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Thursday, March 21, 2024

Science misinformation is being spread in the lecture halls of top universities

Should universities remove online courses that contain incorrect or misleading information?

There are lots of scientific controversies where different scientists have conflicting views. Eventually these controversies will be solved by normal scientific means involving evidence and logic but for the time being there isn't enough data to settle a genuine scientific controversy. Many of us are interested in these controversies and some of us have chosen to invest time and effort into defending one side or the other.

But there's a dark side of science that infects these debates—false or misleading information used to support one side of a legitimate controversy. To give just one example, I'm frustrated at the constant reference to junk DNA being defined as non-coding DNA. Many scientists believe that this was the way junk DNA was defined by its earliest proponents and then they go on to say that the recent discovery of functional non-coding DNA refutes junk.

I don't know where this idea came from because there's nothing in the scientific literature from 50 years ago to support such a ridiculous claim. It must be coming from somewhere since the idea is so widespread.

Where does misinformation come from and how is it spread?

We know that university press releases are a constant source of misinformation and we know that a lot of misinformation is presented in university courses. The quality of biochemistry and molecular biology teaching is a major issue in the pedagogical literature and it comes up frequently in the papers I review for Biochemistry and Molecular Biology Education. (I am on the editorial board.)

Teaching is an ongoing problem. I recently criticized a course taught by Nils Walter at the University of Michigan when his students edited a Wikipedia article. It prompted him to publish an article in BioEssays defending his teaching [Nils Walter disputes junk DNA: (1) The surprise].

The quality of university courses was widely discussed ten years ago when there was a lot of hype about MOOCs (Massive Open Online Courses). This was supposed to be the future of university education and soon big universities like MIT and Stanford began to put their lectures online as the best examples of education. There was a lot of angst in Canada because people feared that these online courses from the "best" universities in the world would replace lectures in Canadian universities [Is Canada Lagging Behind in Online Education?]. I looked at some of the online biochemistry courses and realized that we had nothing to worry about because they were far below the quality that we might expect from such prestigious schools. Many of them were what we would describe as high school level courses. [On the Quality of Online Courses].

This issue come up recently on Facebook when a creationist posted a link to one of those courses in order to refute something I had said. That prompted me to look at some of the lectures and I was appalled at what I saw. It made me realize that some of the misinformation that's common among today's scientists comes from material they were taught as undergraduates (and graduate students).

I'm going to highlight some of the issues I saw in that course—it's an introductory biology course from Stanford—and then I hope to generate a discussion about the responsibility of a university. Is there anybody at these universities (e.g. MIT and Stanford) who reviews the material before it's put online? Is there any quality control or is it simply assumed that if you are a professor at MIT or Stanford you must be teaching accurate facts and information?

If we can show that the online lectures contain lots of incorrect information, misleading statements, and misinformation, can the university remove the lectures? Should it?

Robert Sapolsky is a professor at Stanford University. His main research interest is in the field of neuroendocrinology where he studies stress in baboons. He taught a course called Bio 150/250 Human Behavioral Biology back in 2010 and Stanford posted the lectures online, presumably as an example of the high quality of its courses.

I'm interested in the two lectures on Molecular Genetics (Ⅰ and Ⅱ) since they cover topics I'm familiar with. In the case of Molecular Genetics Ⅰ there have been about one million views, more than 1,200 comments and 23,000 likes. Almost every one of the comments praises Sapolsky and his lecture. If you are interested in the quality of undergraduate education and the source of scientific misinformation then I urge you to watch the entire lecture.

(I contacted Robert Sapolsky by email a few weeks ago and alerted him to some issues with his lectures. I told him that I was preparing this post and asked him if he wanted to comment. He did not respond. I followed up with an email message today (March 22, 2024) and I received an autoreply informing me that he is unable to answer emails because of the popularity generated by his latest New York Times bestseller Determined.)

Sapolsky's objective in those two lectures is to convince students that the regulation of gene expression is important and you can get big phenotypic changes with small changes in regulatory genes. There's nothing wrong with that but the way he goes about it will surprise you.

He begins by teaching his students that the old-fashioned biologists of the 1960s and 1970s were only interested in proteins and the only kind of evolution they recognized was that due to changes in amino acid codons. Crick's central dogma is the classic example of this sort of bias, according to Sapolsky.

Then along came Gould and Eldredge who showed that evolution proceeds in a stepwise manner consisting of long periods of stasis followed by sudden leaps of dramatic change. The old boys rejected this view because they could only conceive of gradualistic change due to small mutations in protein coding regions.

