One of my role models, recognized

My experiences in grad school were mostly happy ones, and I credit that to the fact that I was lucky to work with good people. I entered the lab of Charles Kimmel, working on zebrafish neuroscience, and stumbled my way through several projects before Chuck suggested a new one: he recommended that I use a fluorescent lineage tracer dye, rhodamine dextran, injected into midblastula cells, which we’d allow to develop into a larva in the hopes that some of that dye would end up in the neurons I was interested in.

This was a cunning strategem. First of all, this was a labor-intensive project; we’d have to do a hell of a lot of injections to get the dye into the few cells we cared about by happenstance. We’d eventually do the experiment and get a yield somewhere under 5%. The other angle is that he already had someone lined up to work on the idea, and I was being drafted to assist in the experiment.

I didn’t mind. That someone was a new post-doc, Judith Eisen, and I think we worked well together. Judith was intimidatingly intense, but nice. We got into the rhythm of this experiment smoothly. In the evening (this was a timing-dependent experiment, you had to start with embryos of a certain age) we’d get together over a beaker with hundreds of embryos, and then we had to work fast, because there was a narrow window of time to get the injections done. I’d line up ten or so embryos on a slide, and pass them to Judith, who was poised over the microscope with a microinjector, and bang bang bang, she’d shoot up single cells with the dye. I was the loader, she was the gunner. We’d set up maybe a hundred embryos before stopping and letting them then develop.

The fun work started the next day. We’d go through the previous night’s collection, put each embryo under a fluorescence microscope with a silicon intensified target camera and take pictures. Most of them we’d throw out — they had labeled skin cells, or labeled kidney, or labeled notochord, or whatever, which might be useful to someone, but not us. We wanted labeled spinal neurons. We’d get a few.

The next step might sound crude, but it was the 1980s, it was what we could do. We’d see a glowing cell on the video monitor, and we’d tape a piece of transparent plastic on the screen and outline all the cells with a sharpie. Then we’d come back to that special cell over the course of the day, and draw on that same piece of plastic with a different color. Our data was these sheets with the changing shape of labeled cells.

I vividly remember our eureka moment. We were going through our daily labeled embryos, and we had this one fish that looked familiar, a cell that looked like one we’d seen before. We sat there and made a prediction, I bet we knew exactly how that cell would develop in the next few hours. Judith grabbed all our data and spent an afternoon manually aligning all these drawings — our simple technique had some virtues, in that we could so easily align analog pictures — and came back and could say that we had precisely three cell types that had a stereotyped pattern of outgrowth.

Those were great times, and it was most excellent working with Judith. Some of my happiest memories of working in science were from those years in Chuck’s lab, partnering with Judith, so the latest news from Oregon makes me even happier: Judith Eisen has been elevated to the National Academy of Sciences! That is a well-deserved honor, and I’m happy for her.

What I learned from that experience was that a key ingredient of good research was collegiality, mutual support, and cooperativity. I think that’s what I took away from my training, that I should model my own mentorship in the years since on that of Judith Eisen and Chuck Kimmel.

Mothers have a sneaky way of getting to you

The last time I was in Washington, we had cleaned out a lot of my parent’s old stuff, and I was leaving after having booked a real estate agent to sell off the property. There were boxes and bags of miscellaneous papers that were going to be thrown out or destroyed, and I scooped up a luggage bag full of it without looking closely at it — I just didn’t want to abandon some piece of family history. I haven’t dug into it yet, but I had a moment free and plucked out a few random bits to see what treasures I had rescued.

Here are my parents, sometime in the late 1980s/early 90s.

Here’s Mom’s 5th grade report card (my grandmother also saved everything.)

That’s pretty good, young lady, but we’re going to have to have a little talk about that C in writing. Also, what’s the difference between writing and English?

I didn’t get any further in sorting through the collection because then I discovered she had saved all the mother’s day cards we had sent to her. Aww, Mom. You cared? Now I feel bad for not sending one this year. I am a terrible son.

