Nominally flawless

Apparently, I am in perfect health, a veritable Greek god, perfect in every way. Except…I had to point out to my doctor that I have these terrible flare-ups of joint problems. Just the week before my physical, I had been painfully crippled by inflammation of my Achilles tendon — suddenly, with no warning or precipitating injury, my ankle was swelling up in all kinds of strange lumps and bulges, and I was scarcely able to walk.

This hits me fairly often, I can count on being incapacitated at least once a semester with this nonsense (note that, as a professor, “incapacitated” means still having to hobble in and teach, no matter how much physical agony I’m experiencing.)

This was not a good thing. It’s not what I would call healthy at all.

I complain every time I visit the doctor, but it’s one of those things that will fade away with equal suddenness, so it’s hard to treat. At this last physical, I pushed a little harder, and the doctor decided that we need to do more to get a diagnosis. I went into the blood lab and yielded a quart or two so they can carry out more extensive tests.

All week now, new test results have dribbled into my mailbox. All the usual stuff, like blood pressure, cholesterol levels, a full metabolism panel, etc., etc., etc. are in the perfect range. Uric acid, serum creatine, etc., all good. Thyroid hormones, 5×5. Because I’ve been out in the wilderness more during the summers, they tested for Lyme disease, West Nile, and a whole suite of exotic tick-borne antigens…nope.

If you just go by the numbers, I am like unto Apollo, beautiful and flawless. I don’t think anyone will be sculpting my form, though, and I’m going to remember this when the field season starts up again and my knee swells up like a balloon, again.

(I’ve got it good, though, compared to my daughter Skatje who dislocated her knee on a skiing trip a few weeks ago. Her imminent fate is “Left knee MPFL reconstruction and tibial tubercle osteotomy, open reduction internal fixation of osteochondral fragment from patella dislocation,” in doctorese. It could be worse.)

It almost makes me believe in karma

There were two tragic deaths in Fresno a few days ago.

Jason Phillips, the other half of the Proud Boys associated January 6th Capitol rioter duo called Oreo Express, is dead after drinking and driving for Saint Patrick’s Day and crashing a Tesla. He and his passenger, who also died, weren’t wearing seatbelts.

The details from the news:

Two Fresno men who died in a crash involving a Tesla were identified Tuesday by the Fresno County Corner’s Office.

Jason Phillips, 24, who officers said they believed to have been the driver, and Chase McCutcheon, 32, were in a Tesla Model 3 about 1:45 a.m. Monday when the vehicle collided with more than one guardrail, the coroner’s office said.

The California Highway Patrol said the fatal crash happened on Copper Avenue as the Tesla headed west approaching a shift in the road near Willow Avenue.

The driver failed to traverse the shifting road at “a high rate of speed” and hit the curb, a guardrail and a street sign before the Tesla overturned, CHP said.

The car continued into another curb and guardrail, CHP said.
Neither Phillips nor McCutcheon were wearing seatbelts and were ejected during the crash, CHP said. Both were pronounced dead at the scene.

Let’s see…driving drunk at excessive speed with no seatbelts? I don’t believe in karma, but I do believe that humans can be incredibly stupid.

Apparently, the Tesla did not catch fire.

The Kushner Plan

There is chaos in Gaza — people are starving, they’re being bombed and shot, and the US has so far been disgustingly passive about it all. We need positive ideas and new tactics to change the situation, so let’s get advice from…Donald Trump’s son-in-law? I admit, Jared Kushner is looking at Israel through a different lens.

His remarks at Harvard gave a hint of the kind of Middle East policy that could be pursued in the event that Trump returns to the White House, including a search for a normalisation deal between Saudi Arabia and Israel.

Gaza’s waterfront property could be very valuable … if people would focus on building up livelihoods, Kushner told his interviewer, the faculty chair of the Middle East Initiative, Prof Tarek Masoud. Kushner also lamented all the money that had gone into the territory’s tunnel network and munitions instead of education and innovation.

