What the heckity-gosh-darn is epigenetics?

comfortable

Today in my class we talked for a while about epigenetics. I used it as an example of a term we’d encountered more than once in our ecological developmental biology course, but that has some complicated ambiguity and fuzziness that has led to all kinds of weird popular confusions about the subject. I was also using it as an example of critical analysis of a paper, as I discussed yesterday, and it was a lead-up to having the students discuss papers on relevant topics they were interested in — so we spent most of our time talking about other things.

But I’m going to talk now about just this one paper I read. You see, Larry Moran and I have been having this long-running disagreement about epigenetics — nothing hostile, just an occasional cocked eyebrow in each other’s direction — which you can see on display in this article by Larry on epigenetics, in which he disagrees with my definition of epigenetics, back in 2008. Here’s my definition:

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA.

And here’s the definition used in Gilbert’s text:

…molecular processes around DNA that regulate genome activity that are independent DNA sequence and are mitotically stable.

And here’s Larry’s objection:

Here’s the problem. If this is epigenetics then what’s the point? When I was growing up we had a perfectly good term for these phenomena—it was regulation of gene expression. Why is there a movement among animal developmental biologists to use “epigenetics” to refer to a well-understood phenomenon?

While I agree that “epigenetics” is a huge, broad, diverse category of phenomena, I think he’s overlooking a key point to claim it is synonymous with gene regulation. It is gene regulation that is heritable and mitotically stable. It’s still far too open-ended, but it’s not just any old example of gene regulation.

It’s also clear and consistent. Larry challenges us with eight instances of regulatory phenomena and asks which ones qualify as epigenetic. Easy. 1, 2, 6, 7, 8. Those are the ones where he specifically mentions multi-generational inheritance of a regulatory state. 3, 4, and 5 describe responses within a single cell in a single generation (5 is sneaky, though: Drosophila oocytes are having gene expression modified in ways that might be transmitted through multiple generations — it’s just that those cells are being loaded with bicoid RNA, not having their bicoid genes being set to a sex-specific state).

I am also comfortable with the idea that inheritance of the regulatory state of the lac operon is an example of epigenetics. It’s arguable whether that’s a useful category, but it does fit the definition.

So one approach that could be taken is to come up with a more specific or more practical definition.

Larry has a more recent article in which he agrees with a new paper by Deans and Maggert that tries to do exactly that. It also takes a much appreciated historical approach, giving the various definitions that have been wafting about since the 1930s. For instance, here’s Waddington’s ancient physiological definition:

the branch of biology that studies the causal interactions between genes and their products which bring the phenotype into being

Yes, I agree — that would simply be gene regulation nowadays. You can’t blame us wicked developmental biologists for promoting that one, though, because we don’t use it anymore.

Now we favor the Holliday definition:

the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail change in DNA sequence.

To me, “heritable” is the magic word that makes all the difference. This, however, is not enough for Deans and Maggert. They want to add more focus, often a good thing, and narrow the definition. I was not happy with their argument, and thought it poorly made, though. See if you can find what was objectionable in this section of their paper (I highlighted it to make it easy, an epigenetic modification that does not change the sequence of the letters in the text.)

We don’t feel that it is possible to reconcile Waddington’s focus on gene regulation with Holliday’s more specific criteria within one field and still maintain the level of clarity needed to produce a useful definition. The efforts to preserve a relationship between these two conceptualizations have been impaired by the fact that there are just too many phenomena, with too few mechanistic connections, to categorize into one field. Also, among the definitions that do maintain the requirement of heritability, we feel that many lack the detail to be functionally useful in directing the testing of specific hypotheses, particularly as it relates to the location or site (cytoplasm or nucleus) of epigenetic phenomena. To mitigate these shortcomings, we advocate defining epigenetics as “the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence.”

We feel that this definition makes a strong distinction between gene regulation (Waddington’s definition) and epigenetic inheritance (Holliday’s definition), and also emphasizes that epigenetic phenomena must deal exclusively with chromosome-bound changes. By making these distinctions, we have efficiently separated expressional changes caused by cytoplasmic compounds, which are more closely tied to gene regulation, from those which occur on, or in close association to, the chromosome. Doing so makes the focus of the field much clearer and identifies epigenetic mechanisms more explicitly.

