Happy Birthday Laser!

Quantum Physics of Atoms,
Molecules, Solids, Nuclei, and Particles,
by Eisberg and Resnick.

This month marks the 50^th anniversary of the invention of the laser. In May 1960, Theodore Maiman built the first device to produce coherent light by the mechanism of “Light Amplification by Stimulated Emission of Radiation” at Hughes Research Laboratories in Malibu, making the laser just slightly older than I am. A special website, called laserfest, is commemorating this landmark event. Eisberg and Resnick discuss lasers in Section 11.7 of their textbook Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles (quoted from the first edition, 1974).

In the solid state laser that operates with a ruby crystal, some Al atoms in the Al₂O₃ molecules are replaced by Cr atoms. These “impurity” chromium atoms account for the laser action… The level of energy E1 is the ground state and the level of energy E3 is the unstable upper state with a short lifetime (≈10⁻⁸ sec), the energy difference E3-E1 corresponding to a wavelength of about 5500 Å. Level E2 is an intermediate excited state which is metastable, its lifetime against spontaneous decay being about 3 x 10⁻³ sec. If the chromium atoms are in thermal equilibrium, the population number of the states are such that [n3 is less than n2 is less than n1]. By pumping in radiation of wavelength 5500 Å, however, we stimulate absorption of incoming photons by Cr atoms in the ground state, thereby raising the population number of energy state E3 and depleting energy state E1 of occupants. Spontaneous emission, bringing atoms from state 3 to state 2, then enhances the occupancy of state 2, which is relatively long-lived. The result of this optical pumping is to decrease n1 and increase n2, such that n2 is greater than n1 and population inversion exists. Now, when an atom does make a transition from state 2 to state 1, the emitted photon of wavelength 6943 Å will stimulate further transitions. Stimulated emission will dominate stimulated absorption (because n2 is greater than n1) and the output of photons of wavelength 6943 Å is much enhanced. We obtain an intensified coherent monochromatic beam.

Lasers are an important tool in biology and medicine. Russ Hobbie and I discuss their applications in Chapter 14 (Atoms and Light) the 4th edition of Intermediate Physics for Medicine and Biology. In Section 14.5 (The Diffusion Approximation to Photon Transport) we write

A technique made possible by ultrashort light pulses from a laser is time-dependent diffusion. It allows determination of both μ_s and μ_a [the scattering and absorption attenuation coefficients]. A very short (150-ps) pulse of light strikes a small region on the surface of the tissue. A detector placed on the surface about 4 cm away records the multiply-scattered photons… A related technique is to apply a continuous laser beam, the amplitude for which is modulated at various frequencies between 50 and 800 MHz. The Fourier transform of Eq. 14.29 gives the change in amplitude and phase of the detected signal. Their variation with frequency can also be used to determine μ_a and μ_s.

We also mention lasers in Section 14.10 (Heating Tissue with Light).

Sometimes tissue is irradiated in order to heat it; in other cases tissue heating is an undesired side effect of irradiation. In either case, we need to understand how the temperature changes result from the irradiation. Examples of intentional heating are hyperthermia (heating of tissue as a part of cancer therapy) or laser surgery (tissue ablation). Tissue is ablated when sufficient energy is deposited to vaporize the tissue.

Russ and I give many references about lasers in medicine in our Resource Letter (“Resource Letter MP-2: Medical Physics,” American Journal of Physics, Volume 77, Pages 967–978, 2009):

F. Lasers and optics

Lasers have introduced many medical applications of light, from infrared to the visible spectrum to ultraviolet.

150. Lasers in Medicine, edited by R. W. Waynant (CRC, Boca Raton, 2002). (I)

151. Laser-Tissue Interactions: Fundamentals and Applications, M. H. Niemz (Springer, Berlin, 2007). (I)

152. “Lasers in medicine,” Q. Peng, A. Juzeniene, J. Chen, L. O. Svaasand, T. Warloe, K.-E. Giercksky, and J. Moan, Rep. Prog. Phys. 71, Article 056701, 28 pages
(2008). (A)

A fascinating and fast-growing new technique to image biological tissue is optical coherence tomography “OCT.” It uses reflections like ultrasound but detects the reflected rays using interferometry.

153. Optical Coherence Tomography, M. E. Brezinski (Elsevier, Amsterdam, 2006). Overview of the physics of OCT and applications to cardiovascular medicine, musculoskeletal disease, and oncology. (I)

154. “Optical coherence tomography: Principles and applications,” A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, Rep. Prog. Phys. 66, 239–303 (2003). (I)

With infrared light, scattering dominates over absorption. In this case, light diffuses through the tissue. Optical imaging in turbid media is difficult but not impossible.

155. “Recent advances in diffuse optical imaging,” A. P. Gibson, J. C. Hebden, and S. R. Arridge, Phys. Med. Biol. 50, R1–R43 (2005). (I)

156. “Pulse oximetry,” R. C. N. McMorrow and M. G. Mythen, Current Opinion in Critical Care 12, 269–271 (2006). The pulse oximeter measures the oxygenation of blood and is based on the diffusion of infrared light. (I)

One impetus for medical applications of light has been the development of new light sources, such as free-electron lasers and synchrotrons. In both cases, the light frequency is tunable over a wide range.