It’s a little bit of an unfortunate situation there, but from Israel’s perspective I would do my best to move the people out and then clean it up, Kushner said. But I don’t think that Israel has stated that they don’t want the people to move back there afterwards.

Masoud replied that there was “a lot to talk about there”.

Jesus. Exactly what you’d expect from a developer and slumlord — every piece of land is a property to be seized and exploited. Gaza is a chunk of ocean front without casinos and high rise hotels, let’s fix it!

He doesn’t seem to have put much thought into the people who live there. You know, the ones who had other things to do with their money than pay out exorbitant rents to a landlord.

Kushner also said he thinks Israel should move civilians from Gaza to the Negev desert in southern Israel.

He said that if he were in charge of Israel his number one priority would be getting civilians out of the southern city of Rafah, and that with diplomacy it could be possible to get them into Egypt.

But in addition to that, I would just bulldoze something in the Negev, I would try to move people in there, he said. I think that’s a better option, so you can go in and finish the job.

He reiterated the point a little later, saying: I do think right now opening up the Negev, creating a secure area there, moving the civilians out, and then going in and finishing the job would be the right move.

Finish the job? Finish what job? The extermination of the Palestinians? Sure, just bulldoze a patch of desert and move them there. This is insane.

I’m sitting in Miami Beach right now, Kushner said. And I’m looking at the situation and I’m thinking: what would I do if I was there?

I’m thinking: why the hell was Jared Fucking Kushner, that incompetent hack, invited to Harvard to opine on Israel?

Endocrine disruptors — you’re soaking in them

A human embryo at the 4th week of development is just a tiny bean with a length measured in millimeters, but at this time all kinds of remarkable features are starting to develop. This week in class I talked about urogenital development, which involves forming an array of incredibly delicate, thin tubes from a structure called the urogenital ridge, a thickening of an embryonic membrane which will eventually form a succession of kidneys, the pronephros, mesonephros, and metanephros, only the last persisting into adulthood. The key feature for the story I was telling, though, is that they formed something called the mesonephric duct, and then the paramesonephric duct which parallels it. Another name for the mesonephric duct is the Wolffian duct, and the paramesonephric duct is called the Müllerian duct (personally, I don’t care for the self-serving names given to critical bits of the developing embryo by 19th century men, but it’s what still persists in the embryo. So it goes.)

Both of these ducts are associated with the bipotential or indifferent gonad. There are no sexual differences in embryos this young.

The sex differences emerge later, in response to differential signals. The Müllerian ducts degenerate in males, while the Wolffian ducts persist. In females, the Müllerian ducts persist, while the Wolffian ducts fade away. The bipotential gonad associates with the remaining duct and differentiates into testes or ovaries.

I’ll refrain from delving deeper into the details. My point is that these minuscule ducts and tissues form very early, and are going to expand to form critical, elaborate structures necessary for human fertility. They’re fragile. You really don’t want to perturb the signals and processes going on in a one month old embryo, especially since you may not see the consequences for 15 or 20 years.

In 1941, pharmaceutical companies started to market a synthetic drug with properties similar to estrogen, called diethylstilbesterol, or DES. It wasn’t patented, so anyone could make and sell it, and they pushed it hard to pregnant women. There was weak evidence that it could help sustain pregnancies in women with low progesterone levels, so sure, let’s market it as “routine prophylaxis in ALL pregnancies.” About 4 million pregnant women took this stuff at the suggestion of their doctors, between 1941 and 1971, when it was finally banned.

Think about that. This was an endocrine disruptor, term that wasn’t invented until the 1990s, but everyone knew then that it would have some kind of effect, since it was a functional analog of estrogen. So they gave it to pregnant women, and by that means delivered a potent hormonal signal to their embryos at a time when they were carefully assembling those delicate little tubes. Worse, they knew that high doses given to mice and hamsters caused mammary, cervical, vaginal, and uterine cancers in adult females, and that adult males developed lung cancers, which ought to have set off all kinds of alarm bells. Any tissue that was sensitive to estrogen could be provoked to turn cancerous with DES.

