BRIAN LAMB, HOST: Eric Lax, what is "The Mold in Dr. Florey`s Coat"?
ERIC LAX, AUTHOR, "THE MOLD IN DR. FLOREY`S COAT": It`s a book about the story of how penicillin came to be something other than an odd curiosity to a drug that saved millions of lives and ushered in a medical revolution. The title comes from -- just to get that out of the way, the title comes from an event that happened in 1940. In May of 1940, the scientists at Oxford who were responsible for this, Howard Florey and his team, did the first mouse protection trial with penicillin. And it was so extraordinary in what the result was, even with the pitifully weak penicillin that they had, that it was clear that this was a revolution in medicine.
At the same time that that was going on, the evacuation from Dunkirk was beginning, that night, May 26 . And they realized that the Nazis might come at any moment. And so the question was, they wanted to continue their work, but how could they do that if there was an invasion? And they sought, How would we destroy everything at Oxford but be able to carry it on, because they needed to work with the particular strain of mold that they had. And one of the people on the team, Norman Heatley, said, You know, if we take the spores and put them in our clothes, nobody will see them. They`ll lie dormant forever, and whoever gets to a safe place can extract them and we`ll go on from there.
And when I had a title, when I -- "The Mold in Dr. Florey`s Coat," I knew I was OK for the book because "The Development of Penicillin" was not going to be a book that would get somebody to pick it up, so...
LAMB: Back over a couple of things -- 1940, right before the Americans got into the war, what was Dunkirk?
LAX: There were several hundred thousand British and Allied troops stuck in France, trapped in France by the advancing Germans. And it looked as though they were going to be stuck there forever and that very few -- they thought maybe they`d get 30,000 or 40,000 out. And suddenly, this great flotilla of boats came from England and literally saved hundreds of thousands of them, this great moment, I think, in English -- in history, and I think it was great for the psyche of Britain at a terrible time in the war, when it looks so bleak for them.
LAMB: What`s a spore?
LAX: Spore is just a little bit of mold that`s there, waiting to germinate and grow into something bigger. It`s the seed.
LAMB: What`s mold?
LAX: Mold is like bacteria. They`re two different classes of things, but what they -- they -- they kind of eat up matter. And it -- mold is everything from what you see on bread when it`s been sitting too long in your breadbox or cheese in your refrigerator. It has a wonderful life of its own. And it turns out in the case of penicillium notatum, it has within it a wonderful little capability of attacking a bacteria that`s really deadly to us. And like Joshua at Jericho breaking down the wall, stopping the wall, the wall breaks down, the bacteria can`t replicate, and the disease is halted.
LAMB: What`s penicillin?
LAX: Penicillin is the drug that is taken from penicillium notatum. And it`s so -- it`s so interesting to think of what -- what medicine was before penicillin came along, before the first class of -- before antibiotics were here, is that we were subject to diphtheria, to typhus, to typhoid, to tuberculosis, to any number of diseases that could just lay you out in a second. Literally, a scratch from a rose thorn could start a staphylococcus infection that would lead to death.
Penicillin absolutely changed that. It was suddenly a completely different kind of medicine. Really, doctors -- the only thing doctors really had to give you before penicillin -- and the sulfa drugs, to some extent, which we`ll probably talk about -- was sort of the confidence that they were doing everything that medicine offered, which wasn`t much, and the hope that this would prevail. And if it was properly administered by somebody with a good bedside manner, that lasted the patient until they died.
LAMB: Why or when did you think that this was a book?
LAX: I think when I had the title. I had read an obituary that Wolfgang Saxon (ph) wrote on Anne Miller, who was a character in this book. She was really the first person who was pulled from death`s door by the drug. She was in Yale New Haven Hospital, had been -- for a month had been languishing after a -- of an infection following a miscarriage, had a temperature of 105, 106, wasn`t eating, was wasting away. Sulfa drugs weren`t working. Transfusions weren`t working, operations, nothing was doing -- she wasn`t eating.
And she was literally at death`s door when her doctor, who was also treating John Fulton (ph), who was a professor at Yale and a friend of Howard Florey`s, remembered that Fulton, who was just down the hall with a viral infection, by coincidence, had talked about his friend, Howard Florey. And he said, Is there any chance of getting some of this stuff? And as it turned out, there was a little bit to be had at Merck. And after many phone calls, they were able to get 5.5 grams, about a teaspoon -- less than that, even -- which was about half of the amount in the United States at that time.
Within a few hours, her temperature was down. By the next day, the bacterial count in her blood was gone. After a month`s recovery, she went home and lived a perfectly happy life until she died 55 years later at the age of 90.
LAMB: You have pictures here of most of the characters in your book.
LAX: Right. That`s Fulton at the...
LAMB: But start with Howard Florey.
LAX: This is Howard Florey. Howard Florey was an Australian who came to England as a Rhodes scholar in 1922. What I -- what I love about that picture of him -- he was a very strikingly handsome guy. He looks to me like somebody out of a Fitzgerald novel. And he was -- he could be both very winning in his personality, and also he was a fierce competitor. So when he was -- he was -- in tennis, for instance, he would glower across the net at his opponents, male or female. It didn`t matter that you won, you had to win as convincingly as possible. So even if you were ahead and you let somebody have a point, he would be furious. He had these -- he had what we would call bad social skills today.
LAMB: When did he live?
LAX: From 1898 to 1968.
LAMB: How important was he to the actual discovery of penicillin?
LAX: The penicillin effect had been noticed by a number of people, most prominently by Alexander Fleming, who was -- if anybody associates a name with penicillin, it`s Fleming`s. The story goes, in 1928, Fleming returned from a vacation in the fall and had left a number of petrie dishes of bacteria that he had been growing for an article that he was writing around, and he was kind of cleaning up and suddenly noticed, as a friend came by to see what was happening -- he`d had one that had been discarded and was sitting in a -- in a -- in a -- just a bin of petrie dishes that were being put into disinfectant….was above it because there were so many in there.
He said, Oh, yes, there`s this one. He pulls it over, and he says, Gee, that`s -- that`s funny. He had this very laconic style. Because as I described earlier, suddenly, there was this -- there was this ring where all of the bacterial walls had just crumbled, the bacteria were dead, where this mold that had come onto the plate while he was away and, in a sense, infected it, or at least contaminated it.
