This week we talk to Ben Peters, graduate student at MIT’s Media Lab, about 3-D printing.
RepRap-the 3-D printer that makes some of the parts for itself
Thingiverse-free designs for MakerBot
Our fabulous theme song was created by the always amazing Paul Smaldino.
Links from the show
Arxiv.org (the open access system we discuss)
What is epigenetics?
Michael Meaney (the professor we discussed who studies epigenetics in rats)
Transcript of Episode 1: Manuscripts, mushrooms, and methylation
Transcribed by Luca (thanks, Luca!)
October 2, 2011
Kelly Weinersmith: Hello! Welcome to The Weekly Weinersmith. I’m your host, Kelly Weinersmith.
Zach Weinersmith: As am I, Zach Weinersmith.
Kelly Weinersmith: Thanks for joining us. In this podcast, we’re going to be talking about a variety of different topics ranging from science to geek stuff to dick jokes. And some weeks we’ll just be sort of telling you about cool stuff that we learned this week that we’re excited about, and then other weeks, we’ll also have an interview, so anytime someone awesome crosses our path, we’ll sit them down and make them do an interview with us. This week, we’re going to start off by just talking about awesome stuff that we learned this week that we’re excited about. If you want to check out our website, you should go to weeklyweinersmith.com. If you want to send us an email because you have thoughts on any of the topics that we talk about or you want to ask us a general question, you can send that email to email@example.com, and you can follow us on Twitter @TheWeinersmiths, all one word.
So we also thought that one cool thing to do in this podcast would be to sort of chronicle the life of two geeks who are taking very separate geek paths, so we’re going to start each show by talking about stuff that we did that week that we thought was pretty exciting that we were happy we were able to do that week.
And so this week, the big task that I had to accomplish was to do controlled infections. So I study trematode parasites that infect California killifish, and the trematode parasite that I think is really awesome infects the brains of these killifish, and it changes brain chemistry around and gets the fish to do these really weird behaviours that make them more likely to be eaten by predatory birds. This is good for the parasite because the next host in the life cycle of the parasite is these predatory birds, so by getting the fish to act in these weird ways and getting the fish eaten, the parasite’s able to complete its life cycle. So we know that these chemicals that are changed by the parasite are affecting lots of different behaviours in other fish species, so I’m interested in seeing how the entire personality of the fish is changed by infection.
So I’ve run my fish through a bunch of different behavioural trials measuring general activity and social behaviour and boldness, and this week my job was to infect them with the parasites that I study. The name of the parasite is Euhaplorchis californiensis, and I study another parasite that infects the liver called Renicola buchanani. And so I infected the fish with these parasites, and now I’m going to measure their behaviours again and see what happens. So the really cool thing about this system is that, in most cases, we don’t really know about the life cycle of the parasites that we study, or we don’t know it well enough that we can keep it in the lab. And the thing that I love about my system is that we know that they first infect California horn snails, and if you put these snails in a dark, damp place for a couple days, then they’ll build up a bunch of the parasites, and they’re building up the stage that’s infective to the California killifish, and when you put these snails in water, they’ll release a bunch of the parasites, and now you can infect your fish or whatever organism. It’s got to be fish. You can infect your fish with these parasites.
And so my task this week was to get these parasites, count the different numbers of them, put them in beakers, and then expose the fish to them. And I was really surprised to see that the Renicola buchanani — which is the parasite that infects the liver; it infects the fish when the fish eat it — and I expected the fish to be kind of hesitant about eating these parasites that could affect, could hurt them and alter their behaviour, but they ate them like I’ve never seen them eat anything before. They totally gobbled them up.
Zach Weinersmith: Can I ask a parasite question?
Kelly Weinersmith: Yeah.
Zach Weinersmith: The question I always get asked when I tell people about your parasite system is: Why would a parasite ever evolve a multiple-host life cycle?
Kelly Weinersmith: Right, so questions like that you can’t really answer experimentally well, so we have a bunch of just-so stories that make sense, but again, it’s just a story. And so the idea is that these parasites initially just infected snails, and they would leave the snail, and then they’d go off to find more snails. But the problem is, their free-swimming stage is essentially this packet of energy, so they’re just like little motors, and they get eaten by fish and tons of other stuff, and there have been studies quantifying how many of these parasites that are swimming around get eaten by fish. So if you can turn your predator into the next host in your life cycle, then maybe that increases the probability that you survive.
Zach Weinersmith: And so the idea is that once that takes place, then the parasite benefits from specializing in each environment rather than being able to be anywhere?
Kelly Weinersmith: Yeah.
Zach Weinersmith: Ah.
Kelly Weinersmith: Yeah, so the ones that were able to turn their predators into the next host did better than the ones that couldn’t do that.
Zach Weinersmith: Do you see… I don’t know if this is outside your expertise. Do you see a thing where there’s an average number of intermediates for a parasite, like is there a cluster around, say, three or four, or is it just random?
Kelly Weinersmith: Yeah, most trematode parasites have three, three different species of hosts in their life cycle.
Zach Weinersmith: But, I mean, across all parasites, is there like an optimum… Because it seems to me like there should be sort of a cluster point, because there couldn’t be twenty. That would be very bad, but there’s obviously some advantage to having more than one, so is there like an aggregation?
Kelly Weinersmith: So the different kinds of parasites tend to have a certain number of hosts that is the same, so almost all trematodes have three hosts in their life cycle, but lots of nematodes only have one or two, and I think that a lot of the nematodes that only have one end up being eaten again by the same host, so they leave in the feces, and then that cow comes over and grazes the grass and eats it again, and so then…
Zach Weinersmith: So then you would expect them, like if you were to have a parasite in a really complicated food chain, that it would have more hosts.
Kelly Weinersmith: Yeah.
Zach Weinersmith: Got it. Got it.
Kelly Weinersmith: Mm-hmm. Or whenever a parasite can be preyed upon by something, there’s an increased probability that it will try to turn it into — “try”, quote-unquote — to turn it into the next host in its life cycle.
Zach Weinersmith: Right.
Kelly Weinersmith: Yeah. I think that’s a totally awesome question, but everyone just has just-so stories.
Zach Weinersmith: Yeah. I mean, it would be a really long steady, but you could probably do a study where you take an organism that has only a one-step process, and then you make like a mesocosm environment with a built-in, say, four-step chain and then just watch it for 30 years and see if it starts figuring out ways to be in the other hosts effectively.
Kelly Weinersmith: Hmm… Yeah, I don’t know if 40 years is enough evolutionary time to see that kind of switch. It takes a long time to adapt to a new host. I think there’s…
Zach Weinersmith: I… Go ahead.
Kelly Weinersmith: So I mean, for example, Euhaplorchis californiensis had to find the right location site in the host in order to exert the behavioural changes, and it probably took a lot of guess and check to try like, “Does the liver work now? But maybe the brain is a good spot, and if you’re on the brain stem, then you can control the behaviour,” and…
Zach Weinersmith: Yeah, but I mean, it doesn’t have to be optimum, it just has to be there. And then, I mean, the replication time is probably really low for most nematodes or trematodes. Right?
Kelly Weinersmith: So for the entire life cycle of Euhaplorchis californiensis, it’s so they can live in the snails for up to like 20 years. The fish live for 1 to 2 years, and they need to get eaten in that time, and then they finish their life cycles in the birds in a couple weeks. So 40 years could be, I don’t know, 80 generations or something depending on…
Zach Weinersmith: And how many individuals per generation?
