Robert Hooke, Biological Physicist

In Homework Problem 20 of Chapter 1 in Intermediate Physics for Medicine and Biology, Russ Hobbie and I refer to Hooke’s law, which relates the tension in a spring to how much it’s stretched from its relaxed state. In that problem, we don’t actually deal with a spring, but instead model the elastic properties of an arterial wall. The law is named after Robert Hooke (1635–1703), an English biological physicist.

Did biological physicists exist four hundred years ago? I would argue yes. Let’s learn a little about Hooke and see if you agree.

Robert Hooke is sometimes called “England’s Leonardo.” In the breadth of his interests, Hooke resembles the Renaissance polymath Leonardo da Vinci. However, despite being a scientific and engineering genius, Leonardo rarely published his discoveries so he had little impact on future generations of scientists. Hooke, on the other hand, did publish and was a major contributor to the scientific revolution.

Hooke attended Oxford, the oldest university in England. His family was not wealthy, and he obtained free tuition by serving as an organist. He began his career as an assistant to Robert Boyle, and helped build the vacuum pumps needed in Boyle’s chemical research. London’s Royal Society was founded in 1660 and the 25-year-old Hooke was appointed its experimental curator. Just what does an “experimental curator” do? He was in charge of designing, constructing, and demonstrating experiments at the Royal Society’s weekly meetings. These experiments could be in physics, chemistry, biology, astronomy, or medicine. He must have been a versatile and skilled experimentalist. I can hardly imagine a job that would provide a better liberal education across all the sciences.

During the middle and late 17th century, London was a leading center of science. The most famous scientist was Isaac Newton (arguably the greatest scientist anywhere, ever). But also contributing at this time were Boyle, Hooke, and astronomers John Flamsteed (who established the Royal Greenwich Observatory) and Edmund Halley (of “Halley’s comet,” who convinced Newton to finally publish his Principia).

Hooke was himself an astronomer, and with a telescope he observed the rotations of planets Mars and Jupiter. But he’s best known for his work using the microscope. Whereas the Dutch microscopist Anton van Leeuwenhoek—who worked at the same time as Hooke—used single-lens microscopes, Hooke adopted and improved the compound microscope having two lenses: an objective and an eyepiece. Many of his results, including the first observations of biological cells and spectacularly detailed drawings of tiny insects, were published in his 1665 book Micrographia. It’s because of this book that I claim Hooke was a biological physicist. After all, he introduced the word “cell” into biology’s vocabulary. Hooke was a fine illustrator and he drew the pictures for his book, like that of the flea shown below.

A drawing of a flea, from Robert Hooke’s book Micrographia.

Hooke was brilliant but argumentative. He developed Hooke’s law relating the force to the extension of a spring, but then engaged in a heated argument about priority with Dutch physicist Christiaan Huygens for the invention of the spiral hairspring used in watches. He was also a bitter rival of Newton’s, and they argued about who was the true discoverer of the inverse square law that Newton used in his universal law of gravitation. In Volume 8 of The Story of Civilization, Will and Ariel Durant wrote that Hooke “was probably the most original mind in all that galaxy of geniuses that for a time made the Royal Society the pacemaker of European science; but his somber and nervous nature kept him from the acclaim that he deserved.”

After the 1666 Great Fire of London, Hooke—just barely 30 years old—set aside most of his scientific work to help architect and scientist Christopher Wren rebuild the city. 

For his contributions to physics, chemistry, biology, astronomy, microscopy, and architecture, Robert Hooke deserves to be known as England’s Leonardo.

 

Robert Hooke: The Leonardo of England 

https://www.youtube.com/watch?v=chtxPnS1_GQ 

Asimov on Writing Essays

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:

1. Have something to say. 
2. Cultivate the knack of saying it informally, but saying it. 
3. 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.

Catching Up With David Goodsell

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.

Illustration by David S. Goodsell, RCSB Protein Data Bank. doi: 10.2210/rcsb_pdb/goodsell-gallery-018 

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.

