 Hi everybody, I'm going to go ahead and get started to reward those of you who are here on time and more people may trickle in and that's great also. My name is Liza Mundy, I'm a fellow here at New America and I have the honor and privilege of introducing Meredith Wadman who has written a fabulous new book, The Vaccine Race that she'll talk about. Meredith, well I wanted to say also I realize today is Valentine's Day and we appreciate you're spending your Valentine's Day lunch with us. I actually think that Valentine's Day is a very appropriate day to talk about vaccines because vaccines are one of the main reasons why the people that we love are with us hopefully for a long time. The children that we love are born without disfiguring diseases or more likely to be that fortunate and to stay with us for a long time. So I think there's a strong connection between science and love and particularly between vaccines and love. So it's great to have this today. Meredith Wadman is also a fellow at New America. She is a former Eric and Wendy Schmidt fellow which is our wonderful fellowship to encourage book authors, journalists and other arbiters of reporting and presentation to the public to give people support and time and space and community to do their great work. And Meredith has been part of that and a very valuable part of the New America community. She has covered biomedical research politics from Washington for 20 years. She's a reporter at Science and was formerly a reporter for Nature and a contributing writer at Fortune. Her opinion articles have appeared in The New York Times, The Washington Post and The Wall Street Journal. A graduate of Stanford University and the Columbia Graduate School of Journalism, she began medical school at the University of British Columbia and completed her medical degree as a Rhodes scholar at the University of Oxford. So Meredith is going to chat about her book, then we're going to have a conversation and then we're going to open it up for questions. So Meredith? Hi everyone. I am so delighted to be here and honored and thrilled as well. And this is my first book and this is my first really totally official book talk. So I am especially delighted. I'd really like to thank both Liza for being here and taking time from writing her own fabulous book to spend time interviewing me and introducing me. And also the folks who put this together, especially Ellen who I know put a lot of work into it. Finally, I really want to thank New America because without the Fellows Program which funded me for two full years to work on this book, this would never have seen the light of day. For people who write their books nights and weekends, my hat is off because I don't think I could have possibly achieved this without the really important support of New America. So I'm going to start with a mystery which is what is the relationship between this sporty Swedish gynaecologist, this determined young biologist, this baby who has cataracts and other difficulties, and this Catholic orphanage. All of those photos are from the 1960s incidentally. So I'll leave you to mull that and we'll proceed ahead to talk about how did it all begin? I started writing this book and it's too small for you to see but basically what you're looking at is a policy form that appeared in Science Magazine in the summer of 2012 and it was basically two sides debating should patients be paid when their leftover tissue scraps from surgeries and so on are taken and turned into lucrative medical inventions or research tools. And that sprang out of the book from 2010 that many of you may have heard of the immortal life of Henrietta Lax when an impoverished black woman who could barely read and was dying of cervical cancer, her cervical cancer cells were taken and turned into a hugely important research tool that is used widely, arguably more widely than any other cell line to this day. So that spurred off this big debate because of course she was never paid nor were her descendants paid for much money that has been made from those cells. So that appeared in July of 2012 and then in September of 2012 came this letter responding to the policy form and it basically was from this guy called Lynn Hayflick in California and it said the HeLa cells that's the Henrietta Lax cells are getting all the attention but I'd like to point out that there are some cells called WI-38 and I derived them from an aborted fetus in 1962 and there was a huge intellectual property fight over them and moreover they've been used to make vaccines that have vaccinated hundreds of millions of people and other cells that came from the technology I developed have made vaccines that have vaccinated billions of people and so why isn't anyone paying attention to these? I thought well no one else may be paying attention but I am going to pay attention. I phoned him up and within a couple days, a couple weeks I was able to visit him where he was then living with his wife who is in Northern California. So this is the same young fellow you saw in the earlier photo several years later, Lynn Hayflick. He will be 89 this coming May and he is still a going concern. So I was able to spend three days in Northern California interviewing Lynn and he took me back down memory lane to this place, the Wistar Institute of Anatomy and Biology, a medical research hub on the University of Pennsylvania campus although independent from the University and in the early 1960s when Lynn Hayflick worked there it was the grand central station of virology research which was really important at the time because the only routine childhood vaccine against a viral disease that we had was against polio and that was really a very recent triumph. There was actually, I should correct myself, there was a smallpox vaccine but smallpox was disappearing and it wasn't as urgent a problem. However, measles, mumps, rubella, hepatitis, many other diseases did not have routine childhood vaccines. So this guy, Lynn Hayflick, 1962, age 34, sets about deriving some cells that he thinks and hopes are going to revolutionize vaccine making. Now why does vaccine making need to be revolutionized? Well really short biology here, a little mini bio seminar, viruses to reproduce need to invade cells. They can't do anything outside of cells and so they invade cells, hijack the cell machinery to reproduce many, many copies of themselves and then they burst out of the cell. Well to make a virus vaccine you need cells as essentially little mini vaccine factories because you have to make lots and lots of virus which is then either killed or weakened and then injected into human beings to induce an antibody response that will protect the person the next time they're exposed to a virus. So what was being used as these little mini cellular factories back in the early 1960s? Well the Salk and Saban polio vaccines, the great public health victories of the day, the first polio vaccine came on the market in 1955, were made using cells from monkey kidneys and literally hundreds of thousands of monkeys were imported and slaughtered for this purpose in the late 50s and early 60s. That's all well and good except for the fact that monkey kidneys are home to many, many silent