Kelly Weinersmith: So we don’t know how many eggs are produced by the adults. A lot of cercariae can be produced by the snails. I mean, they’re probably producing millions of cercariae. Once they’re in the fish, there’s no reproduction at all. So they can get to pretty good population sizes, but all of the cercariae, for example, are pretty much genetically the same. There might be some mutations, but it’s all asexual reproduction there, and they can asexually reproduce in the adults too, but if there’s a partner, then they’ll reproduce sexually.
Zach Weinersmith: I mean, it’s kind of a subjective thing, but I feel like in the right environment, evolution maybe happens faster than we suppose it does. Like have you seen the… There were these… I was reading a while back there were these experiments where they sort of took, say, something like an acre of land, fenced it off, and would remove a complete species from it, just sort of meticulously pull out every member of the species in this fenced area, and then watch as its niche got taken over by something else, and it would happen in very short amounts of time, like in, say, 10, 20 years.
Kelly Weinersmith: I think that there’s a difference between changing your resource use a little bit and adding a new host to your life cycle. So it’s not hard for me to imagine that some organism that already existed changed its behaviour and its eating habits a little bit to fill a niche that it wasn’t in before, but it’s a whole different thing… So a cercaria that’s eaten by a fish, it needs to survive, needs to be able to survive stomach acid. It needs to be able to burrow through the stomach wall and move up nerve tracts and stuff, and so you need a whole… It’s not just using a new resource. It’s surviving and not having that immune system destroy you.
Zach Weinersmith: Yeah, but I mean, you’re still assuming that it’s optimized, like so… The animal, the species that burrows through skin didn’t necessarily initially have that capacity. That could have evolved subsequently.
Kelly Weinersmith: True, but then so the other way to get into the host would have been to have been eaten by it, in which case you need to survive the mechanisms that are meant to kill you.
Zach Weinersmith: True. I mean, for the purposes — and we shouldn’t linger on this too long — but for an experiment, you could set it up so that the potential new hosts are relatively similar, like they could all be fish.
Kelly Weinersmith: Yes. Okay, so now we’re not talking about adding a whole new step to your life cycle. We’re talking about switching from one host to another closely related one. That, I believe, could happen in, could maybe happen in 80 generations, but I don’t think…
Zach Weinersmith: Then we agree.
Kelly Weinersmith: Okay. Bam. What did you do this week?
Zach Weinersmith: Is that all of your stuff, all of your excitingness?
Kelly Weinersmith: It was kind of a shitty week. [laughter]
Zach Weinersmith: Let me see. The last couple of days, I’ve been just drawing because of NYCC coming up, but before that began, I did some of the math blogs. I just completed the introduction of derivatives.
Kelly Weinersmith: Nice. Ooh.
Zach Weinersmith: Which is exciting. And then on the physics blogs, I’m doing just motion and one-dimension is where I am right now, and then on the discrete blog which I just started, I’m just working through the sort of basic operations, which is the most fun of them all. What?
Kelly Weinersmith: How would you define discrete math? So most people, I think, are familiar with like calculus and algebra. What is discrete math?
Zach Weinersmith: Discrete math, as the name implies, has to do with sort of discrete logical entities. Does that make sense?
Kelly Weinersmith: So I know what the word “discrete” means.
Zach Weinersmith: Well, so… Oh, I see what you mean. So, well, I should say I don’t know enough to really give a definitive statement on this, but my sense is that it’s a bit of a grab bag. So for example, in I think in the book I’m using, they give a sort of “choose your own adventure”-style flowchart of how you can read the chapters, and it’s not very branched. Which is to say… How do I say this? It would be like you need this chapter 1 to get to chapter 2, and then from chapter 2, you can go to any chapter 3 through 8, and instead of sort of going 1, 2, 3, 4 like a calculus text might go, and so I think it’s a bit of a grab bag having to do with how you sort of logically analyze things and run algorithms and this sort of thing.
Kelly Weinersmith: Cool.
Zach Weinersmith: Yeah. Like I said, I’m not knowledgeable enough to give a sort of blanket statement like I could with some other subjects.
Kelly Weinersmith: You’ll get there.
Zach Weinersmith: Yeah!
Kelly Weinersmith: Oh, oh, the —
Zach Weinersmith: What? What happened? What —
Kelly Weinersmith: The other exciting thing we did this week was, we worked with Jai Ranganathan to talk about the SciFund Challenge a little bit, and which I think is totally cool. So the SciFund Challenge, for people who don’t know, is an experiment in crowdfunding. So they’ve set up a Rocket… RocketHub is this preexisting crowdfunding site where people post video proposals and the people who are posting the proposals ask for donations so that they can make the thing that they proposed actually happen. And scientists don’t really tap into this crowdfunding opportunity yet, and so the SciFund Challenge is trying to get a bunch of scientists all onto RocketHub at once with a bunch of different video proposals so that we can try to see if we can get small experiments from a couple hundred to a couple thousand dollars funded using crowdfunding techniques. And so Zach and I have been thinking about posts to write and helping to put some posts on the scifund.wordpress.org site to try to help people figure out how to do it. And…
Zach Weinersmith: Oh, can we… Let’s talk about peer review. So we had an interesting conversation at Beerscussion this week (or was it last week?) which was, we were sitting and talking, and the one question I did have about the whole SciFund or crowdsourcing science was the peer review question, or maybe a better way to say it would be, we all sort of… I think everyone in academia agrees that the journal system is not perfect, but — and it’s sort of an open question as to whether there’s a genuinely better way. It’s kind of how we feel about like capitalism where we say, “This seems like a pretty good system, but there are all these things that are wrong with it, but it might be the best system available that humans can make work,” but when we were talking, it occurred to me that… I couldn’t figure out the downside to having everything run like it was on arXiv.org. Right? I could not… Like say you just took every journal article and just had a site like arXiv.org. Which is to say, you had a site where everyone could upload and everyone could comment, and there was a sort of voting system and the comment system so that you could retain a lot of the qualities of peer review, which is the ability to comment and complain and the ability to say, “This is bad,” and it’s something like impact factor in terms of people giving some sort of thumbs-up system or something to good stuff and a thumbs down to bad stuff. And so I don’t know what you lose, and it’s clear what you gain. So did you have any thoughts contrary to that?
Kelly Weinersmith: Well, so, first of all, for non-physicists, arXiv is a site where people post the papers that they eventually plan on submitting to a peer-reviewed site, and they’re open to the public, and everyone can see them. And one of the benefits, I think, of arXiv is that it’s a good way to stake your claim, so if you… When you’re waiting for your paper to get through peer-review, someone else can publish the same thing, and sometimes there’s an argument about who did it first. And if it’s up on arXiv, then it’s got a timestamp, and so you can say, “Oh, I did mine on May 3rd.” But so the one thing that I can think of as a downside is that as an… Not an official editor, but as someone who has agreed to do some reviewing for different journals, you’ll see that a lot of papers are really crap when you first get them, and I think that it’s because people either, one, are not good writers or not good at expressing their ideas, or just need some more input, and so their papers get much better after going through and having two people who are dedicated to reading your paper and providing you with comments. And so I think papers get better going through this process, but a lot of that improvement is just getting people to be more clear about their words or cleaning up grammar and stuff, and so… That’s not really stuff that matters a ton, and it’s also stuff that could be dealt with in the comments section.
Zach Weinersmith: Yeah.
Kelly Weinersmith: [unclear 15:28] arXiv.
Zach Weinersmith: I was going to say… You could even do it better by having it be sort of a wiki. I mean, not a… Well, no, I take that back. Not a wiki that everyone could edit, but you could make it so that the authors of a paper could make changes, but the changes were always tracked, so someone couldn’t fudge their data afterward without being caught, but you could make changes just to your verbiage or… You can imagine an example where someone put up a paper, and it was a perfectly good paper, but you didn’t like the statistical technique they used, so you would say, “You should use this other technique and change that,” and so they could actually re-go into the paper after running this other technique and fix it. And so the ideal site would preserve the old version just so you can sort of watch for people running forty statistical tests to get the right answer. You know?
