Mark Hallett (1943–2025)

Mark Hallett,
from the NIH Record.

Readers of this blog may remember neurologist Mark Hallett, who I featured three years ago in a post about his retirement from the National Institutes of Health. Today, I must share some sad news: Hallett died of brain cancer on November 2, 2025.

Mark Hallett was a pioneer in using transcranial magnetic stimulation to study the brain. In Intermediate Physics for Medicine and Biology, Russ Hobbie and I describe magnetic stimulation.

8.7 Magnetic Stimulation

Since a changing magnetic field generates an induced electric field, it is possible to stimulate nerve or muscle cells without using electrodes. The advantage is that for a given induced current deep within the brain, the currents in the scalp that are induced by the magnetic field are far less than the currents that would be required for electrical stimulation. Therefore transcranial magnetic stimulation (TMS) is relatively painless. It is also safe (Rossi et al. 2009). 

Magnetic stimulation can be used to diagnose central nervous system diseases that slow the conduction velocity in motor nerves without changing the conduction velocity in sensory nerves (Hallett and Cohen 1989). It could be used to monitor motor nerves during spinal cord surgery, and to map motor brain function. Because TMS is noninvasive and nearly painless, it can be used to study learning and plasticity (changes in brain organization over time; Wassermann et al. 2008). Recently, researchers have suggested that repetitive TMS might be useful for treating disorders such as depression (O’Reardon et al. 2007) and Alzheimer’s disease (Freitas et al. 2011).

Mark Hallett,
from the NIH Record.

Here is what I wrote about Hallett in a review of my experience with magnetic stimulation.

One of my first tasks at NIH was to meet with two medical doctors in the National Institute of Neurological Disorders and Stroke—Mark Hallett and Leo Cohen—who had recently begun using magnetic stimulation. Hallett obtained his medical degree from Harvard and was chief of the Human Motor Control Section, housed in NIH’s famous clinical center. He is a leading figure in neurophysiology, specifically in magnetic stimulation research, and is often asked to publish tutorials about magnetic stimulation in leading journals. Hallett once told me that he began college as a physics major but switched to a pre-med program after a year or two. Cohen earned his MD from the University of Buenos Aires in Argentina. In the late 1980s, he worked in Hallett’s section, but eventually became the head of his own Human Cortical Physiology Section at NIH. Together Hallett and Cohen were doing groundbreaking research in magnetic stimulation but lacked the technical expertise in physics required to do things like calculate the electric fields produced by different coils…

Hallett and Cohen obtained a magnetic stimulator at NIH in the late 1980s. They described magnetic stimulation and its potential uses in the Journal of the American Medical Association [Magnetism: A new method forstimulation of nerve and brain. JAMA, 262, 538–541, 1989.], where they highlighted how assessment of central conduction times using magnetic stimulation could be useful for diagnosing diseases, such as multiple sclerosis, and also how the method could be suitable for monitoring the integrity of the spinal cord during surgery. They emphasized that although methods existed to measure the conduction time in the brain for sensory fibers, stimulation of the brain was needed to measure conduction times in central motor fibers.

Not entirely realizing the explosion of research I was lucky enough to be wading into, I started collaborating with Hallett and Cohen to calculate the electric fields produced during magnetic stimulation... Our first work together was a technical paper comparing the electric and magnetic fields produced by a variety of coils with different shapes… Hallett and Cohen were most interested in the electric field induced during transcranial magnetic stimulation, so my next task was to use a three-sphere model to calculate the electric field in the brain...

I was anxious to test the prediction of where excitation occurs along a peripheral nerve during magnetic stimulation [that Peter Basser and I had made]. The ideal experiment would be to dissect a nerve, place it in a dish filled with saline, and then stimulate it. However, Hallett and Cohen were focused mainly on clinical applications, so we tested the prediction in humans. The experiment was performed by Marcela Panizza, an Italian medical doctor, and her husband Jan Nilsson, a biomedical engineer originally from Denmark but working with Panizza in Italy. Panizza and Nilsson would often visit NIH to collaborate with Hallett and Cohen. In the experiment, the median nerve was stimulated at the forearm and the motor response was recorded using electrodesattached to the thumb... [They showed that] that magnetic stimulation did not occur where the electric field was largest, but instead where its spatial derivative was largest.

The research at NIH was assisted by an outstanding group of young scientists who worked with Hallett and Cohen. For example, the Brazilian neurologist Joaquim Brasil-Neto examined how the orientation of the electricfield influenced the stimulation threshold... Peter Fuhr analyzed how the latency of motor-evoked potentials depended on the position of thestimulating coil relative to the head... Eric Wassermann—a medical doctor who trained with Hallett and was editor of the Oxford Handbook of Transcranial Stimulation—wrote a review of safety issues... One of the most serious safety hazards was discovered by Alvaro Pascual-Leone, a Spanish MD/PhD who trained at NIH in the 1990s. Pascual-Leone and his colleagues wanted to record the electroencephalogram (EEG) during and immediately following rapid rate transcranial magnetic stimulation, so they stimulated with silver EEG recording electrodes placed over the scalp. One patient suffered a burn under an electrode.

Hallett was one of my most important collaborators throughout my career. In fact, if you look at Google Scholar to examine my most influential articles (those with over 100 citations each), Hallett was my most common coauthor (13), followed closely by Leo Cohen (11), then my PhD advisor John Wikswo (8), and finally my good friend from NIH Peter Basser (6), who also collaborated with Hallett. One could argue that no other scientist except Wikswo had such an impact on my career.

Hallett was a giant in his field of neurology. He will be missed by many, including me.

