The Obscure Virus Club

Aug 22, 2019

Throughout the 1960s, a biologist named Howard Temin became convinced that something wasn’t right in science’s understanding of viruses. His colleagues dismissed him as a heretic. He turned out to be right — and you're alive today as a result.  Season Four ends with a bedtime story about how we should be freed by our doubts, not imprisoned by them. Learn more about your ad choices. Visit megaphone.fm/adchoices

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this episode of revisionist history is brought to you by AT&T business and I'm having a conversation with AT&T business President Chief marketing officer mocad Abba about the coming 5 G Revolution we started the conversation two episodes ago and in this episode I hijack the conversation and make Mo talk about my personal Obsession you got people to think about medicine yep people do you have anyone who thinks about sports we do we have an entire team who thinks about venue experiences no two words have lifted my heart quite like venue experiences will be back with Mo in a little bit and Now ladies and gentlemen episode 10 of revisionist History

in the second half of the 20th century a group of scientists became obsessed with an obscure family of viruses there weren't many people in the Obscure virus Club they all knew each other the rest of the world rolled his eyes at them read the letter okay dear Bob I regret that your paper on the T-cell retrovirus is not acceptable for publication in the journal virologist exhibit a in The Archives of the Obscure virus Club our rejection letter I completely agree with reviewer number one there's little point in perpetuating this controversy about the presumed viral nature of this material

not thank you very much this is fascinating but you're not quite there yet just know I hope you understand we can only accept definite of data to resolve this question therefore I have no alternative but to reject this paper out right I'm advised you we cannot consider the present manuscript in any form in any form if you are in the Obscure virus Club you got the Salat it didn't stop them thank God

my name is Malcolm Gladwell you're listening to revisionist history my podcast about things overlooked and misunderstood this is the final episode of season for a season of Jesuits and lawyers and gangsters and disputatious musicians iconoclasts and Skeptics and I want to finish with the story of the Obscure virus Club may be the biggest band of iconoclasts of all this is a bedtime story for the season of revisionist history and as with any story you have to wait to the very end to understand what it's all about

the Obscure virus Club had adjunct members honorary members hangers-on but I want to focus on the three people at its core ludvig gross Howard temin Robert Gallo Bob Gallo is the only one still alive 82 years old still at the office every day he has pictures of his Old Camp a treats on his walls I think he sent this to me oh there he is like yeah hell yeah is just that you know you Unforgettable character but that that captures of you know yeah first ludvig gross head of cancer research for the Veterans Administration in the Bronx Gallo remembers asking him whether he wanted to get rich gross told him no he had everything he needed and he counted it off first he had his car hit Escape Poland in his car after the Nazis invaded he drove everywhere when he came to see me at NIH stroke from New York and he is

first experiments were in the backseat trunk of his car so he said number two I have my television I can see Perry Mason he was a cremation addict number three I have my work and number four have my wife and that's the that's the crows at scientific meetings in the 1950s people wouldn't sit next to ludvik gross everyone thought he was crazy

next came the ringleader of the Obscure virus Club Howard temin the remarkable Howard temin but really we can do the addition of the screen I can do it right now but yeah and get self-conscious and Vernon where are the controls you don't have any damn controls and you're making too many cleans the hair like you the same hairdo Howard temin ludvig gross Robert gallo and what did they have in common I mean what's in common is we got pissed on hey we all had our time before I would say three scientists shunned by their peers that was the price of admission to the Obscure virus Club

in 1911 a young physician named Francis Peyton Rous set up a cancer research laboratory in New York and what is now Rockefeller University a woman came to see Rouse she had a poultry farm just outside the city and she brought with her a hen with a large lump on his chest the lump was cancer a sarcoma that is a tumor of the connective tissue we don't know why a cancer doctor would be curious about a dying chicken but he was Rouse remove the tumor grounded up mixed it with saline solution and injected the solution into healthy chickens and what happened the healthy chickens develop the same tumors

