Friday, November 26, 2010

Acetylcholine and Loewi’s Dream

In 1936, Otto Loewi was awarded the Nobel Prize in Physiology or Medicine for the discovery of the role of acetylcholine and other chemicals in nerve and muscle transmission. Russ Hobbie and I don’t mention Loewi in the 4th edition of Intermediate Physics for Medicine and Biology, but we do discuss acetylcholine. In Chapter 6, we write
At the end of a nerve cell the signal passes to another nerve cell or to a muscle cell across a synapse or junction. A few synapses in mammals are electrical; most are chemical…In electrical synapses, channels connect the interior of one cell with the next. In the chemical case a neurotransmitter chemical is secreted by the first cell. It crosses the synaptic cleft (about 50 nm) and enters the next cell.

At the neuromuscular junction the transmitter is acetylcholine (ACh). ACh increases the permeability of nearby muscle to sodium, which then enters and depolarizes the muscle membrane. The process is quantized. Packets of acetylcholine of definite size are liberated.
In Homework Problem 20 in Chapter 4, we ask the student to calculate the time required for acetylcholine to diffuse across the synaptic cleft. The release of acetylcholine at the nerve-muscle junction in discrete quanta provides a nice example of Poisson Statistics described in Appendix J. In Chapter 7, when discussing the heart, we mention how acetylcholine, released by parasympathetic nerves, decreases the heart rate.

The Left Hand of the Electron, by Isaac Asimov, superimposed on Intermediate Physics for Medicine and Biology.
The Left Hand of the Electron,
by Isaac Asimov.
I can’t tell you about Otto Loewi and acetylcholine without mentioning the fascinating tale of Loewi’s dream. Since Isaac Asimov is a much better storyteller than I am, I will simply quote from his essay “The Eureka Phenomenon” published in The Left Hand of the Electron.
The German physiologist Otto Loewi was working on the mechanism of nerve action, in particular, on the chemicals produced by nerve endings. He woke at 3 A.M. one night in 1921 with a perfectly clear notion of the type of experiment he would have to run to settle a key point that was puzzling him. He wrote it down and went back to sleep. When he woke in the morning, he found he couldn't remember what his inspiration had been. He remembered he had written it down, but he couldn't read his writing.

The next night, he woke again at 3 A.M. with the clear thought once more in mind. This time, he didn't fool around. He got up, dressed himself, went straight to the laboratory and began work. By 5 A.M. he had proved his point and the consequences of his findings became important enough in later years so that in 1936 he received a share in the Nobel prize in medicine and physiology.

Friday, November 19, 2010

Viral Outbreak: The Science of Emerging Disease

Textbooks such as the 4th edition of Intermediate Physics for Medicine and Biology are essential for studying and learning a new topic, but other ways of learning can be equally effective (or, sometimes, even better). Today I want to mention two examples.

Each December, the Howard Hughes Medical Institute presents its Holiday Lectures on Science. These excellent seminars will be webcast live on December 2 and 3, starting at 10 A.M. This year, the lectures are about “Viral Outbreak: The Science of Emerging Disease.” Joseph DeRisi (University of California, San Francisco) and Eva Harris (University of California, Berkeley) will explain how to detect and fight infectious agents. The lectures will answer questions such as “Why is dengue fever becoming a worldwide health threat,” “What other epidemics are on the horizon,” and “How can we detect and counter emerging infectious diseases?” If you miss the live webcast, you can download an on-demand webcast starting December 6. I have watched these holiday lectures in the past, and they are very good. They are aimed at a serious high school student, or an undergraduate science major. They are also great for a physicist looking for a general introduction to a biological or medical topic.

Of course, the best way to learn science is to do science. For undergraduates (the main readers of Intermediate Physics for Medicine and Biology), the first exposure to doing science may come during a summer research project. Now is the time to start looking for summer research opportunities. One that I recommend is the Summer Internship Program in Biomedical Science at the National Institutes of Health. I worked at NIH for seven years, and it is a wonderful place to do scientific research. My advice is to apply for this internship today. You won’t regret it.

Friday, November 12, 2010


One feature of the 4th edition of Intermediate Physics for Medicine and Biology that distinguishes it from many other medical or biological textbooks is its focus on analyzing biomedical topics quantitatively. This point of view is also promoted at the BIONUMB3R5 (bionumbers) website, established by researchers in the systems biology department at Harvard. There is also a BIONUMB3R5 wiki where many researchers are coming together to provide new insights into key numbers in biology.

