1 00:00:01,840 --> 00:00:07,000 Speaker 1: Welcome to Brainstuff, a production of I Heart Radio, Hey 2 00:00:07,080 --> 00:00:11,600 Speaker 1: brain Stuff Lauren Wogelbaum. Here in the United States, the 3 00:00:11,720 --> 00:00:15,040 Speaker 1: Food and Drug Administration or f d A is responsible 4 00:00:15,120 --> 00:00:18,159 Speaker 1: for approving medication for use by the American public, but 5 00:00:18,239 --> 00:00:21,640 Speaker 1: which means that they've reviewed the medications effects and found 6 00:00:21,680 --> 00:00:26,320 Speaker 1: its potential benefits to outweigh its potential risks. The FDA's 7 00:00:26,360 --> 00:00:29,639 Speaker 1: approval of any drug is no small matter. The process 8 00:00:29,720 --> 00:00:33,239 Speaker 1: is rigorous and often lengthy, and that's by design, but 9 00:00:33,280 --> 00:00:36,720 Speaker 1: it wasn't always that way. For the article of this 10 00:00:36,760 --> 00:00:39,760 Speaker 1: episode is based on hows to work. Spoke with Katherine Donovan, 11 00:00:40,000 --> 00:00:44,680 Speaker 1: a senior scientist at the Dana Farber Cancer Institute in Boston, Massachusetts. 12 00:00:44,720 --> 00:00:47,760 Speaker 1: She explained that back in the day, quote, drugs were 13 00:00:47,800 --> 00:00:50,960 Speaker 1: not developed on target. It was more like trial and error. 14 00:00:53,040 --> 00:00:57,600 Speaker 1: So what's changed Today's FDA drug approval standards developed sixty 15 00:00:57,680 --> 00:01:00,760 Speaker 1: years ago were largely the product of a single drug 16 00:01:01,000 --> 00:01:04,080 Speaker 1: and a woman who refused to give it FDA authorization. 17 00:01:05,640 --> 00:01:09,720 Speaker 1: But we're talking about Francis Oldham Kelsey. She was born 18 00:01:09,760 --> 00:01:13,560 Speaker 1: on Vancouver Island, British Columbia, in nineteen fourteen. She had 19 00:01:13,600 --> 00:01:16,200 Speaker 1: developed an interest in science early in life that She 20 00:01:16,200 --> 00:01:19,000 Speaker 1: earned a master's degree from McGill University in Montreal at 21 00:01:19,040 --> 00:01:21,400 Speaker 1: age twenty, and would go on to complete both an 22 00:01:21,480 --> 00:01:24,840 Speaker 1: m d and PhD in pharmacology at the University of Chicago. 23 00:01:26,520 --> 00:01:29,160 Speaker 1: Unlike many women in science at the time, Kelsey faced 24 00:01:29,160 --> 00:01:34,080 Speaker 1: opposition from the overwhelmingly male scientific establishment. She suspected that 25 00:01:34,120 --> 00:01:37,399 Speaker 1: her gender neutral first name helped launch her career. The 26 00:01:37,520 --> 00:01:40,320 Speaker 1: letter of acceptance for her PhD program was even addressed 27 00:01:40,360 --> 00:01:44,720 Speaker 1: to Mr Oldham. She later wrote, I knew that men 28 00:01:44,840 --> 00:01:47,400 Speaker 1: were the preferred commodity in those days. I do not 29 00:01:47,520 --> 00:01:49,840 Speaker 1: know if my name had been Elizabeth or Mary Jane 30 00:01:50,040 --> 00:01:54,640 Speaker 1: whether I would have gotten that first big step up. Nevertheless, 31 00:01:54,800 --> 00:01:57,800 Speaker 1: she eventually joined the University of Chicago as a full 32 00:01:57,840 --> 00:02:01,720 Speaker 1: fledged faculty member in ninety too. It was there that 33 00:02:01,800 --> 00:02:05,360 Speaker 1: she met and married fellow staff member, Dr. Fremont Kelsey. 