thalidomiders against each other, their parents and the companies and governments involved in the tragic saga.
Fresh from victories in boosting payments and persuading the UK government to waive tax on them, Tweedy and fellow campaigners are making plans to seek compensation from the original manufacturer of the drug, Chemie Grunenthal of Germany. It’s a bold move, and it’s as much about morality as it is about cash.
The story of the world’s most infamous medicine began in the wreckage of postwar Germany. Hermann Wirtz, a partner in the long- established family company of Dalli-Werke, Maurer & Wirtz, a soaps and cosmetics manufacturer, formed the new subsidiary, Chemie Grunenthal, in 1946.
The company expanded rapidly, and by 1954, Grunenthal’s researchers had synthesised the chemical phthalimidoglutarimide, soon abbreviated to thalidomide. It seemed promising, but it was useless as an antibiotic, an antihistamine or an anti-convulsive. They searched for a suitable ailment it could treat. Testers reported feeling calm, and the company’s experiments on rats unearthed a striking characteristic: however high the dose, it appeared to have no toxic side effects. That suggested a powerful new market as a sedative to replace barbiturates, then widely used but frequently abused; often mixed with alcohol, they could also be taken in large doses by those attempting suicide.
There were few laws governing medicines in the 1950s. The regulatory void makes judging Grunenthal’s actions difficult, especially since many of the subsequent reforms in Germany and around the world were introduced principally in response to thalidomide.
On October 1 1957, Grunenthal launched thalidomide as an over-the- counter drug available under the trade-name Contergan. It was marketed as a treatment for morning sickness and stress, but was also sold as Grippex to fight respiratory infections, and in liquid form to help calm children. Within months, it became one of the best-selling medicines in the country, and was soon being distributed directly or under licence in nearly 50 countries.
But in 1959, doctors began asking whether it was causing peripheral neuritis, a numbness that can lead to severe pain and even partial paralysis. The company had confidential discussions with its lawyers about compensation claims. In late 1960, Distillers, which produced the drug under licence in the UK as Distaval, broke with Grunenthal’s practice by placing a warning on the label.
But Grunenthal pleaded ignorance in public, while in private using its influence with doctors and medical writers to suppress concerns about the drug. It was only in spring 1961 that it added warnings on the label, and in August that year it was placed on prescription in a number of German states. By then, peripheral neuritis was affecting an estimated 40,000 people.
Worse was to come. On Christmas Day 1956, the wife of a Grunenthal employee had given birth to a baby girl with no ears. The employee had given his wife samples of Contergan during her pregnancy. Their child became the first of thousands with disabilities caused by thalidomide. Countless more died in the womb. But the trail back to the drug took five years to establish.
Karl-Hermann Schulte-Hillen’s hair is white and his shoulders stoop, but the 78-year-old is still tall and imposing, reflecting the strength and stamina he needed to track down the reason for his son’s disability and seek redress. Documents have been lost or destroyed, memories have faded and most of those originally involved in thalidomide half a century ago have since died. But he and his wife Linde cannot forget.
When their son Jan was born in 1961 with short “phocomelic” (seal- like) arms, doctors told the couple that the likely cause was genetic. They predicted he would die within a day, and advised them to keep the birth secret and avoid having other children. “We were young students,” Linde recalls. “We were deeply hurt. We could not understand how it had happened and what we had done wrong.”
It was only several months later, after her husband and Widukind Lenz, a Hamburg doctor, had painstakingly tracked down dozens of other shocked parents, that they pieced together the truth. After eliminating explanations as diverse as foodstuffs and nuclear test fall-out, they found the common denominator. The mothers-to-be had all taken a sedative so widely used and extensively marketed as safe for pregnant women that it had seemed an implausible culprit.
At first, Linde Schulte-Hillen could not remember taking Contergan. But then she recalled that, when she was just one month pregnant and between two university exams, her father had died. Her sister had handed her a packet of the medicine after taking a tablet herself for the stress. “We still have the box. I just had one pill and you see the effect,” she says, nodding towards Jan, who sits across from his parents in front of a picture window overlooking the green hills of Nordrhein-Westfalen.
In November 1961, Lenz had collected sufficient evidence to contact the company with what Grunenthal would later call the “first plausible suspicions” of links between the drug and the disabilities. He then called the regional health ministry, which summoned executives for a meeting. The company did its best to deny the evidence, threatening officials by saying they would be liable for the lost sales if the drug were withdrawn. Shortly after, a weekly newspaper published extracts of Lenz’s data. Blaming media sensationalism and still disputing the facts, the company withdrew the drug on November 27.
For Karl-Hermann Schulte-Hillen, the battle was only just beginning. He worked with prosecutors to build a criminal case against Grunenthal executives. With limited resources, uncertain legal precedent, stalling tactics and the concealment of documents, the trial did not begin until 1968.
