Slime Mold Time Mold on the global obesity epidemic

Uri Bram: Today I’m delighted to welcome Slime Mold Time Mold, the authors of a fascinating new series about the obesity epidemic -- could you start by introducing that series to our audience please?

Slime Mold Time Mold: Sure! Each of us had been separately following the literature on obesity for a couple years. It was clear that most of the theories that seemed promising in the 1990s and 2000s were falling apart. Even experts have felt this way for almost a decade now, maybe especially experts, since they’re the ones following the literature most closely.

On a long car ride we discussed that some of the mysteries that seem hard to explain otherwise would make sense if obesity were caused by environmental contaminants, so we decided to take a closer look. We started writing and looking into this idea, and the evidence ended up being much stronger than we expected.

Now we’re here. :)

Uri Bram: That's awesome. Before we dig in further to the specifics about obesity, I actually have a meta question for you: how do you evaluate whether a massive social trend is monocausal or multi-causal? Does the pattern around obesity make it seem more likely that the rise is caused by "just one thing", or a bunch of different factors coming together?

One Cause or Many Causes?

Slime Mold Time Mold: This is a really great question. Unfortunately we don't think there’s an easy rule of thumb! We might say generally, you should assume a multicausal explanation until someone can make a monocausal case, because most things are complicated. Obesity looks kinda monocausal because there's such an abrupt shift around 1980. But a lot of things changed around 1980 so it could go either way.

It's good to keep your options open epistemically. Right now we think there is a good case for just a few contaminants. But we keep an open mind about there being more causes, so we’re still looking into others — for example, we recently took a look at glyphosate (the main ingredient in Roundup), and we feel good about that even though we ended up concluding that glyphosate doesn't seem to cause obesity.

Uri Bram: Ok great! I don't want to make you repeat too much from your series -- to everyone reading this I really recommend checking it out starting here, it's just a phenomenally engrossing read and it's definitely started a lot of conversations – but I’m just going to ask some questions that came to mind for me while reading.

Slime Mold Time Mold: Sure! Just to clarify, it's not over yet!

The obesity you don't see

Uri Bram: Ahahah, for sure. So: one question is about the relationship between obesity and either wealth or socioeconomic class. Anecdotally, just from everyday life, it seems that there's a strong relationship there -- I don’t think you see a lot of obesity among the "elite" professional class or on fancy college campuses. But you have some counterintuitive findings around that, so I wanted to ask you to speak a little about how the environmental contaminant model could be compatible with the relationship between socioeconomics and obesity.

Slime Mold Time Mold: So first of all, it's totally compatible with contaminants. Poor people are more likely to have jobs like janitor, coal miner, or factory worker, where they get direct contact with lots of different contaminants. The president of 3M gets a lot less exposure to pretty much everything than his workers do. Same thing for college campuses. And there's a general environmental justice issue here — poor people are more likely to live next to a factory or downstream from a coal mine. See Flint, MI.

But also, we've taken a look and just don't think there is much of a relationship between poverty and obesity! If there is an effect, it's pretty small. This seems pretty well-supported and we’ve done a review of the literature in a recent post.

Uri Bram: That’s pretty surprising for people, isn’t it?

Slime Mold Time Mold: Yeah, like many things in this area it's very counter-intuitive!

Uri Bram: Suppose that someone said to you, though, that they look at their social circle and don’t see a lot of obesity. What would you say to that? Is this a misunderstanding of what "obese" looks like in practice?

Slime Mold Time Mold: It could partially be that. It could also be geographical / profession differences. Where are you/your friends from, and what kind of jobs do you all have? If you all moved to rural West Virginia or Alabama and became truck drivers, we suspect you would all gain a lot of weight.

Also, there are real and pretty large differences in obesity between different ethnicities, which makes sense because there's a large genetic component to obesity. So if you and most of your friends are white and/or Asian, then you’ll be somewhat less obese than average. Similarly, if you're not overweight, probably people in your family aren't either, not surprising since you're closely related to your family.

Also also people gain weight as they age — we think this is super interesting because they didn't used to:

Uri Bram: what can we infer from the fact that people are now getting heavier as they age, whereas they used to get leaner? Does that imply anything about the causal mechanism or not?

