Interviews With Dresden Researchers About Innovation in Dresden, conducted by Oliver Jungen

“It’s all about simplicity.”
 

Prof. Dr. Jochen Guck

Professor Guck, it wasn't so long ago that you moved to Dresden from the Nobel Prize-winning Cavendish Laboratory in Cambridge. How are you settling in?

I've been here for a little while now. I took up my new post here in January 2012 and very quickly felt completely at home in this scientific landscape. I knew some colleagues from before, but also got to know many new ones.

No culture shock, then?

Well, what made the transition easier is that I worked in Leipzig for five years, so I was already familiar with the way things work at German universities. I knew, for instance, that somewhat more paperwork would be required here than in Cambridge, known for being one of the least regulated universities in the world - and that's certainly true. In Cambridge we had flat hierarchies, but that's not necessarily the case here in Dresden. Student support is also more individualised in Cambridge. In terms of research in this field, Dresden doesn't operate in Cambridge's shadow, however, quite the opposite, in fact.

How does Dresden's interdepartmental research compare to that of Cambridge?

Cambridge is truly outstanding in a number of areas, but interdepartmental cooperation is not one of them. Cambridge is almost notorious for the fact that it's virtually impossible to launch joint projects with other departments at the institution. I've experienced this first-hand, because I joined the institution with an aim to bring the physics department closer to the biology and medicine departments... but disappointingly, my attempts were unsuccessful.
This failure is fatal, because cooperation like this led to the birth of molecular biology at the Cavendish Laboratory. James Watson and Francis Crick, who discovered the structure of the DNA double helix in 1953, were both physicists. But after that discovery, the physics department was very much segregated from other fields at Cambridge.

And in Dresden?

Things are quite different. The academic standards in Dresden are comparable to those at Cambridge, but a general attitude prevails that you can achieve incredible things through cooperation. The most interesting things always happen at the point where disciplines converge - and identifying and exploiting these intersections is Dresden's speciality. In fact, this is already very apparent to me here; when you talk to Dresden researchers, you see this instant enthusiasm bubble up for your work, and then a concrete plan is formulated regarding what can be achieved by working together. There are more opportunities here for joint projects and cooperation than anyone could possibly realise.

You were lured from Cambridge to Dresden with an Alexander von Humboldt professorship, bringing the five million euro international research promotion prize with you to Germany. This prize, the largest of its kind in Germany, will enable you to largely avoid bothersome scientific funding applications for five years. However, you're also familiar with the normal conditions at German universities; do you think that cutting-edge research is also possible at our other institutions?

I would say so. But in any case, huge sums of money aren't usually required in my field to make progress. I don't need a billion-dollar particle accelerator or the like. In my field, the most exciting things happen in the mind. Of course, we do need some not-so-expensive devices such as lasers and microscopes in order to test our results. We can normally obtain these through a simple application for third-party funding. A source of funding like the Alexander von Humboldt professorship is naturally always going to be useful, but even without it I would still probably have had better funding opportunities in Germany than in the United Kingdom. As far as I can see, there's probably no country in the world with a better research environment than Germany. At the moment there are cutbacks even in the USA, and many researchers are having to retire from academia.

You've previously worked as a business consultant, and in Dresden there is a strong entrepreneurial spirit. Are you also interested in university start-ups?

Oh yes, I'm definitely interested in them. The reasons for this are founded in the history of research. Those who develop new methods of measurement want to be able to distribute these to as many people as possible, and in order for new methods of diagnosis and prognosis to be implemented, they have to be given up to the private sector. One advantage of setting up your own company is that it enables you to retain control.

You don't have any concrete plans to do this at the moment, then?

Yes and no. I'm still working on commercialising the optical stretcher with my doctoral supervisor in Leipzig. This is a laser-based instrument with which we can study a number of cell characteristics. I first stretched cells with light in 1997, but the process was very much an improvised one at the time. The so-called ‘stretcher' has been a machine in its own right since around 2005. We're currently working on improving the technology further... what's the minimum number of cells required to start the process, for example? But I also have plans to move things forward now and am subsequently in touch with elements of the local biotechnology industry at the moment.

Why has the physical dimension of cells been researched so little in recent years compared with their biochemical and molecular dimensions?

I don't want to diminish what my colleagues in biology have achieved over the last few decades. Our main concern is understanding the genetic code; indeed, it's truly fantastic and terribly important work. And there are still so many important questions that have been left unanswered. The reason our research has been mainly focused on biochemistry is simply that this field successfully unravelled the all-important encryption of our DNA. All of a sudden, we had the opportunity to completely revolutionise our understanding of cells on the molecular level. We became fixated with genes and proteins. At this point, other aspects got pushed into the background a little - even the physical, that is, the study of cells as “physical lumps” with certain characteristics.