We feel that this definition touches on several important elements not encompassed by other definitions, yet commonly implied in most uses. To further explain the reasoning behind our definition, as well as its utility for improving epigenetic research, we would like to offer a clarification and a test.

Yeesh. I don’t feel that your personall feelings are a strong argument, and I cringed when I hit that page. At least edit it to remove the emphasis on your personal discomfort; just say that the old definitions lack detail, rather than that you feel they lack detail.

So let’s pull out their shiny new definition.

the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence

Well. All this fuss for a single change, the addition of the phrase chromosome-bound. That’s it. I agree, it does narrow the topic, but it’s still covering an awful lot of territory. I’m not feelin’ it. I have the impression that the primary virtue of the new definition is that it reduces a class of phenomena to a subset that many people are comfortable studying already, and in part reinforces a gene-centered perspective on cellular behavior.

It also leaves me wondering…what about the inheritance of cytoplasmic or membrane-bound factors that induce consistent changes in gene expression in daughter cells? The gene regulation aspect may be mundane, but it’s the inheritance that is interesting. Under the Deans and Maggert definition, this is no longer under the umbrella of epigenetics — it’s something different for which we have no general name now.

It makes Larry happier, though.

I think this is a useful definition. Nobody cares if dividing E. coli cells inherit molecules of lac repressor and continue to repress the lac operon. That’s a trivial form of epigenetics that never posed a threat to our understanding of evolution.

That’s odd. I do care that the lac repressor is cytoplasmically inherited, but then my primary interests, in the most general form, would be in the patterns of stability and change in cellular properties, rather than the metabolism of sugar. Telling me that I should only pay attention to inherited proteins or methylation states that are directly bound to DNA seems arbitrary.

I also don’t consider “poses a threat to our understanding of evolution” to be a relevant criterion. I agree that lac repressors don’t challenge evolutionary theory, but neither do heritable histone modifications or methylation. I’m one of those people who think epigenetics (even under the old definition!) is important and interesting, but doesn’t affect evolutionary theory much at all.

Larry and I agree.

Methylation is trivial.

Well then, if inheritance of the lac operon is such a trivial form of epigenetics that it should be excluded from the definition, then we apparently need yet another definition that excludes the triviality of methylation.

Or, really, we should recognize that “trivial” is not a good reason to exclude something.

I will still second Larry’s argument that none of this stuff overthrows modern evolutionary theory in any way. It would require extremely persistent inheritance of an epigenetic state over many generations to have those kinds of repercussions.

(The Gilbert text does mention one significant effect: the toadflax plant, Linaria vulgaris, has a radically different flower morph, Peloria, that Linnaeus himself classified as a different species. As it turns out, they only differ in the methylation state of the cycloidea gene, but the DNA sequence is identical. This is a case of an epigenetic change persisting for hundreds of generations. It’s a rare case, though, and also…would still definitely fall under the Deans and Maggert definition.)

Ecological Development: Getting critical

far_side_good_hands

In class last week, we continued our discussion of developmental plasticity and began to talk about epigenetics, and in particular, the underlying molecular mechanisms for epigenetic inheritance. In addition, students had to discuss papers on plasticity that they’d researched. Some of the topics covered were: sneaker males and alternative reproductive strategies; aggression in dog breeds, how much is genetic and how much is training; temperature-dependent and behavior-dependent sex determination in reptiles and fish; and physiological responses to variations in gravity (someone has put pregnant rats in a centrifuge and looked at the effects of 2 gravities on development). It was all fun stuff, and I made the students do all the work. Perfect!

This week they have another assignment. There’s a common problem in student writing about science: they tend to describe what a paper says. That makes for very boring reading, I’m sorry to say — if I just wanted to know what was in the paper, I could read it myself, after all. So this week they’ve been asked to write a critical analysis of a science paper relevant to the course. This is a routine skill that needs to be cultivated and practiced.

What’s involved? You first have to identify a key question or assertion in the paper, or even in a short section of the paper, and ask yourself if the authors have adequately defended the claim. Even if you agree with the claim, and think it’s eminently reasonable, you have to approach it as a critic and try to tear it down.

