The Crucial Decade That Ion Channels Were Proven to Exist

“The Crucial Decade That
Ion Channels Were Proven to Exist:
The Vision of Bertil Hille and Clay Armstrong
and How It Came Through.”

Recently I stumbled upon a nice article in the Pflügars Archiv (the European journal of physiology) that is part review and part history. Its title is “The Crucial Decade That Ion Channels Were Proven to Exist: The Vision of Bertil Hille and Clay Armstrong and How It Came Through.” Ion channels are an important topic in Intermediate Physics for Medicine and Biology, being discussed in Chapter 6 (Impulses in Nerve and Muscle Cells) and Chapter 9 (Electricity and Magnetism at the Cellular Level). The authors are Luigi Catacuzzeno, Antonio Michelucci, and Fabio Franciolini, all with the University of Perugia in Italy.

The article begins with a discussion of Hodgkin and Huxley’s research on a nerve axon. Russ Hobbie and I describe this work in Section 6.13 of IPMB (“The Hodgkin–Huxley Model for Membrane Current”). We focus on their 1952 papers in the Journal of Physiology, and especially the fifth one which developed their mathematical model in detail. It’s a wonderful paper, and when I used to teach my graduate bioelectricity class at Oakland University the students were assigned to read it. I thought I was familiar with the story behind Hodgkin and Huxley’s research, but I learned something new from Catacuzzeno et al. They write (with citations removed)

We wish to recall, in Hodgkin’s words, how in the summer of 1949, in about a month, they managed to complete all the experiments used in the five papers published in 1952, as a special lesson for today’s times, when everything seems to move so fast and often with little thought behind it: “I think that we were able to do this so quickly and without leaving too many gaps because we had spent so long thinking and making calculations about the kind of system which might produce an action potential of the kind seen in squid nerve. We also knew what we had to measure in order to reconstruct an action potential.”

One of the interesting features of the Hodgkin and Huxley work is that they did not know about ion channels. I find it hard to even begin teaching the subject without talking about ion channels, yet they presented all their results without referring to them. Catacuzzeno et al. seem to share my surprise.

Notably, in none of their papers did Hodgkin and Huxley ever mention “ion channels,” only ion currents and conductance. In fact, the concept of an ion channel, as we know it today, did not even exist at the time. Carriers [now known as “transporters”] were more in vogue in the scientific community, also in association with membrane excitation. In the last of their 1952 papers, commenting on the Na⁺ inward current, Hodgkin and Huxley wrote that it could not be excluded “the possibility that Na⁺ ions cross the membrane in combination with a lipoid solubile carrier.” This shows how strongly rooted the concept of the carrier was at the time, and how far removed the concept of the ion channel was.

Ion Channels of Excitable Membranes,
by Bertil Hille.

The main purpose of Catacuzzeno et al.’s article is to explain how the existence of ion channels was established. The heroes of the story are Bertil Hille and Clay Armstrong. Russ and I refer to Hille in IPMB when we cite his wonderful book Ion Channels of Excitable Membranes. I’m embarrassed to say that we don’t mention Armstrong at all. The “crucial decade” in the title of the article is the ten years from roughly 1965 to 1975. 

One nice thing about this review is that it really helps the reader see the scientific method in action. It presents the hypotheses that Hille and Armstrong introduce, and then explains how they designed experiments to test them. Sometimes this perspective gets lost in textbooks like IPMB, but I like how it’s highlighted in Catacuzzeno et al.’s more qualitative and historical review.

Catacuzzeno et al. claim that one of the key pieces of evidence supporting the idea of ion channels that are selective for different ions is the existence of chemicals that block a particular type of channel: tetrodotoxin (TTX) for a sodium channel and tetraethylammonium (TEA) for a potassium channel. Selectivity became a key issue. They write

Classic biophysical experiments beginning in the mid 1960s, which showed distinct conduction properties for different ions, began to provide the first clues as to the architecture and basic physico-chemical properties of the conduction pores and the mechanisms underlying ion permeation and selectivity. Hille focused his efforts on investigating the selectivity properties of these membrane pores with the idea that it would perhaps lead to something instructive regarding their structural and chemical properties. A few studies had already addressed this topic but not in a systematic way as Hille had in mind. By selectively blocking either pathway [sodium or potassium], his studies showed that at least 10 cations could easily permeate through the Na⁺ pores and four through the K⁺ pores of Ranvier’s node [in a myelinated nerve axon]. Considering the size of the ions tested and the length of hydrogen bonds, Hille estimated the Na⁺ pores to have a size, in its most constricted portion, which he called the “selectivity filter,” of 3.1 × 5.1 Å and assumed to be lined by oxygen dipoles that would establish hydrogen bonds with the permeating cations... Most interesting was another observation: all cations with a methyl group were impermeant, regardless of their size. In other words, large hydroxy guanidinium could go through the Na⁺ pore, while small methylammonium could not. These results provided experimental support for previous proposals that permeant ions interact with the pore wall and that this interaction contributes to the membrane’s permeation properties; in other words, the membrane or the pores in it do not merely select by ion size, as if they were simple physical sieves.

