MS. DIANE REHMAnd thanks for joining us. I'm Diane Rehm. Fifty years ago this week, the FDA received an application from a pharmaceutical company, wanting to market a drug that was being used for morning sickness in pregnant women in other countries. Dr. Frances Kelsey, a new medical officer at the agency, refused to approve it despite corporate pressure. That decision changed countless lives and the FDA itself. Yesterday, she became the first recipient of an FDA award named after her. She is 96 years old. I hope she's listening this morning at home. Joining us here in the studio, John Swann of the FDA. Good morning to you, sir.

MR. JOHN SWANNGood morning, Diane.

REHMDr. Douglas Figg of the National Cancer Institute, good morning, sir.

DR. WILLIAM DOUGLAS FIGGGood morning.

REHMAnd Gardiner Harris of The New York Times. Good to see you, Gardiner.

MR. GARDINER HARRISGlad to be here, Diane.

REHMJoining us from the BBC in Scotland, Dr. Neil Vargesson of the University of Aberdeen. Good morning, sir.

DR. NEIL VARGESSONGood morning.

REHMAnd throughout the hour, we'll hope that you will join us. You are always an important part of the conversation. Call us on 800-433-8850. Send us your e-mail to drshow@wamu.org. Join us on Facebook or Twitter. Dr. Figg, let me begin with you. Remind us, what is thalidomide?

FIGGWell, thalidomide was a drug that was originally developed for sedation. It was developed in late 1950s and was used very heavily around the world. Some 10,000 to 20,000 infants were born with deformities from their mother taking as little as one dose of thalidomide in the first trimester of pregnancy. And so at that point, it sort of died off from use but then was found to be active in the treatment of leprosy. It was used for many years for that. More recently, in the 1990s, it was found to inhibit angiogenesis, which is the blood vessel growth inside of a tumor. And so it has been tested for the treatment of cancer and ultimately got approval for the treatment of certain types of cancer.

REHMDr. William Figg, he is head of molecular pharmacology and senior scientist at the National Cancer Institute. He studies the use of thalidomide in prostate cancer patients. Dr. Vargesson, describe for us the kinds of birth defects that were caused by thalidomide.

VARGESSONSo the most common was limb defects, and the classic or stereotypical type of limb defect is phocomelia, which is where the proximal elements of a limb -- the humerus, the upper arm -- are missing. And you're left with the hand or the digits coming from the top of the shoulder. It more commonly affected the upper arm than the lower arm, but it also caused problems to the eyes, the ears, the heart, the liver, the genitals and the gastrointestinal tract. But most children that survived have limb malformations, and some have heart defects as well.

REHMAnd that is the voice of Dr. Neil Vargesson. He is at the School of Medical Sciences at the University of Aberdeen in Scotland. John Swann, as an historian at the Food and Drug Administration, talk about what Dr. Frances Kelsey did 50 years ago.

SWANNWell, 50 years ago, Dr. Kelsey's first assignment when she arrived at the agency in 1960, was to review an application for a drug that her superiors thought would be a pretty easy one to review, a drug application for thalidomide. Well, Dr. Kelsey received this drug on Sept. the 13th of 1960. And it soon became apparent to her that the data that were -- formed part of this drug application were closer to -- more testimonials than actual rigorous clinical data. So under the terms of the law then in effect -- the 1938 Food, Drug, and Cosmetic Act -- she determined that the data did not support the drug's safety. And thus, before the drug would automatically become effective and go on the market, she required the agency to go -- the firm to go back and submit additional data to show that it could be used in the long term.

REHMBut...

SWANNBut the application still was not satisfactory to Dr. Kelsey and her superiors. And in the meantime, the company was lobbying severely of both Dr. Kelsey and her superiors, and it wasn't just the company. There was a number of pharmacologists and other clinicians that they pulled in to also apply pressure to Dr. Kelsey because there was immense pressure on the company to profit from this drug.

REHMJohn Swann, historian at the Food and Drug Administration. And now, turning to you, Gardiner Harris, John Swann has talked about the pressure. What about the freebies that OB/GYNs were already getting of thalidomide here in this country?

