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.
I’m going to play a sound, and I want you tell me what it is:
[hoofbeats]
It’s the sound of a galloping horse, right? Well what if I ask you this: How do you know it’s not a zebra?
There’s a famous phrase in medicine and epidemiology: When you hear hoofbeats, think horses, not zebras. it is essentially, a medical variation of Occam’s Razor… the idea that the simplest explanation is usually the correct one.
In practice, it looks like this: If you come in to the doctor with cold symptoms, it’s probably not Ebola. If your kid has a pink, itchy eye, it’s probably not a flesh-eating bacteria.
Generally, it holds up - which is why it’s referenced in the pilot episode of House MD
[House MD ep1 clips - 1st clip]
But a show like House would never have existed if it was always that easy… Sometimes our first instincts in medicine aren’t always true.
Take for example, stomach ulcers.
[pepto commercial beings]
Back in the good ol’ days, we pretty much thought we had peptic ulcers figured out. They were caused by stress and bad diet.
It was such common wisdom, it used to be an eye-rollyTV trope… Mad Men era husbands working too hard at the office, while their wives fretted over them at home.
[00:01:19] Meet George, the hard worker. His tale is a tear-jerker. His hurry-worry life just dismays his poor wife… all the hustle and bustle the work-a-day tussle… [fades down]
doctors responded according to conventional wisdom - prescribing bedrest, vacations, and super boring foods. And of course, a variety of antacids.
[00:01:32] So when upset stomach strikes take soothing pepto bismol and feel goooood again!... tums taste good… work fast
But then in the late 1970s, a pair of physicians proposed an alternate theory.
John Aucott: So I mean I realize in medical school there's this crazy doctor that said ulcers were caused by a bacteria.
This is Dr. John Aucott, Director of the Johns Hopkins Lyme Disease Clinical Research Center - he’s just one of several doctors who told me this same story…
Marker 28 - John Aucott.wav: I remember sitting in the lecture and the this you know the lecturer is saying well you know there's this kind of fringe guy that thinks ulcers are due to bacteria but it's a bunch of hooey and you know. Yeah. Obviously they can't be due to a bacteria. Bacteria can't live in the stomach acid. You know in our textbook at that point said that ulcers were caused by stress you know.
The fringe guy was one of two Australian physicians… and the bacteria was something called Helicobacter pylori… which, yes… sounds like a spell from Harry Potter. But today, people in the medical world know H.pylori, as its more commonly referred to, the same way that you and I know about E.coli… Because, those Australians were onto something.
John Aucott: the researcher eventually got the Nobel Prize for discovering that ulcers or do they H pylori bacteria and they're now curable with antibiotics, right?
Great story, right? Kind of. The most concerning part of this story… .. Is that this revolution in thought didn’t happen overnight.
13 years after their findings ought to have upended the field… only five percent of ulcer patients were being treated with antibiotics. 90% of patients diagnosed with ulcers were still walking away from the examination room, thinking the problem stemmed from stress and diet.
Today, it’s well understood that H.pylori is among the most frequent causes of peptic ulcers. But tens of millions of patients fell to the wayside in the years that it took the medical community to accept, research, and validate the theory.
Sometimes, the very rules that teach doctors to apply caution and avoid jumping to conclusions, can keep them from catching their own mistakes…
[bring back galloping sfx]
Sometimes, a zebra escapes from the zoo… and if you don’t look up to see it, it’ll gallop by… sounding just like a horse.
I’m Taylor Quimby.
Today, a bonus episode, an extra epidemiology lesson from one of my favorite interviews of the series - a story that I think tells us profound lessons about how medicine fails, succeeds, and evolves. I’m going to be sharing this story with you, and with my producer, Sam Evans-Brown, host of the podcast Outside/In… and we’ll see what, if anything, we can apply to our investigation into Lyme Disease.
….
Taylor: So Sam. How are you enjoying the podcast so far?
Sam: It has been revelatory. There have been a lot of eye opening moments. Now, I can no longer talk to regular humans about Lyme disease without it going way into the weeds.
Taylor: [00:04:59] It devolves, doesn't it?
Sam: Yeah.
Taylor: Plus, you know, so much more Latin.
Sam: [00:05:04] Dear listener, you can thank me right now for all of the Latin words that I've cut out of the script that Taylor has tried to sneak in.