Bertil Hille received his PhD from the Rockefeller University in 1967. It was during his graduate studies that he began his collaboration with Clay Armstrong (both of them were young during the crucial decade when ion channels were established). He did a post doc with Alan Hodgkin of Hodgkin and Huxley fame. He then became a professor for many years at the University of Washington’s School of Medicine.

Clay Armstrong, who was six years older than Hille, is a former student of Andrew Huxley. He received his MD degree from the Washington University School of Medicine in 1960. He is currently an emeritus professor of physiology at the University of Pennsylvania. Catacuzzeno et al. describe his research in their review.

Other findings of that period, in particular Armstrong’s experiments with TEA⁺ derivatives on the outward K⁺ current of the squid giant axon, strengthened the notion that the membrane pores were at least partly made up of protein. Years earlier [Ichiji] Tasaki and [Susumu] Hagiwara had obtained action potentials with a long-lasting plateau, like the cardiac action potential, when they perfused internally the squid giant axon with TEA⁺. These data were interpreted as being due to a TEA⁺-dependent block of the outward K⁺ current (which they called anomalous rectification) and resulting failure of K⁺ current-dependent repolarization. Armstrong and [Leonard] Binstock continued their investigation with TEA⁺ by probing the drug on the K⁺ current under voltage clamp, thinking that these compounds could disclose new mechanisms and the pore architecture. First, they found that internal TEA⁺ eliminated the outward K⁺ current, whereas it was totally ineffective when applied from the outside. However, the most interesting results came when Armstrong began probing a series of TEA⁺ derivatives made by replacing one of the four ethyl groups by a progressively longer hydrophobic chain and found that the efficacy of block increased with the chain length. Using C9⁺ (nonyl triethylammonium ion) from the inside, he found that the K⁺ current no longer reached a steady state level during the voltage step but inactivated in a manner quite like the Na⁺ current.

I love how Catacuzzeno et al. include anecdotes that highlight the human side of science. For instance, they demonstrate the initial resistance to the idea of ion channels with this story:

To further represent the general sentiment on the subject at that time, it may also be helpful to recount what happened at the 1966 Biophysical Society meeting, when Armstrong and Hille presented two separate abstracts, both with the word “channel” in the title. As Hille recalls in a recent retrospective “the Chair of the session, Toshio Narahashi, began by announcing that the word ‘channel’ could not be used in the session. After our vigorous objection, he allowed us to use the word ‘provided it did not imply any mechanism!’”.

I highly recommend the article by Catacuzzeno et al. as ancillary reading when studying from Intermediate Physics for Medicine and Biology. It’s wonderfully written, informative, and fascinating. They conclude

Asked why a skeptical medical student would take an interest in the study of ion channels, Clay Armstrong, upon receiving the Albert Lasker Basic Medical Research Award in November 1999 [along with Hille and Roderick MacKinnon], gave the following answer: “I think that ion channels are the most important single class of proteins that exist in the human body or any body for that matter” Undoubtedly, Armstrong knows well that all proteins of the body are crucial and that we cannot do without most of them; undoubtedly, Armstrong is biased in favor of ion channels after a lifetime spent with them. Yet, if he says that ion channels are of outstanding importance, then there must be something very special around them.

Bertil Hille

 https://www.youtube.com/watch?v=2MmUkaWUbyQ

 

Clay Armstrong

https://www.youtube.com/watch?v=r47ChajRftg

Knife Edge Diffraction

Intermediate Physics for Medicine and Biology doesn’t analyze diffraction. It’s mentioned a few times—in the chapters about images (Chap. 12), sound (Chap. 13), and light (Chap. 14)—but it’s never investigated in detail. In this post, I want to take a deeper dive into diffraction. In particular, we will examine a specific example that highlights many features of this effect: diffraction from a knife edge.

Assume a plane wave of light, with intensity I₀ and wavelength λ, is incident on a half-infinite opaque screen (the knife edge, shown below with the incident light coming from the bottom upwards). If optics were entirely geometrical (light traveling in straight lines with no effect of its wavelength) the screen would cast a sharp shadow. All the light for x < 0 would continue propagating upward (in the y direction) while all the light for x > 0 would be blocked. But that’s not what really happens. Instead, light diffracts off the screen, causing fringes to appear in the region x < 0, and some light entering the shadow region of x > 0.

Optics,
by Hecht and Zajac.

Knife-edge diffraction is one of the few diffraction problems that we can solve analytically. I’ll follow the solution given in Hecht and Zajac’s textbook Optics (1979), which I used in my optics class when I was an undergraduate physics major at the University of Kansas. The solution to the knife-edge problem involves Fresnel sine and cosine integrals

I’ve plotted C and S in the top panel of the figure below. Both are odd functions that approach one half as ξ approaches infinity, albeit with many oscillations along the way. There’s lots of interesting mathematics behind these integrals, like the Cornu spiral, but this post is long enough that we don’t have time for that digression. 

