The Tragic Children of Thalidomide

Babies were born with no legs, no arms. Some had flippers or digits emerging from their shoulders. Many were born with eye and ear deformities, severe internal damage such as anal atresisa, a condition where there is no external opening to the bowel, or malformed kidneys. Some were born with deformed genitals, or no genitals at all. And a few suffered brain damage.

The deformed babies had one thing in common: their mothers had taken the drug thalidomide. Marketed during the 1950s and early 1960s as a sedative, thalidomide produced 8,000 thalidomide babies worldwide. The babies suffered to a greater or lesser degree depending on the stage of fetal development when the mother took the drug.

Today, no pharmaceutical company produces thalidomide and the thalidomide babies have grown up. But for those still living, their deformed bodies are a constant reminder of a system gone awry. Chemie Grunenthal, and a number of other drug companies worldwide, produced and marketed thalidomide with an eye toward the bottom line. The company pushed thalidomide as a nontoxic tranquilizer that had none of the poisonous potential of the barbiturates then flooding the world drug markets.

There were, however, early indications that thalidomide was a less than effective drug that produced a wide range of side effects. Before it marketed the drug, Grunenthal had reports from doctors that thalidomide's side effects included giddiness, nausea, shivering, buzzing in the ears, constipation, wakefulness, and certain allergic reactions. And Grunenthal had results from its own experiments that thalidomide could cause a "disturbance in the nervous system following too high a dosage." This finding, however, did not stop Grunenthal from claiming that thalidomide could be taken "in higher doses" than recommended without any danger.

The company also had test results which suggested that thalidomide had produced an anti-hyperthyroid effect - something that was already known in the 1950s to be associated with birth defects. In addition, Grunenthal was aware of a 1956 test completed by the U.S. firm, Smith, Kline & French, which found thalidomide to be "totally worthless as a sedative."

Despite these warnings and based upon inadequate results from sporadic clinical trials, Grunenthal plunged into the market. The company marketed thalidomide under numerous brand names as an over-the-counter drug for a variety of purposes. The first thalidomide drug hit the German market on October 1, 1957 under the brand name Contergan. Contergan had many derivatives, one to combat the flu, and another as a sedative for adults. A third, Contergan Saft, was aimed at mothers for use in sedating their infants.

Grunenthal pushed its "completely nonpoisonous, completely safe" campaign in 50 advertisements in major medical journals, 200,000 letters to doctors around the world, and 50,000 circulars to pharmacists. By the end of the first year, sales had reached 90,000 packets per month. The drug found its way to all comers of the globe including 11 European, 7 African, 17 Asian, and 11 North and South American countries. Thanks to a wary U.S. Food and Drug Administration (FDA) officer, thalidomide was never mass marketed in the United Suites, but as a result of clinical trials many thalidomide babies were born in the United States.

As thalidomide sales soared in 1959, the complaints steadily grew. From Germany, Dr. Gustav Smaltz complained that thalidomide .vas causing giddiness and a slight disturbance of balance in his older patients. Then came a letter from Pharmakolor AG, a pharmaceutical company based in Basel, Switzerland, which read, in part: "To date 20 well-known doctors have told our representatives that when they themselves or their patients took one tablet of thalidomide they found themselves still under its effects the next morning, suffering from considerable sickness, and involuntary trembling of hands."

Grunenthal also heard directly from customers and from pharmacists who suggested that thalidomide could have an effect on circulation. Dr. Ralf Voss, a well-known Dusseldorf nerve specialist, wrote asking whether Grunenthal had any knowledge of thalidomide's effects on the nervous system. Despite three reports to the company about such effects on the nervous system, Grunenthal wrote Dr. Voss, "Happily, we can tell you that such disadvantageous effects have not been brought to our notice."

Grunenthal stepped up its advertising campaign. For a 1960 promotional mailing, Grunenthal printed another 250,000 leaflets which ignored all of the warnings that were surfacing from around the globe and adhered to the original company line that thalidomide was "non toxic," "completely harmless for infants," and "harmless even over a long period of use."

But letters continued to come in detailing the problems of thalidomide - doctors reported peripheral neuritis, a serious illness that attacks the nervous system. Grunenthal's sales department recognized that "unfortunately we are now receiving increasingly strong reports on the side effects of thalidomide, as well as letters from doctors and pharmacists who [want] to put it on prescription," but went on to observe that "from our side, everything must be done to avoid this since a substantial amount of our volume comes from over the counter sales."

Dr. Voss believed that a connection existed between long term thalidomide use and peripheral neuritis, and "had the strong impression that Grunenthal doctors did not doubt the validity of my observations but were merely anxious to prevent as far as possible their being made public."

