Note: the following transcript is a radio script and contains audio cues and other quirks (including imperfect grammar) of the medium. It may contain typos.
Kelly Oggenfuss: So I’m going to leave the bait in here and close this trap.
Taylor: So it’s uh like a metal box and one side has a door on a hinge, so they go in and the door snaps shut. And they are kind of trapped in the box…
Kelly: There’s a little treadle in the back, and when they step on that treadle it triggers the front door to close…
[ambi]
Taylor: I’m used to seeing squirrels and chipmunks in the forest. But At this moment, I’m standing on the grounds of the Cary Institute for Ecosystem Studies in Millbrook New York, and Senior Research specialist Kelly Oggenfuss is showing me the invisible inhabitants that I never see.
Kelly Oggenfuss: Now take a look.
Taylor: Oh hi little buddy!
Kelly: Buddies! There’s two in there.
Taylor: Oh they’re cute.
Kelly: Those two mice, that’s the species Peromyscus leucopus that’s the white footed mouse. That’s the mouse that’s everywhere.
Taylor: There are two adorable grey cotton balls cuddling at the bottom of the trap that Kelly is holding. They’re probably siblings, she explains. They’ll forage together, and they’ll get caught together. And In this study area, about the size of five football fields put together, they might have hundreds of cousins doing the same.
Kelly: So what I’m doing here is emptying out old bait
Taylor: There are hundreds of traps here too - set up in a grid, each one just a few meters from the next.
Some mice will get caught so often they call them ...
Kelly: “Trap-happy” and that means they’ll go into traps over and over and over again
Taylor: ... you can tell by the tags on their ears if they’ve already been examined before.
But tags aren’t the only thing you’ll find on their ears…
Kelly: Right here… do you see a little dot right at the tip of my tweezers…
Taylor: Oh my god that is so small.
Kelly: That’s the larval tick. So some of the clustering is going on here… where you have bunches of ticks right in the corner of the ear and right here by the tag.
Taylor: For decades, scientists at the Cary Institute have been studying the relationships between ticks, white-footed mice, and Lyme Disease… as well as deer, shrews, possums, squirrels, acorns and more… They’re also testing different tick killing chemicals to see if we can stop Lyme Disease at the border of our backyards, instead of at our doctor’s offices.
We’ll get into some of what I learned here in a future episode.
For now, I just want you to focus on the method… the process.
[Radio click] I have a squirrel at I3 if that’s a demo you’d like to provide.
Kelly: Would you like to see a squirrel? I have plenty of mice, so you’re not going to miss this.
Taylor: The day started with a bouncy drive into the woods, where we started checking traps, and collecting mice.
For me, a guy who is used to working most days in an office, this was a grand day out. A total adventure.
One highlight was the squirrel trap - the team is focused on capturing mice, but counts ticks on squirrels as well. Cornered squirrels are insane, by the way.
But for Kelly and her team, it’s just another day on the job.
Kelly: Alright, H1, hakuna matata
And once they collect the mice, well then the real work begins.
Kelly: That’s 23 ticks on the right ear, here.
Unidentified Male: That is an adult female, vagina 1, nipples 1.
Taylor: Can mice have multiple vaginas?
Kelly: The one and the two indicates sexual reproductive readiness as well [fades down]
[music]
Taylor: They have to take samples - of tissue, blood, urine, feces - and count all of the ticks on every mouse they catch.
Dude: One larva on the right ear… [fades down]
Taylor: And the day I joined them, they had caught nearly fifty of them.
Dude: One larva on the left ear, and one larva on the head
Kelly: Once again I have no feces! Sooo… [fades down]
Taylor: This is what science looks like: Four people, sitting in white coveralls at a plastic poker table in the middle of the woods, counting ticks with tweezers.
All day. Every day.
If this is the soundtrack to epidemiology that you hear in your head:
Taylor: [singing to the music] A clue… science … Eureka!
Then this is the actual pace of epidemiological progress.
[music gets dramatically slower]
Taylor: You’re marveling at the pee right now?
Dude: So much Pee… this might be half a mill
Taylor: Easy to forget when you’re the one waiting for answers. Back in 1975, Polly Murray had been to doctor after doctor, trying to figure out what was happening to the children of Lyme Connecticut. Here’s her daughter Wendy.
Wendy Murray: Hindsight is twenty twenty but oh my gosh you think about all the kids coming in with swollen painful knees and why weren’t they connecting the dots you know… why did it take the moms to put all those pieces together.
Taylor: Why did it take so long to figure out Lyme Disease?
One reason is that science is, by definition, slow. It’s easy in 2019 to look back and say, well duh, Lyme is spread by ticks… that it’s treated with antibiotics. But back in 1975, when researchers were first investigating the disease, they had to rule out all the possibilities. They had to check water supplies, investigate the local schools, collect and test mosquitoes, and count ticks… one by one.
