Friday, September 27, 2013

Hermann von Helmholtz, Biological Physicist

Who was the greatest biological physicist ever? That’s a difficult question, but one candidate is the German scientist Hermann von Helmholtz (1821-1894). Helmholtz was both a physician and physicist who made important contributions to physiology. Russ Hobbie and I mention him briefly in the 4th edition of Intermediate Physics for Medicine and Biology. In Chapter 6 on Impulses in Nerve and Muscle Cells, we write
“The action potential was first measured by Helmholtz around 1850”
That is true, but he made many other contributions to biological physics. To highlight some of these, I turn to Asimov’s Biographical Encyclopedia of Science and Technology. Asimov first describes Helmholtz’s work on vision (some of which I have described previously in this blog).
“Like [Thomas] Young, Helmholtz made a close study of the function of the eye, and in 1851 he invented an ophthalmoscope, with which one could peer into the eye’s interior—an instrument without which the modern eye specialist would be all but helpless…In addition he revived Young’s theory of three-color vision and expanded it, so that it is now known as the Young-Helmholtz theory.”
He also studied sound, the ear, and music (he was a fine musician).
“Helmholtz studied that other sense organ, the ear, as well. He advanced the theory that the ear detected differences in pitch through the action of the cochlea, a spiral organ in the inner ear. It contained, he explained, a series of progressively smaller resonators, each of which responded to a sound wave of progressively higher frequency. The pitch we detected depended on which resonator responded.”
And as Russ and I noted, he made pioneering measurements in nerve electrophysiology.
“Helmholtz was the first to measure the speed of the nerve impulse. His teacher, Muller, was fond of presenting this as an example of something science could never accomplish because the impulse moved so quickly over so short a path. In 1852, however, Helmholtz stimulated a nerve connected to a frog muscle, stimulating it first near the muscle, then farther away. He managed to measure the added time required for the muscle to respond in the latter case.”
He also helped formulate the principle of the conservation of energy, an idea he came upon when studying the behavior of muscle.
“But he is best known for his contributions to physics and in particular for his treatment of the conservation of energy, something to which he was led by his studies of muscle action. He was the first to show that animal heat was produced chiefly by contracting muscle and that an acid—which we now know to be lactic acid—was formed in the working muscle.”
Given my admiration for 19th century physicists, I’m a little surprised that I don’t know more about Helmholtz. This is probably because I am more familiar with the great British physicists—Faraday, Maxwell, Kelvin—than with the Germans of that era (this is odd, given that I am half German). I would not go so far as to claim Helmholtz was as great a physicist as my Victorian heroes, but I do suggest that he was a greater biological physicist. In fact, I think a good argument could be made that he is the greatest of all biological physicists.

Friday, September 20, 2013

Musicophilia

Those who know me well are aware that I spend considerable time walking my dog Suki. Usually during these walks I am listening to recorded books. Being too cheap to spend money on this habit, I borrow these recordings from the Rochester Hills Public Library. They have a impressive selection, but Suki and I have been at this for a while (she is almost 11 years old), and I have slowly worked my way through their stock of recordings in genres that I ordinarily listen to; science, history, and biography. I don’t view this as a problem, because it has forced me to sample books about topics I would not ordinarily listen to. The most recent example is Musicophilia: Tales of Music and the Brain, by Oliver Sacks. Perhaps you object that this is actually a science book, but I view it more as a medical book outside my normal experience. Regardless, I was pleasantly surprised to find considerable medical physics discussed.

I had listened previously to Sacks’s delightfully-titled The Man Who Mistook His Wife for a Hat, so I knew what I was getting into. In Musicophilia, Sacks discusses a variety of abnormalities in the perception of music. For instance, he begins with musical hallucinations. This is more than just having a song stuck in your head. These were examples from his clinical practice of people who had, say, suffered a brain injury and afterward would hear music in their mind that they could not distinguish from real music. They sometimes could not turn it on or off, but were stuck with it more or less continuously. Another example is people who, after a stroke, lost the ability to hear music as music. An opera sounds like someone screaming, and a symphony like pots and pans crashing onto the floor. In one case he related, this occurred to a former professional musician. It is amazing.

