This is one of those weeks

I’m teaching cell biology, but the first thing I have to do is hammer them over the head with…chemistry. They typically haven’t realized yet that biology isn’t all butterflies and cat dissections, it’s also all built on math and chemistry, and we have to get the students thinking quantitative. Today I’m lecturing on small molecules — ions in solution, pH, redox reactions, chemical bonds — and lab is all dilutions and concentrations and basic algebra.

It’s not fun for me, either, but we’ll never get to the fun stuff without it. I’ve been cramming general chemistry all weekend, because I have to know it all better than the students.

Another important matter this week is that I have to get a haircut after a long summer of flowing locks. I’m trying to decide if I should bring back an old style. Here’s what I looked like in the mid-1960s.*

back row: the second wave of cousins, Tim Smith, my brother Jim, Matt Sones.
Front row: first wave cousins, Don Smith, me, Kelly Sones.

That haircut was easy to maintain, and cheap to cut — my mom would just stroke her electric hair clippers over my head, and it would be done. I don’t think I look anything like me now, just a homely, shaggy old man.

I was no prize to begin with, and it’s not fair that I got homelier over time.

I think teaching chemistry over and over aged me. Yeah, that’s the ticket.

*P.S. Only Matt and I are still alive. I should be grateful I’m still here, no matter how ugly I get.

Survival: Day One

I made it! I got through the first day of classes without passing out or having my pants fall down! There are a few things I have to work on, though.

  • No one wanted to talk. I had multiple questions for them and invited them to express their ideas, and as usual, they were reluctant. They were probably afraid of my fierce attitude. After I tore the tape off their mouths and managed to refrain from thrusting my fingers into their eye sockets and ripping out their skull and vertebral column, they started warming up and I got some responsiveness out of them. There is a lot of promise there and I think I’ll get them contributing more soon. Or, you know, eye sockets, skulls, vertebral columns, etc.
  • I think most of them failed to read the paper I’d assigned in the syllabus! That fact may have accounted for their fear of speaking up, beyond just shyness. I gave them an incentive to look it over, though: I told them I know where I’m going to get a lot of questions for the quiz that they’ll get on Friday, which is even better than skull ripping at getting students to do the reading.

I did have a little problem I had last year — my voice starts to give out on me before the class is over. I managed to muscle through it and make my voice heard. I have to resume a habit I started last semester — having a cup of hot tea before class.

The lesson of apples

I grew up in Washington state, and many of my relatives worked the apple orchards in season — they were good, hardworking fruit pickers. But I hadn’t even thought about where apples came from. I was pretty sure it wouldn’t have been the Yakima valley, and of course I knew of the legend of Johnny Appleseed, but wouldn’t have been able to even guess what their origin was.

It turns out they’re from Kazakhstan.

What I thought was most interesting in the video is that it mentions Nikolai Vavilov, and his famous hypothesis — so famous that we take it for granted in any discussion of human origins.

The origin of any cultivated plant can be found where its wild relatives grow with the greatest diversity.

Awesome! I’m going to have expand my discussion of extreme heterozygosity and centers of origin in my Spring semester genetics class (but not now, I have to focus on cell bio for next week). I read this most excellent review, Human-driven evolution of cultivated plants and the origin of early civilizations: The concept of Neolithic revolution in the works of Nikolai Vavilov and found it enlightening.

The concept of centers of origin of cultivated plants (crop biodiversity hotspots) developed by Nikolai Vavilov (1887–1943) is essential for understanding the origin and evolution of human civilization. Vavilov formulated the principles of the Neolithic agricultural revolution and substantiated the basic patterns for the emergence of agricultural civilizations. He established that the center of speciation of the plants that have a potential for cultivation determines the origin of primary civilization. Humans actively performed the selection of plants with valuable properties, which led to the formation of new cultivated species and varieties, while the starting point for such unconsciously human-directed evolution was the presence of potentially useful traits due to the increased genetic diversity in the center of origin. The spreading of agriculturally important cultivars from the center of their origin led to the propagation of beneficial farming technologies over large areas. The establishment of human civilization resulted from the dynamic quasi-symbiotic relationship between humans and domesticated plants and animals, which human-driven evolution became an essential factor for the transformation and dynamics of human societies.

Here’s all the human history you need. (I exaggerate slightly.)

Fig. 5 summarizes the proposed views on the development of agricultural civilizations and phytospreading during the Holocene. The phytospreading process became to a major extent human-driven in the Holocene, which resulted in intensive biomass formation related to the production of crops. Centers of origin of cultivated plants determined the rise of early civilizations, which in turn facilitated the spreading of wild, cultivated, and weed species to higher latitudes. The process of phytospreading in the Holocene was described by Vavilov for the origin and distribution of cultivated plants. He identified the centers of origin of cultivated plants as the hotspots of genetic diversity for the plants potentially having agricultural importance. In these spots, the series of parallel variability (described as Vavilov’s law of homologous series) were very intense.

