I have now written over one thousand blog posts about Intermediate Physics for Medicine and Biology. That’s a lot of posts; one a week for over 18 years (albeit with an accelerated rate of five per week during the first few months of the Covid pandemic). I’ve come to think of these posts as mini-essays. I have two roll models: Stephen Jay Gould, who wrote a monthly essay about evolution for the magazine Natural History; and my hero Isaac Asimov, who wrote monthly about science in general for The Magazine of Fantasy & Science Fiction. It was Asimov who I read as a teenager when I was deciding if I should be a scientist. And it was Asimov who sparked my interest in all the different branches of science, which is one factor that led me to an interdisciplinary subject like physics applied to medicine and biology.
Quasar, Quasar, Burning Bright, by Isaac Asimov.
Asimov wrote almost 400 essays for The Magazine of F&SF between 1958 and 1992. I didn’t read these essays in the magazine itself. Instead, he republished collections of them as books and it was these books I devoured my senior year of high school. Here is what Asimov says in the introduction to one of those books, Quasar, Quasar, Burning Bright (1977).
When I first began to write my monthly science piece for The Magazine of Fantasy and Science Fiction… I thought of them as “science articles.” Gradually, however, there came a shift in my thinking and I began to consider them not articles but “science essays”…
An essay is distinguished from more formal expository works by the personal touch. The author does not hesitate to put himself into the essay; in fact, it would scarcely be an essay if he did not…
If you want to write an essay yourself, you will have to:
Have something to say.
Cultivate the knack of saying it informally, but saying it.
Learn to be unself-conscious so that you can get yourself into the essay without blushing or shuffling about uneasily.
Though it’s rather troublesome to get the knack of the essay, once you have it, it is just about the most pleasurable writing there is.
Science, Numbers, and I, by Isaac Asimov.
Each of Asimov’s essay collections includes 17 of the F&SF essays. In his 1968 book Science, Numbers, and I, he explains
This is my sixth book of science essays taken from The Magazine of Fantasy and Science Fiction and published by Doubleday, and in each of these six I have exactly seventeen essays. The question therefore arises—why seventeen?…
Back in 1949, when I set about writing my very first novel, Pebble in the Sky, I asked my editor, Walter I. Bradbury, how long to make it.
He said, “Make it seventy thousand words.”
So I did. Ever since, I have considered 70,000 words as, somehow, the ideal length of a book…
Again, when I started writing science essays for the magazine, I asked Robert P. Mills, then its editor, how long he wanted them. He said, “Oh, about four thousand words.”
So I did that too, and that remains the ideal length in my mind for essays.
Well, then, when I collect my essays into a book, I ask myself: How many 4000-word essays will fit into a 70,000-word book? And I answer myself: Seventeen.
I own many of these F&SF essay collections, and they sit on the bookshelf right behind me as I write this. My copies are paperbacks that I bought used, often at garage sales. The paper is yellowing and the spines are cracking, but I treasure them nevertheless. I don’t have them all. Much to my annoyance, I don’t own the very first one, Fact and Fancy, although I remember reading a library copy. Now that I’m older and wealthier than when I was 17, I’m thinking of tracking down and buying copies of the ones I’m missing. It would be my way of honoring and thanking Asimov.
The Relativity of Wrong, by Isaac Asimov.
I’ll end with one more Isaac Asimov quote. In his 1988 collection The Relativity of Wrong, he bemoans the poor quality of the science reported in the mainstream media, the rise of pseudoscience, and the imbalance between good science writing and bad. Then he says
Under the circumstances, anything anyone can do to redress the imbalance even slightly is important. Heaven knows that for all the high quality of my readership, its absolute number is relatively low; that my own efforts to educate reach perhaps one person out of 2,500.
However, I continue to try and I continue, indefatigably, to reach out. There’s no way I can single-handedly save the world or, perhaps, even make a perceptible difference—but how ashamed I would be to let a day pass without making one more effort. I have to make my life worthwhile—to myself if to no one else—and writing these essays is one of the chief ways in which I accomplish the task.
It’s been nine years since I wrote a post about scientific illustrator David Goodsell. That’s too long. Russ Hobbie and I cite his wonderful book The Machinery of Life in the very first section of Intermediate Physics for Medicine and Biology. A physicist wanting to learn more about biology but not wanting to wade into all the biochemical details should simply study Goodsell’s art.