And he looked at it , That`s very strange. And he started working with this. And he said, Well, now, what is it in the mold that`s doing this? And he ran a number of experiments, and he -- the best way to get the mold to grow is you put it in -- in a protein-rich broth, and then the mold would get on there and you would extract -- you would try to extract the active ingredient from it.
Penicillin was non-extractable. They had this broth that had this very powerful antibiotic in it, but it also had every contaminant you can think of, so it was useless as a medicine like that. And every time -- he could get it into ether, and pull it out, but then he had a drug this was in ether, which was no good. But as you tried to get the ether out, it was like the Scarlet Pimpernel. He was there, and then he was gone. And he couldn`t -- for four years, he worked on this, and as did some others, and no one was ever able to figure out how you got the active ingredient out.
And penicillin really became a curiosity. He wrote a paper on it, did some experiments with it. By 1932, really, he was -- he was done. And it was only at the end of 1938, when Florey and his collaborator, Ernst Chain, at Oxford were looking around at things with anti-bacterial activity that they came upon the Fleming paper and said, Oh, that`s sort of interesting. Let`s try to do that.
And by good fortune, there was a piece of -- there was some penicillin mold that was in the lab where they were in Oxford, that had been there for 10 years, that was being used kind of as a bacteriological hitman to clean up petrie dishes when they were working with the bacillus influenza, for instance, which is not touched by it. So they started -- they started fiddling with this, said, Well, there must be a way to get this out. And it -- the real genius of this group at Oxford, I think, was the multidiscipline approach that they took.
There was Florey, who was a pathologist, but also a wonderful physiologist in his own way, Chain, who was a biochemist, and Norman Heatley, who was a completely unsung hero, I think, of the penicillin tale, who was wonderful in working with micro methods and was great at practical application of things.
So ….Fleming -- and -- I`m sorry, and Heatley was saying one day, You know -- suddenly, he said, I had this laughably simple idea. We`ve taken penicillin into ether. Now, if we just back-extract it through water, through a neutral buffer, maybe it would come then. And of course, it did, but nobody had thought to do that. So for 10 years, it had kind of languished.
And once they had that, he built this wonderful sort of Rube Goldberg device called a counter-current extraction apparatus, whose frame was a discarded bookshelf from the Bodleian Library, a doorbell, some old bottles that he put together, glass tubing that he had made. And out of that, they filtered the first crude penicillin.
LAMB: Now, you can jump almost to the end of your book, where there`s a big fight over who should get...
LAX: Yes. Yes.
LAMB: ... a Nobel Prize for what.
LAX: For really ushering in the age of antibiotics. And there were two things -- you know, credit is really an interesting notion, on how -- and who -- who deserves the credit. In the case of penicillin, two things happen early on that really set the course for the way the credit was given or not given. Fleming was a very reticent Scottish professor, very kind of unassuming guy at St. Mary`s Hospital, a private hospital in London.
LAMB: In London. OK.
LAX: And it was there that St. Mary`s relied on donations to -- from the public to keep going. Fleming -- Florey was at Oxford and in a lab that was funded in other ways. In the case of Fleming, he had very powerful backers -- Lord Beaverbrook, the press magnate, and Lord Moran (ph), who was Churchill`s personal physician, also a classmate of his at St. Mary`s in the early part of the 20th century, and not even coincidentally, an acting partner of his in some of the medical school plays when they were -- when they were doing ….
When the first story of this came along -- Fleming had asked Florey to -- if he could loan him some -- or give him some penicillin that he had to treat a friend, a lifelong friend of his and his brother, Robert, a 52-year-old man who, it turned out, had meningitis and was at death`s door. And Florey said, Yes, I`ll loan you some, or give you some, if you`ll include it in the clinical trials that we`re doing. We have so little of it. We -- every case we treat, we need to keep a record of it. And he said, Fine. They did that. And there was this really quite miraculous recovery of Mr. Lambert (ph), in the same way of Ann Miller.
Well, Florey had kept a very low profile in this. He had published two pieces in "The Lancet," the scientific journal in England, but had really not wanted to get anybody`s hopes up and -- because it was going to be years before there was enough to really treat anyone. So he was very happy to have no publicity. The people of St. Mary`s were happy to have publicity.
And Almroth Wright, who ran the lab where -- where Fleming worked and who was a great character of British medicine -- he gave us the typhoid vaccine, among other things -- who was this much larger-than-life character, who was a friend of Shaw`s and actually was the subject of -- the subject for the doctor, Colenso Ridgeon, in "The Doctor`s Dilemma" -- he loved debate and he loved publicity. So he talked to somebody at "The Times," and next thing you knew is that "The Times" had a story about -- about -- about penicillin that ran along with an editorial that "The Times" had written, saying it`s time to do a little more, because there had been an article in "Nature" about this. And they tied it to Fleming. They said, Well, if we`re going to give a laurel wreath of credit, it should go to Fleming because he did this in our lab.
And people rushed over to the medical school to see him. Well, three days later, a letter comes from Oxford, from Robert Robison (ph) at the school of chemistry there, said, Well, gosh, if we`re going out laurels, we should probably give a nice bouquet to Howard Florey, who`s actually the guy who turned it into a usable drug.
LAMB: And again, what year is this?
LAX: This is -- this is 1940 -- this is 1942 and...
LAMB: Wait. Let me just make sure, so folks will listening will understand, because these things get confusing with people. Alexander Fleming`s discovery was `28, `29.
LAX: Right, `28, `29.
LAMB: We move ahead to...
LAX: To 1940, when they do the first -- the first -- the first animal trials. In 1941, Fleming -- I`m sorry, Florey treats the first patients at Oxford and learns right away how important it is to have enough penicillin to treat somebody. They treat a man named Constable Alexander (ph), who has literally scratched his cheek on a rose thorn, is taken to the hospital, within four months, is at the brink of death. He`s just -- just suppurating wounds everywhere. He`s just -- it`s like worms in an apple. He was just being eaten from the inside by bacteria.
