Friday, January 17, 2014

George Ralph Mines, Biological Physicist

In Chapter 10 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the contribution of George Ralph Mines to cardiac electrophysiology.
The propagation of an action potential is one example of the propagation of a wave in excitable media. We saw in Chap. 7 that waves of depolarization sweep through cardiac tissue. The circulation of a wave of contraction in a ring of cardiac tissue was demonstrated by Mines in 1914. It was first thought that such a wave had to circulate around an anatomic obstacle, but it is now recognized that no obstacle is needed.
This year marks the 100th anniversary of Mines’ landmark work. Regis DeSilva, in an article titled “George Ralph Mines, Ventricular Fibrillation and the Discovery of the Vulnerable Period” (Journal of the American College of Cardiology, Volume 29, Pages 1397–1402, 1997) describes Mines’ work in more detail.
George Ralph Mines … made two major contributions to electrophysiology. His scientific legacy includes elucidating the theoretical basis for the occurrence of reentrant arrhythmias and the discovery of the vulnerable period of the ventricle.
First, DeSilva discusses Mines’ analysis of reentry in cardiac tissue.
Mines applied his concept of reentry to myocardial tissue and suggested that closed circuits may also exist within heart muscle. Under normal conditions, these circuits are uniformly excited, and an excitatory wave dies out. He suggested that the twin conditions of unidirectional block and slow conduction may occur in abnormal myocardial tissue. Thus, tissue in a reentrant circuit may allow a circulating wavefront to be sustained by virtue of conductive tissue being always available for excitation. In this paper, he also published a now classic figure by illustrating the concept of circus movement in such small myocardial circuits, and this diagram is still used unchanged today in teaching this mechanism to students of electrocardiography (14)
Reference 14 (Mines GR, “On Dynamic Equilibrium in the Heart, Journal of Physiology,” Volume 46, Pages 349–383, 1913) is not cited in IPMB.

DeSilva then addresses Mines identification of a “vulnerable period” in the heart.
Mines’ second major contribution was also his most important discovery. It was published … in 1914, entitled “On Circulating Excitations in Heart Muscles and Their Possible Relation to Tachycardia and Fibrillation” [Transactions of the Royal Society of Canada, Volume 8, Pages 43–52, 1914] (15).…[Before 1914] the most common method of inducing fibrillation was by the application of repeated electrical shocks to the heart through an induction coil. Mines’ innovation in studying the onset of fibrillation was to modify the method by applying single shocks to the rabbit heart, and by timing them precisely at various periods during the cardiac cycle.… Stimuli were delivered by single taps of a Morse key, and the moment of application of the stimulus was signaled by the use of a sparking coil connected to an insulated pointer that produced dots on the kymographic trace. Correlation of the position of the dots on the mechanical trace with the electrocardiogram provided an indication of its timing in electrical diastole…. By so doing, ‘it was found in a number of experiments that a single tap of the Morse key if properly timed [his italics] would start fibrillation which would persist for a time. . . . The point of interest is that the stimulus employed would never cause fibrillation unless it was set in at a certain critical instant’ (15)…. The importance of this work lies in the fact that Mines identified for the first time a narrow zone fixed within electrical diastole during which the heart was extremely vulnerable to fibrillation. An external stimulus, or a stimulus generated from within the heart, if properly timed to fall within this zone, could trigger a fatal arrhythmia and cause death. This observation has spurred three generations of scientists to study the factors which cause death by disruption of what Mines called 'the dynamic equilibrium of the heart' (14).
Clearly Mines made landmark contributions to our understanding of the heart. But perhaps the most intriguing aspect of Mines’ life was the unusual circumstances of his untimely death. DeSilva writes
On the evening of Saturday November 7, 1914, the night janitor entered Mines’ laboratory and found him lying unconscious with equipment attached, apparently for the recording of respiration (25). He was taken immediately to the Royal Victoria Hospital where he regained consciousness only briefly. Shortly before midnight, he developed seizures and died without regaining consciousness. A complete autopsy was performed, including examination of all the abdominal and thoracic viscera and the brain, but no final diagnosis was rendered (26). The presumption was that death resulted from self-experimentation.
Here is how Art Winfree describes the same event, in his Scientific American article “Sudden Cardiac Death: A Problem in Topology”
Mines had been trying to determine whether relatively small, brief electrical stimuli can cause fibrillation. For this work he had constructed a device to deliver electrical impulses to the heart with a magnitude and timing that could be precisely controlled. The device had been employed in preliminary work with animals. When Mines decided it was time to begin work with human beings, he chose the most readily available experimental subject: himself. At about six o’clock that evening a janitor, thinking it was unusually quiet in the laboratory, entered the room. Mines was lying under the laboratory bench surrounded by twisted electrical equipment. A broken mechanism was attached to his chest over the heart and a piece of apparatus nearby was still recording the faltering heartbeat. He died without recovering consciousness.
Winfree notes in the 2nd edition of his book The Geometry of Biological Time that there is still some controversy about if Mines' death was truly from self experimentation. The circumstances of his death are certainly suggestive of this, even if we lack definitive proof.