All of this changed in the 1980s when molecular geneticists came up with a mechanism for big rapid changes. They discovered that only 5% of the genome coded for proteins. At first they thought that all this non-coding DNA was junk but they soon discovered that it was full of regulatory DNA. They also discovered that coding regions were interrupted by introns and that meant that there was no longer a one gene - one protein relationship because each gene produced many different proteins. Then they discovered epigenetics, which demonstrated that DNA wasn't even in control of its own expression. All of this proved that punctuated equilibrium is correct and those big jumps in evolution are due to macromutations that affect gene regulation.

I don't understand why Sapolsky feels it was necessary to trash the founders of molecular biology and all the work they did to elucidate the fundamental principles of regulation in bacteria and phage. I don't understand why he didn't read up on the central dogma before misrepresenting it to his students. I don't understand why he didn't at least check the Wikipedia article on punctuated equilibria before spreading misinformation about it.

I get that he might easily buy into alternative splicing and epigenetics because it's harder to find out about the controversies in those subjects but is that any reason to leave the lectures online now that we know about those controversies?

I'll highlight some of the specific issues below for those of you who can't watch the whole video.

  • (2:00) "Another critique, and one that's also central today, is that whole emphasis on the gradualism, on small incremental changes. And what I alluded to at the end the other day is going to see a viewpoint where something very, very different is proposed to be going on. One that will make sense only eventually when we see some pretty unexpected things about genetics and the molecular biology of." Sapolsky is alluding to punctuated equilibria and his idea that it represents rapid morphological changes due to mutations in regulatory sequences.
  • (4:43) Evolution is about genes. What he means, as we will see later, is that some people think that evolution is only about genes and not things like regulatory sequences. He will develop the concept that molecular biologists have discovered regulatory sequences and this calls into question the traditional view of evolution.
  • (5:43) Proteins are important. Sapolsky is setting up a strawman where genes encode proteins and proteins are thought to be the only important things in evolution. He is opposed to this view but he makes it sound like his own view is revolutionary.
  • (8:33) Proteins fit their substrates like a key fits a lock. "Cliched evolution at it's best." Biochemists abandoned that cliche many decades ago. I think he does science a disservice by teaching first year students that most scientists are wrong about lots of important things.
  • (12:57)"So out of all of this comes the central dogma of life. And this was proposed by Francis Crick of Watson and Crick fame. And Francis Crick was the one who formalized saying the central dogma of how life and information flows is DNA to RNA to protein. And that became defining. An entire generation of babies were told that at birth."

    "This is the flow of information. It has been violated in all sorts of interesting ways, which will dominate a lot of what comes. But this was the central dogma. One way in which it is violated--and again, this notion is not DNA to RNA, but the notion of whatever your DNA sequence is, whatever the gene is, whatever structure of a protein it codes for-- the flow of information is going to be from DNA, RNA, to protein. DNA as running everything."

    The strawman construction continues by misrepresenting the Central Dogma. Sapolsky will demonstrate that there's much more to life than just coding regions in the genome. I agree (partly) with his conclusion but I don't like the misrepresentation of the Central Dogma and the depiction of older scientists as incompetent.

  • (14:01) "It all starts with DNA. DNA is the one sitting here deciding when information is going to flow from DNA to RNA. DNA as knowing what's happening."

    "And a lot of what we will see shortly is DNA knows squat. DNA is not making a whole lot of decisions there. The one simplistic way in which central dogma went down the tubes in the 1970s or so, and one that's tangential here, but just as a first blow against central dogma ...."

    "A class of enzymes that could take the RNA information and turn it back into DNA, viral information. And then it does its thing. Huge blow to the central. Here's information running from an RNA virus somehow being reversed back to a DNA form. And thus these are called retroviruses. Inserting the DNA, and off they go from there. So this was a major blow. Everybody eventually came to terms with this. But it still is a minor footnote in this Crickian world of everything flows from DNA."

    "It is the Bible. It is the law giver. It is the holy grail. It is where it all starts."

    Sandwalk readers will know that Sapolsky is dead wrong about the Central Dogma. What he's doing here is setting up his students for revelations about epigenetics. I don't think this sort of rhetoric is helpful.

  • (16:27) Sapolsky then defines microevolution as classical changes in protein-coding genes, leading to changes in proteins, and that gives rise to gradualistic evolution. He's going to demonstrate that this is all wrong. The important happenings in evolution occur at the macroevolutionary level and they work entirely differently.

  • After a lot of examples of gradual change due to single mutations in protein-coding genes, he gets to his main point.

    (52:28) "And in the 1980s, suddenly a very different model emerged. And this came from Stephen Jay Gould, who we heard about the other day. Stephen Jay Gould and the person, the poor schmook who was always lost in this, another evolutionary biologist named Niles Eldredge who somehow did not quite have the press that Stephen Jay Gould did, so he is lost to history except for people who know what he's up to. And he's an amazing scientist."