34 00:02:05,520 --> 00:02:08,080 Speaker 1: In nineteen sixty, the couple moved with their two daughters 35 00:02:08,120 --> 00:02:11,000 Speaker 1: to Washington, d c. Where Francis accepted a position as 36 00:02:11,000 --> 00:02:13,880 Speaker 1: a drug reviewer for the f d A. A little 37 00:02:13,880 --> 00:02:15,880 Speaker 1: did she know she was about to alter the course 38 00:02:15,880 --> 00:02:20,760 Speaker 1: of history. Just as Kelsey was stepping into her new 39 00:02:20,840 --> 00:02:22,880 Speaker 1: role at the f d A, A new drug was 40 00:02:22,919 --> 00:02:26,919 Speaker 1: making the rounds in Europe, Africa, and Asia, known as 41 00:02:26,960 --> 00:02:29,680 Speaker 1: the litamide, the drug was originally developed in the early 42 00:02:29,720 --> 00:02:34,040 Speaker 1: nineteen fifties as a sedative. Donovan explained. Back then, it 43 00:02:34,120 --> 00:02:36,640 Speaker 1: was post war time and things were a little bit crazy, 44 00:02:36,880 --> 00:02:38,959 Speaker 1: so the world was in need of a decent sedative 45 00:02:39,000 --> 00:02:44,359 Speaker 1: to help people sleep. Patients taking the litamide for anxiety 46 00:02:44,440 --> 00:02:47,480 Speaker 1: quickly realized that it also worked wonders on an upset stomach, 47 00:02:47,760 --> 00:02:50,440 Speaker 1: and it soon caught on as a cure for morning sickness. 48 00:02:51,040 --> 00:02:53,600 Speaker 1: A few people reported tingling in their hands and feet 49 00:02:53,639 --> 00:02:57,600 Speaker 1: after prolonged use. However, these negative effects wore off as 50 00:02:57,639 --> 00:03:00,080 Speaker 1: soon as they stopped taking the drug, and so it 51 00:03:00,160 --> 00:03:04,200 Speaker 1: was generally considered safe. By nineteen fifty seven, it was 52 00:03:04,240 --> 00:03:07,320 Speaker 1: approved for over the counter sale in Germany and available 53 00:03:07,320 --> 00:03:11,560 Speaker 1: by prescription in dozens of other countries. The f d 54 00:03:11,680 --> 00:03:15,400 Speaker 1: A application for the linamide crossed Kelsey's desk in September 55 00:03:15,400 --> 00:03:18,840 Speaker 1: of nineteen sixty, just seven months after she began working there. 56 00:03:19,639 --> 00:03:22,520 Speaker 1: At the time, the FDA's approval process for new drugs 57 00:03:22,600 --> 00:03:26,080 Speaker 1: lasted just sixty days, during which the reviewer would wade 58 00:03:26,160 --> 00:03:29,040 Speaker 1: through a hodgepodge of assorted data from the trials done 59 00:03:29,080 --> 00:03:33,120 Speaker 1: with mice and other materials submitted by the applicants. Given 60 00:03:33,160 --> 00:03:36,720 Speaker 1: the littamne's popularity, it seemed destined to sail through with ease, 61 00:03:38,320 --> 00:03:42,560 Speaker 1: but Kelsey had some concerns. An English study which included 62 00:03:42,600 --> 00:03:46,240 Speaker 1: some reports of tingling and similar nerve related symptoms gave 63 00:03:46,240 --> 00:03:48,920 Speaker 1: her pause. She was also wary of the lack of 64 00:03:49,000 --> 00:03:53,160 Speaker 1: data regarding the drugs effect on pregnancy. Without further research, 65 00:03:53,280 --> 00:03:57,240 Speaker 1: she refused to approve the drug. It was a bold move, 66 00:03:57,720 --> 00:03:59,880 Speaker 1: Donovan said, there was a lot of pressure from a 67 00:04:00,000 --> 00:04:03,760 Speaker 1: own the world to approve it. Still, Kelsey stayed firm, 68 00:04:04,040 --> 00:04:08,400 Speaker 1: and one year later her caution was vindicated. Around the 69 00:04:08,440 --> 00:04:11,200 Speaker 1: same time that the litamide was under scrutiny for approval 70 00:04:11,240 --> 00:04:14,400 Speaker 1: in the United States, doctor William McBride of Australia and 71 00:04:14,480 --> 00:04:17,919 Speaker 1: Dr vindekun Lens of Germany both noticed a strange pattern, 72 00:04:18,440 --> 00:04:22,280 Speaker 1: an unusual number of children born with strikingly similar congenital 73 00:04:22,400 --> 00:04:27,279 Speaker 1: limb abnormalities, all within a relatively small geographic area. The 74 00:04:27,320 --> 00:04:30,480 Speaker 1: common denominator they discovered was that their mothers had all 75 00:04:30,560 --> 00:04:33,920 Speaker 1: taken the litamide for morning sickness early in their pregnancies. 