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Walter J. Gehring: “The scientist has to try the impossible, something which nobody else has tried before”

"What I would like to try is to reconstruct the evolution of the eye all the way back to the most primitive single cell organisms"

"What I would like to try is to reconstruct the evolution of the eye all the way back to the most primitive single cell organisms"

"Evolution is more like renovation than innovation"

"Evolution is more like renovation than innovation"

Walter J. Gehring entering the hall for his investiture as Doctor Honoris Causa, accompanied by Emili Saló (Faculty of Law) and the Dean of the Faculty of Biology, Joaquim Gutiérrez (left)

Walter J. Gehring entering the hall for his investiture as Doctor Honoris Causa, accompanied by Emili Saló (Faculty of Law) and the Dean of the Faculty of Biology, Joaquim Gutiérrez (left)

"There's a genetic eye program, a leg program, a wing program, and the homeotic genes are the master switches which turn on these various programs"

"There's a genetic eye program, a leg program, a wing program, and the homeotic genes are the master switches which turn on these various programs"

"The discovery of this mutation in flies, which produces legs in place of the antennae, was purely accidental"

"The discovery of this mutation in flies, which produces legs in place of the antennae, was purely accidental"

"We must understand living organisms in light of evolution"

"We must understand living organisms in light of evolution"

21/06/2010

Entrevistes

The molecular biologist Walter J. Gehring (Zurich, 1939), Director of the Biozentrum Cell Biology Laboratory at the University of Basel (Switzerland), was awarded the title Doctor Honoris Causa at UB last 21st January, 2010. Gehring is a renowned for his research into the genetic foundations for the development of the body plan in metazoa. Walter Gehring's scientific work made a major contribution to the field of molecular genetics in the latter part of the 20th century, and his findings are crucial to understanding mechanisms of human evolution and, more specifically, the genetic foundations regulating the development of body plans of different organisms.

Gehring completed his PhD in 1965 with a thesis on transdetermination phenomena in the imaginal discs of Drosophila, leading to the discovery of  a mutation that transforms the antennae on the head of the fly into mesothoracic legs. In 1983, Gehring's team and researchers from Indiana University independently discovered the "homeobox", a DNA sequence found in genes highly preserved during evolution that controls the development of the body plan in arthropods and in vertebrates including man. During the 1990s, Walter Gehring made a discovery vital to understanding the physiology of vision, identifying and characterizing the Pax6 master control gene and its associated gene network, responsible for the development of the visual system. This finding shed new light on the evolutionary origin of different eye types.

Gehring is a member of the National Academy of Sciences and American Academy of Arts and Sciences, the Royal Society, the French Academy of Sciences, the Royal Swedish Academy of Natural Sciences and the European Academy, and is the author of over 250 articles that have been cited close to 22,000 times, covering most of the representative organisms in the phylogenetic tree of the metazoa.
 
Can you tell us a little about your connections with the University of Barcelona?
I have a long standing friendship with Emili Saló and also with Jaume Baguñá –Professors of the Department of Genetics in the Faculty of Biology-. We have shared students: I had some students of Emili in Basel and then they came back here. We also have published some papers together. Actually, I first met Emili when he was a post-doc in a lab on the same floor. So all this goes back many many years, thirty years I guess. We have always kept in touch. Emili works on flatworms and we work on Drosophila as a model system. It’s very nice to see in different model systems whether the same rules apply or whether different rules apply. I’ve visited here quite a few times, given seminars here, and then Emili takes me bird-watching on the coast here in the Ebro delta, and so I’m a hobby bird-watcher too. So there’s a long connection to the university.
 
The creation of a national genome centre has just been approved and it will be sited here in the Barcelona Science Park. What conditions does a centre of this kind need to become an international reference point? 
Well, this is a very important new development. The determination of DNA sequences has become relatively easy now, very fast, and it is important for geneticists to be able to read these genomes. In a centre like this you need quite a lot of bioinformatics, you need computer people, and you need the geneticists to make the gene assignments and begin to interpret these data. We are mostly still at the stage of a primary school boy who can read the letters, but to make sense out of the words is much more difficult. To decipher the protein sequences is not that difficult, but then the regulation of the genes is a much more difficult problem. It is very important to have such a centre surrounded by genetics people, by bioinformatics people, in close collaboration, and there should be collaborations fanning out from such a centre all over the world to compare and not to duplicate too much and so on.
 