Oral History 2013: Stanley Fahn Interviews Mark Hallett

https://www.youtube.com/watch?v=eR-D9bLWKhQ 

Madison Spach (1926–2025)

Madison Stockton Spach died recently. An Instagram post by the account for the Duke Pediatric Cardiology Fellowship stated

Very sad to report the passing of Dr. Madison Spach. Dr. Spach was the first Division Chief of Pediatric Cardiology at Duke and the founder of our program. He was a legend in the field and mentored others who also went on to become preeminent in the field. His impact through innovations, the patients he cared for, those he mentored, and the program he built is immeasurable.

I have not been able to find an obituary about Spach (I hope one is published eventually). However, here’s a picture and bio published in the IEEE Transactions of Biomedical Engineering in 1971. 

His wife Cecilia passed away seven years ago. Her obituary said

Cecilia Goodson Spach, 92, died peacefully in her sleep on Oct 20, 2018, after a short illness. Madison Spach, her loving husband of nearly 70 years, was with her when she passed away…

Cecilia Goodson was born and raised in Winston-Salem. She was a star athlete at Reynolds High School, where she met her perfect match in Madison Spach. Cecilia earned a nursing degree from Presbyterian Hospital School of Nursing in Charlotte. When Madison returned from the service, they married and moved to Durham, where Madison attended Duke University.

Madison Spach was born in 1926. This would mean if he entered the service right out of high school, he may have fought in the last year of World War II. He was 98 when he died this year. It’s sad that we are losing so many of our veterans of the greatest generation these days, when we need them most. 

Russ Hobbie and I didn’t mention Spach in Intermediate Physics for Medicine and Biology, although we do discuss his field: cardiac electrophysiology. However, I described his contributions briefly in my unpublished review and history of the bidomain model of cardiac tissue. I wrote

In the 1980s, Duke was the center for research about the electrical behavior of the heart. Not only was Plonsey there, along with his collaborator Barr and his student Henriquez, but also it hosted several other leading scientists. Barr was a long-time collaborator with Madison Spach, a Duke medical doctor known for his electrophysiological experiments on cardiac tissue. Some of their analyses foreshadowed key features of the bidomain model (Spach et al. 1978).

The citation was to Spach’s paper with long-time collaborator Roger Barr and others published in the journal Circulation Research.

Spach MS, Miller WT III, Miller-Jones E, Warren RB, Barr RC (1978) Extracellular potentials related to intracellular action potentials during impulse conduction in anisotropic canine cardiac muscle. Circ Res 45:188–204.

In addition, when reviewing Craig Henriquez and Robert Plonsey’s work on cardiac wave fronts propagating through cardiac tissue surrounded by a perfusing bath, I wrote

The bidomain model represents cardiac tissue as a continuous syncytium, so Henriquez and Plonsey’s mathematical simulations provided a new interpretation of earlier experimental data that had been used to argue that cardiac tissue acted like a discrete collection of cells (Spach et al. 1981).

This citation was to Spach’s hugely influential article 

Spach MS, Miller WT, Geselowitz DB, Barr RC, Kootsey JM, Johnson EA (1981) The discontinuous nature of propagation in normal cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res 48:39–54.

It’s no secret that, like Henriquez and Plonsey, I disagreed with Spach’s interpretation of his data as implying discontinuous propagation in cardiac tissue. But I’ve told that story before and this isn’t the time or place to rehash it. Suffice to say, according to Google Scholar Spach’s paper has been cited about 950 times. Another paper on the same topic (Spach’s most highly cited article) with Paul Dolber has over a thousand citations.

Spach MS, Dolber PC (1986) Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res 58:356–371.

Duke now has a scholarship named jointly for Roger Barr and Madison Spach. Here’s what the Duke scholarship website says about Spach’s contributions.

Madison S. Spach is a James B. Duke Professor Emeritus of medicine and Professor Emeritus of pediatrics in the School of Medicine. A renowned pediatric cardiologist and scientist, his research examined electrophysiology and the mechanisms behind cardiac dysrhythmias. On the faculty from 1960–1996, Spach developed Duke's training program in pediatric cardiology.

As I said in last week’s post, one goal I have for this blog is to support scientists, and that includes  retired ones who’ve made important contributions. Madison Spach helped us advance our knowledge of cardiac electrophysiology. His was a life worth living.

J. Patrick Reilly (1937—2024)

J. Patrick Reilly died on October 28 in Silver Spring, Maryland, at the age of 87. He was a leader in the field of bioelectricity, and especially the study of electrical stimulation.

Russ Hobbie and I didn’t mention Reilly in Intermediate Physics for Medicine and Biology, but I did in my review paper “The Development of Transcranial Magnetic Stimulation.”

J. Patrick Reilly of the Johns Hopkins Applied Physics Laboratory calculated electric fields in the body produced by a changing magnetic field, although primarily in the context of neural stimulation caused by magnetic resonance imaging (MRI) [54, 55].

[54] Reilly, J. P. (1989). Peripheral nerve stimulation by induced electric currents: Exposure to time-varying magnetic fields. Med. Biol. Eng. Comput., 27, 101–110.

[55] Reilly, J. P. (1991). Magnetic field excitation of peripheral nerves and the heart: A comparison of thresholds. Med. Biol. Eng. Comput., 29, 571–579.

The papers included this biography of the author. 

 

Applied Bioelectricity,
by J. Patrick Reilly.

Reilly was also known for his 1998 book Applied Bioelectricity: From Electrical Stimulation to Electropathology, which covered many of the same topics as Chapters 6–8 in IPMB: The Hodgkin-Huxley model of a nerve action potential, the electrical properties of cardiac tissue, the strength-duration curve, the electrocardiogram, and magnetic stimulation. However, you can tell that Russ and I are physicists while Reilly is an engineer. Applied Bioelectricity focuses less on deriving equations from fundamental principles and providing insights using toy models, and more on predicting stimulus thresholds, analyzing stimulus wave forms, examining electrode types, and assessing electrical injuries. That’s probably why he included the word “Applied” in his title. Compared to IPMB, Applied Bioelectricity has no homework problems, fewer equations, a similar number of figures, more references, and way more tables.