They gave him some penicillin. There was an immediate -- there was an immediate reaction for the better. Within a couple of days, he was doing terrifically. They learned early on that penicillin is excreted in the urine. So they were taking his urine, about -- because a good portion of it is excreted -- taking it, freeze-drying it, taking it out of the urine, bringing it back and readministering it. He was in great shape, then they ran out of penicillin, but he looked to be fine. A few days, a couple weeks later, he suddenly starts to fail again. There`s not enough penicillin to give him. And this man who really was brought from the brink of death dies.
And so Florey really early on says, You have to give enough all the way through. You have to keep going until every sign of everything is gone. It`s important to keep it in the system all the time. So that`s 1941 that that`s going on. Ann Miller is 1942, and it`s in the summer of 1942, in August, that Fleming treats Lambert. And it`s in August and September of 1942 that suddenly, the papers grab hold of it.
Now, two things happen. Fleming is a very kind of unassuming guy, wonderful in pictures. He just kind of looks like a rumbled scientist. He`s kind of perfect for the part. And he was very gracious in speaking with them. Then when the word came out about Florey -- Florey was kind of this ill-tempered Australian who didn`t feel that it was appropriate to be doing anything about this now. It was against kind of every canon of medical ethics at the time to do anything that smacked of self-promotion, so he didn`t want to do anything with that. And he hated the notion that he`d be getting people`s hopes up early that there was something that might cure them.
So the press descend upon Oxford. He has his secretary come out and say to them, He`s not available. If you come back next Tuesday, he might give you 10 minutes. Now, by the standards of medicine at the time, he did exactly the right thing. And by his own standards, he did. But in terms of the gentlemen of Fleet Street, it didn`t take long for them to decide who was the person responsible. And really, from that time on, it became Fleming. Fleming was really the face on penicillin.
LAMB: Now, what was the status of penicillin in the early `40s in the United States?
LAX: There was -- in 1941, the war was going so poorly and so badly in England that it was just between the bureaucracy of war and the damage of such bombing that was done that none of the pharmaceutical companies there could do anything to help Florey grow more of the mold juice (ph), as it was, to help -- that they could get the -- that they could extract the drug from. And they needed a tremendous amount -- he needed what -- a kilo of penicillin powder to be able to do a proper clinical trial on people to see if this really worked.
He`d had a very good relationship with the Rockefeller Foundation starting in 1925 and `26, when he was a traveling fellow. And he had met a man named Alfred Newton Richards (ph) at the University of Pennsylvania, who really -- called him a "rough colonial genius," and really admired his work. Florey kept in touch with the Rockefeller people. And there were a group of Rockefeller Foundation executives called the "circuit riders," who were scientists who went from place to place in Europe, keeping track of what was going on. The circuit riders would come through Oxford, or Florey would see them at meetings, and in the 1930s, was able to get them help out with giving him a grant to support the work on penicillin.
One of the asides of it that was so astonishing to me in this story and how medicine has changed between 1940 and 2004 is that the first grant from the Medical Research Council, which is like the NIH of Britain -- Florey asked for 100 pounds to buy -- it was an initial grant, but it was supplies and getting things going. And the MRC said -- who really quite liked the proposal -- Here`s 25 pounds. You can get started with this now, and we`ll consider the other 75 as the time comes along. So really, the first grant for penicillin was 25 pounds.
They were able to get $5,000 from the Rockefeller Foundation, a gigantic amount for them, and as a result of that, were able to continue the work. Then, having been helped by them in terms of just getting the first penicillin made, in -- when Florey realized that there was no way that the British could help them, he went to the Americans, to the Rockefeller people, and said, Is there a way that you can take me to America? We`ll talk to drug companies there and see if we can`t get somebody interested. And I`ll tell them everything I know. All I want is a kilo of powder. And so a quite wonderful story in how they were able to -- how Florey and Heatley were able to go.
LAMB: Again, you`re talking about the war under way -- you know, Americans get into the war late 1941. When -- jumping way ahead, when was penicillin readily available?
LAX: In 1943. What`s interesting is between 1943, there was -- the Americans -- by the end of -- by the end of 1943, penicillin had gone from being a mild curiosity two years earlier, when Florey and Heatley came to the United States, to being No. 2 on the War Department`s wish list. The first thing was the atomic bomb. The second most -- the second highest priority was penicillin.
LAMB: In the United States.
LAX: In the United States. By the -- by the -- by the battle for Italy, which was, what, late 1943 into 1944, the Americans really came on line with penicillin. And by the end of that, there was enough for every Allied fighter in that battle. By the time the British ran out, the Americans were starting to come on. In 1943, penicillin was $200 a dose. In 1945, it was $6.
LAMB: What is it today?
LAX: Oh, cents, a penny. Depending on your health plan, I guess …
LAMB: And how available is it today?
LAX: It is -- today -- there have been so many antibiotics that have followed. And what happened is that penicillin was -- a number of people, myself included, are allergic to penicillin. It sets off -- the first shot is free. The second one, it can set off an antibody reaction, that says, Wait a minute, this is foreign -- and everything from just mild welts or hives to anaphylactic shock that can kill you. Penicillin, which seemed to be a drug that you couldn`t give too much of -- it had no real effect, other than curing the disease -- was suddenly something that was used for every -- there was penicillin lipstick. Doctors were describing it for anything that came along, including viruses, which it`s completely worthless against.
And in fact, what`s happened is that -- is that, as Fleming warned in his Nobel speech in 1945 -- he said the danger was not giving too much, but giving just enough to educate the bacteria to circumvent it. And so two things happened. It was overused and given for things that it had no use against. And it was also under-given in some cases, so that the bacteria had a way to mutate around it and to become resistant to it. Any number of antibiotics that followed, some were effective against others. There`s now, you know, some tremendously strong ones. But there are a number of drug-resistant now bacteria, really in the past 10 years, although others that are just as completely resistant -- unresistant to it now as they were 60 years ago.
LAMB: I always, whenever I can, ask a doctor what is her favorite medicine ever, and one answer you get a lot is aspirin. But the other one I get is penicillin. Today is it being -- how much of it is being used? And how important was this discovery?
LAX: Well, at the time, it was -- it was -- it`s hard to imagine a better discovery that could have come when it did, in the middle of World War II. In World War I, it`s estimated half of the 10 million people who died, died not from the actual wound itself -- the bullet didn`t kill them -- it was the resultant infection that killed them. So hundreds of thousands of lives are saved by -- people who had what would otherwise have been a death sentence, were pulled back because of penicillin.