In your acceptance speech, speech you said that the key thing in science was to ask the right question. How did you find the right question that led you to find the homeotic genes which are the key to the development of individuals?
I accidentally found this mutation in flies, which produces legs in place of the antennae, they are converted into legs. And that was just fascinating to me because it’s such a dramatic kind of effect, and therefore I wanted to understand the mechanism of how you turn an antenna into a leg and why the legs come out here and not there. So I pursued this, all the way from the legs to the atomic level. It was sort of a dream of mine to one day understand how such a complicated thing could work. It seemed impossible. The scientist has to try the impossible, something which nobody else has tried before. It’s not just like the high jumper: the high jumper puts the bar a little higher every time, but the scientist has to find new ways, new directions. And so I had this dream of one day understanding how such a mutation could work and nobody believed that I could ever solve that. So you have to try the impossible.
 
Relative to the resurgence of old theories such as intelligent design and creationism. Does the scientist have the responsibility to try to avoid this resurgence?
Yes, I think we are always trapped. We are thinking in human terms, we are humans, so we think in human terms. We think that nature was constructed by a human engineer or a human being or a perfect God similar to a human being. So I’ll mention one experiment or one hypothesis which I put forward which was completely wrong for that reason. We had an embryo with a graded pattern of one regulatory gene, and this graded pattern, a concentration gradient, was split into seven stripes. So how would you do that as a human being? You would put a wave through it, adjust the wave length so that the total embryo is divided into seven and you would have the seven stripes. But that’s not the way evolution operates: evolution first makes one stripe, then two stripes, three stripes, and takes whatever genes it needs to form these stripes, and you cannot predict that because it’s haphazard, it’s completely stochastic. And therefore I fell flat on my face with my speculations and we had to revise this picture totally. So it’s not intelligent design but it works perfectly well. Why? It has been tried out millions of times and only the good ones have survived, and therefore the seven stripes are nearly perfect. François Jacob has called this tinkering: you know, you’ll take a piece of string and a piece of metal, and you tie this together and so on. That’s the way nature operates and not by designing anything but by selecting for those who survive. And then the other point about evolution that the evolution always has to work because else it dies, so if you want to install something new like an eye you have to use a gene. Usually it’s by gene duplication: the old gene or the gene number 1 retains the old function and gene number 2, the duplicate, now has the freedom to make something new. This is more like renovation than innovation, you see. The house always has to stand: you cannot tear down the house and build it completely new, you cannot do that, you have to build on to the design of the old house, renovate it and renovate it, add some chimney or something, add some eyes, that’s the way evolution operates.
 
Is there a tool box of homeotic genes which produce the developments of living beings. How many genes of this type are needed to create an individual, how do they vary between species?
A. The basic homeotic genes are very highly conserved. It’s a cluster of 13 genes in mammals and in flies it’s only 9 genes. Interestingly enough, they are arranged along the chromosome in the same order as they are expressed, that is, the head genes are on one side, the tail genes are on the other side and the middle genes make the thorax, and so on. But you can take one gene out and transform the head into a thorax with a pair of legs and a pair of wings or you can put an eye on the abdomen or wherever you want. The information is there, there’s an eye program, a leg program, a wing program and these are master switches which turn on these various programs. Then you need something like one thousand, two thousand genes to make an eye, and these are similar in other species but not exactly the same. They are less conserved. But about 65 % of the fly retina is shared by the mouse retina. So a very large majority of the genes is the same, and with the same tool kit you can make various types of eyes.
 
Is the branch called evo-devo  which works in the field of evolutionary and developmental biology the field of research which you are most engaged in at the moment?
That’s right, I’ve come from developmental biology, then we have discovered these master control genes, and now we are moving more and more towards trying to understand evolution. Well there is a famous saying, I think by Theodosius Dobzhansky, that nothing makes sense in biology except in the light of evolution. Because organisms arose by evolution,they are a historical product, and history is still written into our genes. Therefore we have to understand living organisms on the basis of their evolution.
 