Kelly Weinersmith: Yeah, yeah. That would be much better. It would be really good to have a record of how the statistics changed the results.
Zach Weinersmith: Yeah, and so… To your other point, which was that it improves quality, my sense is, I think people think that that sort of thing can’t be done in a crowdsourced way, but I think Wikipedia sort of refutes all that. Like I mean… Well, I got to think about it. So the good thing about crowdsourcing is that if you have enough people, which I think you would with a science arXiv.org, an arXiv.org for every discipline, you would get enough people. The problem is… I suppose I can imagine a situation where a lot of the really good people who don’t like reviewing would just abdicate from reviewing altogether, and so you would get sort of a sieve for a certain type of personality to do the commenting on a site like that. Does that make sense?
Kelly Weinersmith: Yeah, and you could come up with the score point, though, like where the more someone comments, the more that that goes into their like… I’m sure that there’ll end up being a system where the researchers get points for how influential they are and how many people cite their paper, etc., and maybe you could even work into that some system where the more that they comment and the more substantial their comments are, the more points they get for interacting with the community.
Zach Weinersmith: But that’s what… What I should say is that the potential downside, to my mind, of that is, you have these people who are just… You know how most people are either good teachers or good researchers? There are a few awesome people who can kind of do both, but most people are really good at one or the other, and it would be maybe a bad thing if those types of people who are really more into research or those really OCD types who just want to huddle up with their books felt obligated to engage in this point system that made them comment on everything.
Kelly Weinersmith: Yeah, that’s a good point. So there’s actually talk outside of the arXiv system and the normal peer-review system of setting up a system of points where you only get to submit if you’ve accumulated enough reviewer points.
Zach Weinersmith: I don’t like that at all, because… I mean, I don’t know. Can you imagine a system where Einstein wanted to submit a paper and they were like, “Uh-uh-uh, you got to review some stuff”?
Kelly Weinersmith: I think it’s totally fair. You only need to… The system would be, you only need to review as many papers as cancels out what you are submitting, and so they…
Zach Weinersmith: Yeah, so you’re saying it’s not a very onerous obligation.
Kelly Weinersmith: Yeah, so if Einstein wanted to submit a paper, you’d be like, “Fine. Comment on two papers by your colleagues,” which would take him a max of a couple hours, maybe two days if he was really detailed, and now he’s cancelling it out, and that way, there aren’t people who are forced with this burden because they’re good community members who are doing much more than their fair share.
Zach Weinersmith: But that’s… I don’t know. Let me give a couple counterexamples. So take a guy like Paul Erdős, who everyone loves because he did, what was it, something like 1,500 papers in his life, so in this system, if this system had been in place in the mathematical journal system, he would have been obligated to put in something like 5,000 hours of his time commenting on stuff, and it might have taken even longer, because he seemed to be the kind of guy who wouldn’t like doing that sort of thing, so you can imagine a person like him taking this comment thing as a barrier. And another counterpoint would be that there might just be people who really enjoy commenting, so why should they sort of benefit disproportionately? Does that make sense?
Kelly Weinersmith: Yes. So a couple things. So first of all, I believe that this system that was proposed would only apply to first authorship, so Erdős wasn’t first author on 1,500 papers. In fact, I think he was mostly second, third, or fourth author or something. And so he wouldn’t have to review that many papers. And I agree that there probably are some people in the community who really do enjoy reviewing papers. I personally enjoy reviewing papers quite a bit, but I still don’t think it’s fair to let people skate. I don’t think you should be able to submit more papers than you have yourself reviewed. You can’t add more of a burden to the community than you’re willing to negate.
Zach Weinersmith: But then that’s what I’m saying is…
Kelly Weinersmith: [unclear 20:12]
Zach Weinersmith: … it’s not necessarily a burden. Like you were just saying, it’s not really a burden. You said you enjoy it, so that’s what I’m saying. It’s one person’s burden is another person’s treasure, I guess, or…
Kelly Weinersmith: Eh… So I enjoy doing it, but I enjoy doing maybe one every month or one every couple months, enough to cancel me out plus maybe a little bit more, but the kind of…
Zach Weinersmith: Yeah, but…
Kelly Weinersmith: There is no one out there who enjoys reviewing papers so much that they’re willing to cancel out a bunch of other people’s work, and those researchers would… It takes a long time to review a paper. Those researchers would be, in my opinion, so penalized for their community service, that they would end up getting less papers out, and it would diminish their ability to make an impact in the community.
Zach Weinersmith: Yeah. I don’t know. It just sounds like it would be… How do I say? I think I’m probably just circling back to my initial point, which is just that you can imagine that it’s excluding a certain personality of scientist, and that might be bad.
Kelly Weinersmith: So I think that most scientists have the personality you’re thinking of, which is that they don’t want to sit around and review someone else’s paper, and so the vast majority of people don’t want to do it, and the people who do enjoy it don’t enjoy it enough to make up for the fact that 50% or more of people think that reviewing papers is a burden. And so I think that you either have some people who enjoy it and then suffer because they are doing so much or you have some way to strong-arm other people into it. You know [unclear 20:31]
Zach Weinersmith: Yeah. I mean, we already accept, for example, that if you have an adviser, your adviser gets to sort of tell you what you’re going to be working on, say, if it’s your first year. You wouldn’t say, “Well, it’s this big burden on me. We should both have the opportunity to tell each other what to do.” We accept that there’s a system where people who have achieved positions of prominence get more choice over how to spend their time, so why would you not accept that for a system like this?
Kelly Weinersmith: Hey, I feel like that’s different. So are you arguing that when you’re new in the community, you do your adviser’s project even though you don’t want to and that’s similar to having to review a paper you don’t want to review?
Zach Weinersmith: What I’m saying is, we have a system that — and maybe you think this is a bad quality of the system, but it is part of the system that the higher you advance, the most discretion you get over your time, or at least in theory. I mean, maybe you have to be on a bunch of committees and stuff, but in terms of what you’re doing with your career, the people who have really made it up the science ladder or however you want to say it get more discretion, and I think we agree that’s a good thing, because not every first-year grad student is going to be doing topnotch work. They need a little time to settle into it. So it wouldn’t necessarily make sense to just let them roam free unless there’s some compelling reason to do so. So if you accept that system that we give more latitude to the people who are higher-ranking, why is that system not appropriate in the context of an arXiv.org-style website?
Kelly Weinersmith: So I think that senior people have a ton of stuff to do that they don’t want to do, and so I think…
Zach Weinersmith: Yeah, but we agree that’s a bad thing.
Kelly Weinersmith: … you’re wrong.
Zach Weinersmith: Right?
Kelly Weinersmith: Not entirely. I mean, committees are often a huge waste of time, but they also keep the university running, and a lot of professors need to be on the qualifying exam committees of a ton of grad students. I definitely feel like the professors, at least the ones I’ve seen at UC Davis, have a lot more work to do that’s not research.
Zach Weinersmith: Okay, but I’m not talking about what happens. I’m talking about what the ideal would be. Right? The ideal situation would be that you could take these really good scientists who have a proven track record and give them lots of time to pursue their interests. Would you agree that’s the ideal?
Kelly Weinersmith: That you only give that to the best people?
Zach Weinersmith: That you preferentially give it to the best people, yes.
Kelly Weinersmith: I think that that would be good, but I don’t think…
Zach Weinersmith: That’s what I’m saying.