Reilly’s preface begins

The use of electrical devices is pervasive in modern society. The same electrical forces that run our air conditioners, lighting, communications, computers, and myriad other devices are also capable of interacting with biological systems, including the human body. The biological effects of electrical forces can be beneficial, as with medical diagnostic devices or biomedical implants, or can be detrimental, as with chance exposures that we typically call electric shock. Whether our interest is in intended or accidental exposure, it is important to understand the range of potential biological reactions to electrical stimulation.

In 2018, Reilly was the winner of the d’Arsonval Award, presented by the Bioelectromagnetic Society for outstanding achievement in research in bioelectromagnetics. The award puts him in good company. Other d’Arsonval Award winners include Herman Schwan, Thomas Tenforde, Elanor Adair, Shoogo Ueno, and Kenneth Foster.

I don’t recall meeting Reilly, which is a bit surprising given the overlap in our research areas. I certainly have been aware of his work for a long time. He was a skilled musician as well as an engineer. I would like to get a hold of his book Snake Music: A Detroit Memoir. It sounds like he had a difficult childhood, and there were many obstacles he had to overcome to make himself into a leading expert in bioelectricity. Thank goodness he persevered. J. Patrick Reilly, we’ll miss ya.

Willi Kalender (1949–2024)

Medical physicist Willi Kalender died on October 20 at the age of 75. Kalender was an inventor of spiral computed tomography. Russ Hobbie and I describe spiral CT in Chapter 16 of Intermediate Physics for Medicine and Biology.

Figure 16.25 shows the evolution of the detector and source configurations [of CT]. The third generation configuration is the most popular. All of the electrical connections are made through slip rings. This allows continuous rotation of the gantry and scanning in a spiral as the patient moves through the machine. Interpolation in the direction of the axis of rotation (the z axis) is used to perform the reconstruction for a particular value of z. This is called spiral CT or helical CT. Kalender (2011) discusses the physical performance of CT machines, particularly the various forms of spiral machines.

Computed Tomography,
by Willi Kalender.

The citation is to Kalender’s well-known textbook Computed Tomography: Fundamentals, System Technology, Image Quality and Applications. According to Google Scholar, it has been cited over 1800 times. Russ and I reference it often.

Kalender obtained his PhD in 1979 from the University of Wisconsin’s famous medical physics program. He then went to the University of Tübingen in Germany. There, according to Wikipedia, “he took and successfully completed all courses in the pre-clinical medicine curriculum.” This is interesting, because just a few years earlier Russ Hobbie did the same thing in Minnesota.

Between 1971 and 1973 I audited all the courses medical students take in their first 2 years at the University of Minnesota. I was amazed at the amount of physics I found in these courses and how little of it is discussed in the general physics course.

Kalender was much loved in the radiology community. The European Society of Radiology wrote

With deep sadness, the ESR announces the passing of Prof. Willi Kalender on October 20, 2024 at the age of 75. A pioneering figure in diagnostic imaging and medical physics, Prof. Kalender significantly influenced the field through his groundbreaking research and leadership.

You can find a memorial page with many more tributes to Kalender here: https://www.kudoboard.com/boards/xqZwpoWO

Prof. Willi Kalender — Dedicated Breast CT — Interview at RSNA 2013

https://www.youtube.com/watch?v=9Ay-Ry6a8C0 

 

Joe Redish (1943–2024)

Edward “Joe” Redish, a University of Maryland physics professor, died August 24 of cancer. Joe has been mentioned many times in this blog (here, here, here, and here). He was deeply interested in how students—and in particular biology students—learn physics, an interest with obvious relevance to Intermediate Physics for Medicine and Biology.

Redish, E. F., 
“Using Math in Physics: 7. Telling the Story,”
Phys. Teach., 62: 5–11, 2024.

I knew Joe, and valued his friendship. Rather than writing about him myself,  I’ll share some of his thoughts in his own words. He had a wonderful series of papers in The Physics Teacher about using math in physics. The last of the series (published this year) was about using math to tell a story (Redish, E. F., “Using Math in Physics: 7. Telling the Story,” Phys. Teach., Volume 62, Pages 5–11, 2024). He wrote

Even if students can make the blend—interpret physics correctly in mathematical symbology and graphs—they still need to be able to apply that knowledge in productive and coherent ways. As instructors, we can show our solutions to complex problems in class. We can give complex problems to students as homework. But our students are likely to still have trouble because they are missing a key element of making sense of how we think about physics: How to tell the story of what’s happening.

We use math in physics differently than it’s used in math classes. In math classes, students manipulate equations with abstract symbols that usually have no physical meaning. In physics, we blend conceptual physics knowledge with mathematical symbology. This changes the way that we use math and what we can do with it.

We use these blended mental structures to create stories about what’s happening (mechanism) and stabilize them with fundamental physical laws (synthesis).

In an oral history interview with the American Institute of Physics, Joe talked about using simple toy models when teaching physics to biology students.

One of the problems that students run into, that teachers of physics run into teaching biology students, is we use all these trivial toy models, right? Frictionless vacuum. Ignore air resistance. Treat it as a point mass. And the biology students come in and they look at this and they say, “These are not relevant. This is not the real world.” And they know in biology, that if you simplify a system, it dies. You can’t do that. In physics we do this all the time. Simple models are kind of a core epistemological resource for us. You find the simplest example you possibly can and you beat it to death. It illustrates the principle. Then you see how the mathematics goes with the physics. The whole issue of finding simple models is where a lot of the creative art is in physics.