If we solve for the intensity distribution beyond the screen (y > 0), we get 

This is an interesting function. When I first saw this solution plotted, I noticed oscillations on the left (x < 0) but none in the shadow region on the right (x > 0). But C and S are both odd, so they oscillate on the right and left. The middle two panels in the figure above show how this happens. Taking one half minus C and one half minus S just flips the two functions and adds a constant, so the functions vary from roughly zero to one instead of minus a half to plus a half. When you square these functions, the oscillations that are nearly equal to zero get really small (a small number like one tenth, when squared, gets very small) while the oscillations that are nearly equal to one are preserved (one squared is just one). There are still some small oscillations in the shadow region (x > 0), but somehow when you add the cosine and sine parts even they go away, and you end up with the classic solution in the bottom panel, which you see in all the textbooks.

I was curious to know is how this function behaves for different wavelengths. Diffraction effects are most important for long wavelengths, but for short wavelengths you expect to recover plain old geometrical optics. Interestingly, the wavelength λ only appears as a scaling factor for x in our solution. So changing λ merely stretches or contracts the function along the x axis. The figure below shows the solution for three different wavelengths. Note that the argument of the Fresnel sine and cosine functions is dimensionless: x has units of distance, but so do the wavelength λ and the distance past the opaque screen y, and they appear as a product under a square root. Therefore, we don’t need to worry about the units of x, y, and λ. As long as we use consistent units we are fine. As the wavelength gets small, the distribution gets crowded together close to x = 0. The red curve is the geometrical optics limit (λ = 0). The case of λ = 0.1 approaches this limit in a funny way. The amplitude of the oscillations does not change, but they fall off more quickly, so they basically only exist very near the knife edge. You wouldn’t notice them unless you looked with very fine spatial resolution. The intensity does seep into the shadow regions, and this is more pronounced at large wavelengths than at small. 

The picture above was plotted for one distance, y = 1. It’s what you would get if you put a projector screen just behind the knife edge so you could observe the intensity pattern there. What happens if you move the screen farther back (increase y). Since y and λ enter our solution only as their product, changing y is much like changing λ. Below is a plot of intensity versus x at three different values of y, for a single wavelength. Making this plot was simple: I just changed the labels on the previous plot from λ to y, and from y to λ. As you get farther way (y gets larger), the distribution spreads out. But the spreading is not linear. Because of that square root, the spreading slows down (but never stops) at large y.

You can see the full pattern of intensity in the color plots below. Remember, x is horizontal and the opaque screen is on the right, y is vertical and opaque screen is at the bottom, and color indicates intensity. Yellow is the incident intensity I₀, and blue is zero intensity (darkness). The geometrical limit would be a strip of blue on the right (the shadow) and yellow on the left (the unobstructed incident wave). The case for λ = 0.01 closely approximates this. The case of a really long wavelength (λ = 100) is interesting. The light spreads out all over, giving more of a uniform distribution. For long wavelengths, the light “bends” around the opaque screen. This is why you can still hear music even if there is an obstacle between you and the band. The sound wave diffracts because of its long wavelength (especially the low pitched notes).

Diffraction is fascinating, but it’s a bit too complicated to be included in IPMB. Nevertheless, it’s a part of the physics behind visual acuity, microscope resolution, ultrasound transducers, and many other applications.

The Age of Reason Begins

The Age of Reason Begins,
by Will and Ariel Durant.

The title of this week’s post is ironic, because with all the events of the last few months I often suspect that the Age of Reason is coming to a close. The title comes from volume seven of Will and Ariel Durant’s The Story of Civilization. After I retired from Oakland University, I set about reading the entire eleven-volume series. The subtitle of The Age of Reason Begins is: A History of European Civilization in the Period of Shakespeare, Bacon, Montaigne, Rembrandt, Galileo, and Descartes: 1558–1648.

Today I want to focus on Francis Bacon, who is probably the central figure in the Durants’ book (his picture was their choice for gracing the book’s cover). They introduce him this way.

Francis Bacon, who was destined to have more influence on European thought than any other Elizabethan, had been born (1561) in the very aura of the court, at York House, official residence of the Lord Keeper of the Great Seal, who was his father, Sir Nicholas; Elizabeth called the boy ‘the young Lord Keeper.’ His frail constitution drove him from sports to studies; his agile intellect grasped knowledge hungrily; soon his erudition was among the wonders of those ‘spacious times.’

Why bring up Bacon now? Well, the last few months have seen unprecedented attacks on science and scientists: Budget cuts to the National Institutes of Health and the National Science Foundation, climate change denial and vaccine hesitancy, conspiracy theories, political requirements for government funding, the demonization of scientists such an Anthony Fauci, and more. It seems like something horrible happens every day. This makes me wonder: what is the key feature of science that must be preserved above all else? What one thing must we save? I can think of many possibilities. Science drives our economy and prosperity. Scientific discoveries have led to amazing advances in human health. Educating and providing opportunities for our young scientists is a critical investment in our future. Yet, as important as these things are, they aren’t the central issue. They aren’t what we must save lest all be lost. It’s this key element of science, its essence, that brings me to Francis Bacon.

