By Meredith Wadman of Nature magazine
In a new twist of a historic tragedy, 13 Americans who say they are survivors of thalidomide are suing four companies for producing and distributing the notorious drug. They say that the drug -- used by pregnant women for morning sickness until it was discovered to cause severe birth defects--affected more people in the United States than thought, and caused a wider range of deformities. And, they say, the companies have done all they can to hide these facts.
Thalidomide's devastating effects first came to light 50 years ago this month in the German newspaper Welt am Sonntag. In Europe, the drug was implicated in thousands of cases of malformed newborns, but in the United States the damage was limited because the Food and Drug Administration (FDA) refused to approve it for market. Until now, most US cases were thought to originate from thalidomide obtained abroad.
The lawsuit, filed in a Philadelphia court on 25 October, asserts that before thalidomide was pulled from markets around the world, samples were doled out to more than 1,200 physicians in the United States by three companies whose legal liabilities are now the property of Sanofi-Aventis US, based in Bridgewater, New Jersey. Separately, it alleges, citing an FDA memorandum that only came to light earlier this year, the company Smith, Kline & French, now GlaxoSmithKline (GSK), ran a clinical trial of the drug in the US involving 875 people, including pregnant women, in 1956-57. The suit claims that at least one malformed baby was born to a trial participant in 1958. (The German firm Grünenthal, based in Aachen, and Avantor Performance Materials, based in Center Valley, Pennsylvania, are also named in the suit.)
Sanofi-Aventis and Grünenthal say that they cannot comment on ongoing litigation.
Mary Anne Rhyne, a spokeswoman for GSK, says that the company "intends to vigorously defend itself against this lawsuit". She notes that Smith Kline & French never manufactured or sold thalidomide and adds: "The Plaintiffs' complaint is replete with scientific inaccuracies and misstatements."
The company challenges the claim that thalidomide can cause limb defects that are confined to one side of the body, as seen in nine of the plaintiffs. Conventional wisdom has long held that thalidomide's signature defect--a shortened, seal-like 'flapper' arm, known as phocomelia--affects both sides of the body.
The plaintiffs' lawyers argue that this assumption is unproven. "There are no representative, controlled studies documenting the true spectrum of thalidomide injuries," they write in the lawsuit. "A universe of thalidomide related injuries has been thereby excluded from diagnosis." They further suggest that "recently available studies published in medical and scientific journals reveal the flaws in the orthodox medical opinion".
When asked by Nature for relevant studies, the plaintiffs' lawyers at Hagens Berman Sobol Shapiro in Seattle, Washington, pointed to work showing one-sided limb defects in chick embryos exposed to thalidomide and thalidomide analogues (C. Therapontos et al. Proc. Natl Acad. Sci. USA 106, 8573-8578; 2009). The paper's senior author, Neil Vargesson of the School of Medical Sciences at the University of Aberdeen, UK, says that the one-sidedness was due to the physical orientation of the developing chick when the medication was injected into the egg.
Vargesson says his work does not confirm or deny that the plaintiffs' defects are the result of thalidomide. "The biggest issue facing the lawyers is persuading authorities that thalidomide gave rise to a range of other defects, including unilateral limb defects--or that it caused other damage without apparent limb defects at all." However, adds Vargesson, who has advised lawyers for potential plaintiffs in the United Kingdom who do not have apparent limb defects, "it's pretty clear that this drug did an awful lot of things and they don't always centre around limb defects".
Lewis Holmes, an expert in birth defects at Massachusetts General Hospital in Boston, says that the plaintiffs will have an uphill struggle to support their argument from the scientific literature because of the lack of systematic studies that follow up the offspring of women who took thalidomide during pregnancy. Holmes also notes that the relative paucity of thalidomide births in the United States means that few researchers there can speak with authority on the drug's effects. "None of us ever saw thalidomide-damaged children," he says.
This article is reproduced with permission from the magazine Nature. The article was first published on November 8, 2011.