The lost Lyme vaccine

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1:11When I was learning how to make radio, I had a day job in the file room at my aunt's family medicine practice, just outside of San Francisco. They were old school and didn't really do computers. So there was just a pile of paper, taller than I was, of faxes, doctor's notes, checkups, prescriptions, just everything. And as I filed that mountain of paper, I saw the community that they had built at that doctor's office. the generations of families, visit after visit, living their lives, trusting their health and their loved ones with my aunt's care. So it resonates with me when Vijay Seekand describes his work as a family physician.

2:01I take care of newborns to 90, and I say, stop at 90, because if you're 90, you don't need me. Vijay has been a family doctor in a little town in Connecticut. ever since he first drove up there with his wife in the 1980s. And we fell in love with the place. It was a small, charming town where you have a couple of very nice ins on Main Street. And just, you know, it's a lovely spot right there on the Connecticut shoreline at the bottom of the Connecticut River. But this town was special. The center of a newly uncovered disease that Vijay had only really read about in textbooks. Old Lyme is the place where I started my practice of medicine.

2:45It's also the place where Lyme disease was first discovered in this country. And it's consumed much of my life. The story of Lyme disease is long and winding. It's an old disease that's spread across much of the Northern Hemisphere. But in 1976, a Yale professor, Dr. Alan Steer, was the first to pin it down to ticks in Lyme, Connecticut, and give it its name. Over the last 50 years, Lyme disease has impacted millions of lives and has become one of the fastest-growing insect-spread diseases in the United States. But this isn't that story. This is Vijay's story of how a disease and the search for answers can become a career, a community, a life.

3:43I'm Meredith Hodnot, and this is Unexplainable.

4:02So when did Lyme disease tip from like something that was kind of theoretical to becoming a part of your everyday life and your practice as a doctor? Very quickly in the mid-1980s, when the media reports started to come out, there was quite a lot of anxiety. So I started to get phone calls in my office almost every day. I almost spent an hour before going home at the end of the day returning phone calls from parents who asked me what to do about their kids' tick bites. And so all of a sudden we had a snowballing of interest, anxiety, stress, need for understanding, diagnosis, and treatment. How did it feel for you to be a family practice doctor?

4:52Like you said, treating everybody from the infant to the grandma in the household and also be at this like epicenter of Lyme disease in this country. It was a lot of fun. It was a lot of fun. It was a lot of fun. Tell me. How often do you get to be a doctor and treat stuff that's not only seems this new, but to be right in the middle of it? I mean, it's the kind of thing where if you made a phone call to a customer service agent, they asked you what your address was, and you said Lyme, Connecticut, and they said, oh, where the disease is, right? And so it was a kind of, so, you know, as a doctor, it was kind of neat to have something that you can uniquely diagnose and be positioned to diagnose it, as well as to cure it.

5:41Yeah, yeah. I feel like it would be a lot less fun if you couldn't cure it. Right. Right. And there are those cases. One can write a chapter or two in a book about that. But as Vijay saw more and more patients come into his office with Lyme disease, he realized it wasn't always easy to recognize. That's because Lyme disease is a chameleon, a shapeshifter that's always changing. Lyme disease is caused by a corkscrew-shaped bacteria that lives in ticks' bellies. If an infected tick bites you, the bacteria gets in your skin and starts to spread in a rash, sometimes in this iconic bullseye shape. At this point, Vijay says it's often easy to knock out with simple antibiotics.

6:31But if it gets past the skin, untreated, the Lyme disease bacteria can get into the bloodstream and spread to your heart, your joints, your nervous system. Vijay treated patients that had half their face paralyzed, patients who passed out because their hearts were beating too slowly. The longer a patient had Lyme disease, the harder it was to recognize. Lyme disease could look like arthritis. It could look like a summer flu. It could look like meningitis. It could be completely asymptomatic and look like nothing at all. And Vijay was on the front lines, treating his patients, his friends, his neighbors.

7:18He contributed to dozens of academic papers in his spare time, and he was also moonlighting at the local ER. Until one day, he got a call. I was making rounds in the hospital, and the nurse on the floor came up to me and said, uh hey doc there's a guy on the phone he says he's from a drug company he says he wants to talk to you i said drug company why is he calling me at the hospital i'm making rounds and uh she's i don't know he says can you talk to him so i said okay i went over to the nurses station and i picked up the phone and there was a gentleman there on the phone uh his name was david krauss he introduced himself and said, you know, we've developed a vaccine for Lyme disease that's now ready for phase three, which is the actual late stage testing to see if it works.