Bacon was an early promoter of the scientific method. The Durants write

Bacon felt that the old Organon [of Aristotle] had kept science stagnant by its stress on theoretical thought rather than practical observation. His Novum Organum proposed a new organ and system of thought—the inductive study of nature itself through experience and experiment. Though this book too was left incomplete, it is, with all its imperfections, the most brilliant production in English philosophy, the first clear call for an Age of Reason.

Let me explain (and perhaps expand on) Bacon’s idea in my own words. How do we know what is true and what is not? By evidence. By experiment. By data. By comparing our ideas to what we can measure happening in the world. By accepting as true only those hypotheses that survive our best efforts to disprove them. By submitting our conclusions to rigorous peer review from our fellow scientists. Yet the current Republican administration seems to have its own ideas of what is true, regardless of the evidence. This is the very opposite of science. It is anti-science.

For example, the reality of climate change and humanity’s impact on global warming is backed by an enormous body of data. We have records of temperature, carbon dioxide concentration, and increasingly violent storms. We have sophisticated mathematical models with which we can conduct numerical experiments to predict what will happen in the future. The evidence is truly overwhelming. Yet, many—including President Trump—don’t care about the evidence. They claim climate change is a “hoax.” They don’t back these claims with facts. They don’t approach the topic as an inductive study based on experience and experiment. They believe things for their own reasons that have nothing to do with evidence or science.

Another example is vaccines. There are so many clinical studies showing that vaccines don’t cause autism. Again, the evidence is overwhelming. Yet people like Health and Human Services Secretary Robert F. Kennedy, Jr. believe just the opposite: that autism is caused by vaccines. They don’t support such claims by presenting new evidence. While they occasionally drag up discredited studies or cherry-pick data, they don’t systematically examine all the evidence and weigh both sides. They don’t try to falsify their hypotheses. They don’t subject their ideas to peer-review. 

Still another example is the source of covid. The evidence is uncertain enough that we cannot say definitively how the covid pandemic arose. Yet, the data points strongly in one direction: Spillover from an animal to a human. Nevertheless, the government’s covid.gov website now claims that the “lab leak” hypothesis has been proven, and asserts that covid arose from sinister events in a lab in China. No, we don’t know that. While we can’t yet be certain, the evidence suggests that the cause was not a lab leak. Just because some politicians want the source of covid to be a lab leak doesn’t make it so.

One more example, of particular relevance to Intermediate Physics for Medicine and Biology, is cell phone safety. Although again there are uncertainties in the data (especially in laboratory experiments), the evidence suggests that radiofrequency electromagnetic radiation from cell phones does not cause cancer. I think that to say “suggests” is an understatement. The evidence is compelling that cell phones are safe. Yet RFK Jr. and others continue to argue otherwise, as if evidence doesn’t matter.

I would love to be proved wrong, and shown that, say, climate change is actually not happening. That would truly be wonderful, and millions of lives would be saved. But you have to prove that using evidence. You can’t just declare it. My dad was born in Kansas City and he used to say “I’m from Missouri and you have to show me!” That’s the gist of what it means to be a scientist. You have to show me, not tell me. Convince me with the data.

So, what is the feature of science that is essential? What aspect, if we lose it, means we no longer have science at all. I would say the belief that evidence matters. That experiments are how we determine what is true and what is not. If we give that up, all is lost and we’re back to the age of faith. Not religious faith necessarily, but an age where truth is determined not by evidence but by what is consistent with your personal beliefs, your friends and family, your wishful thinking, your fears, or your politics. The supremacy of evidence is where we must focus our resistance. That must be our line in the sand that we will not cross. That must be the hill from which we defend against the onslaught of the Republican War on Science, so that the Age of Reason can resume.

Francis Bacon,
From the cover of
The Age of Reason Begins.

The Durants conclude

Because he [Bacon] expressed the noblest passion of his age—for the betterment of life through the extension of knowledge—posterity raised to his memory a living monument of influence. Scientists were stirred and invigorated not by his method but by his spirit. How refreshing, after centuries of minds imprisoned in their roots or caught in webs of their own wistful weaving, to come upon a man who loved the sharp tang of fact, the vitalizing air of seeking and finding, the zest of casting lines of doubt into the deepest pools of ignorance, superstition, and fear!...

…[Bacon] repudiated the reliance upon traditions and authorities; he required rational and natural explanations instead of emotional presumptions, supernatural interventions, and popular mythology. He raised a banner for all the sciences, and drew to it the most eager minds of the succeeding centuries.

The Philosophy of Sir Francis Bacon, from Let’s Talk Philosophy.

https://www.youtube.com/watch?v=Mj4N0O7QnPY

Women in the IPMB100

Intermediate Physics for
Medicine and Biology.