Science needs specific, informed, productive criticism

Professor Dave demolishes Sabine Hossenfelder.

I feel that. The topic of my history class last week and this week is about bias in late 19th/early 20th century evolutionary biology, and how we have to be critical and responsible in our assessment of scientific claims. It’s tough, because I’m strongly pro-science (obviously, I hope?) but I keep talking about dead ends and errors in the growth of a scientific field, and I have to take some time to reassure the students that our only hope to correct these kinds of problems is…science. I also have to explain that the way the errors are discovered is…science, again.

I’m not specifically interested in Sabine Hossenfelder — I don’t watch her videos, not even the ones that might contain good information — but I am concerned with the general problem of how anti-science propaganda manages to advance the causes of dogma. If science gets something wrong, as it does sometimes, it does not mean that superstition or bigotry are right. Raging against the whole of the scientific establishment and the scientific method is how you get RFK Jr put in charge of the NIH. I don’t think that even Hossenfelder believes that will be an improvement.

Can we demand an ethical standard for government?

A common sense act has been introduced in congress, HR 926, asking for basic ethical requirements for the Supreme Court. It sounds like something that ought to be in place.

This bill makes various changes related to the ethical standards, financial disclosure requirements, and recusal requirements that apply to Supreme Court Justices.

Among the changes, the bill requires the Supreme Court to:

adopt a code of conduct for Justices and establish procedures to receive and investigate complaints of judicial misconduct;

adopt rules governing the disclosure of gifts, travel, and income received by the Justices and law clerks that are at least as rigorous as the House and Senate disclosure rules; and

establish procedural rules requiring each party or amicus to disclose any gift, income, or reimbursement provided to Justices.

Additionally, the bill expands the circumstances under which a Justice or judge must be disqualified; and

requires the Supreme Court and the Judicial Conference to establish procedural rules for prohibiting the filing of or striking an amicus brief that would result in the disqualification of a Justice, judge, or magistrate judge.

That’s excellent, and there’s a push to get everyone to call up your state representative to support this bill.

I agree with the bill, BUT…

I have no hope.

The fascists take over the government in January, and they’ll kill this bill. They already have. It was introduced in February of 2023, and it’s gone nowhere. Are we supposed to expect a miracle in the next two months?

I have another problem. If you actually go to the site promoted in that image, the first thing you will see is a plea for donations. It’s all about money. They also ask for your phone number, which I’ll never give out again. I made a donation to the Harris campaign months ago, and they passed my number to other organizations, so I was getting dozens of text messages every goddamned day. They all had a stop code you could send to end the noise, but I discovered that they honored it in name only. The organization I requested to stop would stop, but then they’d pass my number to a different, related organization, and the texts would continue. “Retired Democrats 2024”? “Blue Battleground Project”? “GenBlue PAC”? I didn’t sign up for any of those, and somehow they got my number. I don’t trust Democratic fundraisers.

Maybe we should start by demanding an ethical standard for all political organizations?

I know this is a mixed message. I think putting an ethical standard on the Supreme Court is important, but the Democrats are proving themselves venal and ineffectual.

You have to admire their cunning

Every year, around this time, as the weather gets colder, we get an influx of mice moving into our house to find refuge. Our cat is useless — she makes a lot of noise, usually in the middle of the night, but she can never deliver the coup de grace.

It seems I already have a potential solution at hand.

Warning: the videos below show mice meeting a horrible end in the webs of black widows.

[Read more…]

So that’s how they missed me

The rich have a well-funded network that has been poisoning the collective mind of the country, yet somehow they have failed to penetrate my soft, permeable, liberal skull. How could that be?

“every common hobby for young men–gaming, sports, fitness–is saturated with right-wing propaganda”
Bluesky

There it is, they targeted “gaming, sports, fitness” thereby completely bypassing all of my interests.

Another point not mentioned: have you ever noticed that the biggest, most popular YouTube channels are typically targeted at…children? Mr Beast, PewDiePie, Logan Paul, etc. Then there are lesser channels with a teenaged audience, like Fresh and Fit or Andrew Tate. I’ve skipped over those by getting old. I’m so lucky.

