Friday, October 27, 2017


A screenshot of the Oakland University Center for Biomedical Research Twitter page.
A few months ago I started an account on Twitter. It is not a personal account, but instead is for the Oakland University Center for Biomedical Research, which I direct. If you are interested, the Twitter handle is @OaklandUniv_CBR. Most of my tweets are useful for faculty and students at OU: announcing seminars, congratulating principal investigators for their new grants, highlighting accomplishments of students, and that sort of thing. However, I follow a lot of accounts that are related to Intermediate Physics for Medicine and Biology. If you are on Twitter, you might like these:
If you use Twitter and know some accounts that readers of IPMB should follow, mention them in the comments.


Friday, October 20, 2017

Galvani’s Spark: The Story of the Nerve Impulse

Galvani's Spark: The Story of the Nerve Impulse, by Alan McComas, superimposed on Intermediate Physics for Medicine and Biology.
Galvani's Spark:
The Story of the Nerve Impulse,
by Alan McComas.
I recently finished a wonderful history of neurophysiology. Galvani’s Spark: The Story of the Nerve Impulse, by Alan McComas, covers several topics that Russ Hobbie and I discuss in Intermediate Physics for Medicine and Biology, such as the nerve action potential, patch clamping, and the structure of the potassium channel. While I enjoyed these parts of the book, I particularly liked the earlier history about scientists like Charles Sherrington and Edgar Adrian.
One of my favorite chapters is about Keith Lucas, an English physiologist who worked at Cambridge. Lucas showed that when he increased the strength of an electrical stimulus to a muscle, the response increased in discrete steps. From this, he deduced that each fiber responded in an all-or-none way, and the increase in response with stimulus strength resulted from recruiting more fibers. Lucas had the skills of an engineer as well as a biologist, and would make his own equipment to record action potentials. He probably would have made many more discoveries, except that during World War I he left academic research to work for the military. McComas describes the work well.
Living in a small wooden hut and rising a 4 in the morning, Lucas grappled with a number of problems that beset the pilots of the early flying machines. One was to improve a bombsight, and another to eliminate the unreliability of the pilot’s compass as the plane was made to turn. Once again, just as it had in the Physiological Laboratory in Cambridge, Lucas’s flair for analysis and design, and for constructing equipment himself, served him in good stead, and the problems were solved. To gain first-hand experience of a particular problem, and to see if his solution was effective, Lucas would fly himself, initially as a passenger and then as a trained pilot. For this, he transferred to the Central Flying School at Upavon in Wiltshire.
Tragically, in October 1916 he was killed in a midair collision between two planes.

Another interesting chapter was about three American neurophysiologists—Joseph Erlanger, Herbert Gasser, and George Bishop—who pioneered the use of an oscilloscope for recording action potentials. Gasser is portrayed as saintly, but Erlanger doesn’t come across as an attractive figure. At one point, Bishop published a paper without passing it by Erlanger first, and Erlanger threw a fit.
Erlanger’s violent temper was well known to this family, but at work it had usually been controlled. Now, however, it was unleashed in its full fury. Bishop was sent for, an accusatory letter written, and then came expulsion from the physiology department.
In 1944, Erlanger and Gasser were awarded the Nobel Prize in Physiology or Medicine, but Bishop was not included. McComas disagrees with this decision, describing Bishop as “the man who should have shared the Nobel Prize with Gasser and Erlanger.”

Another interesting story is of the debate between Henry Dale and John Eccles about the nature of the nerve-muscle synapse. Dale favored a chemical synapse, with acetylcholine as the neurotransmitter. Eccles championed a synapse having a direct electrical connection. Apparently they engaged in a heated battle at the 1935 Cambridge meeting of the Physiological Society. Dale won this battle, and shared the 1936 Nobel Prize with Otto Loewi for their “discoveries relating to chemical transmission of nerve impulses”. Eccles, after a difficult time finding his scientific home, eventually made landmark discoveries about neural transmission in the central nervous system, and won his own Nobel Prize.

American Kenneth Cole is a complex character. On the one hand, Cole was generous in sharing his ideas with the young Alan Hodgkin when Hodgkin visited his Woods Hole laboratory in 1938. Yet, McComas writes
Respected and admired as a pioneer in the study of the nerve impulse, the recipient of medals and honorary degrees, Kenneth Cole was not content. This kind and unassuming man continued to resent the fact that his preparation and his voltage clamp had been used by Hodgkin without due acknowledgement.
He adds this interesting insight: “Unlike Cole, perpetually bedeviled by problems of one kind or another, success always seemed to follow Hodgkin.”