I can't help but notice the similarities between George Ralph Mines and Henry Moseley. Both were Englishmen whose last name started with "M". Both were born at about the same time (Mines in 1886, Moseley in 1887). Both made fundamental contributions to science at an early age (Mines to cardiac electrophysiology, and Moseley to our understanding of the atomic number and the periodic table). Both are probably underappreciated in the history of science, and neither won the Nobel Prize. And both died before reaching the age of 30 (Mines in 1914, Moseley in 1915). Mines died in the mysterious accident in his lab described above, and Moseley died in the Battle of Gallipoli during World War I. And, of course, both are mentioned in the 4th edition of Intermediate Physics for Medicine and Biology.

Friday, January 10, 2014

Happy Birthday, Earl Bakken!

Today, Earl Bakken turns 90 years old. Bakken is the founder of the medical device company Medtronic, and he played a key role in the development of the artificial pacemaker. I had the good fortune to meet Bakken in 2009 at a reception in the Bakken Museum as part of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society held in Minneapolis.

Machines in our Hearts, by Kirk Jeffrey, superimposed on Intermediate Physics for Medicine and Biology.
Machines in our Hearts,
by Kirk Jeffrey.
Kirk Jeffrey’s book Machines in our Hearts tells the story of how Bakken, at the request of the renowned heart surgeon C. Walton Lillehei, developed the first battery powered pacemaker.
Bakken first thought of an “automobile battery with an inverter to convert the six volts to 115 volts to run the AC pacemaker on its wheeled stand. That, however, seemed like an awfully inefficient say to do the job, since we needed only a 10-volt direct-current pulse to stimulate the heart.” Powering the stimulator from a car battery would have eliminated the need for electrical cords and plugs, but would not have done away with the wheeled cart. Bakken then realized that he could simply build a stimulator that used transistors and small batteries. “It was kind of an interesting point in history,” he recalled—“a joining of several technologies.” In constructing the external pulse generator, Bakken borrowed a circuit design for a metronome that he had noticed a few months earlier in an electronics magazine for hobbyists. It included two transistors. Invented a decade earlier, the transistor was just beginning to spread into general use in the mid-1950s. Hardly anyone had explored its applications in medical devices. Bakken used a nine-volt battery, housed the assemblage in an aluminum circuit box, and provided an on-off switch and control knobs for stimulus rate and amplitude.

At the electronics repair shop that he had founded with his brother-in-law in 1949, Bakken had customized many instruments for researchers at the University of Minnesota Medical School and the nearby campus of the College of Agriculture. Investigators often “wanted special attachments or special amplifiers” added to some of the standard recording and measuring equipment. “So we began to manufacture special components to go with the recording equipment. And that led us into just doing specials of many kinds…We developed….animal respirators, semen impedance meters for the farm campus, just a whole spectrum of devices.” Usually the business would sell a few of these items. When Bakken delivered the battery-powered external pulse generator to Walt Lillehei in January 1958, it seemed to the inventor another special order, nothing more. The pulse generator was hardly an aesthetic triumph, but it was small enough to hold in the hand and severed all connection between the patient’s heart and the hospital power system. Bakken’s business had no animal-testing facility, so he assumed that the surgeons would test the device by pacing laboratory dogs. They did “a few dogs,” then Lillehei put the pacemaker into clinical use. When Bakken next visited the university, he was surprised to find that his crude prototype was managing the heartbeat of a child recovering from open-heart surgery.
Russ Hobbie and I discuss the artificial pacemaker in Chapter 7 of the 4th edition of Intermediate Physics for Medicine and Biology
Cardiac pacemakers are a useful treatment for certain heart diseases [Jeffrey (2001), Moses et al. (2000); Barold (1985)]. The most frequent are an abnormally slow pulse rate (bradycardia) associated with symptoms such as dizziness, fainting (syncope), or heart failure. These may arise from a problem with the SA node (sick sinus syndrome) or with the conduction system (heart block). One of the first uses of pacemakers was to treat complete or “third degree” heart block. The SA node and the atria fire at a normal rate but the wave front cannot pass into the conduction system. The AV node or some other part of the conduction system then begins firing and driving the ventricles at its own, pathologically slower rate. Such behavior is evident in the ECG in Fig. 7.30, in which the timing of the QRS complex from the ventricles is unrelated to the P wave from the atria. A pacemaker stimulating the ventricles can be used to restore a normal ventricular rate.
You can learn more about Bakken’s contributions to the development of the pacemaker here or on video here. Visit his website here or read his autobiography. He now lives in Hawaii, where local magazines have reported about him here and here. Those wanting to join the celebration can attend Earl Bakken’s birthday bash at the Bakken Museum, or celebrate at the North Hawaii Community Hospital.

Happy birthday, Earl Bakken!

Friday, January 3, 2014

Integrals of Sines and Cosines

Last week in this blog, I discussed the Fourier series. This week, I want to highlight some remarkable mathematical formulas that make the Fourier series work: integrals of sines and cosines. The products of sine and cosines obey these relationships:
Integrals of products of sines and cosines.
where n and m are integers. In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I dedicate Appendix E to studying these integrals. They allow some very complicated expressions involving infinite sums to reduce to elegantly simple equations for the Fourier coefficients. Whenever I’m teaching Fourier series, I go through the derivation up to the point where these integrals are needed, and then say “and now the magic happens!”