Russ was perplexed cancer is not supposed to be a communicable disease it's caused by a malfunction of the genetic Machinery inside a cell it can't be passed from one person to another like the flu but this is exactly what seemed to be happening the chickens tumor Rouse concluded had to be caused by a virus people didn't believe him they said well maybe that tumor isn't really cancer or so what this is just some weird thing that happens with chickens Ross got discouraged he stopped working on viruses entirely

years later this same problem whether cancer could spread like a virus came to obsess ludvig gross he worked with mice sometimes mice came down with leukemia murine leukemia which is a lot like human leukemia gross bread mice to show how the disease was communicated from one generation to the next he became convinced that the leukemia was caused by a virus passed from mother to offspring but the same thing happened other scientists didn't believe him here was this strange emigres in the Bronx imagining cancer-causing viruses in mice why couldn't that just be a set of faulty genes being passed down he proved it was viral disease but everybody's are you know that is cages are filthy and is no technology whatsoever it is not you know really what he's doing you know there was all that my bad mouth completely essentially virtually straight gross finally won the Lasker award one of the

prestigious prizes in medicine in 1974 when he was 70 in the Obscure virus Club you often had to wait your entire career for validation

after gross comes Howard temin the remarkable Howard temin Taemin was the second of three sons of a lawyer and an activist from Philadelphia the biologist David Baltimore met Taman when they were both part of the student summer program at the Jackson laboratory in Maine if you had a question or there was a lecture you didn't understand something you could go to Howard and Howard knew everything he was an amazing intellect and so I spent the summer in a sense as his student he was famous at Swarthmore actually cuz they said he had read every book in the library and they had to buy more for him

I mean he wasn't the only one to notice that there was something very special about him this is the kind of person he was Tim and donated his bar mitzvah money to a refugee camp years later when he visited the Soviet Union he smuggled in Hebrew prayer books I met Tim and once when I was a cub reporter for the Washington Post I happened to be in Madison Wisconsin at the University of Wisconsin where he taught his whole career I went to see him I don't remember the specifics of what he talked about and I've lost my notes what I remember with absolute Clarity is the feeling I had after leaving his office which is that I had never met someone so completely in command of his own thinking

I've only ever gotten that sense of command of Mastery from watching great athletes never biologists was squeaky voices

Timmons wife rela says that when teman first got to Wisconsin he would sit in on seminars and other departments and as soon as he got here he drew attention of people because he would sit up in the front and then he would ask the most pointed brilliant important questions of the speaker so everyone said well who is he who is he but once you met Howard temin you remembered Howard temin one of his former graduate students Sandy Weller says she could barely keep up with him they rode his bike to work every day he took he never took the elevator he had to go to the ninth floor he walked nine floors and several times he made me do that with our just assumed I would do that with him if we were going up to the seminar on the 9th floor

Tim and could have done anything walked into any field in science and left his Mark but he became obsessed by the chicken tumor that Peyton Rous had discovered 50 years earlier now known as Rous sarcoma virus and so when I was interested in doing was understanding how that virus causes cancer that's 10 min in an oral history taken a few years before his death in the 1950s you could not have picked a more obscure topic to study than a cancer virus people were still avoiding ludvik gross at conferences the University of Wisconsin had a virologist position open at their Cancer Institute no one wanted it

you said when you came to Wisconsin that the virologist position had been offered to several people and they hadn't been interested how come these people had turned down the position viruses at that time we're not considered very important in cancer research they had always been a sideshow for cancer research his first office at Wisconsin was in the basement next to the sump pump and my office was in what had been a transfer room a little isolated room about the size of just where you're sitting a couple of square feet but none of that mattered teman was hooked Rous sarcoma was a weird enthralling puzzle he began to notice all kinds of anomalies for example sometimes the virus will mutate it would take on a strange new shape and then afterwards the cell it infected would take on the same strange shape

as if the virus weren't just occupying the cell it infected the way say a flu virus does the flu just sits inside your cells multiplying until your immune system drives it out the flu is a squatter but Rous sarcoma seemed like it was Conquering the cells it was infecting inserting its own genetic information into the DNA of its host how it did that made no sense at the time the field of genetics had something scientist called the central dogma the central dogma held a genetic information only moved in One Direction DNA gave instructions to RNA which then use those instructions to make proteins DNA to RNA Rous sarcoma was an RNA virus according to the central dogma then it was impossible for it to insert its genetic information into the DNA of the cells that was infecting