HARRISOh, well, as John said, you know, the way you tested drugs back in those days was essentially, the company would send its experimental compound to doctors across the country and say, you know, try this out in your patients -- you know, and let us know how it works. And so they would sort of send the pills there, and the doctors would try it on their patients. There would be no controls. It wouldn't -- there wouldn't be any sort of rigorous testing of it. The doctor would simply give it to their patients and then ask the patients to report back how they felt.

REHMDo you know how long that that drug was in the hands of OB/GYNs before Frances got to the FDA?

HARRISI think it was, like, six months to a year. It was one of the mysteries, actually -- of the thalidomide controversy -- is that nobody really knew how much thalidomide there was out there in the United States. And in fact, for months after the problems with thalidomide became clear, the FDA and other government authorities, you know, put out advertisements and alerts to women across the country to -- if you have this drug in your cabinet, please, send it in. Please bring it back because, you know, it wasn't at all clear -- there was no control in the clinical testing. You know, right now, when a drug gets tested, it's done very rigorously. The doctors know precisely who the patients are. They often have controls associated with the patient. So one set of patients gets a placebo and other set gets the drug, so you can sort of compare the effect. None of that was going on, and, in fact, they didn't even know where the drug was at.

REHMI have a very personal story to tell. My -- our son was born September 12, 1960.

HARRISWow.

REHMWhen I was pregnant with him, I was having morning sickness. And the doctor offered me a drug, and I said, no, thank you.

HARRISWow.

REHMI'll just get through it. Who knows what that drug could or might have been, John Swann?

SWANNWell, as Gardiner said, the law simply didn't provide for enough controls over investigational drugs. That was the -- that was one of the horrors of this from the standpoint of the U.S. And when the agency finally did an accounting of how much drug was on the -- was not on the market because it was not approved, but how much was distributed through so-called investigational use -- and I say so-called because it became pretty clear to the agency that the company might have been trying to market this, build up an early market. But there were about 1200 physicians that had received this drug and...

REHMHere in this country?

SWANNIn the U.S. and almost 20,000 patients and over 600 pregnant patients had received thalidomide.

REHMDr. Vargesson, can you talk about the kinds of birth defects and how many were caused in Europe and around the world?

VARGESSONSo the drug was released in around 46 countries under different names, and at least -- and I think Dr. Figg mentioned at least 10 to 20,000 children were born with severe birth malformations, but there were an awful a lot of miscarriages as well. There's an increase in the miscarriage rights in those years of thalidomide use, so we'll never really know how many children were affected by it. But the infant mortality rate was extremely high as well. Forty percent died in the first year. So of the 10,000 to 20,000 children that survived, 40 percent since died due to internal organ malformations.

REHMAnd Dr. Figg, what about the number here in this country who were born with those malformations?

FIGGI don't have that number. I'm not sure it is known. It's usually thought of in Canada, Australia and Europe as the place where there were big problems. I'm sure there were some here, but it hasn't been recorded.

REHMHaven't I read 20 to 40 children here in this country?

SWANNWell, as we've heard already, it's very difficult to say exactly how many were affected because we can see the number of those that were affected in births, but about 17 -- about 10 from the investigational trial and about seven from imports.

REHMJohn Swann, he is an historian at the Food and Drug Administration. We'll take a short break and take your calls when we come back. 800-433-8850.

REHMAnd welcome back. We're talking about thalidomide and the difficulties, the horrendous birth defects that that drug caused around the world back in the late 1950s and early '60s. We're also talking about Frances Oldham Kelsey who, at the time, was the new medical director at the FDA who refused to approve that drug, saying that she had concerns about not only its efficacy, but its safety. Here's an e-mail from Ben, who says, "Please, name the company that wanted to sell thalidomide in the U.S." It was Merrell of Cincinnati, was it not, John?

SWANNYes. William S. Merrell was the licensee in the U.S. and also in Canada, the licensee of Chemie Grunenthal, the firm in Germany that manufactured the drug and...