viruses. Up until 1961 it was thought that these viruses were completely harmless, that they infected monkeys and so what if they were in the cells being used to make polio vaccine. But in 1961 one of these silent monkey viruses called SB40 was discovered to cause uniformly lethal tumors in hamsters in the lab and there was a quiet panic among regulators who tried to keep it quiet and then the national inquirer, while the mainstream media ignored the problem, got hold of this fact and wrote the great polio vaccine cancer cover up. And even though the headline is hyperbolic, the facts of this story were essentially true which was tens of millions of Salk vaccinee school kids in the 50s had been vaccinated with polio vaccine much of which contained the silent SB40 monkey virus. So that was Hayflick's incentive as he thought we've got to have a better solution than using and slaughtering these millions of monkeys each with possibly their own unique set of silent viruses. Always a new one waiting around the corner and who knows what harm it will do. So Hayflick derived cells from the lungs of a fetus aborted in Sweden legally in 1962 and made this group of cells in a dish. It's called a cell line because they replicate themselves over and over in a dish. Now they don't live indefinitely these cells but they replicate through 50 divisions more or less. That's called the Hayflick limit these days. What happens is if you freeze some of these cells after perhaps they've replicated nine times you can freeze them for a decade or two or four and when you saw them they begin replicating again and they in quotes remember that they have 41 replications still to go. Well if you apply a little exponential math Hayflick created 800 ampoules of these cells and froze them in the summer of 1962. Each ampoule had 2 to 3 million cells in it. Each cell capable of dividing another 40 odd times. Well when you do the math you discover that more than 20 million tons of cells can be made from the cells in just two or three of those little ampoules and guess what he'd made 800. So for practical purposes the supply of these cells called WI-38, WI for the Wistar Institute was infinite. However there was one inveterate obstacle that Hayflick didn't count on. He was the US's vaccine gatekeeper. He was located at the NIH and his name was Roderick Murray and he was having none of Hayflick's new cells. He was extremely conservative. He felt like you know what poliovirus vaccine has been fine for us so far. All these salt kids that have been vaccinated walking around they don't seem to be falling down dead from SV-40 virus. Let's stick with the evil we know and not launch into something we don't know. He was afraid that they would become cancerous. That was his bottom line fear that Hayflick cells would become cancerous even though Hayflick had shown in multiple experiments that they had no tendency to do so nor to this day have these cells ever become cancerous which would scare off vaccine companies from using them to make vaccines. Then Hayflick had another problem and his name was Hillary Koprowski, the middle man in this photo. He was a famous larger than life polio vaccine pioneer and he ran the Wistar Institute. In fact he turned the Wistar Institute from this moribund ancient kind of creepy old museum like place in 1957 into this hub of sort of no bell leveled science in the 1960s. He was very powerful and not super ethical and really ambitious and he wanted Hayflick cells because he needed to, he wanted to capitalize on them in essence to turn them, use them to turn a profit for the Wistar Institute. Well it so happened that the cells were derived by Hayflick on an NIH contract. He had funding from the government and the small print of the contract said title to these cells shall transfer to the government when this contract is up. Well by 1967 Hayflick had had enough of Koprowski. He felt like he was a second class citizen at the Wistar Institute and he found himself a job at Stanford. And so the contract was terminated and arrives from the NIH, a specially equipped station wagon to take possession of all the, now this time there's about 375 ampoules of the cells left in the Wistar basement and liquid nitrogen deeply frozen. So the NIH station wagon arrives to carry the cells back to Bethesda and Hayflick says well I don't have an inventory ready yet, give me a few days. And then when no one's looking he goes to the basement of the institute and pats all the cells into a liquid nitrogen refrigerator, takes them to a friend who's working at Wyeth who hopefully stores them for him for a few months. And then a few months later when he's ready to move to Stanford, he belts the cells literally into the back seat of the four door Buickle Sabre, that was the family vehicle, puts his kids in alongside them. And off they go via the Grand Canyon to the new job at Stanford with the cells merely arriving alongside. Kind of a spectacular act of vigilante-ism. However, later he got what some thought was his comeuppance for making off with what was in many people's views, government property. And what happened in the mid-1960s, I don't want to tell you the whole story of the book, but it was interesting and it involved really the questions of who owns biological inventions when someone who's government funded but used his own brain power actually did the work and made the inventions. And big changes came about in the late 70s and early 80s to enable scientists like Hayflick funded by the government at universities to actually profit from their own inventions. He was just a little too early for his time. So that's the Hayflick piece of my book and I'm gonna stop there and sit down and Liza and I will talk about a whole nother element of the book. Just a riveting tale of science and as you say, vigilante-ism. So let's talk about the rubella piece of this. You've teed us up for this. Talk about the rubella epidemic in of 1964, why there was one, or why they occurred periodically, and how that accelerated the vaccine race. For sure. So rubella like Zika, which you've probably heard of these days, is a mild disease if you or I get it. We might spike a fever, we might have a rash. We might not even be aware we're infected because it's so mild. But if a pregnant woman is infected, and particularly in her first trimester, there is a huge chance of serious damage to the fetus. The virus, which looks like these little black things, you can see them traveling between two cells in this picture. The virus invades virtually every fetal organ and at certain points in the first trimester, there's a 100% chance of fetal damage if a woman is infected. So these babies, and there's a huge epidemic here in 64 and 65, more than 12 million Americans were infected. And as a result, tens of thousands of babies were born blind, deaf, intellectually disabled. They had shrunken heads like the Zika babies you see. Many had autism. They also had congenital heart defects, holes in their hearts. They were really seriously damaged children. And so there was a panic. There was no vaccine. It was a scary time to be a pregnant woman as the March of Dimes poster shows. You had no recourse to even any kind of therapy. You didn't