For two and a half years, he scarcely saw his family as he worked on the hearings. “I recall I had no father I could see,” says Jan, today himself a doctor with two children. Linde adds: “I took Jan on the opening day and said, ‘this is your trial.’ Then we would watch the news on television in the evenings and say, ‘let’s see how far daddy has come today.’”
In December 1970, the trial was stopped. The judges criticised Grunenthal for not acting more quickly on peripheral neuritis, arguing that the problems could have been foreseen. They said the company could easily have included a warning that its safety in pregnant women had not been tested. But they steered away from criminal convictions. The trial concluded with a decision of “minor guilt”. The phrase still riles Linde. “Grunenthal could have said sorry, but the company carried on as though nothing had happened. We had to have this trial. It took 10 years to acknowledge that Contergan was responsible.”
The compromise was a settlement from Grunenthal of DM100m, worth about £100m today, to support the affected children, or three times the overall total Contergan sales and more than the company’s DM84m total valuation in 1970.
Jan Schulte-Hillen believes that the new campaign to pursue Grunenthal ignores a wider point – that society has benefited greatly from stricter drug-testing regulations: “Thalidomide victims paid a terribly high price for the privilege of the western world to take all kinds of medicines. At the time, the solution was the only one to not make Grunenthal completely bankrupt. It is not right today if only they pay. So should the majority of the population which got access to drugs. We should be compensated by society.”
British thalidomiders won compensation after a long struggle by David Mason. A London art dealer, Mason fought for compensation on behalf of his daughter, Louise. When Distillers offered an all-or- nothing £3.3m settlement to affected families in 1971, Mason held out for more, sparking death threats from other parents and a court action that almost wrested away the wardship of his daughter.
Using the media and parliament, he raised the pressure on Distillers, buying shares, forcing an extraordinary general meeting and sharply depressing the share price by calling for an international boycott of the company’s products, including Johnnie Walker whisky and Gordon’s gin. In 1973, Distillers finally caved in, increasing its offer to £20m. The fight put a heavy strain on Mason. “I’m an old man now, my health was flattened by this and my relationship with my daughter was like a roller-coaster,” he recalls, sitting across a green baize table in his art gallery. “You take a pill and it defines your life. You don’t just have a thalidomide victim, you have a thalidomide family. Our friends, my parents, the family: we all had to cope with it. But the fight has been won. The thalidomiders now all have sufficient support.”
Many thalidomiders don’t agree. High inflation and poor investments sharply diminished the value of the trust. During successive campaigns in recent years, thalidomiders have helped win top-up funding from Distiller’s new parents, first Guinness and then Diageo.
If Guy Tweedy is the organiser behind the new wave of campaigns, then Nick Dobrik is the brains. Dobrik describes his upbringing as normal. Born into a comfortably-off family, he attended ordinary schools, graduated from Cambridge and worked for the accountancy firm Touche Ross before joining the family jewellery business. It was only in 2002, on reading an article about the difficulties of other thalidomiders, that he resolved to help.
When Dobrik moved on Diageo, it marked a turning point – in contrast with previous demands, it was the thalidomiders themselves who co-ordinated the talks, not the Thalidomide Trust. After months of negotiation, the company agreed a complex new multi-year deal in 2005 set to cost £153m.
Energised by their success, Dobrik and Tweedy both want to become MPs, for Labour and the Conservatives respectively. Their victories have also spurred them to launch one remaining, still more ambitious thalidomide campaign. “The real guilty part in this is Chemie Grunenthal,” says Dobrik. “They have done everything they can to evade their responsibility. It’s time they helped the thalidomiders lead independent lives.”
So the battle has moved back to Germany, where it all began. And the British campaigners are linking with others in Europe and north America. Germany’s 2,872 thalidomiders receive far less than British victims – a maximum of just €545 a month from the fund created by Grunenthal and since topped up by the German state. Those affected in Sweden, Canada and Japan also have some compensation. In Spain, where thalidomide was withdrawn more than six months later than in Germany, there is no money at all. Italian thalidomiders only won medical recognition last year, and promised support has yet to materialise.
A leading German campaigner takes me to a suburb of Cologne for a private viewing of a TV film, Eine einzige Tablette (A Single Pill). It’s a fictionalised version of Schulte-Hillen’s story: a lawyer and parent determined to find the cause of his child’s birth defects. Teaming up with a principled doctor, the pair pursue the ruthless company that made the drug.
The film was due for transmission in 2006. But at the last minute the courts imposed an injunction: Grunenthal, unsurprisingly, objected to many scenes. But, intriguingly, it was Schulte-Hillen who obtained the script and blocked the broadcast. He was angry at aspects of his portrayal, including a suggestion that his legal practice had once sought business from Grunenthal. The delay has frustrated the new generation of campaigners, but, barring last- minute problems, the film is due to be screened on German television in November. If it goes ahead, it may well relaunch the international debate about compensation.
