A new way of visualizing cells

December 13, 2020 • 2:30 pm

This is a lovely video showing a new way of visualizing cells as they are living and operating. The “microscope” that does this is extremely large and complex. I don’t know much about it, and don’t fully understand the principles, but this video probably tells you all you need to know. The images are stunning, and I love the enthusiasm of the researchers.

Has the problem of protein folding been solved?

December 1, 2020 • 1:00 pm

One of the biggest and hardest problems in biology, which has huge potential payoffs for human welfare, is how to figure out what shape a protein has from the sequence of its constituent amino acids. As you probably know, a lot of DNA codes for proteins (20,000 proteins in our own genome), each protein being a string of amino acids, sometimes connected to other molecules like sugars or hemes. The amino acid sequence is determined by the DNA sequence, in which each three nucleotide bases in the “structural” part of the DNA sequence codes for a single amino acid. The DNA is transcribed into messenger RNA, which goes into the cytoplasm where, connected to structures called ribosomes, and with the help of enzymes, the DNA sequence is translated into proteins, which can be hundreds of amino acids long.

In nearly every case (see below for one exception), the sequence of amino acids itself determines the shape of the resultant protein, for the laws of physics determine how a protein will fold up as its constituent bits attract or repel each other. The shape can involve helixes, flat sheets, and all manner of odd twists and turns.  Here’s one protein, PDB 6C7C: Enoyl-CoA hydratase, an enzyme from a bacterium that causes human skin ulcers.  This isn’t a very complex shape, but may be important in studying how a related bacterium causes tuberculosis, as well as designing drugs against those skin ulcers:

And here’s human hemoglobin, formed by the agglomeration of four protein chains, two copies each from two genes (from Wikipedia):

Knowing protein shape is useful for many reasons, including ones related to health. Drugs, for example, can be designed to bind to and knock out target proteins, but it’s much easier to design a drug if you know the protein’s shape. (We know the shape of only about a quarter of our 20,000 proteins.) Knowing a protein’s shape can also determine how a pathogen causes disease, such as how the “spike protein” or the COVID-19 virus latches onto human cells (this helped in the development of vaccines). Here’s the viral spike protein, with one receptor binding domain depicted as ribbons:

And there are many questions, both physiological and evolutionary, that hinge on knowing protein shapes. When one protein evolves into a different one, how much does that affect shape change, and can that change explain a change of function? (Remember, under Darwinian evolution, gradual changes of sequence must be continually adaptive.) How do different shapes of odorants interact with the olfactory receptor proteins, giving a largely one-to-one relationship between protein shape and odor molecules?

Until now, determining protein shape was one of the most tedious and onerous tasks in biology. It started decades ago with X-ray crystallography, in which a protein had to be crystallized and then bombarded with X-rays, with the scattered particles having to be laboriously interpreted and back-calculated into estimates of shape. (This is how the shape of DNA was determined by Franklin and Wilkins). This often took years for a single protein. There are other ways, too, including nuclear magnetic resonance, and new methods like cryogenic electron microscopy, but these too are painstakingly slow.

Now, as the result of a competition in which different scientific teams are asked to use computer programs to predict the structure of proteins that are already known but not published, one team, DeepMind from Google, has achieved astounding predictive success using artificial intelligence (AI), to the point where other technologies to determine protein structure may eventually become obsolete.

There are two articles below, but dozens on the Internet. The first one below, from Nature, is comprehensive (click on screenshot to read both):

This article, from the Deep Mind blog itself (click on screenshot), is shorter but has a lot of useful information, as well as a visual that shows how closely their AI program predicted protein structure.


In a yearly contest called CASP (Critical Assessment of Structure Prediction), a hundred competing teams were asked to guess the three-dimensional structure of about a hundred sections of proteins (“domains”). The 3D structure of these domains were already known to those who worked on them, but was unknown to the researchers, as the structures hadn’t been published.

The method for how Deep Mind’s AI program did this is above my pay grade, but involved “training” the “AlphaFold” program to predict protein structures by training the program with amino-acid sequences of proteins whose 3-D structure was already known. They began a couple of years ago in the contest by training the program to predict the distance between any pair of amino acids in a protein (if you know the distances between all pairs of amino acids, you have the 3D structure). This year they used a more sophisticated program, called AlphaFold2, that, according to the Nature article, “incorporate[s] additional information about the physical and geometric constraints that determine how a protein folds.” (I have no idea what these constraints are; the procedure hasn’t yet been published but will be early next year.)

It turns out that AlphaFold2 predicts protein structure with remarkable accuracy—often as good as the more complex laboratory methods that take months—and does so within a couple of hours, and without any lab expenses! In fact, the accuracy of shape prediction wound up being about 1.6 angstroms—about the width of a single atom! AlphaFold2 also predicted the shape of four protein domains that hadn’t yet been finished by researchers.  Before this year’s contest, it was thought that it would take at least ten years before AI could be improved to the point where it was about as good as experimental methods. It took less than two years.

Here’s a gif from the DeepMind post that shows how accurately DeepFold 2 predicted two protein structures. The congruence of the green (experimental) and blue (AI-predicted) shape is remarkable.

There aren’t many cases where computers can make a whole experimental program obsolete, but this appears to be what’s happening here.

