The Impact of Physics on Biology and Medicine

For the last few years that I worked at the National Institutes of Health, Harold Varmus was the NIH director. Varmus was a Nobel Prize winner who often rode his bike to work. He began his academic career studying poetry at Amherst College and ended up being awarded the National Medal of Science. He is currently the president of the Memorial Sloan-Kettering Cancer Center.

On March 22, 1999, Varmus gave a Plenary Talk titled “The Impact of Physics on Biology and Medicine” at the Centennial Meeting of the American Physical Society in Atlanta, Georgia. Readers of the 4th edition of Intermediate Physics for Medicine and Biology will find this speech fascinating and inspirational. He began

The organizers of your hundredth birthday party have asked me to describe the impact of your field, physics, on the two fields, biology and medicine, that are most obviously identified with the agency I lead, the National Institutes of Health. They have done me this honor not to recognize any knowledge I might have retained from college course work in your field, but to allow me to discuss one of my convictions about medical research, namely, the opinion that the NIH can wage an effective war on disease only if we—as a nation and a scientific community, not just as a single agency—harness the energies of many disciplines, not just biology and medicine. These allied disciplines range from mathematics, engineering, and computer sciences to sociology, anthropology, and behavioral sciences. But the weight of historical evidence and the prospects for the future place physics and chemistry most prominently among them.

I propose to consider the effects of physics on the medical sciences from three perspectives. First, I will briefly catalog some of the consequences of a simple and obvious connection between physics and medicine, namely, that the human body and its components are physical objects that can be viewed and measured and altered in ways that resemble what a physicist might do with any physical object. Second, I will remind you of an enormously important phase in the history of biology in which physicists transformed the study of living things by helping to discover the principles of heredity. Third, I will describe some contemporary problems in the biomedical sciences that I believe should be inviting challenges to physicists, young and old. In the context of doing this, I will also allude to ways in which the NIH is attempting to ease the path from a formal training in physics to an active investigative role in biomedical sciences.

If you want to read more by Varmus, you can preorder his new book The Art and Politics of Science due out in February. 

Harold Varmus describes how he became a scientist.
https://www.youtube.com/watch?v=ct3bDM6YBEw

Sound and Ultrasound

When Russ Hobbie and I started to prepare the 4th edition of Intermediate Physics for Medicine and Biology, we discussed if we should add any new chapters. After reviewing comments from users of the 3rd edition, we concluded that there was one essential topic not covered in previous editions: medical ultrasound. So, Chapter 13 of the 4th edition is our attempt to describe the physics of sound and ultrasound, as applied to biology and medicine.

Sound (or acoustics) plays two important roles in our study of physics in medicine and biology. First, animals hear sound and thereby sense what is happening in their environment. Second, physicians use high-frequency sound waves (ultrasound) to image structures inside the body. This chapter provides a brief introduction to the physics of sound and the medical uses of ultrasonic imaging. A classic textbook by Morse and Ingard (1968) provides a more thorough coverage of theoretical acoustics, and books such as Hendee and Ritenour (2002) describe the medical uses of ultrasound in more detail.

In Sec. 13.1 we derive the fundamental equation governing the propagation of sound: the wave equation. Section 13.2 discusses some properties of the wave equation, including the relationship between frequency, wavelength, and the speed of sound. The acoustic impedance and its relevance to the reflection of sound waves are introduced in Sec. 13.3. Section 13.4 describes the intensity of a sound wave and develops the decibel intensity scale. The ear and hearing are described in Sec. 13.5. Section 13.6 discusses attenuation of sound waves. Physicians use ultrasound imaging for medical diagnosis, as described in Section 13.7. Ultrasonic imaging can provide information about the flow of blood in the body by using the Doppler effect, as shown in Sec. 13.8.

At 16 pages, this chapter on sound is the shortest in our book. Throughout the 4th edition, we moved many interesting applications into the homework problems, and nowhere is this more evident than in Chapter 13. Many aspects of ultrasonic imaging are only addressed in the problems, so you really need to work them in order to get a full understanding of ultrasound techniques.

Air and Water,
by Mark Denny.

Chapter 13 has the fewest references (only six) of any chapter in our book. To provide some additional guidance, let me comment on some these references. Theoretical Acoustics by Morse and Ingard is excellent but quite mathematical. Don’t look there for a gentle introduction. I always recommend Denny’s Air and Water for insight into biological physics, in this case his Chapter 10, Sound in Air and Water: Listening to the Environment. Hendee and Ritenour's Medical Imaging Physics (4th Edition) has several excellent chapters on medical ultrasound.

