Friday, January 30, 2009

Lady Luck

At the bottom of page 50 in the 4th Edition of Intermediate Physics for Medicine and Biology is a short footnote: "A good book on probability is Weaver (1963)." The reference given at the end of the chapter is to Lady Luck, by Warren Weaver. This book is one of my favorites, and reflects my interest in probability. I particularly enjoyed Weaver's description (in Chapter 6) of a game that at first glance is counter-intuitive:

"Take three identical cards. Make a red mark on both sides of one, a black mark on both side of the second, and mark the third black on one side and red on the other. Mix them up in a hat, pick out a card at random, and put it down on the table without disclosing to yourself or anyone else what color is marked on the concealed side.

Suppose the upper side of the card is marked red. You say to your opponent, 'Obviously we are not dealing with the black-black card. That one is clearly eliminated. We definitely have either the red-black card or the red-red card. We shuffled fairly and drew at random, so it is just as likely to be one of these as the other. I will therefore bet you even money that the other side is red.'

It isn't too hard to find takers, although ... the odds in favor of your bet are not even, but are actually two to one! The catch, of course, is the clause 'so it is just as likely to be one as the other.' It is twice as likely that it is the red-red card! Forty years ago, when graduate students had to work for their living, the author used to teach this particular problem, at reasonable rates and using the experimental method, to his college friends."
Weaver is an interesting figure in 20th century mathematics and science, and fits in well with our theme of applying physics to medicine and biology. He was director of the Division of Natural Sciences at the Rockefeller Foundation from 1932 to 1955. According to wikipedia,
"Weaver early understood how greatly the tools and techniques of physics and chemistry could advance knowledge of biological processes, and used his position in the Rockefeller Foundation to identify, support, and encourage the young scientists who years later earned Nobel Prizes and other honors for their contributions to genetics or molecular biology."
When I teach probability (often in the first week of a class on statistical mechanics or quantum mechanics), I like to use the example of playing craps. Weaver analyzes craps in chapter 15 of Lady Luck:
"The game of craps furnishes a good example of probability calculations in a gambling game; for craps is sufficiently more complicated than 'heads and tails' to raise some nice little problems, but not so complicated (as is bridge, for example) that the calculations are tedious."
It is also interesting for the students, who have visited the casinos and played craps more than I have. (Anyone who understands probability will find gambling at casinos to be financially unwise).

In Intermediate Physics for Medicine and Biology, probability is particularly important in Chapter 3, when Hobbie and I discuss statistical mechanics. Probabilistic ideas also appear throughout the book in the form of the Poisson probability distribution, which we analyze in detail in our Appendix J.

Friday, January 23, 2009

Citation Classic Commentaries

From 1977 to 1993, thousands of Citation Classic Commentaries appeared in Current Contents, a database of journal tables of contents originally published by the Institute of Scientific Information. The full texts of these mostly one-page articles are now available at http://garfield.library.upenn.edu/classics.html. In each article, the author of a highly-cited paper tells the story behind the research and describes how the paper came to be published. I find that these commentaries provide a glimpse into the human side of science. They offer insight into what an author thinks about his own work years after it is completed. I always enjoyed reading them, and wish they were still being written.

Many of these commentaries are related to medical and biological physics. Below I list a dozen that readers of the 4th Edition of Intermediate Physics for Medicine and Biology might enjoy. Each link will download a pdf of the commentary.

N Bloembergen, EM Purcell, and RV Pound. Relaxation effects in nuclear magnetic resonance absorption. Phys. Rev., 73:679-712, 1948.

EL Hahn. Spin Echoes. Phys. Rev., 80:580-594, 1950.

B Lown, R Amarasingham, and I Neumann. A new method for terminating cardiac arrhythmias. J. Amer. Med. Ass. 182:548-55, 1962.

S Meiboom and D Gill. Modified spin-echo method for measuring nuclear relaxation times. Rev. Sci. Instr., 29:688-91, 1958.

