Latent Addition

The usual way to find the time constant τ of a nerve axon is to use various stimuli S(t) of different durations, and then fit the data to a strength-duration curve (discussed in Chapter 7 of Intermediate Physics for Medicine and Biology). Suppose, however, that you didn’t want to vary the duration. Perhaps you own a stimulator that can only output square stimulus pulses of one duration. Can you still determine the time constant?

“The Time Constants of Motor and 
Sensory Peripheral Nerve Fibers Measured 
with the Method of Latent Addition.” 

You can, using the method of latent addition. When I worked at the National Institutes of Health in the 1990s, I was part of a team that used the method of latent addition to measure the time constants of peripheral nerve fibers (M. Panizza, J. Nilsson, B. J. Roth, J. Rothwell and M. Hallett, 1994, “The time constants of motor and sensory peripheral nerve fibers measured with the method of latent addition,” Electroenceph. clin. Neurophysiol., Volume 93, Pages 147-154). The abstract is below.

The time constants of motor and sensory fibers in the human ulnar, median and tibial nerves were determined using the method of latent addition. Two square-wave stimuli were applied: the first one was subthreshold and the second, at various delays relative to the first, was adjusted to achieve threshold activation. Strength-delay curves were obtained, from which the time constant was determined using a mathematical model. Sensory fibers had time constants that were about 3 times the time constant for motor fibers. The strength-delay curves gave similar time constants as those obtained from strength-duration curves.

As the abstract explains, the idea is that you stimulate first with a conditioning pulse and then with a test pulse. You can measure the threshold strength of the test pulse as a function of the delay between the two pulses, and from that data you can determine the time constant. Rather than explain the details, I’ll present the method as a homework problem and let you work it all out.

Section 6.12

Problem 37½. Consider a space-clamped axon with a membrane time constant τ. Initially (t < 0) the transmembrane voltage V is zero (measured as a change from the rest potential). At t = 0, apply a stimulus of strength S₁ for a duration d. We assume this first stimulus is subthreshold. At t = d the stimulus is turned off, and V decays toward rest. At time t = s (where s > d), apply a second stimulus S₂, again having the same duration d. At time t = s + d, the second stimulus turns off and the V again decays back to rest. The voltage obeys the space-clamped cable equation

τ dV/dt + V = S(t) 

(a) Solve for V(t). You should get four expressions, corresponding to different ranges of time.

(b) Set the voltage at the end of the second pulse equal to the threshold voltage, V(t = s + d) = V_threshold. Solve for S₂ (the threshold strength of the second pulse) as a function of S₁, s, d, τ, and V_threshold.

(c) Find an expression for the threshold strength of the first pulse, S_1,threshold, and write the expression you found in part (b) for S₂ as a function of S₁, s, τ, and S_1,threshold.

(d) Divide through by S_1,threshold to get a new relationship for S₂/S_1,threshold that is a function of s, τ, and S₁/S_1,threshold.

(e) Assume that S₁/S_1,threshold = 0.9. What is the expression for S₂/S_1,threshold? Next express S₁/S_1,threshold and S₂/S_1,threshold as percentages rather than fractions of S_1,threshold. What is the final expression for the percentage S₂ as a function of s?

I will let you work out the intermediate steps, but the final expression is S₂ = 100 – 90 e^–s/τ. This equation can be fit to data for various values of s to get τ. The method worked well, and we were able to determine the time constants of motor and sensory fibers. 

Let me add a few limitations. First, nerve fibers are not space clamped. This is an approximation that works best if the electrodes are not too close to the nerve. Second, the model assumes that for a subthreshold pulse the membrane resistance is fixed, but if you stimulate at 90% of threshold some active behavior and ion channel opening or closing might occur. Third, the model was derived for s > d, but it also works for s = 0 (an unexpected bonus). Finally, I recommend using a short duration pulse, d << τ. That way, you can use a wider range of values of s, include some fairly short ones, s << τ.

Now I’ll tell you a bit about the other researchers in this project. I’ve talked about Mark Hallett before in this blog, who died last year. He worked in the intramural program for the National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health. He was particularly well known for his research on transcranial magnetic stimulation, but he also was interested in purely electrical measurements of nerves. He led a large lab in the NIH Clinical Center on the Bethesda campus.

Marcela Panizza and Jan Nilsson were visiting researchers from Italy, who would often come to NIH to collaborate with Hallett. They were a husband and wife team with Panizza, a native Italian, being a medical doctor and Nilsson, originally from The Netherlands, being a biomedical engineer. I published several papers with them, and they were a joy to work with. They were the ones who performed the experiments and obtained all the data.