Slime Mold Time Mold: This is definitely one of the most interesting trends in obesity, and maybe one of the most surprising, since modern people take for granted that people on average get heavier as they get older.

It's hard to draw firm conclusions from this. It could be evidence that the increase in obesity is monocausal, because this is a change in "kind" rather than in degree, so it looks less like a lot of different factors making small contributions. But equally, it could be evidence that the main mechanism is bioaccumulation, and as contaminants build up, people tend to gain weight.

We think this is a really interesting observation but it doesn't narrow things down much — it's mostly just strong evidence that something really changed between about 1970 and 1990.

Small dose fine, big dose bad

Uri Bram: Can you talk a little about bioaccumulation? like, how would we identify that something might be caused by bioaccumulation?

Slime Mold Time Mold: Bioaccumulation is something we need to keep in mind, because there might be a contaminant that truly is harmless in low doses, or even in large doses all at once, but harmful if we get chronic exposure. In this case, you might miss it if you only looked at obvious measures of exposure. You might see something like, serum levels of the contaminant aren't correlated with BMI, but levels in parts of the brain are correlated with BMI. But that's a pretty rough and idiosyncratic example. Ultimately it's hard to tell.

Part of the problem is that "bioaccumulation" could refer to a wide class of mechanisms so there's no clear signal. Just because it gets worse with age, that doesn't mean it's definitely related to bioaccumulation, but given the change in profile of obesity as you age, bioaccumulation might be involved.

Uri Bram: That also reminds me of another really interesting part of your piece -- one thing I hadn't realised was just how rare obesity was before the 1980s across a wide variety of people and diets. Not unheard of -- I think you said 1% -- but we take widespread obesity for granted now and it used to be very uncommon, and maybe could become super uncommon again.

Slime Mold Time Mold: Yeah, can you imagine a world where obesity is at 1% again? Where weight is barely an afterthought?

Anorexia too?

Uri Bram: Yes, and equally surprising was how rare anorexia used to be -- actually, let’s back up and talk about paradoxical reactions, can you explain how the rise in anorexia actually provides really useful evidence for your model of obesity as well?

Slime Mold Time Mold: Yeah, absolutely! For anyone who hasn't read the post, sometimes drugs have what’s called a paradoxical reaction, where the drug does the opposite of the thing it normally does. Most of the time amphetamines are a stimulant, but sometimes they make people drowsy.

If obesity is caused by a contaminant, we might expect a paradoxical reaction like we see in any other drug. This would look like chronic weight loss, or anorexia. You'd expect anorexia to spike around the same time as the obesity epidemic began, you'd expect more obese countries to have higher rates of eating disorders, and you'd expect increases in obesity rates to be related to increases in eating disorder rates. We looked for these signs and found all of them.

It may not be obvious to readers, but this is a prediction we came up with after coming up with the contaminants theory, so it's one case of the theory making testable predictions and coming out successful. It's easy to speculate based on seeing some connections (fun too), but it's hard to make predictions that bear out when you test them. As a result it's particularly strong evidence for the theory.

We also have some work testing another prediction, that we should see evidence of anorexia in animals. This is even stronger evidence since it is a much more specific prediction and it is strong evidence against social explanations for anorexia, just like animal obesity is strong evidence against social explanations for obesity.

Uri Bram: I think on both sides, the anorexia and obesity side, this idea of a lipostat was really interesting to me – kind of like the thermostat in a house, your body has a target weight and will constantly adjust to target that weight. If you’re anorexic or obese it’s because your lipostat has gone haywire somehow, and it really doesn’t matter how much willpower you exert or how hard you try to lose or gain weight (as the case may be), your body will just inevitably revert you to the weight it thinks it’s meant to be at. Whatever is causing the obesity (and anorexia) epidemics is probably doing so by screwing with people’s lipostats.

One of the things I find interesting about this is how it goes against so much of the moralising that happens around weight. A thought experiment that a lot of people are interested in is "what will future generations judge us for?,” as in, which things that we're doing now will just seem incredibly immoral and unimaginable to our descendents? And–

Slime Mold Time Mold: ooh very good. Yeah, probably judging people for their weight… and eating meat. Definitely could see a future where making fun of someone for being overweight would be closer to making fun of someone for having heart disease, similar to the change we're currently seeing around mental illness. Really they’ll probably find making fun of someone’s weight more unthinkable than objectionable? Like how we would have a hard time even imagining judging someone for being Irish or Italian.