AL Hodgkin and AF Huxley. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. London, 117:500-44, 1952.

JH Hubbell. Photon cross sections, attenuation coefficients, and energy absorption coefficients from 10 keV to 100 GeV. Washington, DC: US Government Printing Office, August 1969. National Standard Reference Data Series Report No. NSRDS-NBS 29. 8Op.

ME Phelps, EJ Hoffman, S-C Huang and DE Kuhl. ECAT: a new computerized tomographic imaging system for positron-emitting radiopharmaceuticals. J. Nuci. Mcd. 19:635-47, 1978.

FJ Bonte, RW Parkey, KD Graham, J Moore and EM Stokely. A new method for radionuclide imaging of myocardial infarcts. Radiology, 110:473-4, 1974.

IR Young, DR Bailes, M Burl, AG Collins, DT Smith, MJ McDonnell, JS Orr, LM Banks, GM Bydder, RH Greenspan and RE Steiner. Initial clinical evaluation of a whole body nuclear magnetic resonance (NMR) tomograph. J. Compur. Assist.Tomogr., 6:1-18. 1982.

JH Hubbell. Photon mass attenuation and energy-absorption coefficients from 1 keV to 20 MeV. Int. J. App!. Radiat. Isot., 33:1269-90. 1982.

PA Bottomley and ER Andrew. Magnetic field penetration, phase shift and power dissipation in biological tissue: implications for NMR imaging. Phys. Med. Biol., 23:630-43. 1978.

JW Cooley and JW Tukey. An algorithm for the machine calculation of complex Fourier series. Math. Comput., 19:297-301, 1965.

Friday, January 16, 2009

Cardiac Bioelectric Therapy

In the 4th Edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I introduce some fundamental concepts about the electrical properties of the heart (see, for example, Chapters 7 and 10). A new multi-author book, Cardiac Bioelectric Therapy: Mechanisms and Practical Implications, provides an in depth examination of this topic. In a forward to the book, Ray Ideker writes

"Since pacemakers and defibrillators were developed a little more than 50 years ago, their usage has grown rapidly, so that over 900,000 pacemakers and 200,000 defibrillators are implanted every year throughout the world. During this half century there have been astonishing advances in the efficacy and sophistication of these devices. Yet the devices still have major limitations...

Although there are many books that deal with the practical aspects of pacing and defibrillation, there is a pressing need for a single source that presents current knowledge about the basic mechanisms of cardiac bioelectric theory. This book, edited by Efimov, Kroll, and Tchou [admirably] fulfills this need. The chapters thoroughly and masterfully cover all aspects of this subject and are written by experts in the field.... I predict this book will be the standard source that will be consulted both by experienced workers in this area as well as by students and others who wish to learn more about this subject."
I have two chapters in this book: "The Bidomain Theory of Pacing" written with my former graduate student Debbie Janks, now at the University of Vermont College of Medicine, and "Virtual Electrode Theory of Pacing" coauthored with John Wikswo of Vanderbilt University, a long-time collaborator and my PhD dissertation advisor. Other chapters that I find particularly useful are "Bidomain Model of Defibrillation" by Natalia Trayanova and Gernot Plank, "The Generalized Activating Function" by Leslie Tung (who invented the bidomain model of cardiac tissue in his PhD dissertation), "Critical Points and the Upper Limit of Vulnerability for Defibrillation" by Raymond Ideker and Derek Dosdall, and "The Virtual Electrode Hypothesis of Defibrillation" by Crystal Ripplinger and Igor Efimov. This is only a partial list; other excellent chapters are written by a Who's Who of leaders in the field, such as Craig Henriquez, Steve Knisley, Vladimir Fast, Hrayr Karagueuzian, Niels Otani, Alain Karma, Shiien-Fong Lin, and Wanda Krassowska, among others.