John Rothwell is a leading magnetic stimulation researcher from the Queen Square Institute of Neurology in London. I believe I met Rothwell at a meeting (probably the 1989 International Motor Evoked Potential Symposium in Chicago, which had a big influence on my career), but he wasn’t at NIH working with us, and it was Panizza and Nilsson (or maybe Hallett) who corresponded with him. Rothwell was the one who had proposed the method of latent addition, and had used it initially to determine nerve time constants. 

My job was mainly to write the appendix, which was almost the same as the above homework problem. Now, having solved that problem, any of you, dear readers, could write that.

John Rothwell 

https://www.youtube.com/watch?v=ElXresr5w0Q

The Solution Manual

Cover of the 6th edition of
Intermediate Physics for
Medicine and Biology. 

Gene Surdutovich and I have now submitted the sixth edition of Intermediate Physics for Medicine and Biology, corrected the page proofs, corrected the corrected page proofs, and then checked the corrections of the corrected-corrected page proofs. The book is now in the hands of our publisher, Springer Nature, and we await the arrival of our free copies. You would think that finally we were done and could now rest.

But Nooooo! There’s still the solution manual. We have a draft of the solution manual that I think is 99% complete, but it needs one more pass to check for errors. Today, I want to tell you a little more about the solution manual.

First, it’s almost a second book. We have over a thousand homework problems in the sixth edition, and the solution manual can fit about three solutions per page, so that means it has several hundred pages. IPMB is equation dense, but the solution manual is equation denser. IPMB was written in LaTeX, but for historical reasons the solution manual was written using MS Word. However, I lost access to MS Office about a year ago (long story…) so I use free software called LibreOffice. It’s almost identical to MS Word, except for the equation editor, which is completely different. The solution manual also has many figures and tables. It’s a big production.

Once the sixth edition of IPMB is published (Springer's website says February 2017), we’ll send the solution manual to instructors upon request, although we do check to make sure the instructor is really an instructor. I realize the solution manual would be valuable to students, and especially to students who are working through the book on their own. We have to balance their needs with the desire of most instructors to not have the solution manual widely distributed among students; Solving a homework assignment should not be merely copying from the solution manual. Russ and I solved this dilemma for previous editions by sending the solution manual, for free, to instructors on request, but asking them to pledge not to post it on the web. This has worked fairly well. 

Each solution to a homework problem starts with a preamble: a sentence or two in italics saying why we included the problem and how the student would gain from solving it. For instance, here’s the preamble to a problem in Chapter 1 of the sixth edition, about biomechanics.

1.10  This is the first of a series of problems about biomechanics. In this problem, students practice drawing a free-body diagram and analyzing static equilibrium for a person doing pushups.

Each problem can fit into three special categories: 

* = Higher difficulty 

§ = Complete a derivation from the text 

¶ = New in the sixth edition

The higher difficulty problems are often among my favorites, but they tend to be long or require advanced mathematics. Instructors will have to use their own judgement about if their students are up to the task. The problems that complete a derivation from the text are really meant to force the student to fill in missing steps in the textbook. Sometimes these problems resemble this example from Chapter 5: 

Problem 53 Substitute Eqs. 5.98 and 5.99 into Eq. 5.96 to derive Eq. 5.100. 

We also mark the new problems in the sixth edition. This way, if instructors are already familiar with the 5th edition of IPMB and its solution manual, they can identify the new stuff more easily. 

We try to include enough detail that instructors and students can easily follow the solution. It’s always a judgment call as to how much detail is necessary. We also try to stress the translation of physics to math and then back from math to physics, the plotting of results, and the examining of limiting cases, because we often urge the student to do just these things. We sometimes try to sum up why the calculation is important. And occasionally, we add a little commentary at the end of a problem, but not too often because the solution manual is already long enough.

If you really want to get the most out of IPMB, do the homework problems. That’s where much of the learning takes place. And for students who love biology but don’t like math, view these problems as a way to hone a new skill. Think of them as an opportunity, not a obstacle.

We keep adding more, more, more problems with each edition. I haven’t done the math, but I suspect that at the current rate by the 9th edition of IPMB the homework problems will take up more space than the text itself, and by the 15th edition the book will have become just a homework collection with no text! Who knows? I’ll be long gone by then.

One final warning. Gene and I are trying to eliminate any errors in the solution manual, but I don’t think we have checked it as thoroughly as we checked the textbook itself. If you get an answer that’s different than in the solution manual, it may be your mistake or it may be ours. Please let us know and we’ll try to correct any errors.

Enjoy!

Memories of the National Institutes of Health

These days, when I see the current state of the National Institutes of Health, I grieve for the NIH I once knew. I worked in the NIH intramural research program from 1988 to 1995. Professionally, these were the best, most productive years of my career. I’m feeling a little nostalgic today, and would like to share with you my description of NIH published in the memoirs I wrote for the American Institute of Physics in 2024, just before the present presidential administration took office. My experiences at NIH were the ideal preparation for being a coauthor on Intermediate Physics for Medicine and Biology.

