WASHINGTON – In the annals of modern medicine, it was a horror story of international scope: thousands of babies dead in the womb and at least 10,000 others in 46 countries born with severe deformities. Some of the children were missing limbs. Others had arms and legs that resembled a seal’s flippers. In many cases, eyes, ears and other organs and tissues failed to develop properly.

The cause, scientists discovered by late 1961, was thalidomide, a drug that, during four years of commercial sales in countries from Germany to Australia, was marketed to pregnant women as a miracle cure for morning sickness and insomnia.

The tragedy was largely averted in the United States, with much credit due to Frances Oldham Kelsey, a medical officer at the Food and Drug Administration in Washington, who raised concerns about thalidomide before its effects were conclusively known. For a critical 19-month period, she fastidiously blocked its approval while drug company officials maligned her as a bureaucratic nitpicker.

HER TENACITY MADE HER CENTRAL

Kelsey, a physician and pharmacologist later lauded as a heroine of the federal workforce, died Aug. 7 at her daughter’s home in London, Ontario. She was 101. Her daughter, Christine Kelsey, confirmed her death but did not cite a specific cause.

Dr. Kelsey did not single-handedly uncover thalidomide’s hazards. Clinical investigators and health authorities around the world played an important role, as did several of her FDA peers. But because of her tenacity and clinical training, she became the central figure in the thalidomide episode.

In July 1962, The Washington Post directed national attention on the matter – and on Kelsey – with a front-page article reporting that her “skepticism and stubbornness . . . prevented what could have been an appalling American tragedy.”

The global thalidomide calamity precipitated legislation signed by President John F. Kennedy in October 1962 that substantially strengthened the FDA’s authority over drug testing.

The new regulations, still in force, required pharmaceutical companies to conduct phased clinical trials, obtain informed consent from participants in drug testing, and warn the FDA of adverse effects, and granted the FDA with important controls over prescription-drug advertising.

As the new federal law was being hammered out, Kennedy rushed to include Kelsey in a previously scheduled White House award ceremony honoring influential civil servants, including an architect of NASA’s manned spaceflight program.

“In a way, they tied her to the moonshot in showing what government scientists were capable of,” said Stephen Fried, a journalist who investigated the drug industry in the book “Bitter Pills.” “It was an act of incredible daring and bravery to say we need to wait longer before we expose the American people to this drug.”

‘MOST FAMOUS’ REGULATOR

Kelsey became, Fried said, “the most famous government regulator in American history.”

Kelsey had landed at the FDA in August 1960, one of seven full-time medical officers hired to review about 300 human drug applications per year.

The number of women pursuing careers in science was minuscule, but Kelsey had long been comfortable in male-dominated environments. Growing up in Canada, she spent part of her childhood in an otherwise all-boys private school. She had two daughters while shouldering the demands of medical school in the late 1940s.

In Washington, she joined a corps of reform-minded scientists who, although not yet empowered by the 1962 law that required affirmative FDA approval of any new drug, demanded strong evidence of effectiveness before giving their imprimatur.

At the time, a drug could go on the market 60 days after the manufacturer filed an application with the FDA.

Meanwhile, pharmaceutical drug companies commonly supplied doctors with new drugs and encouraged them to test the product on patients

Thalidomide, which was widely marketed as a sedative as well as a treatment for pregnancy-related nausea during their first trimester of pregnancy, had proven wildly popular in Europe and a boon for its German manufacturer, Chemie Grunenthal.

By the fall of 1960, a Cincinnati-based drug company, William S. Merrell, had licensed the drug and began to distribute it under the trade name Kevadon to 1,200 U.S. doctors in advance of what executives anticipated would be its quick approval by the FDA.The Merrell application landed on Kelsey’s desk within weeks of her arrival at the agency. Immediately the application alarmed her. Kelsey rejected the application numerous times.