Was a biologist's view too detailed?

There's a very apt saying here: we couldn't see the forest for the trees. Anyone who studies the roughly thirty thousand different molecules in a cell, which are each also present in great numbers, will only succeed in isolating and examining a few of these and their interactions. We therefore lost sight of the bigger picture. But it can't hurt to forget all of these details and study the nature of cells on a different level.

Here's an example: Does someone watching a rubber ball bounce up and down look at the ball and see what the enormous number of atoms inside it are doing? It's possible, but so complex that they will have trouble describing the bouncing of the ball in this way. It's more meaningful to say: I know that atoms are there, but they don't interest me right now. I can, however, describe the object formed by all of these atoms together, and I can determine its spring rate - its elastic modulus - which can, in turn, help me to explain quite simply how the ball bounces up and down.

As a professor in cellular machines, you are therefore now applying this perspective to other fields. What could biologists learn from you?

Not all of the ideas we're pursuing are new. Indeed, many of them existed as early as the beginning of the 20th century, but back then we didn't have adequate measuring instruments. We're talking about cells here, after all. Even when looking at them en bloc, they are extremely small. Indeed, the diameter of one cell measures about a tenth of a human hair across. Consequently, the first problem we had to solve was how to examine cells' mechanical characteristics. We asked ourselves: how can we squeeze a cell in controlled conditions? Now - thanks in part to the optical stretcher - we know how to do this. The fact that I'm a physicist helped me a great deal in this endeavour. Indeed, you have to be able to sufficiently empathise with biologists to know what could be of interest to them, but as a physicist, you don't have this glut of specialised biology crowding your mind, which enables you to look at the subject with fresh eyes.

For you then, it's a question of the mechanical and optical characteristics of cells and tissues. Are these not also determined genetically?

Cells are physical objects which move in space and time. If a cell wants to crawl from A to B - where there may be little room - its deformability is important. This deformability is, indeed, partly determined through the presence of certain genes and proteins, but the most important description for us in this case is the one which indicates how rigid or deformable the cell is.

It's a sort of ontology then, to a point? A return from pure theoretical models to the perceptible reality?

It helps me to think in these terms, at least in dealing with this issue, because I cannot think in proteins. The movement of cells, for instance, is always caused by forces, though proteins also influence this. Without forces, nothing moves. And it generally holds true in physics that a theory is correct if it is simple and beautiful. It's all about simplicity.

Let's discuss some specific research in this area - you've studied cancer cells in this way, for example.

Yes. Here, too, we had to answer the basic question of how mechanics are connected to cellular function. Do these cells have an elastic modulus which they can adjust themselves, or is the process pretty arbitrary? All cancer cells - with the exception of the leukaemias - are softer than normal cells. And here we can use the simplification process once again. There are over 200 different genetically defined types of cancer. If you look at cancer on the genetic level, you therefore have to observe 200 different processes. However, if you look at cancer cells from a physical point of view, there is this one group of cells that all become softer. Now you can ask why they do that. Is this a key characteristic? In my opinion, yes, because cells must be soft if they want to move. They have to be able to squeeze through other cells in the group.

As such, what we have here is an easily measurable physical parameter - cellular deformability - through which we may be able to diagnose cancer. This knowledge may even enable us to predict ahead of time which cancer cells might spread, because the cells which metastasise are, once again, softer than other cancer cells. Depending on the number of very soft cells in a tumour, we could therefore be able to determine the probability that metastasis will occur in the future. This was not even conceivable before now. All of this could enable us to respond quicker to metastatic developments when treating the disease, which could, in turn, lead to the development of new cancer treatments. It might then be worth investigating whether cells in tumours can be fortified, and if so, how this can be done. If you fortify the potentially dangerous cells, they will be unable to move or disperse elsewhere. The cancer would then not be able to spread throughout the body.

This is a really exciting development. Is this a major project of yours here in Dresden?

Oddly enough, this is an area in which we aren't really working anymore. We are researchers and we are interested in those things which we have not yet discovered. In this case, we feel we have sufficiently understood and publicised the phenomenon. Now, the medical community needs to take ownership of the matter and carry out further research into this potential new treatment.

What are your main projects in Dresden, then?