The collection of sines and cosines (sinmx, cosnx) are an example of an orthogonal set of functions. How do you prove orthogonality? One can derive it using the trigonometric product-to-sum formulas.
Several trigonometric product-to-sum formulas.
I prefer to show that these integrals are zero for some special cases, and then generalize. Russ and I do just that in Figure E2. When we plot (a) sinx sin2x and (b) sinx cosx over the range 0 to 2π, it becomes clear that these integrals are zero. We write “each integrand has equal positive and negative contributions to the total integral,” which is obvious by merely inspecting Fig. E2. Is this a special case? No. To see a few more examples, I suggest plotting the following functions between 0 and 2π:
Product of trigonometric functions to plot.
In each case, you will see the positive and negative regions cancel pairwise. It really is amazing. But don’t take my word for it, as you’ll miss out on all the fun. Try it.

Nearly as amazing is what happens when you analyze the case for m = n by integrating cosnx cosnx = cos2nx or sinnx sinnx=sin2nx. Now the integrand is a square, so it always must be positive. These integrals don’t vanish (although the “mixed” integral cosnx sinnx does go to zero). How do I remember the value of this integral? Just recall that the average value of either cos2nx or sin2nx is ½. As long as you integrate over an integral number of periods, the result is just π.

When examining non-periodic functions, one integrates over all x, rather than from merely zero to 2π. In this case, Russ and I show in Sec. 11.10 that you get delta function relationships such as
An integral representation of the delta function.
I won’t ask you to plot the integrand over x, because since x goes from negative infinity to infinity it might take you a long time.

The integrals of products of sines and cosines is one example of how Russ and I use appendicies to examine important mathematical results that might distract the reader from the main topic (in this case, Fourier series and its application to imaging), but are nevertheless important.

Friday, December 27, 2013

Fourier Series

One of the most important mathematical techniques for a physicist is the Fourier series. I discussed Joseph Fourier, the inventor of this method, previously in this blog. In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the Fourier series in Sections 11.4 and 11.5.

The classic example of a Fourier series is the representation of a periodic square wave: y(t) = 1 for t between 0 and T/2, and y(t) = -1 for t between T/2 and T, where T is the period. The Fourier series represents this function as a sum of sines and cosines, with frequencies of k/T, where k is an integer, k = 0, 1, 2, …. The square wave function y(t) is odd, so the contributions of the cosine functions vanish. The sine functions contribute for half the frequencies, those with odd values of k. The amplitude of each non-zero frequency is 4/πk (Eq. 11.34 in IPMB), so the very high frequency terms (large k) don’t contribute much.

Being able to calculate the Fourier series is nice, but much more important is being able to visualize it. When I teach my Medical Physics class (PHY 326), based on the last half of IPMB, I stress that students should “think before you calculate.” One ought to be able to predict qualitatively the Fourier coefficients by inspection. Being able to understand a mathematical calculation in pictures and in physical terms is crucially important for a physicist. The Wikipedia article about a square wave has a nice animation of the square wave being built up by adding more and more frequencies to the series. I always insist that students draw figures showing better and better approximations to a function as more terms are added, at least for the first three non-zero Fourier components. You can also find a nice discussion of the square wave at the Wolfram website. However, the best visualization of the Fourier series that I have seen was brought to my attention by one of the PHY 326 students, Melvin Kucway. He found this lovely site, which shows the different Fourier components as little spinning wheels attached to wheels attached to wheels, each with the correct radius and spinning frequency so that their sum traces out the square wave. Watch this animation carefully. Notice how the larger wheels rotate at a lower frequency, while the smaller wheels spin around at higher frequencies. This picture reminds me of the pre-Copernican view of the rotation of planets based on epicycles proposed by Ptolemy.

What is unique about the development of Fourier series in IPMB? Our approach, which I rarely, if ever, see elsewhere, is to derive the Fourier coefficients using a least-squares approach. This may not be the simplest or most elegant route to the coefficients, but in my opinion it is the most intuitive. Also, we emphasize the Fourier series written in terms of sines and cosines, rather than complex exponentials. Why? Understanding Fourier series on an intuitive level is hard enough with trigonometric functions; it becomes harder still when you add in complex numbers. I admit, the math appears in a more compact expression using complex exponentials, but for me it is more difficult to visualize.

If you want a nice introduction to Fourier series, click here or here (in the second site, scroll down to the bottom on the left). If you prefer listening to reading, click here for an MIT Open Courseware lecture about the Fourier series. The two subsequent lectures are also useful: see here and here. The last of these lectures examines the square wave specifically.

One of the fascinating things about the Fourier representation of the square wave is the Gibbs phenomenon. But, I have discussed that in the blog before, so I won’t repeat myself.