One of the great pleasures in writing this book was to be able to put this story against the backdrop of World War II because it was so interesting to me to see how what started off as just kind of a curiosity about substances with anti-bacterial possibilities that nobody really quite understood yet, to how it really changed the course of the war, was really -- was really astonishing. And I -- penicillin became -- was developed so quickly, of course, because of the way -- I mean, everybody put their effort into it, once they understood what it could be.
Now there are, as I say, dozens of antibiotics, but there`s also a problem with that. Antibiotics are, in their own way -- penicillin was done for $120,000, something like that. I mean, that just -- pitifully nothing. A new drug today, to bring it to the market, is $600 million to $900 million. For a drug company to do that, they`re hoping to have something that will be a kind of evergreen that`ll get them their money back.
LAMB: Let me ask you before you go any farther, how can that be? How can it cost $600 million to $900 million to develop a drug?
LAX: Research, testing, demands of the FDA, clinical trials. It is -- it`s an unfathomable figure to me.
LAMB: Where does the money go?
LAX: It goes into salaries. It goes into research. There`s a tremendous amount of research that goes into it. If you look at -- of just equipment that needs to be -- equipment that needs to be purchased, of the -- of the talent that you have to put on it, of the manufacture that goes into it, of the trials that have to be done, it is a big -- it is a big deal. And medicine has changed, in a way, in that there were no -- there were small clinical trials. They couldn`t have brought penicillin to market today, in the way that they did. The idea that they could have done it that quickly and had it so readily available on the basis of, really, only, you know, a very few hundred cases, just wouldn`t be -- wouldn`t be allowed today.
LAMB: Are you saying that all medicine will cost between $600 million and $900 million?
LAX: Yes. I`m not an expert on the pharmaceutical business. But in the people I`ve talked with on this -- John Bartlett (ph) at Johns Hopkins University, probably the preeminent guy on -- in antibiotics, uses this figure. And that`s -- and the probably -- you know, one of the problems is, is that if the -- if it were a money maker, it`d be fine. Two things happen. One is the bacteria change. The other is not everybody uses antibiotics all the time. What you want, you want Lipitor. You want Viagra. You want -- you want something that people are using all the time. You don`t want something that they use 10 days a year, every couple of years.
LAMB: But go back to the way they put penicillin together. What is different today about creating a medicine than there was when you had these three or four men that were involved -- and one woman, two women, actually, which I want to ask you about -- that were involved in -- in actually inventing or...
LAX: Developing or...
LAX: I think it`s how medicine has changed. It was such a shoestring operation then. Science really, until the last 40 years, was kind of like -- you know, it was like Mickey Rooney and Judy Garland, Let`s put on a play. I mean, you did it for the -- you did it for the fun of -- all the medical advances, really into the 1940s, were not for self-advancement. You didn`t do it for the money. You generally made -- you generally made your own equipment. And you did it because you wanted to do it. It was not...
LAMB: Well, what`s different about today?
LAX: Well, now, a drug that hits -- if you look today, you go to an FDA hearing for a drug that`s being -- well, it`ll be filled -- the audience will be filled with -- with stock analysts, who will rush out, depending on the verdict, will say buy or sell shares in Merck, whatever it is -- whoever it is who`s putting up the drug, because a potential drug, as we saw with Imclone, for instance, the -- you know, the most current one, can have tremendous market swings on what goes on. Well, that was not something that these folks at Oxford were ever giving any thought to at all.
LAMB: So are you saying that greed is involved in this today?
LAX: Ambition. I suppose you could say greed. I mean, it -- you want -- you want to maximize your profits. You want a drug that is going to be useful, to sell for a lot and make its money back and get you the Nobel Prize and make you wealthy for life.
LAMB: Has anybody ever taken a drug like Imclone or Lipitor or one of these and followed the whole thing through to see how many human beings worked on it and where the profit or where people did take away money in the process?
LAX: That`s a good question. You know, I don`t -- I don`t -- I don`t know the answer to that. It`s a book I`d like to read.
LAMB: I just wonder if you could even get the information.
LAX: Oh, I think you could. It would -- it would take some …You know, one of the things, though, that -- that -- intellectual property is -- and I`m getting a little bit out of my field here, in terms of how the drug company works, so I don`t want to oversell what I know. But with intellectual property, one of the things you want to do is you want to -- you want to shelter it. So that my understanding is, is that a drug company -- let`s say -- let`s say you and I are working for a drug company, and we come up with something. First thing to do is lawyers take ….Give us all your papers. Tell us everything you know. It all gets sent off to a tax haven someplace. You protect the intellectual property so it`s not subject to U.S. law.
LAMB: Let me get to some of your other characters in the book. This woman right here is...
LAMB: What name?
LAX: That`s Ethel Florey. She was a medical student in Australia at the same time that Howard was. She was one of the very few medical students -- women medical students, at the time. Florey`s sister, Hilda, had also been a medical -- was a medical doctor. She was behind him in medical school, was a very attractive young woman, high-spirited, ambitious, daughter of a banker. He contrived to meet her by asking her to write an article for a review that he edited, and it worked. And the two of them over the next couple of years became very close.
When he went as a young man to -- on a -- on a Rhodes scholarship to -- to Oxford, he was pretty convinced that he wanted to marry her. She was not sure. She wanted to finish medical school, was looking forward to a career there. And the two of them began a correspondence that -- you can only imagine the frustration of it. It took about three months for a letter to go round trip. So he would write her, she would write him -- he would write her in September. In November or December, he`d get an answer to that letter. So if they were having an argument about something -- for instance, would she come to England to marry him or not, or how did she feel about this -- by the time it came, you know, three months later, you can`t even remember what the argument was about in the first place. It was like two people discussing things in an echo chamber. You could never quite figure out what was going on.
But there`s this -- there were 150 letters that have been saved that are in the Royal Society in his papers in London, and they`re quite fascinating. They talk about everything from, Do you like ice cream or not, How do you feel about going to the movies, to the deeper things about medicine and saving lives. They`re both very serious about that. And the question was, was ice cream too frivolous a thing to have?
LAMB: What year did they marry?
LAX: They married in 1928.
