Dire puppies

My genetics students are working on presentations that they’ll give at the end of the semester. One group was very enthusiastic about discussing the idea of Pleistocene rewilding, the idea that we should resurrect extinct species and turn them loose on the Dakotas, and the most dramatic species to de-extinctify was the Wooly Mammoth. Colossal Biosciences is claiming to work on exactly that, although, honestly, I think Colossal is nothing but a hype factory.

Now, though, Colossal has announced that they have successfully resurrected on extinct species, the dire wolf. But have they, really? I don’t think so.

Modern gray wolves are not descended from dire wolves, but that’s the stock they started from. They made a piddling 20 gene edits to a mere 14 genes (that’s a bit unfair, that really is a good technical accomplishment), which is not sufficient to turn a wolf into a completely different species. What they’ve really done is made a mutant wolf and claimed it is a dire wolf.

That’s just as well, because there is no modern habitat to support a dire wolf population — if they had successfully reconstructed the full dire wolf genome, and successfully inserted that into a wolf surrogate, George Church wouldn’t be snuggling up with a cute puppy, and they wouldn’t have a place to release them, and since even modern wolves struggle to survive in the modern world, it would be a population doomed to rapid extinction. I don’t think even Canadians would be nice enough to not take them out with a hunting rifle or a trap.

Further to my argument that it’s all hype, they had to sequence more of the dire wolf genome, since what was known was inadequate, and they’re in the process of publishing that sequence. George R.R. Martin is one of the authors. You know he had nothing to do with the work, so that is just a PR stunt. The wolf puppies are spectacularly white, which was probably not true of the ancient dire wolf…they specifically deleted two pigmentation genes, a trait not present in the dire wolf genome, to get that cosmetic feature.

I asked my students who are researching the idea of Pleistocene rewilding exactly what they would do with woolly mammoths if they could resurrect them. Their answers: build a kind of glorified zoo, like Jurassic Park, but this would have to be a zoo without any ecological/environmental purpose, and I doubt that zoos have the kind of profitability that would allow them to spend tens of millions of dollars to get a single animal that would also have unknown induced genetic disorders. The fall back position was a safari game park, where billionaires could get their jollies gunning down hulking great mammoths to get a unique trophy.

I didn’t have the heart to tell them that after the revolution, the billionaires will be extinct, too.

Georgia Purdom explains sex

As everyone knows, it’s all about the size of the palps

The creationists (and a few scientists) are unhappy that there isn’t a simple, single, concrete factor to differentiate the sexes. They looked to the scientists, and were not satisfied with the answer.

at its annual meeting in 2023, the American Anthropological Association (AAA) canceled a session that aimed to explore biological sex as an analytic category in anthropology. The AAA justified its decision by stating that “there is no single biological standard by which all humans can be reliably sorted into a binary male/female sex classification.”

That’s not the answer they wanted, so they turned to Georgia Purdom, the ex-molecular biologist working for Answers in Genesis to provide that single biological standard by which all humans can be reliably sorted into a binary male/female sex classification. The single criterion! What will it be, you may wonder.

From a genetic standpoint, biological sex is determined by our chromosomes. I often say, “No Y, no guy.” Females typically have two X chromosomes, while males have an X and a Y chromosome. This chromosomal distinction provides a clear biological marker for sex.

The creationist has spoken.

Except…

It’s important to note that sexual development disorders do occur, and we must approach these situations with compassion. However, chromosomal analysis remains a reliable method for determining biological sex.

Except when it isn’t. She’s not keeping up with the times; all the cool kids are saying it’s all about gamete size. Or hormone titers. Or the morphology of primary or secondary sexual characteristics. Or pelvic dimensions. Or muscle mass. Or bone density.

At the very least, they ought to admit that the American Anthropological Association was correct: there is no single biological standard. And all the standards have exceptions and gray areas or ambiguities, sometimes contradict each other, or even conflict with each other. People are complicated, and anyone who claims there is a single obvious parameter that defines sexuality in such a way as to create a simple binary categorization is full of shit.

I wonder how Georgia plans to evaluate the chromosomal complement of everyone who wants to use a public restroom?

Delete your data now!