Sacks describes all sorts of brain studies being done to examine these patients. There is considerable discussion of data measured using electroencephalography, magnetoencephalography, positron emission tomography, functional magnetic resonance imaging, and transcranial magnetic stimulation—all of which Russ Hobbie and I analyze in the 4th edition of Intermediate Physics for Medicine and Biology. For me, hearing these stories makes me nostalgic for my years working at the National Institutes of Health, where I used to collaborate with neurologists such as Mark Hallett (whose research is mentioned by Sacks). Hallett and his team studied all sorts of odd diseases while I was helping them develop magnetic stimulation. In this case, we physicists and engineers were not discovering new biological ideas or medical abnormalities, but we were providing the tools for others to make these discoveries. And, oh, what tools!

Sacks notes there are some patients who have lost their ability to tell which of two tones is the higher pitch (but can still hum a song). These patients are in contrast with those rare individuals with perfect or absolute pitch; they can tell what note a sound is when heard in isolation. My sister has something approaching perfect pitch. When I was in high school, I took piano lessons. Whenever I played a wrong note while practicing (which was quite often) she would call out from an adjacent room “f-sharp!” or “b-flat!”. Do you know how annoying it is not only to have your mistakes pointed out for all to hear, but also to have the specific note identified precisely? Worst of all, she was always right. Some of these piano pieces she had played herself, but others she had not; she was just able to identify the pitch. I have always envied people with perfect pitch, but Sacks raises an interesting point. If people with perfect pitch hear a song played flawlessly but in the wrong key, they get all agitated and upset (he compared this to seeing a painting with all the colors wrong). I, on the other hand, would remain blissfully unaware of the problem. When I was in graduate school in Nashville, I bought a used piano from a blind fellow who refurbished pianos for a living. This particular piano was so old that he could not tighten its strings completely, so the piano was tuned about 3 steps too low (He gave me a good deal on it). The improper tuning never bothered me in the least. However, sometimes my weakness with tonal discrimination has caused me some embarrassment. I played tuba in my high school band, and before concerts the director would have us all “tune up”. The first clarinet would play a note, and we would each play the same note in turn to make sure we were in tune. I always hated this, because I could never tell if I was sharp or flat, and the director would usually end up yelling at me in frustration “You’re flat. Flat! Push the tuning slide in!”.

Sacks’s book got me to thinking about all sorts of unusual sensory perceptions. He describes people who could hear but could not perceive music, and I thought it must be like someone born without sight. But Sacks had a better analogy; imagine someone born colorblind (say, completely color blind, instead of just lacking one of three color receptors). How do you describe color to such a person? It has no meaning. How do you describe music to someone born unable to make sense of it? Then I began thinking of other odd sensory inputs, like magnetoreception and the ability to perceive the polarization of light. Humans can’t perceive these signals, but other species can. If you will let me indulge in a bit of anthropomorphization, I suspect there are some bird families who sit in their nest at night saying to each other “those humans can’t perceive magnetic fields or polarization! How to they ever get home?”

Finally, for those of you who know Suki, let me provide a quick update. Earlier this year she damaged her Anterior Cruciate Ligament, and our walks came to an abrupt halt. After much debate (she is a small dog, and is 10 years old) we decided to have her undergo surgery. The veterinary surgeon Dr. McAbee did a marvelous job, and we are now back to our walks as if nothing ever happened.

Friday, September 13, 2013

Plain Words

When I arrived at graduate school, the main goal given to me by my advisor John Wikswo was to write scientific papers. Of course, I had to write a PhD dissertation, but that was in the distant future. The immediate job was to publish journal articles. John is a good writer, and he insists his students write well. So he recommended that I read the book Plain Words, by Sir Ernest Gowers. (I can’t recall if he made this suggestion before or after reading my first draft of a paper!) I dutifully read the book, which I have come to love. I believe I read the 1973 revision by Bruce Fraser although I am not sure; I borrowed Wikswo’s copy.