There is one bug in the method, though it’s a small one. As Matthew Cobb pointed out to me, in a few cases the sequence of amino acids doesn’t absolutely predict a protein’s shape. As he noted, “Sometimes the same AA [amino acid] sequence can have different isoforms [shapes that can shift back and forth], which can have Very Bad consequences—think of prions, in which the sequence is the same but the structure is different.” Prions are shape-shifting proteins that, in one of their shapes, can cause fatal neurodegenerative diseases like “Mad cow disease”. These are fortunately rare, but do show that the one-to-one relationship between protein sequence and protein shape does have exceptions.

Here’s a very nice video put out by DeepMinds that explains the issue in eight minutes:

We’ll have to wait until the paper comes out to see the details, but the fact that the computer program predicted the shapes of proteins so very well means that they’re doing something right, and we’re all the beneficiaries.

It’s the end of the world as we know it

November 19, 2020 • 3:30 pm

Noted in passing, here’s an “exhibit” put up by the National Park Service itself.

Indeed, things are rarely simple in nature. Queer ecology has put paid to the notion that there are two discrete biological sexes in humans (and in other mammals, birds and fruit flies), as well as to the idea that an American Robin is a “box” differentiated from a Northern Cardinal “box”.

What a great new way to view the world! Thanks to the biologists at the National Park Service, I am freed from my subservience to colonialist and essentialist biology.

Your tax dollars at work . . . .

h/t: Luana


A good article on the meaning of biological sex

September 23, 2020 • 1:30 pm

There’s lot of confusion among laypeople, and even among scentists, about what “sex” is, in the sense of “what do we mean by a biological sex?” This goes along with questions like “Is sex binary?”, “How many sexes are there?” and so on.

For a scientific but accessible discussion of how biologists construe sex, the article below from Aeon (click on screenshot) is quite good.

There’s not much to quibble with in the piece, as it’s a straightforward discussion about how biologists regard sex, so I won’t do anything except list some of the questions it takes up:

  • What do biologists mean by “the sexes” of an animal or plant?
  • Why do we have sexes in the first place? Why doesn’t everything just reproduce asexually by budding or parthenogenesis (production of an offspring from an unfertilized egg)?
  • Why are there only two sexes in the vast majority of animal species? Why can’t there be three or more sexes?
  • Are hermaphrodites or developmental anomalies members of other sexes?
  • Why do biologists define the sexes by gamete size rather than by chromosomal constitution or characters like sexual organs?
  • Why doesn’t the existence of individuals with combinations of male and female traits prove that sex is a continuum?
  • Why we can’t necessarily extend biologists’ views of sex to questions like “who participates in women’s sports?” or “who goes to a women’s prison?”

I have a few minor quibbles with the piece, but they’re so trivial that they’re not worth mentioning. What especially interested me was the evolutionary question. Biologists have long wondered “Why did sexual reproduction evolve in the first place?”, and, truth be told, we don’t have an answer everyone agrees on. There is more agreement on why there are just two sexes in the vast majority of animals, although some organisms like protists have dozens of “mating types” that might be seen as sexes (Griffiths doesn’t).

Have a read of the piece if you want to be informed about biological sex before you wade into the gender wars.

Matt Meselson describes his most famous experiment (with Frank Stahl)

July 18, 2019 • 11:00 am

In 1958 Matt Meselson, whom I knew slightly at Harvard (he was a terrific guy), performed, along with Frank Stahl, an experiment that John Cairns called “the most beautiful experiment in biology”. What he and Stahl did (see description here) was to use density-labeled components of DNA to choose among which of the three methods of DNA replication floated at the time was correct (people didn’t know how DNA replicated in 1958; this experiment settled the issue):

In “semi-conservative replication”, each strand of DNA unwinds and makes a copy of itself, so that each DNA helix in the next generation of DNA has both a parental strand and a new strand synthesized from nucleotides and sugars. “Conservative” replication involves each double strand making another whole double strand.  “Dispersive” replication involved the DNA breaking, with each break synthesizing new DNA, matched to the other strand, in bits. They’re portrayed above.

Meselson and Stahl’s genius was to use an in vivo replication in E. coli producing DNA strands labeled with heavy isotopes (15N) that, while chemically identical to non-radioactive nucleotides, would be distinguishable from the non-labeled strands because the former were heavier and could be separated by vigorous centrifugation. (They used labeled nucleic acids as the components of the original strands; those labeled nucleotides were themselves synthesized by growing the starting bacteria for a few generations on “heavy” ammonium chloride—the only source of nitrogen—a component of nucleic acids—in the bacterial medium.)

The beauty of the experiment is that the results—confirming semi-conservative replication—were visible in a single photograph (below), and were unambiguous. It was a lovely experiment, and I think deserved a Nobel Prize (sadly, one wasn’t given for this).

This nice 13-minute talk by Matt, taken from an iBiology talk website, describes this experiment. He and Stahl started by putting bacteria containing fully “heavy” DNA into medium with non-heavy ammonium chloride, so that all the new DNA synthesized would be light.

Under the semi-conservative hypothesis, the next generation of DNA would be “half heavy”, as each helix would have both an original heavy and new light strand, with the latter containing nucleic acids synthesized from the lighter nitrogen in the medium.

Under the conservative hypothesis, the next generation of DNA would consist of fully light double strands and fully non-heavy original double strands. There would only be two types of strands detectable, and those would stay, with the heavier ones eventually disappearing as their carriers died and new DNA was formed. And under the “dispersive” hypothesis, the next generation of DNA would be not fully heavy or not fully light, but a schmear of ‘partly-heavy helices”. You’d get a mess of mosaic strands in subsequent generations.

