Prof. Gero Miesenböck: A man of the mind

Image credit, www.cncb.ox.ac.uk

Please note this article is co-authored by both Christopher Haggarty-Weir and William Godfrey. William had the idea of interviewing Prof. Miesenböck (one of William’s current favourite scientists) and came up with the majority of questions, in addition to writing up the transcripts from the recorded interview. Christopher conducted the interview and attended the public lecture in Edinburgh. Also fellow readers, please accept our apologies for the delay in posting this piece; our website was hacked and had to be taken down for several weeks until we could sort the issue out. Anyway, I hope the wait was worth it!

In April, Mostly Science editor Christopher Haggarty-Weir had the fortuitous opportunity to interview Prof. Gero Miesenböck at the Edinburgh International Science Festival. As 2015 is the International Year of Light, the theme was on the utilization of light in scientific research. Prof. Miesenböck was part of a panel that were giving a public talk on optogenetics and optopharmacology. For those who have never heard of optogenetics before, I would strongly recommend William Godfrey’s previous article on Mostly Science, which can be found here.

As a quick introduction, Prof. Miesenböck studied medicine in his native land of Austria and eventually found himself conducting post-doctoral research at the Memorial Sloan-Kettering Cancer Center in New York. He started his own lab at Memorial Sloan-Kettering in 1999 and moved to Yale University in 2004. During 2007 he made the jump back to Europe to take up a professorship at the University of Oxford, where he became the founding director of the Centre for Neural Circuits and Behaviour. Prof. Miesenböck was one of the developers of optogenetics and invented several techniques which have taken the scientific world by storm, and this year led to him being made a Fellow of the Royal Society, a truly great honour. So without further ado, here is the interview we were fortunate to get.

Christopher Haggarty-Weir: When you came up with idea of using light activated ion channels to control parts of the brain, and did the experiment for the first time did you think it would work?

Gero Miesenböck: It was a high-risk project with a pretty uncertain outcome. I had just become an assistant professor starting my own lab when I had the idea of optogenetic control. Because of the risk involved, this was not the only project I was working on.

CHW: You started off at the Sloan-Kettering Cancer Center, was that in cancer research?

GM: I worked at a cancer research institute, but the philosophy of the Institute’s leadership at the time was a strong emphasis on basic science; they would support excellence above all. So I never actually did cancer research, but initially worked in a leading cell biology lab – I was a post doc with James Rothman, who won the Nobel Prize in 2013 for discovering the mechanisms of intracellular membrane trafficking.

CHW: So a more abstract question, but one that comes up a lot in popular science, do you think we will be able to store consciousness as data in say a quantum computer?

GM: That’s a really thorny issue. To begin with, people are still struggling to agree on a definition of consciousness. Some say it’s to do with those mental events that require that you attend to something over several seconds. Others say it’s qualia that are key; for instance if I look at your jacket, my subjective, conscious perception is that it is red, but it is difficult to make sure that this subjective sense of redness is experienced in the same way by somebody else.

Thinkers have come up with possible tests to check whether another person (or even a machine) might be conscious. There is the famous Turing test popularised as the “imitation game”: if you were able to have an extended conversation with someone or something, but couldn’t see your conversation partner, and if that someone or something could provide reasonable, convincing answers to your questions, then would you be conversing with an intelligent being? A philosopher at Berkeley, John Searle, came up with the Chinese room test to show that this is not necessarily so. Imagine a question is given to you in Chinese and written down on a tablet, and the tablet is pushed through a slot into the room you are in. You have no comprehension of Chinese, but you can look at the Chinese characters in a huge dictionary and find a plausible answer based on the rules written down in that dictionary. You then find the tablet that corresponds to the seemingly intelligent answer and push that back out and the person outside would be fooled thinking you are a conscious speaker of Chinese. It’s a long winded answer saying that I think that the problem is very very hard, and perhaps also that there are other problems that are more fruitful and interesting to think about.

CHW: How far do you think we are from realising the translational potential of optogenetics to alleviate mental illnesses and brain disorders – through, say, neuroprosthetics?