RNA didn't move in that direction we knew the basic lifestyle of most viruses but now the cancer inducing virus has stood out as different than and hard to understand David Baltimore again what was different in hard to understand about them

well the fundamental thing was that they had RNA as their genome and yet they were able to establish a permanent position inside the cell and run the cell so he turned it from a normal cell door to a Cancer and so here it was behaving a bit like DNA he had it was an RNA virus and that didn't make sense Howard had been driven by that question for 10 years previously

David Baltimore watched his old friend Howard temin stand up at conferences and try to convince everyone else to take this weird anomaly seriously why did that question assumed such importance for him because he was thinking 24 hours a day about these viruses as he obsessed over the puzzle of Rous sarcoma teman decided it could only mean one thing the central dogma must be wrong one of the fundamental facts about human genetics taught in every science textbook and every science classroom in the world had to be in error there must be a class of viruses like Rous sarcoma virus that could somehow work backwards from RNA to DNA it was as if he said yes the Earth rotates around the Sun in an anti-clockwise manner but the only explanation for what I'm seeing with Rouse is that on occasion the Earth must stop and go clockwise

and then he spent about 10 years at University of Wisconsin trying to find an experiment that would convince anybody else of that and he couldn't

Taman had an intuition a hunch but no one was going to overturn the central dogma because some guy from Wisconsin had a hunch it wasn't right

I'm talking to mocad Abba President Chief marketing officer of AT&T business about the 5 G Revolution I made him talk about the implications for my favorite activity watching sports and to use those to tantalizing words venue experience tell me more about the venue experience okay so example if I've G coming to life in a venue is you can deploy literally hundreds of cameras around the venue and so now is a fan when you go in 5G enabled because of the capacity in the latency you can process the video coming off of those cameras locally inside the venue local Cloud instance and then you can give the fans the ability to choose what at which angle they want to watch from which is really cool and I love music and so for me I'm excited about being able to go to a concert inside a venue and I want to watch it from the lead guitarists

you know written yeah soloing yeah yeah or and because latency is essentially instantaneous it wouldn't be like you your you can watch it in real time from whatever perspective you want exactly send me it doesn't matter where you're sitting so as long as you have 5 G coverage broadly available across the entire venue you can be in the suite you can be in the club you can be the secret of the emotional experience of being in the arena which is what you want us but also the luxury of watching it from your own perspective which could only even remotely be duplicated at home and even at home because you don't get to choose your angles at home it's better than that

science is a social process people within a field are in constant contact the show notes the gossip they compete for the brightest graduate students for grant money for prizes when you say something that the group doesn't believe you pay a price and with every year that passes with you saying one thing and the group saying another the price gets higher first of all people thought it was crazy I mean he didn't prove his theory for six years after proposing it Timmons former graduate student Sandy Weller and that six years was a very difficult period for all of his students and for him he was a pariah they thought his students were nuts for working with him at one point Howard temin wrote Francis Crick Sir Francis Crick Nobel Prize winner of Watson and Crick the co discovers of DNA the authors of the central dogma itself Tenon rights Creek a letter gently

adjusting that an amendment to the central dogma might be in order quick writes back very condescending arrogant letter well I'm sure you think this is true but you must realize you're wrong and to talk like that to Howard with Jimmy that's just such most people would have given up but he doesn't because he's Howard temin the word that comes to mind is righteous which has a negative down to it I don't mean to be negative this is Timmons daughter Miriam but he has strong moral compass and it was incredibly incredibly confident person was blessed with that and so it was not shy about speaking his mind yeah where do you think that what was the source of his confidence that's why I asked my uncle Michael teman the source of his stick with it this was and his answer was well he knew he was right and then one day in 1970 he came home to his wife

trailer full of excitement he was going to be away on our anniversary which was May 27th and he was explaining why he had to leave and that we would celebrate later I said well that's fine that's fine and he said that actually he had something that was a bombshell that he was going to announce that the meeting but he couldn't tell me what it was she said let me guess you found it he nodded after years of trying teman had located the part of the virus that enabled it to work backwards and by an incredible stroke his old friend David Baltimore had found it too

by then Baltimore had fashioned his own equally brilliant career at almost exactly the same moment the two old friends independently discover a little enzyme looking in a distant corner of this strange class of RNA viruses an interpreter something that speaks RNA and can translate into DNA so that the virus had a mechanism for inserting its own genetic information into the cells it infected