157. “Free-electron-laser-based biophysical and biomedical instrumentation,” G. S. Edwards, R. H. Austin, F. E. Carroll, M. L. Copeland, M. E. Couprie, W. E. Gabella, R. F. Haglund, B. A. Hooper, M. S. Hutson, E. D. Jansen, K. M. Joos, D. P. Kiehart, I. Lindau, J. Miao, H. S. Pratisto, J. H. Shen, Y. Tokutake, A. F. G. van der Meer, and A. Xie, Rev. Sci. Instrum. 74, 3207–3245 (2003). (I)

158. “Medical applications of synchrotron radiation,” P. Suortti and W. Thomlinson, Phys. Med. Biol. 48, R1– R35 (2003). (I)

Finally, photodynamic therapy uses light-activated drugs to treat diseases.

159. “The physics, biophysics and technology of photodynamic therapy,” B. C. Wilson and M. S. Patterson, Phys. Med. Biol. 53, R61–R109 (2008). (A)

Happy birthday, laser!

Kalin Lucas and his ruptured Achilles tendon

Basketball fans may recall that in this year's NCAA tournament, Michigan State University (located about a 90 minute drive from where I work here at Oakland University in Rochester Michigan) made it into the final four before losing to Butler. They might have won the entire tournament if they were not without their star, Kalin Lucus, who ruptured his left Achilles tendon in a second round game against the University of Maryland. Coach Tom Izzo, who is much beloved here in southeast Michigan, managed two more wins without Lucus, before losing in the semifinals.

Why did Lucus injure his Achilles tendon? There was no collision or accident, he just landed awkwardly. Readers of the 4th edition of Intermediate Physics for Medicine and Biology won’t be too surprised when they hear about sports injuries to the Achilles tendon. In Section 1.5 of our book, Russ Hobbie and I analyze the forces on the Achilles tendon and show that the tension in this tendon can be nearly twice the body weight.

The Achilles tendon connects the calf muscles (the gastrocnemius and soleus) to the calcaneus at the back of the heal (Fig. 1.9). To calculate the force exerted by this tendon on the calcaneus when a person is standing on the ball of one foot, assume that the entire foot can be regarded as a rigid body. This is our first example of creating a model of the actual situation. We try to simplify the real situation to make the calculation possible while keeping the features that are important to what is happening. In this model the internal forces within the foot are being ignored.

Figure 1.10 shows the force exerted by the tendon on the foot (F_T), the force of the leg bones (tibia and fibula) on the foot (F_B), and the force of the floor upward, which is equal to the weight of the body (W)...

We then go one to solve the equations of translational and rotational equilibrium to find that F_T = 1.8 W and F_B = 2.8 W, and conclude

The tension in the Achilles tendon is nearly twice the person’s weight, while the force exerted on the leg by the talus is nearly three times the body weight. Once can understand why the tendon might rupture.

Many sports injuries result from the laws of biomechanics. The problem is often that a tendon must exert a large force in order to create enough torque to maintain rotational equilibrium. For the Achilles tendon, the moment arm between the joint and the tendon is roughly half the moment arm between the joint and the ball of the foot, so the force on the tendon must be about twice the weight. Our bodies are often built this way: large forces are required to make up for small moment arms. I sometimes give a problem on one of my Biological Physics (PHY 325) exams that illustrates this by calculating the forces on the shoulder of a gymnast performing an “iron cross” on the rings. Here again, the torque exerted by the rings on the arm is huge because of the large moment arm (essentially the entire length of the arm itself), while the moment arm of the pectoral muscle is small because it connects to the humerus (the arm bone) only about 5 cm from the shoulder, at a small angle. The problem suggests that the pectoral muscle must supply a force of over twenty times the body weight! No wonder I was so poor at the rings in my high school physical education class. Readers interested in learning more about this topic might want to read Williams and Lissner's classic textbook Biomechanics of Human Motion. Russ and I cite the 1962 first edition, but I believe that the book has evolved into Biomechanics of Human Motion: Basics and Beyond for the Health Professions, by Barney LeVeau, due out later this year.

Hopefully these insights into biomechanics can help you appreciate how Kalin Lucus could suffer a season-ending injury so easily. I’m glad MSU was able to make it to the final four even without Lucus. However, to be honest, the Spartans were only my 4th favorite team in the tournament this year. Oakland University participated in March Madness for only the second time in the school’s history. Vanderbilt University (where I went for graduate school) also reached the Big Dance, and many predicted that the University of Kansas (where I attended college) would win the entire event. Unfortunately, all three schools lost in the first weekend of play. Russ didn’t fare much better, as the University of Minnesota lost in the first round. Congratulations to Duke University (home to an excellent Biomedical Engineering Department) for their ultimate victory.

Single-Pool Exponential Decomposition Models: Potential Pitfalls in their Use in Ecology Studies

In Section 11.2 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss fitting data using nonlinear least squares. Our first example in this section is a fit using a single exponential decay, y(x) = a e^–bx, where a and b are to be determined. We suggest that the reader

“take logarithms of each side of the equation

log y = log a – b x log e

v = a' – b' x.

This can be fit by the linear [least squares] equation, determining constants a' and b' using Eqs. 11.5.”

This method works fine for ideal data, but in almost any real application the data will be corrupted by noise. In that case, fitting a linear equation to the logarithm of the data may not be wise. I discussed this issue last year in the May 22 entry to this blog, but wish to explore it in more detail this week.

Recently, Russ coauthored a paper about his recent results on this topic, published in the journal Ecology (Volume 91, Pages 1225–1236). In collaboration with his daughter Sarah Hobbie (Associate Professor in the Department of Ecology, Evolution and Behavior at the University of Minnesota), and her former postdoc E. Carol Adair (currently with the National Center for Ecological Analysis and Synthesis at the University of California Santa Barbara), Russ examined “Single-Pool Exponential Decomposition Models: Potential Pitfalls in their Use in Ecology Studies.” The abstract to the paper is given below.