Illustration by David S. Goodsell, RCSB Protein Data Bank and Scripps Research. doi: 10.2210/rcsb_pdb/goodsell-gallery-048 

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.

Illustration by David S. Goodsell, RCSB Protein Data Bank; doi: 10.2210/rcsb_pdb/goodsell-gallery-027 

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

https://www.youtube.com/watch?v=Gk8cNkm5NTk

Action Current Propagation Across an Electrical Synapse: Magnetic Measurement on a Septated Earthworm Axon

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.

Igor Tamm, Biological Physicist

“How Physicists Became Biologists”
by Istvan Hargittai.

One goal of Intermediate Physics for Medicine and Biology is to illustrate the close relationship between biology and physics. In particular, in this blog I like to highlight examples of physicists who have contributed to biology. So, I was delighted to discover the paper “How Physicists Became Biologists” by Istvan Hargittai (Structural Chemistry, Volume 36, Pages 1–12, 2025). 

Today, I want to feature just one of the several stories told by Hargittai. This tale centers on Igor Tamm, a Russian physicist who shared the Nobel Prize in 1958 “for the discovery and the interpretation of the Cherenkov effect” (electromagnetic radiation emitted when a charged particle passes through a material at a speed greater than the speed of light in that material). He didn’t switch his research to biology, but he did provide support for biologists suffering during the time of Lysenko. Hargittai writes

Above I have already alluded to Igor E. Tamm’s defiance under the charlatan Trofim D. Lysenko’s dominance of biology, including genetics, in the Soviet Union... Blind dictatorial power existed under Stalin. Although the next Soviet leader, Nikita Khrushchev unmasked some of Stalin’s crimes and brought about a degree of relaxation, Lysenko managed to enamor him to his unscientific views and did not lose his grip on Soviet biology and agriculture until after Khrushchev had lost his power.

Igor E. Tamm... was deeply concerned about the situation of biology in the Soviet Union. He was a great physicist and humanist—not an easy demeanor to represent in the Soviet Union under Stalin and Stalin’s successors. Tamm was aware of the growing gap between the progress in the West and the situation in the Soviet Union. He realized that it would be impossible for the Soviet biologists to change the trend, but the nuclear physicists might be able to do that. Tamm convinced Igor V. Kurchatov, the leader of Soviet nuclear research—atom tsar was his popular label—about the necessity of acting. They did not challenge Lysenko directly; instead, they were taking measures that could be done within their jurisdiction. In the late 1950s, they organized a special seminar, chaired by Tamm, for a closed group of people. First, the seminars were held in private rooms of members of the Science Academy; it was essentially a clandestine movement. As they were gaining strength, in 1958 they organized a section of radiobiology in Kurchatov’s Institute of Atomic Energy. Tamm gave talks on recent achievements in biology, based on his readings. In 1957, in one of his lectures on the molecular mechanism of heredity, he discussed the genetic code, which at that time was not yet solved... 

To Tamm sectarian zealotry, pseudoscience, and unprincipled complicity were the most dangerous enemies of science. He started his struggles against them well before his Nobel Prize would represent a limited shield in his protection. Fortunately, he was not alone in recognizing the danger of Lysenko’s unscientific domination of biology under the protective umbrella first by Stalin, then by Khrushchev. Andrei D. Sakharov, well before his becoming a fighter for human rights, had become interested in the biological consequences of nuclear testing and was appalled by the conditions of the relevant biological research in the Soviet Union. Other leading physicists joined in and, if not at once, eventually, the President of the Soviet Academy of Sciences, the noted organic chemist Aleksandr N. Nesmeyanov waged his own battle in salvaging Soviet biology.

Why did I choose this story from the many examples of physicists in biology presented by Hargittai? I had three reasons: 1) It’s a wonderful example of the interaction of biologists with physicists, 2) It’s a fascinating piece of history, and 3) It has relevance today, in our era of antiscience. My favorite line from Hargittai’s paper is “sectarian zealotry, pseudoscience, and unprincipled complicity were the most dangerous enemies of science.” I believe this as true in America today in as it was in the Soviet Union of the 1950s. We physicists need to stand by virologists, immunologists, and climatologists in the current war on science.