Kelly Weinersmith: … that those people should be free from their community obligations.
Zach Weinersmith: It’s not binary, though. It’s not free or unfree. It’s just that an ideal system would reward more discretionary time to people with a better track record. Would you agree to that?
Kelly Weinersmith: Would reward more time to people who are more productive with their time?
Zach Weinersmith: Yeah, I mean, using whatever quantifier, like a scientist who has contributed great theories or made lots of contributions that that person should be allowed more latitude with his time.
Kelly Weinersmith: Yes and no. Like I don’t think they should be out of the reviewing…
Zach Weinersmith: You’re like agreeing with me, but you’re resisting my argument because it’ll circle back to the other point.
Kelly Weinersmith: I feel like I can’t see how your point is going to circle back to the other point, and I’m trying to figure out how it relates, but I’m not seeing the point you’re trying to make. So Andy, I think, is brilliant and uses his time well, and Andy is my adviser, Andy Sih, and that he could turn the time that he takes to reviewing papers into a bunch of other papers, but because he’s so brilliant and so good at the use of his time, I think he should be reviewing papers, and he is, because he’s brilliant and he should be contributing and helping other people increase the quality of their work. So I personally can’t think of any reason why you should even let a really smart, hardworking person out of their obligation to review journal articles from time to time. And to be fair, I think that almost everybody does review journal articles from time to time, but some of them just reject more than others.
Zach Weinersmith: Okay.
Kelly Weinersmith: Reject more offers to review than others.
Zach Weinersmith: I guess, let me just bottom line, and then we’ll move on. I think the disagreement we’re having is something like, my view is that people who are doing the best work should be given a lot of reward for that, and you would rather have a more egalitarian or ecumenical system where, regardless of what you’ve achieved, you still have to share in some of the obligations.
Kelly Weinersmith: Yeah.
Zach Weinersmith:. Okay. I think you’re wrong. [laughs]
Kelly Weinersmith: We can agree to disagree. And when I think that people who are really advanced do manage to get out of work by buying themselves out of teaching obligations and getting grants and stuff, and I’m totally fine with that…
Zach Weinersmith: Wait, wait, wait. Are you? Because if you’re fine with that, you should be fine with the idea… Ah, I shouldn’t. We should move on.
Kelly Weinersmith: All right, fine. We’ll move on. Okay. We did end up not talking about the SciFund Challenge at all, because what you brought up is completely different.
Zach Weinersmith: Yeah.
Kelly Weinersmith: But that’s fine. We’ll talk about it when it’s actually running.
Zach Weinersmith: Yeah, yeah.
Kelly Weinersmith: Magic mushrooms?
Zach Weinersmith: Yes.
Kelly Weinersmith: Okay.
Zach Weinersmith: [unclear 26:29] let me pull up the document. [singing] Doo-puh-doo-doo-doo-doo.
Kelly Weinersmith: I’m going to pull up the document as well as our list of grievances.
Zach Weinersmith: Oh, [unclear 26:39]
Kelly Weinersmith: Okay.
Zach Weinersmith: You want to give the sort of prologue?
Kelly Weinersmith: Sure. All right. So Zach and I were browsing reddit.com in the science subreddit, and we came across two articles that we thought were worth discussing, and the first one is just mind-boggling. So it’s by MacLean et al., 2011. It can be found in the Journal of Psychopharmacology, and it’s called “Mystical experiences occasioned by the hallucinogen psilocybin” (shoot, I was going to look up the pronunciation first. I’m just going to say “psilocybin”) “lead to increases in the personality domain of openness”. So essentially what they did in this study was, they put out an ad on like community boards, and the ads said they were recruiting participants for a, quote, “a study of states of consciousness brought about by psilocybin, a naturally-occurring psychoactive substance used sacramentally in some cultures.” So essentially, psilocybin is the active ingredient in magic mushrooms that causes hallucinations, and they were interested in long-term changes in personality after taking that active drug. And specifically, they were interested in openness. And how did they define “openness”?
Zach Weinersmith: I mean, I’m actually okay with the idea of openness as like a metric. I mean, as long as we accept that it’s a sort of human-devised metric. We have metrics for things like happiness or sadness. They had some sort of scale. I think the other stuff is so egregious, let’s give them the benefit of the doubt on the openness scale.
Kelly Weinersmith: Oh, I was giving them the benefit of the doubt.
Zach Weinersmith: Oh, okay.
Kelly Weinersmith: For the sake of being clear about what they thought was going to be changing, I just wanted to sort of define “openness” a little bit, and I think it was like “willingness to experience new things and consider other people’s viewpoints”. [unclear 28:34]
Zach Weinersmith: Was creativity a metric, I think?
Kelly Weinersmith: Yeah, I think it was.
Zach Weinersmith: Yeah.
Kelly Weinersmith: So other studies of this type have been done using LSD, and they didn’t really find any personality differences, and this is our first point of WTF while we read this paper together. So they claim that there was a study looking at LSD, and they gave LSD to healthy volunteers, and then they ran them through a number of different personality tests. (So the psychology literature has created these tests that are standardized that you can give to people, and different studies use those exact same tests so you can compare results.) And so they gave people these personality tests, and they didn’t find that LSD changed any personality traits in a statistically significant way. And in the next sentence they say, “Nevertheless, these investigators confirmed the subjective claims of long-term change frequently reported in uncontrolled trials.”
Zach Weinersmith: So just to make sure it’s clear to the audience, as far as we can tell what they’re saying is, “There were no statistical results, but the dudes in the tests said it totally affected them in the way we were looking for.”
Kelly Weinersmith: Right, so statistics be damned. They’re pretty sure the effect was there anyway.
Zach Weinersmith: They should have said that. They should have just said, “Statistics be damned.”
Kelly Weinersmith: They pretty much say that later when they pool the data across different studies.
Zach Weinersmith: No, then they’re using statistics all over the place. They suddenly love statistics at that point.
Kelly Weinersmith: They don’t love sound statistics.
Zach Weinersmith: No, no.
Kelly Weinersmith: Well, so what they do is, they have these two different studies, and they have all of these different participants, and the participants, on average, are, let’s see, 46 years old. It’s pretty much 50-50 sex ratio, but there’s more females than males, and their average education includes some graduate study, so they’re like graduate students or were graduate students at one point.
Zach Weinersmith: Can we just say, I think it would be useful to explain that scale. So the scale was just like 1 is high school, 2 is college. Whatever it was, it was 4 was some grad school, 5 was doctoral degree. Right?
Kelly Weinersmith: Yes.
Zach Weinersmith: And then the average was 4.2, I think. Right?
Kelly Weinersmith: Yeah.
Zach Weinersmith: Okay.
Kelly Weinersmith: Yes, and these participants reported that they got involved in this program, quote, “because they were motivated by curiosity about the effects of psilocybin and the opportunity for extensive self-reflection.” So I suppose that I shouldn’t be…
Zach Weinersmith: Shouldn’t be being snarky with the…
Kelly Weinersmith: Right.
Zach Weinersmith: Yeah.
Kelly Weinersmith: So, sorry.
Zach Weinersmith: Yeah. I can do that with your papers, too.
Kelly Weinersmith: Right, right. Okay. So sorry about the snarkiness. The point is, these are people who are interested in changing something about their personality to begin with.
Zach Weinersmith: Just to be clear, did we state that the claim of the study is that people took mushrooms and then subsequently measured higher on this scale of openness?