In the last episode, we learned that it took scientists about six months to identify the cause of Legionnaires Disease. For the mystery that began in Lyme Connecticut in 1975, it would take them about 7 years. .
[Theme]
I’m Taylor Quimby.
In the last episode, we heard the story of Polly Murray… One of the moms who started putting the Lyme Disease pieces together.
In this episode, I’m going to tell you the story of the scientists who finished the puzzle - who subjected the mystery to a rigorous, epidemiological investigation.
What you’ll hear is a process that sometimes puts patients and scientists at odds… One that is slow, and cautious, and not always very satisfying.
This is a story that foreshadows controversies to come… The fight to define Lyme Disease… and a battle that is still being waged today.
Taylor: They arch their back like cats [yeah]
This is not an adventure.
Woman: Good squirrel [Squirrel noises]
This is not a grand day out.
This is Patient Zero.
[Tape of child singing about tick season…]
<<<<<<<>>>>>>>
Taylor: November, 1975. ...
Epidemic Intelligence Service officer Dr. David Snydman had only been working with the Connecticut State Health Department for just a few months, when he was handed a bizarre mystery: two mothers, unbeknownst to one another, each reporting cases of juvenile arthritis in and around Lyme, Connecticut.
David Snydman: Well my first step was to return the calls to the mothers that had called and try and get some information basically.
Taylor: One of those mothers was Polly Murray, who we learned about in the last episode - and the other was a woman named Judith Mensch. Her fourth-grader, Anne, had a massive swollen knee, and was hobbling around on crutches. At first, she had been diagnosed with osteomyelitis - a type of bone infection - but eventually, they changed it to JRA: Juvenile Rheumatoid Arthritis, an autoimmune disease.
On the phone with David Snydman, each of them was able to point to other kids with JRA living in the same area.
David Snydman: Initially I did a map of the area which I actually have hanging on my wall. Different color coded dots about which months or years they might have been diagnosed or had the onset of the arthritis
Taylor: Maps are important tools in an epidemiologist’s toolbox. Because an epidemic is ONLY an epidemic if the number of cases are above average. So, If you plot patients on a map, and discover their numbers exceed what is statistically expected in a given area, then you’ve got what epidemiologists call “a cluster”... which may be the beginnings of an epidemic.
And given that JRA isn’t supposed to be contagious… Snydman’s map revealed something unusual.
David Snydman: There was clearly a summer/fall distribution of dates of onset of the cases and clearly pretty high rates of arthritis on certain streets or roads.
David Snydman: It’s basically when I called Allen Steere.
Allen Steere: I mean juvenile rheumatoid arthritis, if you had one child affected with juvenile rheumatoid arthritis within the population of children of Lyme Connecticut. That would be maybe what you would expect. Not thirty nine.
Taylor: There are two doctors whose work is most commonly associated with Lyme Disease today - and this man... Dr. Allen Steere... is one of them.
Taylor: Tell me about that first meeting… what was that like? [long pause] I know it was a while back.
Allen Steere: It's 43 years ago.
Taylor: I met with Dr. Steere in his Boston office. His Steere’s white hair runs from above his ears and around his head like a partial halo. He’s measured in his speech - guarded even - But his eyebrows are strangely expressive.
The combined effect is that, no matter the topic, he looks gentle - but sounds deadly serious.
Taylor: So I’m just going to get a sense of your levels. Why don’t you tell me what you had for breakfast.
Allen Steere: I had cereal for breakfast.
Taylor: Can you elaborate?
Allen Steere: Well there was fruit strawberries and raspberries and blueberries and... cereal... and milk.
Taylor: Today Dr. Steere is a researcher and professor of rheumatology at Harvard - but back in 75 he had just finished up two years with the Disease Detectives - The Epidemic Intelligence Service, and was starting a fellowship in rheumatology at Yale.
And because of his training, he knew that he had to begin by focusing on something objective… symptoms that could be measured, or tested, or observed with the naked eye.
Allen Steere: It is important that the people that you're seeing you think have the same disease.
Taylor: This is called a case definition. And it’s like the investigation’s guard rails. A case definition outlines and focuses an epidemiological investigation — says what’s in bounds and what’s out.
Allen Steere: We decided to make it that we would see children who had arthritis and why would you choose children with arthritis. Because that's unusual.
Taylor: Now some of the stories in Lyme were coming from adults - Remember Polly, and her husband Gil were also dealing with strange symptoms… so why not include them too?
Because adults get arthritis for all sorts of reasons - it’s common, and therefore harder to know - KNOW FOR SURE - that what they have is something new - something undocumented
To study a novel disease, you have to start with the narrowest definition possible - and work your way outwards.
In a study like this one, the people who don’t fit inside the narrow case definition may feel like the doctors are ignoring them, … and until there is enough evidence to expand the inquiry, that’s exactly what’s happening. Because this isn’t really a doctor’s visit, in the traditional sense - it’s an epidemiological process.