As an emeritus scientist myself, I suppose it’s unfair to complain that one year ago Goodsell retired. I hope he keeps painting on the side as he enjoys the retired life, and continues to share his work with us. Below I present a few of his more recent creations, all free via a creative commons license at the RCSB Protein Data Bank website. At the risk of sounding corny, what a true gift to mankind. And what a true gift to physics students wanting to gain insight into biological size scales and microscopic structures.
Influenza Virus, 2024
I’ll start with the influenza virus, since it’s still flu season here in Michigan.
Illustration by David S. Goodsell, RCSB Protein Data Bank. doi: 10.2210/rcsb_pdb/goodsell-gallery-049
Cross section through an influenza virion. It is surrounded by a lipid bilayer membrane (light purple) filled with hemagglutinin (purple), neuraminidase (magenta), and a few M2 proteins (small purple proteins). M1 matrix protein (blue) lines the inner side of the membrane. RNA-dependent RNA polymerase (red) is bound to the genomic RNA strands (yellow), which are protected in a helical complex with nucleoprotein (orange).
Flu viruses subtypes are often specified by nomenclature like H3N2, which means it contains type 3 hemagglutinin and type 2 neuraminidase. The flu is an RNA virus, meaning its genetic information is stored in RNA, not DNA, and in this case single-stranded RNA. The RNA-dependent RNA polymerase is an enzyme that catalyzes the replication of the RNA strands.
The influenza virus has a diameter of about 100 nm (in other words, a tenth of a micron)
Measles Virus Proteins, 2019
Next up is the measles virus. I show this one because measles is tragically making a comeback in the United States. Not because of some horrible mutation, but because of a hesitancy by many to get the vaccine. Fortunately, Michigan has not suffered much from the measles... yet.
Cross section through measles virus. The virus is enveloped by a lipid membrane (light magenta) studded with many hemagglutinin and fusion proteins (outermost proteins in blue), which together bind to human cells and enter them. The viral genome is a strand of RNA (yellow) protected by nucleoproteins (green). RNA-dependent RNA polymerase (bright magenta) copies the RNA once the virus infects a cell, assisted by the largely-disordered phosphoprotein (purple strands connecting the polymerase to the nucleoprotein). Matrix protein (turquoise) helps the virus bud from infected cells. Several human proteins, such as actin and integrins, are also caught in the budding virus (shown in purple).
This painting was created for the Molecule of the Month on Measles Virus Proteins and recognized by the 2019 FASEB BioArt Awards.
Goodsell bases these paintings on data about the virus structure. If you hang out on social media too much (as I sometimes do) you hear things like “viruses don’t exist.” Apparently people who think that believe all this data is artifact.
The measles virus is roughly two times larger than the influenza virus, having a diameter of about 200 nm. Notice how the light purple lipid bilayer, with a thickness of roughly 4 nm, appears larger in the influenza virus illustration than in the measles illustration. Goodsell strives to get it right.
Bacteriophage T4 Infection, 2023
In IPMB, Russ and I write that “some viruses, called bacteriophages,
infect and destroy bacteria.” They are important in the history of
molecular biology and genetics, so I thought you might enjoy seeing how
this infection occurs.
Snapshots from the life cycle of bacteriophage T4. At left, a bacteriophage (red) is injecting its DNA genome (white) into an Escherichia coli cell. At center, the bacteriophage has taken over the cell, destroying the cellular DNA (purple) and forcing the cell to make many new copies of itself. At right, the bacteriophage produces a channel-forming protein (magenta) that pierces the inner cell membrane, allowing lysozyme enzymes to break down the peptidoglycan sheath (fibrous molecules shown in turquoise between the two cellular membranes) that supports the cell. The cell bursts, releasing several hundred new bacteriophages.
Unlike the flu and measles viruses, T4 is a DNA virus; it injects its DNA into bacteria. Note that there is a big difference in the spatial scale of this illustration compared to the previous two. Most viruses are on the order of a tenth of a micron in size, and E. coli bacteria are about a couple microns long. Those tiny red dots are the T4's icsahedral head (capsid), and is about the same size as the influenza virus shown earlier. Remember, a human cell has a size on the order of 10 microns, which is giant compared even to those bacteria. You could fit about 2000 E. coli into a typical human cell.