Well, listen to Matt describe this pathbreaking experiment below. I’ll give a link to their paper and the famous figure that convinced everyone below the video.

Here’s the famous figure, beginning with heavy DNA at the top from E. coli (right stripe in generation 0). The density of the centrifuge gradient increases to the right, and strands tend to settle where their density matches the density of the cesium chloride in the centrifuge tubes.

When the bacteria were put on non-labeled medium, and the tubes scanned with UV-absorption, which picks out the DNA, you see that in the first generation all the DNA is heavy (original bacterial DNA). As those bacteria replicate and form new DNA strands, the heavy helices begin to wane and we start to see half-heavy helices (lighter stripe forming in the left, lighter part of the gradient). This stripe gets darker after more “hybrid molecules” accumulate (generation time is shown on the right of the figure). After one generation of replication, you get hybrid strands which are lighter than the original ones (the bands show the position in the density gradient of the centrifuge). Then, after another generation, the hybrid stands themselves replicate, forming a double-light helix from the newly synthesized strand as well as the half-heavy strand containing the original heavy strand of DNA. By generation four, nearly all the helices are fully light (to the left), as the original strands are in a minority in the mix since their carriers have died or been outbred. In other words, the three bands predicted by the semi-conservative hypothesis were seen. The experiment ends three photos from the bottom, at generation 4.1.

The presence of the three well-demarcated strands forming in sequential order shows unambiguously that the semi-conservative model of DNA replication is correct. You don’t need statistics to get the answer here!

You can download the original paper by clicking on the screenshot:

I don’t know of a more beautiful—or unambiguous—experiment in modern molecular biology. And the stuff about Meselson and Stahl being locked in a room with food and a sleeping bag until they wrote that paper happens to be true. (For more, read The Eighth Day of Creation by Horace Freeland Judson).

An interview with E. O. Wilson: He’s still on about group selection

May 11, 2019 • 12:15 pm

Matthew sent me a link to this interview with the renowned biologist E. O. Wilson published in The Chronicle Review (part of the Chronicle of Higher Education). It’s generally okay but has some reportorial errors and, sadly, documents Wilson’s continued insistence that human altruism evolved by selection among groups (“group selection”).  The article appears to have come from The Wall Street Journal; click on the screenshot to read it.

The interviewer, Charlie Tyson, a grad student at Harvard, should have not made the errors below, especially because he’s right there at Wilson’s school. Granted, these errors aren’t important, but bespeak a lack of journalistic care.

Errors of fact

The claim that Wilson’s lab and office were right down the hall from those of his adversarial colleagues Steve Gould and Dick Lewontin, and the claim that during the “sociobiology wars,” a protestor dumped a pitcher of ice water on Wilson’s head.

Here’s what Tyson wrote:

Not since Alfred Kinsey has an entomologist’s career been so marked by controversy. Wilson became a public figure in 1975 with Sociobiology (Harvard University Press), which argued that social behavior, in humans as in other species, has a biological foundation. Some critics — most notably Richard Lewontin and Stephen Jay Gould, both just down the hall in Harvard’s biology department — saw the book as providing scientific cover for racism and sexism. In a well-known incident at the 1978 meeting of the American Association for the Advancement of Science, a demonstrator dumped a pitcher of ice water on his head, shouting, “Wilson, you’re all wet!”

No, their offices were not down the hall from each other, nor even on the same floor. Wilson’s office and labs were on the fourth floor of the MCZ labs, while Lewontin’s was on the first floor (for a year after he arrived at Harvard) and then on the third floor. Gould was located in another building: the Museum of Comparative Zoology proper, with his office on the ground floor. This would have been easy for Tyson to ascertain.

More important, it seem untrue that a pitcher of ice water was dumped on Wilson’s head at that meeting. That’s a biological urban legend that has been repeated many times. But it’s apparently wrong. The New Atlantis reports the truth: it was a cup of water, and was not dumped on his head:

 Most memorably, protesters rushed the stage at a February 1978 meeting of the American Association for the Advancement of Science just as Wilson was about to begin a talk. They chanted “racist Wilson you can’t hide, we charge you with genocide” and threw a cup of water at him (later embellished in legend into a full pitcher of ice water).

The cup-of-water version is the way I’ve heard it from those who were there, and David Hull concurs (though not Ulrike Segerstrale). Wilson could have clarified this, but I guess Tyson didn’t ask him.

But on to the science. In the interview, Wilson maintains, as he has before, that group selection is the explanation for the evolution of altruism in humans. In his most recent set of books, he’s also maintained that nearly all traits that ‘make us human’, including creativity, music, and so on, also came via group selection.  Further, he’s maintained that eusociality in social insects (the division of the colony into non-reproducing but cooperating castes, with a reproductive queen) also had nothing to do with kin selection, but was also the product of differential reproduction and extinction of groups.

Virtually every expert in insect social evolution has objected to Wilson’s view, given in a paper in Nature with Tarnita and Nowak. Apparently the only people who accept Wilson et al.’s view are the three authors of that paper, along with group-selection enthusiasts like David Sloan Wilson. You can see all my posts on this controversy here and here.) I also wrote a critical review of Wilson’s book The Social Conquest of Earth, which laid out his group selection ideas for humans, in the Times Literary Supplement; the review is paywalled, but I have copyright and posted my review here. Finally, you can see links to letters in Nature from the 140-odd evolutionists who objected to Wilson et al.’s view of group selection as the cause of eusociality in insects at this post. (I was one of the signatories.)