Just for dessert, it was determined in 1953 that DES did nothing to maintain at risk pregnancies. They continued to prescribe the stuff. Just in case, you know.

For additional profit, they also marketed it as a growth hormone for livestock. That continued until it was eventually banned for that purpose in 1979.

Here’s the structure of this potent little molecule.

A is DES; B is estrogen; C is BPA, the common, heavily used plasticizer that we now know is an endocrine disruptor.

You might be wondering what happened to those 4 million women who took the drug. They were fine! Humans and other primates seem to be more resistant to the carcinogenic effects of DES, and they were taking much lower doses than those poor rodents in testing labs who were given massive doses of the drug.

And what about the millions of boomer babies who were doped with it in utero? Again, mostly fine — this is the thing about endocrine disruptors, they tend not to have the gross teratogenic effects we associate with chemicals that cause significant birth defects, like thalidomide. They’re more subtle. They perturb the balance of internal organ systems, and in this case, cause problems in the physiology of reproductive organs, which may lead to fertility issues or some kinds of cancers. I emphasize may because I know DES-exposed people who have had children and are cancer-free; it’s more a matter of letting their gynecologists know to keep an eye on potential warning signs.

But it can go very wrong.

DES is still used in experimental studies because it’s such an interesting molecule. Regular readers probably know about the importance of Hox genes; these are genes expressed along the body axis in pretty much all animals that defined anterior-posterior structures. The same genes also get re-expressed to define the proximal-distal axis of the tetrapod limb. They seem to be a handy-dandy molecular tool for establishing tissue identities along a line.

Here’s another instance of Hox genes defining position on an organ: they’re re-expressed in the Müllerian ducts, which become the fallopian tubes of adult women.

Hoxa9 is expressed throughout the oviduct, Hoxa13 in only the cervix, and Hoxa11 and Hoxa10 in between, forming a kind of positional coding system. This is really neat! I like finding examples of molecular recycling in the evolution of developing systems.

What isn’t so neat is that DES downregulates Hoxa10 by inhibiting an important signaling molecule, Wnt7a, creating coding ambiguities in the structure of that delicate little tube. That leads to poor cell specification and disorganized tissue, erasing what should be clear, sharp boundaries in the organ, which may then be expressed in dysplasias, increasing the odds of cancer.

As if that weren’t enough, we don’t really know what perturbing these signaling pathways does to other developing organs, like the brain. Also, DES affects methylation/demethylation of the genome, so it may have transgenerational effects — pregnant women who took DES may have messed up their children, but there is some evidence (weak, I think) that it also affects their grandchildren.

But wait! It’s banned, so we shouldn’t have to worry about it anymore! That’s partly true, but look at the diagram of the molecules above. Estrogen and DES share similarities to another molecule, bisphenol A, a ubiquitous plasticizer used to make plastic materials less brittle. BPA is found in your food packaging. It lines the interior of aluminum cans. Any plastic you have that is at all flexible has been treated with plasticizers, like BPA or phthalates. It’s leaching into your food and your general environment, and it does not go away. The US has banned its use in baby bottles and baby formula packaging, but not from all your snack food packages and your phones.

If you’re of a certain age, you might recall those commercials for a dishwashing detergent that announced, “you’re soaking in it!“, as if that meant the stuff must be safe. We ought to be aware that capitalist industries have us all soaking in a gentle bath of toxic chemicals right now, and it’s not safe.

The end is here! Again!

Spring break is over. I’m heading back to the classroom this morning.

What makes it all sting a little more than usual is that my restful week off was really just a brief interruption in the middle of the semester. I’m only half way through! I should be glad of the reprieve, but today I have to deal with the stress of resuming where I left off.

Oh well. I also spent the last couple of days setting up all of my classes. I’m all ready to go with a lecture on endocrine disruptors, specifically DES and BPA, which at least are interesting. I’ve got so much material here that I’m going to be talking about endocrine disruptors for the next two weeks.