8:14It had only been through the early phases where you just check to see that it's actually sort of safe to give to animals. Then you see if it's safe to give to people. And then as it may be safe in a small number of people's, but you don't check to see if it actually works until you know all of those ducks are in order. So anyway, so Dr. Krauss said, would you be interested in working with us on this vaccine now that we've reached this stage? And I said, wow, that's fascinating, of course. And I signed on. The drug company was SmithKlineBeacham, a huge international pharmaceutical company. And this vaccine was kind of unusual.

8:55The thing about Lyme disease is that But it takes about a day, maybe two days after the tick bite for the bacteria to travel from the tick into your skin. And in that time, there's a window after the bite, but before the transfer. So the vaccine does not work on the bacteria in you. What it does is the tick sucks up your blood, which has the antibodies in it, kills the bacteria before they can come and infect you. So it kills it in the tick itself. Yes. So here we have the vaccine, which is very unusual because it kills the bacteria that cause Lyme disease in the tick before those bacteria can infect you.

9:40It's almost as if we're vaccinating ticks. Exactly. The previous drug trials were promising, but now it was time to test this vaccine in the real world. There were going to be dozens of test sites across the country with thousands of patients. And where better to test a new Lyme vaccine than in Lyme, Connecticut? So Vijay signed up to run a test site as an independent contractor for the drug company. That meant he'd be recruiting participants, enrolling them in the study, and watching over them carefully for the next 20 months. Now, as soon as I just started the process of recruiting patients, I couldn't handle the number that started coming in.

10:27No way. It was just, it was mind-boggling. I put a little ad of the newspaper, and the phone started ringing off the wall. I had to get more phone lines. I had to hire a person just to answer it. And within a couple of weeks, I cut my work at the hospital in half. We ended up recruiting 1 ,200 adults, well, age 15 and over, and had to shut it down because I couldn't handle anymore. I ended up asking a colleague if he would rent space to me because I needed more space just to see all these patients. I lured a couple of nurses from the hospital and ended up having a large staff to take care of 1 ,200 people.

11:14So within about six weeks of that phone call from SmithKline Beecham, I was deeply involved in this study. So we took the baton and we ran with it. My wife volunteered.

11:33Ethically, I'm not the one who did her consent or gave her the shots. And in the pediatric study which followed, both of my kids received the vaccine. And I didn't know and they didn't know whether they were getting a vaccine or placebo. Oh, I had neighbors. All manner of people. I had people, you know, the lady who ran the donut shop across the road. She would, of course, bring donuts every time. I have to mention this. Years later, my son came home and told me he's getting married. And the woman he was marrying was one of those kids from the vaccine study from 15 years earlier. Wow. It's a small world.

12:17And it's fun and it connects you to people. Do you feel like it changed your perspective on the community? Yes, in a way it did. because I was pleasantly surprised to see that so many people would turn out to stick their arms out and have a needle stuck in them. So we gave half the patients a placebo, and we gave half the patients the actual Lyme disease vaccine, and I didn't know what they were getting, vaccine or placebo. It's what we call a double-blind study. It's the gold standard for studies. And then we followed these individuals for a couple of years through tick seasons. We checked them closely to see if they got symptoms of Lyme disease.

13:05We checked them in the most intense detail. We drew blood beginning of the season, end of the season, and any time you had an illness that might or might not have been Lyme disease during those two years, we drew your blood again. I had a photographer helping me with photographing the skin rashes patients came down with etc so we had the guy across the road also next to the bakery who had a photoshop and the photoshop guy every time i had a patient with a skin rash he would go out of his way to get the film develop it overnight provide a high quality picture for me to then fedex to the manufacturer and so we had the fedex guy we had the photo guy we had the bakery lady bringing the donuts And it gave me a sense not only of being a physician in the community, but being a part of it in a unique way.

14:02Beyond the vaccine, the drug company funding fueled Vijay's drive to pin down this shape-shifting disease. Take, for example, the first symptom of Lyme disease, the rash. Everybody talks about the bullseye. But if you have 12 different ways this rash might look, wait a minute, it's not so easy to diagnose. Sometimes the Lyme rash can appear in ways that we never imagined. So we had dozens of different rashes. Anytime a patient in our study had a rash, they'd immediately say, you got to see me, doc. I've got a rash. And because we had the resources of the large pharmaceutical company, we biopsied those rashes.