The importance of litter decomposition to carbon and nutrient cycling has motivated substantial research. Commonly, researchers fit a single-pool negative exponential model to data to estimate a decomposition rate (k). We review recent decomposition research, use data simulations, and analyze real data to show that this practice has several potential pitfalls. Specifically, two common decisions regarding model form (how to model initial mass) and data transformation (log-transformed vs. untransformed data) can lead to erroneous estimates of k. Allowing initial mass to differ from its true, measured value resulted in substantial over- or underestimation of k. Log-transforming data to estimate k using linear regression led to inaccurate estimates unless errors were lognormally distributed, while nonlinear regression of untransformed data accurately estimated k regardless of error structure. Therefore, we recommend fixing initial mass at the measured value and estimating k with nonlinear regression (untransformed data) unless errors are demonstrably lognormal. If data are log-transformed for linear regression, zero values should be treated as missing data; replacing zero values with an arbitrarily small value yielded poor k estimates. These recommendations will lead to more accurate k estimates and allow cross-study comparison of k values, increasing understanding of this important ecosystem process.

The authors performed a massive review of the literature, reading and analyzing nearly 500 papers about litter decomposition, most of which fit data to an exponential decay, e^–kt. The bottom line is that doing a linear least squares fit to the logarithm of the data can cause significant errors. Much better is to use a nonlinear least squares fit. The manuscript concludes “We suggest that careful selection of fitting methods, as we have described above, will lead to more accurate and comparable k estimates, thereby increasing our understanding of this important ecosystem process.” Of course, my favorite thing about their paper is that it cites the 4th edition of Intermediate Physics for Medicine and Biology!

One pitfall can be illustrated by considering measurements of the voltage across a resistor in an RC circuit. The voltage decays with an RC time constant. However thermal, or Johnson, noise is also present (see Section 9.8). Once the voltage decays to less than the Johnson noise, the measured voltage fluctuates between positive and negative values. If you take the logarithm of the voltage, the negative values are undefined. In other words, you can’t do a linear least squares fit to the logarithm of the data if the data can be negative. The problem remains even when the data is nonnegative (as in Hobbie’s paper) if the data can be zero. However, if you make a nonlinear least squares fit of the data itself (rather than the logarithm of the data) the problem vanishes.

In order to explain these observations in Intermediate Physics for Medicine and Biology, Russ and I (mainly Russ) wrote an Addendum available at the book’s website. It lists what changes are needed to properly explain least squares fitting of exponential data. Enjoy!

Hysteresis and Bistability in the Direct Transition from 1:1 to 2:1 Rhythm in Periodically Driven Single Ventricular Cells

When preparing the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I added two homework problems (Problems 37 and 38) in Chapter 10 (Feedback and Control) about “cardiac restitution.” These problems contain a fascinating and elegantly simple example of restitution that provides insight into nonlinear dynamics and chaos. Problem 37 begins

Problem 37 The onset of ventricular fibrillation in the heart can be understood in part as a property of cardiac “restitution.” The action potential duration (APD) depends on the previous diastolic interval (DI): the time from the end of the last action potential until the start of the next one. The relationship between APD and DI is called the “restitution curve.” In cardiac muscle, a typical restitution curve has the form

APD_i+1 = 300 (1 – exp(–DI_i/100))

where all times are given in ms. Suppose we apply to the heart a series of stimuli, with period (or “cycle length”) CL. Since APD + DI = CL, we have DI_i+1 = CL – APD_i+1.

The problem then goes on to have the reader do some numerical calculations using various cycle lengths and initial diastolic intervals. Depending on the parameters, you can get (a) a simple 1:1 response between stimulation and action potential, (b) a 2:2 response in which every stimulus triggers an action potential but the APD alternates between long and short, a behavior called “alternans,” (c) a 2:1 response where an action potential is triggered by every second stimulus, with the tissue being refractory and not responding to the other stimuli, and (d) chaos. I have found this model is an excellent way to introduce students to chaotic behavior; even students with a weak mathematics background can understand it. When discussing this mathematical model with students, I often hand out a particularly clear paper to serve as background reading: J. N. Weiss, A. Garfinkel, H. S. Karagueuzian, Z. Qu, and P.-S. Chen (1999) “Chaos and the Transition to Ventricular Fibrillation: A New Approach to Antiarrhythmic Drug Evaluation,” Circulation, Volume 99, Pages 2819–2826.

Problem 38 explores how to understand this behavior by analyzing the slope of the restitution curve. If the slope is too steep, the behavior becomes more complex. Part (d) of Problem 38 says

Suppose you apply a drug to the heart that can change the restitution curve to

APD_i+1 = 300 (1 – b exp(–DI_i/100)) .

Plot APD as a function of DI for b = 0, 0.5, and 1. What value of b ensures that the slope of the restitution curve is always less than 1? Garfinkel et al. (2000) have suggested that one way to prevent ventricular fibrillation is to use drugs to “flatten” the restitution curve.

There is yet another type of behavior that is not discussed in Problems 37 or 38: a bistable response. Below is a new homework problem that discusses bistable behavior.