The American Institute of Physics Publishing Award for Exceptional Contributions to Biophysics and Bioengineering

This weekend at the Biophysical Society Meeting in San Francisco, John Wikswo will receive The American Institute of Physics Publishing Award for Exceptional Contributions to Biophysics and Bioengineering. This prize honors a member of the scientific community who has made a substantial contribution at the interface of bioengineering and biophysics.

Wikswo was my PhD advisor when I was a graduate student at Vanderbilt University in the 1980s. He is also a collaborator who I have written many papers with, a close friend, and is the godfather of one of my daughters. In a letter of support for Wikswo’s nomination, I wrote

As the name of your award suggests, John’s research has straddled the fields of physics, engineering, and biology. In summary, I think that John Wikswo’s contributions to biomagnetism, cardiac electrophysiology, and bioMEMS, make him a perfect candidate for the Award for Exceptional Contributions to Biophysics & Bioengineering.

If you’re attending the meeting, Wikswo will give a talk at the Bioengineering Symposium at 8:45 Saturday morning, about “Instrument, Measure, Model, and Control: A Directed Walk Through Things Biological.” 

Congratulations, John!

Strange Ideas that Pay Phenomenal Benefits, a conversation with John WIkswo 

https://www.youtube.com/watch?v=xRETnYWDlh0  

Sneak Peak at the New Chapter About Surface Tension in the 6th Edition of IPMB

The first page of Chapter 2 about
surface tension in the sixth edition
of Intermediate Physics for
Medicine and Biology.

For those interested in a preview of the 6th edition of Intermediate Physics for Medicine and Biology, I want to tell you about a new chapter on surface tension. This is the new Chapter 2, following immediately after the chapter about mechanics. It is the shortest chapter in the book. Below is the first paragraph.

Many biological processes occur at the interface between air and water where surface tension is important. Section 2.1 introduces the concept of surface energy, and then Sect. 2.2 relates surface energy to surface tension. Section 2.3 reviews adhesion and cohesion, which indicate if water molecules are more attracted to each other or to an adjacent surface. Section 2.4 describes how surface tension can make water climb up a hollow tube, a process called capillary action. The Bond number is introduced in Sect. 2.5, a dimensionless number that characterizes the relative importance of gravity and surface tension. The ability of an animal to live on the water surface depends on the Bond number. Section 2.6 reviews microfluidics, a modern experimental technique in which fluids flow in tiny chambers where surface tension plays a central role.

I was particularly anxious to include microfluidics in IPMB. We did, although we don't go into much detail. Here is the final section of the chapter.

Scientists have begun performing experiments and analyses using microfluidics: small volumes of fluid (nanoliters) passing through tubes tens of microns wide. In microfluidics, the Reynolds number is small, so flow is laminar, which implies that mixing of different fluids is difficult and must occur by diffusion rather than convection (See Chap. 5). Microfluidic systems often rely on capillary action to pump fluid. When mixing immiscible liquids, surface tension causes droplets to form and the droplet radius is determined by the tube size and the capillary number, a dimensionless number that highlights the competition of viscosity and surface tension (see Problem 18 or Squires and Quake, 2005). 

Microfluidics is used for microanalysis of biomarkers, for cell biology where the tubes have a size similar to the size of single cells, and for drug development. It offers the possibility of analyzing samples rapidly and in parallel, using minute amounts of reagent. Whitesides (2006) discusses many of these applications in detail.

I hope you like it.

Salk's 1954 Polio Clincal Trial

Viruses are rarely mentioned in Intermediate Physics for Medicine and Biology. We do discuss them in the very first section of the book, when we talk about distances and scales. Perhaps we should say more, because viruses and their vaccines are such a hot topic today. Unfortunately, vaccines have become politically controversial. The science often seems to play a secondary role to politics.

Given the current controversy (justified or not) about the safety of vaccines, I thought it would be useful to consider one of the most famous and successful clinical trials: The 1954 trial of Jonas Salk’s polio vaccine. I base this discussion largely on Liza Dawson’s article “The Salk polio vaccine trial of 1954: Risks, randomization and public involvement in research” (Clinical Trials, 1:122–130, 2004).