know who around you was infected. Public health authorities were telling you to stay away from small children because they were most likely to be infected. Well, who spends a lot of time around small children? Pregnant mothers who already have small children. So it was a really scary time. And a scientist at the Wistar, who was Hayflick's colleague named Stan Plotkin, was one of the few scientists anywhere who knew how to run a blood test to show if a woman had rubella. And this would take three to four weeks. He would have to draw blood and then wait three to four weeks and then see if the antibody had changed. And so he would be sieged by these pregnant couples, finding him at the Wistar saying, please tell us. It has my wife that infected and I am infected. And sometimes they just couldn't bear to wait. And they would choose to have an abortion before he got the results of the test, which was, as you can imagine, devastating. It's not so easy to get an abortion in 1964 in the United States. In fact, it was a criminal offense in all 50 states and in Philadelphia and Pennsylvania where Plotkin was working. There was not even an exception for the life of the mother in the state criminal law. However, there was a parallel universe in major university hospitals where essentially women who were whiter, generally wealthier, better connected could get abortions quietly through what was called a therapeutic abortion committee, which was several doctors who would pass muster on a woman's application for an abortion. And so abortions could be had in some cases, but other women chose not to have abortions for obviously ethical or religious beliefs. So there was, as a result, a lot of babies born who were damaged. And as you pointed out in your talk, the cells themselves that led to the Hayflick line came from an aborted fetus. Was that a difficult thing to obtain? Yeah, so Hayflick initially did a lot of experiments trying to launch these cell lines with aborted fetuses from the hospital of the University of Pennsylvania, which was right across the street. It was a day when patients weren't consented. It was sort of like the surgeon there would say, oh, sure, just stop by the Guiney Suite. We're doing an abortion at this time or that time. There was nothing proper or informed consent for the patient or the women wouldn't know basically that their fetuses had been used. And this was the same case with the woman from Sweden who had the abortion, whose lungs became WI-38. She was not informed at the time. And only months later, when Hayflick sent back an emissary to obtain her medical history to make sure, because vaccine makers would want to know if they were going to use these cells to make vaccines, they would want to know, was this woman, did she have any infections? Was there cancer in her family history? How about hereditary diseases? And so, through an emissary who was this very mannerly young Swedish pediatrician from a storied and wealthy Swedish family, she was the one dispatched to go and find this woman, I call Mrs. X in the book, and find out her medical history, which, as you can imagine, was a delicate task. However, it did emerge that Mrs. X was healthy, so was her husband, and so that part is history. And so was this essentially the first example in the United States of prenatal testing, the test that was done on the pregnant women for Rubella? It was just the first experience that American women had had of finding something out when they were pregnant. That's a really good question. I am guessing so, but I'm not sure. And it's not the way we conceive of prenatal testing today, where you do amniocentesis or chorionic villa sampling when you're actually sampling from the fetus. And it was a simple, you know, a blood test, or a throat swab even from the pregnant woman. Oh, really? Yeah, yeah. And then the women had to make decisions. Did this experience in, did this experience drive at all the abortion debate in the United States? Did it influence the abortion? Roby Wade would come along less than 10 years later. Did it have any impact, or did they sort of exist separately? It did, and you would see states start to liberalize their abortion laws. Some states in the late 60s and some of it were in response to the Rubella epidemic, undoubtedly. There was also another really important event in 1962 that hastened some liberalization of state abortion laws, which was this woman, Sherry Finkbine, who was an actress on romper room in Phoenix, who unwittingly took phyllidomide for morning sickness during her pregnancy, was told her fetus would be damaged. It somehow got public, and her local hospital in Arizona would not perform an abortion, and she ended up flying to Sweden to have an abortion with headlines every day, reporters following her every step of the trip. That in itself did a lot, I think. So that was a very public episode, and then there were these private agonies that women were going through and having to make that decision. And one of the things in your book, one of the many, many points in your book that really struck me was if I remember correctly, sometimes the aborted fetuses would end up, well, they would be analyzed to see whether or not they had had Rubella, and sometimes the parents would find out, right? Whether the fetus had or had not. Sometimes the fetus had not. Yes, that's particularly heartbreaking. Stan Plotkin, this young pediatrician who was racing to develop a Rubella vaccine at the Wistar Institute because Rubella epidemics came around every six or seven years. And so the clock was ticking toward 1970 when the next Rubella vaccine was expected, and Congress and the NIH too were under pressure to get a vaccine before then. And so Plotkin, when he advised these couples who came and found him for the blood test, with those couples who chose to abort, he would ask, could I obtain your fetus? And when he got the fetus, he would test it for Rubella because he was trying to capture a virus that he could then weaken and make into a vaccine. And so his actual vaccine is called RA for Rubella Abortus, 27, because it was the 27th fetus he obtained in that year of 1964, and then three because he captured the kidney, rather the virus from the kidney, which was the third organ of that fetus that he dissected. Now, it's so important, it's just hard to believe, but the irony of it is that from the virus that he captured from that fetus and then grew in Haiflich cells from another fetus came this vaccine that has now, as of 2015, wiped out Rubella in the Western Hemisphere and is used virtually worldwide against the disease. And so you've ironically prevented untold numbers of stillvers, miscarriages, or voluntary abortions because people haven't gotten Rubella when they've been pregnant. Just as, I'm sorry, I have to ask this, just as a sideline, why does an epidemic like that come around every six or seven years? I mean, do we know why? You know what? I don't know that we do. I would have to ask a Rubella expert, and I'm not sure. I know that this, like... But they knew that they had this window. Well, they knew because they'd been tracking them. They could see that the last one was 1957 and the one prior was 1950 and the one before