Gowers is an advocate for writing simply and clearly. He states in the introduction
“Here we come to the most important part of our subject. Correctness is not enough. The words used may all be words approved by the dictionary and used in their right senses; the grammar may be faultless and the idiom above reproach. Yet what is written may still fail to convey a ready and precise meaning to the reader. That it does so fail is the charge brought against much of what is written nowadays, including much of what is written by officials. In the first chapter I quoted a saying of Matthew Arnold that the secret of style was to have something to say and to say it as clearly as you can. The basic fault of present-day writing is a tendency to say what one has to say in as complicated a way as possible. Instead of being simple, terse and direct, it is stilted, long-winded and circumlocutory; instead of choosing the simple word it prefers the unusual.”
I have become a strong advocate for using plain language in scientific writing. Over the last three decades I have reviewed hundreds of papers for scientific journals, and I can attest that many scientists should read Plain Words. I have tried to use plain, clear language in the 4th edition of Intermediate Physics for Medicine and Biology (although Russ Hobbie’s writing was quite good in earlier editions of IPMB, which I had nothing to do with, so the book didn’t need much editing by me). Below, Gowers describes three rules for writing, which apply as well to scientific writing as to the official government writing that he focused on.
“What we are concerned with is not a quest for a literary style as an end in itself, but to study how best to convey our meaning without ambiguity and without giving unnecessary trouble to our readers. This being our aim, the essence of the advice of both these authorities [mentioned earlier] may be expressed in the following three rules, and the rest of what I have to say in the domain of the vocabulary will be little more than an elaboration of them.
- Use no more words than are necessary to express your meaning. For if you use more you are likely to obscure it and to tire your reader. In particular do not use superfluous adjectives and adverbs and do not use roundabout phrases where single words would serve.
- Use familiar words rather than the far-fetched, for the familiar are more likely to be readily understood.
- Use words with a precise meaning rather than those that are vague, for they will obviously serve better to make your meaning clear; and in particular prefer concrete words to abstract, for they are more likely to have a precise meaning. ”
For me, the chore of writing is made easier because I like to write. Really, why else would I write this blog each week if I didn’t enjoy the craft of writing (certainly increased book sales can’t justify the time and effort). When my children were young, I once became secretary of their elementary school’s Parent-Teacher Association mainly because my primary duty would be writing the minutes of the PTA meetings. If you were to ask my graduate students, I think they would complain that I make too many changes to drafts of their papers, and we tend to go through too many iterations before submission to a journal. I can usually tell when we are close to a finished paper, because I find myself putting in commas in one draft, and then taking them out in the next. One trick Wikswo taught me is to read the text out loud, listening to the cadence and tone. I find this helpful, and I don’t care what people think when they walk by and hear me reading to myself in my office.

Most Americans have an advantage in the world of science. Modern science is primarily performed and published in the English language, which is our native tongue. I feel sorry for those who must submit articles written in an unfamiliar language—it really is unfair—but that has not stopped me from criticizing their English mercilessly in anonymous reviews. For any young scientist who may be reading this blog (and I do hope there are some of you out there), my advice is: learn to write. As a scientist, you will be judged on your written documents: your papers, your reports, and above all your grant proposals. You simply cannot afford to have these poorly written.

I believe role models are important in writing. One of mine is Isaac Asimov. While I enjoy his fiction, I use his science writing as an example of how to explain difficult concepts clearly. I was very lucky to have encountered his books when in high school. A second role model is not a science writer at all. I have read Winston Churchill’s books, especially his history of the second world war, and I find his writing both clear and elegant. A third model is physicist David Mermin. His textbook Solid State Physics is quite well written, and you can read his essay on writing physics here. You will find learning to write scientific papers difficult if all you read are other scientific papers, because the majority are not well written. If you pattern your own writing after them you will be aiming at the wrong target. Please, learn to write well.