Problem 38 ½ Use the restitution curve from Problem 38, with b = 1/3 and CL = 250, to analyze the response of the system with initial diastolic intervals of 50, 60, 70, 80, and 90. You should find that the qualitative behavior depends on the initial condition. Which values of the initial diastolic interval give a 1:1 response, and which give 2:1? Determine the initial value of the DI, to three significant figures, for which the system makes a transition from one behavior to the other. When two qualitatively different behaviors can both occur, depending on the initial conditions, the system is “bistable.” To learn more about such behavior, see Yehia et al. (1999).

The full citation to the paper mentioned at the end of the problem is

Yehia, A. R., D. Jeandupeux, F. Alonso, and M. R. Guevara (1999) “Hysteresis and Bistability in the Direct Transition From 1:1 to 2:1 Rhythm in Periodically Driven Single Ventricular Cells,” Chaos, Volume 9, Pages 916–931.

The senior author on this article is Michael Guevara, of the Centre for Applied Mathematics in Bioscience and Medicine at McGill University. The introductory paragraph of their paper is reproduced below.

The majority of cells in the heart are not spontaneously active. Instead, these cells are excitable, being driven into activity by periodic stimulation originating in a specialized pacemaker region of the heart containing spontaneously active cells. This pacemaker region normally imposes a 1:1 rhythm on the intrinsically quiescent cells. However, the 1:1 response can be lost when the excitability of the paced cells is decreased, when there are problems in the conduction of electrical activity from cell to cell, or when the heart rate is raised. When 1:1 synchronization is lost in the intact heart, one of a variety of abnormal cardiac arrhythmias can arise. In single quiescent cells isolated from ventricular muscle, 1:1 rhythm can be replaced by a N+1:N rhythm (N≥2), a period-doubled 2:2 rhythm, or a 2:1 rhythm. We investigate below the direct transition from 1:1 to 2:1 rhythm in experiments on single cells and in numerical simulations of an ionic model of a single cell formulated as a nonlinear system of differential equations. We show that there is hysteresis associated with this transition in both model and experiment, and develop a theory for the bistability underlying this hysteresis that involves the coexistence of two stable fixed-points on a two-branched one-dimensional map.

For those interested in exploring the application of nonlinear dynamics to biology and medicine in more detail, two books Russ and I cite in Intermediate Physics for Medicine and Biology—and which I recommend highly—are From Clocks to Chaos by Leon Glass and Michael Mackey (both also at McGill) and Nonlinear Dynamics and Chaos by Steven Strogatz.

Max Planck and Blackbody Radiation

Max Planck is one of the founders of quantum mechanics, and the fundamental constant governing all quantum phenomena bears his name. His historic contribution arose from the study of thermal radiation. Section 14.7 in the 4th edition of Intermediate Physics for Medicine and Biology analyzes thermal radiation (also known as blackbody radiation), but does not tell the fascinating history behind this advance. In fact, Russ Hobbie and I write “we will not discuss the history of these developments, but will simply summarize the properties of the blackbody radiation function that are important to us.” What better place than this blog to fill in the missing history.

Quantum Physics of Atoms,
Molecules, Solids, Nuclei, and Particles,
by Eisberg and Resnick.

Eisberg and Resnick’s textbook Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles is a good place to learn more (I will quote from the first edition having the silver cover, which I used as an undergraduate). In fact, the opening section of their first chapter addresses this very issue.

At a meeting of the German Physical Society on Dec. 14, 1900, Max Planck read his paper “On the Theory of the Energy Distribution Law of the Normal Spectrum.” This paper, which first attracted little attention, was the start of a revolution in physics. The date of its presentation is considered to be the birthday of quantum physics, although it was not until a quarter century later that modern quantum mechanics, the basis of our present understanding, was developed by Schroedinger and others… Quantum physics represents a generalization of classical physics that includes the classical laws as special cases. Just as relativity extends the range of application of physical laws to the region of high velocities, so quantum physics extends the range to the region of small dimensions; and, just as a universal constant of fundamental significance, the velocity of light c, characterizes relativity, so a universal constant of fundamental significance, now called Planck’s constant h, characterizes quantum physics. It was while trying to explain the observed properties of thermal radiation that Planck introduced this constant in his 1900 paper…

Eisberg and Resnick end their first chapter with “A Bit of Quantum History”

At first Planck was unsure whether his introduction of the constant h was only a mathematical device or a matter of deep physical significance. In a letter to R. W. Wood, Planck called his limited postulate “an act of desperation.” “I knew,” he wrote, “that the problem (of the equilibrium of matter and radiation) is of fundamental significance for physics; I knew the formula that reproduces the energy distribution in the normal spectrum; a theoretical interpretation had to be found at any cost, no matter how high.”

To better understand the mathematics underlying blackbody radiation, try the new homework problem below, based on Eisberg and Resnick’s analysis (you may want to review Sec. 3.7 of our book about the Boltzmann factor before you attempt this problem).

Section 14.7

Problem 22.5 Let us derive the blackbody spectrum, Eq. 14.37.
(a) Assume the energy E_n of radiation with frequency ν is discrete, E_n = h ν n, where n=0, 1, 2, … Let the probability P_n of any state be given by the Boltzmann factor, C e^−nhν/kT. Normalize this probability distribution (that is, find C by setting the sum of the probabilities over all states equal to one).
(b) Find the average energy E_ave for frequency ν by performing the sum E_ave = P₀ E₀ + P₁ E₁ + … .
(c) The number of frequencies per unit volume in the frequency range from ν to ν + dν is 8πν²dν/c³. Multiply the result from (b) by this quantity, to get the energy density of the radiation.
(d) The spectrum of power per unit area emitted from a blackbody is equal to c/4 times the energy density. Find the power per unit area per unit frequency, W_ν(ν,T) (Eq. 14.37).
You may need to use the following two infinite series

1 + x + x² + x³ + … = 1/(1−x) ,

x + 2x² + 3x³ + … = x/(1−x)² .