Taman finds the enzyme in Rous sarcoma virus Baltimore went looking for it in Mouse leukemia virus the same virus that had haunted ludvig gross teman and Baltimore call it reverse transcriptase and the class of viruses that had obsessed them all for so long now had a name retroviruses because by virtue of their onboard translator they had the ability to work in Reverse how hard was it to find this particular enzymes that is a trivial oh really it's really the issue dated notion of two days of experiments two days

so it's just the idea of knowing where to look and what to look for and what to look for right you have to design very specifically design your search so that it will show up this enzyme right if you don't look in exactly the right way you're not going to spot it right just like that the great puzzle was resolved

when I got to the point where I knew that the enzyme was in the virus particle the first thing I did was to call Howard and say I want to tell you about this we did he how did he respond he responded by saying we're doing those experiments to I think you're right in 1970 Baltimore and teman jointly published a famous series of papers in the prestigious journal Nature five years later they were awarded the Nobel Prize along with their old teacher were not Odell Beckham time in trades in his two first-class tickets to Sweden for Coach seats so we can take along his two daughters that's always seven when he got the Nobel Prize and one of the things I remember is that his pants were too long and they were sort of all bunched around the bottom of his talks at the ceremony yes did you go to the ceremony yes oh you did yes I kind of remember meeting The King and I definitely remember a banquet

very very fancy in this enormous wide staircase where the laureates came down and their spouses all paired with somebody else so my father had a I believe a Danish princess on her arm if I'm remembering correctly in a long pink dress I remember that in my mother was escorted by some lesser Prince person and the waiters you know all in this procession with the most beautiful food it was the 75th anniversary of the Nobel Prize so all previous laureates were invited there was a huge banquet in the golden Hall by tradition one representative from each set of new laureates was allowed to speak teman was chosen he stood up with his baggy tuxedo trousers and his squeaky voice and he went up to the microphone in front of these 1200 people and thank them very very much for the prize you have given us for cancer research

which is why frail I was sitting in the audience with their daughters and then teman said here we are being rewarded for a work in understanding cancer and you're all smoking the King was smoking the queen was smoking everybody there was smoking so they were just a gas that he would get up and say that in front of all the royalty did they put out their cigarettes yeah I think many of them did because I was down in the floor and the table I was sitting next to the prince of Denmark was my partner that night and I looked and they people just looked shocked when he said it I remember the look on the faces and then they stubbed out the cigarettes the story of the Obscure virus Club could end here Baltimore and teman getting their medals from the king of Sweden then teman calling out the whole crew for their hypocrisy happy ending

but there's a whole other chapter to come

mocad about and I have been talking for the past three episodes about 5G what it is and what it means so this something is going to hit the business world first yes our perspective on it my perspective is absolutely businesses or first businesses were calling and saying hey we want to understand how this technology allows us to drive different outcomes you know take out costs create new Revenue change the experience for our workers or our end customers and so they want to play with it right it's entirely New Era and if I'm a consumer civilian wondering when this technology starts to move beyond the business world to the individual consumer if you had to guess about a timeline without you guess what I'd say you know the future starts with today and just like we were talking about we've already forgotten when did ways come out when did Airbnb come out when did these things that feel like magic now you know

they weren't even things we'd imagined a few short years ago the consumer experience is going to be the same way a few years from now we're all going to wake up and be like hey my toothbrush talks to me

when David Baltimore and Howard temin discovered reverse transcriptase and shattered the central dogma Bob Gallo the third charter member of the Obscure virus Club was still in his early 30s the son of Italian working class immigrants lean ambitious raw a rising star at the National Cancer Institute he went to a scientific conference in Paris was stuck in a cab when he looked out the window and saw Howard temin he's walking in the streets in Paris like a lost soul remember 1970s now hero already hero Howard temin the hero walking down a Paris Street and window shopping or something by himself that just seems different yeah hey there you are I said yes there you are