What is the Fourier series used for? In IPMB, the main application is in medical imaging. In particular, computed tomography (Chapter 12) and magnetic resonance imaging (Chapter 18) are both difficult to understand quantitatively without using Fourier methods.

As a new year’s resolution, I suggest you master the Fourier series, with a focus on understanding it on a graphical and intuitive level. What is my new year’s resolution for 2014? It is for Russ and I to finish and submit the 5th edition of IPMB to our publishers. With luck, you will be able to purchase a copy before the end of 2015.

Friday, December 20, 2013

The Last Question

Entropy and its role in the Second Law of Thermodynamics is one of the fundamental ideas of all science. One can think of entropy roughly as a measure of the disorder within a system. An interesting feature of entropy is that it is not conserved. Rather, it tends to increase over time (the system becomes more disordered). In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I write
…under what conditions can the entropy of a system be made to decrease?

The answer is that the entropy of a system can be made to decrease if, and only if, it is in contact with one or more auxiliary systems that experience at least a compensating increase in entropy. Then the total entropy remains the same or increases. This is one form of the second law of thermodynamics. For a fascinating discussion of the second law, see Atkins (1994).
Nine Tomorrows A short story collection by Isaac Asimov containing The Last Question, superimposed on Intermediate Physics for Medicine and Biology.
Nine Tomorrows,
A short story collection by
Isaac Asimov containing
“The Last Question.”
The reference is to P. W. Atkins’ 1994 Scientific American book The 2nd Law: Energy, Chaos and Form. It is a great book written for a layman with little or no mathematics that clearly conveys the insights provided by the second law.

The very first course I ever taught, at Vanderbilt University in the fall of 1995, was an undergraduate thermodynamics class. When we talked about entropy, I had all my students read the short story “The Last Question” by Isaac Asimov. This marvelous tale speculates about what will happen to the universe as entropy slowly but steadily increases. Regular readers of this blog know that I am a big Asimov fan (for instance, see here), and The Last Question is one of his best stories. That is not just my opinion. Asimov himself said it was his favorite short story of all he had written. You can read it here, or listen to the Good Doctor himself read it below.

I Robot, by Isaac Asimov, superimposed on Intermediate Physics for Medicine and Biology.
I Robot, by Isaac Asimov.
For those wanting more Asimov short stories, I recommend “Nightfall”and “The Ugly Little Boy.” Also I, Robot is a collection of loosely related short stories based on the three laws of robotics (please, skip the 2004 film by the same name featuring Will Smith). One big Asimov fan posted reviews of all Asimov’s books. Enjoy.

Finally, let me share one more crucially important point. Amazon.com says you still have time to order IPMB and have it delivered by Christmas. If you plan on putting a copy of IPMB in each of your loved one's stockings (and who doesn’t?), you had better order soon!

Friday, December 13, 2013

Electricity and Magnetism

Electricity and Magnetism, 3rd Edition, by Edward Purcell and David Morin, superimposed on Intermediate Physics for Medicine and Biology.
Electricity and Magnetism, 3rd Edition,
by Edward Purcell and David Morin.
I have always enjoyed Edward Purcell’s textbook Electricity and Magnetism, which is Volume 2 of the Berkeley Physics Course. I love the book so much that I included it in My Ideal Bookshelf that I presented in this blog a few weeks ago. I own a copy of the first edition, with its orange cover that is now faded and falling apart. The second edition was published soon after I completed my undergraduate physics degree from the University of Kansas, so I have not used it much.

This year, a 3rd edition of the book was published, with coauthor David Morin (Purcell died in 1997 so he had no input on the 3rd edition). In the preface to the 3rd edition, Morin describes his goals:
For 50 years, physics students have enjoyed learning about electricity and magnetism through the first two editions of this book. The purpose of the present edition is to bring certain things up to date and to add new material, in the hopes that the trend will continue. The main changes from the second edition are (1) the conversion from Gaussian units to SI units, and (2) the addition of many solved problems and examples.
The use of SI units is interesting, because apparently Purcell resisted this change when preparing the 2nd edition. When I was an undergraduate around 1980, almost all introductory textbooks had switched to SI units, so I “grew up” with them. Therefore, I agree with Morin about the usefulness of this change. In the preface he writes
The first of these changes [to SI units] is due to the fact that the vast majority of courses on electricity and magnetism are now taught in SI units. The second edition fell out of print at one point, and it was hard to watch such a wonderful book fade away because it wasn’t compatible with the way the subject is presently taught. Of course, there are differing opinions as to which system of units is “better” for an introductory course. But this issue is moot, given the reality of these courses.
The other big change is a lot of new homework problems and worked examples. This resonates with me, because one big change that Russ Hobbie and I made to the 4th edition of Intermediate Physics for Medicine and Biology is many new homework problems. Morin offers some advice to the reader in his preface, which applies equally well to readers of IPMB. One reason we only distribute homework solutions to instructors rather than students is to encourage students to struggle with these problems on their own.
Some advice on using the solutions to the problems…If you are having trouble solving a problem, it is critical that you don’t look at the solution too soon. Brood over it for a while. If you do finally look at the solution, don’t just read it through. Instead, cover it up with a piece of paper and read one line at a time until you reach a hint to get you started. Then set the book aside and work things out for real. That’s the only way it will sink in. It’s quite astonishing how unhelpful it is simply to read a solution. You’d think it would do some good, but in fact it is completely ineffective in raising your understanding to the next level.
One unique feature of Electricity and Magnetism is that magnetism is introduced as a consequence of electricity and special relativity. In almost all other books, this relationship is omitted or presented as an advanced topic. It is an interesting approach, about which I have mixed feelings. Morin writes
The intertwined nature of electricity, magnetism, and relativity is discussed in detail in Chapter 5. Many students find this material highly illuminating, although some find it a bit difficult. (However, these two groups are by no means mutually exclusive!)
If I was teaching our undergraduate electricity and magnetism class next semester, would I use the 3rd edition of Electricity and Magnetism? I would certainly consider it. In my opinion, its main competition would be David Griffiths’ textbook Introduction of Electrodynamics. I used that book last time I taught electricity and magnetism, and it is also outstanding. It is not cited in IPMB, which makes me rather sad, as it is another one of those much-treasured books. Just the thought of reading first Purcell and then Griffiths, trying to decide which to use, sounds so fun that I am tempted to volunteer to teach electricity and magnetism again.