Redish and Cooke,
“Learning Each Other’s Ropes:
Negotiating Interdisciplinary Authenticity”
CBE—Life Sciences Education,
12:175–186, 2013.

My favorite of Joe’s papers is “Learning Each Other’s Ropes: Negotiating Interdisciplinary Authenticity” which he coauthored with biologist Todd Cooke (CBE—Life Sciences Education, Volume 12, Pages 175–186, 2013).

From our extended conversations, both with each other and with other biologists, chemists, and physicists, we conclude that, “science is not just science.” Scientists in each discipline employ a tool kit of different types of scientific reasoning. A particular discipline is not characterized by the exclusive use of a set of particular reasoning types, but each discipline is characterized by the tendency to emphasize some types more than others and to value different kinds of knowledge differently. The physicist’s enthusiasm for characterizing an object as a disembodied point mass can make a biologist uncomfortable, because biologists find in biology that function is directly related to structure. Yet similar sorts of simplified structures can be very powerful in some biological analyses. The enthusiasm that some biologists feel toward our students learning physics is based not so much on the potential for students to learn physics knowledge, but rather on the potential for them to learn the types of reasoning more often experienced in physics classes. They do not want their students to think like physicists. They want them to think like biologists who have access to many of the tools and skills physicists introduce in introductory physics classes… We conclude that the process is significantly more complex than many reformers working largely within their discipline often assume. But the process of learning each other’s ropes—at least to the extent that we can understand each other’s goals and ask each other challenging questions—can be both enlightening and enjoyable. And much to our surprise, we each feel that we have developed a deeper understanding of our own discipline as a result of our discussions.

You can listen to Joe talk about physics education research on the Physics Alive podcast.

We’ll miss ya, Joe.

Bill Catterall (1946–2024)

William Catterall, known as “the father of ion channels,” died on February 28 at the age of 77. Russ Hobbie and I cite Catterall’s article on the structure of sodium ion channels in Chapter 9 of Intermediate Physics for Medicine and Biology.

Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475:353–358.

Catterall worked in the intramural program at the National Institutes of Health in the laboratory of Marshall Nirenberg. He then moved to the University of Washington, where he was a professor of Pharmacology for over 40 years. There he was a collaborator with Bertil Hille, the author of the landmark textbook Ion Channels of Excitable Membranes. An obituary published by the University of Washington website states

First and foremost, Bill was an exceptional scientist. He pioneered the biochemical investigation of calcium and sodium ion channels; molecular portals that allow the controlled passage of ions across cell membranes. The proper passage of ions into the cell is essential for healthy brain, heart, and muscle function. Early work from Catterall elucidated the molecular basis of ion channel gating whereas later studies with UW Pharmacology colleague Dr. Ning Zheng revealed details of how these clinically relevant macromolecular machines operate at the atomic level. With this latter information, Catterall was able to ascertain how a variety of toxins as well as local anesthetics and antiarrhythmic drugs act to “lock the gate” on these ion channels. Bill was recognized for these pivotal discoveries by election to the National Academy of Sciences USA and the Royal Society London. He also received prestigious awards including the Gairdner Award from Canada, the Robert R. Ruffolo Career Achievement Award in Pharmacology from the American Society of Pharmacology and Therapeutics, and a Lifetime Achievement Award from the International Union of Pharmacologists.

To learn more, listen to Catterall discuss his work in a three-part series of lectures for iBiology. 

William Catterall (U. Washington) Part 1: Electrical Signaling: Life in the Fast Lane  

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

 

William Catterall (U. Washington) Part 2: Voltage-gated Na+ Channels at Atomic Resolution

 https://www.youtube.com/watch?v=hfXGsJCOC9A

 

William Catterall (U. Washington) Part 3: Voltage-gated Calcium Channels

https://www.youtube.com/watch?v=bUE8gzMqqb8

Robert Kemp Adair (1924–2020)—Notes on a Friendship

Robert Adair.
Photo credit: Michael Marsland/Yale University.

I try to write obituaries of scientists who appear in Intermediate Physics for Medicine and Biology, but for some reason I didn’t write about Robert Adair’s death in 2020. Perhaps the covid pandemic over-shadowed his demise. In Chapter 9 of IPMB, Russ Hobbie and I cite seven of his publications. He was a leader in studying the health effects (or, lack of heath effects) from electric and magnetic fields.

Recently, I read a charming article subtitled “Notes on a Friendship” about Adair, written by Geoffrey Kabat, the author of Getting Risk Right: Understanding the Science of Elusive Health Risks. I have Getting Risk Right on my to-read list. It sounds like my kind of book.

I admire Adair’s service in an infantry rifle platoon during World War II. I loved his book about baseball. I respect his independent assessment of the seriousness of climate change, although I don’t agree with all his conclusions. He certainly was a voice of reason in the debate about health risks of electric and magnetic fields. He led a long and useful life. We need more like him.

I will give Kabat the final word, quoting the last paragraph of his article.

In early October 2020, Bob’s daughter Margaret called me to tell me that Bob had died. I looked for an obituary in the New York Times, and was shocked when none appeared, likely due to the increased deaths from the pandemic. I wrote to an epidemiologist colleague and friend, who knew Bob’s work on ELF-EMF [extremely low frequency electromagnetic fields] and microwave energy, and who had served on a committee to assess possible health effects of the Pave Paws radar array on Cape Cod. My friend Bob Tarone wrote back, “Very sad to hear that. Adair was not directly involved in the Pave Paws study, but we relied heavily on his superb published papers on the biological effects of radio-frequency energy in our report. He and his wife were superb scientists. Losing too many who don’t seem to have competent replacements. Too bad honesty and truth are in such short supply in science today.” He concurred that there should have been an obituary in the Times.