Here’s a snippet from Tyson’s interview:

Q. Your new book, Genesis, offers for the general reader an introduction to how complex societies evolve. But for the more specialized reader, it doubles as a manifesto for group-selection theory.

A. I realized we needed to get it straight on where advanced eusocial behavior comes from. I’ve felt, without fail, that it comes from group selection.

I had been a main proponent of kin selection. In fact, I was the guy who met W.D. Hamilton way back, who promoted him and helped him. And I think kin selection does in fact occur.

Having introduced kin selection, Hamilton had, in my view, explained the origin of nepotism. But then he came up with something called “inclusive fitness.” He said: Maybe societies as a whole originate when a lot of individuals together are helping one another, or cooperating, to the degree that they are related to them. If they were all closely related, then there would be a lot of individuals cooperating, and you might have the origin of a society — particularly a society based on altruism. I favored that idea and mentioned it as far back as The Insect Societies (Harvard University Press) in 1971.

Inclusive fitness carried the day. But it just wasn’t working. I saw that there were big flaws in it.

Nope, there are no big flaws in inclusive fitness arguments. And they still carry the day. The idea of group selection creating major features of human evolution, or of evolution in general, is not widely accepted, for it has major flaws. Although Tyson characterizes Wilson’s argument accurately, saying “Within groups, selfish individuals beat altruistic individuals — but altruistic groups beat selfish groups”, this is deeply flawed. As I wrote about Wilson’s words to that effect in his Chicago discussion with Alan Alda:

Wilson then said he was going to give the audience an equation about how group selection worked, and my heart sank as I imagined him trying to spout math. Fortunately, he said just this: “Within groups, selfish individuals outcompete altruistic ones. But altruistic groups outcompete selfish ones.” The audience applauded loudly, but of course didn’t realize that that is one of the big problems of group selection. Not only is the turnover of individuals within groups faster than the turnover of groups themselves (via splitting and extinction), but once you have a group of all altruists, it’s unstable to the invasion of selfish individuals who gain but do not give. One selfish person in an altruistic group will begin breeding like rabbits compared to the others. It’s thus quite problematic to assert that some many aspects of human behavior and morphology evolved by selection among groups rather than among individuals. If you want to read a comprehensive critique of the problems with group selection, you couldn’t do better than Steve Pinker’s Edge piece, “The false allure of group selection.

Pinker’s essay lays out far better than I could the problems with group selection, including the fact that there’s no evidence for it playing a role in the evolution of a single biological trait (I hold out sexual reproduction as a possible exception). The unfortunate situation is that Wilson is the best known evolutionary biologist alive, and has won two Pulitzer Prizes. When he speaks, people listen, and when he extolls group selection, the layperson believes him. They don’t know the problems with Wilson’s Big Hypothesis.

I’m not sure why Wilson, at the end of his career, has fixed his colors to the leaky vessel H. M. S. Group Selection. I’ve heard some of his colleagues give explanations, but I won’t repeat that gossip. It’s just sad that a man who became famous for having so many good ideas is chaining himself to a very bad one to ensure his legacy. But his legacy was assured a long time ago, and will only be tarnished by his tenacious clinging to group selection.

One other error in the interview, this time made by Wilson himself when discussing the opponents to his view of human sociobiology (now called “evolutionary psychology”):

Sociobiology got a book review on the front page of The New York Times. I think — well, I know — that some very small number of professors at Harvard, in my own department, were upset, because they thought that theories they were working on were the kind that should get recognition.

Wilson is wrong here. He’s referring, of course, to Steve Gould and Dick Lewontin. I knew both of them, for Dick was my advisor and Gould was on my thesis committee, and I never got any inkling that they objected to sociobiology because it dimmed their own professional lights. That’s an uncharitable statement, and not true. Lewontin and Gould fought against sociobiology (along with a lot of other students who then had no lights to dim) because they were ideologically opposed to it: they were pretty much blank-slaters and opposed to biological determinism, thinking that sociobiology would somehow justify a hierarchy of races and sexes and buttress the status quo. I heard Dick and Steve talk about this many times, and also knew Dick very well—certainly well enough to know that the man didn’t have a jealous bone in his body. Steve was more ambitious for public acclaim, but even so I don’t see him going after Wilson because he was jealous.

But what is true is Wilson’s claim that he won the sociobiology debate. In the end, people have accepted sociobiology for many species, and even in humans the discipline of evolutionary psychology is well established, though sometimes prone to exude weak papers.

And the good stuff in the interview. I like how Wilson says people should get into biology:

Q. What are some questions that scientists today should be asking but aren’t asking? What’s causing our blind spots: Funding? Overspecialization? Politics?

A. You’re asking me an impossibly large question. Let me make one suggestion, and maybe that’ll lead to another.

I am unhappy about STEM. That is, I’m unhappy about how it’s presented as the principal portal for careers in science and technology. Young people — in some cases, young enough to be as far back as grammar school — are presented with this intellectual triathlon in order to go into science and technology.

There’s no question that we need all the ablest people that can be recruited to go into science and technology to keep this country strong. But STEM is an unnecessarily forbidding set of stairs.