Another step in the evolution of multicellularity

I’m not a fan of phys.org — they summarize interesting articles, but it’s too often clear that their writers don’t have a particularly deep understanding of biology. I wonder sometimes if they’re just as bad with physics articles, and I just don’t notice because I’m not a physicist.

Anyway, here’s a summary that raised my hackles.

Chromosphaera perkinsii is a single-celled species discovered in 2017 in marine sediments around Hawaii. The first signs of its presence on Earth have been dated at over a billion years, well before the appearance of the first animals.

A team from the University of Geneva (UNIGE) has observed that this species forms multicellular structures that bear striking similarities to animal embryos. These observations suggest that the genetic programs responsible for embryonic development were already present before the emergence of animal life, or that C. perkinsii evolved independently to develop similar processes. In other words, nature would therefore have possessed the genetic tools to “create eggs” long before it “invented chickens.”

First two words annoyed me: Chromosphaera perkinsii ought to be italicized. Are they incapable of basic typographical formatting? But that’s a minor issue. More annoying is the naive claim that a specific species discovered in 2017 has been around for a billion years. Nope. They later mention that it might have “evolved independently to develop similar processes”, which seems more likely to me, given that they don’t provide any evidence that the pattern of cell division is primitive. It’s still an interesting study, though, you’re just far better off reading the original source than the dumbed down version on phys.org.

All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii—a close relative that diverged from animals about 1 billion years ago—undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types. Our findings about the autonomous and palintomic developmental program of C. perkinsii hint that such multicellular development either is much older than previously thought or evolved convergently in ichthyosporeans.

Much better. The key points are:

  • C. perkinsii is a member of a lineage that diverged from the line that led to animals about a billion years ago. It’s ancient, but it exhibits certain patterns of cell division that resemble those of modern animals.
  • Symmetry breaking is a simple but essential precursor to the formation of different cell types. The alternative is equipotential cell division, one that produces two identical cells with equivalent cellular destinies. Making the two daughter cells different from each other other opens the door to greater specialization.
  • Palintomic division is another element of that specialization. Many single-celled organisms split in two, and each individual begins independent growth. Palintomic division involves the parent cell undergoing a series of divisions without increasing the total cell volume. They divide to produce a pool of much smaller cells. This is the pattern we see in animal (and plant!) blastulas: big cell dividing multiple times to make a pile of small cells that can differentiate into different tissues.
  • Autonomy is also a big deal. They looked at transcriptional activity to see that daughter cells had different patterns of gene activity — some cells adopt an immobile, proliferative state, while others develop flagella and are mobile. This is a step beyond forming a simply colonial organism, is a step on the path to true multicellularity.

Cool. The idea is that this organism suggests that single-celled organisms could have acquired a toolkit to enable the evolution of multicellularity long before their descendants became multicellular.

I have a few reservations. C. perkinsii hasn’t been sitting still — it’s had a billion years to evolve these characteristics. We don’t know if they’re ancestral or not. We don’t get any detailed breakdown of molecular homologies in this paper, so we also don’t know if the mechanisms driving the patterns are shared.

I was also struck by this illustration of the palintomic divisions the organism goes through.

a, Plasma membrane-stained (PM) live colonies at distinct cell stages, highlighting the patterned cleavage divisions, tetrahedral four-cell stage and formation of spatially organized multicellular colonies (Supplementary Video 5). b, Actin- (magenta) and DNA-stained (blue) colonies at distinct cell stages showcasing nuclear cortical positioning, asymmetrical cell division (in volume and in time) and the formation of a multicellular colony. This result has been reproduced at least three independent times.

Hang on there : that’s familiar. D’Arcy Wentworth Thompson wrote about the passive formation of cell-like cleavage patterns in simple substrates, like oil drops and soap bubbles, in his book On Growth and Form, over a century ago. You might notice that these non-biological things create patterns just like C. perkinsii.