REHMAnd here's a comment from Facebook. Cheri says, "We need more federal employees like Frances Oldham Kelsey, who won't buckle to pressure from corporations." How did that incident change the FDA?

HARRISWell, you know, what's interesting about this story is how it's been told over time and how the stories of Frances Kelsey reflect always the views of FDA of the day, right? I mean, when it was originally told, the first story was by Morton Mintz in The Washington Post. And he sort of talked about Frances Kelsey as this shining light of ethics in the midst of this squalor agency where there were no ethics, and in the midst of an agency that just rolled over to the industry. Now, that story was rather exaggerated. And it wasn't quite true that, in fact, she was part of a cadre of new tough scientists who had been brought into the FDA over the previous five years. And then in later years, in the '90s, when there were attacks on the FDA for being slow to approve drugs, Republicans actually sought legislation that would have essentially outsourced much of FDA's authority.

HARRISThe story of Frances Kelsey then changed again and was told again as, you know, she just had sat on this application and really done nothing and was not -- there was no great story here. She was just -- you know, once again, it was an example of FDA delay. And again, that story is untrue because, actually, she was one of the co-authors of one of the most important pharmacology books of the day. She was a very rigorous scientist. She was an MD and a PhD. And she knew, looking at this application, that it was just terribly lacking, not only in long-term safety data, but in the teratogenic data, you know, the data to see whether it would cause birth defects. And she knew that the only thing that the William S. Merrell company had given her were these sort of...

REHMHmm.

HARRIS...useless testimonials. So what's fascinating about the thalidomide story is how telling the story often tells you what the person thinks about the FDA because it is the iconic story.

REHMMm hmm. Hmm. Mm hmm. And Dr. Swann, how did this story change the FDA?

SWANNIt changed it on many levels, and it changed the way people look at FDA in many ways. Probably, one of the biggest changes was the impact it had on the way drugs are regulated because there was in place, a bill that was floundering in Congress that did not have much support from the White House, if any, that was sponsored by Estes Kefauver, who was the senator who was primarily interested in price-fixing. However, in the hearings that he conducted, he discovered other things about the drug marketplace, including problems with the drug effectiveness and clinical trial oversight as well. So he had proposed a bill, again, with an emphasis on price issues, but that bill was going nowhere. Then, during this time, thalidomide comes along, and the public finds out about what's happened in other countries. So it's the incredible response...

REHMInteresting.

SWANN...in the public.

REHMDr. Vargesson, turning to you, for years it was really a mystery of exactly how thalidomide caused these birth defects. Can you tell us about your own research?

VARGESSONYes. So the drug is complicated, and it breaks down into many different products. And some of the products are anti-angiogenic. They affect blood vessels, which is why it's used to treat cancer. And some of them are anti-inflammatory, so it inhibits the inflammatory response, which is why it's used to treat leprosy. So in collaboration with Dr. Figg, we've taken these different breakdown products and asked which of them -- or do all of them -- cause birth defects, and if so, how? And we found that it's only the component of the drug that affects blood vessels that causes birth defect. And we found that it's only a special type of blood vessel.

VARGESSONIt's the brand-new forming vessels that migrate through the body or through the tissue to help make the new tissues that are targeted by the drug. And because the drug is given at a time when morning sickness is at its peak, this is a time period when the limbs are being formed at that time as well. And that's why the limbs were so primarily targeted because the blood vessels were destroyed. Limbs can't form, and you're left with -- not much left.

REHMAnd, Dr. Figg, how is it being used now?

FIGGWell, I think Neil just hit on it. It's the inhibition of the blood vessels inside of a cancer that we're trying to target. Okay? And so it is approved for the treatment of multiple myeloma, a bone type of cancer. But it is also being tested in solid tumors -- in particular prostate cancer -- and showing very good promise there in treatment of prostate cancer with chemotherapy.

REHMWhat about HIV and Crohn's disease?

FIGGIt has been tested there as primarily TNF inhibitors to prevent some of the complications of HIV. But from an efficacy point of view, it is not very effective, and those trials have pretty much ended, is my understanding.