I’m going to try to lead by example, so I have given them a couple of papers to read ahead of time. One is “Novelty and Innovation in the History of Life” by Douglas Erwin, which makes an argument that should be familiar to the students, because we’ve already talked about some of the concepts. Here’s the abstract:

The history of life as documented by the fossil record encompasses evolutionary diversifications at scales ranging from the Ediacaran–Cambrian explosion of animal life and the invasion of land by vascular plants, insects and vertebrates to the diversification of flowering plants over the past 100 million years and the radiation of horses. Morphological novelty and innovation has been a recurrent theme. The architects of the modern synthesis of evolutionary theory made three claims about evolutionary novelty and innovation: first, that all diversifications in the history of life represent adaptive radiations; second, that adaptive radiations are driven principally by ecological opportunity rather than by the supply of new morphological novelties, thus the primary questions about novelty and innovation focus on their ecological and evolutionary success; and third, that the rate of morphological divergence between taxa was more rapid early in the history of a clade but slowed over time as ecological opportunities declined. These claims have strongly influenced subsequent generations of evolutionary biologists, yet over the past two decades each has been challenged by data from the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology. Consequently a broader view of novelty and innovation is required. An outstanding issue for future work is identifying the circumstances associated with different styles of diversification and whether their frequency has changed through the history of life.

Let’s take that apart. Erwin is saying that there are some long-held assumptions in evolutionary biology that he is going to suggest are possibly invalid. Those assumptions are:

  1. Diversity is the product of adaptive radiations;

  2. Radiations are driven by ecological opportunities; and

  3. Most morphological variants emerge early, in the process of filling open niches.

He’s going to propose alternative processes.

  1. Initially non-adaptive variants are going to generate morphological diversity;

  2. Novel forms construct the niches that they will fill; and

  3. Variation is a constant event in a lineage.

I am predisposed to like those new perspectives, and I’m also biased by the evidence we’ve discussed in class, that ecology and development are in a constant state of reciprocal feedback. But rather than reporting and describing this paper as something that reinforces my views, I need to examine it critically. Does Erwin adequately support his claims? Are there significant questions he does not address? He’s also given us a list of sources of evidence that he’ll use to challenge orthodoxy: “the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology”. Does he succeed?

I’m just going to consider his first point, whether it is adaptive variation that drives radiations (lesson for students: focus. Better to do one thing well than 3 things poorly). His evidence in this section comes primarily from analysis of the fossil record, which is going to raise some objections.

Erwin does not deny the existence of adaptive radiations, and wisely begins by discussing known examples. He cites the work on Galapagos finches, where we have strong evidence of morphology being shaped by adaptive necessity. He also discusses cichlids, where variations in the environment have clearly played a role in, for instance, feeding adaptations. To then argue for alternative mechanisms using the fossil record is problematic: adaptive radiations are seen in cases where you’ve got close-up, fine-grained observations of single clades, but the evidence for adaptation fades when you use a more coarse-grained, less well-sampled method?

One piece of evidence presented is basically an absence-of-evidence argument. There is a lack of evidence of character displacement in the fossil record. Character displacement is the shift in morphology away from each other from two similar species competing in an overlapping range; it ought to be seen if two populations are adapting to avoid competition.

His argument that solutions to adaptive problems can exist for milllions of years without a radiation occurring is more interesting. He points to Anolis lizards in the Caribbean that converge on similar strategies when they evolve on different islands as an indication that the potential for particular morphologies is present in the species before they find themself with fresh opportunities on a new island. The carnivore fossil record shows a limited repertoire of optimal feeding strategies, which canids exploited repeatedly. Sea urchins have been evolving to follow similar feeding patterns repeatedly, as well.

It’s a somewhat frustrating argument, though. He’s trying to show that a radiation can’t have been driven by the acquisition of an adaptation if the adaptation had existed for long periods previously without a radiation. I can see the point, but one could argue that the radiation depended on both the prior potential in the organism and ecological circumstance, which is part of his second point…which makes point #1 and point #2 codependent on one another.