Consider a young person who’s thrilled by seeing a natural system, a remarkable geological formation that stirs the imagination, or a group of animals or plants. This youngster says, Boy, when I get to college, I would like to move on to a career in science, and biology especially. Now, the STEM-oriented teacher — if we are following the STEM ideology as we hear it — says: “I think that’s a good ambition. But remember that biology is based substantially upon chemistry. So, I advise you to start getting a good background in chemistry. Oh, and while you’re at it, you should keep in mind that chemistry is based upon, to a major degree, principles of physics. So consider starting to get a background in physics, too. And, oh, I almost forgot: To get into physics, and a lot of the best parts of chemistry, you’re going to need ‘M,’ mathematics. So I want you to get started on math courses right now.”

Now, I’m going to say something startling. And I’m going to get myself in trouble. But heck, that’s why you’re here.

Q. Yes.

A. And I’m going to say: Nonsense!

The right way to create a young scientist who’s going to be on fire by the time they’re in college is to let them pick something, some subject, that has really excited them. If they dream of space exploration, if they dream of curing a cancer, if they dream of going to distant jungles and discovering new species — whatever their dream is, let them dream.

Indeed: let them dream! And give them the resources to fulfill their dream!

While I don’t think that science is going to claim hegemony over art, literature, and all the humanities, I also like Ed’s discussion about how consideration of animal perception and consciousness might give art and literature a shot in the arm. This is the kind of poetry that I admire in Wilson’s writing. Here’s his discussion how an infusion of science in the creative arts could create A Great Leap Forward:

Let me give an example. A female moth comes out from the pupa. She’s got to mate. She releases a sex-attraction pheromone that’s carried downwind. In some moths, that pheromone can go downwind for kilometers. The males pick up on it and head upwind. In some species they start flying zigzag.

Imagine those puffs and ellipses of odor: spreading and dying away, spreading and dying away. If you could visualize all of that and walk into nature, you would see an entirely different picture. On the ground, the smallest of the creatures finding one another. Prey. Rival males. Females. A constant maelstrom of chemical communication.

Humans don’t have the capacity to understand the chemical communication going on around us that makes up the real world. We are dumb to that, or anosmic.

But the other thing is that we can’t see beyond a tiny fraction of the electromagnetic spectrum. Other organisms can see ultraviolet, or the infrared on the spectrum. Here is a whole opportunity in the humanities. It would be interesting if you could create the optical world of a spider or a bird, and show the world what would be seen or heard by them. You’d be painting an entirely different landscape. You could have a cottonmouth landscape, or a timber rattlesnake landscape. It would be nice to have a gallery of visual representations with the electromagnetic spectrum shifted over, from the point of view of a butterfly or an ant, translated into our narrow human sphere of perception so that we can see what they feel or see.

The humanities should not tolerate limits on themselves. There are so many exciting things to be done with the arts.

I don’t share Wilson’s optimism here, but I like the approach. Still, I don’t think it will replace anthropocentric art and literature.

Finally, Ed emphasizes the importance of collections in museums and—something I especially mourn—the loss of taxonomists and other specialists on groups of organisms. Take Drosophila, for example: perhaps the most studied group from an evolutionary-genetic point of view. If you’re studying biodiversity and speciation in that group, as I have, it’s crucial to have specialists who can help identify and place new species. Yet I can think of only about two Drosophila taxonomists on the planet. There’s no professional acclaim or recognition for such work, which is a damn shame given its importance. You can’t catalogue biodiversity without such people, and biodiversity is something we really need to understand now.

More scientific puffery at The New Yorker

April 6, 2019 • 12:30 pm

I’ve often carped about the New Yorker‘s science writing (see here and here, for instance), something that became a pet peeve when it published Siddhartha Mukherjee’s wonky ideas about epigenetics and then refused to correct them after many famous geneticists called it to their attention.   After I was getting tired of its attempt to wrap every subject in baroque and orotund prose, including science, I finally gave up my subscription when its self-important editor, David Remnick, caved in to public pressure and disinvited Steve Bannon from the New Yorker Festival (writer Malcolm Gladwell dissented). The magazine was also becoming increasingly Woke, as its target audience, rich Leftists, wanted the rag to flaunt more virtue.

But I still have a stack of back issues, and have been working my way through them, feeling most of the time that canceling my subscription was the right thing to do. For one thing, I can read a lot more books.  On the plane to Amsterdam, I read the January 14 issue, which included this article by Jerome Groopman, a staff writer and physician. It’s a review of a new book, Nine Pints: A Journey Through the Money, Medicine, and Mysteries of Blood, by Rose George, which describes the history of research on blood, starting with ancient mythology through the first transfusions and on to modern knowledge. The book sounds good, but Groopman has to trick out his review, à la New Yorker style, with irrelevant flourishes. You can read the article, which does contain some fascinating facts, by clicking on the link below.

Perhaps I’m being captious here, but after reading the article, a piece that recounts some good history of science and interesting medical facts (the account of Harvey’s discovery of blood circulation is fascinating), it winds up saying that the Big Mystery of Blood remains. Yet what that “profound mystery” actually is is never elucidated.

Groopman begins with a literary flourish, referring to Leviticus:

During my training as a hematologist at U.C.L.A., forty years ago, a senior faculty member introduced the program of study by citing a verse from Leviticus: “The life of the flesh is in the blood.” For the assembled young physicians, this was a biological truth. Red cells carry oxygen, required for our heart to beat and our brain to function. White cells defend us against invasion by lethal pathogens. Platelets and proteins in plasma form clots that can prevent fatal hemorrhages. Blood is constantly being renewed by stem cells in our bone marrow: red cells turn over every few months, platelets and most white cells every few days. Since marrow stem cells spawn every kind of blood cell, they can, when transplanted, restore life to a dying host.