It’s also an example of how this type of investigation can feel anti-patient.
Allen Steere: The next thing you need to do is decide what your universe is. And we decided on three contiguous communities Lyme, Old Lyme, and East Hadam, Connecticut. That was the beginning
Allen Steere: We wanted to find as many children as we could in those communities who had arthritis.
Taylor: In order to find kids with JRA, Steere deputized lyme locals… He spoke with the school nurse, and local doctors… and he met with at least one of the two mothers that had initially called David Snydman… Polly Murray. Polly’s son, Todd, who had been with her the last time she was belittled by a doctor, remembers how differently she was treated by Dr. Steere.
Todd Murray: He didn’t have the answers but he was clearly somebody who was caring and willing to listen and trying to get at the truth.
He was really the first person who listened and really consider that this was something new going on.
Taylor: And of course, Polly had come prepared. She had been documenting her family’s health for years - but over the past few months, she had become a veritable amateur epidemiologist… interviewing neighbors and parents, conducting her own miniature investigation. Here’s Polly’s daughter, Wendy.
Wendy Murray: She wrote up like 33 names and symptoms and contact information, and brought it to her first meeting to Dr. Steere. She had them in her safety deposit box, you know that’s how important they were to her. She put them in there.
Taylor: I had read about this stack of contacts that Polly had handed Steere… it’s the sort of thing that news outlets have written about over the years… citizen sleuth slash local mom assists in investigation. The details would shift a bit… sometimes it was 30 names and numbers she gave him, sometimes it was forty. But either way, I always thought it must’ve been a huge alley-oop for the investigation.
Which is why I was a little surprised when Dr. Steere politely acknowledged Polly’s help, and then moved on.
Allen Steere:: Polly Murray was a source of information and an important source of information. ...But there were other people as well.
Taylor: Wendy had told me that she still had the initial stack of contacts that her mother had given Dr. Steere, so I asked her to send me copies. And having seen them, I think I understand why Steere might have deflected that question
[voice reading from notes]: Laubach, Gerald. Blood st. Lyme. Steven - 19. 6 or 7 years ago, joint problems, saw doctor in New London. Hospitalized, traction. Hip, knee, several recurrences. Better now.
Polly had handed him more than two dozen pages, filled with little bursts of shorthand, and notes scribbled in the margins.
[voice reading from notes]:
Doll - Childs name Ted. Goes to Madison Country Day school.l Under 14. December 1974, joint problems, multiple involvement. Hospitalize yale, new haven.
David, Becker Hill Rd.
Kim on crutches. Bell’s palsy, beginning encephalitis.
Bloom, Barry - Makintosh Rd. Lyme. Joanna, age 12. Summer swelling of knee - on crutches. Blood test done - none positive. Pains in joints off and on since.
Taylor: In some cases, the handwriting is hard to read, and it’s not always clear what qualifies as a “contact.” But the biggest problem, from an epidemiology perspective, were the illnesses themselves. Remember: Steere had a case definition… a narrow universe in which he had to work. Primarily, he was studying children and teenagers with arthritis. But many of the contacts that Polly provided were way outside of that universe.
Mrs. Ronald Sternicki - age 30 to 40. Trouble started while skiing in Colorado. Very sick with upper respiratory problems. Later in June, had pain and stiffness in her neck. Face would swell. Felt faint. Her jaw would crack and it would be hard to open her mouth. She had blurred vision at times.
Taylor: Regardless of whether or not they were sick, or suffering, many of the contacts she provided would not qualify for Steere’s study. In fact Polly herself did not qualify. Two of her boys did - but her own symptoms were stranger, harder to pin down.
And yet, she clearly believed that she and her kids were all suffering from the same sickness.
The very last page of the documents she gave to Dr. Steere is her own detailed medical history: written neatly in half-cursive script, a litany of symptoms, like a side effect warning from modern-day drug commercials.
Polly age 42 - History of allergies, sore throats, hoarse voice, nausea, diarrhea, fever, purpura, joint pains, facial and eye swelling, asthma, sudden weight loss, rashes on face, hands, arms, behind ears, cold and numb fingers, cankers sores, chronic cervicitis and irregular bleeding.
They were tackling the same problem, but looking at it from completely different perspectives.
Steere was a scientist, trying to connect the dots of a single illness… to outline an isolated constellation of points… Polly, by comparison, was providing a map of the entire night sky.
...
Taylor: New Haven. December, 1975
About a month after meeting with Polly Murray, Dr. Steere’s investigation had been approved by an internal review board and began in earnest.
It was called Protocol 1125: Evaluation of Epidemic Arthritis in the Lyme, Connecticut area.
And here, another basic lesson about epidemiological methodology, one that I found really surprising: There are just three basic ways that agents and hosts - people- come together. Just three.
First off, agents - pathogens - can be passed from person to person.