Aggregations of oil-drops. (After Roux.) Figs. 4–6 represent successive changes in a single system.

Aggregations of four soap-bubbles, to shew various arrangements of the intermediate partition and polar furrows.

An “artificial tissue,” formed by coloured drops of sodium chloride solution diffusing in a less dense solution of the same salt.

That does not undermine the paper’s point, though. Multicellularity evolved from natural processes that long preceded the appearance of animals. No miracles required!

A theological dilemma

A silly speculation: what if you die, go to heaven, and discover that a god had a set of fundamental rules that it didn’t tell anyone about?

I was initially sympathetic to the idea that a god would judge you for doing harm to small helpless creatures — I avoid killing insects without cause — but then there were a few disparaging comments about spiders, natural given the god’s nature, and I started tallying up my invertebrate body count, and I realized that the video character’s tally of having killed 11,000 insects was pathetic.

I’d be going to bug hell, wouldn’t I?

My unpleasant Christmas memory

I’m in the mood for some self-abasement, and also to nod in the general direction of the Xmas season. I’m going to tell you about the most horrible, embarrassing moment of my life so far. Maybe it’ll inspire you to mention your moment of humiliation in the comments to make me feel a little better.

In my youth, I was a regular church-goin’ kid. Sunday school every week, choir every Wednesday, confirmation every Thursday. I was not a believer, but it was the only club that would accept me, and I also liked the music–I was attending more for the choir than anything else. I had a few friends in the group, although…we weren’t good friends, I guess. We never socialized outside the church.

One year we were organizing for a giant Christmas concert involving dozens of churches in the Puget Sound area. We had to do multiple practices every week, and it wasn’t just walking down the street to my local Lutheran church. We were rotating among various churches, a different one every time, to practice together. It was a huge effort, my parents were ferrying me all over the region for a few months ahead of time. I didn’t mind. I had zero patience for the religious nonsense, but if you’ve ever been in a choir, you know that the feeling of singing in harmony with a large group is an almost primeval, inspiring sensation.

The day of the Christmas concert, we loaded up in vans and busses and journeyed to the site of the event: the Kingdome. I told you it was big. The stadium was filled up. All the Washington state choirs were seated in a vast array in the center. When we started singing, we made the whole place vibrate.

Unfortunately, I wasn’t feeling my best. In the hours we were there, I started feeling a little woozy. Then I was trembling. Then I had a cold sweat. Was I nervous? Not really. It’s not as if I had a solo, I was one among many hundreds.

Then it was time for my church group to sing their special song. We stood up, and we started singing the song we’d practiced so hard: “O Come O Come Emmanuel and ransom captive Israel That mourns in lonely exile here,
Until the Son of God appear.” Maybe you know it; I still remember the lyrics because damn, we repeatedly sang that thing so many times before the concert. I stood with my church group, raising my voice before the entire Kingdome audience with cameras aimed at us to record the event.

“O COME O COME…” I sang, wobbling and sweating, and then, suddenly, I felt Satan rising up in my body, like a greasy bubble of demonic filth, then “EMMANUE…” and it hit me, unexpectedly and irresistible, and I started vomiting. Projectile vomiting. A horrific geyser of godliness was instantly purged from my body in an terrible public display.

I did immediately feel better, with one regret: the girl in the row in front of me had a lovely cashmere sweater folded over the back of her chair, and I destroyed it. Sorry.

Our choir director, Mrs Whalen, was incredibly nice and gracious, given that all anyone was going to remember of our hard work and our performance was the kid in the middle who grossed out the entire Kingdome with his horrifying expulsion of bodily fluids. She was one of my favorite people, and she treated my ghastly spectacle with nothing but kindness. I continued on with the choir for maybe a year afterwards, before my inability to reconcile my complete lack of faith and aggressive skepticism with the whole goofy church scene drove me away.

That memory still comes back occasionally these many years later, usually around the holiday season, and I can never hear that hymn without being triggered. I also don’t sing anymore.

So what psychic scars do you all still carry?