that was 44 or whatever. It had only been discovered that Rubella and fetal anomalies were linked in 1941. So this was still fairly new knowledge. Yeah. So another of the vulnerable populations that's involved in your story are orphans. And I wondered if you could talk or read a bit about that part of the story. Sure. And I'm gonna read about this orphanage that is behind me on the slide now. It was called the St. Vincent's Home for Children and it was in Southwest Philadelphia, only a few blocks from, in fact, Len Hayflick's childhood home there. It was a working class area, a lot of Irish and Jewish immigrants, but the home itself took in kids from all over the city and also from a maternity hospital, a home for unwed mothers, so-called, just across the lane from the orphanage. So I will read you just a couple minutes. The St. Vincent's Home for Children at 6900 Greenway Avenue in Southwest Philadelphia was made of red brick, stood three stories tall and took up most of the city block. Its two symmetrical wings were marked by long rows of rectangular windows. The pediments high above the doors were crowned with stone crosses for the Roman Catholic Archdiocese of Philadelphia owned and operated the home where the cornerstone had been laid in 1937. While many called the St. Vincent's Home an orphanage, not all the parents of the 65 children who lived there in 1964 were dead. Some were sick or destitute or in jail or heading that way, or they were unmarried girls and young women who had chosen or been forced to give up their children, their babies for adoption. Many of those young mothers gave birth at the Home and Hospital for Unwed Mothers across the lane where more than 400 babies would be born in 1965. Those babies born at St. Vincent's Hospital for Women and Children who weren't adopted or placed with foster families within the first year of their life were then turned over to the Home for Children across the lane. Often these were black or mixed-raced infants who weren't adopted. Five nuns staffed St. Vincent's Home, helped by a corps of hired childcare workers who dressed and fed the toddlers, changed diapers, played with the children, and bathed them each evening assembly line fashion. There were also two cooks, two adopted stray dogs named Jamie and Steve, and a grumpy maintenance man named Mr. Messina. The nuns belonged to the missionary sisters of the precious blood and were friendly if impractical white habits up whose wide sleeves more than one stream of pee found its way during diaper changing. They lived in simple single rooms on the third floor and worshiped in a small chapel on the ground floor. The nuns worried about the children. Sister Damien, a petite Austrian-born nun in her late 20s, knew that they were children after all and there were so many of them. Every one of them needed one or two adults they could call their own, a level of attention that she could not possibly provide. There were crushing moments. The day that a foster family arrived to take one boy away and he arrived in a cacophony, unraveled in a cacophony of desperate screams and wails. The unforgettable lost look that an unnamed sister, Mary Joseph, observed on the face of the deaf girl, E, when she discovered that the beautifully wrapped present that Archbishop John Joseph Kroll handed to her at the annual Christmas party at a downtown hotel was, in fact, just a decoration, an empty box. It was from the bald, the spectacled Archbishop Kroll who was Philadelphia's top prelate at the time that Stanley Plotkin got a green light to study his new Rubella virus vaccine in the children living at St. Vincent's home. In his letter requesting the Archbishop's permission, Plotkin did not explain that he had captured the virus from one aborted fetus and grown it in cells from another. Kroll was passionately anti-abortion. In 1973, he would call the Supreme Court's Roe vs. Wade decision striking down state criminal abortion laws, quote, an unfeakable tragedy for this nation that sets in motion events which are terrifying to contemplate, unquote. But in 1964, the Archbishop gave the Rubella study to go ahead, quote, the subjects were 31 healthy, normal children aged 14 to 29 months, average age 21 months from an orphanage supervised by the Archbishop of Philadelphia Plotkin would write in the paper that resulted, quote, permission to include the children in this study was obtained from parents or guardians, unquote. So I'll stop there. Well, not to give away the narrative, but can you talk about what went on at the orphanage, what the experiment consisted of and what came of it? Sure, so to produce a viral vaccine, you take a virus that has caused disease in the human being and you grow it through generations in a lab dish. With each generation, it adapts a bit more to life in the lab and as it so does, it becomes less able to cause disease in human beings. And so the number of generations you've grown it through weakens the virus. Well, when Plotkin first took his rubella virus to St. Vincent's home and it had only been grown through four generations, and when he put it into the kids, they got rubella. They got these rashes, swollen lymph nodes, fevers, and so it reminds me a bit of if you've ever trimmed your own bangs, you just want to cut a little bit off to begin with because if you go too far, then you've gone too far. So same with weakening the virus, Plotkin didn't want to weaken it too far where it would be an ineffective vaccine. So he weakened it a bit at a time, but the first round of kids that received it did get rubella. It needs to be said that unlike the polio vaccine that was experimentally tested on premature newborns at the largely black hospital in Philadelphia called Philadelphia General in 1959 and 60, a polio vaccine on rogue can kill you. Rubella is generally a mild disease and I think that was some of Plotkin's thinking when he took it there. It's still hard for us to imagine today but it also should be pointed out that physicians at major institutions, not bad apples, but really big fellows with the backing of the NIH were doing these kinds of studies in institutionalized children all over the country. This was the norm, I'm sorry to say. In any event, Plotkin went through several more iterations with the vaccine. Eventually he grew it through 25 generations. By that time he had gone through all the kids at the orphanage and he had taken the vaccine 90 miles northwest of Philadelphia to a state institution for mentally disabled children where he continued to test it until it was more or less perfected. When did that stop being the norm? Well in 1966, an anesthesiologist at Harvard named Henry Beecher published this medical establishment shaking article in the New England Journal of Medicine that outlined more than a score of studies where he just introduced the paper by saying these are unethical, had these subjects known the uses to which they were being put in these experiments they would never have been allowed. It was like he was saying sorry the emperor has no clothes and then only then did the NIH move to require informed consent for participation in human studies and ethics committees to sign off on all human studies before any medicine or other