REHMNow, what about its use around the world for leprosy and the kinds of problems that may continue to result in terms of birth defects, Dr. Figg?

FIGGWell, there have clearly been some examples in Third World countries of children being born with birth defects from their mother taking thalidomide because of leprosy. And there's been examples in Africa and South America, et cetera. The current marketing of it doesn't have the prevention of trying to educate the patients as we do here in this country.

REHMAnd doctors as well, Gardiner.

HARRISSure. I mean, what -- there are fascinating aspects in the thalidomide story. I mean, it -- you know, what's great is that the FDA's history is essentially filled with examples of companies that essentially test their products on their customers, right? I mean, that's essentially what was happening with thalidomide. And there's been three to four major incidences in FDA's history -- you know, the first with Upton Sinclair's, you know, the book of "The Jungle" about the Chicago meat...

REHMMeat markets.

HARRIS...markets and how, you know, rats were in the food. And that led to the creation of FDA. Then in 1938, there was this cough syrup that led to more than 100 deaths, many of them children, because the company simply put its cough syrup into an industrial solvent like anti-freeze, didn't test it, sent it out, and all these children across the country died. That led to new legislation. Then thalidomide, again, a company didn't test anything. Then the Dalkon Shield, which then people realized, hey, we have to sort of do the same thing with medical devices.

HARRISAnd arguably, we're in a sort of a moment right now where there's, you know, the chocolate chip cookie dough. We also have eggs. There is this legislation on Capitol Hill that could transform the FDA, again, to give it new powers because people generally want things that they buy in the store or in the pharmacy to be safe. And lastly, the other interesting thing about this is the price issue. You know, the Kefauver hearings were all about price. People go nuts about the expensive things. And once again, thalidomide is probably among the most intriguing stories about price. If you go to Brazil right now, you can buy thalidomide for 7 cents a pill. In the United States, it's about 160 bucks a pill.

REHMWhy?

HARRISRight. Well, because the company that makes thalidomide in the United States for multiple myeloma just has decided to make a lot of money on it. And so you'll spend about $60,000 for a treatment for multiple myeloma in the United States using thalidomide. They now have a successor compound called Revlimid that you would spend about 200 bucks for in Brazil. And, you know, the company argues that it needed the money for research. But Dr. Figg basically at the NCI did most of the research, and then the clinical program at NCI did nearly all of the research paid for by U.S. taxpayers. So Celgene basically has paid for almost none of the research around thalidomide, and the shareholders and the executives at Celgene have made a killing on this drug.

REHMNow, help us understand, Dr. Vargesson, why it's used for leprosy.

VARGESSONLeprosy is an inflammatory disorder caused by bacteria, and it induces the inflammatory response, I think, through TNF alpha. And thalidomide works effectively because it actually prevents the release of this -- of TNF alpha. So it reduces the inflammatory response so that you no longer get the pain that is associated with the leprotic lesions, and that's why it's so effective. And it's used -- I think it's a standard treatment in Africa or India.

REHMBut what kinds of precautions are patients given, or are doctors given, before prescribing thalidomide?

VARGESSONIn the U.K, in the U.S., it's -- you would go through a very, very detailed set of procedures where you will be tested for pregnancy regularly. You'll be checked out to make sure that you -- that there's no chance of being pregnant. You're given lots of information. You have to sign lots of documents. You have to be seen by a GP regularly. In countries like India and Africa, it isn't so strict. And, I think, due to miscommunication of the drug's effects and how you must take it with oral contraceptives, that's where -- that's why babies are still being born today in those countries.

REHMAnd...

HARRISThe capsules in the United States, by the way, Diane, have a little symbol of a pregnant woman with a circle with a slash through it.

REHMBut the World Health Organization does not recommend use of it for even leprosy. Dr. Figg.