LAMB: And she was deaf, you say, or going deaf?
LAX: From the time -- she had a -- she -- early on, she had a degenerative hearing disease. She also had a number of -- she had had some lung diseases that were -- that were very problematic. So she was in failing health, in a sense. Florey was notoriously uncomfortable around illness. He was a doctor, but he`s notoriously uncomfortable around illness. When she comes -- he had clearly idealized her in the five years that they were -- that they were apart. And she called him on it, on a number of occasions, but he wouldn`t respond to it or said it wasn`t the case.
But when she arrived, it was not, I think, what either of them expected. And they did marry. The first three years were, I think, pretty good for them, but the marriage disintegrated over time. There`s an astonishing memo that I found in the Royal Society papers that was a response to something she had written. They went from talking to each other to leaving notes for each other on the table as their -- as their form of communication, too. One day, this extraordinary memo comes that he responds to. Hers doesn`t exist anymore, but his does. His is 15 hand-written pages, going over everything from lunch to sexual matters to whether the marriage can -- can -- can survive to how she had disappointed him by a cavalier attitude, how -- point by point against the charges she had made. And it is -- it was -- it was breathtaking -- it`s breathtaking to read it.
I -- I -- I always have mixed feelings about using very personal papers from people. This was clearly put in the archives for somebody to read. This -- I didn`t -- you know, this was -- this was there in a box. I said, Well, if it`s there in the box, they put -- they decided what the papers are. So I quoted it at some length because it`s such a remarkable thing about the two characters.
LAMB: What was the difference in their age?
LAX: Oh, three years.
LAMB: And how long did each one of them live?
LAX: She died in 1966. He died in 1968.
LAMB: Who is this woman right here in this picture?
LAX: That`s Margaret Jennings. Margaret Jennings was -- came on as Florey`s assistant in 1935. And the two of them worked together, they collaborated on papers. She had -- she was a very good writer, so she cleaned up his prose for the papers that he published. Over a course of years, they -- in 1940, she became his mistress, and remained so throughout the next 25 years.
LAMB: Did his wife Ethel know about her?
LAX: At some point she did. It is -- it was in some ways the worst-kept secret in Oxford, but everybody had such regard for Florey that nobody kind of -- it was sort of never spoken about. It`s one of -- there`s two kinds of knowledge. There`s what you know and then there`s what you see and therefore have to acknowledge. And so if it was never seen, it was never acknowledged.
LAMB: I get the impression from some of the material you have in here that Margaret Jennings was not very well liked.
LAX: I think that`s probably true. The surviving people, anyway, from the lab had said that she could be brusque and presumptuous and sort of a tattletale on Florey. But there is a letter in there that she wrote -- that she appended to one that Florey written to Norman Heatley when he stayed behind in America for several months to work on penicillin at Merck, that I found engaging and sweet and talks -- that is -- she comes off as a very sort of caring person.
Sure, her father was a baron, and they had these sort of feudal lands. They were talking about the 80th birthday of her father and how the farmers were coming out, and the four prominent farmers are coming out in their suits and ties, the shuffling of feet and speeches being made, and the best you could have made. The best you could make, the meager celebration you could do in wartime, and there was a glass poured in a piece of cake, and the rosy-cheeked clergymen who was in attendance.
But she captured, I thought, a really interesting scene that was played out over hundreds of years in England. And she was very sweet to Norman Heatley and saying, your letter is the highlight, every one of your letters coming is the highlight of the week in the lab, both for the personal bits, which are read with great -- with great amusement, and for the scientific bits which we all read with great enthusiasm. So.
LAMB: Again, you have Florey, Dr. Florey at Oxford, and you name Norman Heatley. Who else was around? You named...
LAX: Ernst Chain.
LAMB: Ernst Chain. Now, Ernst Chain ...
LAX: Ernst Chain shares the Nobel -- chain, Florey, and Fleming eventually share the Nobel.
LAMB: In what year did they get the Nobel?
LAMB: Here`s a picture of Dr. Chain.
LAX: Yes, a picture of Dr. Chain.
LAMB: What`s Chain`s real name?
LAX: Ernst Chain, but it`s -- he was a Russian Jewish immigrant who came to -- the initial name was Chanathan (ph), and the family immigrated from Russia to Germany. He grew up in Germany, left when Hitler came to power. Came to England to work. And was a quite brilliant biochemist.
What he brought to the work was a wonderful reductionist philosophy of taking a biological problem and reducing it to its chemical components. So by doing that, it was taking it to its simplest -- to its simplest root, and then trying to solve it from there. So he did quite wonderful work on snake venoms, for instance, that by doing that.
And that kind of philosophy was something that Florey was really looking to do. I don`t think it`s possible to really overstate how Florey set in motion and approached the medicine that really allowed this to happen, which is that you brought in people of a number of disciplines working on the same problem or different aspects of the problem. And it was not -- it was not building an elephant or a camel by committee. It was actually saying, you take this part of the elephant, you take the other part, and I`ll do this. And as a result of that, they were able to make this extraordinary stride in a very short amount of time. Because they had people with complementary disciplines that could work together.
LAMB: In the middle of all this, you say that a man named Abraham ...
LAX: Edward Abraham, yes.
LAMB: Made something like 80 million pounds from patents.
LAX: Edward Abraham, who was the chemist who came on and -- with Chain, but I think Abraham really took the lead on this, was able to get the molecular structure of penicillin. It was very -- something called the betalactin ring (ph) that doesn`t really -- hadn`t really been seen before, and made it very hard to synthesize. But once he got that, it was possible to understand how it worked and to understand the curious nature of antibiotics.
He -- the difference in patent laws, patenting was a really contentious issue between Florey and Chain, and Chain, in fact, and the whole medical establishment in England. Chain came from a German background, in which industry and academia worked together hand in hand, and patents were a natural outcome of what you did. The English law is really the reverse of it. Is that you didn`t patent. You did it and then you gave it away. It was for everyone. It was not a patentable thing to do. It was a noble thing to do, this. But Chain said, are you crazy? We`ve done this work. Somebody is going to come along and patent it if we don`t. He said the money is not for us, it goes to the Dunn School at Oxford, where they were, or to the Royal Society, or to the Medical Research Council. He didn`t care where it went. But he said, if we don`t own the intellectual rights to this, we`re going to end up paying royalties for what we`ve started, and in this he was prophetic.