Last week I presented the IPMB100, a list of the one hundred people who most influenced Intermediate Physics for Medicine and Biology. In that post, I noted that my list contained few women. Because I support diversity, equity, and inclusion—and because students reading IPMB may be wondering where all the women in biological and medical physics are—this week I’d like to explore the contributions of women to IPMB in more detail. My list last week included Marie Curie, Eugenie Mielczarek, Eleanor Adair, and Irene Stegun. What other females might I have added? 

One would be my friend Natalia Trayanova (born 1960?). I collaborated with Trayanova back in the 1990s, when I was at the National Institutes of Health and she was at Duke University. She is cited in IPMB when Russ Hobbie and I discuss the bidomain model of cardiac tissue. She’s been inducted into the Women of Technology International Hall of Fame and has received the Distinguished Scientist Award from the Heart Rhythm Society. She’s now on the faculty of Johns Hopkins University. 

Another candidate is Rita Hari (born 1948). Russ and I included the biomagnetism researcher Matti Hämäläinen in the IPMB100 list, and Hari is from the same Finnish research group and has made similar contributions as Hämäläinen. She was in fact second author after Hämäläinen on the definitive review article that Russ and I cite about magnetoencephalography (MEG). We cite another paper by Hari when discussing the clinical applications of the MEG.

Bettyann Kevles (1938–2023) was an award-winning author in the Department of History at Yale. Russ and I cite her book Naked to the Bone: Medical Imaging in the Twentieth Century when we discuss the history of imaging.

Frances Ashcroft (born 1952) is an Oxford physiologist known for her work on ion channels. Her popular science book The Spark of Life: Electricity and the Human Body is cited in IPMB when Russ and I discuss channelopathies.

I knew Carri Glide-Hurst (born 1979) when she was at Wayne State University here in southeast Michigan. She’s currently associated with the famous University of Wisconsin medical physics program. In IPMB Russ and I cite her Point/Counterpoint article in the journal Medical Physics, which examines the use of ultrasound for breast cancer screening.

Elizabeth Cherry (born 1975?) at Georgia Tech is a biomedical engineer who works on modeling cardiac electrophysiology. She is a co-author on a landmark paper looking at ways to perform low-energy defibrillation.

The contributions of three of my graduate students—Marcella Woods, Debbie Janks, and Debbie Langrill Beaudoin—are honored in IPMB by having their research turned into homework problems. And Russ’s daughter Sarah is cited for her studies on fitting ecological data using exponentials.

Several other women scientists have influenced IPMB but are not explicitly mentioned or cited in the textbook. These include Lisa Meitner (who worked on Auger electrons simultaneously with but independently of Auger); Rosalind Franklin (whose x-ray diffraction data was critical in Watson and Crick’s model of the structure of DNA); Dorothy Crowfoot Hodgkin (another x-ray crystallographer who discovered the structure of penicillin and insulin); Irene Joliot-Curie (a daughter of Marie Curie who, together with her husband Frédéric Joliot-Curie, discovered induced radioactivity); Rosalyn Yalow (invented the radioimmunoassay); Marie Goeppert Mayer (helped develop the nuclear shell model), Wanda Krassowska (a friend of mine and a colleague of Trayanova’s at Duke University in the 1990s, and who made fundamental contributions to the bidomain model of cardiac tissue); Maria Stuchly (a Polish/Canadian electrical engineer who studied the effect of microwaves on the body); and Marcela Panizza (an Italian clinical neurophysiologist who I collaborated with at NIH when working on magnetic stimulation).

So yes, many females have contributed to IPMB, and could easily have been included in the IPMB100. You could probably name even more. I suspect that future editions of IPMB will feature many more women.

IPMB100

I’m a regular reader of TIME magazine. Every year they publish an issue devoted to the TIME100: the hundred most influential people of that year. I thought I would do the same, except I’d focus on Intermediate Physics for Medicine and Biology. So, below is a list of the one hundred scientists, physicians, engineers, and mathematicians who most influenced IPMB. I list them by impact, with the most influential first.

Like for the TIME100, selecting the list is not an exact science. It’s based on mentions in IPMB, numbers of citations, and my own personal opinions. I’m sure your list would be different, and that’s okay.

There are many brilliant scientists who didn’t make the list (for example: Newton, Faraday, Maxwell, Rutherford, and Einstein). I tried to focus on people who had a direct impact on IPMB, rather than fundamental but not biomedical contributions to physics, so these and other luminaries were left off. 

The oldest scientists are Brown (born 1773) and Poiseuille (1797). The youngest are Basser, Goodsell, Hämäläinen, LeBihon, MacKinnon, Mattiello, Strogatz, and Xia (all more or less my age). I’m embarrassed to say there are only three women (Curie, Eleanor Adair, and Mielczarek; four if you count Abramowitz’s coauthor Stegun). Thirty three are alive today. Twenty are Nobel Prize winners (marked with an asterisk). I know ten personally (marked with a §). When I wasn’t sure about the year a scientist was born or died, I guessed and marked it with a question mark. There are many more I would like to honor, but I decided to—like TIME—stop at 100.

Enjoy!

