Friday, March 26, 2010

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 am 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 'Maristenschulbr├╝der'. 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.

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