Allen Steere: If an organism is being transmitted by person to person you can usually trace one contact with another.
Taylor: Or they can be passed through some sort of collective environmental exposure - contaminated food or air or water.
Allen Steere: A common source.
Taylor: Or spread by a third party: An insect or arthropod… what we call, a vector.
This is where all of the efforts I mentioned before were required to determine which of these three methods the mysterious pathogen was using.
Allen Steere: We weren't not able to trace contacts. We were not able to identify a common source.
Allen Steere: When people had been in fact infected in the same family it was usually in a different year.
David Snydman: First impression actually was that this might be a virus or a vector-borne disease perhaps transmitted by mosquitoes.
Taylor: From the case histories they collected, one detail stood out. One symptom that could be traceable.
Allen Steere: It was in a quarter of the children. Not a lot. There was a history of an unusual skin lesion.
Taylor: A bullseye rash
[music swell]
Spring 1976.
When the weather was warming up, and kids were playing out in the woods again, Steere and Snydman started looking for people with bullseye rashes. If they could confirm that the rashes were connected - and not a coincidence, then they’d have something to study… something narrow. Something they could see.
Allen Steere: We were able to come up with 12 people. Not a lot.
And 75 percent of the group that we entered into the study developed arthritis.
Taylor: This was the sort of connection they were looking for.
In May, Steere wrote to all of the study participants about his as-of-yet unpublished findings.
All in all, there were 39 children, and 12 adults who met their criteria… who fit inside the universe they had created. Most of whom were suffering from bouts of arthritis, especially in the knees, preceded by a flu-like illness some time before.
There were other strange symptoms reported too - nerve pain, facial paralysis, trouble sleeping - but these were inconsistent, not as easily defined, and by design not the current focus of the investigation.
Steere was a rheumatologist, so he focused on the one thing he knew best. He called the unknown disease Lyme Arthritis.
June, 1976. Joshuatown Rd. The Murray House One year in.
Wendy Murray: It took over, like I remember looking down and seeing all the NBC TV producers and stuff out on the lawn, and Dr. Steere was there, and they were filming and looking down from my bedroom window. And just for the b-roll, you know like cut flowers. And there was one flower, maybe she was trying to break it without scissors, and it just wouldn’t break. And she was just tugging at this flower for the camera and I was just kind of like, half-admiring, half grumpy cynical daughter and thinking oh my god.
[tape sfx]
TV Clip/reporter: Lyme resident Polly Murray, the first to bring the pattern of symptoms to medical researchers, insisting that she had some sort of disease.
Polly Murray: I felt that there was something there, but the medical profession said well there is no such disease that exists that has the number of symptoms that you are exhibiting
[tape sfx]
Taylor: People in the town of Old Lyme were not pleased. A novel form of infectious arthritis had just been named after their quaint New England town. Real estate agents were up in arms, and people were freaked out for their kids.
Someone called a meeting at Town Hall where Dr. Steere presented his findings and answered questions from the public. A risky proposition, given Steere had so few answers to give.
There’s a lot I don’t know about the scene - if it was hushed, or noisey. If there was hot and stuffy, or if a rattly air conditioner working overtime in the corner.
What I do know, is that there were about 100 people there… and that the public witnessed something that often takes place behind closed doors: Complete and utter scientific disagreement.
Allen Steere: I mean it's both exciting and it's also frustrating trying to sift out what may be correct what may not be correct. I mean for example nuclear power plants had been built in Watertown Connecticut in the 1960s and there were people who thought that was surely the reason this was happening.
Taylor: Dr. Steere told the crowd that he believed Lyme arthritis was caused by a virus. That it was probably self-limited… meaning it would get better on it’s own, like a flu. He was advising patients to treat pain and swelling with Aspirin, until they felt better.
But there was a pair of Navy researchers there too that were floating another theory… that Lyme arthritis was caused by a bacteria… that in order to treat it, patients should be given antibiotics.
This disagreement wouldn’t have only rattled the public - it would have also confounded local physicians, who would largely be the ones actually treating people.
They would have to choose between theories of treatment: antibiotics or aspirin, without sufficient evidence to choose one over another. .
Allen Steere: I mean one's trying to balance what you think is happening and that people need to know and one's balancing that with not giving out false and are trying the best you can not to give out false information.
Taylor: I hope I’m not giving away here, when I tell you: Dr. Steere’s theory was wrong: Often, Lyme Disease does not go away on it’s own… and it is not treated with aspirin. Steere was making an educated guess. And it didn’t pan out. But that’s science.
Allen Steere: You publish it. You put it out there and people react. Some of it holds up and some of it does not. And in the process that is how progress is made.
Taylor: That variety of progress…the one where mistakes are made, and corrected… is hard to handle when you’re sick… and suffering..