Therapeutic Touch

Therapeutic touch is a “healing technique” in which a therapist places their hands near a patient and detects or manipulates the patient’s “energy field.” Russ Hobbie and I don’t discuss therapeutic touch in the 4th edition of Intermediate Physics for Medicine and Biology, nor will we include it in future editions. However, since this egregious example of “voodoo science” hasn’t gone away (see http://www.therapeutictouch.org), let me address it here in this blog.

Bob Park described therapeutic touch in his delightful April 3, 1998 entry to his What’s New weekly column.

3. HUMAN ENERGY FIELD: SCIENTIST, AGE 9, TESTS TOUCH THERAPY.
More than 40,000 health professionals have been trained in TT and it's offered by 70 hospitals in the US. And yet no one had ever checked to see if practitioners can, as they claim, tactilely sense such a field—until now. The Journal of the American Medical Association this week published the research of a fourth-grade girl. For a science fair project, the little girl persuaded 21 touch therapists to submit to a beautifully simple test. In 280 trials, the 21 scored 44%. According to the editor of JAMA, reviewers found the study to be “solid gold.” The James Randi Educational Foundation has been offering $1M to anyone who can pass a similar test—only one tried (WN 27 Mar 98) , but a 9-year old must have seemed less threatening. The girl, Emily Rosa of Loveland, CO, now 11, plans to take on magnet therapy next.

Recently, Russ called my attention to Eugenie Mielczarek’s insightful commentary “Magnetic Fields, Health Care, Alternative Medicine and Physics” in the April 2010 edition of Physics and Society, the quarterly newsletter of the Forum of Physics and Society, a division of the American Physical Society. Mielczarek writes

In Therapeutic Touch the protocol requires that a therapist moves his or her hands over the patient’s “energy field,” allegedly “tuning” a purported “aura” of biomagnetic energy that extends above the patient’s body. This is thought to somehow help heal the patient. Although this is less than one percent of the strength of Earth’s magnetic field, corresponds to billions of times less energy than the energy your eye receives when viewing even the brightest star in the night sky, and is billions of times smaller than that needed to affect biochemistry, the web sites of prominent clinics nevertheless market the claims.

Iron, Nature's Universal Element:
Why People Need Iron
and Animals Make Magnets,
by Eugenie Mielczarek.

Mielczarek is an emeritus professor at George Mason University. In 2006 she published a Resource Letter in the American Journal of Physics: “Physical Frontiers in Biology: A Resource for Students and Faculty” (Volume 74, Pages 375–381). Russ and I mentioned this publication in our 2009 “Resource Letter on Medical Physics,” where we wrote that Mielczarek’s letter “begins with a fascinating three-page essay on the role of physics in biology.” This week I discovered that the published black-and-white pictures in that 3-page essay are available in color at Mielczarek’s website. Mielczarek is an editor of the 1993 book Biological Physics, a collection of landmark biological physics papers. One of her research interests is the role of iron in biological systems, and in 2000 she coauthored the book Iron, Nature’s Universal Element: Why People Need Iron and Animals Make Magnets, which I just put onto my summer reading list. We cite this “very readable” book in Section 8.8.3 of Intermediate Physics for Medicine and Biology, but it must have been one of those things that Russ added to the 4th edition because I haven’t read it yet. We also cite Mielczarek’s American Journal of Physics paper “Experimental and Theoretical Models of Nonlinear Behavior" in Chapter 10 of our book.

For more information about the physics of therapeutic touch, see the article “Emerita Professor Makes a Case Against Distance Healing” in the Mason Gazette, and the press release “Think Tank Objects to Taxpayer Funding for Therapeutic Touch, other Alternative Medicine Therapies” from the Center of Inquiry.

Let us hope that hope that Bob Park and Eugenie Mielczarek continue to debunk the techniques of “alternative medicine” when they violate the laws of physics.

PHY 530, Bioelectric Phenomena

This week I finished up my PHY 530 class (Bioelectric Phenomena), which I discussed once before in this blog. Rather than adopting a textbook, I based this graduate class on a collection of scientific papers. Below I list the three dozen papers we studied. It should not be regarded as a “greatest hits” list. Some are Nobel Prize winning papers, but oftentimes I selected a lesser-known article that happened to cover a specific topic I wanted to teach. Many are cited in the 4th edition of Intermediate Physics for Medicine and Biology (indicated by a *). Students were assigned the 16 papers marked in bold: they had to take a quiz on each of these before we discussed them in class, and the exams often contained questions drawn directly from these papers. The other 20 articles are supplementary: consider them recommended reading, rather than required.

I had two goals in the class: to teach the basic elements of bioelectricity, and to lead a workshop on how to write a scientific paper. The students were given two projects (one was to simulate a squid nerve axon using the Hodgkin-Huxley model, and the other was to determine a dipole source from simulated EEG data) and had to write up their results in a brief (4 page maximum) paper having the classic structure: Abstract, Introduction, Methods, Results, Discussion, References. We read essays related to writing scientific papers, such as "What's Wrong With These Equations?" and "Writing Physics," both by N. David Mermin, and learned to use the Science Citation Index. I am pleased with how the class went, and I hope the students were too.