I'm kee— I'm always fighting for ‘em.
TQ: Okaay, Sam… I want to reintroduce you to Dr. Yvette Cozier. We heard from her in the first episode talking about Sarcoidosis, but in reality, she helped me understand so much about disease, and science, and certainty. She told me we always have to keep one thing in mind...
48 - Keep in mind and keep the humility that we don’t know everything. And what we do know could be truth within one part of the population, but not the entire part of the population.
This is pretty basic, right? People who live farther from hospitals have worse health outcomes, people who don’t have a lot of money tend to have higher risk of diabetes. And assuming populations like that will have the same degree of health risk as the entire populace will get you into trouble. No surprises yet, yes??
So here’s the story I wanted to share:
In 1980, a team of investigators from Harvard Medical and Brigham and Women’s Hospital launched a first of its kind trial - composed entirely of licensed Physicians.
Why?
28 - It is terribly hard for a physician to become “lost to follow up” which is basically when study subjects ghost the study investigators.
27 - This is a population that is likely to be compliant. It’s a group that you can track pretty easily.
The Physicians Health Study was the first randomized trial of this size to be conducted entirely through mail.
A total of twenty-two thousand seventy-one doctors from around the country - volunteered to test the efficacy of a simple and cheap intervention that could save countless lives.
20 - The trial was basically taking a baby aspirin a day, if that decreased risk of first heart attack.
Sam: Oh, I've heard about this on the commercials.
Taylor: Yeah. And I wouldn't be surprised. Like if you've ever noticed your parents or somebody else who might take an aspirin every day.
Sam: Better living through chemistry.
Taylor: The basis is that aspirin is a blood thinner. Investigators are trying to figure out if the small daily dose prevents blood clots in coronary arteries, and — you know — has minimal side effects.
21 - It was slated to be a five year study, but they ended it early when they saw a significant benefit. There was something like a 50% decreased risk of first attack. They were required ethically to end the study.
Sam: [00:07:19] At this point do we play that foreboding music?
Taylor: [00:07:21] What do you mean? That's a great result, 50 percent. That's huge.
So so they end the study. They put out the results. It's, you know, kind of like a miracle. Wow, we can we can prevent heart disease and like lots of people from here, doctors and major medical organizations start recommending that adults over 40 start taking a daily dose of aspirin. When we look back on this experiment, now that we’re a slightly more enlightened society… there’s a hole with the experimental design that you could drive a truck through.
25 - believe it or not, it seems like not that long ago, they would not have been able to randomize sufficient number of women physicians into study groups in order to have meaningful analysis.
Sam: [00:08:10] Yes. This is ...
Taylor: Do you see what she said there?
Sam: Yeah. So this is a persistent problem in in studies of medical interventions. They're not studying women enough. I mean, is she saying that they literally studied no women, or there weren’t enough women in the sample?
Taylor: [00:08:20] Literally, they studied no women. The physicians health study was conducted using only male doctors because there weren't enough women doctors at the time to make it worth their while.
Sam: Or at least they thought there weren’t enough.
18 - Many studies were based entirely on men, and the results extrapolated to women.
And of course years later, they did a similar study called the Nurse’s Health Study, using nurses and the results about taking aspirin everyday were not nearly as conclusive.
24 - They did not find the exact same benefit.
26 - Yeah, so that points to a serious disparity problem institutionally in medicine.
Yes, absolutely.
<<<<mux>>>>
Sam: [00:08:58] Well, OK. So taking an aspirin a day doesn’t have the same benefit for women, but does it hurt?
Taylor: [00:09:02] Yes. So literally, it increases the risk that you have, for example, bleeding in the brain. That's not good. No.
Taylor: [00:09:12] And it just goes to show you that, I mean, this is the tip of the iceberg when it comes to all the different ways in which men and women or people of color versus people of non color, white people.
Sam: [00:09:27] It's a color.
Taylor: [00:09:29] Right. But, you know, all these all these disparities between different groups and you're trying to like figure out what is what is socioeconomic, what is this and what is the physical difference between different bodies and different people? It's just a lot.
Sam: [00:09:43] yeah. As I said, we were playing the foreboding music because you're leading me down a path towards just questioning all knowledge. Period. We know nothing.