SARS-CoV-2 mRNA Vaccine, 2020
Finally, I end with the Covid vaccine. In particular, it’s an mRNA Covid vaccine, as produced by Pfizer or Moderna.
Messenger RNA (mRNA) vaccines developed for the COVID-19 pandemic are composed of long strands of RNA (magenta) that encode the SARS-CoV-2 spike surface glycoprotein enclosed in lipids (blue) that deliver the RNA into cells. Several different types of lipids are used, including familiar lipids, cholesterol, ionizable lipids that interact with RNA, and lipids connected to polyethylene glycol chains (green) that help shield the vaccine from the immune system, lengthening its lifetime following administration. In this idealized illustration, all of the lipids are arranged in a simple circular bilayer that surrounds the mRNA and the PEG strands have both extended and folded conformations.
It is interesting how much the vaccine looks like a virus. The main difference is that it only contains mRNA that codes for the spike protein—the protein that is recognized by the immune system—and not any other proteins, so it can't make functional copies of the Covid virus. Eventually, these nanoparticles of vaccine will bind with human cells, the mRNA will enter the cell (but not the cell nucleus), and it will produce spike protein by the cell's usual translation process. The immune system will recognize the spike protein and develop defenses against it. Elegant, life-saving science at work, beautifully illustrated by David Goodsell.
The size of the nanoparticle is about 100 nm, roughly the same size as the Covid 19 virus itself. Again, you can use that lipid bilayer (whose thickness is essentially a biological constant) as a size scale.
I’ll end with a wonderful video about Goodsell and his art. Enjoy!
Inside the Cell: The Molecular Art of David Goodsell
It’s been 40 years since I attended the Biophysical Society Annual Meeting in San Francisco (February 9–13, 1986), coauthoring a poster about earthworms. The lead author was Frans Gielen, a post doc working in John Wikswo’s laboratory at Vanderbilt University when I was a graduate student there. The last author was Peter Brink, a friend of Wikswo’s and an expert on electrical synapses, particularly in an earthworm axon.
Wikswo and I had been performing experiments on crayfish axons, which are long, straight, and uninterrupted along their length (I’ve written about these experiments before in this blog). We used a wire-wound, ferrite-core toroid to measure the action current along the axon, and compared it to the action potential measured simultaneously with a microelectrode. The interesting thing about the earthworm is that their medial giant axon is divided into segments by septa, which are low resistance electrical synapses also known as gap junctions. At the University of Illinois Brink had studied septa with Lloyd Barr, one of the first researchers to make electrical measurements on a septum (“The Resistance of the Septum of the Median Giant Axon of the Earthworm,” Journal of General Physiology, Volume 69, Pages 517–536, 1977). Our goal was to see if the gap junctions had high enough resistance to reduce the axial action current at the site of a septum.
Using a toroid to measure the action current in a nerve axon.
According to my research notebooks, Brink visited Vanderbilt twice in 1985 for these experiments: first on April 18 and again on July 30. He taught us the dissection—which was easier than the crayfish dissections I had been doing, because the earthworm nerve is robust and not damaged by stretching—and brought the Lucifer Yellow dye needed to visualize the septum. We scanned the toroid along the axon looking for a change in current near the septum. Looking back at the data, it was pretty noisy and inconclusive. But the initial results were enough for a meeting abstract, and we submitted the data to the Biophysical Society meeting.
I enjoyed working with Brink, who was about Wikswo’s age, meaning he was several years older than me but still a young professor, fun-loving and irreverent. He went on to a long career at the State University of New York at Stony Brook, rising to become chair of the Department of Physiology and Biophysics. Throughout his career he did a lot of highly cited work on gap junctions, particularly in cardiac tissue.
Below is our abstract to the Biophysical Society Meeting. We never obtained enough good data to write a full research article, so this abstract is my only contribution to earthworm physiology. What I remember most about the meeting was riding a cable car, walking out onto the Golden Gate Bridge, and eating lobster at Fisherman’s Wharf.
I am an emeritus professor of physics at Oakland University, and coauthor of the textbook Intermediate Physics for Medicine and Biology. The purpose of this blog is specifically to support and promote my textbook, and in general to illustrate applications of physics to medicine and biology.