therapy went into human beings. That was only a policy, it wasn't a law until the mid 1970s at which time our current human subjects protections more or less came into being. There are also special provisions for institutionalized children, for prisoners, for other categories of vulnerable human beings today. So it really took one member of the establishment to speak out against it and was there a groundswell of support from other members of the medical community saying yes, I sort of thought this also all along. No, I think most medical people more or less rolled their eyes. You could sort of read that in the reactions at the time. They were required to do this to get NIH funding but there was a sort of a sense of entitlement and that took some time to go away, that's interesting. So the principles in your story, I was really amused by your presentation of Hayflick's response to the Henrietta Lacks narrative becoming so popularized saying, hey, wait a minute. I had a controversy also. Did the principles in your story embrace your telling of the controversy? Is that what he was looking for? Hayflick loved attention. However, I think at the beginning he was more open to me than he eventually became if my question's got tougher. He's very proud and he has a very extreme keen sense of justice and a keen sense of how he is perceived publicly. And he went through the ringer with the NIH in the 1970s which I haven't even got into where there was this massive investigation of him for taking the cells and the threat of criminal charges and many researchers rallied to his side and said, hey, he's done a lot with these cells for public health and for our research community, lay off him. But there were also people downtown here who were out to get him and succeeded in blocking him from receiving NIH money. It was a very painful time for him and some of this reawakens those wounds, I'm quite sure because the story of his ultimate downfall is told in some detail in the book. So did your reporting relationship become more and more difficult as it went on? It did, although I have to say he was cooperative to the end in terms of answering my technical questions of which there were many and hours been answering emails and so on. Sam Plotkin who developed the Rubella vaccine was the polar opposite. He was like, come to my house north of Philadelphia. I'm happy to talk to you but I'm not gonna sort of thrust my story upon you. I was allowed to draw it out but then he opened these cardboard boxes in his basement that basically had the entire story of the race for a Rubella vaccine and how he Plotkin, being an independent academic scientist got sidelined for political reasons because there was another Rubella vaccine candidate developed at the NIH, which by the way was at the time the vaccine regulator for the country. So FDA wasn't involved yet and so you had these two scientists developing a vaccine right up the stairs and around the corner from Rod Murray who approved vaccines for the US public and so guess which vaccine got approved first? Even though Plotkin, it emerged, was safer and more effective and would finally be approved in 1979 and has been given to all of our kids ever since. It's the R in the MMR vaccine. That's all just fascinating. And another really interesting point that you made in the book is this was also a kind of a pivot point in terms of biology moving from kind of pure academic research into a very commercialized industry realm, right? I mean, could you talk a little bit about that? Sure, so several important events happened in the late 70s and early 80s. In 1980, the Supreme Court ruled that living things were patentable so Hayflick couldn't have patented the cells when he first developed them. That changed and that opened the floodgates to the development of the biotechnology industry. That same year, 1980, Congress passed a law. Sounds boring, but it's the BiDole Act and it was extremely important because it said scientists who developed inventions at this or that university on government funding, their universities could take title to those inventions and some of the royalties had to flow back to the scientist, him or herself. So there was like a 180 degree term because up until then scientists who tried to make a buck were completely disparaged. They were persona non grata. It was seen as unseemly and beneath the pure pursuit of biology to think of making any money from your inventions. I mean, inventors of insulin licensed their vaccine to Lilly or their product and their method to Lilly for $1 because they wanted to get it out quickly to diabetics who needed it. That was in the 1920s. It's just, it was a complete about face. And so Hayflick you can understand who'd been basically seriously persecuted for trying to make, well I left out an essential element which is after he made off with the WI itself, 38 cells and took them to Stanford, first he started supplying them to other scientists that cost packaging, shipping, time spent preparing 30 bucks or something. But in 1974 he began selling them to drug companies and that was sort of the fatal flaw and that's where NIH just came down on him. He inked with Merica contracts that had it been executed would have been worth $1 million to Hayflick himself in 1974, well before these changes came about. So you can imagine when they did come about he looked at them with some irony and sense of having just been born a few years too early. Wow, wow. So would you say that the sort of the right to make money off of your scientific discovery now has become normalized in the same way that the experimentation on institutionalized populations was normalized? Absolutely and it was seen as, I mean the bylaw law was enacted in 1980 because the U.S. economy was more abundant and it was felt that the government was parking in these inventions at universities. It was, I think it was commercializing fewer than 5% of government funded biological inventions. Well that just completely changed. Yes, now bio-entrepreneurs are like objects of Indian admiration at their campuses rather than scorn and appropriately. And is that overall, is that a good thing? I mean do we end up with more? I think we do, yeah. That's my opinion. What would have happened with the cells if Hayflick hadn't strapped them into his view and taken them to Stanford? Would they have languished or would they have been also used and distributed to people who wanted and needed them? You know I think they might have been not just of the nine neglects. They were going to go back to basically a cell bank that stewarded them for the NIH. Hayflick was their greatest ambassador. He would like carry a liquid nitrogen refrigerator that looks like a hundred pound bomb minus the fins. He would carry it on to whatever airplane he was getting on, tuck it under his seat. It had to keep it upright because if it spilled the liquid nitrogen would, if it was on its side the liquid nitrogen would go up and terrify everyone in the cabin. But in those days he would take them all around the world and he would introduce them into labs and teach scientists how to use them and provide them gratis to drug companies back in the 60s. So he was like, he called them at one