Dr. Frances Oldham "Frankie" Kelsey was a pharmacologist and physician who for many years worked in the New Drug Division of the US Food & Drug Administration. Born in Canada in 1914, she was graduating from college in the midst of the Great Depression, and getting a master's degree seemed a better choice than standing in bread lines. A year later, she faced the same choice, and went on to get her Ph.D. in pharmacology--and in the process connected with a professor who encouraged her, pointed her in new directions, and crucially, when the time came, connected her with an opportunity in the US. That embarked her on a path that led to her meeting her husband, Fremont Ellis Kelsey, also a Ph.D. in pharmacology, getting her M.D., and ultimately becoming a medical officer at the FDA.

So why do we care about a "faceless bureaucrat"?

Because Frankie Kelsey is the "faceless bureaucrat who looked at the NDA (New Drug Application) for thalidomide, and started asking questions and insisting on real answers.

Thalidomide was developed in the 1950s in West Germany, and marketed as a sedative and morning sickness preventative for pregnant women, and advertised as completely safe, virtually no side effects. It's true that, unlike other sleeping pills on the market at the time, you effectively couldn't fatally overdose on it. It could cause peripheral neuritis in some cases, but the company assured everyone it cleared up completely when use of thalidomide ended.

No one looked at effects on unborn babies. It was assumed, despite the fact that fetal alcohol syndrome had been known for decades, that drugs wouldn't cross the placental barrier, so they couldn't affect the unborn baby.

In 1960, Frankie Kelsey was assigned to review the NDA for thalidomide when Wm. S. Merrell Corporation applied to market it in the USA. By that time, it was approved in not only West Germany, but the UK, much of Europe, Canada, Australia, parts of Africa, Japan. Merrell expected their application to sail through.

Kelsey asked for studies showing that the peripheral neuritis cleared up after thalidomide use ended. She asked for animal studies. She asked for the US clinical studies--and when Merrell gave her what they had, she said she wanted real studies, not testimonials.

No one had bothered to do the controlled clinical studies that are required and expected today.

There had been some animal studies involving pregnant rats, but not intentionally and systematically looking for effects on the fetus. The data they had said it was safe, but they didn't have much data. As it turned out, thalidomide turns out to be a case where animal studies wouldn't have been as useful as hoped, because thalidomide affects primates really differently than most other animals. (For instance, it doesn't even have much of a sedative effect on rats, which should have been a clue that maybe rats in this case weren't the useful model they are for many other drugs.)

And there was no systematic collection of data on results in patients given thalidomide either in the countries where it was licensed, or in the "investigational" use of it in the US.

Dr. Kelsey didn't initially have any reason to suspect it would cause serious birth defects; she just knew that the data provided didn't remotely establish safety. And she did not see it as her job to rubber stamp the application merely because it had been approved elsewhere. It was her job to be sure it was safe, so she kept asking for the data that would show that.

Merrell tried to pressure her, calling her and calling her bosses. They provided German papers, with translations--but one of her colleagues in the department had worked in West Germany for several years and read German fluently. The translations weren't accurate.

As it became clearer and clearer that the peripheral neuritis really didn't always clear up when use of the drug stopped, she started to be concerned about possible effects on the unborn baby.

And as she held up the application for months, doctors in the UK and Australia started reporting on normally extremely rare birth defects, failure of the arm and bone legs to form and grow, appearing in unexpectedly high numbers in babies born to women who had nothing in common except having used thalidomide in the early stages of their pregnancies.

Frankie Kelsey prevented thalidomide from being widely released in the US before clinical experience in the countries where it had been released proved it should never be released, at least for its proposed uses. I say "at least for its proposed uses," because in fact years later it became clear that thalidomide's terrible effects in fact had real clinical promise in treating some forms of leprosy as well as some forms of cancer. As a medical librarian, I was shocked when I first started seen reports of it being in use again, but in specific circumstances with those conditions, it can be extremely beneficial. Yet even in those cases, it has to be handled extremely carefully, because it remains extremely dangerous to unborn babies.

Frankie Kelsey was a hero, and was widely recognized as such at the time. Today, I think most people have no idea who she was, nor do they know what thalidomide is unless they are or know someone who is one of the small category of patients who do actually benefit from it. She ought to be remembered, and this book is an excellent, engaging, very readable account of her life and her most notable professional contribution to the well-being and safety of Americans using medications for their health.

I received a free electronic galley of this book from the publisher, and am reviewing it voluntarily. ( )