Shiplake College News

Shiplake Spotlight on…. Science

We celebrate our Old Viking Community and what they have gone on to do after leaving the College. This is a great source of inspiration to our current students and our alumni.

Our spotlight is on Science and we are delighted and honoured to speak to Arthur Burghes (74E) on how he turned his passion into a career.

Name: Arthur H.M. Burghes PhD

Job Title: Full Professor from Ohio State University (since 2002), recipient of the Distinguished Scholar Award from Ohio State University (2019).

Which field of science do you work in?

It is important to understand that as for everyone, there is a historical timeline. My undergraduate work was in microbial and cell biology, my doctoral work was in protein biochemistry, and my research from postdoctoral research scientist to this day has been in molecular genetics with an emphasis on human genetics and genetic diseases. This progression is partly due to the fact that molecular genetics did not exist as a filed when I was a university student.  The majority of my work has used molecular techniques identify causative genes and develop therapies particularly for neuromuscular (Duchenne Muscular Dystrophy) and motor neuron diseases (Spinal Muscular Atrophy).

When did you realise you had a passion for science?

Early in my education at Shiplake (1969 to1974) I realized that science was my passion. My first influences were from my mother who graduated in honours Physics from the University of Manchester. She developed an updated and accurate mathematical calculation (late 1950’s) that allowed radiation of the lungs for cancer treatment without burning the tissue. In other words, she took into account the lung is like a balloon, not a solid object when working out the radiation dosage calculation. I also had an early fascination with chemistry resulting in the throwing of a chemistry kit out the window when it caught fire at home.

At Shiplake, I quickly realized that my abilities did not lie in the arts, literature or anything that required lots of writing.  I am dyslexic, and at the time, this posed quite a problem for getting through some of my courses. As it turns out, I do a fair amount of writing, but spell checkers and some of my senior laboratory scientists help considerably. However, I have improved immensely over the years (lots of mistakes, corrections, practice). The sciences attracted me as I realized that I loved trying to understand how something worked even if it had to be dismantled first. I also enjoyed mathematics I do recall one time doing everybody’s homework problems making deliberate mistake in each one such that the grades should turn out to be identical. They did not which also helped give me a certain disrespect of authority. I was lucky when I entered Shiplake, my housemaster was Malcolm Mash; he was a mathematician, and recognized not only my ability in maths, but that I needed direction. He helped me along the right track, and later taught me more advanced mathematics which became useful in university.  I also had great teachers in Mr Wright (Biology) and Chemistry (I cannot recall his name). All of these teachers helped me navigate O and A-levels. I can’t overemphasize what a difference they made not only to my time at Shiplake, but to my future academic pursuits.

I attended the University of Calgary, Alberta, Canada (partly because I love the mountains and downhill skiing), where I majored in Cell and Microbiology. In my final (senior) year, I had the opportunity to work in Dr. Sanderson’s laboratory on an undergraduate research project.  I developed a series of protocols that allowed isolation of the outer membrane of bacteria that become standard protocols in the laboratory.  This really opened the door as I realized that I enjoyed research, problem solving, and working at the ‘bench’.

I returned to London with a BSc, and worked, at first, as a technician at the Hammersmith Hospital, West London, and then, as a graduate student. The unit specialized in neuromuscular disorders in children the majority of which are genetic. This really stimulated my interest in genetics, and how the causes of these disorders could be determined as well as treatments developed.

What was it about the field of science that captured your imagination?

 The ability to understand or work out how something works from basic principles is what captures my imagination. There are a number of things I have to say in this regard. I liked explosions, particle Physics and the story of the atom bomb – a recent invention, and often discussed in the media in the post-war/Cold War period [I recommend the recent movie Oppenheimer]. What truly captured my imagination was the lack of understand in particular of the many, varied genetic disorders. How does the normal gene work? What process is the mutation disrupting in the affected individual? Can this defect be repaired or compensated for, thus providing a therapeutic effect, or a cure (the Holy Grail)? When I entered the field, there were so many opportunities to explore genetic diseases, find out what caused them, and then attempt to fix them. Technology in this field has developed at lightspeed. Now, finding the location of a gene amongst the millions of other sequences for monogenetic disorders is now relatively straight forward; understanding the function of the gene or gene product, identifying other modifying sequences or proteins, and developing a therapeutic strategy is substantially more complex.

What areas of science did you study, where did you study and how did your time at Shiplake influence that journey (if applicable/ or any other learning institution)? Were there any teachers along the way that inspired you?