Another scientist depicted almost tragically is the Spaniard Rafael Lorente de No. McComas says
The publication of the Hodgkin-Huxley papers had been a bitter blow. Having labored for 10 years on his monumental study of peripheral nerve, Lorente now found that it was largely irrelevant, or, even worse, wrong in its main conclusions….Yet he refused to capitulate, let alone to walk away from a battle that only he wished to right. He would appear at international meetings, rejecting the general applicability of the Hodgkin-Huxley findings, and referring dismissively to the “so-called sodium hypothesis.” It was a sad end to a career that had been so full of promise.
The climax of the book is the story of Alan Hodgkin and Andrew Huxley developing their model of the squid giant axon, a model described in Chapter 6 of IPMB. Here is my favorite passage:
It was the intention of Hodgkin and Huxley to use the Cambridge University computer—the only computer in the entire university—to carry out the formidable amount of calculation involved, but the machine was undergoing major modifications at the time and would not be available for six months. Huxley then suggested to Hodgkin that he, Huxley, attempt to solve them himself, with the aid of his hand-operated Brunsviga calculating machine. It was an extraordinarily ambitious undertaking. The calculator, rather like an old-fashioned cash register, required that the data were entered by moving small levers in slots to appropriate positions beside numerically inscribed wheels. A handle at the side of the machine would then be turned so many times in one direction or another, and the results read off on the numbered wheels. These results would then have to be written down on paper, before proceeding to the next stage of the calculation. And these steps had to be repeated over and over again. The reconstruction of the action potential required numerical integration, and a complete set of data had to be produced for each small time interval. To calculate a complete ‘run’ required 8 hours of intense mental and physical activity. It has been said that, in all the calculations, more than a million separate steps were involved. It is doubtful if anyone other than Huxley could have brought it off.
If you are looking for a history of the early years of neuroscience, I highly recommend Galvani’s Spark. To tell you the truth, when I started the book I didn’t think it would be this good. Enjoy!

Friday, October 13, 2017

John Clark, Biomedical Engineer (1936-2017)

The first page of an article by Clark and Plonsey about the extracellular potential of a nerve axon.
John W. Clark passed away on August 6, in Houston, Texas. He was a professor of Engineering at Rice University for 49 years.

When I was a graduate student at Vanderbilt University in the 1980s, I was influenced by the papers of Robert Plonsey and his graduate student Clark. They calculated the extracellular electrical potential outside a nerve axon from the transmembrane action potential by expressing the transmembrane potential in terms of its Fourier transform, and then using Bessel functions to calculate the Fourier transform of the extracellular potential. Russ Hobbie and I outline this technique in Problem 30 of Chapter 7 in Intermediate Physics for Medicine and Biology. James Woolsey, my PhD advisor John Wikswo, and I used a similar method—inspired by Clark and Plonsey’s work—to calculate the magnetic field of a nerve axon (see Problem 16 of Chapter 8 in IPMB). Moreover, my first work on the bidomain model of the heart was analyzing cylindrical strands of cardiac tissue using methods that were an extension of Clark and Plonsey’s work. If I were to list the articles that had the biggest impact on my own work, near the top of that list would be Clark and Plonsey’s 1968 paper in the Biophysical Journal (Volume 8, Pages 842-864).

Clark graduated from Case Western Reserve University at about the time this Biophysical Journal  paper was published, and joined the faculty at Rice. Rarely do you see a professor’s career span half a century at one institution. He was a Life Fellow of the Institute of Electrical and Electronics Engineers (IEEE) “for contributions to modeling in electrophysiology, and cardiopulmonary systems.” He played a role in establishing the field of biomedical engineering, and served as President of the IEEE Engineering in Medicine and Biology Society.

To learn more about Clark and his contributions, see obituaries here, here and here.

Friday, October 6, 2017

Implantable Biocompatible Lasers!

Russ Hobbie and I discuss lasers several times in Intermediate Physics for Medicine and Biology. For instance, Homework Problem 6 in Chapter 14 is:
Problem 6. The left side of Fig. 14.1 shows the emission of a photon during a transition from an initial state with energy Ei to a final one with energy Ef . Usually the Boltzmann factor ensures that the population of the initial state is less than the final state. In some cases however, when the initial state is metastable, one can create a population inversion. Photons with energy corresponding to the energy difference EiEf can produce stimulated emission of other photons with the same energy, a type of positive feedback. Lasers work on this principle. Suppose a laser is made using two states having an energy difference of 1.79 eV. What is the wavelength of the output light? What color does this correspond to? Lasers have many uses in medicine (Peng et al.2008).
I thought I was familiar with most biomedical applications of lasers, until I read the recent article by Tami Freeman in
Sep 27, 2017
Implantable biolasers line up for therapy, monitoring
Biolasers -- miniature implantable lasers made of biocompatible materials -- are the subject of increasing research interest. Such lasers, which offer narrow emission linewidth, high coherence and high intensity, could enable novel imaging, diagnostic and therapeutic applications, as well as real-time physiological monitoring of temperature or glucose levels...
Implantable lasers made of biocompatible materials? Wow! The article concludes
...The researchers concluded that the availability of biocompatible and biodegradable microlasers made from materials approved for medical use or substances already present in the human body may open new opportunities for light-based diagnostics and therapies, as well as basic research.

“One of the first applications could be sensing and diagnostics,” [Marjaž] Humar [from the Jožef Stefan Institute] told medicalphysicsweb. “For example, the biolasers could be functionalized to be sensitive to glucose. A person having these lasers implanted into the skin would simply measure their glucose level by reading the laser output with a small optical reader.”
A screenshot of medicalphysicsweb
Not only is this article fascinating, but also it reminds me: have you been keeping up with medicalphysicsweb? Anyone interested in medical physics should read it regularly. Medicalphysicsweb is a community website from IOP [Institute of Physics] publishing. The English IOP is similar to the USA’s American Physical Society, supporting physics education, research, and industry. Tami Freeman does a superb job editing medicalphysicsweb. To hear more about her story, see