76 00:04:35,600 --> 00:04:38,520 Speaker 1: McBride raised the alarm with a bombshell piece published in 77 00:04:38,560 --> 00:04:41,559 Speaker 1: the journal land Set in nineteen sixty one, sending shock 78 00:04:41,600 --> 00:04:44,720 Speaker 1: waves through the medical community. The littamide was pulled from 79 00:04:44,760 --> 00:04:49,040 Speaker 1: shelves in Germany almost immediately. Other countries followed suit shortly thereafter. 80 00:04:50,320 --> 00:04:53,320 Speaker 1: Kelsey's contribution in keeping the litamide largely out of U 81 00:04:53,360 --> 00:04:56,120 Speaker 1: S pharmacies might have gone unnoticed by the public if 82 00:04:56,160 --> 00:04:59,239 Speaker 1: not for a Washington Post article published in nineteen sixty two. 83 00:05:00,279 --> 00:05:03,280 Speaker 1: That same year, President John F. Kennedy awarded Kelsey the 84 00:05:03,320 --> 00:05:07,240 Speaker 1: President's Award for Distinguished Federal Civilian Service and signed the 85 00:05:07,320 --> 00:05:10,960 Speaker 1: key Father Harris Amendments into law. This key bit of 86 00:05:11,040 --> 00:05:13,800 Speaker 1: legislation is the reason that drugs in the US must 87 00:05:13,839 --> 00:05:16,839 Speaker 1: meet strict clinical trial standards in order to be approved 88 00:05:16,839 --> 00:05:20,520 Speaker 1: by the f d A. Kelsey would go on to 89 00:05:20,560 --> 00:05:23,440 Speaker 1: serve the FDA for forty five years, helping hone the 90 00:05:23,560 --> 00:05:29,280 Speaker 1: organization's drug approval process all the while. But curiously, and 91 00:05:29,400 --> 00:05:32,159 Speaker 1: that's not where the story of the litamide ends. In 92 00:05:32,200 --> 00:05:35,680 Speaker 1: the wake of its disastrous legacy, scientists began looking deeper 93 00:05:35,720 --> 00:05:38,159 Speaker 1: into the mechanism of the drug itself to discover why 94 00:05:38,200 --> 00:05:43,160 Speaker 1: it caused such unexpected side effects. Okay, so most drugs 95 00:05:43,160 --> 00:05:45,560 Speaker 1: that bind two nerve receptors in the body will only 96 00:05:45,600 --> 00:05:50,479 Speaker 1: bind to one. Donovan explained that the litamide actually recruits 97 00:05:50,480 --> 00:05:53,560 Speaker 1: other things to bind and that leads to those proteins 98 00:05:53,600 --> 00:05:58,160 Speaker 1: being removed from the body completely. This can be either 99 00:05:58,240 --> 00:06:01,680 Speaker 1: good or very bad to ending on which proteins get removed. 100 00:06:02,240 --> 00:06:06,320 Speaker 1: But by fine tuning the litamides molecular structure, A researchers 101 00:06:06,360 --> 00:06:09,960 Speaker 1: believed it might be possible to target specific bad proteins 102 00:06:10,000 --> 00:06:13,880 Speaker 1: for removal. In two thousand and six, this research revealed 103 00:06:13,880 --> 00:06:17,479 Speaker 1: the drugs potential for treating leprosy and plasma cell my aloma, 104 00:06:17,880 --> 00:06:21,840 Speaker 1: an uncommon type of bone marrow cancer. Since then, two 105 00:06:21,839 --> 00:06:24,200 Speaker 1: different drugs based on the structure of the litamide have 106 00:06:24,240 --> 00:06:26,400 Speaker 1: been approved for cancer treatment by the f d A. 107 00:06:31,200 --> 00:06:34,159 Speaker 1: Today's episode is based on the article Francis Kelsey stopped 108 00:06:34,160 --> 00:06:36,839 Speaker 1: the litamide in its tracks and changed the FDA forever 109 00:06:37,000 --> 00:06:39,320 Speaker 1: on hous to works dot com. Written by Joanna Thompson. 110 00:06:39,800 --> 00:06:42,080 Speaker 1: Brain Stuff is production of iHeart Radio and partnership with 111 00:06:42,120 --> 00:06:44,400 Speaker 1: hous to works dot com, and it's produced by Tyler Clang. 112 00:06:44,880 --> 00:06:47,920 Speaker 1: Four more podcasts my heart Radio. Visit the iHeart Radio app, 113 00:06:47,960 --> 00:06:50,640 Speaker 1: Apple podcasts, or wherever you listen to your favorite shows.