Craig Henriquez (1959–2023)

I just learned that my friend Craig Henriquez passed away last summer. Craig earned his PhD at Duke University in their Department of Biomedical Engineering under the guidance of the renowned bioelectricity expert Robert Plonsey. His 1988 dissertation, titled “Structure and Volume Conductor Effects on Propagation in Cardiac Tissue,” was closely related to work I was doing at that time. Craig sent me a copy of his dissertation after he graduated. I really wanted to read it, but I was swamped with my my new job at the National Institutes of Health and helping care for my newborn daughter Stephanie. There wasn’t time to read it at work, and when I got home it was my turn to watch the baby, as my wife had been with her all day. The solution was to read Craig’s dissertation out loud to Stephanie as she crawled around in her play pen. She seemed to like the attention and I got to learn about Craig’s work.

Craig and I are nearly the same age. He was born in 1959 and I in 1960. Our careers progressed along parallel lines. After he graduated he stayed at Duke and joined the faculty. I recall he told me at the time that he didn’t know if he would make a career in academia, but he certainly did. He was on the Duke faculty for 35 years. In the early 1990s three young researchers at Duke—Craig, Natalia Trayanova, and Wanda Krassowska—were all from my generation. They were my friends, collaborators, and sometimes competitors as we worked to establish the bidomain model as the state-of-the-art representation of the electrical properties of cardiac tissue.

In my recent review about bidomain modeling (Biophysics Reviews, Volume 2, Article 041301, 2021) , I wrote (referring to myself in third person, as required by the journal; in the quotes below references are removed):

Roth’s calculation was not the first attempt to solve the active bidomain model using a numerical method. In 1984, Barr and Plonsey had developed a preliminary algorithm to calculate action potential propagation in a sheet of cardiac tissue. Simultaneous with Roth’s work, Henriquez and Plonsey were examining propagation in a perfused strand of cardiac tissue. For the next several years, Henriquez continued to improve bidomain computational methods with his collaborators and students at Duke. His 1993 article published in Critical Reviews of Biomedical Engineering remains the definitive summary of the bidomain model.

I’ve cited his 1993 review article (Crit. Rev. Biomed. Eng., Volume 21, Pages 1–77) many times, including in Intermediate Physics for Medicine and Biology. It’s a classic.

Craig and I were both interested in determining if Madison Spach’s electrical potential data from cardiac tissue samples should be interpreted as evidence of discontinuous propagation (Spach’s hypothesis) or a bath effect.

The original calculations of action potential propagation in a continuous bidomain strand perfused by a bath hinted at different interpretations of Spach’s data. As discussed earlier, the wave front is not one-dimensional because its profile varies with depth below the strand surface. The same effect occurs during propagation through a perfused planar slab, more closely resembling Spach’s experiment. The conductivity of the bath is higher than the conductivity of the interstitial space, so the wave front propagates ahead on the surface of the tissue and drags along the wave front deeper below the surface, resulting in a curved front. The extra electrotonic load experienced at the surface slows the rate of rise and the time constant of the action potential foot. Plonsey, Henriquez, and Trayanova analyzed this effect, and subsequently so did Henriquez and his collaborators and Roth.

Craig became an associate editor of the IEEE Transactions on Biomedical Engineering, and he would often send me papers to review. He was a big college basketball fan. We would email each other around March, when our alma maters—my Kansas Jayhawks and his Duke Blue Devils—would face off in the NCAA tournament. His research interests turned to nerves and the brain, and he co-directed a Center of Neuroengineering at Duke. He eventually chaired Duke’s biomedical engineering department, and at the time of his death he was an Associate Vice Provost.

I found out about Craig’s death when I was submitting a paper to a journal. This publication asks authors to suggest potential reviewers, and I was about to put Craig’s name down as a person who would give an honest and constructive assessment. I googled him to get his current email address, and discovered the horrible news. What a pity. I will miss him. 

Short bio published in the IEEE Transactions on Biomedical Engineering in January, 1990.

 Craig Henriquez talking about cardiac tissue and the bidomain model.

https://www.youtube.com/watch?v=OiSiLwP1ZPo

Paul Maccabee (1944–2023)

Paul Maccabee (1944–2023).
Photo used with permission from the
Downstate Health Sciences University website.

My friend and collaborator Paul Maccabee died on July 24. Paul was a pioneer in the field of magnetic stimulation, a topic that Russ Hobbie and I discuss in Chapter 8 of Intermediate Physics for Medicine and Biology. Paul’s career and mine had many parallels. We both worked on magnetic stimulation in the late 1980s and early 1990s. We both collaborated with a leading neurophysiologist: Paul with Vahe Ammasian and me with Mark Hallett. We both recognized the importance of laboratory animal experiments for identifying physiological mechanisms. We both were comfortable working with biomedical engineers, I entered that field from physics and Paul from medicine. 

Paul was about 15 years older than me and I viewed him as a role model. I believe I first met him at the 1989 International Motor Evoked Potential Symposium in Chicago, a key early conference dedicated to magnetic stimulation. Our paths crossed at other scientific meetings and his research had a major impact on my own. For years I taught a graduate class on bioelectricity at Oakland University and I had my students read Paul’s 1993 Journal of Physiology paper (described below) which I assigned because it’s a classic example of a well-written scientific article. According to Google Scholar that paper has been cited 374 times, and it should be cited even more.

I wrote about Paul in my review of the development of transcranial magnetic stimulation (BOHR International Journal of Neurology and Neuroscience, Volume 1, Pages 8–20, 2022, https://doi.org/10.54646/bijnn.002). Below I quote part of that article. I put his name in bold so you can find it easily.