14:47Now, nobody in his right mind, or even if they had a million dollars, would be able to have their patient in their private practice office, have their skin lesion biopsied and sent to a lab. But we had. We had to prove if it was really Lyme disease or not. So we did a little biopsy from the edge of all of those skin rashes to see if they could find the Lyme disease bacteria in it. You would be amazed at half the time there were rations that I had no idea whether they were Lyme disease or not that turned out to be Lyme disease, which if we hadn't had the study, we would never have known. We would never have known.

15:26Vijay was managing one of the biggest test sites for this phase three vaccine trial. As a matter of fact, it got so busy, I had to stop my private practice completely. He stopped moonlighting at the ER. He stopped working extra jobs in local clinics. The study was his life, and he was the face of this study for his community. Was there ever, ever for you even the smallest moment of doubt? I love that question because being a double-blind study, I had no idea whether patients were receiving vaccine or placebo. And as you can imagine, during the course of those few years where we were blinded, I had patients out of 1 ,200 coming down with all kinds of things.

16:16Whether it's heart attacks, strokes, things that people have in the normal course of their lives when you're adults. And I always wondered, gosh, I hope the vaccine's not causing it. But fortunately, we had what's called a data safety monitoring board, independent board, which was not blinded. So they were able to look at all these things that were happening that were sort of worrying me and other investigators and know whether there was a signal or not that the vaccine was involved. So fortunately, this data safety monitoring board never called and said, hey, stop the study, which I wondered, gosh, I hope I'm not doing this.

16:59Vijay had to sit with these open questions. Did the vaccine actually work? Was it safe? Were there side effects? Vijay monitored his patients for nearly two years, but then the study was out of his hands. As you can imagine, the very vast amount of data that were accumulated from all the sites around the country had to be collated, analyzed, sliced and diced by statisticians, run by data safety review boards where they're looking at adverse effects that patients had reported throughout the study to see whether they may or may not have been related to the vaccine. So the patients actually became impatient in a way, no pun intended, because they wanted to know.

17:47And of course, patients, we didn't unblind the study until after it was over. So patients were wondering, did I get the real thing or not? And then, of course, it was a game. There were people who'd say, I know I got the real thing because I felt my arm really ached or I had this achiness the next day or this little temperature. So I think I got the real thing. But it'd be amazing how often they were wrong. Finally, after months of needles and months of waiting, the people of Lyme got their answer. The study results were published in the New England Journal of Medicine in July 1998. Sixty-six people in the placebo group got Lyme disease that year, compared to 16 cases in the fully vaccinated group.

18:33So it prevented roughly 80 % of cases of Lyme disease that would have occurred in people who were vaccinated compared to people who weren't. With over 10 ,000 patients, this wasn't the biggest of studies, but it was a perfectly respectable phase three trial, showing that there were no major side effects over the 20 months that the patients were monitored. Most symptoms from the vaccine, as reported by the study, were a sore arm, a little fever, nothing a few days and some ibuprofen didn't resolve. I was thrilled. I was thrilled. Vijay was a lead author on the paper, with scientists from some of the biggest research universities in the country.

19:17He contributed to textbooks and helped educate doctors around the world about Lyme disease. And with the study over, Vijay took on a new role, advocacy. Being the physician on the ground there in Lyme, Connecticut, my job was to tell these folks from the FDA why we even needed a vaccine for Lyme disease. In 1998, Vijay and other sponsor representatives for the drug company went to a holiday inn in Bethesda, Maryland, to present the vaccine study to an FDA advisory committee. This meeting lasted all day. Going into the weeds of the study design, the efficacy results, the safety data, Vijay shared what he had learned about the many faces of Lyme disease, how it could look like so many different things.

20:11It's often difficult to diagnose. It may be difficult to treat. It can have adverse consequences, which may be serious and untreatable or become chronic. And now we have a vaccine that is safe and effective in preventing it. What can we do except for give this to the American people? Then the coordinating investigator of the vaccine study, Dr. Alan Steer, shared some new findings of his own. Dr. Steer was a big deal. He's the one that first discovered that Lyme disease came from ticks decades before. And he'd been studying Lyme on his own, apart from the vaccine trial. He was particularly focused on how Lyme disease impacted the immune system.

21:06He noticed some cases where people with Lyme disease developed arthritis that was resistant to treatment with antibiotics. And he thought the immune system might be involved. It was pretty rare. We're talking about a fraction of a fraction of a percent of people with Lyme disease. And Dr. Steer wanted the FDA panel to know because he thought an even smaller subset of these rare patients with vulnerable immune systems might react differently to the vaccine. Even though the study showed that for thousands of patients, the vaccinated groups and placebo groups didn't have any significant difference in arthritis side effects.