Where can you get additional information? First, there is always Wikipedia. Another online source can be found at How Stuff Works. The American Institute of Ultrasound in Medicine has a useful website, and publishes the Journal of Ultrasound in Medicine. Hendee and Ritenour repeatedly cite Zagzebski’s Essentials of Ultrasound Physics. Although I haven’t read it, my understanding is that it is aimed at students who are preparing to take the ARDMS exam. The American Registry for Diagnostic Medical Sonography (ARDMS) administers accreditation examinations in the area of diagnostic medical sonography, and publishes a list of topics covered on the Ultrasound Physics and Instrumentation exam. Another book that I haven’t read but have heard good things about is Diagnostic Ultrasound, by Rumack, Wilson, and Charboneau. At $325, the third edition of this two-volume tome is a bit pricey, but perhaps your library will have a copy. Finally, Russ and I always like to point out good American Journal of Physics articles, such as Mark Denny’s “The physics of bat echolocation” (Volume 72, Pages 1465–1477, 2004). Those brave souls who are teaching medical or biological physics with a lab incorporated into the class may find the paper “Undergraduate experiment to measure the speed of sound in liquid by diffraction of light” (Luna et al., American Journal of Physics, Volume 70, Pages 874–875, 2002) useful.

Theory of Sound,
by Lord Rayleigh.

Before I end, let me acknowledge one physicist who contributed much to our understanding of sound, Lord Rayleigh. I am a big fan of Victorian physicists (such as Faraday, Maxwell, and Kelvin), among whom Rayleigh is one of my favorites. This Nobel Prize winner, who published the two-volume Theory of Sound, was one of the first to discover how humans localize sound. He is one more of a long list of physicists who have made fundamental contributions to biology and medicine.

Note added October 26: A friend of mine, Neb Duric of the Karmanos Cancer Institute, has developed a way to detect breast cancer using ultrasound. For more, see the video on the Medical Physics in the news website.

Nonlinear Dynamics

Nonlinear dynamics is discussed in several chapters in the 4th edition of Intermediate Physics for Medicine and Biology, and particularly in Chapter 10. Where can you go to get a more information about this topic? Several fine books are cited in our references.

Nonlinear Dynamics and Chaos,
by Steven Strogatz.

One book that Russ Hobbie cited in earlier editions of our text is Nonlinear Dynamics and Chaos, by Steven Strogatz. Even though we still cite the book in the 4th edition, I was not really familiar with it until last year, when my daughter Stephanie used it in a class on nonlinear dynamics at the University of Michigan. She loved the book, and recommended it to me. In the preface, Strogatz writes

This textbook is aimed at newcomers to nonlinear dynamics and chaos, especially students taking a first course in the subject. It is based on a one-semester course I’ve taught for the past several years at MIT. My goal is to explain the mathematics as clearly as possible, and to show how it can be used to understand some of the wonders of the nonlinear world... A unique feature of the book is its emphasis on applications. These include mechanical vibrations, lasers, biological rhythms, superconducting circuits, insect outbreaks, chemical oscillators, genetic control systems, chaotic waterwheels, and even a technique for using chaos to send secret messages. In each case, the scientific background is explained at an elementary level and closely integrated with the mathematical theory.

When Time Breaks Down,
by Art Winfree.

For anyone who reads Intermediate Physics for Medicine and Biology and wants to learn more about nonlinear dynamics, I recommend this delightful text. Strogatz, the Jacob Gould Schurman Professor of Applied Mathematics at Cornell University, was a collaborator and student of one of my heroes, the late Art Winfree. Art’s book When Time Breaks Down had a tremendous influence on my early career. I have not yet read Strogatz’s newest book Sync: How Order Emerges from Chaos in the Universe, Nature, and Daily Life, but reading it is on my list of things to do.

From Clocks to Chaos,
by Glass and Mackey.

A book that came out when I was working at the National Institutes of Health is Leon Glass and Michael Mackey’s From Clocks to Chaos. While this book may not present the math as elegantly as Strogatz’s book, it does focus specifically on biological and medical problems. In particular, it introduces the idea of a “dynamical diseases”: diseases characterized by abnormal temporal organization.

Dynamics:
The Geometry of Behavior,
by Abraham and Shaw.

When explained well, nonlinear dynamics is a very visual subject. An older book that makes much use of pictures is Dynamics: The Geometry of Behavior by Abraham and Shaw. In fact it could be called a “picture book,” but don’t let that description fool you. The math is presented at a high level, but in a primarily visual way. It was a great help to me when I was first learning the subject.

The Visual Display of Quantitative Information

The Visual Display
of Quantitative Information,
by Edward Tufte.