FIGGThat's correct. For other countries, that's the case. In this country, it is approved for FDA for the treatment of leprosy. And the reason why is the strict steps program to try to prevent any kind of birth defects, making sure that it is a registered physician that sent -- that's prescribing it. Certain pharmacies are allowed to give it out, but mainly it's the patient education aspect to make sure that the patient does not become pregnant while getting it.

REHMHow many cases of leprosy do we see in this country?

HARRISWell, that's the point here, Diane. I mean, let's be honest. This company, Celgene -- look, thalidomide is a wonderful thing in multiple myeloma. But Celgene got this drug approved for leprosy because there was absolutely clear data across the world that it would work in leprosy. Now, it knew very well that there was also a lot of hope for it in cancer, but Celgene, at the time that it was approved, didn't have any of the data around cancer. So it got it approved for leprosy, and then it basically sold it as a cancer medicine for --which was its unapproved use for seven years, wasn't it, Dr. Figg?

FIGGVery close.

HARRISAnd then it wasn't until the NCI actually developed the research that showed -- that proved that it used -- that the FDA approved it for multiple myeloma.

REHMGardiner Harris. He is science reporter for The New York Times and author of the mystery novel, "Hazard." And you're listening to "The Diane Rehm Show." We're going to open the phones now, 800-433-8850. First to Durham, N.C. and to Robert. Good morning to you.

ROBERTGood morning, Diane. Yes. I'm a retired radiologist and -- can you hear me?

REHMCertainly can, sir. Go right ahead.

ROBERTI'm a retired radiologist and was asked to look at the X-rays of a woman in -- a pregnant woman in her last trimester of pregnancy in 1963, and I noted phocomelia. It was very obvious on the X-rays. And we subsequently X-rayed the delivered baby, and it was a phocomelic baby. We raised the question of the thalidomide syndrome and went to the physician, the patient, every possible resource, and it was denied that she had taken thalidomide. In my review of the literature at that time, particularly Helen Taussig, who did very extensive writing on this in 1962. She pointed out that there was a lot of denial about this syndrome for medical legal reasons. And it was a fascinating experience for me and an illustration of the impact of the pharmaceutical industry on medical decision-making and a very egregious example of the necessity of more careful review of the use of drugs.

REHMJohn Swann, do you want to comment?

SWANNYes. I -- two things. One is, there was a presidential press conference in August of 1962 where President Kennedy reminded everyone to look in their medicine cabinets, and if they found any Kevadon -- the brand name of thalidomide -- get it off the -- get it off your shelves.

REHMHe personally gave Frances an Award.

SWANNThat's correct. About a week later, she was added to the list of those receiving the president's distinguished service award. And just one more thing, you mentioned what impact this had on FDA. One thing it did was it did show the country how important it was to have a strong science-driven agency reviewing applications like this.

HARRISAnd that picture of Frances Kelsey accepting the award from this very handsome president, you know, who's younger than she is -- Frances Kelsey was 40 or was 50 at the time.

REHMFifty-one, I think.

HARRISYeah, she was 51. That's right.

REHMYeah...

HARRISSo -- and she had this great, like, black dress with the hat and the white gloves and the white purse, and the president was actually in a -- yeah, he was in a light suit himself. And that picture of Frances Kelsey became the sort of iconic picture of the FDA which was sort of proper, prim and very smart. So it was a very important picture for the agency for a long time.

REHMAnd we do have that photograph on our website. So if you'll go to drshow.org, you'll see it. Even today, the FDA is under this kind of pressure. Turn those drugs out fast. Get that approval done more quickly. The pressures are still there.

HARRISYes, ma'am. And it's why Frances Kelsey's example is so important.

REHMSo important even today. Gardiner Harris. He's science reporter for The New York Times. We have three other guests with us. We'll take your calls, read your e-mail and your other messages.

REHMAnd welcome back. We'll go right back to the phones, now, to Barbara who's in South Florida. Good morning, Barbara. Go right ahead.

BARBARAGood morning. My mother was a military wife and pregnant with me late '50s, early '60, and suffered morning sickness the entire pregnancy. And she told me that they tried to get her to take this stuff. And I had -- have later learned that the military was one place where they really tried to push this drug to be used for such illnesses. And I was curious if anybody on the panel knew anything to that effect.