    "But Gould and Eldredge came up with a very different model. And I alluded to it the other day and drew it right there. And their notion was that gradualism is nonsense. There are not gradualistic incremental changes. Evolution is not being driven by small gradualistic changes. Instead, what their model was is that there's long periods of nothing happening, of stasis. Long periods of nothing happening. If there's changes in DNA sequences thanks to mutations, they're not consequential. Or if they're consequential enough to change the fitness of one organism 1%, that's not going to make a difference."

    "Most of the time, no change is occurring and when it does occur, it is in incredibly fast, explosive periods of change followed by a new period of stasis. Evolutionary change comes in step functions rather than smooth gradualism."

    There's no mention of speciation and what we know to be the correct interpretation of punctuated equilibria that Eldredge and Gould proposed (cladogenesis). Sapolsky then says that Gould was a Marxist and this stepwise view of evolution is classic revolutionary change and dialectical materialism (54:34).

  • (55:59) Sapolsky goes on to explain where the idea of punctuated equilibrium (his version) comes from. You really have to hear this for yourself.

    "OK, so where did the idea of punctuated equilibrium come to these guys? Mainly because Gould was not a biologist. He was certainly not an evolutionary biologist. What he was was a paleontologist. He studied fossils. ... And when you do that, you notice something, which is you've got gaps in the record. You've got your famed missing links."

    Sapolsky then draws a steplike diagram of change that represents his view of punctuated equilibrium. The consequences are that "little genetic changes don't matter" and small adaptive changes don't matter. Competition doesn't matter and that whole view of evolution is wrong.

  • (1:01:00) He then summarizes the criticism of punctuated equilibrium from the old-fashioned biologists who he has set up as his strawman. They demand that Gould and Eldredge show them the molecular mechanisms that could produce such a pattern. According to Sapolsky, those critics say you can't get long periods of stasis followed by rapid change according to their view of evolution.

    Now he gets to the point. He says that the punctuated equilibrium people had no response to the demand to show a molecular mechanism but then along come the molecular geneticists to rescue them.1 The molecular geneticists discovered introns in the 1980s (?) and then discovered alternative splicing. That means that the old-fashioned view of one gene - one protein has been "trashed" and replaced by a model where a single gene can produce many different proteins under different circumstances.

  • (1:11:23)"The next thing that went down the tubes was looking at, well how much of DNA is actually devoted to coding for amino acids? And the answer was obvious, like 99.99%, each one of these [genes] would just have to have a stop codon, a stop signal at the end. And otherwise this was just a continuous flow of information once you have factored in these intron things. Ok, so they're part of this gene but immediately starts the next one. The next major discovery was one gene would very rarely start immediately after the next one. There would be long stretches of DNA in between that didn't code for a protein—non-coding DNA."

    "That's mighty puzzling. What that? Just junk or stuff? And around that time the phrase junk DNA was actually floating around. People trying to make sense of this. And when people sat and started actually like doing the numbers, out came a number that knocked people on their rears it was so flabbergasting. 95% of DNA is non-coding. 95% does not code for a gene specifying a protein. In other words, in between here [between genes] on the average would be a stretch of DNA 19 times the length of that, or whatever the math winds up being. And suddenly calling that stuff junk DNA starting to seem a little bit tenuous, because 95% of your DNA just can't be packing material for the whole thing. It's got to be doing something. And during that period [1980s], came the sort of the insight into this that all the intervening, non-coding stuff was—what was that? That was the instruction booklet. That was the instruction booklet on when to activate these genes. ... Implication right there off the bat, which is Crick was wrong. DNA sequences are not the starting point of the central dogma of life."

    You can see where this is going. Sapolsky now tells his students that regulatory sequences are the really important parts of the genome. That's true but his history is all wrong and his gratuitous attacks on Crick and others is despicable. He goes on to say that because the expression of genes is controlled by transciption factors that means that genes are controlled by the environment because the activity of transcription factors can be affected by internal and external signals. (The main part of his course is about how hormones change behavior.) Plus, he says, you have a whole world of chromatin regulation that controls genes and that brings up a whole new field called epigenetics. What does all this mean? It means that now you can get mutations that give rise to big changes that aren't just gradual.

    You have to watch the first 30 minutes of next lecture (see below) to see how Sapolsky ties macromutations to punctuated equilibrium. He refers to King and Wilson and their discoveries in the 1980s2 that the most important differences between humans and chimps are due to regulatory mutations. (You will have to hold your nose if you listen to the part about Barbara McClintock and the part about irreducible complexity.) The punch line comes at 57 minutes. Gould was right. You can have "massive macro changes" in a short period of time.