This was a huge clinical trial, involving over a million children in 44 states. There were essentially two parts, or arms, in the trial. In one arm about 400,000 children in second grade were injected with either the vaccine or a placebo. This part was randomized and double-blind (neither the children, their parents, nor their doctors knew if they received the vaccine or a placebo). In the other arm, about a quarter million second graders received the vaccine, and their results were compared to about three quarters of a million “observed controls” in first and third grades who did not receive an injection.

The trial design had many controversies. First, Salk’s vaccine was based on a virus killed using chemicals. A competing virologist, Albert Sabin, created a vaccine based on an attenuated but live virus. Many medical doctors had concerns about safety, especially with a live virus. Although the implications of contracting polio were terrible, often leading to paralysis or life spent breathing in an iron lung, the incidence of polio in the general population was low. In that case, the safety of the vaccine must be extraordinarily high in order to justify its use. Moreover, the trial needed to be huge in order to have enough statistical power to provide reliable results. Salk had enough confidence in his initial results that he wondered if the use of a placebo was even ethical (an issue often raised today among vaccine advocates and opponents). However, most virologists (including Thomas Francis of the University of Michigan, who was recruited to oversee the study) insisted that at least part of the study include a placebo injection. There were three different strains of polio virus, and the vaccine had to protect against all three. Many epidemiologists worried about bias influencing the “controlled observation” arm of the study. This part was not randomized, and parents consenting to have the vaccine may have represented a subset of families with a different economic or educational background compared to the controls, which could be a confounding factor influencing the results. Above all, the trial would be conducted on children, heightening any ethical concerns. 

Given the distrust of scientists and doctors that many have today, I was impressed by the public support for this trial. The number of polio cases was at its peak in the early 1950s, and parents were terrified of the disease and desperate to slow its spread. The trial was conducted with funding from the National Foundation for Infantile Paralysis (commonly known as the “March of Dimes”). Thousands of volunteers went door to door to raise over $40 million dollars, with the average donation being 27 cents. More than 200,000 lay volunteers helped with the trial, along with 60,000 doctors and nurses and 64,000 teachers and school principals. The study had no difficulty finding parents willing to sign up their children; about two thirds of the parents chose to have their kids participate. There was truly a national ownership of the trial. It was a time, unlike our own, when scientists and medical doctors were held in high regard.

Children received their vaccines between April 26 and June 15, 1954. Blood samples were taken from 40,000 children after inoculation to check for the production of antibodies. On April 12, 1955 the results were announced at the University of Michigan. The overall trial results were clearly positive for all three strains of polio. In the placebo part of the trial, about 200,000 children received the vaccine and another 200,000 the placebo, and roughly twice as many unvaccinated children contracted polio compared to vaccinated children (80 versus 160). A nationwide vaccination program began two weeks later. Within a decade, the number of deaths per year in the United States from polio dropped from about 1000 per year to about 10 per year. Now polio is nearly eradicated from the USA. Let’s do our best to keep it that way. 

 

Celebrating 70 years of the Salk polio vaccine 

https://www.youtube.com/watch?v=SlojaBXCs5o&t=16s

If Anything Is Proven, Climate Science Is Proven

Intermediate Physics for Medicine and Biology, being a textbook, talks a lot about scientific theories, models, and facts, but not much about why we believe these are true. Every once in a while, it’s useful to step back and ask how we know what we know. This is becoming even more important as anti-science forces in our society become louder and more powerful.

Today, I am going to present a video that helps answer the question “Why should we trust science?” It features Harvard Professor Naomi Oreskes, who was awarded the 2025 Volvo Environment Prize “for her groundbreaking research on scientific consensus, climate change, and the often-turbulent journey toward truth in science.” My favorite quote from the video is “if anything is proven, climate science is proven.”

I’ll shut up and let you watch the video. Enjoy! 

