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Questions and answers with William Bialek

In his quest to discover general biophysics principles, the theoretician found some that govern seemingly disparate phenomena—for example, protein folding, embryonic development, and neural computation. 

William “Bill” Bialek is the John Archibald Wheeler/Battelle Professor in Physics at Princeton University in New Jersey and Visiting Presidential Professor of Physics at the Graduate Center of the City University of New York. He conducts theoretical research at the interface of physics and biology, from the dynamics of individual biological molecules to learning and cognition. Bialek is a member of the National Academy of Sciences, a fellow of the American Physical Society, and recipient of the Society for Neuroscience’s 2013 Swartz Prize for Theoretical and Computational Neuroscience for his work on neural coding and computation in the brain. 

Bialek earned his bachelor’s degree in 1979 and doctoral degree in 1983 from the University of California, Berkeley. He returned to teach there in 1986 after postdoctoral stints at the University of Groningen in the Netherlands and the Institute for Theoretical Physics (now named in honor of the Kavli Foundation) in Santa Barbara, California. In 1990 he moved to Princeton, New Jersey, to work for the NEC Research Institute (now the NEC Laboratories). He joined the Princeton University faculty in 2001.

In addition to his research, Bialek has been working to establish biophysics as a subdiscipline within physics. At NEC, he organized the Princeton Lectures on Biophysics to introduce young physicists to problems at the interface of physics and biology. From 1998 to 2002, he codirected the computational neuroscience summer course at the Marine Biological Laboratory in Woods Hole, Massachusetts. Currently he is participating in an educational experiment at Princeton to create an integrated and mathematically sophisticated introduction to the natural sciences for first-year college students.

Looking to capture the breadth of his field, Bialek has written his first textbook, Biophysics: Searching for Principles (Princeton University Press, 2012). Physics Today recently caught up with him to discuss the book. 

William “Bill” Bialek

William “Bill” Bialek

PT: How does your approach to biophysics compare with others, and how is that approach reflected in the layout of your text?

Bialek: I think most previous textbooks have presented biophysics as a biological science, or perhaps as a cross-disciplinary amalgam. I have taken the view that there is a physics of biological systems and that this is to be understood in the same way that we talk about the physics of solids or the physics of the early universe. So this book tries to present biophysics as a branch of physics.

The physics of biological systems is a very broad subject, and I have tried to capture as much of this breadth as I could: from the dynamics of single molecules to the collective behavior of populations of organisms. This is in contrast to most other books on the subject, which really are focused at one level of organization. It is popular to organize the subject by scale, starting with the molecular building blocks of life, but as I explain in the introduction to the book, this creates the illusion that we actually know how to build from one scale to the next, and we don’t. And physicists recoil from the memorization of details, so starting with long lists is a good way to turn off a physics audience, especially if it turns out that all those details don’t immediately help you understand the really interesting questions that are raised by the macroscopic phenomena of life.

By the time I sat down to turn my lecture notes into a book, I felt that we could see the outlines of more general physical principles. I found myself teaching about protein folding, ion channels, embryonic development, and neural networks in the same segment of the course, because there is a common physics problem running through all these systems (see chapter 5). Of course, our current best guesses about these principles could be wrong, but eventually I decided that this is OK: I really wanted to teach about the search for principles, rather than focusing solely on individual examples, and this determined the organization of the book.

PT: As you may know, nearly two decades ago, a debate ensued from Adrian Parsegian’s Physics Today article “Harness the hubris: Useful things physicists could do in biology” (July 1997, page 23) and your Princeton colleague Robert Austin’s opposing viewpoint (page 27). In your opinion, is there room for multiple viewpoints, especially with respect to teaching the subject?

Bialek: Good teaching involves bringing your personality and taste into the classroom, and so there should be as many approaches to teaching a subject as there are people teaching it. That said, I would caution that the interface between disciplines seems to invite more than the usual frequency of ex cathedra pronouncements by otherwise sensible scientists: biologists lecturing physicists about what is or is not “biologically relevant,” physicists lecturing other physicists about what is and is not physics, and so on. Even the words we choose can carry implicit pronouncements, as when we talk about physicists “switching to biology,” as if we all stop being physicists in the process. I try to give some view of all this in the introduction to the book, emphasizing that physicists and biologists really do ask different questions when faced with the same phenomena, and that this is something to celebrate.

To the extent that Adrian was arguing for a limited view of what physicists can or should be doing, and Bob was arguing for a more expansive view, I’m definitely on Bob’s side, as I suspect is clear by now. I’m a theoretical physicist, and I would like to understand the phenomena of life in the same way that I understand the beautiful phenomena of the inanimate world. This is an ambitious goal, but physics is not a modest enterprise, and I don’t feel the need to apologize for my ambition.

PT: What specific feedback have you received from practicing physicists, biologists, and physics students who have used the book?

Bialek: It's not an easy book, and I hear that loud and clear. Nonetheless, most people who have talked to me about it seem to find the breadth of topics exciting, so that even if they have worked in the field for some time, there are whole new subjects that they can learn. A few people have told me—sometimes by a gentle, indirect path—that their favorite things are missing, or that the whole set of things isn't matched to what they usually teach in a biophysics course. But courses evolve.

PT: Given the chance, what are some topics that you would have added to or subtracted from the book?

Bialek: I didn't do anything about evolutionary dynamics, a fundamental problem that many physicists have been working on in the past decade. As a theorist, I didn’t talk as much about experimental methods as I might have, but this also is a reaction to the very common view of the interactions between physics and biology, in which physics contributes tools for answering biologists’ questions. Of course, there are many more specific things, but the book already is much longer than I intended, so just adding stuff wouldn't have been attractive.

Although there are 200 homework problems in the book, there are sections where I had a hard time constructing good problems to test the reader's understanding of recent developments. So rather than wishing I could add topics, I wish I could have written the right problem to go with every topic.

PT: What role, if any, are you playing in President Obama’s BRAIN Initiative, and what do you think it needs to accomplish to be considered a success?

Bialek: My colleagues and I have been very interested in building models for neural networks that use the ideas of statistical physics but make detailed contact with real data, notably the growing body of experiments where one measures simultaneously the activity of many neurons in the network. These sorts of experiments will get a great stimulus from the BRAIN Initiative. 

It will take some time for the relevant technologies to develop, but the need for a theoretical framework will soon be urgent. What is the nature of the collective activity in a neural network? Are there “order parameters” that capture the essence of this activity and provide a coarse-grained view of the dynamics involved in perception, memory, planning, or even thinking? How do we connect the enormously complex molecular events in individual cells and synapses with what we see at the macroscopic scale of networks and, ultimately, behavior? Even though theory will be a small fraction of the whole effort, I think that if we don’t meet the theoretical challenges, we won’t truly realize the potential of this initiative.

PT: What books are you currently reading?

Bialek: I'm doing a bit of recreational reading, going back through the series of mystery novels written by Sue Grafton [the Kinsey Millhone alphabet series; 1982-]. They are set in Santa Teresa, which is a lightly fictionalized version of Santa Barbara, California. The first books in the series came out around the time I was a postdoc at the Institute for Theoretical Physics, and I remember the fun of exploring the town then and trying to find the correspondence between places in the novels and the places in the real world. I am digging more deeply into my colleague Andrei Bernevig’s book Topological Insulators and Topological Superconductors (Princeton University Press, 2013), hoping to get a better view of the current excitement in that field.

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