Frank, Tom, Dee and where is Merrill?

In 1980 Bill Anlyan gave me some space old Chem  to begin to expand our computer science and bioengineering activities.  At the same time Joe Greenfield took over Cardiology and Jim Wyngaarden was running Medicine.  To continue, I learned that I needed to have some outlet for energy – and Ellen (my wife) decided I should start running.   Maddy Spach made it possible and he and I started running together in 1977 – and suddenly I had a 1 hour seminar each day about discontinuous propagation and a chance to decide how to untangle (during the afternoon) all that I messed up (in the morning).  Between Maddy, Joe, Jim and Gene Stead, I had probably the most unique group of  mentors that one could imagine.  All the research skills I learned from them and from Jim Grizzle, who was chairman of Biostatistics at UNC Chapel Hill.  When I finally moved to the old Chem building, I actually built a wet lab for tissue studies, to complement the facilities for cellular studies that Gus Grant (my long time friend and collaborator).  During this time we did lots of interesting things.  We acquired UNIX in 1973 – and have a letter signed by Ken Thompson when we acquired an update in 1978.  I was sitting on the board of the Triangle Universities Computer Center and became interested in porting UNIX to the 370 and Amdahl machines.  Fred Brooks (chairman of UNC computer science) started a project to do this.  It was too early, though – sigh.  In addition, I had the good fortune to work with friends at Roche in Basel, and this started my international adventures.  It was a very serious virus that infected me – resulting in work in Russia (USSR), India, Greece, Spain, France, UK, Germany, Nepal and Egypt.  The NIH was gracious to fund many of these adventures.  Below are photos that capture some of our lab without walls.  First,  Maddy, Gus (co architect of the guarded receptor paradigm) and David (Wendt).

Here is Anselmo (Lastra), Beth (Rusnak) and David (Cherveny) -  these guys did all the UNIX and network magic that made our international collaborations really happen

We lived in the crazy tin-hut, designed to optimize people chemistry.  As you see, no one took anything seriously.  Here is Yvonne (Walker),  Ed (Darken), Jo (Smaltz), Margie (Dietz) – and Marge without a doubt has the most profound effect on everything we did.  Without her imagination and problem solving – we would still be crawling in the dark

I had two homes: one in the tin hut and one in the SRB.  Here I found another mentor.  Xiaobai (Sun) was my friendly neighbor in the Computer Science department and my teacher of numerical methods and linear algebra.  When I had algorithm problems (e.g. how to efficiently solve a problem with a circulant matrix) Xiaobai stopped what she was doing and led the way.  Her thinking was fun to watch.  Xiaobai sat in on my seminar-course: Computing, communication and memory in biological systems.  She had no biological background but suddenly becamse a net contributor to the class.  We explored models of excitable cells (cardiac and neuronal) and demonstrated many interesting problems that are inherent in cellular arrays, e.g. that the circuitry associated with horizontal cells in the retina computes an approximate laplacian of the visual field, a neat way to detect motion.  She and I discussed teaching strategies where the role of the teacher and the students was blurred, i.e. sometimes we were the learners and sometimes others were learners.  To test these ideas, Xiaobai and I explored problem-based learning in her numerical methods course.  Actually, I challenged Xiaobai to come up with a problem whose solution would touch all the essential areas in numerical methods.  She initially thought it was not possible, but then decided an excitable single-cell would be a good model.  With our first group of students, Xiaobai took the role of the facilitator and I watched from the side lines and was the cheer leader.  The strategy was a success and now her courses, although tough as nails, are among the most popular computer science courses at Duke.  Xiaobai and her gentle manner,  had a profound influence on the way I thought about problems and how to understand the nature of different types of errors.

It’s a little known fact – I really did some experiments.  Here are two students,  Frank (Tong) and Melanie trying to keep me from tripping over the apparatus.   We explored  vulnerability in isolated rabbit left atrium where we were able to demonstrated drug-induced prolongation of the vulnerable period which was predicted by Anselmo’s Ph.D. work (Proarrhythmic response to Na channel blockade:  Theoretical model and numerical experiments.  Circ. 84: 1364-1377, 1991.).  It was one of those interesting times where the model and computer studies actually predicted something not previously observed.  We were pleased and put these results together in a paper for  the American J. Physiology:  Cardiac instability amplified by use-dependent Na channel blockade.  Amer. J. Physiol 262:H1305-1310, 1992.  As you can see from the expression on Frank’s face, we were quite lost in the fascinating world of antiarrhythmic drugs, proarrhythmic responses and reentrant arrhythmias.

Because of our work in Moscow and Pushchino, we were fortunate to acquire Yuri (Zilberter) and Josef (Starobin).  Yuri’s experimental skills were unbelievable and he worked through ideas of ion channel blockade that had escaped us.  Josef brought an unbelievable degree of mathematical sophistication to our group, and worked out the quasi-analytical characterization of the vulnerable period.  His mathematical and computing skills led us to a new appreciation of the importance of the wavefront in propagation and also he developed on his own, the interaction between waves and obstacles.

In parallel with the Duke work were our collaborations:   here is our Egyptian team with David and Marge and to the right is a demonstration of our indestructible medical record in Kathmandu, Nepal

Here is our Moscow / French link:  Nail (Burnashev) and Guy (Vassort) and Rene (Clapier) in  the Moscow lab and in Heidelberg

Here is Jorg (Weirich) in Freiburg and T. Sada, Ban and colleagues in Japan

Finally here are Valentin (Krinsky),  Vicente (Perez-Munuzuri) and his wife Natalia in Santiago de Compestello Spain.  Valentin liked this photo with a potato digger: the fate of many Pushchino scientists in the post Gorbachev era.   I came to know Vicente through Valentin Krinsky’s lab in Pushchino.  Natalia’s sister, Olga, was Valentin’s secretary. Valentin taught me the power of identifying generic properties of complex systems, in our case, generic properties of an excitable cell or an array of excitable cells.  Whether BZ chemical media, cardiac cells or coupled nonlinear differential equations (FHN), the generic properties were always there.  It was a refreshing insight because it said that adding complexity to a mathematical model in order to achieve more “realism” may be a distraction.  Rather, study the generic properties of a minimal model and from here, develop your insights.  Example of generic properties of an excitable cell (or array of cells): threshold of excitation, spatial threshold of excitation (liminal region) and vulnerability.  None of these properties disappear when you increase the complexity of the model.  Vicente deeply understood this and took our ideas to his laboratory in Spain.  Vicente was a chemical and circuit magician, and transported our ideas about vulnerability to the excitable BZ chemical medium and arrays of Choa circuits.  He demonstrated experimentally to us, that vulnerability was truly a generic property in a series of elegant studies published in Phys Rev.

Although I’ve moved to MUSC, our  lab still functions.  Gus and I continue to collaborate.  Maddy and I continue to talk about propagation and when together, we have our usual noon seminar on the Duke track (or somewhere else).  My  current work continues to focus on the ion channel blockade (with Gus), vulnerability and the math aspects of excitable media with Tassos (Bountis) and two special Romanian students at the University of Patras (Adi and Laura, and look at our camping trips). 

I continue to search for new ideas, new insights and new adventures.  Stay tuned for more.