Today, Dr. Steere is credited with naming and investigating Lyme Disease… But the two other doctors at the town hall meeting, the ones who correctly guessed that Lyme is a bacteria, and who studied it for many years afterwards, are largely left out of the narrative.
Why might that be?
Well, a cynic might point out that Dr. Steere and his team were from from a little institution named Yale.
And the other two were just a couple of Navy docs working at some submarine base.
[mux sting]
Of course, the elitism of the medical world cuts both ways.
Sometime after the meeting, Steere and Snydman tried to publish their first study on Lyme Arthritis.
Allen Steere: Which interestingly enough was rejected by the NEJ because it was felt that there was too much pre-publicity.
Taylor: As it turns out, they had broken a cardinal rule of research, in the 1970s. Don’t give away the scoop. Medical journals, like the New England Journal of Medicine, want to make the news… even if it’s in the public’s interest to know the information beforehand.
Allen Steere: It had been on the front page of the New York Times and they weren’t interested. It was ridiculous.
Taylor: They were being punished for saying too much, too soon… even though they were wrong. Some of these internal battles are a part of the scientific process, and some are part of scientific bureaucracy… For those of us on the outside, it’s hard to tell which is which… and the end result can be mistrust. Patients don’t care who gets credit… they just want to feel better.
BREAK
<<<<<<<<<<<<<<<<<>>>>>>>>>>>>>>>>>>>
Taylor: Reggie White was an ordained Evangelical minister… and one of the greatest defensive ends in NFL history.
[clip]
But early one morning in 2004, the day after Christmas, he was rushed to the hospital, where he was pronounced dead at just 43. He had died from a combination of cardiac arrhythmia - irregular heartbeat - and sleep apnea...complications from a disease called Sarcoidosis.
Dr. Yvette Cozier: It’s sort of been classified as the most common rare disease. It is a rare disease, but it seems like it’s much more common than we think.
Taylor: This is Dr. Yvette Cozier. An epidemiologist and investigator in The Black Women’s Health Study. And I promise - this little diversion here is very, very relevant to our story about Lyme Disease.
Yvette Cozier: The puzzle that Sarcoidosis is, and this is something I like about studying it, is that for a large segment of those who have it, they’re completely unaware.
Taylor: And so it’s basically like a mini… like a mini tumor that comes and goes?
Yvette Cozier: So It’s not a cancer, but it’s all immune cells. Cells that are rushing to a point where they are coming with the intention of fighting something and sort of walling it off but you cannot identify what it came to fight… [fades down]
Taylor: Despite the fancy sounding name, doctors don’t really know what causes sarcoidosis… an infectious agent, or some kind of immune problem, they’re still not sure. But either way, the disease is characterized by the formation of granulomas - little balls of immune cells that bunch up like tumors - and wherever they go, they cause inflammation. In the joints it’s arthritis… they can attack the eyes, and cause blindness, or the heart - which in rare cases can be fatal. Like it was for Reggie White.
But despite all the places it can go, sarcoidosis is most commonly known as a pulmonary disease - because symptomatically, it can look a whole lot like lung cancer.
Pulmonologists have led the way in identifying and studying sarcoidosis - because once upon a time, it was normal to screen job applicants for tuberculosis through a mandated chest X-ray.
Taylor Quimby: So routine chest X-rays used to be a thing in jobs?
Yvette Cozier: Yeah they used to be a thing in jobs, particularly federal jobs, in the military I still believe they still are, and also people coming into prisons.
Taylor: Here’s another thing you need to know: in the United States, African American women have the highest rates of sarcoidosis. But...
Yvette Cozier: In Northern Europe, it seems to be white men that have the highest rates of disease.
Taylor: Got all that? Okay.
Not long ago, Dr. Cozier went to a conference on sarcoidosis. At that conference, among all of the patients there, she met a white man.
Yvette Cozier: He was the only male that was there. And had for many, many years - had suffered with joint problems.
Taylor: The pain in his knees was so bad he wound up having them replaced.
Not once. Three times.
And then he started to have issues with his vision.
Yvette Cozier: The opthamologist actually had a biopsy done, and noticed he had sarcoidosis.
Taylor: This, you might imagine, was a revelatory diagnosis.
Yvette Cozier: The next time his knees began to flare up they did a biopsy and recognized it had been sarcoidosis all along.
Taylor: So why did it take so long to figure out? Why did this guy have to get his knees replaced three separate times before they got it right?
Yvette Cozier: It seemed like an orthopedic problem so why would anyone look any further? But also, he didn’t really necessarily fit the description.
Taylor: In other words, he wasn’t a black woman with sarcoidosis of the lungs. He was a white guy with sarcoidosis of the knees.
Science is compartmentalized by necessity. Frankly there’s too much to learn in the world - so experts have to focus that knowledge in order to make progress.
But disease leaps from one discipline to another, with no regard to the silos of medical education and practice.