1. Alan Hodgkin* (1914–1998) English physiologist who discovered how nerve action potentials work and developed the Hodgkin-Huxley model. 
2. Andrew Huxley* (1917–2012) English physiologist and computational biologist who discovered how nerve action potentials work and developed the Hodgkin-Huxley model. 
3. Godfrey Hounsfield* (1919–2004) British electrical engineer who invented the first clinical computed tomography scanner. 
4. Paul Lauterbur* (1929–2007) American chemist who developed a method to do magnetic resonance imaging using magnetic field gradients. 
5. Edward Purcell* (1912–1997) American physicist who co-discovered nuclear magnetic resonance, was author of the article “Life at Low Reynolds Number,” and wrote volume 2 of the Berkeley Physics Course titled Electricity and Magnetism. 
6. Allan Cormack* (1924–1998) South African physicist who developed much of the mathematical theory behind computed tomography. 
7. Hermann von Helmholtz (1821–1894) German physicist and physician; First to measure the propagation velocity of a nerve action potential. 
8. Adolf Fick (1829–1901) German physician and physiologist who derived the laws of diffusion (Fick’s laws). 
9. Willem Einthoven* (1860–1927) Dutch medical doctor and physiologist who was the first to accurately measure the electrocardiogram. 
10. Marie Curie** (1867-1934) Polish-French physicist and chemist who discovered the elements radium and polonium; The unit of the curie is named after her. 
11. Jean Léonard Marie Poiseuille (1797–1869) French physicist and physiologist who determined the law governing the flow of blood in small vessels. 
12. Max Kleiber (1893–1976) Swiss biologist who established a ¾ power law relating metabolic rate to mass. 
13. Felix Bloch* (1905–1983) Swiss-American physicist who co-discovered nuclear magnetic resonance and derived the Bloch equations. 
14. Peter Mansfield* (1933–2017) English physicist who developed techniques used in magnetic resonance imaging, including echo planar imaging. 
15. Roderick MacKinnon* (1956) American biophysicist who determined the structure of the potassium ion channel. 
16. Erwin Neher* (1944) German biophysicist who co-invented the patch clamp method to record from single ion channels. 
17. Bert Sakmann* (1942) German physiologist who co-invented the patch clamp method to record from single ion channels. 
18. Tony Barker (1950) English engineer who invented transcranial magnetic stimulation. 
19. Robert Plonsey§ (1924–2015) American engineer who contributed to theoretical bioelectricity and wrote Bioelectric Phenomena and other books. 
20. Peter Basser§ (1959?) American engineer who invented the magnetic resonance imaging technique of diffusion tensor imaging. 
21. William Oldendorf (1925-1992) American medical doctor who first designed a computed tomography device. 
22. J. B. S. Haldane (1892–1964) British evolutionary biologist who published “On Being the Right Size,” an essay about scaling. 
23. Geoffrey West (1940) British theoretical physicist who derived a model to explain the ¾ power law of metabolism. 
24. George Ralph Mines (1886–1914) English cardiac electrophysiologist who demonstrated reentry in cardiac tissue. 
25. Bernard Cohen (1924–2012) American physicist who opposed the linear no-threshold model of radiation risk. 
26. John Wikswo§ (1949) American physicist who measured the magnetic field of a nerve. 
27. Arthur Winfree§ (1942–2002) American mathematical biologist who studied cardiac arrhythmias and wrote When Time Breaks Down: The Three Dimensional Dynamics of Electrochemical Waves and Cardiac Arrhythmias. 
28. Richard Blakemore (1950?) Researcher who discovered magnetotactic bacteria. 
29. John Moulder (1945–2022) Radiation biologist who debunked suggestions that radiofrequency electromagnetic fields are dangerous. 
30. Kenneth Foster§ (1945) American bioengineer and expert on the biological effects of electromagnetic fields. 
31. Paul Callaghan (1947–2012) New Zealand physicist who wrote Principles of Nuclear Magnetic Resonance Microscopy. 
32. Paul Nunez (1950?) Analyzed electroencephalography using mathematics, and author of Electric Fields of the Brain. 
33. Charles Bean (1923–1996) American physicist who studied porous membranes and reverse osmosis. 
34. John Hubbell (1925–2007) American radiation physicist who measured and tabulated x-ray cross sections. 
35. Arthur Compton* (1892–1962) American physicist who analyzed Compton scattering of x-rays. 
36. William Bragg* (1862–1942) English physicist who discovered the Bragg peak of energy deposition from charged particles in tissue. 
37. Mark Hallett§ (1943) National Institutes of Health neurophysiologist who helped develop transcranial magnetic stimulation and wrote, with Leo Cohen, the article “Magnetism: A New Method for Stimulation of Nerve and Brain.” 
38. Selig Hecht (1892–1947) American physiologist who performed a classic experiment on scotopic vision. 
39. Milton Abramowitz (1915–1958) American mathematician who, with Irene Stegun, coauthored the Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables. 
40. Knut Schmidt-Nielsen (1915–2007) Norwegian-American comparative physiologist and author of How Animals Work and Scaling: Why Is Animal Size So Important? 
41. Steven Vogel (1940–2015) American biomechanics researcher and author of Life in Moving Fluids: The Physical Biology of Flow and other books. 
42. Mark Denny (1951) American physiologist and author of Air and Water: The Biology and Physics of Life’s Media. 
43. Howard Berg (1934–2021) American biophysicist who studied the motility of E. coli and wrote Random Walks in Biology. 
44. Frank Herbert Attix (1925) Radiologist who is the author of Introduction to Radiological Physics and Radiation Dosimetry. 
45. Steven Strogatz (1959) American mathematician and author of Nonlinear Dynamics and Chaos and other books. 
46. Frederick Donnan (1870–1956) British chemist who analyzed Donnan equilibrium. 
47. Gustav Bucky (1880–1963) German-American radiologist who invented the Bucky grid used in x-ray imaging. 