point like my children and he was invested in getting them into the world and getting them used. I think the answer to your question is and do almost certainly they would not have been made the use of that they were had they just gone back to the NIH. And this is not something presumably that anybody could do. This is what I've never understood about these cell lines that last forever. Like, could just any biologist go and replicate this particular cell line and presumably not? Cell cultureists were looked a bit as like the sort of the magic guys of biology at the time. They were, it was sort of an art more than a science to get cells to grow in dishes at the time when Hayflick developed these cells. That being said, I think it took as much persistence and willingness to tolerate mundane repetitive work as it did any particular flashes of genius. That's really interesting. And so this would be my last question and then we'll open it up. Given the problems and publicity around the Zika virus and the parallels in terms of prenatal testing and the damage to the fetus, is there any hope on the horizon for a Zika vaccine? Or is it still too small of a population for a pharmaceutical company to you don't wanna make that investment? Or I'm happy to say there's several Zika vaccine candidates that are in development by a number of labs and companies. And the reason is that Dengue is a cousin of the Zika virus and people had been working on the Dengue vaccine. So the sort of technological platform is there. They're starting the race with an advantage. With that being said, the World Health Organization announced last month that it's gonna be at least 2020 until a vaccine that you can vaccinate women of childbearing age with safely is available. And are we looking at the same deadline? Does Zika come around in the same way that Rubella did or is it always with us or do we not know? It was sort of lingering in Africa and then it somehow transmuted in the Western Pacific. I don't think it's known as well how it behaves. But I may stand to be corrected on that. I'm not an in-depth expert on Zika. Well, that's really interesting. So I'd like to open it up for other questions from the audience and raise your hand. Hi, I'm just curious. How did you decide how far back to go? So it sounds like you didn't start with, say, cowpox, smallpox, which I believe was the first vaccine. Right, well, I felt like my real story began with Len Hayflick in the early 1960s. But to talk about that, you more or less had to talk about the slow development of cell culture in the 20th century. So there's a quick tour through how cell culture had struggled vis-a-vis viruses in the 1900s, essentially the first half of the 20th century. In terms of vaccine making, again, really I mentioned the polio vaccine, but by way of introducing Hayflick's work and why it was important because of the monkey kidney cell problems and so on. Does that answer your question? Not really. I couldn't go back to Louis Pasteur and his rabies vaccine. It would just have become way too long a book. But yeah, so I had to draw some lines. I guess the in-depth stuff begins more or less at the middle of the 20th century. Let's wait for the night, thank you. I come from a small town in Michigan named Coldwater and it was the home of a mental institution. And I learned as I grew up that it wasn't just a mental institution, it was an orphanage. Was that common? I understand they got the records confused and some of these kids who were really orphans stayed in the mental institution and having lived with people who were mentally ill became mentally ill themselves. Was this just common throughout the United States? You know, I don't know the answer. I'm not an expert on that. But I know that a lot of these mental institutions were really just big warehouses for kids whose families couldn't deal with them and didn't have the services and the supports that we have today. I don't know the answer, I'm sorry. Hi, can you hear me? I wanted to know if you found any like, because you guys were talking about how you did testing, not you, but they did testing in orphanages and your research looks like it's from many years ago. Were you able to find any sort of generational side effects of certain vaccines if that was a common thing to happen that maybe wasn't tracked or kept records of, if that makes sense? You mean side effects once they were marketed to a large population or do you mean like kids that were? No, no, just the children that it was tested on. So the babies and in the orphanage? Right, I don't think serious follow-up was done on them. So I did not, that would be a tough question to answer. The children in the orphanage basically got rubella. And the first group did, I see. And then as he weakened it a little bit, then the successive generations did not actually get it. So he was calibrating, he was weakening it a little at a time. Yeah, for that I just meant like in general in vaccine testing in your research, in general, not just rubella because more vaccines were tested on these children like historically. So was there any information on what happens after these children get tested? Yeah, I didn't delve into, for instance, measles, mumps, hepatitis A in terms of long-term group effects on kids that were subject to testing. So I can't answer, I'm sorry. No problem. The other eye-opening testing moment in the book I found was when the scientists were doing their own children, were testing their, they would vaccinate themselves which seems okay. But they were also sort of testing it on their own children. Oh yeah, Hayfoot gave experimental polio vaccine to at the time two, three and four-year-olds. Yeah, yeah. Yes. So for polio, you have Salk and Saban who are competing and ultimately it turns out that the vaccine that was not the first one out is the one that ends up being used. In the vaccine race that you explore which is around rubella, you've got these competing labs including the one that's run by the director of the NIH facility. Were they developing the same vaccine as the race progressed or were their vaccines biologically different? And was their administration different if they were different? Right, so they were different. The vaccine that was developed at the NIH was captured from the throat of a soldier with rubella at an army base in I think it was 1961. And then grown in African green monkey kidney cells of different species than the Rhesus and one that does not harbor that SV-40 virus. So thought to be safe. Another company, Phillips Roxanne, based in Missouri grew its virus in puppy kidney cells. Over in Belgium, a company called RIT captured the virus from the urine of a sick 10-year-old girl, grew it in rabbit kidney cells. So there were all kinds of different recipes if you will for lack of a better word that were developed. And three vaccines approved in 1969, were approved in 1969 and none of them used the human cells. They all used animal cells and they all eventually disappeared from the market when Plotkin's vaccine was finally approved in 1979. And in fact, the Phillips Roxanne vaccine that was approved in 69 only lasted months on the market because once it was used in a bigger population it