Bad news: 23andMe has gone bankrupt and is up for sale. Who knows where all that data they store is going to end up? I sent in my saliva sample years ago, they’ve got my genetic sequence on file, and I hadn’t worried about it until now, but now I am concerned. So is Rebecca Watson.

Another issue that came to light in the past few years is how can a for-profit corporation remain solvent when they make all their money on a product that, by definition, a customer can only buy once? And that’s why today, the biggest problem everyone has is that 23andMe has, in fact, declared bankruptcy. And that means that if you’re one of their customers, your genetic data might end up in the hands of someone you don’t trust.

23andMe has stated that they’ll be protecting that data throughout the bankruptcy proceedings, but people are understandably skeptical of that considering that they already gave hackers access to the data for 7 million users a few years ago, giving up user passwords and allowing the hackers to see users’ family trees.

That’s why California Attorney General Rob Bonta issued a consumer alert reminding people that the Genetic Information Privacy Act and the California Consumer Privacy Act give customers the right to demand that23andMe delete all their data and even destroy any samples they might still have on file. Obviously that’s for Californians, but it’s part of the reason why customers anywhere can in fact log in and do that, and Bonta gives step by step instructions for anyone who wants to.

Here’s the steps you can take to clear your data:

To Delete Genetic Data from 23andMe:

Consumers can delete their account and personal information by taking the following steps:
Log into your 23andMe account on their website.
Go to the “Settings” section of your profile.
Scroll to a section labeled “23andMe Data” at the bottom of the page.
Click “View” next to “23andMe Data”
Download your data: If you want a copy of your genetic data for personal storage, choose the option to download it to your device before proceeding.
Scroll to the “Delete Data” section.
Click “Permanently Delete Data.”
Confirm your request: You’ll receive an email from 23andMe; follow the link in the email to confirm your deletion request.

I’ve started the process for my data. However, there is an option to first request that they email your genetic data, and yes, I clicked on that…and it’s been 3 days, and I still haven’t received it. I think I’m going to have to cancel and just go ahead and delete everything without saving a copy. This is a comment that ought to chill you right down to the nucleus of all your cells: Charles Murray wants someone to buy the company for him, or his racist friends:

Charles Murray: Okay, my billionaire friends. $23m is pocket change! And it would make me so happy.

Nope, nope, nope. I’m going to have to kill my data fast.

Hey, I don’t have any billionaire friends. What have I done right in my life?

That problem is too easy

I’ve seen this game of Telephone played out in my cell biology class, but to a greater degree.

Square units? Far too easy. Our first lab in cell biology is about observing cells and then doing a bunch of unit conversions — but we’re working with volumes and cubic units. For instance, we look at a sample of microorganisms taken from a local lake, and they calculate the density and size of cells, and have to estimate how many cells are in the lake and the volume they take up. I hate to tell you this, but our lake either contains one gigantic cell that fills the entire thing, or is a thick soup containing 10googolplex cells…mmmm, sounds tasty and nutritious.

Categories

You know, categories are arbitrary, subjective, and human constructed, right? This is an excellent illustration of the idea.

I appreciate that each example includes a tidy, neat rationalization, so we can see that the rationalizations are arbitrary, too. I just wish he’d do the same thing for categories of DNA sequences so I’d have an excuse to use it in my classes.

A science rally!

I was in St. Paul, or transiting to and from St. Paul, all day yesterday for the grand #StandUpForScience rally. As you might expect for an event organized by science nerds, it was flawlessly executed: it started exactly at 3pm, had about 10 speakers, and finished precisely at 5pm. The speakers were all brief and to the point. We had several state legislators talk about the importance of science education and the contributions of science to our state’s economy, and several people with direct experience of the impact of Trump’s chaos — one young woman had just finished a post-doc and got a job with a state agency (the forest service, I think) the week after the election, and walked into a demoralized office where no one knew what was going to happen to them. She found out: she was fired 3 weeks after starting, with 2 hours notice.

Some people talked about social and economic justice, in particular, the Hennepin Energy Recovery Center (HERC), which I knew nothing about until yesterday. It’s a big incinerator which converts trash to energy, which is nice, but somehow it got located to the center of a district filled with low-income and minority residents. Funny how that happens.