 

Why should we trust science? Naomi Oreskes.

 https://www.youtube.com/watch?v=y04gUN86Djs

Walter Gilbert, Biological Physicist

Walter Gilbert, 
provided to Wikimedia by the Science History 
Institute as part of a cooperation project.

I like to collect examples of successful scientists who straddled physics and biology. One example is Walter Gilbert. Intermediate Physics for Medicine and Biology doesn’t discuss Gilbert or cite his work, mainly because the textbook does not focus on molecular biophysics. But he is just the sort of broadly trained scientist with one foot in physics and one in biology that IPMB tries to promote.

Here is what Horace Freeland Judson said about Gilbert in the Eighth Day of Creation: The Makers of the Revolution in Biology, after interviewing him extensively.

The Eighth Day of Creation,
by Horace Freeland Judson.

By far the most important part of [James] Watson’s work on the messenger [mRNA] though, was his recruitment of Walter Gilbert to molecular biology. Gilbert was a theoretical physicist at Harvard when, in the summer of 1960, Watson stopped by the physics department to visit him. “He said, ‘There’s something very nice going on in the lab; whyn’t you come look at it?’ so I came around and looked at it and I joined the experiment,” Gilbert said. “Jim and I and Francois Gros did all the experiments together—just ran them continuously day and night; it was a very exciting period…”

“The experiments we did at that time were, conceptually, terribly trivial,” Gilbert said after a few minutes. “To take a radioactive compound that’s going to be a precursor of RNA—uracil, radioactive phosphate. Feed it to bacteria and look for an RNA species which is made quickly and broken down again… The major problem really was that when you’re doing experiments in a domain that you do not understand at all, you have no guidance to what the experiment should even look like.”

Judson then discusses with Gilbert about his view of how the scientific community responded to their work on mRNA.

“There were large elements in the community who did not believe in the hypothesis at all—that is, that there was an intermediate that was not the ribosomal RNA,” Gilbert said. “The original experiments have an element of interpretation in them. They didn’t actually prove the hypothesis as the hypothesis was stated. One couldn’t do what one can do now, take a known piece of RNA and make a known protein with it. One couldn’t do that then.”

Gilbert’s work on messenger RNA was only one of his contributions. He was an early proponent of the human genome project and developed one of the first automatic DNA sequencers. He also helped establish the biotech industry, cofounding Biogen. In 1980 he shared the Nobel Prize in Chemistry for his “contributions concerning the determination of base sequences in nucleic acids.”

In his Nobel Prize biography, Gilbert tells of his early interest in science.

I always had an interest in science, in those years minerology and astronomy (I was a member of a minerological society and an astronomical society as a child). I became interested in inorganic chemistry at high school. In my last year in high school, 1949, I was fascinated by nuclear physics and would skip school for long periods to go down to the Library of Congress to read about Van de Graaf generators and simple atom smashers. I went to Harvard and majored in chemistry and physics. I became interested in theoretical physics and, as a graduate student, worked in the theory of elementary particles, the quantum theory of fields. I spent my first graduate year at Harvard, then went to the University of Cambridge for two years, where I received my doctorate degree in 1957. My thesis supervisor was Abdus Salam; I worked on dispersion relations for elementary particle scattering: an effort to use a notion of causality, formulated as a mathematical property of analyticity of the scattering amplitude, to predict some aspects of the interaction of elementary particles. I met Jim Watson during this period. I returned to Harvard and, after a postdoctoral year and a year as Julian Schwinger’s assistant, became an assistant professor of Physics. During the late fifties and early sixties, I taught a wide range of courses in theoretical physics and worked with graduate students on problems in theory. However, after a few years my interests shifted from the mathematical formulations of theoretical physics to an experimental field.

Gilbert’s success suggests one path from physics to biology: find a good collaborator who can steer you toward important topics. Then, use your tools from physics to help you solve key biological problems. It may not be the only path (it wasn’t mine), but it is the path that led to Walter Gilbert’s Nobel Prize. 

Scientist Stories: Walter Gilbert, Reminisces of Genomics 

 https://www.youtube.com/watch?v=l0StdYta8ok