Dr. Snydman initially contacted Allen Steere because he was a rheumatologist… an expert in arthritis. But as the scope of the lyme investigation broadened, the usefulness of his expertise narrowed.
First there was the vector… Yale scientists were at this time collecting tens of thousands of mosquitoes… and thousands of ticks as well, searching for the pathogen that might be causing Lyme Arthritis.
Allen Steere: I'm not an entomologist. I knew nothing about ticks and it started as an investigation of children with arthritis.
Taylor: And then there was the skin rash - typically, the domain of dermatologists.
Allen Steere: It was in general a slowly expanding skin lesion that would last for several weeks and then go away. There was a Danish dermatology resident who when we presented this at a conference said this rather sounds like Erythema Migrans
Taylor: Erythema Migrans… latin for Migrating redness.
This is the part of the story, where I tell you that, even in 1975 - Lyme Disease was not new. And long before it was ravaging the knees of Connecticut schoolchildren, it was documented in the clinics of Europe.
[Voice reads] Germany, 1883.
Physician Alfred Buchwald of Germany describes a patient with a chronic skin rash he calls ACA - which now recognized as a rare condition caused by some strains of Lyme Disease.
Sweden, 1909:
[Background] Swedish Dermatologist Arvid Afzelius presents a new skin rash he calls Erythema Migrans at a meeting in Stockholm - and thinks the rash is caused by a tick bite.
Taylor: Just as there are silos between scientific and medical disciplines, there are silos that exist between places. Between languages. When Steere started his investigation, he had no idea that Lyme Arthritis - or whatever it was - was global… Again, for those of us putting the puzzle together forty years later, it might seem like a huge oversight. Why would he have known? He was a rheumatologist.
[background] Germany, 1950:
Sven Hellerstrom, publishes a paper connecting Erythema Migrans patients to cases of meningitis successfully treats a patient using penicillin.
Wisconsin, 1970:
A dermatologist who knows about the European history of Erythema Migrans successfully treats a 57 year old patient with a bullseye rash with penicillin. The man had been bitten by a tick.
New Haven, 1976: Dr. Steere learns all of this from a Danish dermatology resident who sees the rash and tells him…
Allen Steere - this rather sounds like Erythema Migrans… or EM.
Taylor: He wasn’t familiar with the research in other specialties of medicine. Besides, the swedish papers were written in Swedish. An early french paper was written in French. The German papers were written in German. It was complicated.
And even then, there was a lot missing from the European literature.
Allen Steere: Not associated with arthritis. It wasn't clear that it was the same thing.
Like Legionnaires, this was a puzzle being put together in the dark. Nobody had finished the thing… not even in Europe… only matched up a few wayward pieces here or there.
Allen Steere: In Europe a number of people who are dealing with this had thought that it responded to antibiotic therapy. Some others did not. By the way so that wasn't so clear either.
Taylor: Dr. Steere has amassed a long career working with Lyme Disease and he is an expert.
But he’s an expert in rheumatology who has branched out into other disciplines. And in Lymeworld, there is no such thing as a single authority. Lyme is bigger than any one person.
...
Taylor: Summer, 1979.
About three years after that town hall, where residents were advised to treat Lyme Arthritis with aspirin, the Yale researchers released a statement.
It was a reboot of sorts. They were no longer studying Lyme Arthritis… they were studying Lyme Disease… a multisystem illness that could invade the joints, the heart, the facial nerves, and the lining of the brain.
And, after years of recommending aspirin - their studies on the efficacy of antibiotics had started to show results. And so they changed course.
They started recommending antibiotic treatment for patients with a bullseye rash and unusual bouts of arthritis - but they didn’t know for sure which type of antibiotic was best, or for how long.
They had collected enough evidence to widen the case definition, and confirm what Polly Murray had believed all along - that the disease was more serious than originally thought.
But the reboot was a double-edged sword. Because by expanding the definition of Lyme, without a clear diagnostic test in place, they were opening a door that isn’t easily closed.
Allen Steere: It is a complex infection but of course that doesn't mean that everything that can happen to people is manifested in that infection.
Taylor: After the announcement, cases started pouring in - more cases of actual lyme disease… AND more cases of what maybe… probably… was something else entirely.
Allen Steere: I mean we were saying this was an unusual illness that had not been seen before. So people who had other unusual illnesses wondered if what they had was this illness that we were calling Lyme disease.
Taylor: But one thing was certain… Lyme Disease wasn’t being spread by mosquitoes, like Steere had initially speculated. Cases were coming from a number of states, roughly matching the geographic range of what we now call the black legged tick. And that’s bad. Because ticks are disease bombs. They carry so many pathogens, it’s hard to separate them all out.
Remember how I said that this process is like putting a puzzle together in the dark? If there’s a tick involved, it might be more like three or four puzzles all scrambled together.
Dr. Steere had been searching for the agent of Lyme Disease longer than just about anybody.