I’d have to say that I wasn’t entirely satisfied that he’d supported his first conclusion to my satisfaction. It’s also the case that he’s arguing that both adaptive and non-adaptive radiations occur, meaning it’s a quantitative question of which of the two is most important under what conditions, and he hasn’t done anything to measure that balance. I don’t reject the hypothesis, but I also don’t think the work has been done to confirm it — yet. He concludes the whole paper by predicting that gene regulatory networks are characterized by stability, so morphological novelties may be based on features established outside the core GRNs, and are thus more flexible. I don’t know. That’s definitely well outside anything you could figure out with fossils, so it’s going to require a different approach.

That’s how I’m going to talk about a paper I enjoyed with my students (and you Pharyngula readers think I’m harsh with my mere movie reviews). I’m also going to discuss a second paper on epigenetics that I didn’t care much for — the heart of the paper is a painful exercise in writing about how they feel about certain definitions of epigenetics which made me snarl — but I still think it made some valid points.

That’s really the purpose of the whole exercise. Stop treating science papers as holy writ that you can’t challenge; think critically about everything, and try to find logical holes that can be plugged with better evidence. That’s how science gets better and better. These are smart students and they just need to learn that they can actually disagree with Famous Scientists.

The real challenge, too, is that my plan is to talk about these examples for maybe 15 minutes, and then put the students into groups to discuss the papers they’ll have brought with them, trying to punch holes in them. It might be fun. It might be difficult and frustrating. As mentioned, one of the annoyances of student writing is that too often they think of it as reporting, describing what’s in it rather than engaging with the ideas with their very own brain and questioning what the paper says.

Hey, maybe I shouldn’t call it “reporting” since that’s also what journalists should be doing, but too often aren’t. Reciting summaries credulously shouldn’t be what either scientists or journalists do.


Erwin DH (2015) Novelty and Innovation in the History of Life. Curr Biol 5;25(19):R930-40.

The resurrection of the mammoth will not occur in two years

Not even in the next decade. For a good debunking of the claim of cloning a mammoth that’s in all the news, John Hawks has you covered.

When I heard the story came from George Church, I admit that I rolled my eyes and moved on. Church is a very smart guy, but he also tends to start babbling far out science fiction when he’s got an audience. As Hawks points out, he’s made 45 edits to elephant cells in a dish; that’s an awful long way from the thousands he’d need to begin to re-engineer an extinct animal, and a single cell is even further from a healthy, functioning large mammal.

Someone needs to start a Journal of Pizza Quality Research, stat

We need somewhere to bury sloppy research on fast food, after all. Brian Wansink gets interviewed on Retraction Watch (y’all remember Wansink, the fellow who ground his data exceedingly fine to extract four papers from a null result), and he does himself no favors.

Well, we weren’t testing a registered hypothesis, so there’d be no way for us to try to massage the data to meet it. From what I understand, that’s one definition of p-hacking. Originally, we were testing a hypothesis – we thought the more expensive the pizza, the more you’d eat. And that was a null result.

But we set up this two-month study so that we could look at a whole bunch of totally unanswered empirical questions that we thought would be interesting for people who like to eat in restaurants. For example, if you’re eating a meal, what part influences how much like the meal? The first part, the middle part, or the last part? We had no prior hypothesis to think anything would predominate. We didn’t know anybody who had looked at this in a restaurant, so it was a totally empirical question. We asked people to rate the first, middle, and last piece of pizza – for those who ate 3 or more pieces – and asked them to rate and the quality of the entire meal. We plotted out the data to find out which piece was most linked to the rating of the overall meal, and saw ‘Oh, it looks like this happens.’ It was total empiricism. This is why we state the purpose of these papers is ‘to explore the answer to x.’ It’s not like testing Prospect Theory or a cognitive dissonance hypothesis. There’s no theoretical precedent, like the Journal of Pizza Quality Research. Not yet.

That last bit sounds like a threat.

Here’s the thing: we all do what he describes. An experiment failed (yes, it’s happened to me a lot). OK, let’s look at the data we’ve got very carefully and see if there’s anything potentially interesting in it, any ideas that might be extractable. The results are a set of observations, after all, and we should use them to try and figure out what’s going on, and in a perfect world, there’d be public place to store negative results so they aren’t just buried in a file drawer somewhere. There’s nothing wrong with analyzing your data out the wazoo.