1. A. L. Hodgkin and A. F. Huxley (1939) “Action Potentials Recorded from Inside a Nerve Fiber,” Nature, Volume 144, Pages 710–711. *

2. A. L. Hodgkin and B. Katz (1949) “The Effect of Sodium Ions on the Electrical Activity of the Giant Axon of the Squid,” Journal of Physiology, Volume 108, Pages 37–77.

3. A. L. Hodgkin and A. F. Huxley (1952) “A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve,” Journal of Physiology, Volume 117, Pages 500–544. *

4. D. A. Doyle, J. M. Cabral, R. A. Pfuetzner, A. Kuo, J. M. Gulbis, S. L. Cohen, B. T. Chait, and R. MacKinnon (1998) “The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity,” Science, Volume 280, Pages 69–77. *

5. O. P. Hamill, A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth (1981) “Improved Patch-Clamp Techniques for High-Resolution Current Recording From Cells and Cell-Free Membrane Patches,” Pflugers Archive, Volume 391, Pages 85–100. *

6. A. L. Hodgkin and W. A. H. Rushton (1946) “The Electrical Constants of a Crustacean Nerve Fibre,” Proceedings of the Royal Society of London, B, Volume 133, Pages 444–479. *

7. W. A. H. Rushton (1951) “A Theory of the Effects of Fibre Size in Medullated Nerve,” Journal of Physiology, Volume 115, Pages 101–122. *

8. R. FitzHugh (1961) “Impulses and Physiological States in Theoretical Models of Nerve Membrane,” Biophysical Journal, Volume 1, Pages 445–466.

9. W. Rall (1962) “Theory of Physiological Properties of Dendrites,” Annals of the New York Academy of Sciences, Volume 96, Pages 1071–1092.

10. F. Rattay (1989) “Analysis of Models for Extracellular Fiber Stimulation,” IEEE Transactions on Biomedical Engineering, Volume 36, Pages 676–682.

11. A. T. Barker, R. Jalimous, and I. L. Freeston (1985) “Non-Invasive Magnetic Stimulation of Human Motor Cortex,” Lancet, Volume 8437, Pages 1106–1107. *

12. M. Hallett and L. G. Cohen (1989) “Magnetism: A New Method for Stimulation of Nerve and Brain,” Journal of the American Medical Association, Volume 262, Pages 538–541. *

13. B. J. Roth, L. G. Cohen and M. Hallett (1991) “The Electric Field Induced During Magnetic Stimulation,” Electroencephalography and Clinical Neurophysiology, Supplement 43, Pages 268–278.

14. R. Plonsey (1974) “The Active Fiber in a Volume Conductor,” IEEE Transactions on Biomedical Engineering, Volume 21, Pages 371–381.

15. B. J. Roth, D. Ko, I. R. von Albertini-Carletti, D. Scaffidi and S. Sato (1997) “Dipole Localization in Patients with Epilepsy Using the Realistically Shaped Head Model,” Electroencephalography and Clinical Neurophysiology, Volume 102, Pages 159–166.

16. M. Schneider (1974) “Effect of Inhomogeneities on Surface Signals Coming From a Cerebral Current-Dipole Source,” IEEE Transactions on Biomedical Engineering, Volume 21, Pages 52–54.

17. B. J. Roth and J. P. Wikswo (1985) “The Magnetic Field of a Single Axon: A Comparison of Theory and Experiment,” Biophysical Journal, Volume 48, Pages 93–109. *

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Galileo's Daughter

Galileo's Daughter,
by Dava Sobel.

As is my habit, I listen to recorded books when I walk my dog Suki each day. Recently, I listened to the book Galileo’s Daughter, by Dava Sobel. I was surprised how touching I found this story (like Galileo, I have two daughters). It is a biography of Galileo Galilei (1564–1642), the famous Italian scientist, but also tells the parallel story of Sister Maria Celeste (1600–1634), Galileo’s daughter who was a nun at the San Matteo convent near Florence. The book quotes Maria Celeste’s letters to Galileo, which Sobel herself translated from Italian. (Unfortunately, Galileo’s replies are lost.) Maria Celeste comes across as a loving, intelligent and extremely loyal daughter who played a central role in Galileo’s life. “She alone of Galileo’s three children mirrored his own brilliance, industry, and sensibility, and by virtue of these qualities became his confidante.”

I tend to see biological physics everywhere, and I found some in this story. Late in his life, Galileo published his final book, Two New Sciences. One of these sciences was the motion of projectiles, and the other was what we would now call the strength of materials. In the part about materials, Galileo addressed the issue of scaling in animals. I quote Sobel, who quotes Galileo:

I have sketched a bone whose natural length has been increased three times and whose thickness has been multiplied until, for a correspondingly large animal, it would perform the same function which the small bone performs for its small animal. From the figures here shown you can see how out of proportion the enlarged bone appears. Clearly then if one wishes to maintain in a great giant the same proportion of limb as that found in an ordinary man he must either find a harder and stronger material for making the bones, or he must admit a diminution of strength in comparison with men of medium stature.

Scaling: Why is Animal
Size so Important?
by Knut Schmidt-Nielsen.