Building 1

The National Institutes of Health is the best place in the world to do biomedical research. I worked in the intramural program where scientists and medical doctors perform their studies on the NIH campus in Bethesda, Maryland. About 15% of NIH’s funding goes to the intramural program. The rest is for the extramural program, which awards grants to faculty at universities across the USA. NIH consists of an alphabet soup of disease-oriented institutes, such as the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the biggest of all, the National Cancer Institute (NCI). When I was at NIH, Tony Fauci was the head of the National Institute of Allergy and Infectious Diseases (NIAID) and was already acclaimed for his investigations of HIV and AIDS. During part of my stay, Harold Varmus—known for his work on cancer-causing genes—was the NIH director. He would ride his bike to work at NIH’s impressive James Shannon Building (also known as Building 1). We all loved him.

Bethesda is just inside the Capital beltway. It’s lovely but expensive. We couldn’t afford to live there, so first we rented an apartment in Wheaton and later bought a fixer-upper house in Kensington. [While living there] our second daughter, Kathy, was born in April 1991.

NIH has its own subway stop on the red line, with an extraordinarily deep escalator. Once Wikswo [my PhD advisor] visited me at NIH. I was escorting him there on the subway and when we reached the NIH stop I mentioned that he was about to ride on the longest escalator he ever saw. Wikswo is always up for a challenge and chose to climb the stairs instead (I rode up). He did fine initially, but as he approached the top even he was exhausted.

Tens of thousands of people were employed at NIH. It was far bigger than Morrison where I grew up. It had tenured investigators like at a university and many post doc trainees, but no students. It even had its own newspaper: the NIH Record. NIH is a federal lab. In 1990 when the federal government shut down I had to stay home.

Building 10

The heart of the intramural campus is NIH’s unique Clinical Center (Building 10). This state-of-the-art hospital is entirely dedicated to clinical research. Patients who are treated at the Clinical Center must fit into one of the ongoing research protocols, but if they do they receive medical treatment at no cost. Many clinical trials require normal volunteers who are paid to serve as healthy controls. I remember a guy who was a normal volunteer in so many studies that it became his full-time job.

Building 16

Another landmark on the NIH campus is the beautiful Stone House (Building 16), located near the entrance from Rockville Pike. The Stone House is part of the Fogarty International Center, which focuses on supporting biomedical researchers who come to NIH from around the globe. I had the privilege to work with international scientists from all over the world.

When I was at NIH, most of its research was focused on genetics. The Human Genome Project began in 1990, with James Watson (of DNA fame) and Francis Collins (future director of NIH during Covid) leading the effort to sequence the human genome while Craig Venter competed with them from his private company, the Institute of Genomic Research. I wasn’t interested in genomics, but NIH was so large that there were still plenty of people for me to interact with.

I worked in the Biomedical Engineering and Instrumentation Program (BEIP). The National Institute of Biomedical Imaging and Bioengineering (NIBIB) didn’t exist yet and BEIP was part of the National Center for Research Resources (NCRR). The purpose of BEIP was to supply engineers, physicists, and mathematicians to collaborate with the biologists and medical doctors in the disease institutes. Our program was funded by a “tax” on the other institutes and we were expected to focus on collaboration and limit the time we spent on our own research. We didn’t have to apply for grants, like faculty at a university had to, which was a one of the best features of the intramural program.

Within BEIP I was part of the Mechanical Engineering Section led by Seth Goldstein. I wasn’t a mechanical engineer but Seth wanted his section to contain a broad mix of scientists. He was a great boss. When I needed help overcoming some administrative obstacle or assistance with an engineering issue he was always there for me. Otherwise, he left me alone to follow my own path. Some of the other members of my section were Ron Levin, an expert in magnetic resonance imaging and computers; Richard Chadwick, whose mathematical models of heart biomechanics would later influence my work on mechanotransduction; Steve Leighton, an excellent design engineer who spent his summers at the Woods Hole Oceanographic Institute building a ultramicrotome for use in a scanning electron microscope (Leighton had a sign in his office that read “Good, Fast, Cheap: Pick any two”); and Peter Basser, my best friend at NIH who arrived a year before I did. He was an expert on tissue mechanics and porous media. All the guys in the Mechanical Engineering Section used Apple Macintosh computers instead of PCs, so I did that too and have been a loyal Mac user ever since.

At NIH you could spend all your time listening to science talks. Each week the “yellow sheet” was published listing about a dozen lectures each day. I can remember a speaker who gave a talk about a recent invention called the “world wide web.” All of us from the Mechanical Engineering Section attended. As we walked back to our offices after the seminar, we shook our heads and asked each other “but what good is it?” We would soon learn.