Science and DEI are intertwined — so many first generation scientists were reliant on DEI initiatives to get their careers started. One speaker suggested a good question to ask critics of DEI: What, specifically, are they opposed to? Is it diversity, do they dislike people of color working in science and engineering? Is it equity, the idea of equal pay for equal work, do they think brown people should get less support? Or is it inclusion, the idea that minorities should be able to work shoulder to shoulder with existing, dominant groups? There’s no good answer to those kinds of questions, and they’re all just hiding behind an acronym, afraid to spell out what they actually want.

Another theme of speakers and participants was the raging inequality in this country. Mention the word “corporations” and you heard a chorus of “boos”. A lot of the signs people were waving targeted the wealthy and unfair tax laws, that the Trump regime was robbing science to make the rich richer. Everyone in this crowd hated billionaires in general and Elon Musk in particular. That guy is so desperate for attention and respect and popularity, and he has made himself the #1 enemy and object of contempt by scientists & engineers & teachers & health experts. Chalk that up to yet another tremendous failure by Musk the Incompetent.

It seems the greed of the wealthy in this country has inspired a lot of people to look favorably on communism and wealth redistribution and the social safety net and mutual aid. That’s going to backfire spectacularly on the upper class. This event sounded like a communist rally at times, good for them.

Also, I got to meet many fellow angry supporters of science, including commenter foolishleader who does have a spectacular octopus hat.

I’m looking forward to more Stand Up for Science events!

Furious overconfidence does not counter the evidence

Here’s another wild creationist claim that just popped up from the YouTube algorithm. It’s a shouting match between a Muslim creationist (Subboor Ahmad) and an individual from the crowd, who is challenged to define evolution. He says “natural selection plus mutation,” which prompts this furious response from Ahmad.

If it’s natural selection plus random mutations, it becomes epigenetics.

What? No it’s not. That’s absurd. It just tells me that Subboor Ahmad knows nothing about evolution.

It also includes a clip of an encounter between Ahmad and Aron Ra, in which Aron correctly points out that drift is the major driver of evolutionary change, and Ahmad blows up in fury and accuses him of being drunk.

A creationist denies molecular evolution

Last night, Aron Ra got into a discussion about a claim that protein evolution is impossible, specifically, that different protein families could not have evolved. Here is the provocative and baseless claim.

There is no research that says protein evolution is possible, unless you appeal to evolution. That’s circular.
There is no research published that explains how a new protein family, with stable novel folds, can evolve in the rugged evolutionary landscape. Only conjecture and always with an appeal to the theory. That’s called theory laden evidence.

I have issues with the premise that evolution is fact (bad science). That demands a better definition of evolution so I’ll clarify, I have problem with the premise that random mutation, gene duplication, gene transfer, gene shift, and anything I may have missed, under the influence of natural selection is sufficient to produce biodiversity.

Perhaps a new mechanism will be discovered, but at present there is no evidence that evolution is possible beyond an appeal to evolution.

There is a barrier to protein evolution. Gradual change doesn’t provide a path from one protein family to another because the landscape is rugged. Point mutations will lead proteins off the functional cliff. Duplication doesn’t fit the bill either, not enough variety. Fact is, without some sort of bridge protein evolution is inconceivable. No bridge has been found.

I’m not claiming that there isn’t one or that it will never be found, I’m saying there is no evidence for one. It’s a leap of faith to say it happened.

I know you’re not a fan of that word, faith, but there is no alternative. The only justification for that faith is ontology. It’s your belief in naturalism which cannot be proven one way or the other. in fact, the very problem I’m discussing here is a thorn in the side of naturalism.

You’ve waged a lifelong war against theism and always appeal to intellectual honesty. Well, I’m being intellectually honest. There in no evidence that evolution is possible because protein evolution has no known solution.

Proteins exist on peaks separated by valleys where function drops off completely. The “rugged landscape”. The peaks play home to a variety of related proteins with limited variety of amino acid sequences called families. A peak is more like a plateau. Small changes can produce variety of function and fitness. Large changes cause function to collapse into a valley where the protein gets deselected.