Grunenthal then attempted to stave off adverse publicity. Through connections with a friendly editor of a German medical magazine, Grunenthal successfully delayed publication of a paper which showed a strong link between thalidomide use and peripheral neuritis. But the flood of evidence continued. "Sooner or later we will not be able to stop publication of the side effects of Contergan," an internal Grunenthal memo read. "We are therefore anxious to get as many positive pieces to work as possible."

The negative reports that were coming to light were so devastating that even the company's clinical research director was forced to admit that thalidomide caused serious problems. In a memo dated May 10, 1961, he wrote, "I personally maintain the view that there is no longer any doubt that, under certain circumstances that I am unable at present to understand or explain, Contergan can cause the nervous injuries described." He then added, "I consider it simply impossible that the company should officially adopt the standpoint that these reports are exclusively a matter of unqualified polemics."

The dam was beginning to break. Dr. Heinrich Mueckter, Grunenthal's staff doctor, admitted to his colleagues during a staff meeting in July 1961, "If I were a doctor I would not prescribe Contergan any more." But thalidomide was an overthe-counter drug and did not require a prescription. By August 1, 1961, three German states had already required prescriptions for thalidomide use. Slowly, Grunenthal began spreading the word about potential problems with thalidomide. In letters to licensees in developed countries, Grunenthal urged that words such as "nontoxic" be dropped, but the company continued to send out promotional literature to West Africa in which thalidomide was described as "completely harmless."

In Britain, Grunenthal's distributor was Distillers Company Biochemicals Ltd. (DCBL), a subsidiary of Distillers Ltd., the giant liquor merchant. In July 1957, DCBL signed a lengthy 16-year contract with Grunenthal to market thalidomide in England. From the beginning of this agreement, DCBL accepted everything that Grunenthal said about thalidomide and, as one observer put it, "was prepared to turn a vacuum of knowledge about thalidomide into specific assurances of safety."

In April 1958, DCBL began marketing thalidomide under the name Distaval. Its advertisements claimed that the drug was "completely safe," that "side effects are virtually absent," and that the drug was "nontoxic." Distaval was advertised as an answer to the "mounting toll of deaths due to barbiturate poisoning."

These advertisements were publicly aired despite the concerns raised by DCBL's development manager, R. Grasham. Grasham thought that the phrase "no known toxicity" was "rather sweeping" and suggested it be I replaced with "exceptionally low toxicity."

DCBL saw thalidomide as a potential wonder drug. DCBL marketed Distaval with no backup technical information on the , drug except for a one-sided report provided by Grunenthal.

By March 1961, DCBL had sold nearly 64 million thalidomide tablets. In the same year, it sent pamphlets to ', doctors claiming that: "Distaval can be given with complete safety to pregnant women and nursing mothers without adverse affect on mother or child." At that time, Grunenthal's knowledge (on which DCBL relied) of thalidomide's effects on the reproductive system was at best speculative. Grunenthal failed to conduct a clinical trial to examine thalidomide's safety in pregnancy, nor did the company conduct any reproductive studies on animals.

When DCBL did run tests on thalidomide, it tended to ignore those results which cast a negative light on the drug. Two months before Distaval went on sale in Britain, the British Medical Journal published the results of DCBL's own clinical tests. James Murdoch, one of the men who conducted the tests for DCBL wrote, "it would seem unjustifiable to use the drug for long term sedative or hypnotic therapy, pending the results of more detailed study of its long term effects in a larger series of patients, notably those suffering from mild or moderately severe hyperthyroidism."

By the winter of 1961, neither Grunenthal nor DCBL could ignore the information detailing thalidomide's devastating effects. In November, Grunenthal pulled the drug off the market and in December, DCBL followed suit. For thousands of pregnant women who had used thalidomide as a sedative, however, it was too late. In all, approximately 8,000 thalidomide babies were born in 46 countries. Some estimates put the number of stillbirths at twice that number.

In 1967, a public prosecutor in Achen, West Germany, drew up a bill of indictment charging Grunenthal with intent to commit bodily harm and involuntary manslaughter. After more than two years of trial, the court, with the agreement of the prosecution, dropped the criminal charges and Grunenthal agreed to pay the German thalidomide children $31 million, with the German government agreeing to contribute an additional $15-27 million.

In 1973, after years of litigation, threatened boycotts of Distillers' products, and a massive pressure campaign administered by a group of concerned citizens representing the thalidomide children, Distillers was forced to pay two million pounds a year for 10 years into a trust fund to care for 400 British thalidomide children.