Although the penicillin we know today is a step beyond what they did at Oxford, and in fact, the patent wouldn`t have lasted that long, but the idea in fact was right.
But the difference between the early 1940s, when he was doing this, and the end of 1940s and 1950 when Abraham is working on …He`s the man who brought us the next generation of drugs …He patented the entire betalactin (ph) ring. All of the side chains, every possibility that you could come up with, he took a patent out on that. And he made free -- he made two trusts for Oxford, one for the university, one for the Sir William Dunn school, which is the laboratory where Florey was, which is part of Lincoln College, and then he kept some for himself.
But the royalties of that over the past 50 years have been in excess of 50 million pounds. There`s a beautiful new building now behind the Dunn School that`s entirely done out of these royalties.
LAMB: And Abraham patented it where?
LAX: In England. And but held a worldwide patent on it. So the benefit -- when people realized that the English had come up with this, and somebody else had the patent on it, first the idea was sort of the Americans had pinched it, which in the end is not really true, but that was the feeling. Suddenly, the attitude toward patenting changed. But medicine changed so much after World War II. It became a much more for-profit venture.
LAMB: Who made then the money? Who made the initial big money off of penicillin?
LAX: Pfizer made a lot of money. They really solved the big problem of how to get it to grow.
LAMB: American company?
LAMB: Who else?
LAX: Merck, all American companies. There were a number of American, Pfizer and Merck in particular, made tremendous moneys off penicillin. Because they did, you know, they patented what they could from it, and -- Pfizer did an extraordinary thing there, is that one of the problems both in England and initially with American drug companies, talking about why it`s $600 million or $900 million, is that there`s a tremendous capital investment in machinery and equipment that you need to do -- to make this happen.
The great concern was that you would put in this initial investment, and then suddenly there would be a way to synthesize it and you would have all of this capital investment that went for naught. Pfizer was willing to take a gamble that that wouldn`t happen that quickly, and they came up with what amounted to this huge sort of washing machine.
And I`ll explain. Penicillin grew on the surface culture. It grew in half an inch of medium. And you would extract it off that, but it was really one-dimensional or two-dimensional. And the way they were doing it at the Dunn School, because there was no equipment, they had pie tins, cracker boxes, bed pans, a china plate, they had a dog bath, looking for the best vessel to grow this in.
Pfizer said, all right, here`s what we need to do to grow this basically in 3-D, it`s like brewing beer, and how do you get the oxygen to the spores? Well, you came up with something so they wouldn`t go to the top. They put in great, big blades that would keep it going around. They were shooting in air from the bottom with a high-powered hose. So as all this was being churned around, there`s very violent shaking to make sure that the air got into everything. So these mold spores, instead of just growing on the top, were now getting enough air that they could grow anywhere in this huge vat. It was like they had an aqualung.
So suddenly when you went from really surface culture, almost a single dimension, to 3-D, you were having an exponential yield on that. And out of that, then Pfizer was able to manufacture vast amounts of penicillin.
LAMB: I didn`t ask you earlier, but what`s the definition of an antibiotic?
LAX: It`s simply as this, it really is -- it`s -- against life. It`s the notion of something that kills another. So, and the notion of antibiosis is -- really only goes into the 19th century. But Pasteur had a great line, that life hinders life. That notion of life hindering life is really the basis of medicine for what you can use, what you can use in science (ph).
LAMB: I`ve got to ask you. There are two people that praise your book on the back of the book. Scott Turow and Walter Isaacson.
LAMB: How did that get there?
LAX: When I finished this, I wanted somebody going to a bookstore to say, gosh, this is scary, you know. I didn`t want them to say, gosh, this is scary. If I thought if a novelist and a biographer could say, this is really about people, because that`s what drew me to this book, these wonderful characters, then it would not be a scary thing. I -- Scott Turow I actually know, though not well, because we`re both involved with PEN, the writers organization. Walter I met very, very briefly once, and we have a mutual friend, and I said -- our mutual friend had said that he had liked some other books that I had written, and I said, gosh, I said, in terms of somebody saying something about this book, here`s the biographer of Benjamin Franklin, who tells such a wonderful story. If he could like it, maybe the readers would say, gee, this is not a scary book. So then he wrote this extraordinarily kind -- I mean, I couldn`t have written that. My mother couldn`t have written this.
LAMB: From Woody Allen to penicillin?
LAX: Well, Woody Allen takes a lot of penicillin. So it`s not -- he`s a great hypochondriac. But I`ve also written about...
LAMB: But when did you start -- when did you do the Woody Allen book?
LAX: Well, I did a couple of them, actually. 1991 was the biography that I did of him, and I did a book called "On Being Funny" in the 1970s that was a way of looking at humor, and I used him. But then in the 1980s, I wrote a book called "Life and Death on 10 West," which was an account of doctors and nurses and patients on the bone marrow transplantation ward at UCLA. I wanted to write a book about modern medicine, about the frontier of medicine, and that was really the place to go.
LAMB: Where do you live?
LAX: In Los Angeles.
LAMB: Why Los Angeles?
LAX: Well, my wife and I -- my wife lived here in Washington when we were engaged, and we were both really from New York and thought that when we got married we`d go to New York. But I haven`t finished "Life and Death on 10 West" yet, and in the course of a four-story elevator ride, we decided to go to Los Angeles for a couple of years so I could finish "10 West," and then we`d move back to New York. And that was 1982. And we just haven`t quite gotten there yet.
LAMB: And you do writing only for a living?
LAMB: How did you get into it in the first place?
LAX: Through the Peace Corps, a strange way to do it. I was working -- I had been a Peace Corps volunteer for two years in Micronesia, and then I was something called a Peace Corps fellow here in Washington, with the notion that you spend a year here and then you went overseas to run a program. And Robert Rice, who was a writer on "The New Yorker" for 25 years, his father was Elmer Rice, the playwright. I was sent to Turkey to look at the Peace Corps program there. And at the time, the evaluators who did this really wrote what amounted to "New Yorker" articles about what was going on with the program. It was about the people and events, and it really read like a narrative.
