Evan Eichler is Professor of Genome Sciences at the University of Washington in Seattle.  He will be giving the Mendel Lecture at ESHG 2012 on Tuesday, June 26, 2012 at 13.30 hrs on genome structural variation, disease and evolution.  He talked to Mary Rice about his life and work.

Apart from a handful of animated filmmakers, few people can claim to have had their destiny shaped by rabbits.   Evan Eichler is one of those few.   “I grew up on a farm and my mother bred angora rabbits for yarn.   She wanted to introduce some new colours, but without using dyes.  She told me that she'd read that there were rare colours such as fawn, blue and chocolate cream, and I decided to try to help her derive lines of rabbits with these colours.”

Eichler read the subject up in textbooks.  “In fact it looked pretty simple.  There were five coat colour genes and I used this information along with Mendel's laws to help my mother mate the correct pairs until we came up with the right colours and lines that bred true.”   His mother was delighted, but his father was less enthusiastic. “He wanted me to be a proper farmer or go to university and become an M.D., not just play around with rabbits.”

But his father was already too late.   The experience had decided Eichler that he wanted to do genetics.  “By the time I was fourteen I knew that I was going to be a geneticist for the rest of my life, but I can truthfully say that the only time in my life that I did real, classical, genetics was when I was breeding those rabbits!”

As an undergraduate at the University of Saskatchewan, he was disappointed by the dearth of molecular biology.   “I wanted to learn about recombinant DNA and genome sequencing, but the curriculum had a heavy emphasis on ecology, population biology and evolution.”   The University allowed him to do some advanced biochemistry as part of his electives.  In retrospect, though, he says, he remains grateful to the evolutionary content of his degree course.  “It forced me to think about populations and hardcore evolution, and it's stood me in good stead with my subsequent work.”

He then headed to Baylor College of Medicine in Houston, Texas, to join the lab of David Nelson, who had just discovered the mutational mechanism that causes Fragile X syndrome.     “David was a fantastic mentor - hugely knowledgeable and very approachable, but the most important thing for me was that he let me go off on tangents that were unrelated to his own research agenda.  I think that's when I began my duplication work - in my last couple of years as a graduate student.”

It's this work that has driven the rest of his career to date.    Understanding how genomes evolve, and how genes are disrupted during evolution, has led him to discover copy number variants associated with developmental delay and how his research can make a difference in people's lives.   “This has been incredibly important to me. Even though I'm not a clinician, my work has meant that  families seek me out, leading to lots of unexpected interactions as well as insights.   There have been some really heartbreaking stories, but also a lot of appreciation for the work we are doing.  To me, this is far more important than a high-profile paper in Nature or Science - we are making really fundamental discoveries as to why kids suffer from autism, developmental delay and intellectual disability.   Even though we're only solving a small piece of the puzzle, for affected families this is the only piece that is relevant to them.” 

His work has led to the discovery of around 15 different genetic forms of developmental delay. The fact that families with a specific mutation can come together and support each other is hugely important, he says.  “Even if only a small fraction of individuals are affected by a particular copy number variant and mental handicap, for example, those families are empowered by this knowledge.  They can share practical real-life solutions for dealing with it, and mothers who have been raising kids for thirty years can now talk to mothers of newborns with the same mutation. 

“To me this is priceless, but it's the part that scientists miss all the time.   They say: ”˜What is the value of discovering such rare mutations?' or ”˜How can this possibly lead to a cure?' Cures and treatments may come later but knowing why your child has mental illness and then finding other families with children with the same mutation can provide immediate help via support groups.    Moreover, if there are going to be therapies down the road that won't cure but will improve quality of life, we now know which groups to go to with that information.   Breaking down “umbrella disorders” like autism and mental illness into their different genetic causes, I believe, will be hugely important in the future,” he says.

His hectic schedule doesn't leave a lot of time for recreation, but growing up on a farm, Eichler has retained an interest in the great outdoors.  “I do quite a bit of skiing, I like winter sports and love to hike in the mountains around Seattle.   Apart from that, I try to spend as much time as I can with my family - my wife, three sons and a daughter.”

If he hadn't been a scientist, Evan Eichler thinks he would have liked to be an historian.  “It fits in well with my work and my own interest in evolution and population history”, he says.  “As a kid, I became interested in my own family history including traits that were passed down from grandparents and great-grandparents.  I loved to hear stories about the “Old Country” and I can remember talking to my father about what the life of a historian might be like.  He said it would probably be pretty tough; you'd spend many years in school to become a professor, with little pay, and spend countless hours researching areas of understudied history.   I could have done that, and probably enjoyed it.  

“But the thing I prefer about genetics to history is that history is often too subjective and genetics is so, in principle, objective.   Either you have a mutation or you don't.  Either it leads to a trait or it doesn't.  Genetics and genomes, in my mind, are black and white””a tabula rasa upon which the predispositions to disease and the history of our species is written.  It's less partial than a historian who, however good he is, always puts a slant on it or has been biased by those who kept records.”