You can read Plain Words online (and for free) here.

This week’s blog entry seems rather long and rambling. Let me conclude with a paraphrase of Mark Twain’s famous quip about letter writing: If I had more time, I would have written a shorter blog entry.

Friday, September 6, 2013

The Art of Electronics

A biological physicist needs many skills, and an important one for experimentalists is electronics. In graduate school, I began my career as an experimentalist, and my PhD advisor John Wikswo required all his students to design and build at least one piece of electronics. My job was to make a timer for our microelectrode puller. I wasn't experienced with circuit design, so at John’s suggestion I turned to  The Art of Electronics, by Paul Horowitz and Winfield Hill. This wonderful book taught me almost all I know about the subject (OK, that’s not saying much). I used the first edition, but in 1989 a second edition came out. Below is the preface from edition two.
“Electronics, perhaps more than any other field of technology, has enjoyed an explosive development in the last four decades. Thus it was with some trepidation that we attempted, in 1980, to bring out a definitive volume teaching the art of the subject. By ‘art’ we meant the kind of mastery that comes from an intimate familiarity with real circuits, actual devices, and the like, rather than the more abstract approach often favored in textbooks on electronics.”
The Art of Electronics is particularly useful for understanding active circuits, such as those including transistors and operational amplifiers. I recall that in graduate school my education had a conspicuous hole in that I didn’t understand transistors, and the Art of Electronics helped me learn about them in an intuitive way (I still recall fondly Horowitz and Hill’s “transistor man”).

Russ Hobbie and I don’t discuss electronics explicitly in the fourth edition of Intermediate Physics for Medicine and Biology, but it is implicit in some chapters. For instance, thin film transistor arrays are discussed briefly in Chapter 16, used for detecting x-ray images. In Chapter 6, Figure 6.32 shows the apparatus for making voltage-clamp measurements. The “controller” in that figure is basically an op-amp, and in order to understand how it works one needs to appreciate their “golden rules”: 1) the output does whatever is necessary to make the voltage difference between the inputs zero, and 2) the inputs draw no current. You can do a lot with an op amp, including simple circuits such as a voltage follower (which is needed if you want to record a voltage using a large input impedance, something that is important in bioelectric recordings), simple amplifiers, integrators and differentiators. Horowitz and Hill describe all these circuits and more, in a way that can be understood by the beginner. For me, The Art of Electronics is to electronic circuits what Numerical Recipes is to computational methods: a well-written book that lets you learn the essence of the subject and the practical applications, without getting bogged down in all the esoteric details.

My timer for our microelectrode puller worked, although it wasn’t pretty. As I recall, it was build using leftover parts, and looked something like a big toaster with gigantic, 1950s-style knobs. But it allowed me to pull glass microelectrodes with a reproducible resistance to use in intracellular measurements of voltage in nerve axons. My experimental work culminated in the first simultaneous measurement of the transmembrane potential and magnetic field of a nerve axon (see Barach, Roth, and Wikswo, IEEE Trans Biomed Eng, 32:136-140, 1985; and Roth and Wikswo, Biophys J, 48:93-109, 1985). The Biophysical Journal paper is one of my favorites, and represents the high water mark of my experimental career. However, I also like the less-cited IEEE TMBS paper for two reasons: it was my very first journal article (appearing in February of 1985, whereas the Biophysical Journal paper appeared in July), and it is my only paper in which I supplied the experimental data and someone else (in this case, Prof John Barach) performed the theoretical analysis. However, it soon became apparent that my talents and interests were more in mathematical modeling and computer simulation. Nevertheless, I have always had enormous respect for experimental work, which in my view is more difficult than theoretical analysis. I have suffered from a case of “experimentalist envy” since those formative years in graduate school.

Rumor has it that a 3rd edition of The Art of Electronics will appear soon.