And I was assigned to him. He got stuck with this Peace Corps fellow. We went to Turkey and we spent six weeks. And he called me up after I turned in my portion of the report, and he said, gosh, he said, you know, you have a flare for this. He said, my father taught me some things, and if you`d like, I`d be happy to teach you some things.
Well, you know, that was, to me, kind of along the lines of the burning bush talking to a pedestrian. And I said, OK. I guess I could spare the time, thank you very much. So that was 1970.
LAMB: Where did you go to school?
LAX: Hobart College in Geneva, New York.
LAMB: There`s a note from John Fulton. I want to ask you first who he is, back to the book, about this Nobel Prize. I mean, one of the things you get from your book is that credit was very important to so many people.
LAMB: Do you have any sense, just from living your life, why people want so much credit?
LAX: I think with the case of -- the attitude of those at Oxford especially was, if nobody`s getting credit, it`s fine if nobody gets credit. But if some people are getting credit, we`re all human, wait a minute, let`s share this. It was not for the money. The prize wasn`t that great at the time, but it was, of course, as high an honor then as it is now.
LAMB: So what is it, like a million now?
LAX: Oh, the money now is, yes, in excess of...
LAMB: And what was it then?
LAX: Oh, it was a few thousand pounds, 3,000 pounds.
LAX: Yes. Maybe 8,000. But it was split between the three of them.
LAMB: And this fellow, John Fulton? What role is he playing in all of this?
LAX: John Fulton is one of the most interesting characters in this, and was instrumental in two very specific ways. One is that Fulton was completely tied -- he taught at Yale, was completely tied into the entire medical establishment of the United States, and was very highly regarded, knew everyone. He and Florey were Rhodes scholars together. And both got a first in their exams. And Florey and Fulton were very good friends. I`d say Fulton was probably the closest friend that Florey ever had. Florey was never a particularly warm, outgoing person. He would be very generous about people behind their backs, but to their face he could be just terrible. He would see you, for instance, come into the lab, he`d say, oh, Lamb, still shuffling your feet? It would just -- it would just be awful. But then behind people`s back, he`d say wonderful things.
One of his lab workers won a prize one year, he said, oh, congratulations, and then followed it up almost immediately by saying, of course, it was a very poor field this year. But as I say, at the same time would say wonderful things.
LAMB: Was that his humor or was that...?
LAX: I think it was just an awkwardness. He would catch himself being kind of emotional, and then he`d say, oh, that`s a little too personal, and then would pull -- would pull back.
LAMB: You say the Florey couple, Ethel and Howard, sent their kids to John Fulton.
LAX: Yes, Fulton came back to America after some years in England, really established himself at Yale, and he -- just to finish another point, Florey always called people by their last name, didn`t matter how long he`d done it. Fulton was the only person he called John. He was actually the only person he called by his first name, of all the letters that I was able to read, anyway.
In 1941, when the war was so bad in England, there was an evacuation offered by Yale and other colleges and universities on the East Coast, to bring children from Oxford to the United States. And Florey`s children`s were among those who came. And when Fulton saw that the Florey children`s name was on the list, he immediately sent a cable saying, may we claim them, may we take them. And Florey said, well, how wonderful, wonderfully kind of you. And they were there with them for four years.
LAMB: You have a bunch of interviews in the back, and the names are familiar. The last names -- the first names aren`t familiar. I know you know what I`m getting at here. You see a lot of Sir Henry Harris.
LAMB: You also see -- I think there was -- I`m looking for it right now -- of course I can`t find it. Is there a Florey?
LAX: Charles Florey, the son.
LAMB: How old is he now?
LAMB: Where did you find him?
LAX: Through Norman Heatley. Norman Heatley was the last surviving member of the team. He died just in January, unfortunately. I`d hoped that he would be alive when this came out.
LAMB: But you got it in the book. That was interesting.
LAX: I got him. Yeah, he was wonderful. I spent -- I spent, oh, hours. I spent a week, a month in England for about a year and a half doing the research, and would see him on every trip. And he was just wonderful. And as a result of that, they had the Florey children out there. There is Paquita and Charles. Paquita was the daughter, slightly older, who was in Edinburgh, and Charles, who was living in the south of England.
And they, once they understood what I was doing and believed that it was OK, were really very helpful, very forthcoming, and provided me a great deal of material. And what was interesting for me is that it`s always a surprise for a writer coming in cold to something, is that often you can tell things to a family that they never knew. I came upon things that they had no knowledge of.
LAX: A letter that Margaret Jennings wrote shortly after Howard died, explaining really why she was -- their relationship of 25 years, in a sense making the argument of why she was willing to be his mistress for this amount of time, how close they were. And when I sent it to Charles and Paquita, I said -- I explained what it was, I said, would you -- I don`t know if you`d be interested in seeing this. They said, oh, yes, absolutely.
And they were both, as Paquita said, she said we were just gobsmacked by it, we just had no idea. And she said, when my father said that he was marrying Ethel, I said to him -- I said when he was going to marry Margaret, I said, how long has this been going on? And his response was, not long.
LAMB: Here it is, right here, why don`t you read it? You got...
LAX: See, I need my glasses.
LAX: See what we can do here.
LAMB: Probably do better than I can. Now, this is from Margaret Jennings.
LAX: This is from Margaret Jennings. This was a note that was sealed in the bottom of the box, of Florey`s -- there are 300 and some boxes of Florey papers at the Royal Society.
LAMB: They were a mistress -- she was his mistress for how many years?
LAMB: They married what year?
LAX: About a year and a half. They were married for a very short period, 1967 to 1968. It was very...
LAMB: And then he died, and she lived in 1994.
LAX: Yes, that sounds right. Yes.
LAMB: How old was she when she died?
LAX: She was well into her late 80s, certainly, maybe even early 90s.
LAMB: Why don`t you read a little bit of it if you don`t mind.
LAX: "Howard had a tenderly romantic attitude towards women, which was completely stultified in his relations with his first wife. When he made me his mistress in 1940, his tender solicitude and wish to give me happiness through his physical powers, as well as by caring for me, were most touching. I was then separated from the husband who had done nothing to repair my physical and emotional immaturity. Howard understood this, and with great compassion, expressed particularly through his physical care and restraint, did all he could do to help me. And I think I made him happy. I was his dream. And I always received with melting warmth his tributes. Were they presence, or love making, or confidences which he was much too reserved to give elsewhere."