But the process is messy. Sometimes, it’s random. And he wouldn’t be the one to find it.
[typewriter SFX]
1980. Rocky Mountain Laboratories , Hamilton Montana.
Alan Barbour: Typically he would be the Santa Claus for the Christmas party.
Taylor: Dr. Alan Barbour is a microbiologist…Round glasses, looks a bit like an owl... and in 1980, he was working with a man named Willy Burgdorfer.
Alan Barbour: He was Schweitzer-dutch. So he was Swiss.
Taylor: I think that makes for a pretty jolly Santa Clause. Good santa.
Alan Barbour: Yeah and his face, sort of a roundish face. Worked very well.
Taylor: When he wasn’t playing Santa, Burgdorfer was a medical entomologist… somebody who studies the various insects and arthropods that can spread disease… lice, ticks, mosquitoes et cetera.
Dr. Barbour had just gotten back from a meeting of infectious disease experts, where Alan Steere had been presenting something on Lyme Disease…
Alan Barbour: it may have been the first time that he announced that he could use penicillin to treat it, and this was the first time that there was some evidence that it could be a bacteria.
He told me in effect, funny you should mention that because I’ve just been finding something in the microscope.
Taylor: Burgdorfer was dissecting a batch of ticks from Long Island… and he had found something unusual inside two of them… bacteria floating around inside the ticks teeny… tiny… midgut.
Alan Barbour: They were prepared for examination under the microscope and under those conditions he could see something that looked like a spirochete.
Taylor: A spirochete is a phylum of bacteria… a thin noodle of a pathogen that twists like a corkscrew.
The most famous spirochete is probably the little bugger that causes syphilis.
But this was something else… something neither he, or Dr. Barbour recognized.
Alan Barbour: So he provided me with some of the intestines of these ticks where he had seen these spirochetes, he gave me a little vial of them.
Taylor: Growing pathogens is a vital part of research and diagnostics… For easy to grow pathogens, like e.coli for example, all you’ve got to do is put a sample in a dish, give it some food, and bloop: the pathogen multiplies exponentially.
Alan Barbour: So for people with a urinary tract infection, they actually grow it in the laboratory and they know what it is.
Taylor: But spirochetes are finicky. They don’t grow as quickly or reliably as some other bacteria.
Alan Barbour: Initial results, I could see the spirochetes growing, but there was some other bacteria in there from a contamination. But eventually we were able to get a pure culture, all by itself, just the one bacteria.
[bloops and music fade]
Alan Barbour: The time that I saw that we had a pure culture was one of the most memorable days of my life. You don’t forget something like that.
Taylor: It was a hitherto undiscovered pathogen … the causative agent of Lyme Disease.
It was named after Willy Burgdorfer... the man who had identified it…
Alan Barbour: Borellia Burgdorferi.
Borrelia burgdorferi.
...
Allen Steere: I’ve said many times that the study of medicine is humbling. Well it was eight years from initial observations to the first identification of the infectious agent. It means that a lot of what one does trying to find it didn't work out well that's what science is like. That's what research is like.
Taylor: The truth about science and epidemiology, I think, is a little unsettling. That it’s slow. That there’s guesswork, false starts, red herrings.
But this is the process. It takes people like Polly Murray…
Wendy Murray: She literally had doctors saying oh just go play tennis…
Taylor: ...to push through the status quo, to challenge the system, and yes the sexism of medicine and epidemiology.
And it takes people like Allen Steere, to take on the slow work of categorizing what we know, and what we don’t.
But obviously, I wouldn’t be telling this story if it were that simple. Because, the uncertainty that plagued those early years has not gone away. Instead, it grew and grew until it was big enough to have it’s own name, it’s own case definition, it’s own alternate universe.
This is “Chronic Lyme Disease”.
It sounds like the same thing - but it’s not.
From a literal point of view, Lyme can be a chronic disease… left unchecked it can last for months or years. And once treated, not everybody feels better right away - some will have lasting symptoms that can take a long time to resolve.
But ultimately, it is treatable with a relatively short dose of antibiotics.
Chronic Lyme Disease is the term used by a community of doctors and patients that believe Lyme is much harder to treat than authorities say it is. A number even believe that Lyme Disease is nearly, or entirely incurable… That practically anything can be a symptom… and that the tests can not be trusted.
Jorge Benach: It is the perfect storm, but I am troubled. Why Lyme? What was it about Lyme that sparked this? Because I’ve never seen this in any other disease, not even in HIV with all it’s social stigma, right? …
Taylor: This is Jorge Benach. Benach is a lifelong Lyme researcher, currently working at Stony Brook University in New York. He’s the one who sent Willy Burgdorfer the batch of ticks that he used to identify the bacteria.
Dr. Benach says in the early days, people like Polly weren’t taken seriously.
Jorge Benach: Very often they were brushed aside, and nobody likes to be brushed aside.