(You can find the picture of the two bones here.) This example of how the strength of bones must scale with animal size did not make it into the 4th edition of Intermediate Physics in Medicine and Biology, although I sometimes discuss it when I teach PHY 325 (Biological Physics) at Oakland University. It serves as an excellent example of how physics can constrain the structure of animals. I won’t hold it against Galileo that he didn’t get his drawing of the bones quite right; it was the 17th century after all. According to Knut Schmidt-Nielsen (Scaling: Why is Animal Size so Important)

The need for a disproportionate increase in the size of supporting bones with increasing body size was understood by Galileo Galilei (1637), who probably was the first scientist to publish a discussion of the effects of body size on the size of the skeleton. In his Dialogues [Two New Sciences was written in the form of a dialogue] he mentioned that the skeleton of a large animal must be strong enough to support the weight of the animal as it increases with the third power of the linear dimensions. Galileo used a drawing to show how a large bone is disproportionately thicker than a small bone. (Incidentally, judging from the drawing, Galileo made an arithmetical mistake. The larger bone, which is three times as long as the shorter, shows a 9-fold increase in diameter, which is a greater distortion than required. A three-fold increase in linear dimensions should give a 27-fold increase in mass, and the cross-sectional area of the bone should be increased 27-fold, and its diameter therefore by the square root of 27 (i.e., 5.2 instead of 9)).

Russ Hobbie and I discuss the issue of scaling in Chapter 2 of Intermediate Physics for Medicine and Biology. In Problem 28 of Chapter 2, we ask the reader to calculate the falling speed of animals of different sizes, taking into account air friction. The solution to the problem indicates that large animals, with their smaller surface-to-volume ratio, have a larger terminal speed (the speed of descent in steady state, once the acceleration drops to zero) than smaller animals. We end the problem with one of my favorite quotes, by J. B. S. Haldane

You can drop a mouse down a thousand-yard mine shaft; and arriving at the bottom, it gets a slight shock and walks away. A rat is killed, and man is broken, a horse splashes.

When listening to Galileo’s Daughter, I was surprised to hear Galileo’s own words on this same subject, which are similar and written centuries earlier.

Who does not know that a horse falling from a height of three or four braccia will break his bones, while a dog falling from the same height or a cat from eight or ten, or even more, will suffer no injury? Equally harmless would be the fall of a grasshopper from a tower or the fall of an ant from the distance of the Moon.

Of course, the climax of Galileo’s Daughter is the great scientist’s trial by the Catholic Church for publishing a book supporting the Copernican view that the earth travels around the sun. Although I was familiar with this trial, I had never read the transcript, which Sodal quotes extensively. Listening to the elderly Galileo being forced into a humiliating recantation of his scientific views almost made me nauseous.

Sobel is a fine writer. Years ago I read her most famous book, Longitude, about finding a method to measure longitude at sea. Galileo himself contributed to the solution of this problem by introducing a method based on the orbits of the moons of Jupiter, which he of course discovered. However, the longitude problem was not definitely solved until clocks that could keep time on a rolling ship were invented by John Harrison. I have also listened to Sobel’s book The Planets, which I enjoyed but, in my opinion, isn’t as good as Longitude and Galileo’s Daughter. I hope Sobel continues writing books. As soon as a new one comes out (and arrives at the Rochester Hills Public Library, because I’m too cheap to buy these audio books), Suki and I plan on taking some long walks. I can’t wait.

Kids: Don’t Try This At Home

Russ Hobbie and I included a new chapter on sound and ultrasound in the 4th edition of Intermediate Physics for Medicine and Biology. In that chapter, we discuss how to calculate the speed of sound from the compressibility and the density of the tissue (Eq. 13.11). We then go on to describe, among other things, hearing, ultrasonic imaging, and the Doppler effect. One topic we do not mention is the behavior of objects moving faster than the speed of sound. Such a discussion, often found in physics and engineering books, usually is based on the Mach number, defined as the speed of an object divided by the speed of sound. If the Mach number is greater than one, the speed is supersonic and a shock wave develops. When an airplane travels faster than the speed of sound, people on the ground can hear the shock wave as a “sonic boom.” This is all very interesting, but it has nothing to do with biology and medicine, right?

Guess again. A recent article in the New York Times describes the plans of Felix Baumgartner, who intends to be the first human to break the sound barrier. I know, dear readers, that some of you are now saying “No, Chuck Yeager was the first to break the sound barrier, and that happened over 60 years ago.” Well, Yeager broke the sound barrier when flying in a plane, whereas Baumgartner plans to break the sound barrier while in free fall! The Times article states

But now Fearless Felix, as his fans call him, has something more difficult on the agenda: jumping from a helium balloon in the stratosphere at least 120,000 feet above Earth. Within about half a minute, he figures, he would be going 690 miles per hour and become the first skydiver to break the speed of sound. After a free fall lasting five and a half minutes, his parachute would open and land him about 23 miles below the balloon.

No one is certain what will happen to a human near the sound barrier. The NYT article says that turbulence may set in, causing havoc. Turbulence is a subject Russ and I discuss briefly in Chapter 1 of Intermediate Physics for Medicine and Biology, when introducing the Reynolds number. Most fluid in the body flows at low Reynolds number, with no danger of turbulence, although blood flow in the heart and aorta can get so fast that some turbulence may develop. Of course, any animal that flies in air will experience turbulence, which includes birds, bats, pterodactyls, and, in Baumgartner’s case, humans.

Physics With Illustrative Examples
From Medicine and Biology, Volume 1,
by Benedek and Villars.

These high altitude exploits remind me of a delightful section in the textbook Physics With Illustrative Examples from Medicine and Biology, by George Benedek and Felix Villars. In their Volume 1 on Mechanics, they describe balloon ascensions and the physiological effects of air pressure. After reviewing the medical implications of a lack of oxygen at high altitudes, they present the fascinating tale of a 19th century balloon ascension.