You know, what`s interesting about this, is that this person who`s described here, in all of the papers that exist between the two of them, he always addresses her as Mrs. Jennings. Her name was Margaret Jennings, through the name of her first husband, who she left after she came home one day and apparently found him in bed with a nurse. That -- but even -- even as Florey knows that he`s going to soon die, and just as they`re getting married, he writes this very formal note to her, Dear Mrs. Jennings, here it is. But that`s their whole -- if you`re looking at the formality of the man, the reserved nature of him, I was always struck by that whenever I came upon it.
LAMB: Well, the other note I wanted to read a little bit was the John Fulton on the Nobel Prize.
LAMB: He wrote -- and who`s he writing to here, Dr. Purjey Hendanias (ph)?
LAX: Yes. There were two people -- as the prizes come in, the prize was not given for a couple of years during World War II. It was -- and then they heard in 1944 that it was going to be given for 1943 and `44, and there was a rumor that the people were really happy to spread around is that the award was going to go to Fleming and Fleming alone for this. And there was -- there was some reason to be concerned about this. At that time, the New York Academy of Sciences had made Fleming an honorary member, but not Florey, who had actually turned it into -- turned into the drug. So there was some concern that it really wasn`t clear who was responsible for this, and how much had gotten out. Fulton, who knew all these people, wrote very, very strong letters to the Nobel Committee.
LAMB: Let me read a little bit. He says, "I learned yesterday from a friend who had just flown from England that the British press has published a rumor that Fleming and Fleming alone is to be recognized for the discovery of penicillin. I sincerely and most earnestly hope that this is only a rumor. Informed opinion in this country would look upon an award to Fleming alone as most unfortunate and an almost complete disregard for credit where really it is due."
At the bottom of this, "P.S.: Our recommendation would be, in the order of preference, Florey alone," that was his friend and pal, "Florey and Chain," who we talked a little bit about, "or third, Florey, Chain, and Fleming." And in the end, the Nobel Committee did what?
LAX: They split it evenly between the three of them. What was interesting is I was able to get to the Nobel archives also to read all of the discussions that were done over this over the years. And they started off very cautiously about penicillin, said, well, let`s wait and see, was their first attitude. And then it was -- for the first year and a half, it was, well, Fleming is clearly prize worthy, and then Florey and Chain came in, and they said, we`ll divide it half and half. It will be half to Fleming and the other half to Florey and Chain. And it was really I think only the letters from Fulton and also from Henry Dale, who was the president of the Royal Society, who wrote also pretty convincing letter saying, let`s be very clear about how this happened. Let`s not sleight Fleming, but let`s not overlook the contributions of Florey, Chain and Heatley and the others.
LAMB: How long did Alexander Fleming live?
LAX: Until 1955. And he was a national hero. He was -- he`s literally a hero on every continent and on the moon, where a crater is named for him. When he died, it was literally a national hero passing. From the earliest time, Fleming really became the only face associated with penicillin, in part I think because as the biographer Wynn McFarland (ph) said, he`s kind of a wonderful sort of anti-hero. After the war, you were looking for somebody other than -- but he`s in -- he`s buried in St. Paul`s, in the company of 200 great heroes.
LAX: Now, if you go to a doctor today, when are you more often to get penicillin?
LAX: Less and less on penicillin, because it`s moved on, although it has -- it`s enjoying kind of a renaissance now.
LAMB: You get it for what, though?
LAX: Oh, infection, bacterial infections.
LAMB: Mouth or shots?
LAX: Shots. One of the problems -- they learned early on that the stomach acid kills the active ingredient. So the best way to do it is just give it intramuscularly. And the best way, actually, was just a drip, when they were -- because you want to keep a steady stream in the blood. So when they were first doing it, just a steady drip would often work very well.
LAMB: This is way out of context, but it was an interesting little part of your book, and that is Peoria, Illinois. We don`t have much time.
LAX: Oh, yes.
LAMB: How did Peoria, Illinois in the middle of all this figure?
LAX: Yes, the Northern Research Laboratory, put up by the -- from the Department of Agriculture was doing a great deal with fermentation. They were trying -- and it was clear that what needed to be done was essentially what you`re doing when they were doing ….Fit`s a fermentation problem, it`s a brewing problem. And so they were looking for effective ways to do it. So that`s where so much was going on, and they used this substance called corn steep (ph) liquor, which was left over from when you made cornstarch and other things. And there`s this tremendous amount of gooey waste that if you couldn`t find something, you`d have to dispose of it. Well, corn steep (ph) liquor turned out to be a great medium for...
LAMB: And who went to Peoria?
LAX: Both Fleming -- I`m sorry, both Florey and Heatley, and then Heatley stayed on.
LAMB: And last couple of questions. The Rockefeller Foundation played what role in the money for all this?
LAX: Not only just the money. I think the Rockefeller Foundation`s imprimatur on this was really the difference between penicillin being developed or not. I don`t think you can overstate what they did. Not only their support of Florey, whom they had known for a long time and whom they`d valued very highly, but also the imprimatur of his -- of their supporting his coming to the United States, and that coupled with John Fulton, who was able to use both their backing and his own contacts to really -- here two people who come over, don`t really know anybody here, and are suddenly introduced to the heart of the scientific establishment. And it was that imprimatur that allowed them to go forward.
LAMB: You`ve dedicated this book to your son John?
LAMB: How old is he? Where is he?
LAX: He`s 14, he`s in Los Angeles. I have two sons. Simon. Simon got the last book so it`s...
LAMB: And how old is Simon?
LAX: Simon`s 17. And interesting, Simon`s the one who is actually interested in biology and biochemistry, but you know, you never know what you`re going to write, so.
LAMB: What`s your next book?
LAX: I`m working on it now. Something completely different I think is the only way to -- it`s an idea that I haven`t quite figured out, but it`s neither show business nor medicine.
LAMB: Is it about a person?
LAX: It`s about -- it`s about an idea.
LAMB: We`ll just leave it at that. The story of penicillin is the subject of this book. It`s called "The Mold in Dr. Florey`s Coat," and our guest is its author, Eric Lax. Thank you very much.
LAX: My pleasure, thank you.
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