Fig. 5. Schematic illustration of the development of agricultural practices, spreading of cultivated plants, and social evolution of human civilization.

The law of homologous series is a very evo-devo concept. It’s the idea that similar variations can be found in members of the same genus, the same family, that is, that there seems to be something in the ancestral form that recurs spontaneously in later descendant forms, that the feature is an intrinsic property that can pop up in multiple branches of a lineage. These are brilliant observations rooted in Vavilov’s extensive study of native populations. Yes, he visited Kazakhstan and studied the apples there.

It’s especially impressive that he was doing this work that merged the disciplines of evolutionary biology and genetics in the 1920s.

You may have heard Vavilov’s name in another context: he was hated by the anti-science ideologue Trofim Lysenko, who eventually had him arrested and condemned to death in 1940. Vavilov died in prison in 1943, all because he recognized the scientific validity of Mendelian genetics, and opposed the nonsensical delusions and wishful thinking of Lysenko (delusions that led to the death of millions by famine). I can’t help but notice the similarities in the conflict between American science and the lies of MAHA and our modern Lysenko, RFK jr.

Vavilov’s mugshot

Thank goodness no scientists are being harassed in show trials and threatened with prison here! How many great scientists are going to wither on the vine thanks to the current radical politicization of science in this country?

Makin’ mealworms

We have a big container here in the house for raising mealworms, but it starts getting decrepit after a few months. It’s more frass than food, the adult beetles start taking over, and while it’s still productive for now, the writing is on the wall — a few more months and I’ll be dumping it into the compost bin. If I were smart, I’d start a fresh mealworm colony now, before the old one fades away.

I am smart, S-M-R-T, so that’s what I did this morning. Here’s what a mealworm paradise looks like:

I poured in a mix of oats and cornmeal, with some barley for variety, and chopped up some old carrots for gnawing on. Then I transferred a bunch of larvae from the old colony, and also a few adults to start laying eggs. The cardboard and toilet paper rolls are for shelter, and they also lay eggs on those. Now I wait for the population to explode, and then I can start harvesting the worms for the more important spider colony.

Biology is so easy. Provide the right environment, and your subjects proliferate with little effort on your part.

Kangaroo court is in session

“COVID “”Cures”””

Anthony Fauci was hauled up in a senate hearing where ignorant, ideologically-poisoned buffoons like Rand Paul harangued him with absurd accusations. He rightly responded by taking the fifth — there is no point in arguing with delusional idiots. At one point, Paul had Fauci’s lawyer thrown out of the hearing.

Dr Anthony Fauci, who served as a key adviser to Donald Trump and Joe Biden during the Covid-19 pandemic, has refused to answer questions at a high-profile congressional hearing, accusing a Republican senator of having an “unhinged obsession” with him.

Fauci, the veteran former director of the National Institute of Allergy and Infectious Diseases (Niaid), invoked his constitutional right against self-incrimination when appearing before a Senate committee on Wednesday.

Fauci said Republican Kentucky senator Rand Paul had, who called the hearing, led a years-long investigation into himself and the origins of the pandemic aimed at “embarrassing and intimidating me”, and ultimately landing him “behind bars”.

This is the way. Paul’s harassment was ultimately fruitless, except that the current political regime gave him the opportunity to try and browbeat an 85 year old scientist who had espoused a rational, evidence-based approach to the COVID pandemic. Fauci’s approach reflected the scientific consensus.

A 2024 survey of virologists from the Global Catastrophic Risk Institute found that most believed the pandemic began as a so-called spillover event, or a virus jumping from an infected animal to a human. Similarly, a group of virologists argued in the Journal of Virology that the “preponderance” of evidence points to a natural origin, even as the “lab leak” theory received outsized attention. Gain-0f-function research, meanwhile, has split the scientific community for years.

There is no good evidence for the lab leak hypothesis. It’s just a xenophobic contrivance made up to place the blame on China. It’s a political distortion of the evidence.

What was most bizarre is that Rand Paul exposed Fauci’s diary, in which he stated his opinions about certain political figures (and some journalists) without any diplomatic hesitations.

The scheduled hearing comes just days after Paul released what he described as Fauci’s “diary”, a more than 1,100-page document characterized as revealing Fauci’s inner conflicts about the lab leak theory. Scientists have said this is a normal part of scientific debate.

The diary also contained entries about Trump, who he advised closely during the early days of the pandemic. He described the president as “rambling”, “crazy”, “desperate”, “bumbling”, “incompetent”, “an idiot”, “a true embarrassment”, “totally nuts” and “truly an obnoxious adolescent”.