Building 13

Before 9/11 the security at NIH was lax. I generally rode the bus to work because we owned only one car (suburban Maryland had the best public transportation of anywhere I’ve lived). Sometimes [my wife] Shirley, [my oldest daughter] Stephanie, and Kathy would come pick me up to go home. They would simply drive onto the NIH campus, park in a visitor’s spot, and take the elevator up to my office in Building 13. Nowadays you can’t even enter the campus without the proper ID and permission.

If you want to learn more about the current state of NIH—the good, the bad, and the ugly—I suggest you read the NIH Vigils newsletter each week: an underground publication by current and former NIH employees, and definitely not an official mouthpiece of the administration. Assuming the NIH someday returns to its former glory, I encourage young people to search for summer internships and other opportunities to work there. I hope that someday I can again say that NIH is the best place in the world to do biomedical research.

 https://www.youtube.com/watch?v=ezpi8J1UQA0&t=43s

Biophysics at Kalamazoo

I’m always curious how colleges and universities structure undergraduate biological physics and medical physics programs. At Oakland University in Rochester, Michigan (where I worked until I retired in 2020) we have a Medical Physics major. As a Michigander, I want to introduce you to another program in our state: the Biological Physics concentration at Kalamazoo College.

To reach Kalamazoo from where I live in Rochester Hills, which is just north of Detroit, get on I-94 and drive west about three fourths of the way across the state, until you’re roughly 40 miles from Lake Michigan. There you’ll find a small, private liberal arts college founded by Baptist ministers in 1833. Kalamazoo College is known for its flexible curriculum, with an emphasis on study abroad, internships, undergraduate research, civic engagement, and a senior capstone project (they call it the “K-plan”). I’m a fan of a liberal arts education, so their program sounds attractive to me.

All students have a major, but many also focus on a concentration, which is an interdisciplinary set of courses centered on a theme (to me, it seems like a beefed up minor). One concentration is Biological Physics. It consists of six prerequisite courses: two semesters each of physics, chemistry, and calculus. Then the required courses are two semesters of biology, organic and physical chemistry, and two specialty courses on topics such as biophysics, neuroscience, complex systems, or chaos.

The biological physics concentration is light on physics compared to OU’s medical physics program, but that’s probably because it’s a concentration and not a major. A combination of a Kalamazoo physics major with the biophysics concentration would provide the strong base in physics I would want. But the biological physics concentration might also be appealing to students who seek a deeper math and physics background than a biology major would supply. Also, the concentration has a lot of overlap with the curriculum required to get into medical school. I would guess it attracts premed students (at least the ones who are not afraid of math, which is just a handful).

At Oakland we have a two-semester course sequence of Biological Physics and Medical Physics that’s based on Intermediate Physics for Medicine and Biology. The course at Kalamazoo most similar to these appears to be the Biophysics course (PHYS 205). The catalog description is given below. I put in italics the parts covered in IPMB.

PHYS 205 Biophysics 

How can we observe and comprehend the size and scale of living systems? How can we use physics to aid our understanding of biology? How large are bacteria and viruses? What size of torque can molecular motors develop? How does the flexibility of a molecule contribute to its biological function? What is the scale of membrane potentials? How efficient are different organisms at encoding their genes? Which animal can jump the highest per its size? How can we make sense of vast amounts of complex and sometimes "messy" biological data? This course is an introduction to the advantages and limitations of using physical techniques and models to address biological questions. We will focus on molecular-scale systems and dynamics, with topics to include modeling dynamic molecules and systems, optics and microscopy, physical properties of biomolecules and gaining numerical literacy. We will explore current biophysical research and help you develop the interdisciplinary toolset to engage with it.

I see a lot of overlap with IPMB, but clearly there is more of a molecular emphasis in PHYS 205.

What’s the perfect preparation for graduate study and a career in biological physics? I suggest students follow Kalamazoo’s Biological Physics concentration, but during the first summer after they complete the required prerequisite courses in physics and math, they rent an isolated cabin along Lake Michigan and spend three months reading and working the homework problems in the 6th edition of Intermediate Physics for Medicine and Biology, taking an hour off each evening to watch the sun set over the lake. Now that would be a great program! 

 

William Hendee (1938–2026)

Medical Imaging Physics,
by William Hendee and E. Russell Ritenour.

I recently learned that William Hendee died on March 14, 2026 at the age of 88. The book Medical Imaging Physics, by Hendee and E. Russell Ritenour, had a big impact on Intermediate Physics for Medicine and Biology. Russ Hobbie and I cite Medical Imaging Physics in IPMB several times in the chapters on ultrasound and on medical x-rays. In fact, we even reproduce some of the figures from their book.