Taylor: This is complicated stuff, and we’ll talk about it more later.
For now, the important thing to know is that the CDC and major medical organizations do not recognize the term Chronic Lyme Disease... in part because that diagnosis has led some doctors to put patients on powerful antibiotics for months or even years… Treatments that have little to no benefit, but hefty costs and can even be harmful.
Jorge Benach: I heard a colleague say, the genie’s out of the bag. And we’re never going to put him back. And it’s so sad in a way, because it soured the field. And it’s made it almost a laughing matter in the larger medical community. You know when people say Lyme Disease and they smirk at each other. I’ve seen it with my own eyes.
Taylor: So what we have is a divided medical world. Two opposing camps. One made up of old-school doctors like Steere, and Barbour, and Benach… and another one, made up of what people call “Lyme literate medical doctors” as well as naturopaths, and chronic lyme advocates.
This split is the reason why it's so confusing for patients who get a diagnosis of Lyme.
Hannah McCarthy: I felt… I don’t know if unsafe is the word.
Taylor: This is what my colleague Hannah, whose diagnosis we talked about in Episode 1, was witnessing, when her doctor insinuated that it was bad to be a “lyme doctor”.
Hannah McCarthy: I’d never seen a doctor imply mistrust in another doctor before.
Allen Steere: It’s not a question of are they suffering? I know that. I too want to help. But how do we help? We do not always know, we have… uh well, just our knowledge isn’t there...
...
Taylor: April. 2019.
I went to Lyme, CT this spring, and used Dr. David Snydman’s old 1975 epidemiological map to knock on doors and try to find some of the first cases of Lyme Disease.
Taylor Quimby: Does Mary Beth live here?
I met a couple people that way who remembered the investigation - but mostly people had moved away.
Unidentified Neighbor: She just started feeling really sick. She ran a lot.
Some of Polly Murray’s old neighbors remembered her fondly, but never knew her well.
Unidentified Neighbor: Some woman who had a neurological disorder.
Taylor: While I was working on this series, Polly was living in a memory care facility. I would have loved to interview her, but she had been diagnosed with Alzheimer’s years before, and it was her kids who wound up telling me her story.
This July, while I was in the process of revising this episode, Polly’s daughter Wendy called me to let me know that she had passed away. Polly was 85.
In the years after the bacteria was identified, Polly was invited to scientific conferences to speak about her experiences in Lyme. She collected piles and piles of medical journals and scientific papers about the disease.
In 1990, fifteen years after the investigation had started, Dr. Allen Steere returned to Lyme Connecticut to talk about new research..
Polly was there of course… sitting in the audience, with a handheld recorder.
[clip: Steere introduces Polly, round of applause, music swell]
Taylor: But Polly’s legacy is fading with time… becoming more of a footnote than a plot point. And it makes me wonder if a hundred years from now, people will still remember her at all. If they’ll remember that before you can put out a fire… first you need someone to raise the alarm.
Wendy Murray: Her father said something like, I’m so worried about Polly because the whistleblower always gets hurt. And Polly, you know it IS tough to be the whistleblower, it takes incredible strength. So… I’m in awe of her. Because she could’ve been crushed. And she wasn’t.
...
Taylor: In 1975, 51 people in Connecticut were diagnosed with what would later be known as Lyme Disease.
Today, it’s the most common vector-borne disease in the United States. The Centers for Disease Control and Prevention estimate there are more than 300,000 new cases a year and climbing… More than 90% of which come from just 14 states.
On the next episode, we’ll take you from tick bite to bull’s eye… and dive into the science behind Lyme Disease.
That’s next time, on Patient Zero.
Patient Zero is produced, and reported by me, Taylor Quimby.
Projects like this one take time, and resources. If you like what you hear, consider making a $20 donation at patientzeropodcast dot org. You’ll get early access to future episodes, ad-free, and some bonus episodes as well.
Editing help for this episode came from Annie Ropeik, Jason Moon, Cori Princell, Justine Paradis, Jimmy Gutierrez, Nick Capodice, Jacqui Helbert, Todd Bookman.
Sam Evans-Brown is Patient Zero’s senior Producer.
Erika Janik is Executive Producer.
Fact-checking for this episode by Amy Tardiff.
Graphics by Sara Plourde.
Maureen McMurray is Director of Content.
Special Thanks to Allie Cerretani
Ben Borgmann-Winter
and
Stephanie Dea,
For letting me tag along for an amazing day out counting ticks...
Samantha Searles and Casey McDermott for contributing their voices to this episode.
If you’ve got questions, concerns, or comments about Patient Zero - we want to hear from you. Email us at patientzero@nhpr.org.
Patient Zero’s Theme was composed and performed by Ty Gibbons.
Additional music from Jason Moon, Blue Dot Sessions, and Disasterpiece.
Credit music by Deerhoof.
Patient Zero is a production of New Hampshire Public Radio.