Hey, that was also just an echo of the scientific consensus! Trump is a bumbling incompetent. Some of us have been unabashedly saying that in public for many years. I would just rebuke Fauci for hiding his feelings away in his private notes. Let it all hang out, Anthony! It’s not as if being reserved about your true feelings has spared you any suffering at the hands of morons like Paul.

The true purpose of the hearing was obvious — the goal was to intimidate scientists from speaking out about biomedical approaches to disease, and to pander to all the frauds and influencers who profit off medical misinformation.

Gary Peters, a Democratic senator of Michigan, described the hearing as damaging to science and ignoring ongoing public health threats, such as the outbreak of the food-borne parasite cyclospora and measles, both at record highs.

“It’s attempting to turn one person into a scapegoat for a crisis that that hundreds of officials across the Biden and Trump administrations’ were responsible for handling,” said Peters, who did not ask Fauci any questions. “This is only going to deter other scientific experts from public service.”

While the politicians are scapegoating Fauci, they’re giving a free pass to the MAHA goons who have enabled a cyclospora outbreak, watered down food safety regulations, and fueled criminal anti-vax mythologies that are allowing a measles comeback. The USA is at risk of losing our measles elimination status, thanks to people like RFK jr.

These people ought to be more self-aware. If they can drag the guy who successfully led the fight against the pandemic, I’m hoping we have the opportunity someday to turn the tables and confront the disease enablers with the butcher’s bill. There’s a better case to be made that they caused millions of deaths.

Oh no, science to get the Trump “gold” treatment

This is not good news. The Trump administration wants to radically change how science is done in this country.

On Tuesday, the White House Office of Science and Technology Policy (OSTP) released a report entitled “Science: A New Golden Age,” in which it lays out how it has viewed science, found it lacking, and believes the Trump administration is in the perfect position to fix things. It’s a bit unexpected coming from an administration that has been proposing crippling funding cuts to research and trying to enable political appointees to terminate grants awarded based on scientific merit.

The report presents itself as the spiritual successor of “Science, the Endless Frontier,” a policy document that laid out the case for government-funded science in the wake of World War II. The New Golden Age (SNGA) says that, while the concepts promoted by the original remain vital, the circumstances have changed such that we need major revisions to how the government is implementing things.

The result is an odd mix. It completely ignores or glosses over many things that the administration is doing to harm scientific progress. In some cases, it identifies issues that have already been discussed as problems within the scientific community. Elsewhere, it’s a mixture of political grievances, ideas without a solid intellectual foundation, and an injection of Silicon Valley’s perspective on innovation (Michael Kratsios, the director of the OSTP, formerly worked with Peter Thiel). As a result, it’s unlikely to have anything like the impact of “Science, the Endless Frontier.”

“Gold standard”? So he wants to buy some cheap crap from Home Depot, spray paint it gold, and call it science?

Jesus, but he made the oval office kitschy and cheap, and now he’s going to give science the same treatment.

The University of Minnesota creates life in the laboratory!

Well, sort of. Researchers in the College of Biological Sciences on the Twin Cities campus have created a synthetic cell from scratch that has many of the properties of evolved cells, but they also have significant limitations. Kate Adamala and Aaron Engelhart have combined 7 plasmids in a lipid bubble, that they’ve called a spudcell, that can do many of the cool things that natural cells can do.

This is likely the most exciting project I’ve ever worked on,” said Adamala. “We’ve replicated in chemistry what only used to be possible in biology: the complete set of behaviors of a cell. It proves that the most fundamental functions of life, like growth and replication, do not need a mysterious magical spark.

You can almost hear the mad cackle. So what can it do?

Among the characteristics of SpudCell:

• Replicates a biological cell’s life cycle: SpudCell is capable of selection, genome replication, growth, resource acquisition via feeding, and genetically encoded division.
• Cell division without a cytoskeleton: Natural cells divide using internal scaffolding called a cytoskeleton, which has been a bottleneck in synthetic cell research. SpudCell sidesteps the need for a cytoskeleton with proteins that crowd together on the membrane surface until the mechanical stress makes the membrane split.
• Selection and competition: Researchers introduced a genetic change that increased production of the fusion protein, resulting in cells that grew faster and produced more offspring. After five generations, the faster-growing variant had outcompeted the original. Under nutrient scarcity, the advantage increased, demonstrating selection and competition operating in a fully synthetic chemical system.

It’s basically a minimal, defined biochemical system in a liposome, with a tiny genome. It doesn’t have any organelles (other than ribosomes), and is a uniform soup of enzymes, which is why I think they called it a SpudCell, because it’s got all the character of a potato. You can read a preprint which gives all the details.

The system contains 36 purified enzymes, a 90,000 base pair genome spread across nine separate DNA molecules, and a lipid membrane. SpudCell is able to grow, replicate its genome, divide, and undergo selection and competition across multiple generations.