I particularly like the “Bionumber of the Month” feature. The March 2010 entry (“What are the Time Scales for Diffusion in Cells”) could easily be made into a homework problem for Chapter 4 of Intermediate Physics for Medicine and Biology. The January 2010 entry (“What is Faster, Transcription or Translation?”) is fascinating.
Transcription, the synthesis of mRNA from DNA, and translation, the synthesis of protein from mRNA, are the main pillars of the central dogma of molecular biology. How do the speeds of these two processes compare? …

Transcription of RNA by RNA polymerase in E. coli cells proceeds at a maximal speed of about 40–80 bp/sec… Translation by the ribosome in E. coli proceeds at a maximal speed of about 20 aa/sec… Interestingly, since every 3 base pairs code for one amino acid, the rates of the two processes are quite similar…
The “collection of fundamental numbers in molecular biology” found at the bionumbers website has the same tone as the first section of Chapter 1 in Intermediate Physics for Medicine and Biology, in which Russ Hobbie and I look at the relative size of biological objects. The collection contains this gem: “concentration of 1 nM in a cell the volume of E. coli is ~ 1 molecule/cell.”

The bionumbers website arose from an article by Rob Phillips and Ron Milo in the Proceedings of the National Academy of Sciences (Volume 106, pages 21465–21471, 2009), “A Feeling for the Numbers in Biology.” The abstract of their paper is given below:
Although the quantitative description of biological systems has been going on for centuries, recent advances in the measurement of phenomena ranging from metabolism to gene expression to signal transduction have resulted in a new emphasis on biological numeracy. This article describes the confluence of two different approaches to biological numbers. First, an impressive array of quantitative measurements make it possible to develop intuition about biological numbers ranging from how many gigatons of atmospheric carbon are fixed every year in the process of photosynthesis to the number of membrane transporters needed to provide sugars to rapidly dividing Escherichia coli cells. As a result of the vast array of such quantitative data, the BioNumbers web site has recently been developed as a repository for biology by the numbers. Second, a complementary and powerful tradition of numerical estimates familiar from the physical sciences and canonized in the so-called “Fermi problems” calls for efforts to estimate key biological quantities on the basis of a few foundational facts and simple ideas from physics and chemistry. In this article, we describe these two approaches and illustrate their synergism in several particularly appealing case studies. These case studies reveal the impact that an emphasis on numbers can have on important biological questions.
Russ and I introduce similar order-of-magnitude estimates (Fermi problems) in Chapter 1 of our book (for example, see homework problems 1–4, which are new in the 4th edition). One of my favorite Fermi problems, which I first encountered in the book Air and Water by Mark Denny, is to calculate the concentration of oxygen molecules in blood and in air, and compare them. Not too surprisingly, they are nearly the same (about 8 mM). I suspect the bionumbers folks would enjoy Air and Water. (I hope they would enjoy Intermediate Physics for Medicine and Biology, too.)

For those of you who find all of this interesting but prefer video over text, see the bionumbers video on YouTube.

Bionumbers: The data base of useful biological numbers. 

Friday, November 5, 2010

Seeing the Natural World with a Physicist’s Lens

One theme of this blog—and indeed, one theme of the 4th edition of Intermediate Physics for Medicine and Biology—is the role of physics in the biological sciences. So imagine my delight when Russ Hobbie sent me a similarly themed article from the November 1 issue of the New York Times (a publication that, alas, has more readers than does my blog). Natalie Angier, who studied for two years at that little college down the road in Ann Arbor, wrote an article titled Seeing the Natural World With a Physicist’s Lens. Its thesis is that many biological systems have evolved to perfection, in the sense that physical laws don’t let them get any better. Angier writes
Yet for all these apparent flaws, the basic building blocks of human eyesight turn out to be practically perfect. Scientists have learned that the fundamental units of vision, the photoreceptor cells that carpet the retinal tissue of the eye and respond to light, are not just good or great or phabulous at their job. They are not merely exceptionally impressive by the standards of biology, with whatever slop and wiggle room the animate category implies. Photoreceptors operate at the outermost boundary allowed by the laws of physics, which means they are as good as they can be, period. Each one is designed to detect and respond to single photons of light—the smallest possible packages in which light comes wrapped…

Photoreceptors exemplify the principle of optimization, an idea, gaining ever wider traction among researchers, that certain key features of the natural world have been honed by evolution to the highest possible peaks of performance, the legal limits of what Newton, Maxwell, Pauli, Planck et Albert will allow. Scientists have identified and mathematically anatomized an array of cases where optimization has left its fastidious mark… In each instance, biophysicists have calculated, the system couldn’t get faster, more sensitive or more efficient without first relocating to an alternate universe with alternate physical constants.
Angier has written a lot of articles for the NYT, and has published several books, that will be of interest to readers of Intermediate Physics for Medicine and Biology. Enjoy!