The amount of change required to find a new stable fold with novel function, a.k.a. a new family on its own plateau, far exceeds what proteins can tolerate by incremental change without losing all function. This is not controversial.

Proteins need to leap or require a bridge. Leaps in sequence change are irrational because the search space is too large and the target too small.

The presumption is that there is an unknown “bridge” that allows proteins to make the transition from one peak to another. That bridge has yet to be found (or even adequately hypothesised), and without it proteins are trapped on local peaks. Meaning evolution is limited to variety of what is, with no access to cool new stuff. Micro but not macro.

The premise that evolution is a fact allows for the presumption that “we don’t know yet” is a valid placeholder for the bridge. A glaring “god of the gaps”. My “dilemma” is how can evolution be called a fact, when the facts exist to challenge it? It can only be reckoned that belief is the “Jesus nut” that keeps it from flying apart.

Anyone who is a materialist will naturally, and justifiably, search for that bridge. Dualists can as well, but it’s discovery isn’t an imperative. For the theist, that bridge may well be agency. In any case, agency is no worse than “we don’t know yet” as a filler.

My question is, on what basis do you declare the materialist ontology correct and the dualist ontology false? The inability to test is a feature, not a test in itself.

What does it matter if the problem was before Eukaryotes? Evolution covers the first cell to everything. From what I’ve read, the Cambrian Explosion is where the problem is most evident with many new protein families that have no observed precursors. All within a tiny fraction of evolutionary time.

“A protein family is a group of proteins that share a common evolutionary origin, typically reflected in their similar amino acid sequences, structural features, and often their biological functions. These proteins are usually derived from a single ancestral gene that has undergone duplication and divergence over time, leading to variations within the family. Members of a protein family may differ in their specific roles or expression patterns but retain enough similarity to be classified together.” -Grok (I trust AI is allowed for definitions?)

I understand the standard hypothesis. Gene duplication allows one to remain stable while the other continues on down the evolutionary trail. I also understand there is a vast leap required for a protein to diverge into a new family. Recombination is most commonly considered for large leaps, though no evidence exists it can be done.

I understand the standard hypothesis. Gene duplication allows one to remain stable while the other continues on down the evolutionary trail. I also understand there is a vast leap required for a protein to diverge into a new family. Recombination is most commonly considered for large leaps, though no evidence exists it can be done.

I also understand that proteins are intolerant of big change. That paper by Axe estimated that only 1 in 10^63 random sequences fold right. Leaps mean a big change which hits that small target.

On the other hand, incremental changes enjoy a similar problem of losing functionality (which can kill all progress), while also facing time constraints. There isn’t enough time for evolution to search out functional sequences. Even a nice new protein with a stable fold must break the barrier of epistasis.

Finally, I’m talking about entirely new families. Think Superfamily. Like a transporter to the first protease. The information hurdle is massive, and the serendipity required makes Powerball look like a sure bet.

Evolution is not really varying allele frequencies. That works for HS kids but it falls short. Evolutionary theory is the explanation for those varying frequencies. Theories explain HOW, not what.

So we talked for a while about this silly claim. As Aron points out this is just the old show me a cat giving birth to a dog creationist claim translated to show me a transport protein evolving into a protease. It’s the same thing and the same answer. We can trace the ancestry of cats and dogs and see that they converge on a common ancestor in the distant past; we can trace the ancestry of various proteins and follow them back to a distant duplication event to the modern diverse pattern. The creationist wants to argue that the process is simply impossible by throwing around various sciencey terms. He uses the old creationist claim that the probability of a particular functional sequence is only 1 in 1063, a calculation built on faulty premises. He invokes the barrier of epistasis…what barrier is that? I don’t think he knows what epistasis is, let alone the nature of his imagined barrier. He throws around the term rugged fitness landscapes without recognizing that landscapes are an explanatory metaphor, not an actual physical entity.

If you don’t want to listen to us babble, I sent Aron a link to a paper by Tomoko Ohta that summarizes it all.

In eukaryote genomes, there are many kinds of gene families. Gene duplication and conversion are sources of the evolution of gene families, including those with uniform members and those with diverse functions. Population genetics theory on identity coefficients among gene members of a gene family shows that the balance between diversification by mutation, and homogenization by unequal crossing over and gene conversion, is important. Also, evolution of new functions is due to gene duplication followed by differentiation. Positive selection is necessary for the evolution of novel functions. However, many examples of current gene families suggest that both drift and selection are at work on their evolution.