The day after seeing the film, I arrive in the 17th-century building in Stolberg which houses Grunenthal’s headquarters, and am shown into a large boardroom. Sebastian Wirtz, grandson of the company’s founder and now the most senior executive, enters the room and extends a hand. His pleasantries are in English, but he quickly switches into German, as, unprompted by me, he raises the subject of thalidomide – and continues talking long beyond our allotted time. “Thalidomide is and will always stay an important part of our history. It’s something the whole family is very sorry about,” he says. “I was born in 1970 and was not alive at the time. I only knew my grandfather till I was three years old, but I could very clearly feel the gloomy atmosphere. I’m convinced one of the reasons for his death so young was as a consequence of the thalidomide tragedgy.”
He opens a file of extracts from the final court ruling, highlighted with a fluorescent yellow marker. “It’s extremely difficult with our perspective to look back to this time when the events happened. The court said there was no way Grunenthal could have known that the sedative could have these dramatic effects. According to everything I have read and heard, there was no way the tragedy could have been avoided. The tragedy for the Wirtz family is that we cannot undo it.”
Others disagree. Frances Kelsey, a novice regulator at the Food & Drug Administration, refused to approve the drug for use in the US in 1960. During hearings a decade ago on whether to reintroduce the drug [see box], she said: “We were concerned about the peripheral neuritis, even if the companies did not seem to be. Neurologists… felt that [it] could be serious, painful and often irreversible. The risk of developing this would not be justified in a drug that was used simply as a hypnotic and sedative, since there were other drugs on the market for this purpose.”
The likelihood of a successful legal challenge against Grunenthal itself – already judged once and so long ago – seems next to zero. But I ask Wirtz three times, phrasing my question in different ways, whether he thinks there is nonetheless a moral case for the company to pay out more. It has thrived in recent years, with sales likely to be close to €1bn this year. Its sister company, Maurer & Wirtz – in part controlled by the Wirtz family – has global cologne brands such as 4711 and Tabac.
Wirtz stresses that the original DM100m paid out was “gigantic”; that dealing with the tragedy cannot be reduced to a sum of money; and that there is no question of paying compensation or even seeking forgiveness in a way that suggests the company’s guilt. He says the controversial television film has created a “very difficult” atmosphere in which to negotiate.
But then he ventures that as the third generation of his family, he has “a new way of treating the issue, a different approach” and that the company is considering a “gesture”. He is struggling with whom to negotiate, in which countries and what sort of support – financial, medical or other – would be appropriate. “This takes time, it’s extremely sensitive,” he says in conclusion.
One thing is certain. If Wirtz does not come to the thalidomiders in the months ahead with more to offer them than his current defensiveness, they will find a way to come to him. They aren’t sensitive about opening old wounds. They are determined, and they are angry.
British campaigner Nick Dobrik is ready for the fight of his life. “This is going to be a nasty, horrible campaign which could take three or four years with dramatic tactics. With Diageo we just had to put the pistol on the table. With Grunenthal, we’ll have to shoot three times in the head first.”
Andrew Jack is the FT’s pharmaceuticals correspondent.
THE SECOND LIFE OF THALIDOMIDE
Thalidomide stopped being sold as a mass-market drug nearly half a century ago, but it never disappeared. It has since been used by tens of thousands of patients, and prescriptions are rising as doctors find new uses for the compound.
By the mid 1960s, Jacob Sheskin, an Israeli doctor, was already using it to treat ENL, a complication of leprosy. While the drug’s maker, Grunenthal, says it never again actively sought to use thalidomide commercially, it was in contact with researchers studying alternative uses and formulations, and, by 2003, had provided – at cost or free – more than four million tablets for treating ENL.
In 1998, the US Food and Drug Administration (FDA), which had refused to authorise the drug in 1960, approved a request for its use to treat ENL by the company Celgene, under the label Thalidomid. That allowed Celgene to sell it to doctors who were in fact prescribing it “off label” for multiple myeloma, a form of blood cancer. The FDA formalised this other use in 2006, and last year it generated $433m in sales for Celgene.
The patent on thalidomide has long since expired, but Celgene has been able to protect its market in the developed world through a monitored prescribing system which imposes tough safeguards to minimise the risk of tablets being taken by pregnant women. Celgene’s researchers are still studying thalidomide – and related compounds such as a less toxic derivative, Revlimid – for use in a range of other illnesses.
At the start of this decade the World Health Organisation advised against thalidomide’s use for ENL because of limited effectiveness and the possible side-effect of serious peripheral neuritis.
And while western thalidomiders are approaching 50, lack of monitoring elsewhere means there have been many children born in other parts of the world far more recently who have thalidomide- induced birth defects.