Uri Bram: Yes I often think that people trying to imagine those futures now are kind of cheating at the game by choosing things that are already pretty widely viewed as immoral at least in their own social circles – factory farming, modern prisons – whereas the real strength of the game is choosing things that we take for granted now and which in future people will just find unfathomable, unthinkable, incomprehensible.

On a similar note, I suspect that if we find the contaminant then whoever or whatever is producing it might become villainised in a moralising sort of way – they’ll be the future equivalents of the tobacco companies.

Slime Mold Time Mold: Well it kinda goes either way: 3M deserves to be villainized either way for PFAS, which are definitely bad for you and maybe cause obesity. But if it's lithium then it really looks like no one in particular is to blame.

Kind of embarrassing for doctors, though.

Canaries in the Coal Mine

Uri Bram: Speaking of embarrassment, this is actually another meta-question: why do you think this research hasn't been done already, and perhaps especially why hasn’t it been done already inside the traditional institutions? You said earlier that it might be especially the experts who have noticed that previous explanations for the obesity epidemic didn't really make sense. And this is obviously a topic of great interest to the whole population and to public health establishments, it’s not some obscure niche. You're not the first to work on this thesis, and you credit other authors throughout the piece, but you also seem to have done a surprising amount of new work just from reading and writing online.

Slime Mold Time Mold: Yeah, so we say it's embarrassing but also we wouldn't have been able to do any of this without all the work that has been done before. We do a little original analysis in A Chemical Hunger but there’s no original data. We’re relying on work from hundreds of papers and probably thousands of researchers.

The special sauce is the new theoretical direction, but that isn’t entirely original either. Some experts had already been thinking in this direction. Very little focused work, but people had started speculating. We've talked to a couple senior researchers about this, and the responses were split between “I hadn’t thought of that but it seems plausible” and “yeah I’ve also been thinking contaminants might be a big deal”. One close paper is Canaries in the Coal Mine from 2010, David B. Allison was one of the main authors on that. That paper says “the aetiology of increasing body weight may involve several as-of-yet unidentified and/or poorly understood factors,” and as possible factors they mention viral pathogens, epigenetic factors, and “the collection of endocrine-disrupting chemicals (endocrine-disruptors), widely present in the environment.”

What is totally original to us are some of the contaminants we suspect — PFAS and especially lithium.

It's more embarrassing for doctors than for researchers. Researchers were mostly on the right track. Meanwhile there's a big disconnect between doctors and the literature, which is part of the problem. That said, we also talked to one researcher who tried to publish something in this direction and peer reviewers made him cut a bunch, so it’s not like things were perfect in the research world either.

We really wouldn't have been able to do this ten years ago, or even a few years ago. If you look at our sources, something like 50% of the papers we cite were published since 2010. We're lucky to have been working on this problem at this time.

The internet and public availability of data and tools are also changing research enormously. OurWorldInData.org was a major source for us, and projects like that are pretty dang new. We think we are just some of the first, and that there will be many, many more projects like this in the future, maybe even the near future.

Uri Bram: That's great. There's something very interesting about this one in that it affects all of us, I think a lot of us have done "experiments" ourselves in one sense or another, whether that's going on a diet or changing an exercise regimen. And obviously it's hard to draw conclusions from ad-hoc one-person experiments, but that feeling that something about the current model doesn't add up is.... well, let's just say it accords with a lot of people’s personal experiences.

Slime Mold Time Mold: Yes! The series definitely speaks to a lot of people in that way.

How to be taken seriously as a random from the internet

Uri Bram: On which note: you're two "random" people from the internet, and you had this big idea that you've now written up at length. I think in any situation like that there’s obviously a possibility that the writers will be labelled as kooks, and also a possibility that they're going to revolutionise science and society – I mean, there’s also lots of possibilities in the middle where they're going to incrementally add something positive to a useful body of knowledge, but you get the idea.