REHMJohn Swann.

SWANNWell, I don't know -- I'm sorry to say -- if the military pushed patients to take this. I do know that some of the cases in this country were a result of military families coming back with thalidomide in tow, and that's how we had about a half-dozen cases in this country. But I don't know what the policy was as far as pushing it. It was, you know, it was an effective treatment for morning sickness as a sedative, but -- yeah...

REHMInteresting. All right. To St. Louis, Mo. Good morning, Dawn. Thanks for joining us.

DAWNThank you so much, Diane. I know this is a really heavy topic, but I wanted to share an inspiring story. I was born in 1964. And a girl, a student in my high school -- it was shocking at first when I first met Laura, to look at her hands. She didn't have fingers. She had nubs. I don't know if it was because of thalidomide. But once you got past the shock of seeing her fingers, you never looked at Laura as somebody who had a handicap, a problem. And I don't know if she decided to join the band and play the drums because she wanted to prove that she could do it without fingers...

REHMHmm.

DAWN...but she did.

REHMShe did.

DAWNAnd she could write, and she could do everything...

REHMHmm.

DAWN...we all could.

REHMDr. Vargesson, is there an indication that some of the individuals who had birth defects would have manifested it in hands without fingers?

VARGESSONThe thalidomide caused a massive range of problems in the hands and the limbs. Normally, it would be the thumb and the small finger that would be first affected as well as the radius in the forelimb. But the digits were -- there's a wide range of digit problems in thalidomide survivors today. I'm not aware of someone having no fingers at all...

REHMHmm.

VARGESSON...but bear in mind also, there were an awful lot of thalidomide survivors with no limbs at all. So...

REHMExactly.

VARGESSON...a very wide range.

HARRISDiane...

REHMGo ahead, Gardiner.

HARRIS...I got an e-mail, after my story on Dr. Kelsey, of a woman who said she was one of -- a survivor in the United States. And she said that she had no thumbs. She had an extra finger. She -- her hips were permanently dislocated and with short femurs and that -- but that she had a full career in PR. She couldn't do anything athletic, of course. And the other thing that was interesting, I thought, about her e-mail was that she said that she's, of course, started through the internet to become connected with other survivors in the United States as well as in Europe. And apparently, in Europe, there's a very active network as well as there's a German trust fund that helps support survivors, but that in the United States, there is no -- because of the few number of survivors, there is nothing specifically that helps folks with the thalidomide difficulties here. So she has actually found that those in Europe have many more places to go and...

REHMI see.

HARRIS...much more support than those in the United States.

REHMThen we have an e-mail from Samuel who'd like to know -- he wanted to know, "Which company made the -- made thalidomide?" And you've already said it was...

SWANNWell, William S. Merrell Company of Cincinnati.

REHMAnd then, "What were the consequences to the company? Were any of those who leaned on the FDA and Dr. Frances ever punished?"

SWANNWell, as far as the company goes, there -- the agency attempted to take action against the company for unlawful distribution of the drug based on its widespread investigational study, assembled a great deal of evidence. However, the Justice Department decided this was not going to go forward, and that's the way it stood. As far as civil actions, I can't comment on those. I don't know. However, there were consequences in terms of the law.

REHMAnd...

SWANNThe law changed significantly.

REHMAnd finally, he'd like to know, "Is the company still in business?" Do we know?

SWANNIn the way firms have merged right and left these days, I think you'd have to have an...

REHMHard to know.

SWANN...anthropological degree to find out.

REHMYeah...

HARRISRight. I think it was eventually bought. I'm trying to remember who bought that.

SWANNYeah, I thought it became Merrell Dow...

HARRISYeah, that's right.

SWANN...and then it went to...

HARRISIt was part of Dow.

SWANNMm hmm.

REHMInteresting. All right, to Joan who's in Bonita Springs, Fla. Good morning, you're on the air.

JOANGood morning. I recently discovered your show, and I really appreciate it.