Although this experiment [performed by Jan Nilsson and Marcela Panizza at the National Institutes of Health, see reference 49] confirmed [Peter Basser and my] prediction [that neural excitation occurs where the gradient of the induced electric field is largest, see reference 58], there were nevertheless concerns because of the heterogeneous nature of the bones and muscles in the human arm. At about the same time Nilsson and Panizza were doing their experiment at NIH, Paul Maccabee was performing an even better experiment at the New York Downstate Medical Center in Brooklyn. Maccabee obtained his MD from Boston University and collaborated in Brooklyn with the internationally acclaimed neuroscientist Vahe Ammasian [1, 40–43]. This research culminated in their 1993 article in the Journal of Physiology, in which they examined magnetic stimulation of a peripheral nerve lying in a saline bath [44]. First, they measured the electric field E_y (they assumed the nerve would lie above the coil along the y-axis) and its derivative along the nerve produced by a figure-8 coil located under the bath (Figure 9). They found that the electric field was maximum directly under the center of the coil, but the magnitude of the gradient dE_y/dy was maximum a couple centimeters either side of the center.

Figure 9. Contour plots of the electric field (E_y, red) and its spatial derivative (dE_y/dy, blue) induced by a figure-eight coil (purple) placed under a tank filled with saline and measured using a bipolar recording electrode. The y direction is downward in the figure, parallel to the direction of the nerve (see Figure 10). Adapted from Figure 2 of Maccabee et al. [44].

Next they placed a bullfrog sciatic nerve in the dish and recorded the electrical response from one end (Figure 10). They found a 0.9 ms delay between the recorded action potentials when the polarity of a magnetic stimulus was reversed (the yellow and red traces on the right). Given a propagation speed of about 40 m/s, the shift in excitation position was about 3.6 cm, consistent with what Basser and I would predict.

Figure 10. Recordings from an electrode (black dot) at the distal end of a bullfrog sciatic nerve (green) that was immersed in a trough filled with saline (blue) and stimulated with a figure-8 coil (purple). The nerve emerged from the saline to rest on the recording electrode in air. The compound nerve action potentials were elicited by a stimulus of one polarity (orange), then the other (red). Adapted from Figure 3 of Maccabee et al. [44].

So far, their study was similar to what we performed at NIH in a human, but then they did an experiment that we could not do. To determine how a heterogeneity would impact their results, they placed two insulating cylinders on either side of the nerve (Figure 11). These cylinders modified the electric field, moving the negative and positive peaks of the activating function closer together. They observed a corresponding reduction in the latency shift. This experiment provided insight into what happens when a human nerve passes between two bones, or some similar heterogeneity.

Figure 11. Magnetic stimulation of a sheep phrenic nerve immersed in a homogeneous (left) and inhomogeneous (right) volume conductor. The figure-8 coil (purple) was positioned under the nerve (green). The yellow circles indicate the position of the insulating cylinders. The electric field E_x (red) and its gradient dE_x/dx (blue) were measured along the nerve trajectory. The compound nerve action potentials at the recording electrode were measured for a magnetic stimulus of one polarity (orange) and then the other (green). Adapted from Figure 5 of Maccabee et al. [44].

Finally, they changed the experiment by bending the nerve and found that a bend caused a low threshold “hot spot,” and that excitation at that spot occurred where the electric field, not its gradient, was large. This result was consistent with Nagarajan and Durand’s analysis of excitation of truncated nerves [47].

In my opinion, Maccabee’s [44] article is the most impressive publication in the magnetic stimulation literature. Only Barker’s original demonstration of transcranial magnetic stimulation can compete with it [2].

Later in that review, I discussed a collaborative paper that Paul and I published.

One frustrating feature of the activating function approach is that excitation does not occur directly under the center of a figure-8 coil, where the electric field is largest, but off to one side, where the gradient peaks (Figure 9). Medical doctors do not want to guess how far from the coil center excitation occurs; they would prefer a coil for which “x” marks the spot. It occurred to me that such a coil could be designed using two adjacent figure-8 coils. I called this the four-leaf coil (Figure 12). John Cadwell from Cadwell Laboratories (Kennewick, Washington) built such a coil for me. Having seen the excellent results that Maccabee was obtaining using his nerve-in-a-dish setup, I sent the coil to him so he could test it. The resulting paper [65] showed that for one polarity of the stimulus the magnitude of the gradient of the electric field was largest directly under the coil center so the axons there were depolarized (“x” really did mark the spot of excitation). In addition, if the polarity of the stimulus was reversed, the magnitude of the gradient remained large under the coil center, but it now tended to hyperpolarize rather than depolarize the axons. Maccabee and I hoped that such hyperpolarization could be used to block action potential propagation, acting like an anesthetic. The Brooklyn experiments verified all the predictions of the activating function model for the four-leaf coil. Unfortunately, Maccabee never observed any action potential block. Perhaps, the hyperpolarization required for block was greater than the coil could produce.

Figure 12. A four-leaf coil (purple) used to stimulate a peripheral nerve (blue). Adapted from Figure 1 of Roth et al. [65].

[1] Amassian, V. E., Eberle, L., Maccabee, P. J., and Cracco, R. Q. (1992). Modelling magnetic coil excitation of human cerebral cortex witha peripheral nerve immersed in a brain-shaped volume conductor:The significance of fiber bending in excitation. Electroenceph. Clin. Neurophysiol., 85, 291–301.

[2] Barker, A. T., Jalinous, R., and Freeston, I. L. (1985). Non-invasive magnetic stimulation of human motor cortex. Lancet, 1, 1106–1107.

[40] Maccabee, P. J., Amassian, V. E., Cracco, R. Q., and Cadwell, J. A. (1988). An analysis of peripheral motor nerve stimulation in humans using the magnetic coil. Electroenceph. Clin. Neurophysiol., 70, 524–533.