The preprint also discusses some of the major limitations of this system. It’s not going to compete with natural cells, and it will die out within a few generations if released. It needs to be fed specially prepared liposomes filled with nutrients that can spontaneously fuse with the cells, which is kind of cheating. But also…

• Building ribosomes from genetic instructions. SpudCell currently uses ribosomes from E. coli bacteria. Without the capability to remake ribosomes, SpudCell runs for 5-10 generations before the machinery degrades. Building ribosomes from scratch means synthesising dozens of proteins and RNA molecules, then getting them to assemble in the right order.
• Improving genome distribution. After five generations, about 30% of daughter cells have the complete set of seven DNA plasmids. Natural cells solve this with cytoskeletal machinery that pulls chromosomes apart during division. SpudCell does not have that yet, and better genome inheritance will need more sophisticated division mechanisms.
• Reducing dependence on external feeding. Nutrient-carrying liposomes have to be added regularly, and division requires streptavidin and molecular linker proteins from outside. Making the system more autonomous will require building metabolic pathways that can synthesize components from simpler starting materials.

It’s not sophisticated enough to assemble its own ribosomes, which is a major limitation. It’s going to need at least an order of magnitude more complexity to do that.

I’m more interested in the lack of a cytoskeleton. You’ve got 23 pairs of chromosomes in your cells, and the cytoskeletal machinery in mitosis works to guarantee that each daughter cell inherits the same 23 pairs; there are cells that don’t have that cytoskeleton, and they can do just fine with a single strand of circular DNA, but these SpudCells have at least 7 separate plasmids that have to be sorted. They rely on chance distribution of the plasmids to daughter cells, so they have to point out that after 5 generations 70% are nonviable.

What it’s good for is that it’s greatly reduced, bare-bones cell where every component is precisely known so you can track every molecule for at least a few generations. There are toy cells, but good educational toys.

Respect the intelligence of all living things!

As an undergraduate, my introductory neuroscience course was taught by Johnny Palka, a developmental biologist and neuroscience who worked with Drosophila, who had to explain to us on the first day of class that flies have brains. It was memorable because I was surprised that anyone thought otherwise (don’t worry, the class got much more sophisticated and mathematical after that). But it’s true that there are an awful lot of people with that degree of ignorance.

Confirmation:

“Most people think insects are reflex-based machines,” said Dr Olli Loukola, a behavioural ecologist at the University of Oulu, Finland, and senior author. “That they can’t have any emotional states or feel pain. Some people don’t even realise that they have brains. I hope that these results change the worldview about that.”

That’s from an article about bee intelligence, and if you think insect anatomy is a confusing topic for the general public, wait until you find out there are people who think intelligence can be reduced to a single number.

Only…biology can surprise you. We don’t even understand what intelligence is, so you should avoid limiting preconceptions. All it takes is a simple test to demonstrate the capabilities of insects.

The bees, which were only a couple of weeks old, were first trained to associate a blue artificial flower with a reward of sugar water. During the test, the flower was moved to the ceiling of a transparent petri dish-style chamber whose ceiling was too high for them to reach, but with insufficient space for them to hover. A ball was also introduced into the chamber. To reach the flower, the bee had to roll the ball under it and climb on top – a behavioural sequence they had never previously encountered or been trained to perform.

In the most basic version of the test, 75% of the bees were successful in reaching the flower. “This is essentially an insect version of the classic ‘box-and-banana’ problem,” said Loukola. “The animal must realise that an object can be repositioned and then used as a tool to reach an otherwise inaccessible goal. What stands out about the result is that this kind of spontaneous problem solving is now demonstrated in an insect.”

This is not to say that bees have the breadth of ability that a chimpanzee has. It’s saying that some things we regard as a significant intellectual capability can be implemented with a tiny number of neurons, and that includes tool use.

“There’s a general perception that intelligent behaviour requires big brains because we are big-brained and relatively intelligent among animals,” Chittka added. “Bees are a model of how much intelligence you can squeeze into a small nervous system … It’s a good reminder of there being a motivation to pay some respect to these other beings.”

Another example I’d point to is corvids — teeny tiny little bird brains that are remarkably smart.

A science star!

My daughter won first prize in a poster session at UW Madison, presenting her work on “Evaluating Retrieval-Augmented Generation vs. Long-Context Input for Antibiotic Timeline Extraction from EHRs”. I struggled to follow it, but got the gist of it — they’re working on methods to more efficiently extract information from patients’ medical records using LLMs. She sent us the poster image, maybe you can extract more details from it.

Near as I can tell, it’s perfect, and her peers also thought so. The only suggestion I could possibly make is to maybe add a few spider photos…or a picture of my granddaughter? I don’t know that my suggestions would necessarily help.

It’s nice to have a vague idea of what she’s been up to!