The problem is that he then published it all under the guise of papers testing different hypotheses. Most of us don’t do that at all. We see a hint of something interesting buried in the data for a null result, and we say, “Hmm, let’s do an experiment to test this hypothesis”, or “Maybe I should include this suggestive bit of information in a grant proposal to test this hypothesis.” Just churning out low-quality papers to plump up the CV is why I said this is a systemic problem in science — we reward volume rather than quality. It doesn’t make scientists particularly happy to be drowning in drivel, but Elsevier is probably drooling at the idea of a Journal of Pizza Quality Research — another crap specialized journal that earns them an unwarranted amount of money and provides another dumping ground for said drivel being spewed out.

Wansink seems to be dimly aware of this situation.

These sorts of studies are either first steps, or sometimes they’re real-world demonstrations of existing lab findings. They aren’t intended to be the first and last word about a social science issue. Social science isn’t definitive like chemistry. Like Jim Morrison said, “People are strange.” In a good way.

Yes. First steps. Maybe you shouldn’t publish first steps. Maybe you should hold off until you’re a little more certain you’re on solid ground.

No one expects social science to be just like chemistry, but this idea that you don’t need robust observations with solid methodology might be one reason there is a replicability crisis. Rather than repeating and engaging in some healthy self-criticism of your results, you’re haring off to publish the first thing that breaches an arbitrary p-value criterion.

There really are significant problems with the data he did publish, too. Take a look at this criticism of one of his papers. The numbers don’t add up. The stats don’t make sense. His tables don’t even seem to be appropriately labeled. You could not replicate the experiment from the report he published. This stuff is incredibly sloppy, and he doesn’t address their failings in the interview, except inadequately and in ways that don’t solve the problems with the work.

Again, I’m trying to be generous in interpreting the purpose of this research — often, interdisciplinary criticism can completely miss the point of the work (see also how physicists sometimes fail to comprehend biology, and inappropriately apply expectations from one field to another) — but I’m also seeing a lack of explanation of the context and relevance of the work. I mean, when he says, “For example, if you’re eating a meal, what part influences how much like the meal? The first part, the middle part, or the last part?”, I’m just wondering why. Why would it matter, what are all the variables here (not just the food, but in the consumer), and what do you learn from the fact that Subject X liked dessert, but not the appetizer?

It sounds like something a restaraunteur or a food chain might want to know, or that might might appeal to an audience at a daytime talk show, but otherwise, I’m not seeing the goal…or how their methods can possibly sort out the multitude of variables that have to be present in this research.

Women in science tumbling off a cliff

Since someone in this thread is trying to suggest that there might be a gender-based difference in ability to pursue careers in STEM fields, this chart is most appropriate.

graphic-proportion-women-men-graduates

That fits with my experience. On average, the undergraduate women I teach are just as capable as the men — if they weren’t confidential, I could show you my gradebook and you’d see that it’s women who consistently stand at the top of the class. Yet somehow, after they graduate, their participation in science careers plummets. I don’t think they turn stupid after getting their degree; I remember my peers from my graduate school and post-doc days, and no, all of them were scary smart or they wouldn’t be there. I think it’s more that harassment takes its toll (most of which I was oblivious to at the time, but afterwards, I’ve had women tell me about it, and it was an eye-opening “Oh, yeah, he was kind of creepy, wasn’t he” sort of revelation), and disrespect (I definitely knew older faculty who saw women as good technicians, but not smart enough to do creative work) and judgmental attitudes (“she’s just going to get married and pregnant and leave the field anyway”).

We are not yet creating equal opportunities. Don’t try to tell me that women are less capable when I deal with brilliant, hard-working women in science every day.

Bobby and Bobby are very foolish boys

There’s a popular scam among creationists: they offer big prizes to anyone who can “prove” that evolution is true. They never award these prizes, and I suspect they usually don’t even have the cash on hand, because they’ve got an ace up their sleeves. They set unreachable criteria. For example, to win Joseph Mastropaolo’s evolution prize, one must present evidence that persuades a team of judges — judges who are hand-picked by Mastropaolo. I think the game is stacked.