The book covers two topics in detail: the bidomain, a mathematical model of the heart's electrical properties that I have worked on much in my career, and optical mapping of transmembrane potential. This second topic is an experimental technique that involves a fluorescent dye that is bound to the cell membrane. This amount the dye fluoresces depends on the transmembrane potential, which allows researchers to record an electrical quantity using optical methods.

I can think of only one problem with the book: at $199 it is expensive (you could get two copies of the 4th Edition of Intermediate Physics for Medicine and Biology for that price and still have money left over). But for students and researchers serious about understanding pacemakers and defibrillators, this book is worth the money. For students interested in browsing the book to expand their knowledge, all I can say is try your library, and there is always interlibrary loan.

Friday, January 9, 2009

The National Institutes of Health

About now, you undergraduate students studying from the 4th Edition of Intermediate Physics for Medicine and Biology are probably starting to wonder what you'll be doing this summer. I suggest you consider an internship to do biomedical research at the National Institutes of Health (application deadline: March 1). I can't think of a better first step toward a career applying physics to medicine and biology.

For seven years (1988-1995), I had the privilege of working at the National Institutes of Health in Bethesda, Maryland. According to wikipedia:
"The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical and health-related research. The Institutes are responsible for 28%—about $28 billion—of the total biomedical research funding spent annually in the U.S., with most of the rest coming from industry. The NIH is divided into two parts: the 'Extramural' parts of NIH are responsible for the funding of biomedical research outside of NIH, while the 'Intramural' parts of NIH conduct research. Intramural research is primarily conducted at the main campus in Bethesda."
I was part of the intramural Biomedical Engineering and Instrumentation Program, which no longer exists. (Now Bioengineering has an entire institute, the National Institute of Biomedical Imaging and Bioengineering.) The mission of our group was to provide expertise in physics, engineering, and mathematics, and to collaborate with NIH's biologists and medical doctors. I learned much during my stay at NIH about how physics is applied to biomedicine. It was the ideal preparation for working on a book like Intermediate Physics for Medicine and Biology.

Doing research at NIH was a joy and an honor, and I highly recommend it to any physicist (or physics student) interested in biomedical applications. Apply for an internship today.

Friday, January 2, 2009

Isaac Asimov

Isaac Asimov (1920-1992) was born 89 years ago today. He is best known as a science fiction writer, and is considered one of the "big three" of science fiction (along with Robert Heinlein and Arthur C. Clarke). He was also a great author of science popularizations, and wrote or edited over 500 books.

I started reading Asimov's nonfiction when in high school, and it had a big influence on me. In fact, one of the main reasons I decided to study science in college was because of his books. I particularly enjoyed his collections of essays originally published in The Magazine of Fantasy and Science Fiction. Asimov's writing covered all areas of science: biology, chemistry, physics, geology, astronomy, and medicine. My personal intellectual journey--from physics to biological physics to coauthor of the 4th Edition of Intermediate Physics for Medicine and Biology--began with the scientific liberal education he provided. When I was young, my goal was to read every book Asimov had ever written. I read scores of them, but soon I realized that he was writing them faster than I could read them.

Which of Asimov's books do I recommend? Among his fiction, I suggest
I, Robot and the The Foundation Trilogy. Unfortunately, his science popularizations are a bit dated now, but you might still enjoy many of his books, including his three-volume Understanding Physics, The Genetic Code, The Wellsprings of Life, The Human Body, and The Human Brain. For those wanting an Asimov sampler, try Opus 100, Opus 200, or Opus 300. Asimov aficionados will enjoy his two-volume autobiography In Memory Yet Green and In Joy Still Felt. The Isaac Asimov Home Page has much information including a complete list of his books. One obsessive Asimov fan provides summaries and reviews of all his work.

Readers of Intermediate Physics for Medicine and Biology may sometimes wonder how they will ever obtain the prerequisite background in physics, chemistry, biology and medicine necessary for such an interdisciplinary field of study. My solution was to start by reading Isaac Asimov. I don't know of any single author who could provide a better introduction to these topics.

Happy Birthday, Dr. Asimov. You left us too soon.