I think sometimes we overestimate the importance of ideas in science yes you read a paper in nature and it changes the way you think about the central dogma but what is it that really changes the way you think about the central dogma when you meet the person who challenged the central dogma and because that person is so remarkable you realize oh I want to be like that

Bob Gallo met Howard temin and decided that in there to join the Obscure virus Club he was a hero to me you know when I was a child it was Joe DiMaggio okay how is that ultimate sort of it so you know when you would not that much older than me as a bit decade or so but no it's I couldn't identify with him like that I just appreciate it a lot I was just fascinated by him I was just taken in by it and I just said you know I don't listen to every goddamn things guy says you

Gallows specialty was leukemia cancer of the blood cells and what Drew him to retroviruses was the fact that so many of them were leukemias Ludwig grosses Mouse leukemia being the first and most famous but soon people found others bovine leukemia feline leukemia Gibbon ape leukemia + chicken and mouse so five different animal systems all infectious viruses what no one could find was a human retrovirus there was a growing feeling that they simply didn't exist the baby humans Were Somehow protected against this kind of infection but Gallo didn't buy it there had to be one

he decided to focus on a specific subset of leukemia leukemia that affected the blood cells known as T cells at the time no one knew how to grow T cells in the laboratory and if you couldn't grow T cells you couldn't find your study anything that infected them Gallo's lab figured out how to grow T cells then he began searching and in 1979 he found it in the blood of a 28 year-old African-American from Mobile Alabama Gallo called what he found human T lymphocyte Tropic virus one htlv-1 it turned out the man's whole family had leukemia to

Gallo then found a man in the merchant marines with a history of sexual contacts in Japan and the Caribbean same thing leukemia and a weakened immune system in his blood Gallo could see traces of a virus with that Telltale bit of reverse transcriptase a human retro virus spread by mother to child sexual contact and blood to blood transmission previously unknown most definitely obscure

Gallo submitted his findings to the Journal of virology the leading scientific journals in the field and what happened the same thing that happened to Howard temin and Ludovic gross the world wasn't ready to accept the idea of a human retrovirus the paper was rejected Gallo keeps that letter on his wall dear Bob I regret that your paper on the T-cell retrovirus is not acceptable for publication in the Journal of Urology there's little point in perpetuating this controversy about the presumed viral nature of this material oh my goodness anyway keep it give me the date September 15 1990

September 15 1980 that's the key fact because what's happening in the fall of 1980 it's know it kills and it's spreading young previously healthy men were starting to died of a mysterious disease AIDS a disease that has Medical Science baffled

if you did not live through the early days of the AIDS epidemic you have no idea what it was like it leveled the gay communities of major cities around the world people were wasting away their skin disfigured by strange lesions preacher stood up and denounced homosexuality from their pulpits doctors refuse to treat gay patients Public Health officials started talking about quarantines in those early years I once heard a presentation at a scientific conference from a demographer trying to figure out if AIDS could cause the population explosion in Africa to go into reverse no one knew what it was or how its spread it was a mystery except to the Obscure virus Club who thought it looked a lot like the leukemia viruses they had been studying for years what point in this process did you say I think it's a retrovirus

wouldn't you going involved in it evolved it was a retrovirus so they buy that by definition I the day I got in it I'm thinking gets a retrovirus the paper by Bob Gallo rejected by the Journal of virology in September of 1980 was about human t-lymphocyte Tropic virus one htlv-1 and the possibility that this strange new retrovirus had found its way into humans now a year later Bob Gala looked at AIDS and thought it was behaving a lot like a cousin of htlv-1 well why don't what led you to suspect it was a retrovirus our experience with htlv-1 and feline leukemia virus what is that experience glug sex mother to child

it infected T-cells check it caused immune dysfunction check it spread from mother to child check it spread through blood-to-blood contact or sexual transmission check by 1983 Gallo's lab had isolated and described the AIDS virus and figured out how to grow it in the laboratory by 1985 they had developed a test for it by 1995 there was a class of drugs available to treat HIV that meant the virus was no longer a death sentence that is an astonishingly short amount of time to detect understand and treat a new disease and why was the progress so fast because we had a head start in the mountains that have been said and written about AIDS the usual tone is one of horror at the indifference and incompetence and resistance that greeted the epidemic