Now look who is playing a similar game: Robert Kennedy Jr. and Robert De Niro are offering a $100,000 prize for proof that vaccines are safe. I don’t quite know what they expect would constitute proof, since they seem to disregard the extensive clinical trials that have been carried out, or the lack of significant numbers of dead babies from their shots (almost 90% of infants get a thorough series of vaccinations, yet somehow we don’t have piles of dead babies), or the historical evidence (visit a 19th century graveyard, and you will find those piles of dead babies…modern graveyards are mostly full of old dead people), or the remarkable improvement in public health with the introduction of, for instance, the polio vaccine, and the effective eradication of smallpox, or that measles kills about 100,000 people a year (but very few in the US), all of which would be preventable by vaccines.

You know, that $100,000 prize would help a lot in vaccinating all the people in Asia and Africa who are suffering from measles — about 20 million people each year.

So what are the criteria for winning this prize?

Kennedy explained that the WMP will pay $100,000 to the first journalist, or other individual, who can find a peer-reviewed scientific study demonstrating that thimerosal is safe in the amounts contained in vaccines currently being administered to American children and pregnant women. Kennedy believes that even “a meager effort at homework” will expose that contention as unsupported by science.

Hold your horses, everyone! <rushes to the PubMed link I always keep handy>

Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder.

CONCLUSIONS:
No convincing evidence was found in this study that MMR vaccination and increasing thimerosal dose were associated with an increased risk of ASD onset.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Vaccines and autism in primate model.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

GIMME MY MONEY, BOBBY2. Those were a few papers that turned up in just the first page of a search — there were 180 more pages, but I didn’t bother looking, because I like the idea of winning a couple of years’ salary for the minimal amount of work. I wonder — could I be even lazier and just send them a link to PubMed?

I suspect that I won’t get paid, because there are other, mysterious excuses they’ll have for rejecting the evidence, just like the creationists do. The stated criteria are just to obvious and simple and have been met over and over in decades of peer-reviewed research.

They won’t pay up, because like the creationists, they’re only going to accept ‘evidence’ that supports their presuppositions, and the purpose of the reward is not to get information delivered to them — that information is freely available already — but to promote a lie. “We offered all this money, and no one could provide evidence, therefore you know that evolution/vaccines are false!” It’s a pretty tacky tactic.

It’s sad, too. I’ve liked many of De Niro’s movies. Now I’ll never be able to watch them again without being conscious that the actor is a colossal dumbass.

Someone needs to start a foundation to help victims of Physicist Syndrome

William Happer is a distinguished emeritus professor of physics. His specialty is optics and spectroscopy, but he’s got Physicist Syndrome bad — he thinks he’s an expert in everything to the point that he can disagree with distinguished professors in other fields, on their specialty. Yes, he’s that kind of idiot.

And he’s being considered for the position of Science Advisor to Donald Trump. Are you surprised? Trump’s chief skill seems to be in ferreting out the worst people and elevating them to positions where they can do the most damage. If you’re wondering why Trump is at all interested in this crank professor, it’s because he’s already been bought and paid for by the fossil fuel industry.

William Happer has accepted funding from the fossil fuel industry in the past. In a Minnesota state hearing on the impacts of carbon dioxide, Peabody Energy paid him $8,000 which was routed through the CO2 Coalition.

In 2015 undercover investigation by Greenpeace, Happer told Greenpeace reporters that he would be willing to produce research promoting the benefits of carbon dioxide for $250 per hour, while the funding sources could be similarly concealed by routing them through the CO2 Coalition.

But make up your own mind. Here’s an interview with the sublimely confident Dr Happer. Let’s start with something I can agree with.

Well, I guess where I see the big problem in our country is science illiteracy in the general population. If I were King, I would figure out some way to get better science teaching into the schools, you know, K through 12, and especially middle school and high school. It’s a disgrace that people get out with high school degrees knowing as little as they do. And I think it’s getting worse. I think it was much better in the ‘30s than it is today. And teaching makes a difference.

I often tell the people this anecdote — I once asked Edward Teller [a key architect of the hydrogen bomb] how it was possible that there were all these Hungarians, you know, there was him and Eugene Wigner and Szilard, von Neumann — a real constellation. They were all about the same age, and made enormous contributions to science. It was easy, he said. We all had the same high school teacher in the Fasori Gimnázium in Budapest. So there’s an example. Whoever this teacher was deserves a medal, you know. Nobody pays any attention to him. But at least in Hungarian society, teaching was an honorable profession, so that this really good guy — probably better than most university professors — produced this galaxy of stars. So I think we should seriously think about improving general education.