Kelly Weinersmith: I’m not sure if we said that, but that is the point, so it’s good. Thank you for clarity. Okay, so here is the really galling thing about this study. So it’s actually two studies that they later combined in the statistical analysis because it increased their sample size (because that’s a valid reason). And what they did was, in study 1, they had individuals like sit in a chair, and they either gave them this drug or they gave them Ritalin, and they did this multiple different times, and after they gave them either the drug or Ritalin, they asked, they gave them this list of, this questionnaire about how mystical their experience was, but the point, first, is that this study did not actually have a good control.
Zach Weinersmith: Yeah.
Kelly Weinersmith: So go for it, Zach.
Zach Weinersmith: So it was really weird. So we were expecting it to say something like they had this one group they took and they gave mushrooms and then measured their personality metrics later. Then we had this other group, our control group, which we gave a sugar pill and measured their personality metrics later, but in fact, I believe it was three groups. They had one group that was given shrooms, one group that was given a whole lot of shrooms… [laughter]
Kelly Weinersmith: That was study 2.
Zach Weinersmith: Oh, [unclear 32:49]
Kelly Weinersmith: In study 2, everybody was given a little shrooms, more shrooms, more shrooms, and a lot of shrooms, or they were given in a different order a lot of shrooms, less shrooms, less shrooms, and then less shrooms.
Zach Weinersmith: Yeah.
Kelly Weinersmith: And so…
Zach Weinersmith: So the point being, the philosophy of science point being that if you don’t have a control group, there is no sense of what the error bars on this would be.
Kelly Weinersmith: Right, and importantly, these are all people who went into the study wanting some self-reflection, so like wanting to change their personality in some way. So these are people who are likely — after an experiment where they’re told, “This might change your personality” — are likely to change their personality, so you really need a good control, because these are people who are prone to personality changes or wanting to make changes in their personality to begin with. So having no control is ridiculous.
Zach Weinersmith: I would even say the control thing is bad enough, but I almost feel like you couldn’t really control for it. I mean, because you’re self-selecting a group of people who have, according to this study, either never done mushrooms or had little experience with it who were agreeing to do it based on seeing a flyer on a college campus. There’s this crazy level of sieving going on.
Kelly Weinersmith: Yes.
Zach Weinersmith: And so I feel like even if they had done what I would think would be smarter, which is that you have a genuine control group that just is given a sugar pill or something (a sugar mushroom, I don’t know), and…
Kelly Weinersmith: They never actually gave them mushrooms. They extracted the drug…
Zach Weinersmith: Some extract.
Kelly Weinersmith: … and specifically…
Zach Weinersmith: Okay, great.
Kelly Weinersmith: … gave them the drug.
Zach Weinersmith: Yeah, so you would just give them a sugar pill. Even if you had that, I don’t know that I could be convinced that you proved anything, because… Can I tell a story that might be elucidative? So I just remembered this when you were reading the paper is, James and I, when we were like probably 16 and 17, we used to watch lots of bad movies, and like we… It was… You know that time when you’re 16 and you just have nothing to do? So we’d seen all the movies in the theatres, and we would rent four movies a week, and we’d just watch all these bad movies, and we decided as a joke… I think we had probably just taken a psychology class in high school. We decided to joke we would sort of invent this big personality metric list for how much you believe in certain things, so it would be like how feminist are you, how nihilistic are you, this sort of thing, on a scale of 1 to 5. And then we decided we were going to have a night where we just picked five romantic comedies, and we watched them, and we would fill in the boxes on the sheet after each romantic comedy and to see how it was personality altering. And I, because we were… [laughs]
Kelly Weinersmith: You guys were really fun kids.
Zach Weinersmith: So cool. And so I remember what happened was, and I think that this actually is a good illustration, perhaps, of the difference between our personalities, which is that I’m kind of stodgy, maybe kind of extremely stodgy, which was that James was sort of being good and playing along. He would lower his feminism score after watching The First Wives Club. You know? [laughter] And whereas I was taking this test, and I was like, “I don’t actually feel any different about any of this stuff,” so I think I, yeah, probably filled that in, but my scale would have looked really boring and unhilarious, and his would have looked funny, but it was just sheer stubbornness on my part. But so I wonder, you can imagine you get people who are taking this test for the shrooms thing, and they clearly know what their experimenter’s expectation is. Right? So it’s kind of like me and James where he’s sort of playing along because I’ve built this little experiment. He wants to play along because I’m doing this stupid thing, and so he knows what my expectations are. Like clearly the joke to a 16-year-old is, “Haha, after you’ve watched You’ve Got Mail, you’ll hate women for 30 minutes.” And… Right? [laughs]
Kelly Weinersmith: Or love them.
Zach Weinersmith: Or… Mm… Maybe. [laughs] You’d probably hate men, too, I don’t know.
Kelly Weinersmith: Yeah.
Zach Weinersmith: But anyway, so I suspected in part the reason he was willing to lower his scores and I wasn’t is because he was, I had made this little test thing, and then invited him over, and he knew exactly what I wanted, what I thought would be funny. And I think he was, at least to an extent, playing along. I mean, I’m sure he was playing along, because we were joking around, but I wonder if the same…
Kelly Weinersmith: He was being a good sport.
Zach Weinersmith: Yeah, exactly. And I wonder if the same effect would be going on when you take this test, like you see a flyer. It says, “Come take shrooms. We want to see how it alters your personality.” They take the test — as they said in the paper, they actually counsel people on how to deal with shrooming, and then they have them take these, fill out these questionnaires at intervals afterward, and they all must know what the game is. The game is clearly, you feel more open. You feel [unclear 38:48] these weird metrics like, do you feel more sacred, more mystical, more unified with the universe? And there’s no way you take these shrooms in this test environment and don’t know what the game is, so you can imagine the situation where you either have nice people or people who are just sort of buying into this idea, they want it to be true, who are filling out the questionnaire in correspondence with that belief. So even if all this downstream stuff, like their control group, their crappy use of statistics, even if all that was fine, it would still be completely polluted by the way they’re doing their finding, their sourcing of individuals for this test and how they’re doing their questionnaire.
Kelly Weinersmith: Yeah, and very similarly, it’s like when you go to a hypnotist and you’re in this big audience and a bunch of people go up on the stage because they decide they want to be hypnotized, those are like the people who decided they wanted to participated. And then when you’re up there, you sort of realize, “Oh, I know what they’re looking for, and I think it’s crap. I’m not really willing to give it to them,” and then some people just kind of don’t participate and get off the stage, but they’re still sort of involved, and then the others really go for it and give the hypnotist exactly what they want. And right. It’s pretty much exactly the you and James situation, and I think that that is what happened here. And so not only did they find that openness was increased in certain people who had mystical experiences when they were high, but they also found that the degree to which they reported having these mystical experiences correlated with how open they were afterwards. And so I think you can explain those findings based on these similar things. The people who bought into it more were the ones who were like, “Oh, yeah, I had a mystical experience. I transcended space and time.” Which is specifically something that was in the questionnaire. “How much did you transcend space and time?”
Zach Weinersmith: Yeah. [laughs]
Kelly Weinersmith: And so yeah. I think that these all could be explained in that way. And so they started off the paper in a somewhat promising manner by talking about how this drug and other hallucinogens affect serotonin receptors in the brain, and we know that serotonin and serotonin receptors are associated with personality in ways that we’ve been able to experimentally test, so we’ve been able to block receptors and look at how that affects behaviour and then take those blocks off and see how behaviour changes again. And so you can actually manipulate and see how it affects things. If you were to figure out the physiological mechanisms that underlied openness, so maybe you found that serotonin really is associated with openness, and then you looked at how this drug affected the expression of receptors and then looked at behaviour, that would be convincing to me. Like maybe you could find that people who took this drug had more receptors in a specific part of the brain, and then if you injected them with the drug to block those receptors, the openness went away, that to me would be convincing. But you can’t really do that sort of thing on people, which is why animal studies are good, because you could do that sort of mechanism stuff in like a rat, but you can’t give them a personality test. But point is, I think that for this study, there’s absolutely no way to get around that picking the right study group thing.