Early in my graduate school career (back when I used to have time to read widely), a fascinating book was published titled The Visual Display of Quantitative Information. Its author Edward Tufte describes the book as a “celebration of data graphics.” In the introduction, he writes

Modern data graphics can do much more than simply substitute for small statistical tables. At their best, graphics are instruments for reasoning about quantitative information. Often the most effective way to describe, explore, and summarize a set of numbers—even a very large set—is to look at pictures of those numbers. Furthermore, of all methods for analyzing and communicating statistical information, well-designed graphics are usually the simplest and at the same time the most powerful.

A page from The Visual Display
of Quantitative Information,
by Edward Tufte.

Tufte suggests ways to improve data graphics. For instance, Chapter 4 concludes by summarizing these five principles: 1) Above all else show the data, 2) Maximize the data-ink ratio, 3) Erase non-data-ink, 4) Erase redundant data-ink, and 5) Revise and edit. Chapter 9 offers this recommendation: “Graphical elegance is often found in simplicity of design and complexity of data.” Perhaps Tufte’s poem at the end of Chapter 8 summarizes these ideas more succinctly:

For non-data-ink, less is more.
For data-ink, less is a bore.

Of course, words can’t convey the lessons of this book. You need to see the graphics appearing on every page to appreciate his points.

Many of the readers of the 4th edition of Intermediate Physics for Medicine and Biology will go on to become research scientists, engineers, or medical doctors, and will publish papers full of interesting data. That data will be presented more clearly, simply, and elegantly by following the principles and techniques outlined in The Visual Display of Quantitative Information and Tufte’s other books. 

Listen to Edward Tufte talk about the Art of Visualization.
https://www.youtube.com/watch?v=AdSZJzb-aX8 

The Bends

Physics with Illustrative Examples
from Medicine and Biology,
by Benedek and Villars.

When I teach about hydrostatics from the 4th edition of Intermediate Physics for Medicine and Biology, I like to make a little digression and discuss a biomedical application of hydrostatic pressure: decompression sickness. Also known as “the bends,” this illness occurs after breathing high-pressure air, which causes nitrogen to be dissolved in the blood. If the pressure is then released suddenly the nitrogen can form bubbles that block circulation. This effect is not unlike the formation of foam—made from bubbles of carbon dioxide—when you open a bottle of pop. You can find a nice discussion of the physiological effects of increased fluid pressure in Physics With Illustrative Examples from Medicine and Biology: Mechanics, by George Benedek and Felix Villars.

Engineers of Dreams:
Great Bridge Builders and the
Spanning of America,
by Henry Petroski.

Often you can teach best by telling a story, and when discussing decompression sickness I like to tell the story of the Eads Bridge. James Eads built the first bridge over the Mississippi River at St Louis. It is a beautiful arch bridge that opened in 1874. When building the supports for the bridge under the river, Eads used “caissons,” watertight structures sunk under the river and filled with compressed air. The high air pressure prevented water from filling the caisson, allowing workers to excavate the river bottom. In his book Engineers of Dreams: Great Bridge Builders and the Spanning of America, Henry Petroski has described decompression sickness experienced by men working in Eads’ caissons.

When the caisson reached a depth of seventy feet, the workmen began to experience some difficulty climbing the stairs to the surface. As the caisson was sunk deeper, men suffered increasing attacks of cramps and paralysis, which were thought to be due to insufficient clothing or poor nutrition. In March 1870, when the caisson had reached ninety-three feet, the air pressure inside it was about four times what it was in the open air, and workmen began dying upon emerging from the caisson, or after being hospitalized for an ailment that came then to be called "caisson disease" but today is known as “the bends.” Eads asked his family physician, Dr. Alphonse Jaminet, to look after the workmen, but Jaminet himself became paralyzed one day, having spent time down in the caisson and come up after only a few minutes in the air lock.

Perhaps somewhat to his own surprise, Jaminet recovered, and began to conduct research into these mysterious attacks. He shortly concluded that the major cause was too-rapid decompression in the face of a drastic difference in air pressure between the submerged caisson and the outer air above. Thereupon he placed restrictions on the amount of time the men could work inside the caisson, and on the speed with which the pressure in the air lock could be reduced.

Incidentally, Petroski has written many fascinating books about engineering, including To Engineer Is Human: The Role of Failure in Successful Design and The Evolution of Useful Things. He also has a monthly essay on engineering in American Scientist, the magazine of Sigma Xi, the Scientific Research Society. Although there’s not much medicine or biology in Petroski’s work, certainly a biomedical engineer studying from Intermediate Physics for Medicine and Biology will find many important lessons about engineering design. I give Petroski’s books two thumbs up.

Inside Story: Physics in Medicine

The Institute of Physics has an excellent website called “Inside Story: Physics in Medicine,” which contains some fascinating animations with colorful images. It is at a significantly more elementary level than the 4th edition of Intermediate Physics for Medicine and Biology, but might be used as a fun “extra” in a medical physics class based on that book. MRI Scans, Colonoscopy, PET Scans, and Radiotherapy are the featured topics.