Taylor: [00:09:56] You know, I think that we don't want to systematically dismantle everything we've ever learned. But but I wonder, knowing how complicated this is, how might we apply some of the lessons that we're talking about here to something like Lyme disease? What ways should we be critical of our understanding of Lyme? And in areas that we may just not have thought about?
Sam: [00:10:13] Well, I mean, the first thing that leaps to mind is obviously that the diagnostic tools that were available in the early days of Lyme were flawed. Right. So they're relying on bullseye rashes and not everybody gets a bull's eye rash. Right. And so you wind up with a whole population of patients who may have an infection but aren't getting studied.
Taylor: [00:10:31] Right. But what about how the bullseye rash might look differently to people with darker skin?
Sam: Right.
Taylor: So there was there was this study that was done and it's like the one study that sort of tackles this. And it showed that people with darker skin color were more likely to be misdiagnosed when they presented with a bull's eye rash. Now, if you go to the CDC Web site and it shows you a range of different presentations of the rash, it can be like a little wobbly, a little oblong. It's not quite as bullseye ish. They're all white people, all the all the rashes. Even there are white skin. So it’s pretty likely that proportionally speaking, more people of color who are infected with the Lyme pathogen are not being diagnosed.
Sam: [00:11:27] And so it might be develop lasting symptoms because the infection will go longer before it gets treated if it gets treated at all. .
Taylor: Correct.
Sam: So so in terms of who gets Lyme disease. Yeah. What was the breakdown in terms of men and women?
Taylor: [00:11:46] So it's pretty close to 50/50. But when it comes to Chronic Lyme disease, which is not tracked in the same way, so this would be more like self-reported diagnoses of chronic lyme disease, the rates of women with it seem to be higher. And that has been used to say well hold on there’s something wrong with this chronic lyme diagnosis these people probably have something else. But you have to entertain the possibility that Lyme disease affects men and women differently, and that they get different symptoms that maybe are harder to diagnose. That is a possibility.
Sam: [00:12:19] yeah I mean, because like why should it affect men and women the same, right? I mean, didn't we just talk about how the genders may have different physiology, or even if there is no physiological difference, the way the medical system treats men and women might be different enough that it could lead to a higher rate of incidence of certain symptoms.
Taylor: [00:12:29] Right. And I just think that the argument that, ‘oh they must have something else,’ it’s born on the assumption that Lyme disease affects men and women in exactly the same ways… and you know… we have different body parts. I’m just saying that is a truth.
Sam: That is a fact.
Sam: [00:13:31] And also, this is also I encountered this a lot in my reporting about the limits of science. There are topics that that receive a huge amount of attention and study and have had hundreds and hundreds of studies dedicated to them. And each of those studies is answering a very small, tightly bracketed question. But in their aggregate there — they are a lot of knowledge. And then there are these other topics in which there just isn't that body of literature. But people talk about science, the science surrounding the subjects in the same way that is like, well, science says right. The studies have shown. But when you look at what the studies can actually tell you, each individual study is a very, very small, precise statement. And and if like something hasn't gotten a ton of attention, you really can't say much based on science.
Taylor: [00:14:22] Yeah. and I think you can see how over time, you know, what we are doing is narrowing our uncertainty. You know, like there's there's so much uncertainty. The world, the best we can do is keep shaving off a little bit at a time. So the aspirin study, since it was published, you know, our understanding of coronary heart disease has grown enormously. And now new evidence suggests that even for healthy men with a low risk of heart attack, that daily dose of aspirin is actually not worth it.
Taylor: [00:14:52] There are more costs than there are benefits. And specifically, this one that I mentioned, increased risk of bleeding in the skull. And so in 2019, just this year, two major health organizations on this issue changed their guidelines and said daily low dose aspirin should only be taken if directed by a doctor. You could look at this and be like, oh, we were wrong. That's not the case. You know, aspirin is a powerful way to prevent heart attacks, but back thenr we couldn’t figure out what was driving that fifty percent drop, we couldn’t see it was all just coming from this one high risk group. Now we know more. And we can narrow who actually needs this medicine and who doesn't.
Taylor: [00:15:29] And I think the other lesson about this is how long will it take for us to actually internalize it?
Taylor: [00:15:36] My dad is a doctor and he's still taking a daily dose of aspirin.
Sam: and i’ve met your dad… he’s a very fit healthy guy!
Taylor: yeah he can deadlift like a bazillion pounds! He’s super fit! He doesn’t need it.