For those wanting to learn more about Morin’s new edition of Electricity and Magnetism, read the interview with him on the Physics Today website. You can find a review of the book here. Additional information is on the book's website.

Friday, December 6, 2013

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times

I am one of the coauthors on a paper published recently that analyzes how to determine properties of a cardiac wave front from measurements of wave front arrival times (Mazeh, Haines, Kay, and Roth, “A Simplified Approach for Simultaneous Measurement of Wavefront Velocity and Curvature in the Heart Using Activation Times,” Cardiovascular Engineering and Technology, Volume 4, Pages 520–534, 2013). The lead author, Nachaat Mazeh, is a former grad student of mine who obtained his PhD from Oakland University, and now works in the Beaumont Health System. David Haines is the Director of the Heart Rhythm Center at Beaumont, and is well known for his work on radiofrequency ablation of cardiac tissue. Matthew Kay is a professor of engineering at The George Washington University. In this paper, we obtain the wave front properties from measurement of four arrival times. The result is just simple enough to make into a new homework problem, typical in difficulty to those in the 4th edition of Intermediate Physics for Medicine and Biology.
Section 10.11

Problem 43 Suppose you measure the arrival time of an action potential wave front at four points (1-4) in a diamond pattern, each a distance b from the central point (red). Calculate the wave front speed, direction, and curvature from these four measurements.
A figure showing how to measure the speed, direction, and curvature of a cardiac wave front using four electrodes.

a) Assume the wave front is circular and propagates outward from the origin. Use the law of cosines to write r1, r2, r3, and r4 (the distance of each electrode to the origin) in terms of r0, b, and the angle θ.
b) Pull a factor of r0 outside of the square root in each of your four expressions from part a).
c) Assume r0 is much greater than b, and perform a Taylor expansion of each of the four expressions in terms of the small parameter ε = b/r0. Include terms that are constant, linear, and quadratic in ε.
d) Write the arrival time at each electrode (n=1, 2, 3, and 4) as tn=rn/v, where v is the wave speed.
e) Let Δtij=ti – tj. Find expressions for Δt13 and Δt24 in terms of b, θ, and v. Solve these expressions to determine v and θ in terms of Δt13, Δt24, and b.
f) Find expressions for Δt14 and Δt23 in terms of b, θ, and v. Now (and this is the most difficult step), find an expression for the radius of curvature, r0, in terms of b, Δt13, Δt24, Δt14, and Δt23.

There are several advantages and several disadvantages to the expressions you will derive. The advantages are that the calculations require only four measurements of arrival time, and they provide not only the speed and direction but also (somewhat unexpectedly--at least to me) the radius of curvature, r0. The radius of curvature is important for propagation, because highly curved wave fronts propagate more slowly than nearly flat wave fronts. The radius of curvature at the core of a spiral wave is highly curved, and this curvature influences properties of the spiral wave such as how fast it rotates. There are some important limitations. First, a close examination of your expression for the radius of curvature will reveal that the method gives an indeterminate expression for propagation at angles of θ = 45, 135, 225, and 315°. Second, the expressions contain the differences of activation times. In fact, the radius of curvature depends on the difference of a difference of activation times. If these activation times are all similar, then they need to be known precisely for the calculation of their differences to be accurate. The calculation assumes the wave front is circular, although really the wave front only needs to be circular locally, so this should not be too bad an approximation. The method also is based on the assumption that b is much less than r0.

Despite these limitations, I think the expressions should be useful for characterizing properties of wave fronts in the heart. It may be particularly useful for obtaining wave front speed, direction, and curvature in computer simulations, where the calculation is computed over a regular two-dimensional Cartesian grid and where noise in the activation times may not be a big concern.