[41] Maccabee, P. J., Eberle, L., Amassian, V. E., Cracco, R. Q., Rudell, A., and Jayachandra, M. (1990). Spatial distribution of the electric field induced in volume by round and figure ‘8’ magnetic coils: Relevance to activation of sensory nerve fibers. Electroenceph. Clin. Neurophysiol., 76, 131–141.

[42] Maccabee, P. J., Amassian, V. E., Cracco, R. Q., Cracco, J. B., Eberle, L., and Rudell, A. (1991a). Stimulation of the human nervous system using the magnetic coil. J. Clin. Neurophysiol., 8, 38–55.

[43] Maccabee, P. J., Amassian, V. E., Eberle, L. P., Rudell, A. P., Cracco, R. Q., Lai, K. S., and Somasundarum, M. (1991b). Measurement of the electric field induced into inhomogeneous volume conductors by magnetic coils: Application to human spinal neurogeometry. Electroenceph. Clin. Neurophysiol., 81, 224–237.

[44] Maccabee, P. J., Amassian, V. E., Eberle, L. P., and Cracco, R. Q. (1993). Magnetic coil stimulation of straight and bent amphibian and mammalian peripheral nerve in vitro: Locus of excitation. J. Physiol., 460, 201–219.

[47] Nagarajan, S. S., Durand, D. M., and Warman, E. N. (1993). Effects of induced electric fields on finite neuronal structures: A simulation study. IEEE Trans. Biomed. Eng., 40, 1175–1188.

[49] Nilsson, J., Panizza, M., Roth, B. J., Basser, P. J., Cohen, L. G., Caruso, G., and Hallett, M. (1992). Determining the site of stimulation during magnetic stimulation of a peripheral nerve. Electroenceph. Clin. Neurophysiol., 85, 253–264.

[58] Roth, B. J. and Basser, P. J. (1990). A model of the stimulation of a nerve fiber by electromagnetic induction. IEEE Trans. Biomed. Eng., 37, 588–597.

[65] Roth, B. J., Maccabee, P. J., Eberle, L., Amassian, V. E., Hallett, M., Cadwell, J., Anselmi, G. D., and Tatarian, G. T. (1994a). In-vitro evaluation of a four-leaf coil design for magnetic stimulation of peripheral nerve. Electroenceph. Clin. Neurophysiol., 93, 68–74.

Although my name was listed first on our joint 1994 article, Paul could easily have been the lead author. The coil shape was my idea but he performed all the experiments. I never set foot in Brooklyn; I just mailed the coil to him.

Paul was a giant in the field of magnetic stimulation. The articles I list above are only a few of the many he published. For a medical doctor he had a strong grasp of electricity and magnetism. I lost track of him over the years but had the good fortune to reconnect with him a few months ago by email.

I miss Paul Maccabee. Anyone who studies, uses, or benefits from magnetic stimulation owes him a debt of gratitude. I know I do.

John Moulder (1945–2022)

John Moulder,
from Khurana et al. (2008) Med. Phys.,
35:5203, with permission from Wiley.

John Moulder, a leading expert in radiation biology, died about a year ago (on July 17, 2022; I wasn’t aware of his death until last week). When Russ Hobbie and I discuss the possible health risks of weak electric and magnetic fields in Intermediate Physics for Medicine and Biology, we cite a website about powerlines and cancer “that unfortunately no longer exists.” (However, in a previous blog post I found that is does still exist.) We also cite several papers that Moulder wrote with his collaborator Ken Foster about potential electromagnetic field hazards, including

Moulder JE, Foster KR (1995) Biological Effects of Power-Frequency Fields as they Relate to Carcinogenesis. Proceedings of the Society for Experimental Biology and Medicine Volume 209, Pages 309–324.

Moulder JE, Foster KR (1999) Is There a Link Between Exposure to Power-Frequency Electric Fields and Cancer? IEEE Engineering in Medicine and Biology Magazine, Volume 18, Pages 109–116.

Moulder JE, Foster KR, Erdreich LS, McNamee JP (2005) Mobile Phones, Mobile Phone Base Stations and Cancer: A Review. International Journal of Radiation Biology, Volume 81, Pages 189–203.

Foster KR, Moulder JE (2013) Wi-Fi and Health: Review of Current Status and Research. Health Physics, Volume 105, Pages 561–575.

Perhaps my favorite of Moulder’s publications is his Point/Counterpoint article in the journal Medical Physics.

Khurana VG, Moulder JE, Orton CG (2008) There is Currently Enough Evidence and Technology Available to Warrant Taking Immediate Steps to Reduce Exposure of Consumers to Cell-Phone-Related Electromagnetic Radiation. Medical Physics, Volume 35, Pages 5203–5206.

Here is how Moulder is introduced in that paper.

Dr. Moulder obtained his Ph.D. in Biology in 1972 from Yale University. Since 1978, he has served on the faculty of the Medical College of Wisconsin, where he directs the NIH-funded Center for Medical Countermeasures Against Radiological Terrorism. His major research interests include the biological basis for carcinogenesis and cancer therapy, biological aspects of human exposure to non-ionizing radiation, and the prevention and treatment of radiation-induced normal tissue injuries. He has served on a number of national advisory groups concerned with environmental health, non-ionizing radiation, and radiological terrorism; and he currently serves as a radiation biology consultant to NASA.

Are Electromagnetic Fields
Making Me Ill?