What I would like to try is to reconstruct the evolution of the eye all the way back to the most primitive single cell organisms. We probably can trace it back to cyanobacteria. These are the earliest fossils known on earth. They have survived 3.5 billion years. The earth has about an age of 4.2 billion, and at 3.5 billion you already have cyanobacteria. These are bacteria which can use sunlight to photosynthesize, they make sugars and organic compounds using the energy of the sunlight having chlorophyll, membranes and so on. But they also already developed vision. I think it would be nice to be able to see the evolution all the way back to cyanobacteria.
 
Does the discovery of these common genes in the development of individuals like the Pax-6 gene involved in the formation of the eye confirm Darwin’s theory?
I think my work very strongly supports Charles Darwin. Charles Darwin had a big problem with eye evolution, because not even his wife believed him when it came to the eyes. She said it’s absurd to think that an eagle’s eye would evolve simply by variation and selection. So he was in serious trouble. But in the final version of his book, his basic book The origin of the species, he devotes an entire chapter to difficulties with the theory. It’s a very honest book, you show me another book where an entire chapter is concerned with the difficulties, and he rules them out more or less one by one, and he can also rule out his wife’s concerns about the eye. The way he thinks about it is that he thinks there may have been a prototypic eye, a very simple kind of structure, just consisting of one photo-receptor cell, which is capable of sensing light, and one pigment cell which shields the light from one side. And if you have this arrangement, it was hypothetical at this time, this animal could determine the direction of the incoming light, because if you have to shield here the light must come from here. And fifty years later this was found, this prototype, in planarians, in flatworms which are studied here in this laboratory. They have multiple eyes of this kind just consisting of two cells, a pigment cell and a photo-receptor cell. Then some planarians have put this together, there are multiple photo-receptors, multiple pigment cells, some have developed lens-like structures and so on, and there you can see how you can start from a prototype and by selection you can improve and improve the eye until you have an eagle’s eye simply by selection.
 
Is having reached such a profound knowledge of the formation of life compatible with religious belief?
Well, it depends on what your religious beliefs are. I mean, if you are convinced that life was created in just a few days then you are definitely wrong, this is incompatible. We perhaps have to change that, and we have to adapt it to more of an evolution. I personally don’t belief in a personal God that is like a human being. I told you evolution shows that it’s not a human engineer sitting in the sky on a cloud who designs life, but life has generated by itself and this doesn’t mean that there is a divine superior kind of being behind nature. We couldn’t possibly grasp that. I’m trying to find out how nature works, and if there is something else behind nature it is difficult to say. But I would say it is not true a superior being is creating the laws of nature which are responsible for that. Physics, astrophysics can go and the cosmos can evolve and human beings can evolve in the lifeline. But I think it’s naive to think that it’s literally as described in the Bible – these fundamentalists are completely wrong. This is incompatible with what we know now, simply by measuring the time. For example, we know that the earth is about 4.2 billion years old, and it took a long time from cyanobacteria to man. But I still think it’s marvellous to have a human eye evolved. As I said at the end of my talk we can’t rationally understand everything, so the beautiful eyes of a beautiful woman will always be an enigma for us.
 
What new applications do your discoveries have in the field of the health sciences?
People always think it’s nonsense to put eyes on the legs of a fly or on the wing of a fly. We did this in order to prove that we had the master control genes for eye development. It’s relatively easy to destroy an eye, but it’s not so easy to make one. Now what is this good for, people ask in the street. My mother has macula degeneration, age-related macula degeneration. She saw very well for seventy years, and after 70 years her retina began to degenerate in the macula which is the point of highest acuity of vision, and she is becoming progressively blind. So I thought, you know, we now know a lot about eye development, can I use that for some medical application.

It was first accomplished in dogs – you always have these model systems first, and now the first few patients have been treated with the gene which they are missing or which they are partially defective, and if you provide this gene by injection into the eye and penetration into the retinal cells they can see again. One injection was sufficient for over a year now, so it is very hopeful that this may have dramatic medical applications. People now see it is not nonsense to try to prove you have the master control gene to do that because it may have very important medical applications. The wildest speculations may become true.

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