was discovered that it caused these really bad side effects in kids. They got this catcher's crouch problem where they had really sore knee joints and would have to bend like this and serve like a baseball catcher because of the inflammation in their knees and stuff. And within months, U.S. government agencies started refusing to accept the Phillips Roxanne vaccine and it was off the market quickly. So, and then the Merck vaccine. So Merck took an IHS vaccine, tweaked it a bit in duck embryo and that became the very first approved Rubella vaccine in this country in 69. But it gave women side effects. A lot of women would get arthritis or pain in their joints from taking the vaccine. And of course women were a primary customer base for the vaccine. Anyone thinking of becoming pregnant wanted that Rubella vaccine. So that was a problem. So there were issues with the early vaccines and yet Plotkin's remained an obscurity for quite a period of time. Plotkin's was a bit better. It emerged. Of course, yeah. Neasles, mumps, Rubella still requires a rejection which for an injection for some families that's a barrier to receipt. Why hasn't the oral vaccine been developed for any of the three diseases in MMR or a compound oral administrative vaccine? Polio is known to invade through the intestinal tract. So that's its natural route of infection. So it makes sense to have an oral vaccine that you swallow down. Plotkin experimented with an inhaled Rubella vaccine because Rubella first lands in the back of your throat and nose. Right, but it turned out that it was not very cost effective. You have to get a lot of vaccine to make it into the nose to develop a response. So I'm assuming that it's all about pragmatics and cost effectiveness in terms of measles and mumps, but once Rubella is injectable and then if you're packaging it with measles and mumps it only makes sense to inject all three, if that makes. Yeah. You described how we went through a transition in the mid 60s, 70s in the testing of vaccines from seem to be an era when whoever was in control of the institution would decide, okay, prisoners here can be tested or orphans can be tested to one that later required informed consent. But I wonder if you could expand a little bit on that with in a couple of particular areas. One is exactly how does the regime work today? Is it legal or common to pay people? How many people would actually volunteer to be a participant in a dangerous test if there wasn't some incentive? How do you test children who can't give you informed consent or mentally disabled people who can't give you informed consent and what is the practice outside of the United States? This describes what happened in the United States but there's a big world out there where vaccines are being tested. So couldn't I just go to country X, Y or Z and get the exact same test without having to bother with whatever the FDA or the Congress is requiring. Thanks. Sure, so what's required today? There's essentially two elements. One is that an ethics committee at the researchers institution that includes at least one lay person has to sign off on what the experimenters are proposing to do on the whole of the informed consent form on virtually every aspect of the trial. And at the same time, anyone participating has to give informed consent. And they take that really seriously. I have the opportunity to observe an Ebola vaccine trial when fellow participating in it that was being run up at the NIH and the informed consent had been sent back by the ethics committee as being too long and complicated. They said, get it shorter and get it so an eighth grader can understand it. So they really are trying to meet people where they're at and in fact are being required to meet people where they're at. At the same time, you would never put a vaccine for the first time into children today. The fellow I watched in the Ebola vaccine trial was a healthy 20 something year old apartment manager from downtown DC who had started volunteering in trials to make a couple hundred bucks pocket cash because you are as a volunteer compensated for your time and inconvenience. It's no way to get rich, but if you want to supplement your income and you're so inclined, people do do it. And that's why most people do it. Well, this is, I didn't ask a lot of participants that I asked this guy. So this was a cash thing for you. He said, you know, it started as a cash thing, but more and more it's come to feel like a sort of a civic duty. I'm healthy, I'm young. Why should I not contribute? It takes years to develop these vaccines. He gets high rate when there's like a panic about how do we get an Ebola vaccine? You know, like let's suddenly work on one now that it's in West Africa and might come over here instead of realizing that this is a marathon. This is not a sprint for each of these vaccines because you have to put it first in a small group of healthy adults and that's just testing for safety. Then it goes into a somewhat larger group of healthy adults looking for safety and efficacy, that it's doing what it's supposed to be doing in the human body. And then finally into a larger group of people with whatever condition, I'm taking medicines here, that you're trying to treat or protect against. So it's a staged thing. It takes years, not months or weeks, as it did in the 60s. I'm sorry, I'm forgetting the rest of your question. I can't speak to how it works in other countries. I know Europeans have stringent safeguards. I also know that these so-called contract research organizations, they're basically hired by pharma companies to go and run testing for them. They're excellent at running clinical trials, but I do know that oftentimes they will go to developing countries. And that's not only perhaps because the ethical safeguards are less stringent there, but also because there are what's called treatment naive populations. If you have, for instance, a new cancer drug for a certain kind of cancer, that a lot of times the requirement is you must test this in someone who hasn't had any other cancer drugs yet. So it's very hard to find a cancer patient in this country who hasn't already had some kind of cancer drug. So you go to Sub-Saharan Africa where people aren't getting treatment. And that happens with regularity. I hope I answered at least some of your questions. That's fascinating. So if you're gonna test the efficacy of an Ebola vaccine, at a certain point you're gonna expose somebody to Ebola. Well, so I should have added that the Ebola vaccine does not have whole-killed Ebola or weakened Ebola virus. It has a snippet of Ebola virus DNA that produces an Ebola protein that your body then produces antibodies to. So we've moved along in our sophistication. So you can test whether somebody's producing the antibodies. Right, and that's the other thing. These volunteers up at NIH had to pass a test, a true and false test on the nature of the trial they were enrolling in. I can get Ebola from this trial, yes or no. No, because you're just getting a snippet of DNA. I might feel this during, if I feel anything during the first 24 hours, I am to immediately call the nursing hotline, yes or no. I mean, yes. So they're watched very carefully. They're