In my book Are Electromagnetic Fields Making Me Ill? I wrote:

Radiation biologist John Moulder, of the Medical College of Wisconsin, began maintaining a website titled “Power Lines and Cancer FAQs [frequently asked questions],” which exhaustively summarized the evidence pro and con. Although this website is no longer available online, an archived pdf of it is [13]. In a 1996 article published by IEEE Engineering in Medicine and Biology, Moulder reviewed dozens of studies, and concluded that:

Given the relative weakness of the epidemiology, combined with the extensive and unsupportive laboratory studies, and the biophysical implausibility of interactions at relevant field strengths, it is often difficult to see why there is still any scientific controversy over the issue of power-frequency fields and cancer. [14]

13. large.stanford.edu/publications/crime/references/moulder/moulder.pdf. Access date: January 12, 2022. 

14. Moulder JE (1996) Biological Studies of Power-Frequency Fields and Carcinogenesis. IEEE Engineering in Medicine and Biology Magazine, Volume 15, Pages 31–49.

In a special issue of the International Journal of Radiation Biology dedicated to Moulder, Andrea DiCarlo and her colleagues discussed his work on radiological terrorism.

Through his awarded research grant and cooperative agreements from the NIH and beyond, John leaves behind a legacy of excellent, rigorous, and robust scientific findings, research collaborators who benefited from his expertise and dedication, and a cadre of well-trained students. Although it is impossible to list here all the lives that were touched, and the careers that were impacted by John’s influence, the authors can state with certainty that the field of medical preparedness for a radiation public health emergency would not be where it is now without the steadying hand and role played by Dr. Moulder, both in the early days in the program and during his final years as an active researcher. We are grateful for his years of research and join the entire radiation community in mourning the loss of a great investigator and person.

John Moulder, you were a voice of reason in a crazy world. We’ll miss you.

To hear Moulder in his own words, go to times 4:40 and 5:05 in this video about Power Line Fears.

https://www.youtube.com/watch?v=kf7KWkod3Zw

Abraham Liboff (1927–2023)

Abe Liboff, in his
office at Oakland University

Oakland University physicist Abe Liboff died recently. A notice from President Ora Hirsch Pescovitz, published on the OU website, stated:

It is with deep sadness that I inform you of the death of Professor Emeritus Abraham Liboff who passed away on January 9, 2023. Dr. Liboff joined the Oakland University community in the Department of Physics on August 15, 1972, where he served until his retirement in August 2000.

During his tenure here at OU, Dr. Liboff was Chair of the Department of Physics. He is credited with 111 research publications, more than two dozen patents and nearly 3,400 scholarly citations during his career.

I arrived at OU in 1998, so his time at OU and mine overlapped by a couple years. I remember having a delightful breakfast with him during my job interview. He was one of the founders of OU’s medical physics PhD program that I directed for 15 years. His office was just a few doors down the hall from mine and he helped me get started at Oakland. I’ll miss him.

Although I loved the man, I didn’t love Abe’s cyclotron resonance theory of how magnetic fields interact with biological tissue. It’s difficult to reconcile admiration for a scientist with rejection of his scientific contributions. Rather than trying to explain Abe’s theory, I’ll quote the abstract from his article “Geomagnetic Cyclotron Resonance in Living Cells,” published in the Journal of Biological Physics (Volume 13, Pages 99–102, 1985).

Although considerable experimental evidence now exists to indicate that low-frequency magnetic fields influence living cells, the mode of coupling remains a mystery. We propose a radical new model for electromagnetic interactions with cells, one resulting from a cyclotron resonance mechanism attached to ions moving through transmembrane channels. It is shown that the cyclotron resonance condition on such ions readily leads to a predicted ELF-coupling at geomagnetic levels. This model quantitatively explains the results reported by Blackman et al. (1984), identifying the focus of magnetic interaction in these experiments as K⁺ charge carriers. The cyclotron resonance concept is consistent with recent indications showing that many membrane channels have helical configurations. This model is quite testable, can probably be applied to other circulating charge components within the cell and, most important, leads to the feasibility of direct resonant electromagnetic energy transfer to selected compartments of the cell.

In my book Are Electromagnetic Fields Making Me Ill? I didn’t have the heart to attack Abe in print. When discussing cyclotron resonance effects, I cited the work of Carl Blackman instead, who proposed a similar theory. What’s the problem with this idea? If you calculate the cyclotron frequency of a calcium ion in the earth’s magnetic field, you get about 23 Hz (see Eq. 8.5 in Intermediate Physics for Medicine and Biology). However, the thermal speed of a calcium ion at body temperature is about 440 m/s (Eq. 4.12 in IPMB). At that speed, the radius of the cyclotron orbit would be 3 meters (roughly ten feet)! The mean free path of a ion in water, however, is about an angstrom, which means the ion will suffer more than a billion collisions in one orbit; these interactions should swamp any cyclotron motion. Moreover, ion channels have a size of about 100 angstroms. In order to have a orbital radius similar to the size of a ion channel, the calcium ion would need to be moving extremely fast, which means it would have a kinetic energy vastly larger than the thermal energy. The theory just doesn’t work.

Since Liboff isn’t around to defend himself, I’ll let Louis Slesin—the editor and publisher of Microwave News—tell Abe’s side of the story. Read Slesin’s Reminiscence on the Occasion of Abe Liboff’s 90th Birthday. Although I don’t agree with Slesin on much, we both concur that Abe was a “wonderful and generous man.” If you want to hear about cyclotron resonance straight from the horse’s mouth, you can hear Abe talk about his career and work in a series of videos posted on the Seqex YouTube channel. (Seqex is a company that sells products based on Abe’s theories.) Below I link to the most interesting of these videos, in which Abe tells how he conceived of his cyclotron resonance idea.

Abe Liboff discussing the cyclotron resonance theory.
https://www.youtube.com/watch?v=YL-wqJ-PMAQ&list=PLCO-VktC6wofkMeEeZknT9Y4WhMnP76Ee&index=6