REHMI'm so glad. Thank you.

JOANGreat show. I was born in August of 1960 -- my mother's first child -- in New Jersey, and I later found out that thalidomide was available to her. But she's always been hesitant to take pharmaceuticals, and so she didn't. Then when I was growing up in Ontario in my teens, I had the occasion to spend chunks of time at a children's home in London, Ontario, with my younger sister (unintelligible) disabled for a different reason. And I met -- the problems, the thalidomide kids. I met groups of them at that time, and they told me why they looked like that. And it (unintelligible), finally, I went to my mother, and I said, my goodness, they're my age. I love my mother.

REHMOf course you do. She had the courage to say no. Joan, I'm afraid your line is breaking up on us, so I thank you for calling. Let's go to Traverse City, Mich. Good morning, Forest.

FORESTHi, Diane, I just wanted to tell you that I'm a young mother. And I suffered from morning sickness for almost nine months, lost a bunch of weight, had been to the hospital a few times, and I was prescribed two drugs. And one of them, I think, is being advertised on TV right now. Lawyers are advertising it, if you've taken this drug to please call them. And I read an article in Mothering Magazine about people using marijuana. And I had never used marijuana, and I decided to try the smallest amount. And I could actually drink a glass of water and eat something. And I think that's the only reason I have a healthy little girl right here.

REHMHmm. Interesting. Have you ever heard of any such thing, Harris?

HARRISOh, well, yes. I mean, I've written stories on the science behind marijuana.

REHMYeah...

HARRISI mean, there's actually an FDA-approved product called Marinol, which is the --which is THC. The essence of marijuana, you know, it is effective in nausea. There are other drugs that are more effective, but for some people, marijuana seems to work very well.

REHMNow, even today, yesterday there was a story about Meridia, a weight-loss drug, that the FDA has, I gather, decided to remove the statement that it's effective. It's staying on the market?

HARRISWell, actually, there are a group of FDA advisers meeting today to discuss what to do about Meridia. Meridia is a weight-loss drug. It does seem to increase the risks of heart attacks. The European regulators, in January, decided to withdraw it from the market because of those risks. In the United States, it is -- the label indication is that if you have any heart problems, you're not supposed to take Meridia. But the problem with Meridia is that it -- it's not very effective in getting rid of weight.

REHMAnd they said it produces, maybe, a 5-pound weight loss.

HARRISRight. About five -- little less than 5 percent in the trial of your weight, which is not, for most people, considered clinically significant. The weight tends to go right back on when you stop taking the drug. The drug is -- because of its heart risks, in the United States, you're only supposed to take it for two years or less. So what's the point? There are all kinds of questions about Meridia, and the FDA has been at something of a loss to figure out what to do with it.

REHMIt seems that almost every single day there's a question about a blood pressure medication or a heart medication or something, and we're still at that point where we don't know whether to trust the FDA or not. What do you think, John Swann?

SWANNWell, Diane, risk benefit is a consideration that FDA medical officers have to take into account every day. And it's something that Frances Kelsey had to take into account when she evaluated thalidomide, when she learned that it was causing a severe illness called peripheral neuritis. That was something that she realized. Here's a sedative. It's causing this serious disease. Is this worth the risk for a sedative? There are other sedatives available. She decided, no, it wasn't.

REHMDr. Figg.

FIGGYeah, I think, though, we have to be clear that it's impossible in the clinical trials to know all the side effects associated with drugs. And with large populations that receive the drug, you may start seeing patterns. And that's the point that you're seeing, that comes up in the news today, yesterday, et cetera. There can be genetic reasons that they cannot -- individual may not be able to metabolize, but that frequency may be at .01 percent. In a clinical trial of a thousand people, you may not have detected that that was the -- a side effect associated with that drug. So there is a little bit of expectation that, with time, you may find different side effects.

HARRISWhat's going on here, Diane, is the yin and yang of FDA regulation is speed and certainty, right? If you want access to medicines as quickly as you can, because, of course, in some diseases like...

REHMYou're desperate.