GM: There is a bunch of issues to consider here. The first is legal and ethical issues.Is it OK for us to interfere with someone else’s brain? I think we are already doing that to some extent – whether you prescribe a psychopharmaceutical or are offer your friends a scotch at the end of the day, you are interfering with the brain. Whether you interfere through chemical or physical means makes really no qualitative difference at all. Then there is the technical issue. In order to achieve optogenetic control, you have to introduce a foreign gene product into the nervous system. In other words, optogenetic control requires some form of gene therapy, but with the added complication that you are not just repairing a defective human gene but putting in something foreign. And finally there’s the intellectual problem. In order to correct a brain disorder like schizophrenia or depression, and in order to do this rationally, you have to have a mechanistic understanding of what is going on in these disorders and what you need to change to correct them. In most cases we simply lack that understanding. I would therefore consider it unlikely that optogenetics will be used any time soon for actually curing something like schizophrenia. But we will probably see the first clinical applications in simpler conditions where we have a better mechanistic understanding, in particular, in the correction of retinal lesions for the restoration of vision.

CHW: Are there any novel applications of the technology you would like to see?

GM: There are two major developments that I think need to happen. One is to exert control at the level of individually resolved neurons. In most of the experiments that we do right now, a whole population of neurons is exposed to the same kind of control signals, and we know that the brain does not really operate like that, with large populations of neurons firing in synchrony. So to play with activity patterns in a more refined way would be a very important technological development. Secondly and related to the first point, is the need to address specific sets of neurons with greater precision using novel, unconventional address labels. That will be achieved through improvements in the genetic targeting of the genetically important proteins.

CHW: Has doing neuroscience and examining the brain in a reductive manner changed the way you see others, if yes or no, how so?

GM: We all have this feeling that somebody is home, that there is a “self” residing somewhere within us. I do think that my conscious self is something that the brain creates and that there’s nothing to it but the concert of large numbers of neuronal impulses. Francis Crick wrote a book that he called ‘The Astonishing Hypothesis’ in which he says exactly that – that you are nothing but the sum of the neuronal activity patterns in your brain. I don’t find that particularly astonishing; I find it almost a commonplace.

CHW: What do you look for in a young scientist?

GM: It’s a combination of traits I look for. The most important traits are independence, intellect and curiosity, because everything else you can learn. Intellectual independence is very high on the list. All my post docs are expected to manage their own projects. We obviously talk each week about what they are going to do, but not on a day-to-day basis; they have to be capable of doing that themselves. It’s also really important to have passion for doing research because there’s few other rewards in science. It’s a tough, tough career to pursue and so just doing it has to be its own principal reward.

CHW: You have a medical background, but did you ever practice clinically? What made you go into research?

GM: I like being able to give a failed experiment a second try, and in medicine, if you have a failed experiment it’s hard to repeat that. Joking aside, I’ve always felt that one stands on quite shaky ground intellectually in medicine. One does incredibly invasive things to other people, and yet there’s this saying that 50% of medical knowledge is wrong, but the problem is we don’t know which 50%. I was uncomfortable with that.

Another major difference is that, in science, you look out for the non-routine, for the new, for the unexplained. In medicine, the better, the more experienced you get, the more automated your reasoning becomes. If you run through a differential diagnosis of some kind of condition, you have the flow chart internalised completely, which is quite the opposite of what you are doing if you’re a scientist operating in uncharted territory.

CHW: With ever more people entering scientific research and with the grants system being stretched out, how can we have sustainable investment in research?

GM: I think that the situation is quite difficult because there is simply not enough money for basic research. I particularly deplore that many funding agencies have shifted their support from basic to translational research. I as a taxpayer would always insist that my money goes to basic rather than translational research, because in a capitalist Western system, as soon as there is something to translate, as soon as there is a product that can be brought to market, there are mechanisms to take care of that. Basic research has historically provided the most valuable ­insights – valuable not only in the intellectual sense but also in the economic sense. That tends to get lost at the moment. There is also a tendency of some funding agencies to force conglomerates of researchers into collaboration. Innovative science is ultimately a grass roots enterprise driven by individuals – it’s people being allowed to follow their ideas, and that needs to be protected.

Prof . Miesenböck and Christopher Haggarty-Weir

(taken with my low res camera phone).

A very thought provoking interview. Please give your thoughts down in the comments section. We at Mostly Science would like to thank Prof. Miesenböck once again for taking time out of his very busy schedule to allow this interview to take place. I know that William and I would relish the chance to chat with him again in the future.

Also readers, if you have any questions for Mostly Science, don’t forget that you can submit them and we will not only answer your question, but we may even turn it into an article if it is interesting enough.