Another way Hendee influenced IPMB is by developing the “Point/Counterpoint” series in the journal Medical Physics. He was the first editor of point/counterpoint articles, in charge of them from 1998 to 2005. Russ and I cite several of these articles, which are wonderful tools to teach students about current controversies in medical physics. We only cite point/counterpoint articles that were moderated by Hendee’s successor, Colin Orton, but when I taught medical physics at Oakland University, every Friday we would end class with a discussion of one pint/counterpoint article, many of them moderated by Hendee. They’re such an important contribution to medical physics education. Hendee was editor-in-chief of the entire journal Medical Physics from 1985–2004. 

Often in this blog I discuss how physicists make the transition from physics to biology or medicine. Hendee tells his story in an interview with the American Society for Radiation Oncology. He grew up near Jackson, Mississippi and became interested in physics because of an inspiring high school physics teacher. He obtained a bachelors degree in physics from Millsaps College, and then went to Vanderbilt (where I got my PhD) on an Atomic Energy Commission fellowship. He worked with with Robert Lagemann in acoustics (from 1995–1998 I was the Robert T. Lagemann Assistant Professor of Living State Physics). When his wife became pregnant, his meager fellowship salary could not support a family. At a conference, he saw a advertisement for a medical physics fellowship with more pay at the University of Texas. He talked to the person who had posted the ad and his first question was “what is medical physics?” The rest is history, as he accepted the position, went to Texas, and got his PhD in 1962. I guess sometimes the transition from physics to medicine is motivated in part by financial considerations.

Other interesting facts about Hendee: 

• He was in the Marine Corps Reserves from 1956 to 1963.
• After his PhD, he returned to Millsaps College on the faculty, in part to participate in the civil rights movement in Mississippi. He eventually left Millsaps because of a disagreement about the dean’s efforts to identify homosexuals on the faculty. 
• He was at the University of Colorado for 20 years, and then was a dean at the Medical College of Wisconsin.  
• He received many awards, including from the American Association of Physicists in Medicine (Coolidge Award), the American Roentgen Ray Society (Gold Medal), the Radiological Society of North America (Gold Medal), the International Organization for Medical Physics (Harald Johns Medal), and the Health Physics Society (Elda Anderson Award).
• After he retired, be bought a lake house in Wisconsin, and enjoyed fishing and being close to nature.
• His obituary says that “Bill is most remembered by people who knew him as inspiring, passionate about learning, kind-hearted, charming, devoted to his family, and a friend you could count on.”

Russ Hobbie and I owe a great debt to Hendee, because Medical Imaging Physics had such an influence on the last half of Intermediate Physics for Medicine and Biology. His passing is sad for us all, and especially for us medical physics textbook writers. He had a long, productive life. Rest in peace, William Hendee. 

The History of Medical College of Wisconsin: Our Voices, Our Legacies featuring William Hendee

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

 

Radiological Society of North America Luminaries Series: William Hendee

https://www.youtube.com/watch?v=Me06HwRQNvc

Advice for Young Scientists

I’m so worried about the state of American science. The layoffs in government research centers, the budget cutbacks, the difficulty of getting grants, the demonization of scientists, and the denial of entire branches of knowledge such as climate change and vaccines... it’s just terrible. I’m especially concerned about young scientists. The ones just starting out, trying to establish a career. It must be devastating for many.

Today I want to share some stories about another difficult time for young scientists, the mid 1990s. President Clinton was cutting federal funding for scientific research to try and balance the budget, scientists and engineers from the former Soviet Union and Eastern Europe were flooding the US job market, and former industry scientists were looking for jobs as centers like Bell Labs were cutting basic research. I don’t want to imply that 1995 was as bad as 2026, but there were some parallels.

I worked at the National Institutes of Health in Bethesda, Maryland in the late 1980s and early 1990s. I loved NIH, and believed that it was the greatest biomedical research institution anywhere, ever. I was in the Biomedical Engineering and Instrumentation Program (BEIP), which hired physicists, engineers, and mathematicians to collaborate with NIH biologists and medical doctors. BEIP wasn’t funded directly from Congress, but instead was a service organization that was supported by a “tax” on the other institutes.

When the cutbacks began in the mid 1990s, I was just about ready to be put up for a permanent position. BEIP didn’t hire “tenure-track” faculty like the institutes did. It did, however, have a tradition of deciding after six years if a staff fellow like me would be promoted into a permanent position, in a process similar to a tenure decision at at a university. Suddenly around 1994, we in BEIP who had been expecting to go up for a permanent spot started being called “postdocs” and were told we needed more “mentoring.” A month or two later we were told there was a hiring freeze and no BEIP staff fellows would be moved into permanent positions. I started looking for another job.