. . . and, in a literary trope of circularity, Groopman also ends his piece with Leviticus. But what on earth is the “oldest, most profound mystery of blood.” Groopman’s last sentence, which says that “the life of the flesh” could also mean “the soul of the flesh” in Hebrew, doesn’t clarify things a bit.

Last month, in San Diego, the American Society of Hematology had its annual meeting. The program featured new discoveries about blood’s biology and accounts of recent advances in patient treatments—including an alternative to chemotherapy for one of the most common and incurable forms of leukemia. But, even as the field probes ever more deeply into the ways that blood serves living tissues, my colleagues and I are no closer to unravelling the oldest, most profound mystery of blood. In the verse from Leviticus, the word nefesh, translated as “life,” also means soul.

This is an example of how not to write popular science: ending with a claim that The Big Mystery Still Remains. This is how the magazine’s penchant for the humanities at the expense for science actually corrupts the science in an almost metaphysical direction. For how else can you interpret “the oldest, most profound mystery of blood”? Clearly, science will not suffice.


As an addendum, here’s how Groopman (and the New Yorker itself) often present the Jesus myth as if it were literally true, with no doubt cast upon it:

Yet, despite the firm proscription against ingesting blood, one breakaway Jewish sect of the first century A.D. made the idea of doing so central to its rituals. Its leader, Jesus of Nazareth, told his disciples that the bread and the wine at the Last Supper were his body and blood, and should be consumed thereafter in memory of him. The ritual of the Eucharist became a cornerstone of early Christianity, and with it the doctrine of transubstantiation—that a literal, not just figurative, transformation occurred during the sacrament.

Here we see the credulous acceptance that Jesus of Nazareth not only existed, but was leader of a Jewish sect, as well as the implication that the Last Supper really did happen. Where is the “reportedly” that should occur at least twice in this paragraph?

Once again: Why sex is binary

December 11, 2018 • 12:30 pm

Over at Medium, Alex Byrne, who happens to be a professor of philosophy, and chair of the Department of Linguistics and Philosophy at the Massachusetts Institute of Technology (MIT) has written an article criticizing Anne-Fausto Sterling’s NYT Op-Ed, “Why Sex is not binary.” Click on the screenshot below to see Byrne’s take, which is pretty sensible.

I also criticized the NYT article, as did psychologist Debra Soh.  My own criticism concluded that sex—defined as either “male” or “female”, each of which has a correlated suite of primary and secondary sexual traits connected with (and the evolutionary result of) the production of large or small gametes—is pretty much binary, and certainly strongly bimodal, with only a very small fraction of people who don’t fit neatly in the slots. For all practical purposes, sex is a binary, and it should be, since evolution produced (in most animals) two sexes that must mate to produce offspring. If you’re neither, or an intermediate, you don’t leave offspring and you don’t leave your genes.

Gender, on the other hand, is perhaps a bit less binary, as there are more people who identify as either an intermediate, something else, or a sex that wasn’t their birth sex. But gender, too, is bimodal.

The shameful part of all this is that the scientific journal Nature, as well as three evolutionary biology/ecology societies, who should know better, made statements or editorials that neither sex nor gender are binary. That’s a flat-out abnegation of both their responsibility and of science itself. Evolution itself produces a binary of sex! To be anthropomorphic, evolution wants a binary of sex.

Why, then, do people harp on the non-binary nature of sex? It’s clear: because if they see sex as a spectrum, then that supposed continuum will help eliminate discrimination against transgender people (who still, I should add, adhere to one biological sex or another) or against those rare intermediate folks who don’t fall into the sex binary. But, as Byrne points out, you don’t need to twist biology to construct a caring and inclusive morality. But have a read:

Byrne’s definition of “sex,” which leads to his binary, is that of Simone de Beauvoir herself in The Second Sex, one of the founding documents of modern feminism:  the sexes “are basically defined by the gametes they produce.” Big gametes = female, small gametes = male; these are, in our species, eggs and sperm, respectively.

But what about those who produce no gametes? Well, Byrne, being a philosopher, has already thought of that:

There is a complication. Females and males might not produce gametes for a variety of reasons. A baby boy is male, despite the fact that sperm production is far in his future (or even if he dies in infancy), and a post-menopausal woman does not cease to be female simply because she no longer produces viable eggs. Female worker honeybees are usually incapable of producing eggs because their ovarian development has been inhibited by chemicals secreted by the queen. (In one species of bee, the female workers are all permanently sterile, even in queenless colonies.)

In the light of these examples, it is more accurate (albeit not completely accurate) to say that females are the ones who have advanced some distance down the developmental pathway that results in the production of large gametes — ovarian differentiation has occurred, at least to some extent. Similarly, males are the ones who have advanced some distance down the developmental pathway that results in the production of small gametes. Definitions in biology are never perfectly precise, and these are no exception. Still, they give us some traction in examining whether there are any humans who are neither female nor male.

He concludes that yes, there are some intersex conditions, but also that, arguably, “there are no clear and uncontroversial examples of humans who are neither male nor female”. By that that he also means that there are no humans who are both male and female, though I’d think that if there are true hermaphrodites and intersexes—which there appear to be—those would qualify.

