Herbert Levine is a Professor of Bioengineering and Director of the Center for Theoretical Biological Physics at Rice University in Houston, Texas. Though not a PS-OC member, he has been a regular attendee at PS-OC meeting to provide his perspective and expertize.
Herbert Levine: That's correct. I've been to several of these meetings. I think of the PS-OC staff, sometimes, wants advice from people in the biophysical community, who are a little bit more neutral about individual PS-OCs. So the way they do that, is they bring other people in who are interested in the subject, but are not committed to working on any particular projects within the PS-OC framework.
Pauline Davies: What do you think of this meeting because this is dealing with theory in cancer?
Herbert Levine: It’s rather far-reaching for the PS-OC to try something like this, as I think we've seen in some of the presentations and a lot of the discussion, it's still a rather controversial area to figure out what role theory is playing, what role theory could be playing, and where we’ve gotten to in that effort; and I think it makes it quite interesting, but rather controversial to see all the different viewpoints expressed by the people at the meeting.
Pauline Davies: You were involved in a session yourself, weren’t you?
Herbert Levine: I was serving as chair of the session this morning on the stochastic effects.
Pauline Davies: I thought that session was fascinating; can you tell me what it was about?
Herbert Levine: I think there's ongoing debate going on about the role of genetic changes, mutations and non-genetic changes in many aspects of cancer. I think maybe the most important being the process of drug resistance emerging once treatment is applied and the traditional viewpoint, at least the viewpoint that is expressed in most of the published literature, is that resistance emerges from specific genetic changes that perhaps pre-existed the treatment or maybe occurred because mutation rates were very high due to genomic instability. While that may be the case sometimes, I think the viewpoint be expressed in those talks was that there's a whole other set of possibilities that roughly emerge from thinking about phenotypic changes of the type that occur regularly in differentiation from stem cells onto very specialized cells. Those phenotypic changes can also encode genes and processes that enable cells to be drug-resistant. Either that can cooperate with the genetic mechanisms such as the possibility that those enable cells to survive long enough to then find genetic solutions to the drug that are applied, or can in some such a supersede genetic mechanisms whereby some cells are in various states that are just inherently less sensitive to some of the drugs. I think that was what the session was about and we heard both from a more theoretical, more mathematical perspective from Sui Huang and then a more clinical application orientation from Thea Tlsty. So it was quite an interesting session, as indicated I think by the vast amount of questions and discussion afterwards that unfortunately had to be cut off when the time limit ran out.
Pauline Davies: Yes, that was certainly a very fascinating session that you chaired. What else has struck you about the meeting?
Herbert Levine: The community seems to be struggling towards understanding, in some sense, what a theory would look like or what theory would predict and what types of things it would encompass. I think one of the things that might be useful is for people to look at other examples where theory, I think, has more advanced in terms of playing an acknowledged role in the field; there are certainly physical science examples of that - that’s easy. But also, I think, there are medical examples of that in admittedly simpler cases. I think that would actually help people see what we’re all struggling for. Some people understood that, but some other questions seem to be in some sense, not really understanding what this amorphous notion of a theory was actually going to do for them. So, that struck me as an area which maybe needs to be pushed forward a little bit within the program.
Pauline Davies: Looking to the future, what questions do think physicists and physical scientist can help oncologist with?
Herbert Levine: We need some type of theory that explains why cancer is sort of an inevitable consequence of multicellular organization. We need to understand if cancer were just a simple disease that was due to a couple of genes that went wrong, we would have found ways, evolutionarily speaking, to prevent those are happening; we would've found ways in terms of pharmacology of treating that. So, somehow it's a disease that inherent within multicellular organization and evolution of multicellular structure. I think there was broad agreement with that, although stated very differently by different people, but I think there was broad agreement that understanding cancer really does mean understanding how multicellular systems evolved, how they develop and how they maintain some type of homeostasis in functioning organisms. But that hasn't been translated yet into some, I hate to say mathematical, but maybe I should, but at least some concrete framework that then allows you to say: “Well if we want to study this aspect of cancer we need a model system which is at least as complex as this. We can work with lampreys but we can't work with sponges,” in the language that was just used in one of the recent questions. We don't understand which aspects of the problem really require cell-cell communication and which parts don't, and so what are we going to learn by experiments done by drugs given to single cells? We clearly can learn a lot but clearly there are things that we can’t learn. Those questions don't have a natural way to be answered, so they are all being answered sort of in scattershot approaches that, I think, hopefully over time will become a more coherent theoretical framework. We’re all struggling towards that and it looks good in the sense that it's nice that people understand that would be useful, but I think we're also not there yet.
Pauline Davies: And finally do you find that this PS-OC has value?
Herbert Levine: At the topmost level it absolutely has value in the sense of the NCI making a clear statement to the community - and the community now being very broadly defined; everybody from the Washington administration, to oncology boards, to cancer biologists - that moving forward in cancer treatment and understanding cancer really does require participation of the physical science community. I think at that level it was an absolutely brilliant way to go about doing that and it’s been absolute success. So, whenever I describe it to physics students or bioengineering students (and explain) that this is an area that they really can be working in, I use the PS-OC as a clear example. So at the topmost level absolutely, no question. Something like this will continue to be essential in drawing people into the cancer field who have enough of a different perspective, and enough of a different set of methods at their disposal, that one can really make progress faster than one would've otherwise.
Pauline Davies: Thank you so much.
Herbert Levine: Thank you.