HARRISExactly. In cancer and others, you -- and in AIDS, in fact -- of course, in the late '80s and early '90s, there were protests outside of FDA offices because AIDS patients were saying, you know, you're holding up the cures that could save our lives. We don't care about certainty. We want something now. And so FDA set up an accelerated approval program. FDA has, in some of these life-saving instances, allowed drugs to be sold when there is scant evidence that that actually works. There's just sort of hope. And what the FDA has sort of asked is that once it then starts being sold, that trials be done to ensure that it works. But this issue about, do you emphasize speed to get things to needy patients, or do you emphasize certainty to make sure that people are not going to be hurt, is always a difficult one.

REHMAnd we're talking about the FDA, thalidomide and Frances Oldham Kelsey, who, yesterday, received a special award from the FDA named in her own honor. You're listening to "The Diane Rehm Show." Let's go, now, to Columbia, Mo. Good morning, Dan. You're on the air.

DANGood morning, Diane. Thanks for taking my call.

REHMSure.

DANI'm somewhat amused by the fact that the way the FDA's being portrayed here is -- as if this is a problem that happened in the '60s, and everything's okay there now. Marcia Angell, in the current edition of The New York Review of Books, does a review of a book written by a man who reviewed the history of the FDA. And she points out that all the problems that exist today, and one of -- a couple of those things have been alluded to by your panelists --one being that the drug manufacturers actually pay to have these tests done. And there's all kinds of conflicts of interest between the people that are on the FDA or people on the oversight committees that review these drugs. And then, you know, the fact that the drugs are marketed directly to consumers via television, you know, any kind of newsprint ad, just creates a market for, you know, the exploitation and over-treatment of people on -- and the FDA really needs to do something about this. We're really at risk.

REHMJohn Swann.

SWANNWell, as far as the membership of advisory committees -- and FDA does rely heavily on the input from advisory -- outside advisory committees -- in its decisions to approve or not approve products. That membership is -- their interests are certainly taken into account. If they have vested interests in those decisions, they'll be considering. So that is something that's very carefully monitored by the agency.

REHMHere's an e-mail from Francis who says, "I had a friend who has since passed away, who had multiple myeloma. Her doctor prescribed thalidomide, which was not on her insurance formulary. The purchase price without insurance was prohibitively expensive, so she did without." Dr. Figg, if the U.S. government funded the development of this as a cancer -- anti-cancer drug, can you explain to us why the pharmaceutical company is allowed to charge such an outrageous price per pill?

FIGGWell, Diane, this is one of those very controversial and very difficult questions. And most of science -- most of drugs that have been approved in this country have some form of government funding, whether it's funding the hospital that was doing the clinical trial, the investigators. But everything ultimately has some part of it that's coming mainly from the NIH. So it is hard for the NIH then to request that there's some kind of reduction in price. And ultimately, a decision was made about 20 years ago, 15 years ago, that we would not get into that aspect, that the NIH would not get into the aspect of trying to tell or have some control over pricing of drugs that may have had a component of federal funding.

HARRISDiane, it's a debate that's been going on in NIH for decades. And oddly enough, the head -- Dr. Figg's boss right now -- Dr. Harold Varmus is the one who decided, 15 years ago, to end this program to try to control the prices of drugs that were developed by -- essentially by NIH. So it's an entirely free market, and your tax dollars are going to work to help it.

REHMGardiner Harris. He's science reporter for The New York Times. Dr. William Douglas Figg of the National Cancer Institute, John Swann, historian at the FDA and Dr. Neil Vargesson at the University of Aberdeen in Scotland. Once again, congratulations to Dr. Frances Oldham Kelsey. Thank you all so much. Thanks for listening. I'm Diane Rehm.

ANNOUNCER"The Diane Rehm Show" is produced by Sandra Pinkard, Nancy Robertson, Susan Nabors, Denise Couture and Monique Nazareth. The engineer is Tobey Schreiner. Dorie Anisman answers the phones. Visit drshow.org for audio archives, transcripts, podcasts and CD sales.