Anyway, I’ve noticed a lot of cynical people on Twitter posting your series and saying "these people are smart, this work is serious" – of course a lot of them disagree with your arguments in small or big ways, that’s only to be expected, but I think everyone I’ve seen agrees that you're doing real and interesting work

I wondered if you could talk about your experience here, and how you would advise other people in similar situations – they have an interesting idea on a car ride and want to write it up on the internet, what should they do to be taken seriously?

Slime Mold Time Mold: Yeah, well first of all thank you! It's been very cool to see all the positive feedback. When we started this we really expected it would languish in obscurity.

It's easy to assume that most people are close-minded and only think about credentials, fame, whatever. But we think that's a big misconception — most people can look at a piece of work and judge it critically on its merits! We already believed in people's ability to pay attention to substance, but even so we've been very impressed with the thoughtful responses, even from people who disagree. Very little spam, lots of substantial critique and intelligent questions.

The question of advice is a really good one. Our main advice is to just go for it! Have faith in people's ability to give your idea a chance, and faith in your own ability to evaluate the world. There have been many fewer barriers than we expected, and most of the barriers we hit were self-imposed. It's not historically weird to do science as a hobby. We like the example of Van Leeuwenhoek, who was a cloth merchant who just really liked playing with microscopes, and basically invented microbiology.

That said we can give a little specific advice — you have to give attention to your writing and how you present the idea. Good writing doesn't have to be fancy, but you do need to think about how to express your idea. You need to trust your audience to consider your ideas in good faith. This means all the classic stuff — being open rather than secretive, giving arguments both for and against your position, expressing areas of doubt, describing what you could discover that would make the case for the idea stronger or weaker, etc. Trusting your audience also sets the tone. If you assume people will dismiss you, if you treat them like they’re stupid, if you’re defensive, suspicious, aggressive, people will notice this. But if you write with the assumption that people are open-minded, curious, kind, intelligent, and will give you a fair shake, people will take you seriously even if they end up disagreeing.

It’s also good to work on projects that don’t end up working out. We’ve written a lot of things that we haven’t published, and probably will never publish. We have a lot of projects that were dead ends. So don’t pin all your hopes on your first idea. Try a bunch of things, just go for it, and don’t worry if some of them don’t pan out.

At the same time, don't take it too seriously! We love writing on a blog with a silly name. Even very good work is full of mistakes and dead ends. Even if the contaminant theory ends up being 100% correct, there will still end up being dozens, hundreds(?) of mistakes in the blog posts, and that's cool, it's ok. Research is about exploration.

(Our best advice is to choose the silliest blog name you can think of).

Uri Bram: ahahh yes it really delights me that I'm having this conversation with two molds.

Slime Mold Time Mold: MOLD MOLD MOLD MOLD

Uri Bram: Is one of you Slime Mold and the other Time Mold, or is it a collective designation?

Slime Mold Time Mold: Yeah it's collective, like a band name.

Kuwaiti vets

Uri Bram: It's a great band name. Ok, last question: is there anything you'd like to hear about from any readers who might have specific access or intel, any information that would help you advance your work?

Slime Mold Time Mold: That is a great last question! We've really loved getting emails and comments from people. One of the coolest things is that people have sent us things that were really helpful but that we never would have thought to ask for! People know better than us what is out there and what we would never know to think about, it's a classic unknown unknowns. So we'd love to hear from anyone who has anything they think is relevant.

More specifically, we're curious to hear from vets about animal anorexia (they might think of it as "failure to thrive"), and from anyone who has experience with water treatment in the Middle East, especially Saudi Arabia and Kuwait.

Uri Bram: What a delightfully eccentric wishlist. Slime Mold Time Mold, it's been a pleasure chatting, and I can't wait to see what's next for the band, both on the rest of the Chemical Hunger album and all your future records: can you please tell people where to find you online and read more of your work, and how to get in touch with you (for all the Kuwaiti veterinary water engineers out there)?

Slime Mold Time Mold: Thank you! Our blog is at slimemoldtimemold.com and you can find us on twitter as @mold_time. Thank you so much for the great questions, this has been really fun!

This interview was conducted over instant messenger and has been lightly edited.

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