Zach Weinersmith: Yeah. No ethical way, anyway.
Kelly Weinersmith: Right. Yeah, so I think that that’s just a fatal flaw in this kind of study that you could kind of get around if you were able to actually, you know, look at mechanisms or something, but so their big findings, I guess, were that the degree to which people claimed that they had mystical experiences while high determined how open they were not just a month or two after the study, but a full year afterwards, and so they were claiming that this can like help loosen people up, or make them more okay with stuff that’s going on in their lives, so if they have cancer maybe they’ll feel better. And maybe, if you can find the people who are willing to be duped into thinking that this drug is going to make them open a year later, maybe it is fine and it’s more of a trick, but it might have the right effect in the end, but…
Zach Weinersmith: Yeah, but I think that, to me, that’s part of the problem is, it could very well be the case — in fact, maybe there’s reasons to suppose it is the case — that there could be people who have some sort of personality disorder, and by taking this chemical, they actually have long-lasting good effects. The problem is that sort of by doing this low-quality study where they’re participating in all sorts of scientizing — they’re saying… They want to make the idea of “mysticality” into a science, so they call it something like “mysticality index”, but it means the same thing. And by having these statistics cheats that they’re doing and all this stuff, they’re taking something that really could be taken seriously and help people, and they’re marginalizing it. I think, because I’ve been trying this whole time not to make any “ha ha stoner” jokes on the basis that it could actually be useful, you know. And we’re finding that in cannabinols that they might have some cancer-fighting quality; they certainly have an anti-nauseating quality that could be very useful, and it’s been hindered by people who just sort of laugh it off because it’s a drug that people take. And so I feel like there should be an extra onus on people who steady things like shrooms or LSD or marijuana to take it very seriously, and it’s… Reading this paper, which got a decent amount of press, they clearly didn’t take it seriously in the way scientists in other areas would, and I think that’s unfortunate.
Kelly Weinersmith: Yeah, I agree. Especially since some other studies apparently have tied it up with serotonin, and we know that serotonin is important for depressive disorders and all sorts of other personality things, so there’s definitely something here that we could be working with, but this study just sort of made it all sort of seem laughable, in my opinion.
Zach Weinersmith: Whenever I read a paper like this, I think about that time I think Sarah Palin was talking about how these fancy-pants scientists had to go to Paris, France, to study fruit flies, and the whole scientific community was annoyed because, of course, fruit flies are very important in genetic studies. It may sound stupid just to say it, but it’s important, and so I hate when I read a paper and I say, “Here’s something a person like this could complain about, and I would be compelled to agree that this was really a waste of taxpayer money.”
Kelly Weinersmith: Mm-hmm.
Zach Weinersmith: And I think that that always bothers me, like it’s clear from this paper that there is not a sort of level of seriousness commensurate with the public trust given in the form of dollars to these people.
Kelly Weinersmith: Yeah. It still made its way into a high-impact journal, though, so…
Zach Weinersmith: Yeah. Well…
Kelly Weinersmith: I don’t know.
Zach Weinersmith: We could talk about impact factor sometime, but…
Kelly Weinersmith: Yeah. Right. Maybe not tonight.
Zach Weinersmith: Yeah.
Kelly Weinersmith: On to the super awesome paper?
Zach Weinersmith: [unclear 45:40] super awesome paper?
Kelly Weinersmith: You didn’t read the super awesome paper. Ooh. But I can tell you about it.
Zach Weinersmith: That won’t stop me from having opinions.
Kelly Weinersmith: It never does. Okay, so the next paper is a paper that was in Human Molecular Genetics, published this year also, by Dempster et al., and it’s called “Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder”. So essentially what this study did was, it looked at the epigenome of two identical twins and then determined how differences in gene expression were associated with having schizophrenia or bipolar disorder. So quick intro on exactly what is epigenetics. So the like Wikipedia answer is that epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. So you’ve got these genes, and when the genes in your body are turned on, they’re producing proteins, and they’re producing proteins in the way that you are taught in high school biology where first they are transcribed, creating complementary RNA, and then they’re translated into proteins. So when your genes are active and being expressed, they’re making a protein, but your genes aren’t on all the time. They’re not constantly making proteins, so when they’re off, they’re all coiled up and wrapped up really tight, and they’re wrapped around these things called histones. And when they’re wrapped up really tight, then the machinery that’s needed to read those genes and to create the proteins can’t get to them. So you can change how easily accessible these genes are by adding different chemical groups on there. So, for example, if you add a methyl group, which is just a carbon which has three hydrogens attached to it, then you can make it much more difficult for this gene to unwind and for the machinery that reads it to get in there, whereas if you add some other group like an acetyl group, then it makes it easier for that gene to open up and be read. And so these different chemicals seem to be attaching themselves to the genes based on things that happen early on in the life of the organism, so it could be something that happened to the organism in its womb while it was still in the womb or an early-life experience right after it was born, but you end up with these changes in how easy it is to turn a gene on or off that seem to persist throughout almost the entire life of that individual.
So what this study did was, it looked at twins that were monozygotic, which means that they have the exact same genome (or at least very, very similar genomes), and they looked that, given that these individuals have the exact same gene sequence, how does this machinery that turns the genes on and off between the individuals differ? So they found genes where one group had schizophrenia, one of the twins had schizophrenia and one of the twins didn’t, or twins in which one had bipolar disorder and one didn’t, and they ran their genomes through, looked at the entire genome, and compared methylation patterns to see if they could in some way figure out which genes were important and how expression differed to predict schizophrenia or bipolar disorder to try to understand it.
Zach Weinersmith: Could I stop you real quick?
Kelly Weinersmith: Yeah.
Zach Weinersmith: So just to clarify methylation, my basic understanding of methylation is something like this is, you have your big long DNA code that’s all the letters in your code, and methylation is when you get a methyl group just attached somewhere on that line so it alters, it changes a letter or a couple letters of the sequence. Is that about right?
Kelly Weinersmith: No.
Zach Weinersmith: No. [laughs]
Kelly Weinersmith: So you have your long sequence of genes, and they’re wrapped up and they’re curled around these histones, and when you… Methylation means that you’re sticking a methyl group, I believe, onto one of those histones, and that makes…
Zach Weinersmith: Oh, it goes on the histone.
Kelly Weinersmith: Yeah, and that makes it so that there’s nothing that’s changed about the sequence of the genes. The sequences in these twins are still exactly the same. The only thing that differs is the fact that if you’ve got a methyl group on there, then the gene can’t unwrap itself so that it can be read.
Zach Weinersmith: So that would mean, to me, then, that it could have a very significant change, then it’s not just little stuff?
Kelly Weinersmith: Yeah, right, like being schizophrenic or not being schizophrenic. That’s pretty big. Does that all make sense now?
Zach Weinersmith: Yeah, yeah, yeah. Continue.
Kelly Weinersmith: Okay, awesome. So what they found was that by doing this whole genome approach, they found that some genes that had previously been associated with schizophrenia or with bipolar disease showed up as being expressed differently between these twin groups, and so that was really good evidence that these genes were really important, but also by doing this entire genome approach on individuals that were similar in so many different ways but mainly differed in being schizophrenic or bipolar or not, they were able to identify some new genes, also, that might be important, but we need to do more work to sort of see exactly how important they were. And then another pretty neat thing they did was that once they had an idea as to which genes mattered, they then went and found postmortem brain tissue samples of random individuals who didn’t have schizophrenia or bipolar disorder and were therefore controls and brain samples from schizophrenics and people with bipolar, and they compared the expression of those genes in the brain and found that there were indeed differences in how those genes were expressed, or specifically differences in methylation patterns.