1. I'm guessing that Sapolsky hasn't read Gould's 1977 book Ontology and Phylogeny.

2. Actually, 1975, and their idea wasn't new even at that time. (King and Wilson, 1975)

King, M.-C. and Wilson, A.C. (1975) Evolution at two levels in humans and chimpanzees: Their macromolecules are so alike that regulatory mutations may account for their biological differences. Science 188:107-116 [doi: 10.1126/science.1090005]


Chris said...

I see a lot of equating exons with coding sequences, and I'm not sure where the students are getting this from. They are mixing up gene models. One model being exon/intron structure (genome) the other being untranslated and coding sequences (mRNA).

Gabo MH said...

I cannot believe this. Most of my students also arrive with the wrong notions about the Central Dogma, and I get them to actually read the darn articles and check if claims done here, there, or elsewhere make sense now that they know what the Central Dogma is really about.

Either way, thanks for sharing this Larry. Very useful.

John Harshman said...

It's a common creationist mistake to confuse punctuated equilibria with saltation. Gould may have invited it by dabbling in the latter, but at least he never conflated them. Surprising to see a biologist, one who presumably has read Gould, make the same mistake. And it's odd to see that the one of the founders of Paleobiology isn't a biologist.

Zach Hancock said...

Contrarians of standard evolutionary theory love to prop-up Gould as this radical figure whose hypothesis of punctuated equilibrium fundamentally challenged the field. In reality, if Gould hadn't been such a talented popularizer, no one today would be talking about PE. And it was (in my humble opinion) thoroughly debunked in the 1980s.

Population geneticists showed that Gould had misread much of the early theory, especially Sewall Wright, and that stasis and rapid change was a fundamental component of his shifting-balance theory and of the adaptive landscape metaphor (see Newman et al. 1985: "Neodarwinism implies punctuated equilibria" - they masterfully show that selection on many alleles of small effect can produce rapid change that appear instantaneous on a geological timescale). The fossil record was discussed in the context of stabilizing selection and rapid shifts in fitness peaks as early as G.G. Simpson (1944; Tempo & Mode in Evolution). Gould's proposed mechanisms of PE (e.g., developmental constraints, genetic revolutions following founder events) were also eviscerated by Charlesworth, Lande, & Slatkin (1982; "A neo-darwinian commentary on macroevolution").

More recent reviews have come to similar conclusions, that Gould's ideas have been or should be largely abandoned (see Pennell et al. 2014: "Is there room for punctuated equilibrium in macroevolution?"; Pennell et al. 2014: "Speciation is unlikely to drive divergence rates").

For interested parties, I also have a review of PE: Hancock et al. (2021): "Neo-darwinism still haunts evolutionary theory: a modern perspective on Charlesworth, Lande, and Slatkin (1982)".

In short, the characterization of early evolutionary theorists as these zealots of gradualism is a gross mischaracterization perpetuated by both Gould and his intellectual descendants who would rather peddle in polemics than actually bother reading Fisher, Wright, or Haldane.

John Harshman said...

Let's recall that Eldredge and Gould were disciples of Ernst Mayr, and considered PE to be the consequence of Mayr's ideas about speciation, peripheral isolates, and "genetic revolutions". Stasis was maintained by "coadapted gene complexes" and only upset in small populations, but the whole process was still gradual in ordinary time. The weird parts of the theory were the mechanism of stasis and the connection of evolution to speciation, and of course Mayr's ideas haven't aged well.

Larry Moran said...

Let's not quibble about the precise meaning of punctuated equilibria and exactly what Gould and Eldredge meant. I think we can all agree that what they did NOT mean was the that the evolution of a single lineage was marked by long periods of stasis punctuated by rapid periods of substantial morphological change.

In other words, the steplike process that Saplosky drew on the whiteboard is a misrepresentation of PE. I think we can also agree that PE was not the reason why molecular biologists became interested in regulation. PE was proposed in 1972 and Jacob & Monod got their Nobel Prize in 1965.

The important question for today is whether a prestigious university like Stanford should continue to host and promote an online lecture that's full of errors.

John Harshman said...

Sure, Larry, they didn't mean that. But there's much more they didn't mean that Sapolsky seems to be claiming, and that doesn't seem to me to be the most important thing. More important to me would be his notion that PE proposes saltation or macromutation and his claim that PE is representative of current ideas in evolutionary biology.

Gerdien de Jong said...

This just came to my notice:

John Mattick, A Kuhnian revolution in molecular biology: Most genes in complex organisms express regulatory RNAs
BioEssays. 2023;45:2300080.

I've never been able to grasp how Mattick etc thing regulation can work at with some 50 or so regulatory sequences to a protein gene, and worse, even more RNA that interferes with everyting.

Larry Moran said...

@Gerdien: I've discussed John Mattick's views frequently on this blog and I cover them in my book. Here's a post from last Fall where I cover his most recent attempt at a paradigm shaft.

John Mattick's new paradigm shaft