21:48So what did this mean for the vaccine and autoimmune arthritis? The FDA panel wanted more clarity and asked for additional testing on long-term safety. But ultimately, they concluded the vaccine was safe and effective. Later that year, the vaccine, branded with the name Lymerix, was approved by the FDA. But the questions from the advisory panel meeting haunted the vaccine. There were some dark clouds on the horizon. There were unanswered questions. That's after the break.

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24:11There were two things that changed the course of vaccine medicine in the late 90s. First, a British medical journal published a small, now very soundly debunked study connecting the MMR vaccine to childhood autism. So here, this researcher had his license stripped from him at the end of the day. He had the black eye, the journal had the black eye, but the damage was done. And then, just a few months later, another childhood vaccine, this one against rotavirus, was taken off the market because it had a rare but dangerous side effect. And so the public perception of bad vaccines took off. So we had a perfect storm back then.

24:58Wait a minute. How do you guys know that this vaccine's safe? Look at that MMR. We read about it in the paper. This was the beginning of the modern anti-vax movement. And the newly approved Lyme disease vaccine, Lymerix, was one of their first targets. One of the things that people were worried about with the Lyme disease vaccine was whether it might cause an unusual form of arthritis related to autoimmunity. Scientists were still digging into how the immune system was connected to chronic Lyme symptoms like arthritis. And so the FDA and the drug company wanted to keep close tabs on a vaccine that used the immune system to fight Lyme disease.

25:43After approval, one and a half million people received the Lyme vaccine over the following three years, two or three years. What happens afterwards? The manufacturer actually collected a large amount of data on the people who received the vaccine after it was approved. This is called a post-marketing surveillance study, and it's common for new drugs. Basically, it's a trial period. to make sure there aren't any side effects that are so rare, the other smaller phases of the trial missed them. Another retrospective study showed that of the nearly 1.5 million people who had the vaccine, a few hundred people reported any joint or muscle pain, and 59 developed arthritis.

26:28A similar number of people would have developed arthritis in a group of 1.5 million people who hadn't had the vaccine. But in the wake of all the other vaccine skepticism unfolding at the time, it was a good story. A day didn't go by where I didn't get contact from one of the national or international media asking to talk about that vaccine that we heard might be causing arthritis or other autoimmune problems. How did all this media attention, what did it mean for your patients? Were they starting to get worried? That's a good question because these patients covered the whole spectrum. We had patients who said, hey, I was in the study.

27:14I came down with multiple sclerosis, doc. My neurologist diagnosed it. Do you think it's connected in any way to the vaccine? Because I read that there were maybe problems. I mean, you get stuff and you wonder, is it connected? Beyond the study, some patients were worried, confused. Maybe they had unexplained symptoms they didn't understand, or a health care system that they didn't trust. And then some doctors were confused too. They were getting mixed messages from the government. The CDC recommended that only people at high risk for getting Lyme disease should even consider getting the vaccine.

27:55Lyme disease was dismissed as a yuppie problem, a frivolous concern. and the vaccine, which could cost hundreds of dollars, was a luxury. Everybody else was doing just fine, wearing long socks, doing tick checks, and taking antibiotics if they caught it. And then the lawsuit started. It all happened so fast. Within months of Limerick's going on the market, a law firm in Philadelphia sued the drug company, claiming over 100 people experienced bad reactions from the vaccine, often citing crippling arthritis. And more lawsuits followed that. One of the people who enrolled in the class action lawsuit to sue the company, and indirectly me, was the wife of a doctor colleague of mine at the hospital.

28:50So it got that close. The pressure ratcheted up, And the FDA called back the advisory panel in 2001 to go over all of the safety data again. Reports from the time say the meeting was riotous. By this point, scientists had learned a little more about the interplay between the immune system and the rare treatment-resistant Lyme arthritis that had originally sparked confusion back in 1998. They found that these patients were more genetically vulnerable to getting arthritis with or without getting Lyme disease, and that the Lyme disease antibodies weren't necessarily causing an autoimmune reaction.

29:34I mean, scientists still don't fully understand all of the complexity of Lyme disease and the immune system, especially for people with chronic Lyme. So while there were no absolute definitive answers, this research made the hypothetical connection between autoimmune arthritis and the vaccine even more tenuous. Once again, the FDA found that Lymerix was safe and effective, a recommended tool against a significant disease that was spreading fast. But sales of the vaccine took a nosedive. and by 2002, the Lyme vaccine just wasn't good business. I'll never forget that. I'll never forget that meeting because I actually almost missed the ferry.