Will Knowland knows nothing

Will Knowland was a teacher at Eton who was dismissed for making a video claiming that patriarchy was good after being told not to — I’m not keen on the idea of firing someone for expressing an opinion, but I do think it’s reasonable to fire teachers for ignorance and incompetence. Knowland has gone on to make more videos to demonstrate just how stupid he is. He has chosen to claim that evolution is false. Big mistake. Especially since his arguments are pathetic.

I have the transcript. Let’s see how big a dumbass Will Knowland is.

here are eight things about Evolution that I wasn’t taught in school

Correct. He wasn’t taught the following things in school because they are wrong.

0:05 number one because Free Will is real and humans are rational any materialistic account of our Origins is certainly false this means darwinian materialistic evolution is and that’s why people who hold that worldview end up denying human rationality and Free Will including their own the two stand or fall together

I think free will arguments are all bad, no matter what side you take, so I’m not going to touch that one. The argument about rationaility, though, I think, is already refuted, because his claims are all irrational. Humans aren’t particularly rational — we’re all creatures of emotion and bias, and I note that Knowland fails to provide any supporting evidence or arguments otherwise. It’s an assertion with no rational support.

It’s also false to claim that science and evolution, specifically, require the rejection of rationality.

0:32 number two the oldest rocks on Earth date from 3.8 to 3.98 billion years ago but life was present 3.81 billion years ago so life had only 100 to 170 million years to evolve that is an instant a blink of the eye in evolutionary time

Remember that: 100 to 170 million is a blink of the eye. I’m inclined to think that 100 million years is an incredibly long time — lots can happen in a million years or a thousand. The origin of life was a process of chemical evolution. How many chemical reactions can occur in that span of time?

0:58 number three there’s no evidence for concentrated organic pools on early Earth no empirical evidence whatsoever and without a blueprint to direct it and convert it raw energy isn’t usable anyway but since these are only produced by life this is the Catch-22 and don’t say life came from space that just pushes the problem one step back where did it begin if it came from space

How concentrated is concentrated? Is he claiming to be a quantitative organic chemist now?

The best models for the origin of life now suggest it arose in deep-sea volcanic vents, which are rich in the precursors for organic molecules, and also provide the energy necessary for the reactions to produce them. Right now, electrons are being shuffled across inorganic substrates, reducing compounds and creating the building blocks of life without “blueprints.” It’s all chemistry. All of life is chemistry.

OK, I won’t say life came from space. That’s just bullshit anyway. Why does Knowland feel the need to put bogus arguments into his critics’ mouths?

1:33 number four there are millions of transitional forms organisms observable across successive Generations appear fully formed they have no ancestors or Bridges and they don’t change and don’t say punctuated equilibrium that is empirically equivalent to creationism

At least he admits that there are many transitional forms, but it’s weird that he then claims they can have no ancestors. All organisms are functional, or they wouldn’t exist. Evolution is all about changes from one fully functional organism to a different fully functional organism by small successive variations. We’d be very surprised to discover a species that arose from a non-viable population of incomplete organisms.

Again, he puts a bogus argument in our mouths. Punctuated equilibrium is about rates of change in subsets of a population. It’s not a version of creationism. Eldredge and Gould would be very surprised to be told that they have invented a creationist theory.

1:57 number five some structures require the whole structure to be in place to be functional imagine having one tenth of an eye or one one hundredth of a heart or one one thousandth of a penis

Most birds, to name one counter-example. Most birds (excepting ducks, obviously) lack a penis and mate by cloacal kissing. Clearly you don’t need a whole massive 3mm long penis to successfully reproduce, as he should know since he has 7 children.

Similarly, we evolved from organisms that have little more than a muscular tube for a heart and an open circulatory system, or that have only an eyespot that can only sense light and dark. We have a plethora of examples of simpler hearts, eyes, and reproductive organs that are entirely functional.

2:19 number six there are built-in limits to genetic material Darwin thought natural selection worked a bit like dog breeding but humans can’t make a dog the size of an ant or a whale and we definitely can’t create a new species out of dogs and that’s despite centuries of intelligent intervention speciation has never been observed

What are the mechanisms that impose these limits? He doesn’t say. Creationists never do. Besides, speciation has been observed.