Putting too personal a slant on things is alien to his character.  “One thing that has always bothered me in science is the degree to which it is influenced by politics.  In science, just as in any kind of business no matter what it is, there's politics and the politics is linked to ego.  Certain people's egos are huge in science.   Everybody's guilty of this to some degree; every scientist has to have an ego.  In order to do quality work you want to be best, you want to be first, and that's normal.  But what I don't appreciate is when ego becomes so big and influential that political considerations outweigh what's best for science in the long term.”

So what will he be telling the conference?  “I'll be talking about the role of duplicated sequences, their role in predisposing our genome to copy-number mutations associated with autism, developmental delay and epilepsy and their role in the creation of gene innovations important in the evolution of our species”, he says.  

There seems little doubt that this work will lead to further discoveries of benefit to mankind, and that many more people will have a reason to be grateful to those rabbits.

Professor Peter Lichter is Head of the Division of Molecular Genetics at the German Cancer Research Center (DKFZ).  He will be giving the ESHG Award Lecture at ESHG 2012 on Tuesday, June 26, 2012 at 14.15 hrs.  He talked to Mary Rice about his life and work.

Peter Lichter was fascinated by the natural world from an early age.  “Ever since I was a little boy I had a very close relationship with and a great interest in nature, observing things and so on.  From very early on I watched the development of frogs from the eggs and that sort of thing.  This was entirely my own interest, but my parents supported me in it.”

Later on he became interested in animal behavior and at around fifteen years old he decided that he would study biology in order to become a behavioural scientist. “Then, during my studies at the University of Heidelberg I went through, let's say, an evolution.   I realised that simply being able to describe behaviour would not be enough to satisfy me, in particular because many of the main principles of imprinting and so on had already been discovered.  I wanted to dig deeper into understanding behaviour.   So I joined the human genetics department in Heidelberg in the groups of Professor Vogel and Professor Buselmaier.  They were running programmes on behavioural genetics, and I worked there for four to five years, looking at the genetic background of certain behaviours in mice.   During that time I became very much acquainted with the overall development of human and molecular genetics as such, and later on I switched to molecular genetics for my PhD thesis.”

Lichter has been at Heidelberg for a quarter of his life, he says.   Its location allows him to indulge in his other passion - the mountains.   “Whenever possible I go hiking, skiing and try to go on long trips, in particular in the Alps.  I'd like to extend that to some other mountain ranges outside of Europe.”

As well as allowing him to discover the mountains of North America, it was during his post-doctoral stint at Yale he became involved in developing the protocols of FISH.   “I'm proud that I've contributed to a number of new technologies which opened up many new fields, such as the development of certain FISH protocols which allowed us to bridge the molecular world with the world of cell biology /cytology.   That was really a breakthrough”, he says.

He is proud, also, of the way in which the technologies he helped to develop have made it into applications that benefit patients, particularly in the diagnostics that are so important when making therapy choices.   “In cancer, we have identified prognostic sub-groups in certain types of tumours; if you look at the treatment of patients today, particularly in leukaemia, but also in many other tumours where our work has made a contribution, many of the treatment decisions are fully dependent on the genetic make-up of the tumors to allow stratification of patients into different risk groups.   Although in some areas genetics hasn't yet produced the patient applications we might have hoped for, that's not the case in cancer.

 “In the tumour field we have had great success; in the practical world we are using targeted therapies with far fewer side effects of the treatments, so it's also an improvement of quality of life.  And it is absolutely feasible and foreseeable that we will develop many more of these approaches to the benefit of patients.  It's not unrealistic to say that we at least will be able to see many types of cancer  become chronic rather than an acute diseases and in many cases we even hope to be able to cure cancer like we can do these days already for some tumour types”, he says.

Science continues to excite and surprise him.   “There are so many new things coming out every day.  At the moment we're very involved in full genome sequencing and I'm constantly surprised about how many novel things we find.   But the downside of that is that you end up having to do a lot of paperwork to get enough money to be able to work all this up.”

Lichter says that he has never wanted to be anything other than a scientist.  “I was in the lucky situation that I knew pretty much what I was most interested in and my goal was to find a profession where I could do these things, and it all turned out ideally from my point of view.”  He would like to have the chance to spend some more time in his beloved mountains, though.   Perhaps when he retires?  “Under German law I should retire in twelve years, but who know what will happen twelve years from now?” he says. 

So what will he be telling the conference?   Primarily, he says, he wants to get across the immense enthusiasm he feels about working in science and making discoveries.  “I will try to give a short summary of some of the findings we have made in the past, with the breakthrough methods that we have contributed to, but most important, I think, is to share the excitement that we are experiencing at the moment with the new findings in the course of high resolution genome analysis using ultra-deep sequencing approaches.

“If I have a normal life expectancy I should be able to learn about all the genetic changes that can occur in tumours before I die - maybe not understand all of them, but at least know about all of them.    That is something that only a few years ago was unthinkable.  So it's very thrilling, and on top of the genomic information we now learn slowly even more about the epigenetic regulation of the genomic information, which is probably as important for understanding disease pathophysiology as the genomic information itself.    Almost every week we learn something new.   We have just contributed to the further deciphering of a novel genetic instability phenomenon called chromothripsis, which I am eager to work up and understand further, and I think that this is the type of excitement I would like to bring across.”

Given his track record of discovery, it seems likely that science will continue to excite Peter Lichter for a very long time to come.