Friday, November 29, 2013

From Vision to Change: Educational Initiatives and Research at the Intersection of Physics and Biology

A few months ago, the journal CBE—Life Sciences Education published a special issue about education at the intersection of physics and biology. This topic is of great interest to readers of the 4th edition of Intermediate Physics for Medicine and Biology. The special issue was motivated by the American Association for the Advancement of Science report Vision and Change in Undergraduate Biology Education. While there were many interesting articles in this issue, my favorite was the essay “Learning Each Other’s Ropes: Negotiating Interdisciplinary Authenticity” (Volume 12, Pages 175–186, 2013), by Edward Redish and Todd Cooke, both from the University of Maryland. They describe their goals in the paper’s abstract.
A common feature of the recent calls for reform of the undergraduate biology curriculum has been for better coordination between biology and the courses from the allied disciplines of mathematics, chemistry, and physics. Physics has lagged behind math and chemistry in creating new, biologically oriented curricula, although much activity is now taking place, and significant progress is being made. In this essay, we consider a case study: a multiyear conversation between a physicist interested in adapting his physics course for biologists (E.F.R.) and a biologist interested in including more physics in his biology course (T.J.C.). These extended discussions have led us both to a deeper understanding of each other’s discipline and to significant changes in the way we each think about and present our classes. We discuss two examples in detail: the creation of a physics problem on fluid flow for a biology class and the creation of a biologically authentic physics problem on scaling and dimensional analysis. In each case, we see differences in how the two disciplines frame and see value in the tasks. We conclude with some generalizations about how biology and physics look at the world differently that help us navigate the minefield of counterproductive stereotypical responses.
I found this paper to be fascinating, and it will be helpful as Russ Hobbie and I prepare the 5th edition of IPMB. It is interesting that the authors use the word “negotiating” in the title, because I felt that Redish and Cooke were involved in an extended negotiation about how much physics to include in an introductory biology class. This process is not restricted to instruction; I go through an often painful negotiation regarding the emphasis of biology versus physics with the reviewers of almost every research article I’ve ever published. I like the conversational tone of Redish and Cooke’s paper, and how it describes the growth of a close collaboration between a biologist and a physicist, each with a different worldview. Probably the most important contribution of the article is the story of how they uncovered and dealt with their hidden biases (they use the term epistemologies, which is one of those words from the science education literature that I dislike). Readers of this blog may remember Redish; one of my blog entries earlier this year discussed his article in Physics Today about “Reinventing Physics for Life Science Majors.” At first, I was annoyed by Redish and Cooke’s habit of referring to themselves collectively in the first person and individually in the third person (as in, “our physicist” and “our biologist”), but as I read on this technique began to grow on me and in the end I found it endearing. I particularly enjoyed their discussion about the role of problem solving in physics and biology, and what makes a good homework problem.
In our interdisciplinary discussions, we also learned that biologists and physicists had dramatically different views of what makes a good biological example in physics… We came to understand that what would be of value in a physics class is biological authenticity—examples in which solving a physics problem in a biological context gives the student a deeper understanding of why the biological system behaves the way it does.
Russ and I strive to achieve authenticity in our end-of-chapter homework problems. Our book is aimed at an intermediate level--we assume the student is comfortable with calculus--so we may have an easier time constructing nontrivial physics exercises applied to biology than an introductory instructor would, but I sometimes wonder if the biologists and medical doctors find them as useful as we think they are.

Redish and Cooke present a list of “cultural components” of both physics and biology that are illuminating.
Physics: Common Cultural Components
  • Introductory physics classes often stress reasoning from a few fundamental (usually mathematically formulated) principles. 

  • Physicists often stress building a complete understanding of the simplest possible (often highly abstract) examples— “toy models”—and often do not go beyond them at the introductory level.
 
  • Physicists quantify their view of the physical world, model with math, and think with equations, qualitatively as well as quantitatively.
 
  • Physicists concern themselves with constraints that hold no matter what the internal details (conservation laws, center of mass, etc.).
Biology: Common Cultural Components
  • Biology is often incredibly complex. Many biological processes involve the interactions of component parts leading to emergent phenomena, which include the property of life itself. 

  • Most introductory biology does not emphasize quantitative reasoning and problem solving to the extent these are emphasized in introductory physics.
 
  • Biology contains a critical historical constraint in that natural selection can only act on pre-existing molecules, cells, and organisms for generating new solutions.
 
  • Much of introductory biology is descriptive (and introduces a large vocabulary).
 
  • However, biology—even at the introductory level—looks for mechanism and often considers micro–macro connections between the molecules involved and the larger phenomenon.
 
  • Biologists (both professionals and students) focus on and value real examples and structure–function relationships.
As I read these lists, it is clear to me that I am definitely in the physics camp. It would not be an exaggeration to say that a primary goal of IPMB is to force introduce the physicist’s culture, as described above, to students interested in biology and medicine.