Oh man, yes. There was one teacher I’d name as extremely influential in getting me to pursue a career in science — thanks, Mr Thompson, and that chemistry class my junior year in high school. I think we all know of strong teachers who confirmed our commitment to do this thing…we here at the college level are mainly dealing with young men and women who’ve already made up their minds. We should pay public school teachers more, don’t you think?

But then he mounts his high horse.

I don’t know. First of all, just the term denier to someone like me is extremely offensive because it’s carefully chosen to make me look like a Nazi sympathizer. And you know, I dodged Nazi submarines when I was a kid [on a ship carrying immigrants to the United States] and my father fought against them and my mother worked on the Manhattan Project, and I found it profoundly offensive, you know, and many other people feel the same.

I think toning down the rhetoric would help a lot. And it has been very uneven — for example under the previous eight years the President and secretary of state kept talking about the deniers, you know, about the baskets of deplorables, the knuckle draggers, the Neanderthals. That was me they’re talking about.

I don’t think it was the anti-Nazi science kook they are talking about. It’s the, you know, Nazis. Literal Nazis. The people who do Nazi salutes, talk about white supremacy, and voted for Trump — the guy considering you for science advisor. I’m more than a little tired of indignant people who profess their contempt for Nazis while embracing the political party that counts on Nazi/racist support to get elected.

But also it’s impossible to take his concerns about toning down the rhetoric seriously when he just said this:

“There’s a whole area of climate so-called science that is really more like a cult,” Happer told the Guardian. “It’s like Hare Krishna or something like that. They’re glassy-eyed and they chant. It will potentially harm the image of all science.”

But even worse is the simplistic crackpot science he is peddling.

I see the CO2 as good, you know. Let me be clear. I don’t think it’s a problem at all, I think it’s a good thing. It’s just incredible when people keep talking about carbon pollution when you and I are sitting here breathing out, you know, 40,000 parts per million of CO2 with every exhalation. So I mean it’s shameful to do all of this propaganda on what’s a beneficial natural part of the atmosphere that has never been stable but most of the time much higher than now.

You know what else I’m pumping out as I sit here? Water. It’s just oozing out of my pores, evaporating out of my breath. Water is good, right? So more of it would be better. Let’s dump Happer in a big vat of water and let him paddle there, bathing in the life-giving fluid.

Another natural product of my metabolism is urea. I’m going to be even more generous and suggest that he be immersed in a vat of urine. More is better, always, right? So water plus urine has to be an improvement. Also, plants love water, and they love nitrogen. Therefore, it’s even more beneficial and natural.

OK, I forgot. He also likes gasses. We’ll top off the vat with pure, natural, healthful CO2. It’s a win:win!

I would like to remind Dr Happer of an old familiar (and true) phrase: the dose makes the poison. No one is going to deny that CO2 (and water, and nitrogen) are necessary components of a healthy atmosphere for life as it exists on earth. But we need balance in all things: just the right amount of carbon and nitrogen and water, balanced dynamically in cycles of renewal and reuse. That’s how we maximize growth in a sustainable way. Happer thinks throwing the balance out of wack is just as good as a balanced cycle. That ain’t gonna work.

Furthermore, he denies all the chaos and disruption as we roll our atmosphere back to the state it was in during the Carboniferous — which was admittedly a very nice environment for the plants and animals adapted to the Carboniferous, but probably isn’t as favorable to a species that evolved out of the ice ages.

He also ignores the possibility that we have no check on a runaway greenhouse effect — there is no guarantee climate change will stop at a swampy, hot, carbon-rich Carboniferous. I don’t think we’re predicting a roll-back to the Hadean, but it doesn’t take much change to make human life uncomfortable and possibly untenable.

Ultimately, though, his problem is that he’s not as bright as he thinks he is, and that he has a limited, one-dimensional view of geophysics, ecology, biology, and climate…yet, as a victim of Physicist Syndrome, he still thinks his narrow perspective trumps that of geophysicists, ecologists, biologists, and climatologists. That makes him a perfect Trump advisor, although it may chafe when he discovers that Trump thinks he’s even smarter than physicists.