At Shiplake, I studied Physics, Chemistry and Biology at A-Level and 1 year of Mathematics. It was having passed 3 A-levels that got me into university.  In the autumn of 1974, I began my studies at the University of Calgary, Alberta, Canada where I completed a BSc in Cell and Microbiology (1978). Returning to London, I initially worked as a technician in a Biochemistry lab at the Jerry Lewis Muscle Research Centre as a technician (Dept. of Paediatrics and Neonatal Medicine, Hammersmith Hospital). Soon after, I began a PhD program in the same lab (Royal Postgraduate Medical School, part of University College London). I completed my degree in Biochemistry on the protein biochemistry of Duchenne Muscular Dystrophy (1984). I was awarded a Muscular Dystrophy Association Post-doctoral Fellowship to identify the gene that causes DMD. This took me to The Hospital for Sick Children, Toronto, Ontario, Canada. Remarkably, I (in Toronto), and another post-doctoral researcher in Boston, Tony Monaco, identified the gene at the same time by different methods. It was the largest gene ever found to date, and is still one of the largest genes cloned. My next step was to get on a ‘path to professorship’. I could have gone to work for industry, pharmaceutical companies, etc., but my heart has always been in academic research.   I was hired as a tenure-track Assistant Professor (1988), and moved with my American wife and Canadian-born son, to Columbus, Ohio, home of The Ohio State University and the famous ‘Buckeye’ American football team. I wrote grants, was successful at getting some of them, worked closely with some charities (Families of SMA, now Cure SMA, MDA, etc.) in order to fund my research program. I moved up the ranks from Assistant to Associate, and finally Full Professor.

My time at Shiplake influenced this in a number of ways. From my early days at Shiplake, I felt that my house master, Malcolm Mash, encouraged me, and this resulted in my first academic success.  I did well or at least better than anybody expected at O-levels. Even passing English Language and Literature I think largely due to the influence of Mr. Esau who also coached Rugby (one of my teams at Shiplake). He suggested that I memorize a series of words (so that I could spell them correctly) for the English Language O-Level, then pick the more descriptive category (no stories or anything imaginative) for the writing piece. I managed to insert these words in the appropriate place, and passed the English O-level.  Naively, I thought this would end my need to write. However, I have written many long, detailed grants and scientific papers since then papers since then, but I have a system for doing that.

The true major Shiplake influences were: Mr. Wright (Biology), an excellent instructor and mentor. Malcom Mash was the first teacher in my life who encouraged me; he was understanding and a very positive influence. Later, he taught me the early parts of advanced mathematics, imaginary numbers, and some basic calculus which was really useful to me latter in university.

How did you decide on which area of science to pursue?

I decided based more or less on what I enjoyed which was mostly the biological sciences as there seemed to be so many unanswered questions. These ranged across all facets of life. Initially, I was interested in viruses and bacteria, basically microbial genetics. Genetics is key because it gives you the ability to traces the activity of the gene from a normal (wild type) state to an abnormal (mutated) state. Microbes can be easily grown in laboratory conditions, and make a great in vitro system to study. Interestingly, my undergraduate research was my first use of what is now called molecular genetics. It was a revelation to be able to insert DNA into bacterial plasmids (circular DNA), and propagate these cloned DNA fragments. My first project at the Hammersmith Hospital is when I began to learn about neuromuscular disorders, most of have a clear genetic basis. The world of genetics was advancing rapidly at the time. My background in microbiology and cloning was perfect preparation. I knew this stuff, and I really enjoyed genetics which also became a passion.  I loved how it mixed basic techniques at the bench with how mathematics could be used to decipher where genes were located. These scientific tools were a bit like a lock and key. If I could open the lock, I could start to develop strategies for a therapy or correction of the genetic defect.

Did you have a career in mind when you were considering your which area to pursue?

The honest answer is not really. I considered medicine, but really what interested me was how things worked. The issue in medicine is you kind of know what causes things but are not necessarily on the front lines of discovering what you do not know or how things work. Research is where the boundaries are rolled back and new discoveries are made.

Is there an area of science that you wish you had pursued?

The whole particle physics story, and the physics and chemistry of explosions is still fascinating to me. I think I could envision how to unwind what is going on in some genetic disorders. It is very appealing to hope that one day I could be part of a solution to a terminal human disorder.  

What skills outside of academic do you need to be successful in the science world?

The number one skill is persistence. In trying to do something new, or blaze any trail, most of what you do doesn’t work. Same thing with experimentation – most experiments do not work. When something does work, the first thing you have to do is repeat it or work out another way around the problem. So, research science involves lots of failures, but persistence (and good collaborations) can allow you to push through and find new information/understanding.

 A second thing that helped me a lot in my younger years, and getting through Shiplake was sports. Apart from cricket, of which I was not a fan, sports helped me push through barriers, achieve successes, and give me confidence that was essential to a successful scientific career.  My ‘varsity’ sport was Rowing, but I also enjoyed Rugby and Football. Team sports are very much about collaboration, and so is science, and most careers, I think.

What do you see as the big future trends for science? Are there areas of science that concern you?

The future trends for science are very broad.

1. I think we will be able to master nuclear fusion reactions such that they produce considerable net energy (without radioactive bi-products). This is certainly not easy on a large scale, but I think the current technical difficulties can be overcome. This will result in an energy source just like the sun with no harmful bi-products, and a virtually unlimited energy source that does not result in global warming (another Holy Grail).

2. The use of machine learning (AI) is at very early stages. Its continued development will be very useful in analysis of DNA variants that pose either risk of disease or cause the disease. Combined with statistics, it should be possible to determine the cause of certain conditions.