I applied to colleges and universities throughout the country. I searched for industrial positions too, and as time went by I even began looking for jobs at community colleges. I had no luck for months. Between April 1994 and September 1995 I received over one hundred rejection letters, and many more potential employers didn’t even bother to respond at all to my application. I began to worry how I was going to feed my two children. I had seven job interviews, but only two offers. One was verbal and informal (“we can make this happen if you are interested”) and the other (which I accepted) was for a non-tenure track Assistant Professorship at Vanderbilt University, where I had been a graduate student seven years earlier.

I wasn’t the only one in this situation. BEIP had four young researchers coming up for a decision about a permanent position, and we all were in the same boat. Let me tell you about the four of us. Perhaps our stories will provide hope to young people today facing the current job market. 

 

Akram Aldroubi

Akram Aldroubi (PhD, Carnegie Mellon 1987) was a mathematician who worked with the BEIP director, Murray Eden. He, Eden and Michael Unser published a series of highly cited papers about signal processing, investigating topics like b-splines and wavelets. In 1997 Akram moved to the Department of Mathematics at Vanderbilt University (he and I were reunited at Vanderbilt for a year until I left in 1998). He was coauthor with Peter Basser (more on Basser later) on a landmark paper about using MRI diffusion tensor imaging to do fiber tractography. Akram is still at Vanderbilt today, and in 2014 he was inducted as a fellow in the American Mathematical Society for his “contributions to modern harmonic analysis and its applications, and for building bridges between mathematics and other areas of science and engineering.” 

Akram Aldroubi 

https://www.youtube.com/watch?v=sn4GNGnFovY

 

Cynthia Sung

Cynthia Sung (PhD, Harvard-MIT, 1988) was in the Chemical Engineering Section of BEIP. There she worked with Robert Dedrick and Paul Morrison to study pharmacokinetics. After she left NIH she held a variety of positions, such as with the Gates Medical Research Institute and with the Food and Drug Administration. Cynthia went to Singapore and established her own consulting firm, Rainbow Pharma Consulting, and worked with the Singapore Health Sciences Authority. She’s now an Adjunct Associate Professor in the Centre of Regulatory Excellence at Duke-National University of Singapore Medical School. In 2023 she won the Titan Award for Community Collaboration to recognize her collaborative spirit in helping fellow community members reach their goals. 

Cynthia Sung 

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

 

Joe Schmitt

Joe Schmitt (PhD, Stanford, 1986) worked in the Electrical Engineering Section of BEIP with Robert Bonner, studying how light propagates through tissue. After leaving NIH he was an Associate Professor in the Department of Electrical and Electronic Engineering at the Hong Kong University of Science and Technology. There he wrote a highly cited review about Optical Coherence Tomography (a topic discussed in Chapter 14 of Intermediate Physics for Medicine and Biology). He then entered industry and is now the Chief Technology Officer of LightLab Imaging. 

Joe Schmitt

https://www.youtube.com/watch?v=HqEuxXHW7Cs

 

Brad Roth

My PhD was from Vanderbilt in 1987. At NIH I worked for Seth Goldstein in the Mechanical Engineering Section of BEIP, the same section where my friend Peter Basser (the inventor of MRI diffusion tensor imaging) also worked. Basser was a year ahead of me, and he obtained a permanent position at NIH just before the hiring freeze took effect. After leaving NIH, I went back to Vanderbilt for three years, and then took a tenure-track faculty position at Oakland University in Rochester, Michigan, where I taught and did research for over two decades. One of my main accomplishments at OU was to become coauthor with Russell Hobbie on the textbook Intermediate Physics for Medicine and Biology. Though I was never again quite as productive as during those wonderful years at NIH, I nevertheless had a happy and successful career at Oakland. 

 Brad Roth

https://www.youtube.com/watch?v=IKjab7_unRA

Those are the stories of four young researchers who faced a rough patch in their careers just a little over 30 years ago. Fortunately, we all survived—and eventually thrived—in our lives after NIH, whether in academia, industry, or government. I know what young scientists face now is so much worse than what we encountered, and I don’t want to minimize their challenges. But we four friends did overcome our obstacles and managed to remain in science, making a living and contributing to knowledge. Our paths were sometimes tortuous, but with perseverance and patience—and a resurgence of science funding in the late 1990s—we managed to stay in the game. I hope you young scientists facing obstacles now (obstacles that are unfair and no fault of your own) can likewise find a way to stay in science and keep contributing. One thing I know for sure: our country needs you now more than ever.

Good luck. Have courage. Have hope.

The Page Proofs are Here!!!