monitored very carefully. It's just, it's like a world different than it was 50 years ago, which isn't to say it doesn't have its issues today. It's not perfect, yeah. Okay, my question is kind of like his, what are some of the moral concerns? And then what is kind of playful about what can't be replicated in maybe cells, whether it is measles or something like that? Because I was interested in kind of like making it more scientific and saying that is this something that can be replicated? And like, what can we learn from either, like he was saying morally, where are we going with this? Is there a moral issue or concern? Or is it that this is science in terms of other cells and the body can be showing symptoms of having some of these diseases? Are you saying is there a way we can avoid using abortive fetal cells? No, is there a way to make sure that it can be replicated? Because if it's not able to be replicated in terms of case studies in certain cells, then it seems to have some type of moral concern that can't really, maybe there's more research to be done? I don't know. My real overall question is, are there any moral concerns if the science isn't leading someone to believe that this is a universal understanding of what you're seeing about cells and particularly this disease? So you're talking in the Rubella context? Well, we know how to track it by seeing if someone has produced antibodies to it and we know they're infected. I'm sorry, I'm not understanding your question. Well, I mean, there's whole cores of epidemiologists both at CDC and the World Health Organization and comparable agencies to CDC and other countries who spend their lives tracking infectious diseases, measuring them in populations, tracking their spread, containing epidemics. So there's definitely really solid science around this. And I mean, the fact that Rubella, there's no more homegrown Rubella in this hemisphere is definitely a victory of the Rubella vaccine. So you can see, to me, that's a really important public health achievement. I'm sorry, I got it. I have a quick question. Once the vaccine was out, was there any issue with making it accessible to the general population? The general population? So there were a couple of important acts, laws that passed in the early 60s in the Kennedy administration, both to mandate CDC to work with local public health authorities to get populations vaccinated and then to fund vaccinations for poor kids. So that has made vaccination here virtually universally accessible. I think our bigger problem today is with vaccine resistance as opposed to folks not having access. Yeah, sure. Thanks. Congratulations, by the way. I know how much hard work went into this, like an irrational level of hard work probably went into this book. I'm just wondering about the ethical parameters around culturing cells from an aborted fetus. Is it widely known that that is the source of these cells? Does that cause any kind, because I'm not familiar with this issue, does that create opposition maybe in pro-life camps? Oh yeah, there's sort of, there've been two chapters of opposition. The first was in 1972 and into 73 when this marriage counselor in Brighton, Michigan produced a set of alternative facts about what Hayflick was up to and announced in several pro-life newsletters that Hayflick was slaughtering infants at Stanford, keeping them alive just long enough for the virus to multiply in them and then draining their blood to produce the vaccine. And this just went wildfire throughout the pro-life community and he eventually had to get Stanford's lawyers involved to shut the sky down to get a retraction but he was still putting out brush fires and taking the retraction to tiny little newspapers all around the country for several months after that. And I think possibly the only reason that went away is because the Rovers' Wade decision came down and that became a much bigger and more important focus of activity by those who feel strongly opposed to abortion. But then a second round came around the turn of this century when a woman named Debbie Vintage, who is very strongly against abortion, discovered that a couple of her grandchildren had been vaccinated with Rubella vaccine and that it was made using fetal cells. And she became basically a one woman show called, her group is called the Children of God for Life but it's largely her but she obtained several hundred thousand signatures that she took to Merck and presented to the, which is the maker of Rubella vaccine in this country and has been for decades saying, find an alternative. We should not be forced to choose to either act against our conscience or not have our kids vaccinated against Rubella and this is ethically intolerable to those of us on this list. And she also bought a bunch of shares so that they brought a shareholder proposition calling the practice unethical which was loaded down at Merck shareholders meeting but they got it in front of the meeting which was a small achievement. Finally, she wrote to the Vatican in 2003 and asked them, please give us guidance for Catholics. I mean, should we be subjecting our children to this Rubella vaccine? We don't feel good about it and we're getting pushed back from our local school authorities when we say why we don't want our kids to have it. And the Pope actually, he was about to become the Pope, rat singer, referred it to this Pontifical Academy for Life which is this group of moral philosophers and so on in the Vatican and they mulled it for two years. And in 2005, they wrote back to her and said, in the absence of alternatives, it's a bigger evil to not vaccinate your kids against Rubella than it is to take this vaccine. At the same time, they said, all good Catholics should be making life miserable, doing their best to make life miserable for the companies that unethically manufacture these vaccines because apart from Merck, there's another fetal cell line from an abortion in London in 1966 that is even more widely used in antiviral vaccine making. Chickenpox, shingles, hepatitis A, couple other vaccines are all made in these MRC5 cells so Vintage and her activities went around both these two cell lines. But I think she's kind of reached the critical mass of people she's going to reach and when the Vatican responded that way in 2005, I mean, they're still really unhappy with the fact that there's no choice in this country but to take the Merck-Rubella vaccine. And actually there was another blow for them because Merck used to make monovalent meaning a vaccine just with measles, another one just with months and another one just with Rubella. So at least if you didn't want your kid to have Rubella, you could get them vaccinated for measles in months and Merck stopped doing that in 2010. So they were really unhappy and when there was that measles outbreak in 2015 at Disneyland, she put out a press release saying, don't blame the parents, blame Merck. They're making the feeble vaccine and they're not giving us an alternative. Okay, I'm winding up. I'm happy to take questions up front if there's something that you still would like to talk about and thank you so much for being interested in for your time. Great. Thank you. Thank you. Thank you.