And I thought this was a really good study. And what I really liked about this study, which you don’t see in a lot of studies, is that they really outlined all of the different ways in which their experiment was weak, whereas usually you see people try to not really mention it. These guys were really clear about it, so they were really clear about the fact that they had a low sample size, so they only had 22 sets of twins, which means they had an n of about 11 for looking at schizophrenia and for looking at bipolar, so that’s not really big — although they point out that for this kind of study, it is pretty big because finding not only monozygotic twins, but monozygotic twins in which only one of them has a disease and the other one doesn’t, and then getting people who are interested in being in your study, is pretty hard. And so for this kind of study, this was a big sample size, but in general, it’s a small sample size.
Also, what you really want when you’re looking at methylation patterns is to look at specific regions of the brain, because methylation patterns can differ in different parts of the body. So you’ve got the same genes in all of your different cells, but you can still have genes in different cells being methylated in different ways. And so for the twin study, they had to look at blood and methylation patterns in the genes that were in the blood. And the cool thing was that they were able to actually tie that into what was going on in the brain by looking at postmortem brain samples. So they agreed that it would be better if they could find monozygotic twins that died at approximately the same time, and you could do this stuff on their brains right after they’ve died, but they did the next best thing.
And then the other thing that I hadn’t even thought about that I thought was a really good point they made was that the twin that was schizophrenic or bipolar was being treated for that, and so whatever medications they were taking could be what’s changing the methylation pattern in their brain, because we know that a lot of the drugs are affecting similar mechanisms in the brain. And so they were arguing that it would be really great if they could have caught these diseases before people got treated and got a real quick blood sample and then put them on the treatment, but they weren’t able to get that sample.
So I found this to be a fairly convincing paper. I really like that they added all of those caveats about things that weren’t great, but in general, they at least showed where the promising future avenues are for looking at how epigenetics might be affecting schizophrenia and bipolar.
Zach Weinersmith: Yeah. It seems like regarding the second point you made about how it might be drug-related, I mean, there must be some, or it seems to me very likely that there’s some genetic quality of schizophrenia, right, because it tends to have a certain rate of onset. I think it tends to be more common in men, and it tends to onset around early to mid-20s, I believe.
Kelly Weinersmith: Right, and it’s highly heritable, but not completely heritable, because both twins didn’t have it.
Zach Weinersmith: But so what’s interesting that that would make me wonder how much the methylation pattern can be involved. So I guess based on that, you would suppose that the methylation pattern was a sufficient, like it would add to the likelihood, but it would not be sufficient to actually give you schizophrenia?
Kelly Weinersmith: Probably. So the thing with schizophrenia that I think it difficult is, I’ve read a bunch of different papers, all of which are like, “Oh, and schizophrenia is totally associated with having toxoplasmosis,” and so there’s all these different mechanisms that seem to be able to cause schizophrenia, so it could be that this is one way that you get schizophrenia, but not the only way that you get it.
Zach Weinersmith: Ah, I see what you mean. Yeah. I mean, schizophrenia is a human-made idea, right, so it could be that schizophrenia encompasses 40 different…
Kelly Weinersmith: Actual quote-unquote…
Zach Weinersmith: … actual…
Kelly Weinersmith: … “problems”.
Zach Weinersmith: Yeah, exactly. That’s interesting, too, because I got an email last week. I’d done a joke ages ago about schizophrenic speech patterns, and a guy wrote me to say thank you because he had a… I want to say a brother-in-law or something who was in the process of getting worse as a schizophrenic, and he took some comfort from it. I mean, we were talking about how it was kind of sad that it seemed like it was something that as the disease did not have an on-off switch. Right? It’s like something that, if it’s going to happen to you, you just have to live with it, but if it’s methylation-related, at least conceivably, not now, but conceivably there could be some way to sort of mitigate it.
Kelly Weinersmith: Yeah. So there’s a paper I read a while ago that was talking about how certain foods can affect methylation patterns, maybe, and so eating diets of a certain type might be able to help you change your methylation patterns over a long term, and there are also, if you have like really stressful life events, I think that that can sometimes change methylation patterns, but so yeah. There is some evidence that these methylation patterns do not have to be persistent throughout your entire life, and so you do have some hope of changing them and fixing it, but I think at the moment we don’t have a clear idea as to how that’s done.
Zach Weinersmith: That’s interesting, because it could explain stuff. Like you know how it is when if you’re stressed out for something like a month, then you feel stressed out for six months, even though you’re thinking to yourself, “I shouldn’t be stressed out anymore”? I wonder if that’s a similar sort of thing.
Kelly Weinersmith: I think methylation is, in general, a much more persistent thing than six months. Like we’re talking it will last… It will start when you’re young and last for your entire life unless something major happens.
Zach Weinersmith: Oh, really?
Kelly Weinersmith: And so I don’t think that it explains like six months of feeling a certain way, but I’m not an epigeneticist, so maybe if someone’s listening, it would be interesting to hear their opinion if they happen to know about it. To me the interesting question, and perhaps this is one that socially is not really good to ask, is, we know that early life experiences affect methylation patterns, so what is the different thing that happened to that twin who got schizophrenia versus the one that didn’t? Like was one held more or fed a slightly different diet, or some things…
Zach Weinersmith: I remember when I was in college I was in a psychology class, and I asked a question of a professor, and I wasn’t really satisfied with the answer. My question was this. “Does the field think that adult personality is based more on a sort of general childhood experience, or is it more based on particular events?” Right? So you can imagine a situation where you have two twins, and they end up very differently, and it could be the case that just there was one day where one of the twins got beat up or something, and that, though we couldn’t really scientifically detect it, explains everything.
Kelly Weinersmith: So I don’t actually know the great answer to that question. My sense is that it has to be a combination of the two, and so I feel like this is a decent time to talk about Michael Meaney’s rat stuff, which I think I’ve mentioned to you a million different times. So Michael Meaney is this researcher who noticed that if he handled these rat pups that he had in his lab, and rat pups are just really the baby rats before they can even open up their eyes, that if he handled them a little bit, then they responded much differently to stress when they were adults, and he found that that’s because they had receptors popping up in parts of their brain that controlled stress, and the more you handled these guys, the more likely they were to be less anxious like when they were adults when you stress them out. And so he felt that was kind of interesting, and then eventually he figured out that his handling was sort of mimicking the carer of the mom when these guys are pups. And he found that moms who lick and groom their offspring more often have offspring who later respond to stress by freaking out less. They exhibit less behaviour that humans describe as anxiety-like, and they also have this totally different suite of behaviours that change additionally. So the females who are not cared for by their moms reach puberty earlier, are more likely to solicit sex from males, so like they’ll walk next to the male and try to get their attention. They’re more likely…
Zach Weinersmith: Nice.
Kelly Weinersmith: Yeah. Right.
Zach Weinersmith: Awoo awoo!
Kelly Weinersmith: They’re more likely to get pregnant at a younger age, and then they are bad moms just like their moms, so that bad parenting seems to be inherited. And they’ve…
Zach Weinersmith: Right, but just to be clear, this is only in rats. There’s not like a human analogue that’s been done, right?