The page proofs for the sixth edition of Intermediate Physics for Medicine and Biology have arrived, and they’ve taken over my life. I’ve got no time for much of anything else, including writing blog posts. My coauthor Gene Surdutovich and I are trying hard to fix all the errors, but man oh man is there a lot to check. The pdf of the proofs has about 580 pages, whereas the 5th edition had more like 650 (from title page to end of the index). So the book is down about 7% in number of pages. That’s good, because we cut out a lot of what we rarely teach in our classes. That decrease is even more impressive when you consider that we added a chapter on surface tension, we added a chapter on damage from ionizing radiation, and we split the chapter on feedback and nonlinear dynamics into two. In addition, readers now have over 1000 homework problems to test their understanding. So, really, we cut at least 10% from the chapter text present in the fifth edition.

That’s all for now, but just let me add a big thank you to all the readers of Intermediate Physics for Medicine and Biology. And let me assure you traditionalists out there that there’s still a lot of Russ Hobbie here in the sixth edition. It’s still his book, and he’s still first author.

Leon Glass and the Wandering Thoughts Podcast

From Clocks to Chaos,
by Glass and Mackey.

Chapter 10 of Intermediate Physics for Medicine and Biology talks about nonlinear dynamics, and in particular how simple sets of nonlinear differential equations can lead to chaotic behavior. One researcher who Russ Hobbie and I mention often is Leon Glass. We cite his book with Michael Mackey, From Clocks to Chaos, which influenced me as a young scientist, and his textbook with Daniel Kaplan, Understanding Nonlinear Dynamics.

Recently I discovered a wonderful interview with Glass where he describes his life and work. It’s part of a podcast series titled Wandering Thoughts, and you can listen to it below. It’s over two hours long, but Glass talks slowly and I could understand it at 2× speed or even faster. It’s well worth the time.

Several topics covered in the interview will be interesting to readers of IPMB and of this blog. I’ve always been interested in how physicists end up learning and studying biology, and conversely how biologists learn physics. Right at the start of the interview Glass outlines his own circuitous path toward biological physics. Everyone has their own unique path, but Glass’s highlights one feature I find common in many: it isn’t part of a grand master plan, but just sort of happens, and is catalyzed by interactions with other scientists. Glass describes his work on the periodic electrical stimulation of chick heart cells, which Russ and I illustrate using a figure from one of his papers (in IPMB, it’s Fig. 10.36). Stimulation can simply drive the system in a 1:1 behavior, or give a more complicated periodic behavior at a lower frequency, or produce deterministic chaos. This is lovely work and Glass was one of the pioneers. He also talks about the modeling of spiral waves as an example of a heart arrhythmia, a concept studied by his friend and collegue Art Winfree. (In 2013 Glass won the Arthur T. Winfree Prize awarded by the Society of Mathematical Biology.) When asked what traits were most valuable to him in his career, Glass mentioned curiosity and tenacity. Those two traits would be useful to anyone wanting to learn biological physics from IPMB.  

This podcast provides insight into what a career in biological physics is like. Enjoy! 

Chaos in Biological Systems, with Leon Glass, on The Wandering Thoughts podcast.

https://music.youtube.com/watch?v=aDx9t2vA9s0  

The Good Friday Meeting and mRNA

Messenger ribonucleic acid (mRNA) is in the news these days because of mRNA vaccines. But how was mRNA discovered? One reason I'm interested in this question is because mRNA (at least, our knowledge of mRNA) is almost the same age as I am: we were both born in 1960.

First, what role does mRNA play in biology? The central dogma of molecular biology is that DNA with its genetic code is stored in the cell nucleus. Transcription—where the base pairs in double stranded DNA are transcribed into bases in single-stranded mRNA—occurs in the nucleus, catalyzed by enzymes like RNA polymerase. Then, the mRNA leaves the nucleus and enters the cytoplasm. There, the mRNA attaches to the cell organelle called a ribosome (itself made from another type of RNA, rRNA) where the genetic code of base-pairs is translated into a string of amino acids in a protein. Yet another kind of RNA, tRNA, aids in this translation. In short:

DNA > transcription > mRNA > translation > Protein

Clearly mRNA plays a crucial role in all protein synthesis and is essential to life.

The Eighth Day of Creation,
by Horace Freeland Judson.

Russ Hobbie and I talk a little about DNA and proteins in Intermediate Physics for Medicine and Biology, but not much about mRNA. If you want to learn how mRNA was discovered, I suggest reading The Eighth Day of Creation: The Makers of the Revolution in Biology, by Horace Freeland Judson. It’s a long and complicated story, but a key moment was an informal meeting on April 15, 1960 (Good Friday), attended by biologists Francis Crick, Sydney Brenner, François Jacob, and others (Jacques Monod, a collaborator of Jacob, was not present) in Brenner’s rooms at Cambridge University. At that time, the structure of DNA and its role in creating proteins was already known, but the details of how that occurred was uncertain. Out of that meeting came the idea that mRNA was the messenger between DNA and Protein.