When you first link to the webpage, you have two choices. If your computer has Macromedia Flash Plugin 7, then definitely enter the “flash” site, as it is much more interesting than the “html” site.“Inside Story” was produced by the Institute of Physics and the Medical Research Council, a English organization that “promotes the balanced development of medical and related biological research in the UK.” It was developed as part of the 2005 Einstein Year, a worldwide celebration of the one hundredth anniversary of Einstein’s miraculous year, when Albert Einstein, at age 26, published his theories of Brownian motion, special relativity and the photoelectric effect.

Virtual Colonoscopy

Ever had a colonoscopy? It’s not pleasant. A paper published this week in the New England Journal of Medicine (Volume 359, pages 1207—1217), titled “Accuracy of CT Colonography for Detection of Large Adenomas and Cancers” suggests an alternative to the traditional procedure for detecting colorectal cancer: a “virtual colonoscopy.” This X-ray technology uses Computed Tomography (CT), which Russ Hobbie and I discuss in Chapter 12 of the 4th edition of Intermediate Physics for Medicine and Biology. The NEJM article concludes that “in this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer.” To learn more about this study, see the Associated Press article by Mike Strobbe, and an article in US News and World Report.

Any X-ray procedure does have a risk associated with the radiation dose. A typical virtual colonsocopy has a dose of 5 to 10 mSv. By comparison, the yearly dose from the natural background radiation is about 3 mSv. (The sievert is a unit of dose equal to a Joule per kilogram, adjusted for its biological effectiveness. A mSv is one thousandth of a sievert.) See my December 7, 2007 entry in this blog, or Chapter 16 of the 4th edition of Intermediate Physics for Medicine and Biology, for more information about radiation safety and CT scans. Of course, any risk of radiation must be weighed against risks involved with traditional colonoscopy procedures.

Now for the bad news: You still need to “clean out your bowels” before the procedure, regardless of which method you use: traditional or virtual.

Particle Physics Rap

Today’s post (a rare non-Friday message) has nothing to do with the 4th edition of Intermediate Physics for Medicine and Biology, and nothing to do with medicine and biology at all. But if you are a physics fan, you must check out the particle physics rap at www.physicscentral.com (see the video highlight). This rap celebrates the Large Hadron Collider (LHC), which was turned on September 10, beginning what may be some of the greatest particle physics experiments ever. The rap is too delightful to miss. Enjoy.

Note added October 26: Physics central took the blog off their site, but you can still find it at youtube: http://www.youtube.com/watch?v=j50ZssEojtM. 

 Listen to a physics rap celebrating the Large Hadron Collider.
http://www.youtube.com/watch?v=j50ZssEojtM 

Switching from Physics to Biology

Physicists studying from the 4th edition of Intermediate Physics for Medicine and Biology may be interested in entering the field of biological physics. If so, I suggest reading “Switching From Physics to Biology: Physicists in Transition Help Shape Biological Theory” by Jennifer Ouellette (The Industrial Physicist, Volume 9, Pages 20–23, 2003). The article, which can be found online, begins

Many in physics chafe at the oft-quoted maxim that the 21st century is the “age of biology.” Others see the biological boom as offering unique opportunities for physicists—and not just in the traditional area of building instrumentation for experimental research. Physicists are well positioned by their training to contribute to the development of a theoretical framework in biology, a field that has matured to the point where sufficient quantitative data and sophisticated experimental tools exist to test biological theories.

For other physics-to-biology stories, see Yuh-Nung Jan’s interview in Current Biology and Chris Sander’s story told on the Sloan-Kettering Institute website. Also, here is some advice from the “Grant Doctor” published in Science. 

 Listen to Jennifer Ouellette talk about change.
https://www.youtube.com/watch?v=tGZn0IdFHp4 

Biocurious

While surfing the internet one evening, I stumbled upon a fascinating website that will interest readers of the 4th edition of Intermediate Physics for Medicine and Biology. It is called “Biocurious, a biophysics blog.”

Biocurious is a weblog about biology (and physics, grad school, and miscellenaeous other things!) through the eyes of physicists.

As best I can tell, Biocurious is maintained entirely by two graduate students, Andre Brown of the University of Pennsylvania and Philip Johnson of the University of Toronto. The blog is interesting, well-written, and provides insight into the interface between physics and biology, as well as the lifestyle of biological physics grad students. One enjoyable feature of this site is the “molecule of the month” (from the protein data bank), and another is the extended list of other related blogs, which I have only begun to explore. I particularly like their header image, a picture by David Goodsell of a macrophage and bacterium at a magnification of 2,000,000.

Nice blog, Andre and Philip.