But it doesn’t matter. If you adhere to the gamete-based definition used by most biologists, sex is effectively binary. In his footnote #2, Byrne argues that intersex individuals have a frequency of 0.015%, or about 1 individual in 6700. That would be the number of individuals falling in the “valley” between the male and female frequency peaks, making sex almost a pure binary.  And that frequency, or even the 1% touted by Fausto-Sterling, neither effaces the binary nor should have any bearing on how we treat transgender or intersex individuals.

That’s the main point here, and one that Byrne emphasizes. I can’t say this too often: you should not base human rights on biological facts, for then those rights become susceptible to changes in scientific thinking. Of course some morality must be informed by biology (abortion is one example), but whether or not a class of people should be afforded equal treatment and equal opportunities should have nothing to do with biological differences. If you think otherwise—if you think that sexes and ethnic groups must be equal in all respects, genetically, behaviorally, in brain structure, and so on, because otherwise we succumb to sexism and bigotry—then you’re leaving yourself wide open to the finding of differences that would undermine your scientific claims, and hence your biologically-based morality.

And so Byrne, as a philosopher, points out the obvious (my emphasis below to make it even more obvious):

That sex is not binary is evidently something that many progressives dearly wish to believe, but a philosophically sound case for treating everyone with dignity and respect has absolutely no need of it. People with intersex conditions have historically been subject to ethically dubious genital surgery as children, or deceived about their medical status by (usually well-meaning) doctors. It would be a huge mistake to think that such surgery is unjustified because the patients fall outside the binary, and so should not be surgically fashioned to appear to be within it. The main arguments against surgery (there are risks with little compensating benefit, and patients are too young to consent) have nothing to do with whether the patients are female, male, both, or neither.

Further, the issue of whether sex is binary, although of academic interest, is of no relevance to current debates about transsexuality and the changing models for treating gender dysphoria. To those struggling with gender identity issues, it might seem liberating and uplifting to be told that biological sex in humans is a glorious rainbow, rather than a square conservatively divided into pink and blue halves. But this feel-good approach is little better than deceiving intersex patients: respect for autonomy demands honesty. And finally, if those advocating for transgender people (or anyone else) rest their case on shaky interpretations of biology, this will ultimately only give succor to their enemies.

As a (former) scientist, it’s distressing to me to see my fellow progressive scientists twist and deform biology out of all recognition so that it buttresses their ideology. We don’t need to do that. Our ideology is a good one—much preferable to discriminating against groups based on (supposed) biological differences—but we should ground it in reason, not biology. And the reason is simple, recognized long before biology became a discipline: we should, in a good and caring society, treat all people as we would wish to be treated were we in their position. (This reciprocity is embodied in the ethical philosophy of John Rawls.)

Of course the Authoritarian Left will demonize people like Byrne (I can already anticipate him being called a “transphobe”), and it’s not pleasant for me to criticize the Society for the Study of Evolution, of which I was once President, for distorting biology in the interest of social justice. I share their goals, but as a biologist I don’t share the “scientific” assertions cooked up to buttress those goals.

Wary of all this, Byrne put this on his MIT webpage:

h/t: Cesar

The journal Nature conflates sex and gender, decries “pigeonholing” people even though we do—and must

November 29, 2018 • 11:30 am

Lots of sites, including three scientific societies, have rejected the new Health and Human Services guidelines that provide a classification of a person’s sex into two categories. But these sites, and now an article in the prestigious journal Nature (click on screenshot below), conflate “sex”—which I take as biological sex recognized in humans by chromosomal constitution, which gametes you produce, and secondary sex characteristics—with “gender”, which I take as “the sex that an individual identifies with, whether or not it corresponds to their biological sex”. In this construal, which seems to make biological sense, a transgender woman would be a biological male but their gender would be female. There are also genders that aren’t “male” or “female”, as I note below.

Now the editorials that have appeared in scientific journals are well-meaning: their intent is to prevent intersexes and transgender individuals (the former much rarer than the latter) from discrimination. But that can be done without conflating sex and gender. For some purposes, like sports, recognizing an individual as either “male” or “female” (or “intersex”) is not only useful, but necessary.

As far as I can see, the Trump administration’s proposal, which may indeed be motivated by a desire to discriminate against intersexes or “non-binary” genders, is a definition not of gender but sex, at least as reported by the New York Times:

“Sex means a person’s status as male or female based on immutable biological traits identifiable by or before birth,” the department proposed in the memo, which was drafted and has been circulating since last spring. “The sex listed on a person’s birth certificate, as originally issued, shall constitute definitive proof of a person’s sex unless rebutted by reliable genetic evidence.”

The new definition would essentially eradicate federal recognition of the estimated 1.4 million Americans who have opted to recognize themselves — surgically or otherwise — as a gender other than the one they were born into.

But sex and gender are not equivalent, and if the Trump administration wants to equate them, it’s making a serious mistake and hurting people as well. Still, scientific societies do themselves (or progressivism) no favor by the constant conflation of sex and gender. Sex is a useful concept whose binary nature has served biology well for centuries.

As I’ve written before, while sex is not completely binary, in general it’s effectively so, for the vast majority of individuals can be classified as either “male” or “female”. And this dichotomy is the result of evolution, in which two sexes are the result of natural selection, while those rare individuals who are intersex result from genetic or developmental anomalies. A paper by Dr. Leonard Sax in Journal of Sex Research gives this clinical definition of “intersex”, that is, of individuals who fit in the nonbinary valley between the big frequency modes of “male” and “female”:

A more comprehensive, yet still clinically useful definition of intersex would include those conditions in which (a) the phenotype is not classifiable as either male or female, or (b) chromosomal sex is inconsistent with phenotypic sex.