48. Gopalasamudram Narayanan Ramachandran (1922–2001) Indian physicist who, with A. V. Lakshminarayanan, developed mathematical methods used in computed tomography. 
49. Peter Agre* (1949) American molecular biologist who discovered membrane water channels called aquaporins. 
50. Eleanor Adair (1926–2013) American physiologist who studied the health risks of microwave radiation. 
51. Robert Adair (1924–2020) American physicist who studied the biological effects of weak, extremely-low-frequency electromagnetic fields. 
52. Yuan-Cheng Fung (1919–2019) Chinese-American biomedical engineer, and author of Biomechanics. 
53. Herman Carr (1924–2008) American physicist and pioneer in magnetic resonance imaging. 
54. Matti Hämäläinen (1958) Finnish physicist who was lead author on the article “Magnetoencephalography—theory, instrumentation, and applications to noninvasive studies of the working human brain”. 
55. Saul Meiboom (1916–1998) Israeli researcher who, with David Gill, co-invented of the Carr-Purcell-Meiboom-Gill pulse sequence used in magnetic resonance imaging. 
56. Oskar Klein (1894–1977) Swedish physicist who, with Japanese physicist Yoshio Nishina, developed the Klein-Nishina formula for Compton scattering of x-rays. 
57. Chad Calland (1934–1972) Medical doctor, kidney transplant patient, and author of the paper “Iatrogenic Problems in End-Stage Renal Failure.” 
58. Walter Blount (1900–1992) American orthopedic surgeon who advocated for the use of a cane. 
59. Albert Bartlett (1923–2013) American physicist and author of The Essential Exponential! For the Future of Our Planet. 
60. Pierre Auger (1899–1993) French physicist who studied the emission of Auger electrons. 
61. Rolf Sievert (1896–1966) Swedish medical physicist who studied the biological effects of ionizing radiation; The unit of the sievert is named after him. 
62. Louis Gray (1905–1965) English physicist who worked on the effects of radiation on biological systems. The unit of the gray is named after him.
63. Richard Frankel (1943?) American researcher who studied magnetotactic bacteria. 
64. Frederick Reif (1927–2019) Austrian-American physicist who wrote volume 5 of the Berkeley Physics Course, titled Statistical Physics. 
65. Richard FitzHugh (1922–2007) Co-inventor, with Jinichi Nagumo, of the FitzHugh-Nagumo model of a neuron. 
66. Arthur Guyton (1919–2003) American physiologist and author of the Textbook of Medical Physiology. 
67. Leon Glass (1943) American researcher and co-author, with Michael Mackey, of From Clocks to Chaos: The Rhythms of Life. 
68. Ken Kwong (1948) Chinese-American nuclear physicist who studied functional magnetic resonance imaging. 
69. Seiji Ogawa (1934) Japanese biophysicist who studied functional magnetic resonance imaging. 
70. Jay Lubin (1947) National Cancer Institute epidemiologist who battled with Bernard Cohen over the linear no-threshold model and the risk of radon. 
71. Eugenie Mielczarek (1931-2017) American physicist and author of Iron: Nature’s Universal Element: Why People Need Iron and Animals Make Magnets. 
72. David Goodsell (1960?) American structural biologist and science illustrator who wrote the book The Machinery of Life. 
73. Philip Morrison (1915–2005) American physicist who was lead author on Powers of Ten. 
74. Henri Becquerel* (1852–1908) French physicist who discovered radioactivity; the unit of the becquerel is named after him. 
75. Wilhem Roentgen* (1845–1923) German physicist who discovered x rays; The unit of the roentgen is named after him. 
76. Bertil Hille (1940) American biologist and author of Ion Channels of Excitable Membranes. 
77. George Benedek (1928) American physicist who co-authored, with Felix Villars, the three-volume Physics with Illustrative Examples from Medicine and Biology. 
78. William Hendee (1938) Coauthor, with E. Russell Ritenour, of Medical Imaging Physics. 
79. John Cameron (1922–2005) Medical physicist and coauthor of Physics of the Body. 
80. Lawrence Stark (1926–2004) American neurologist and expert on the feedback system controlling the size of the pupil in the eye. 
81. Ernst Ruska* (1906–1988) German physicist who invented the electron microscope. 
82. Britton Chance (1913–2010) American physicist who developed biomedical photonics. 
83. Johann Radon (1887–1956) Austrian mathematician who developed the radon transform used in computed tomography. 
84. Alan Garfinkel (1944?) American researcher who analyzed cardiac restitution for controlling heart arrhythmias. 
85. Eric Hall (1950?) Author of Radiobiology for the Radiologist. 
86. Osborne Reynolds (1842–1912) British engineer who studied fluid mechanics; the Reynolds number is named after him. 
87. Bernard Katz* (1911–2003) German-British biophysicist and author of Nerve, Muscle, and Synapse. 
88. William Rushton (1901–1980) British physiologist who worked with Alan Hodgkin studying nerve conduction. 
89. Robert Eisberg (1928) Coauthor with Robert Resnick of Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles. 
90. John Clark (1936–2017) American bioengineer who worked with Robert Plonsey. 
91. Raymond Ideker§ (1942) American physiologist and medical doctor who studied the electrical activity of the heart. 
92. Denis LeBihan§ (1957) French physicist and medical doctor who developed diffusion magnetic resonance imaging, and worked with Peter Basser on diffusion tensor imaging. 
93. Ronald Bracewell (1921–2007) Author of Fourier Transforms and Their Applications. 
94. Robert Brown (1773–1858) Scottish botanist who discovered Brownian motion. 
95. Louis DeFelice (1940?–2016) Wrote Introduction to Membrane Noise. 
96. H. M. Schey (1930?) Author of Div, Grad, Curl, and All That. 
97. Warren Weaver (1894–1978) American mathematician and science administrator who wrote Lady Luck: The Theory of Probability. 
98. Peter Atkins (1940) English chemist and author of The Second Law. 
99. Yang Xia§ (1955) Oakland University physicist who studied the magic angle in magnetic resonance imaging. 
100. James Mattiello§ (1958-2017) Oakland University alumnus and American physicist who worked with Peter Basser and Denis LeBihan to developed diffusion tensor imaging.