Judson writes

That fall, Jacob and Monod christened the unstable, information-bearing intermediate between gene and protein “messenger RNA.” Out of the amorphous biochemistry of RNA, three distinct anatomies had now been differentiated: rRNA, tRNA, mRNA. Two had begun their scientific careers as purely intellectual creations, function postulating structure. .Jacob and Monod wrote the idea of the messenger, and the term, into a theoretical summation they were preparing. Meanwhile, Brenner had written up the experimental work… At the end [of Jacob and Monod's article] they came to the function of the ribosome.

The property attributed to the structural messenger of being an unstable intermediate is one of the most specific and novel implications of this scheme… This leads to a new concept of the mechanism of information transfer, where the protein synthesizing centers (ribosomes) play the role of non-specific constituents which can synthesize different proteins, according to specific instructions which they receive from the genes through M-RNA.

There, in a sentence, was the first published statement of the pivotal realization that had come to Crick, Brenner, and Jacob in their conversation on Good Friday, eight months earlier….

Jacob and Monod titled their paper “Genetic Regulatory Mechanisms in the Synthesis of Proteins.” It reached The Journal of Molecular Biology on 28 December 1960.

So, next time you hear someone arguing about mRNA and vaccines and you aren’t sure what it is all about, go get a copy of The Eighth Day of Creation. At least you'll learn what mRNA is. Judson's book is one of the best about the history of science, and the absolute best I know of about the history of modern biology.

Physics in Medicine and Medical Education

Over the last few years, I’ve been contributing to a group called Physics in Medicine. It focuses on how physics contributes to, and indeed is essential to, the practice of medicine. The team consists of both physicists and medical doctors collaborating to demonstrate how physics can be better taught to medical students. My interactions with this team influenced the preparation of the sixth edition of Intermediate Physics for Medicine and Biology (which you can now find listed at Amazon with a projected publication date of October of this year).

Physics in Medicine
and Medical Education.

Recently, we published a proceedings titled Physics in Medicine and Medical Education. You can purchase a hard copy of this book on Amazon, or view it for free as a flip-book. Here is the table of contents.

My role was to lead the effort on the chapter “The Integrated Cardiovascular-Pulmonary System: The Underlying Principles That Make It Work.” When working on it, I often used the shorthand title “Physics of the Heart.” The abstract states 

The Physics in Medicine program is an attempt to improve medical education in a way consistent with the AAMC-HHMI 2009 report on the Scientific Foundations for Future Physicians. Our aim is to illustrate how the findings of this report can be applied to the cardiovascular system. We do this by examining one specific case study of an elderly man with shortness of breath, and review the physics required in his diagnosis and treatment.

The amount of physics in the medical treatment of cardiovascular disease is astounding. One of the figures from our chapter illustrates this. Many topics in physics—fluid mechanics, acoustics, optics, electricity and magnetism, and nuclear physics—play a role in the treatment of just one disorder (patent foramen ovale, or an opening between the left and right atria). 

The editor of our Proceedings, Ed Szuszczewicz, is the visionary that leads Physics in Medicine. Ed is a plasma physicist who was asked by his department chairman to teach a physics-for-premeds class. That got him hooked. If you just read his Preface and Epilogue in Physics in Medicine and Medical Education you’ll get the gist of our effort. 

In Chapter 4 of the Proceedings, one of my coauthors, Nancy Donaldson, describes her experience directing a Physics of Medicine undergraduate major at Rockhurst University in Kansas City. Nancy is a passionate advocate for active learning and describes several of the modules used in her classes. It kind of makes me want to retake my physics major. I especially like her analysis of the lungs, a topic that doesn’t get as much attention as it should have in IPMB. Nancy is also one of the founders the Living Physics Portal, where you can find high-quality materials for teaching physics to life science students at the college level. The other two coauthors on my chapter, Chad Miller and Andrew Olson, are MDs who helped keep the story focused on medicine. I have a tendency to stress the physics too much, and they helped counterbalance that.

Another contributor to Physics in Medicine and Medical Education was the late Joe Redish. He was a central figure in our effort until he passed away at age of 82 in 2024. I made sure to cite his helpful “Using Math in Physics” articles published in The Physics Teacher, and I featured his wonderful “warp and weft” figure connecting subareas of physics to learning techniques in our Physics of the Heart chapter. I miss Joe. 

I hope you enjoy Physics in Medicine and Medical Education. Instructors who are teaching from Intermediate Physics for Medicine and Biology might want to take a look at it, to get an idea about the physics needed in modern medicine.