Refer back to his objection number two, where he says 100 to 170 million is an eyeblink, yet now he argues that the limitations of a few centuries refutes evolution.

2:49 number seven DNA is literally not figuratively a code it embodies meaningful information it’s like the typewriter not the message there’s currently a 10 million dollar prize for anyone who can demonstrate a naturally encoding and decoding system nobody can

Man, that metaphor went kablooieeee. So DNA is literally a code, like a typewriter? What? None of that makes sense.

The existence of loons who want to offer a prize for demonstrating something that silly is not a point in its favor, especially since they’re going to automatically reject the existence of the “encoding and decoding system” embodied in cells. This $10 million prize does sort of exist, at least as a PR stunt and hype engine for Perry Marshall, a guy with a degree in electrical engineering and no understanding of biology at all. He doesn’t have $10 million to give away, so the entire “prize” is contrived to make sure no one can possibly win. That is not a point in its favor.

3:12 number eight cells edit their own DNA in real time in response to threats this isn’t random and there is variation and adaptation before natural selection can occur talking about selfish genes also assumes the very teleology and purpose that Darwin explicitly denied

I don’t think he’s talking about gene editing here — that’s a completely different phenomenon. Since it’s “in response to threats” I suspect he’s mangling the idea of modifying gene expression in response to the environment. There’s nothing in that counter to the idea of evolution whatsoever. It’s a natural and well-understood biochemical and physiological process.

The selfish gene concept does not assume teleology. Some gene sequences can use cellular machinery to amplify their representation in the genome. That’s all.

3:37 and then we’ve got metaphysical problems life didn’t come from non-life animal life didn’t come from plant life man the rational animal didn’t come from non-rational animals these are all differences in kind not degree go into your garden pick up a stone and look at it and think of it one day evolving into being able to compose a symphony solve a theorem write a novel you can’t evolve a thin line into a thick one by simply extending it that’s what it’s like trying to get life from non-life animal life from plant life rational life man from non-rational Life The Brute animals

Those look like metaphysical assumptions, not problems. Animals evolved independently from the lineage that gave rise to plants, for one thing. Life had to have come from non-life, unless you think life has existed eternally. Stones don’t evolve, since they don’t reproduce. This all sounds like incoherent word vomit from a guy who doesn’t understand anything he’s babbling about.

Now for his grand conclusion…

4:24 so what do I think about Evolution now the church fathers are clear that God could have worked through evolutionary processes in creating man’s body but certainly not in creating his intellect and at least some creatures were created fully formed and many stemmed evolution of the others was involved

I don’t give a flying fuck what the “church fathers” said. They aren’t authorities on evolution by any stretch of the imagination.

Well, that’s all he’s got. Once again, a creationist demonstrates the paucity of intellect behind their reasoning, and their whole position goes down in flames. Maybe he needs to stop assuming that he is a rational being and try to earn that adjective.

AI poisons everything

Here we go again. Another paper, this time in Radiology Case Reports, got published while including obvious AI-generated text. I haven’t read the paper, since it’s been pulled, but it’s easy to see where it went wrong.

It begins:

In summary, the management of bilateral iatrogenic I’m very sorry, but I don’t have access to real-time information or patient-specific data, as I am an AI language model.

That is enraging. The author of this paper is churning them out so heedlessly that they provide no time or care to the point they’ve given up writing and now have given up reading their own work. Back in the day when I was publishing with coauthors, we were meticulous to the point of tedium in proofreading — we’d have long sessions where we’d read alternate sentences of the paper to each other to catch any typos and review the content. Ever since I’ve assumed that most authors follow some variation of that procedure. I was wrong.

If I knew an author was this sloppy and lazy in their work, I wouldn’t trust anything they ever wrote. How can you make all the thought and effort you put into the science, and then just hand off the communication of that science to an unthinking machine? It suggests to me that as little thought was put into the research as in the writing.

No wonder there is such a glut of scientific literature.