I do have one minor criticism. Initially I was impressed by Redish’s analysis of the relationship of flow to pressure in a blood vessel (Hagen-Poiseuille flow), with the appearance of the fourth power of the radius, using simple arguments involving no calculus. Upon further reflection, however, I’m not totally comfortable with the derivation. Here it is in brief:

Fpressure = ΔP A

Fdrag = b L v

Q = A v

where ΔP is the pressure drop, A is the cross-sectional area of the vessel, L is the vessel length, v is the speed (assumed uniform, or plug flow), b is a frictional proportionality constant, and Q is the volume flow. If you set the two forces equal, and eliminate v in favor of Q, you get

ΔP = (b L/A2) Q

The 1/A2 dependence implies that the flow increases as the fourth power of the radius. My concern is this: suppose a student approaches Redish and says “I follow your derivation, but shouldn’t the drag force be proportional to the surface area where the flow contacts the vessel wall? In other words, shouldn’t the drag force be given by Fdrag = c (2πrL) v?” (I use c for the proportionality constant because it now has different units that b.) Of course, if you do the calculation using this expression for the drag force, you get the wrong answer (a 1/r3 dependence)! I wonder if any of his students ever brought this up, and how he responded? The complete derivation is given in Chapter 1 of IPMB, and the central point is that the frictional force depends on dv/dr rather than v, but the analysis uses some rather advanced calculus that would be inappropriate in the introductory biology class that Redish and Cooke consider. The trade-off between simplifying a concept so it is accessible versus being as accurate as possible is always difficult. I don’t know what the best approach would be in this case. (I can always make one recommendation: buy a copy of IPMB!)

Despite this one reservation, I enjoyed Redish and Cooke’s paper very much. Let me give them the last word.
We conclude that the process [of interdisciplinary collaboration aimed at revising the biology introductory course] is significantly more complex than many reformers working largely within their discipline often assume. But the process of learning each other’s ropes—at least to the extent that we can understand each other’s goals and ask each other challenging questions—can be both enlightening and enjoyable. And much to our surprise, we each feel that we have developed a deeper understanding of our own discipline as a result of our discussions.

Friday, November 22, 2013

My Ideal Bookshelf

My Ideal Bookshelf, by Thessaly La Force, with artwork by Jane Mount.
My Ideal Bookshelf,
by Thessaly La Force, with
artwork by Jane Mount.
While browsing at the library recently, I ran across the book My Ideal Bookshelf, edited by Thessaly La Force, with artwork by Jane Mount. Their preface describes the book well.
The assignment sounds straightforward enough. Select a small shelf of books that represent you—the books that have changed your life, that have made you who you are today, you favorite favorites. You begin, perhaps, by walking over to your bookshelf and skimming the spines on the top shelf. You pull down a handful that you remember loving; you grab a couple that you read over and over again. Some you know just by the color of their dust jackets. One is in tatters—it was passed down by your mother—and it’s dog-eared and carefully held together by tape and tenderness. The closer you look, the trickier the task turns out to be….

We asked more than one hundred creative people in a variety of disciplines from around the world to do exactly this. Chefs and architects, writers and fashion designers, filmmakers and ballet dancers all agreed to share their ideal bookshelves.
It’s not the words that make this book is so interesting; it is the pictures. Each contributor had their bookshelf painted. The dust jackets says “Jane Mount’s original paintings of the colorful and delightful book spines and occasional objects d’art from the contributors’ personal bookshelves showcase the selections.” You can probably guess where this is going. I just had to collect the ideal bookshelf for the 4th edition of Intermediate Physics for Medicine and Biology. (Someone had too much time on his hands this week.) Here it is:

My Ideal Bookshelf, for Intermediate Physics for Medicine and Biology.
My Ideal Bookshelf, for
Intermediate Physics for Medicine and Biology.

My illustration does not have the charm of Mount’s quirky paintings (see her create one of these illustrations below). I put mine together in powerpoint, and every book spine is a rectangle. If you like this sort of thing, browse through My Ideal Bookshelf and enjoy her enchanting artwork. If you REALLY like My Ideal Bookshelf, you can pay big bucks and get prints of various book collections (see http://www.idealbookshelf.com).


How did I choose which books to include in my illustration? The book had to be cited in IPMB, it had to deal with either physics or the application of physics to biology, and I had to have access to a copy (either from my own office bookshelf or from the Oakland University library) so I could recall what the spine looked like. The towering blue volume of IPMB dominates the skyline that is my bookshelf. Some great authors are represented, including Edward Purcell, Philip Morrison, Art Winfree, Knut Schmidt-Nielsen, Leon Glass, and Howard Berg. Two volumes of the wonderful Berkeley Physics Course appear. Powers of Ten and The Machinery of Life are both beautifully illustrated, and would be the best choices from my shelf for mathophobes. I wanted to include Strogatz’s Nonlinear Dynamics and Chaos, but I couldn’t reproduce the marbled coloration of the spine using powerpoint.

Do you want to learn more about books related to IPMB? I listed my top ten books in an earlier blog entry, and a catalog of 40 books can be found in an Amazon.com Listmania! list for IPMB that I put together a while back. Click one button on that webpage and you can buy them all (I hope your credit card has a high limit).

Whose collection of books in My Ideal Bookshelf is closest to my taste? I resonated with the bookshelves of Atul Gawande (doctor and writer), John Maeda (graphic designer and computer scientist), and most of all Jonathan Zittrain (legal scholar and professor). For you voyeurs who want to peak further into my personal bookshelf, see another of my Listmania! lists containing my favorite books.