The creationist says that all of that is inconceivable, of course. Never mind that we have evidence of each incremental step and can see intermediates in the process preserved in the genome.

Then he falls back on free will and morality as obstacles to evolution, somehow.

Do spiders count?

My new experimental animal?

A couple of Republicans have introduced a bill in congress to ban all research on animals. All animals, although I’m not sure they understand the breadth of that term. They do helpfully declare that The term ‘‘animal’’ does not include a human. So, according to the ‘Safeguard Pets, Animals, and Research Ethics Act’, we’re going to have to shut down all research involving any kind of animal, except humans. They don’t have the first clue what an “animal” is, or how devastating this would be to biomedical research.

Specifically, this legislation would ban animal testing in federal labs, establish a three-year phase-out, rehabilitate and re-home former lab animals, saving taxpayer dollars while enhancing research outcomes, and ensuring accountability and transparency. American taxpayers spend an estimated $20 billion funding experiments here in the US and overseas including in countries with subpar safety conditions in China, Russia, and Iran.

“I am proud to work alongside Congressman Aaron Bean to end the cruel and unnecessary spending on animal experiments that have wasted billions of tax dollars and inhumanely kept hundreds of thousands of innocent animals in captivity to be tortured and sentenced to painful death,” said Congresswoman Malliotakis. “From administering transgender hormone therapy to monkeys to infesting beagles with fleas and drilling into cats’ skulls for so-called ‘research purposes,’ the American taxpayer would be outraged to learn how their money has been spent. As Co-Chair of the Congressional Animal Protection Caucus and the Cosmetics Caucus, I am committed to advancing our legislation, promoting humane research alternatives, and ensuring taxpayer dollars are spent responsibly.”

“What Fauci did to beagles and other animals is disgusting. The federal government needs to get out of the business of torturing Snoopy. I am proud to join Congresswoman Malliotakis in introducing the SPARE Act.” said Congressman Bean.

Of course she brought up transgender hormones, Fauci, and saving money, the current Republican shibboleths. I can’t believe this would ever pass into real legislation, but I don’t know…congress and the president have been pushing some insane stuff lately. If it did become the law of the land, you can kiss most biological research goodbye.

Welp, I guess I better go release my spiders and all those fruit flies. Then I’ll go raid the local orphanages for small children I can still legally use in my experiments, before my colleagues get the same clever idea.

What would you tell people who want to gut basic research?

In 1997, Arthur Kornberg wrote an article for the Nobel Foundation, Basic research, the lifeline of medicine. It’s a good read.

The pursuit of curiosity about the basic facts of nature has proven, with few exceptions throughout the history of medical science, to be the route by which the successful drugs and devices of modern medicine were discovered. Though it seemed unreasonable and impractical, counterintuitive even to scientists, to solve an urgent problem of disease by exploring apparently unrelated questions in biology, chemistry and physics, these basic studies proved time and again to be utterly practical and cost-effective.

Then he goes on to give the examples of x-rays, penicillin, polio vaccine and genetic engineering.

The lessons to be learned from these four histories and so many others should be crystal clear. No matter how counter-intuitive it may seem, basic research has proven over and over to be the lifeline of practical advances in medicine. Without advances, medicine regresses and reverts to witchcraft. As in biomedical science, pioneering industrial inventions have not been mothered by necessity. Rather, inventions for which there was no commercial use, only later became the commercial airplanes, xerography and lasers on which modern society depends. Curiosity led to the inventions that became the source of industrial strength. It is imperative for a nation, a culture, a university and a company to understand the nature of the creative process and to encourage its support.

It’s too bad that we have a government that rejects this idea.

Reminder: the Stand up for science rally is taking place next week. The St Paul rally is from 3-5pm on Friday at the state capitol — I’ll be there.

I’m going to have to make a sign this weekend. Any suggestions for what I can put on it? I’m not going to put a copy of Kornberg’s paper on it — I need something short, pithy, and catchy.