3. The world of gene editing and gene therapy has only recently led to approved drugs for treating Spinal Muscular Atrophy, Sickle Cell Anaemia, Haemophilia A, Battens Disease (one form) along with a few other genetic disorders. This is truly only the beginning. There will certainly be refinements leading the second and third generation versions of these therapies hopefully making them more effective, more accessible, and less expensive. The CAR-T and CRISPR gene technologies are highly successful at treating heretofore devastating cancers such as leukaemia(s), genetic blood disorders (sickle cell, haemophilia, and thalassemia). Part of the power of these technologies is that the treatment is customized for the individual patient. This is going to become more and more the case, especially for cancer treatments. There are many other advances in other fields, but this is a flavour of what science can bring in the future.

As for areas of concern, the possibility that machines (AI) might be responsible for independent intelligence is worrying.  I feel the biggest issue is not so much that a specific area of science is a concern but more what we do with the advances, and who makes these decisions. Not all outcomes can be predicted. It is seldom the scientist who decides how their research should be applied in the public domain (Einstein’s letters and the development of atomic weapons is a stark reminder of this). We should have informed debate about how to employ the increasingly powerful advances in science, medicine, military weaponry, use of natural resources including the satellites and other vehicles that are sent up in space. I know this is a rather idealistic perspective, but it is what I believe.

Why is Science so important to society?

The first example I would give of the value of science/engineering is how the invention of the modern sewer system allowed the development of cities, and the prevention of many human diseases.  A lot of piping systems did exist for many years, but with the industrial revolution, cities grew immensely (London and the big stink). The modern sewer system began with James Neuland in Liverpool, and was taken up by Joseph Bazalgette in London. This improved the situation for the populus at large, and allowed for population growth. One could infer that it led to the development of the fields of Public Health, Sanitation, and Infectious Disease & Epidemiology.

Understanding how a pathogen is transmitted and produces infection has been studied for a long time. A great deal is known about this from previous pandemics, and other disease outbreaks that still occur in underserved parts of the world. (You might not have guessed this considering the random statements made by the former US President during the COVID pandemic). Vaccination development has also existed for hundreds of years beginning with Dr. Jenner’s smallpox vaccine in 1796!

As we move forward, do we work towards new technologies that enhance and improve humankind and all life on our planet, or do we not? I would say we do move in more positive directions than not. Science/engineering have already led to so many improvements for mankind.  A recent example are the mRNA vaccines for COVID.

It is up to all of us, not only scientists and inventors, but the public to encourage, and insist upon investments in research and development for the betterment of everyone.

Who are the scientists that inspire you or have shaped your thinking over the years?

The first scientist I will pick is Rosalind Franklin. She was a physicist who used X-ray diffraction techniques to elucidate molecular structures. Her commitment to excellence set her apart (may also have made her difficult to work with). She was the first to take pictures of DNA, which led to the determination that the structure of DNA was a double helix (read The Double Helix by James Watson). That is not to say that she was the most sharing individual, but given the fact that women in science were often overlooked at best, undermined at worst, this is not surprising. It should also be noted that the Noble Prize Committee made the worst decision possible by awarding the Noble Prize for DNA structure after she died thus deliberately eliminating her.  The significance of her work continues to be studied, and its value has come to light albeit posthumously.

The second person I pick is Professor Sydney Bremmer a South African researcher at Cambridge University. He performed elegant genetic analysis of C. elegans (a worm) that allowed the genes involved in the nervous system to be identified. He always had an elegant way of presenting a problem, and giving a simple and equally elegant solution. He could also be controversial. As a graduate student, I heard him speak at the Hammersmith Hospital, where, in my opinion he gave an outstanding talk which as a young scientist I found inspiring.

Finally, I would pick David Botstein, who in a paper together with his colleagues Ray White, Mark Skolnick and Ronald Davis laid out what was the most remarkable argument for how to create a linkage map of the human genome. This led to the identification of so many genes that cause human disease. I feel this was a very fundamental realization, and certainly I have used it in my work often.    

If there’s one piece of advice that you could give your younger self or an aspiring scientist about a career in Science, what would it be?

You need to realize that most experiments fail so persistence is an essential quality.

The second thing I would say is take the opportunities that present themselves. It may not have been your first choice, but if it is interesting, grab it and run with it. It is often surprising what happens. There will be many hours doing experiments which do not produce results to get to the one that does produce a result. It is a great joy when a breakthrough occurs, often in a rush, and not totally clear at the time, but when the dust settles it is clear as a bell.

Use the resources around you to the fullest, and perhaps in ways that were not obvious. Collaborate, share your thoughts, and listen to the ideas of others. Learn to keep a few of your best ideas slightly vague, until you have gathered some pieces of the puzzle. Good ideas and insights are the currency of success in science. Turn them into data, and you have made a gold mine.

A massive thank you to Arthur for a wonderfully interesting and insightful interview, it was an absolute privilege to meet him and understand how he transformed his passion for science into an illustrious career. 

Some of the highly deserving causes Arthur supports; Cure SMA - CureSMA.org, (US) Muscular Dystrophy Association - MDA.org and the World Muscle Society - worldmusclesociety.org

If you are an Old Viking and would be interested in sharing how you turned your passion into a career, please contact [email protected].