These symptoms are shown very clearly in the tragic balloon ascent of the “Zenith” carrying the balloon pioneers Tissandier, Sivel, and Corce-Spinelli on April 15, 1875. During this ascent Sivel and Corce-Spinelli died. The balloons maximum elevation as recorded on their instruments was 8600 m. Though gas bags carrying 70% oxygen were carried by the balloonists, the rapid and insidious effects of hypoxia reduced their judgment and muscular control and prevented their use of the oxygen when it was most needed. Though these balloonists were indeed trying to establish an altitude record, their account shows clearly that their judgment was severely impaired during critical moments during the maximum tolerable altitude.

Then Benedek and Villars present a 3-page extended quote from the account of the surviving member of the trio, Gaston Tissandier. It makes for fascinating reading. However, concerns about oxygen depletion aren’t relevant for Fearless Felix, because he will be wearing a space suit during his jump, with its own oxygen supply.

The New York Times story ends with the following quote. One wonders if we should admire Baumgartner’s pluck, or commit him to an insane asylum.

Private adventurers have more freedom to take their own risks. The Stratos medical director, Dr. Jonathan Clark, who formerly oversaw the health of space shuttle crews at NASA, says that the spirit of this project reminds him of stories from the first days of the space age.

“This is really risky stuff, putting someone up there in that extreme environment and breaking the sound barrier,” Dr. Clark said. “It’s going to be a major technical feat. It’s like early NASA, this heady feeling that we don’t know what we’re up against but we’re going to do everything we can to overcome it.”

Erwin Neher

I subscribe to a monthly magazine, The Scientist, which was founded by Eugene Garfield (who also was a founder of the Science Citation Index). It provides print and online coverage about biomedical research, technology and business. I’m not sure what I did to deserve it, but I get a paper copy delivered to my office for free, and I can tell you for certain that the magazine is worth the price. Seriously, it is a valuable resource, and the articles are general enough that I can follow them without having to consult my physiology and biochemistry textbooks. The online site contains many of the articles for free, and also has career information for young scientists. I recommend it.

The March 2010 issue of The Scientist contains a profile of Nobel Prize winner Erwin Neher, the developer of the patch clamp technique. Russ Hobbie and I discuss patch-clamp recording in Chapter 9 of the 4th edition of Intermediate Physics for Medicine and Biology.

The next big advance was patch-clamp recording [Neher and Sakmann (1976)]. Micropipettes were sealed against a cell membrane that had been cleaned of connective tissue by treatment with enzymes. A very-high-resistance seal resulted [(2-3) × 10⁷ Ohm] that allowed one to see the opening and closing of individual channels. For this work Erwin Neher and Bert Sakmann received the Nobel Prize in Physiology or Medicine in 1991. Around 1980, Neher’s group found a way to make even higher-resistance (10¹⁰-10¹¹ Ohm) seals that reduced the noise even further and allowed patches of membrane to be torn from the cell while adhering to the pipette [Hamill et al. (1981)]…

The profile in The Scientist provides some insight into how this research began.

[Neher’s former postdoc Fred] Sigworth remembers it well. “I came into lab that Monday morning and Erwin said, with a twinkle in his eye, ‘I think I know how you’re going to see sodium channels,’” he says. These channels—essential to neural communication—had proven elusive because they produce such small currents and remain open for such a short time. But thanks to the team’s new “patch-clamp” technique—and in particular, the formation of an incredibly tight seal, or “gigaseal,” between the pipette tip and the cell membrane—“seeing sodium channels suddenly became really easy,” says Sigworth, who, along with Neher, published these observations (and the first description of the tight-seal patch-clamp technique) in Nature in 1980.

I always enjoy reading about the quirks and odd twists of fate that often accompany scientific advance. The profile in The Scientist provides an entertaining anecdote.

You also needed to suck. “You had to apply a little bit of suction in order to pull some membrane into the orifice of the pipette,” says Neher. “If you did it the right way, it worked.” At least for Neher. “There was a weird period where we could no longer get gigaseals,” recalls [Owen] Hamill [a postdoc at the time]. “Then Bert suggested you have to blow before you suck.” Gently blowing a solution through the pipette as it approaches the surface of the cell keeps the tip from picking up debris during the descent. Between the blowing and the sucking, Hamill says, “our effeiciency went up to 99 percent.”

I fond it interesting that Neher’s undergraduate degree was in physics, and it was only after he arrived at the University of Wisconsin on a Fulbright Scholarship that he began studying biophysics. In his Nobel autobiography he describes his early motivation for studying biological physics.

At the age of 10, I entered the “Maristenkolleg” at Mindelheim [...] the local “Gymnasium” is operated by a catholic congregation, the “Maristenschulbrüder.” The big advantage of this school was that our teachers—both those belonging to the congregation and others—were very dedicated and were open not only to the subject matter but also to personal issues. During my years at the Gymnasium (1954 to 1963) I found out that, next to my interest in living things, I also could immerse myself in technical and analytical problems. In fact, pretty soon, physics and mathematics became my favourite subjects. At the same time, however, new concepts unifying these two areas had seeped into the literature, which was accessible to me. I eagerly read about cybernetics, which was a fashionable word at that time, and studied everything in my reach on the “Hodgkin-Huxley theory” of nerve excitation. By the time of my Abitur—the examination providing access to university—it was clear to me that I should become a “biophysicist.” My plan was to study physics, and later on add biology.

Neher provides a classic example of how a strong background in physics can lead to advances in biology and medicine, a major theme underlying Intermediate Physics for Medicine and Biology.