Using this definition, Sax estimates that 0.018%, or 18 individuals out of 100,000, are intersex. This is much lower than Anne Fausto-Sterling’s estimate of 1.7%, which includes many individuals who don’t fit the definition above. But it doesn’t matter. Under either construal sex is binary, or nearly so. Saying that sex is a “continuum” is palpably misleading (if technically correct), for the “continuum” includes at most 1.7% of all individuals between the two well-defined “binary” modes. As a biologist colleague of mine said, “Of course sex is binary.  No biologist in their right mind would question that.” 

The same might be largely true, though less true, for transgender individuals, estimated at about 0.6% of the U.S. population. But that figure doesn’t include individuals who identify as bisexual, polysexual, and so on, so the bimodality for gender may be a bit less pronounced than for sex.

At any rate, Nature shoots itself in the foot with this well-intentioned editorial that maintains that sex is not a binary concept (they don’t mention sex in the title but it’s in the text):

First, Nature estimates, without giving a source, that the frequency of people with “differences or disorders of sex development” can be as many as 1%, though these aren’t intersexes, nor blur the strong bimodality of sex. Most of these aren’t people who would be the subject of oppression or discrimination.

Worse, Nature conflates gender and sex several times, to wit:

The proposal — on which HHS officials have refused to comment — is a terrible idea that should be killed off. It has no foundation in science and would undo decades of progress on understanding sex — a classification based on internal and external bodily characteristics — and gender, a social construct related to biological differences but also rooted in culture, societal norms and individual behaviour.

We do understand sex, and it’s for all practical purposes binary in most animal species, and certainly ours. Here’s another of Nature‘s conflations:

Political attempts to pigeonhole people have nothing to do with science and everything to do with stripping away rights and recognition from those whose identity does not correspond with outdated ideas of sex and gender.

Outdated ideas of sex? What are the updated ideas of sex? Is Nature rejecting the ideas of male and female based on the existence of biological anomalies or intersexes? If so, are they rejecting, for similar reasons, the ideas of male and females in deer, fruit flies, and most other animals?

Yes, ideas of gender may be outdated—we now know well that someone’s self-identity may not correspond to their biological sex—but not of sex. Please, Nature, stop distorting biology in the service of ideology. It’s neither seemly nor necessary, as we can protect transgender and intersexual individuals without deep-sixing the sexual binary that has served biology so well.

As for the practice of pigeonholing people being useless and having nothing to do with science and everything to do with oppression, surely Nature doesn’t really mean that. For one thing, pigeonholing by sex is necessary in two important cases: Title IX regulations, in which it’s illegal to discriminate against programs funding college education (including sports) on the basis of sex. To enforce that regulation, which is a good one based on civil rights, you have to recognize women’s opportunities and sports teams versus men’s. Individuals have to be pigeonholed, and there must be some guidelines. 

Pigeonholing is also important for sports, as in professional sports teams or the Olympics, where competitions involve either male teams or female teams, usually playing against same-sex teams. Without “pigeonholing” you simply have a mess. Does Nature advocate doing away with “men’s” and “women’s” teams? If not, then they recognize the usefulness of pigeonholing, and clearly must go along with some standard, even if it’s a somewhat arbitrary one. (How to define “male” and “female” in sports is a sticky issue, one that is above my pay grade.)

Second, does Nature oppose pigeonholing by ethnicity? Surely they don’t: they recognize the value of classifying individuals by ethnic backgrounds for the purpose of achieving either equal opportunity or equal outcome. In such cases “pigeonholing” on political grounds is generally salubrious, and certainly does not strip away people’s rights in the way the journal suggests above.

In the end, we progressives don’t need to distort biology to achieve our aims of treating people fairly. We don’t need to pretend that the idea of two distinct sexes in our species is “outdated.” It isn’t, and when Nature tries to pretend it is, they simply look silly.


This year’s Physiology or Medicine Nobel goes to two cancer researchers (and a contest)

October 1, 2018 • 8:15 am

Here’s the video announcing today’s Nobel Prize, awarded to James P. Allison, an American who works at the M.D. Anderson Cancer Center, and Tasuko Honjo, a Japanese immunologist at Kyoto University, for the discovery of ways to cöopt the human immune system to attack cancer cells.  (See announcement and press release here).

Here are the winners, and the long announcement is below:

James P. Allison
Tasuko Honjo


I thought that some CRISPR workers would win the prize this year, but I suppose that a.) it needs to be proven to work in humans given that the prize is for work relevant to our own species, and b.) there are several contenders, more than the three allowed to share a prize.

We’ll also have a contest, which is open until 5 a.m. tomorrow. Please post below your guesses for the winners in these TWO categories for 2018:

  • Chemistry
  • Physics
  • Literature NOTE: Literature prize not awarded this year.

The science prizes may be shared, but you will be counted as “correct” if you give a single winner in the group. But if you give an incorrect name among several winners, that won’t be counted as a correct answer.  The first person to get a correct answer in all three categories will win an autographed copy of my book (either trade book of your choice), with a Nobel cat drawn inside. Last year, as I recall, there were no winners. The literature category is always hard! However, that category is not being filled in 2018 because of a sexual assault scandal.