There are two key projects that I can talk to you about today. In addition to the Humboldt professorship, I have secured a 1.5 million euro starting grant from the European Research Council for five years. I'm using this grant money for a project regarding the diagnosis of blood poisoning. Inflammatory diseases are usually combated by our white blood cells. As such, it seemed appropriate to examine whether the white blood cells of people who are ill are softer or more rigid than normal white blood cells when inflammation is present in the body. We wanted to investigate whether it is possible to use this knowledge to infer the severity of the inflammation and thus make an earlier diagnosis of blood poisoning. As a result, we're using a method we've got down to a fine art in a new field, with this work requiring the use of the optical stretcher. Alongside this project, however, is another truly visionary research project on the central nervous system which I would like to fund using my Humboldt professorship grant.

Are you breaking new ground with this research?

The project deals with how cells respond to the mechanics of their environment, and the foundations for this work were actually laid some years ago by a colleague in the USA. In his experiments, he showed that when cells - stem cells, for example - are placed on a very soft substrate, they spontaneously differentiate towards nerve cells, which are found in very soft tissues in the brain. When applied to a somewhat more rigid substrate, the same cells would spontaneously differentiate towards muscle cells - and muscle tissues are more rigid than nervous tissues. On a more rigid substrate again, the stem cells would differentiate towards bone cells. This therefore means that cells react to the rigidity of their environment. We're drawing heavily on these results for our own research.

Can you briefly outline your key research questions?

Firstly, we need to know whether nerve endings are predisposed to grow in soft tissue, that is, if they generally stay away from more rigid areas. If you have a damaged central nervous system, if you have paraplegia caused by injury to the spinal cord, for example, then an inflammatory reaction takes place almost immediately, since blood cells make their way into the affected area and orchestrate an immunological response to the injury. Consequently, material is distributed which reinforces the injured area, so-called fibrosis. It is well-known that no nerve endings can grow through this scar tissue, which is formed by the supporting glial cells.

A biologist will look at this process and say that this scar tissue must exhibit certain biochemical factors which signal to the surrounding cells ‘I shouldn't grow here anymore'. Without a doubt, this is partially correct, but it's not the whole truth. The hypothesis on which we are currently working is that the mechanics of this scar tissue also play a role in the process. We are working from the premise that scar tissue is more rigid. This is actually pretty obvious, but has never been scientifically proven, so we're now measuring this rigidity.

We believe that nerves do not grow in scar tissue simply because it is more rigid than the surrounding tissues. We also believe that the glial cells remain in the scar tissue and continue to provoke an inflammatory reaction. Finally, we are hoping that we can modify the mechanical characteristics of the scar tissue so that the glial cells are less reactive and thus cause less inflammation, meaning that nerve endings are more likely to grow into this area. We think that these mechanical components could, alongside biochemical processes, play a vital role in healing paraplegia. If we are able to prove this within the next five years, it would be, well...

... revolutionary! That leads me to completely different question. I detected a prevailing sense of release when reading articles about your research. Is it not a sometimes a great burden to represent such a beacon of hope - particularly for those affected, cancer patients and paraplegics, for example? It's quite possible that your research won't throw up the expected results.

It can be. It would surely be presumptuous to say that within the next five years, I can make a vital contribution to this area of research which has puzzled scientists for so many years. At best, I can say that I have an interesting approach to the problem and that I am going to study it exhaustively. This implies that mine is perhaps not the right approach. Indeed, it is the scientific method to formulate a hypothesis and then try to disprove it. The longer you fail to do this, the more likely it becomes that the hypothesis is correct.

However, your point about giving hope is an interesting one. For example, a few years ago I received a call from a sheikh in Saudi Arabia who said that his brother had cancer and that he would fly him out to me immediately - he would be in Leipzig in two days. The sheikh asked me to fetch his brother from the airport and then do everything in my power to heal the cancer. At this point, I had to tell him that he'd unfortunately misunderstood something; that I'm a researcher, not a physician. I told him that his brother would be best treated in a hospital. This is a scenario which we academics face time and time again.

Perhaps we sometimes get carried away with enthusiasm for our own work and thus awaken these hopes. What do you think? Should we researchers be more careful?

I don't think you can have any real influence on the matter. It's almost an unwritten rule of the media to hype up anything potentially sensational.
Perhaps we scientists should provide clearer explanations regarding the nature of our research. It may well be that the general population does not always truly understand that we can't carry out targeted research. A researcher simply cannot guarantee, even for five million euros, that he or she will be able to reveal a finished product after five years. All you can do with this kind of funding is create the possibility of trying things out which you would otherwise be unable to try. Indeed, all of the great leaps made in medicine - like penicillin - were the result not of targeted research, but of experimentation and play in a laboratory.

Do you feel that Dresden is a good playground?

Yes, especially given that prominent local cell and developmental biologists are trying to answer similar questions and are open to cooperation. This is something that makes Dresden incredibly attractive to me as a researcher. Simply put, there is currently no better place in the world for my kind of research than Dresden.

Thank you for the interview.
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