Friday, November 15, 2013

Upcoming Events

I like to use this blog to remind readers of the 4th edition of Intermediate Physics for Medicine and Biology about upcoming events they might enjoy. Here are a few:


1. Each December, the Howard Hughes Medical Institute webcasts its Holiday Lectures on Science. This year, the topic is “Medicine in the Genomic Era.”
Sixty years after James Watson and Francis Crick revealed the structure of the DNA double helix and only a decade after scientists published the first complete read-through of all three billion DNA bases in the human genome, the ability to routinely sequence and analyze individual genomes is revolutionizing the practice of medicine—from how diseases are first diagnosed to how they are treated and managed. In the 2013 Holiday Lectures on Science, Charles L. Sawyers of Memorial Sloan-Kettering Cancer Center and Christopher A. Walsh of Boston Children’s Hospital will reveal the breathtaking pace of discoveries into the genetic causes of various types of cancers and diseases of the nervous system, and discuss the impact of those discoveries on our understanding of normal human development and disease.
Although there may not be a lot of physics in these lectures, the analysis of genomic data is a fine example of how mathematics and medicine are intertwined. The webcast schedule is
December 5th, 2013
Live webcast
10:00 a.m. ET “Sizing up the Brain, Gene by Gene,” by Christopher A. Walsh
11:30 a.m. ET “Cancer as a Genetic Disease,” by Charles L. Sawyers
Re-webcast
10:00 a.m. PT “Sizing up the Brain, Gene by Gene,” by Christopher A. Walsh
11:30 a.m. PT “Cancer as a Genetic Disease,” by Charles L. Sawyers 
December 6th, 2013
Live webcast
10:00 a.m. ET “Decoding the Autism Puzzle,” by Christopher A. Walsh
11:30 a.m. ET “From Cancer Genomics to Cancer Drugs,” by Charles L. Sawyers
Re-webcast
10:00 a.m. PT “Decoding the Autism Puzzle,” by Christopher A. Walsh
11:30 a.m. PT “From Cancer Genomics to Cancer Drugs,” by Charles L. Sawyers
I have seen these HHMI lectures in the past, and they are excellent. Aimed at the layman, the audience consists primarily of young scientists (high school students interested in science, if I recall correctly). They say you should register for the lectures, but I don’t think it costs anything. Enjoy.


2. During the Christmas season, the Royal Institution (home to one of my heroes, Michael Faraday) presents its Christmas Lectures. This year, they are about developmental biology.
The 2013 CHRISTMAS LECTURES® presented by Dr Alison Woollard from the University of Oxford, will explore the frontiers of developmental biology and uncover the remarkable transformation of a single cell into a complex organism. What do these mechanisms tell us about the relationships between all creatures on Earth? And can we harness this knowledge to improve or even extend our own lives? - See more at: http://richannel.org/christmas-lectures/2013/life-fantastic#sthash.eGBmtufx.dpuf
These lectures will take place December 14, 17, and 19, in front of a live audience (again, mainly of students) at the Royal Institution in London. We Yanks who can’t afford to cross the pond will have to wait until January to view the recordings at the Royal Institution website.

If you think there is no physics in developmental biology, then you haven’t read Biological Physics of the Developing Embryo. (Honestly, I haven’t read the whole thing either, but I have skimmed through it and there is a lot of physics there.)


3. This time of year is when students should start thinking about research opportunities for summer 2014. One way to find such opportunities is by looking at the Pathways-to-Science website. I recommend the National Institutes of Health Internship Program in Biomedical Research. Having worked at NIH, I know that it is the best place in the world to do biomedical research. For an undergraduate student (or even high school student), working at NIH is the chance of a lifetime. Apply!

Oakland University, where I work, has a website listing many other summer research programs, such as the many Research Experiences for Undergraduates programs funded by the National Science Foundation. Some of them are for OU students, but we also list many programs that anyone can apply to. Set some time aside over the holiday break to review these programs.


4. I am the Oakland University representative for the Barry M. Goldwater Scholarship, which is the most prestigious honor available for undergraduate science, math, and engineering majors. I suspect many readers of IPMB are top students at their university. If you are currently a sophomore or junior at a United States university, you should ask around and find your Goldwater representative. Hurry, because the deadline is approaching fast! (Sorry, my friends from other countries, but only US citizens and permanent residents can apply.)


5. I just learned about the Science News for Students website. It is interesting, and worth a look. How did we survive without sites like these when I was growing up?


6. This week, Oakland University sent five of our top undergraduate researchers to the Sigma Xi 2013 Student Research Conference. This is a great meeting for young scholars, and undergraduates should explore the possibility of attending with their research mentor. This year’s meeting was November 8 and 9 at the Sheraton Imperial Hotel in Research Triangle Park, North Carolina. I realize I was tardy in announcing this meeting…you just missed this year’s conference. But students should keep the meeting in mind for next year. Plan ahead! I am a big fan of Sigma Xi, the Scientific Research Society.