of that is true but you can also make the case that we got lucky not lucky in some ephemeral way but massively unequivocally epically lucky lucky because ludvig gross insisted doggedly year after year that a virus could cause cancer because Howard temin insisted that the central dogma was wrong because 10 min in Baltimore found a crucial little enzyme called reverse transcriptase because Bob Gallo got it into his head that if they were mice retroviruses and chicken retroviruses and Cat retroviruses there had to be human retroviruses and then he found a human retrovirus and learned how it worked and learned to isolate it and grow it in the laboratory and every one of those lessons turned out to be perfect preparation for the most terrifying retrovirus ever known if HIV arrives as a force 10 years earlier what

opens scientifically medically disaster this is David Baltimore again the worst thing that can happen and it was proved in the HIV epidemic is not to know what's causing a disease because that gives Liberty to Fantasy we could know it was infectious and know it was a virus but not be able to couldn't find it couldn't find it

remember what David Baltimore said of the experiment in 1970 the led him to reverse transcriptase it took two days it was a trivial thing but only because he knew what he was looking for if you're faced with a retrovirus and you don't know what you're looking for you're lost you can't find it unless you know it's this particular class of bright it was the search for reverse transcriptase in the virus particles that opened up the knowledge that it was a virus that was causing the disease the world may not have been ready for HIV but the Obscure virus Club was

little bit gross died in 1999 at the age of 95 of stomach cancer caused by infection with the bacterium helicobacter pylori which he himself had researched Howard temin died five years earlier in 1994 at the age of 59 of lung cancer the Obscure kind you can get even if you've never smoked Bob Gallo is still very much alive with pictures of his old friends on the walls of his office now there is life yeah hell yeah he's just he's this is not long before he died oh he's so young it was so sad yeah it's awful at 10 mins memorial service Gallo told the story of his first encounter with his friend yours before in Paris I found a copy of his eulogy it's like the beginning of a love story

I was in a traffic stalled taxi with a few others and we saw Howard walking alone and he was poking his nose in and out of the store Windows he was smiling he was looking quizzical he was the picture of happy Boyhood curiosity retained in a man

I think maybe you've been inside of it so long maybe you miss how astonishing it is

yeah that's true that's true my wife would put it in the mystery so you know into something more powerful than you were b or anything else or look what if them in Baltimore discovered reverse transcriptase there is no field start with that too

I would start here what if any of these people Peyton Rous the gross Howard temin Robert Gallo in their Pursuit Of Truth had been motivated by the expectation of reward where would we be or if they listen to what others said as opposed to trusting in what their own experiments revealed or if they had only been willing to wonder five years in the wilderness instead of 10

many of the stories in this season of revisionist history have come down to the same issue how we should act in the world in novel and difficult circumstances how we should think about what matters for a profession or think about those who choose a crooked path or descent from Orthodoxy or borrow the traditions of others or engage with someone loathsome I could go on but if you are looking for one example to be your guide start with this one the grace and Persistence of Howard temin and the Obscure virus Club

thank you for listening to season 4 of revisionist History every week on revisionist history I say the names of the people behind the revisionist History Podcast and for this episode I wanted to let you hear them say their names for themselves this is my team nothing would happen without them Mia Lobel Jacob Smith Julia Barton flan Williams Camille Baptista Luis Guerra

special thanks to Carly Migliore Heather Fain Maggie Taylor Beth Johnson Maya Koenig and Jacob Weisberg El Jefe

by the way you can hear a longer version of my interview with David Baltimore on the solvable podcast which Pushkin produces with the Rockefeller Foundation

revisionist history is brought to you by Pushkin Industries I'm Malcolm Gladwell

this is the final episode of season 4 of revisionist history but that does not mean we're done next week we're going to bring you a special treat it's an excerpt from my new book talking to strangers which comes out September 10th we've created a special kind of audio book based on what we've learned over four years of doing this podcast and next week I'm going to bring you a chapter from talking to strangers to whet your appetite it's a spy story about one of America's most notorious Traders I know you'll love it