Kelly Weinersmith: There is, sort of. So you can’t… It would be totally unethical to have babies that you hug and babies that you don’t hug, but there have been some natural experiments with like orphanages where there was a mom who, or the woman who ran the orphanage held the babies, the kids more, and others that didn’t, so there are experiments that you could look at, but specifically the study that I know of that looked at epigenetics as opposed to other long-term effects was, they found mothers who were stressed out or depressed during their third trimester, and I think that they measured cortisol by… Cortisol is a hormone that’s released when you’re stressed out, and people who get more stressed out tend to release more cortisol. And so you can find cortisol in the saliva, so I think that they took saliva samples from these moms, and then they correlated the amount of saliva cortisol to the amount of cortisol that they found in the cord blood when the baby was born. And they found that moms who were stressed out had offspring who were surrounded by high cortisol levels and presumably, yeah, also had high cortisol levels, because that blood is shared with the offspring, and they found that the effect persisted in three months later when they did swabs of saliva to find cortisol levels in the offspring. So the offspring who had moms were stressed out also had babies who three months… Sorry. The offspring whose moms were stressed out were also producing high cortisol levels three months after they were born. So it seems like there’s some long-term effect of having a mom who’s stressed out, but they so far have not followed those kids through. And they’ve also been able to look at differences in methylation patterns between kids who committed suicide and those who didn’t, and I think that they were able to determine that the kids who committed suicide had really stressful childhoods, like they were abused, and they tried to correlate that with these methylation patterns, but in humans, it becomes totally messy, because you can’t do… Like I said, for ethical reasons, you can’t do the manipulative experiments you would want to, but the correlational evidence that suggests that the stuff matches up with what we see in rats is coming in and seems fairly convincing.
Zach Weinersmith: But, I mean, it does sound convincing, but like some of that stuff with the humans, like you could argue maybe that people who are stressed have this feature of having… So say… I believe this is not the case, but say it were the case that if you get really stressed out, you start having damage to your gallbladder. You wouldn’t later then say, “Look, we found that people with gallbladder damage tend to be stressed, so therefore changing the gallbladder results in stress.” Like you see what I mean? Like the methylation could be an indication of the problem that exists, not the cause of it.
Kelly Weinersmith: Right, and with that cortisol study I talked about, it could just be a heritable thing. Moms who have high cortisol levels have kids who have high cortisol levels. But at least in the rats, they’ve done really good cross-fostering studies where they’ve took the offspring of moms who didn’t lick, groom, or care for their kids, and then put them in the nest of moms who did care, and then the moms would lick and groom and care for those little guys a lot more. And they found that it didn’t matter what your genotype was or who your mom was. What mattered was what kind of care you got. Which is…
Zach Weinersmith: Yeah, that’s more convincing.
Kelly Weinersmith: Right, and then they also did things where they thought that they had determined the mechanism, and then they gave drugs to that rat that blocked the mechanism, and then they saw a reversal in the behaviours. So at least in rats, we have a pretty good sense that these changes are definitely epigenetic and we definitely know which genes are involved because we can shut them, we can change their methylation patterns using drugs, and we can get it to do what we think it should do. But yeah, in humans, it’s just a lot more of a mess.
Zach Weinersmith: Right.
Kelly Weinersmith: But totally cool.
Zach Weinersmith: Yeah. Yeah. It’s definitely cool. It’s definitely… It’s a good example of… You remember we were talking a while back about how there’s this scary thing in science where you could be working in an area where you think you’re doing good work, and what you don’t realize is, you’re in the wrong framework? I mean, not to say that there’s not tons of awesome genetics work, but it would really freak me if I were a geneticist to find that there’s just this whole separate system that changes things, because you could imagine… Like the example I like to use is, and there are people who work on fusion reactors now, and they all use either high-strength magnet systems, like they use tokamaks, or they use these plasma Wiffle balls, or they use lasers. And most of that stuff didn’t exist till at least the ‘60s. The strength of laser, for example, you’d need didn’t exist until very recently, and so there are all these people trying to figure out how to make a fusion reactor to work, and the technology for it just didn’t even exist yet and wouldn’t exist until it came sort of out of a separate field. And so this whole epigenetics things is really exciting, because it just seems like it’s this whole different framework for how to think about phenotypes and genotypes.
Kelly Weinersmith: Yes. I think it’s good that scientists in general don’t think about the point that you just made…
Zach Weinersmith: [laughs]
Kelly Weinersmith: … because it might stifle future work. But yeah, I think a similar thing kind of, I feel like, happened with me this week. So you sent me that article about how we figured out that there are adenosine receptors on the blood-brain barrier, which is a layer that covers the brain and makes it really hard for stuff to get into the brain unless it’s really small and specifically made to be able to go through the blood-brain barrier, but if you have a compound with adenosine on it that can bind to these receptors, then the receptors will open up gateways that let chemicals through. And so the parasite that I study sits on top of the blood-brain barrier, and we’ve been trying to figure out how it changes brain chemistry, and we hadn’t been considering that it could be secreting really big molecules that might be able to cross the blood-brain barrier by binding to this receptor because historically, you had just been told that it’s only small molecules that can get through, and now we have to consider that it could be big molecules also.
Zach Weinersmith: Yeah.
Kelly Weinersmith: Unfortunately, the methods that we’re using would also catch big molecules, but we hadn’t really expected anything to happen in that region, but now it might also be that the big ones matter, because if humans figured it out now, probably this parasite that has a long evolutionary history with its host, it’s possible that that parasite figured it out too. And I think in science, you always have this possibility that things will become much easier, in fact maybe even really simple, once this thing is figured out in the future, but that shouldn’t stop you from trying now, because otherwise no one would get anything done.
Zach Weinersmith: Yeah. Well, that’s a good argument for just to bring it full circle for freedom of information, because the reason you’re thinking about that is just because you happen to come across this article on Reddit about this discovery in a more-or-less unrelated field. I mean, not completely… Unrelated by academic standards, let’s say.
Kelly Weinersmith: Right.
Zach Weinersmith: And what’s really interesting to me about this adenosine thing is, even if it is the case that you find that your parasite is doing this, then I would say you have every reason to suspect that it’s a general thing in the environment, because it would be really random if you happened to be looking at the right one that has this adenosine trick.
Kelly Weinersmith: Yeah.
Zach Weinersmith: Like so if you find it, you would probably expect that any parasite that is involved in neurology in that sort of way is flipping the switch, because it’d just be crazy not to. It seems like if it could evolve, it would evolve.
Kelly Weinersmith: Well, lots of brain parasites actually just break through the layer and burrow into the brain.
Zach Weinersmith: That’s another way to break the blood-brain barrier.
Kelly Weinersmith: Yeah. Right. I’m pretty sure that my parasite sits on top of it, but yeah, so there are different ways of solving the problem, but I think that there are a number of different trematode parasites specifically infecting fish that sit on top of the brain and do their thing, so yeah. Yeah. it’s a good argument for freedom of information and a good argument for trying to read broadly.
Zach Weinersmith: Sweet.
Kelly Weinersmith: Bam. Thus concludes episode 1 of The Weekly Weinersmith.
Zach Weinersmith: Do you want to do like a coming attractions?
Kelly Weinersmith: Do we know what our coming attractions are?
Zach Weinersmith: No, but you could make some up, and I could make exploding noises.
Kelly Weinersmith: All right. Coming soon: more stories about science, and perhaps some geek stuff, and more boring details about what Zach and I have been doing this week. The next time on: The Weekly Weinersmith!
Kelly Weinersmith: Anything else you want to say?
Zach Weinersmith: Off the record, I don’t like your hairdo.
Kelly Weinersmith: I don’t like your face. I feel like I win. [laughter] Bam! All right. Yeah, that was good. Let me make sure that the recorder worked. [laughter]