Where Have You Gone, Physicist Bob Park? Our Nation Turns Its Lonely Eyes to You. Woo, Woo, Woo.

Voodoo Science, by Bob Park, superimposed on
Intermediate Physics for Medicine and Biology.

Bob Park died five years ago this week. He had been in poor health since suffering a stroke in 2013. Park was a physicist and the director of public information at the Washington office of the American Physical Society. He was a leading voice against pseudoscience, both in his weekly column What’s New (which, when in graduate school, I used to look forward to seeing in my email every Friday) and in his books such as Voodoo Science.

I wonder what Park would say if he were alive today? I suspect he would be horrified. But I doubt he would have said that. He was not a whine-and-fuss sort of guy. His tools were humor, irony, and sarcasm. Here is what I imagine What’s New would have looked like this week.

What’s New, by Bob Park

Friday, April 25, 2025

1. VITAMIN A FOR THE MEASLES

The Texas measles outbreak continues. Over 600 cases have now been reported, which is more than for the entire year in 2024. Health and Human Services Secretary Robert F. Kennedy, Jr. encouraged parents to treat their children suffering from measles with vitamin A, and now children are suffering from liver disease because of vitamin A overdosing. Why don’t parents simply ask their pediatrician what to do? Because pediatricians are part of the conspiracy, of course!

2. IF WE IGNORE IT, IT WILL GO AWAY

The Trump administration is trying to undo all the progress fighting climate change that has accumulated over the last few decades. His thinking is: if you ignore climate change, the problem goes away. Besides, it’s all a HOAX! King Canute tried this. He commanded the tide to stop coming in. How do you think that turned out? Physics has a way of winning in the end, whether or not it’s politically popular.  

3. LAB LEAK

The Trump administration has rewritten the covid.gov website to advocate for the lab leak hypothesis for the source of covid-19. Don't worry that the evidence is flimsy! If covid resulted from a lab leak, then it’s the scientists fault. Blame those arrogant liberal elitists like Fauci. But watch out for the next spillover event! (Can I interest anyone in some bird flu?)

4. LYSENKO

Back in the USSR, when Stalin was in charge, a crackpot named Lysenko took control of Russian science. He didn’t believe in modern genetics, regardless of the evidence. Russian agriculture collapsed and millions died. Here in the United States, we have our own version of the Lysenko affair. Trump is Stalin, RFK Jr is Lysenko, and vaccine hesitancy and climate change are genetics. I fear the outcome will be the same, which is bad for science and worse for humanity.

5. HOORAY FOR HARVARD

The NIH (remember that place that used to be the greatest biomedical research institution anywhere, ever?) has stopped funding grants to several universities, including Harvard. HARVARD! Apparently these universities will not cave in to Trump's ideological agenda. What will happen next? Who knows. Maybe Trump will be stopped by the Supreme Court. Maybe the House and Senate will decide they’ve had enough. And maybe, just maybe, it will be the end of American science.