Professor Jack Szostak on the fascinating and addictive nature of scientific research

November 26, 2017

Prof Jack Szostak is the 2009 Nobel Laureate in Physiology or Medicine. He has made extensive contributions to our understanding of the nature and function telomeres, which are the caps at the end of chromosomes. He is an Investigator at the Howard Hughes Medical Institute, a Professor of Genetics at Harvard Medical School and a Professor of Chemistry and Chemical Biology at Harvard University. He is also the Alex. A. Rich Distinguished Investigator in the Department of Molecular Biology at Massachusetts General Hospital. Prof Szostak studied chemistry as an undergraduate student at McGill University, where he discovered biochemistry as his true love, and then earned a PhD in it from Cornell University. Always interested in answering fundamental questions, his focus has now shifted to the origins of life on earth. In this conversation, he shares with us his aversion to competition in research, and the addictive nature of scientific discovery.


“…scientific research is even more fascinating because it enables you to potentially make new discoveries. It is totally addictive when you realise that you might be the first person to discover something new in your field or understand a previously unknown process or mechanism!”


What fascinates you about science, and why should people study it? How can we encourage the new generation to choose to study and practise science?


I personally find science really interesting and fascinating. It is full of cool puzzles and helps us to understand our place in the world, and how the world around us works. It may not necessarily be the right career choice for everyone. However, for people who are curious and really like to understand natural phenomena at a more fundamental level, a science education is a great fit. Studying science equips one with a rigorous methodology, which develops analytical thinking, problem solving, and creativity. Apart from the intellectual stimulation, a science education is also so much fun!


In particular, scientific research is even more fascinating because it enables you to potentially make new discoveries. It is totally addictive when you realise that you might be the first person to discover something new in your field or understand a previously unknown process or mechanism!


What should be done to improve the understanding, excitement and appreciation for scientific research in society? What goes wrong even with children who do take an interest in science at a young age? Do you personally do outreach activities?


Increasing the awareness and appreciation for science is a big challenge. There are many different aspects one needs to address in order to change the current situation.


The first point is that scientists must take part in communicating what they do. They must actively outreach. There are more and more organisations, including universities which are trying to spread the word regarding what scientists do. In Boston, where I live and work, we have something called the Cambridge Science Festival, where all the universities and hospitals open up and show people what scientists do.


Teaching is another big issue which needs addressing. A really good teacher can be a role model who can inspire students and can convey the wonders of science, particularly if he/she is personally very enthusiastic about his/her subject. Care should be taken that school classes are not too big and all kids, regardless of their academic level can actively participate and learn from the course.


Furthermore, there are great television shows on science. There are also dedicated science museums and planetariums which try to enthral younger children. All these avenues expose children to new discoveries and help captivate their interest in science.


As for what goes wrong, I think it is the educational system. Currently, the scientific education in schools focuses on learning a lot of facts and memorising what has already been discovered. However, science is about thinking of how to find solutions to problems, not learning by rote. We should teach students to look at past problems with the aim of seeing how the learnings of the past can be used to help address the problems of today and tomorrow. If you need to check a fact, you can always look it up!


With regards to my personal outreach activities, I do give talks to schoolchildren and do school visits and also participate in public discussions and talks. There are two kinds of outreach talks I do; one is about my personal story, while the other (generally at a public forum) is about my research.


The talks I give about my personal journey revolve around how I got interested in science, what my student experiences were, how I started my lab and have made my discoveries. The theme of the other talks is about my research. These are usually at larger public events, where I talk about the origin of life, which is quite a popular theme these days! People like this topic because it is so fundamental, and everyone is curious if there is life outside the solar system!


In many scientific departments, there are more men than women. How can we attract more women to science? If there are obstacles, how can those be overcome? Do you think that female role models in science helps young girls get into the sciences?


In my lab, I try to encourage everybody and let them be independent. People do well in such an environment.

I am actually very proud of the fact that many prominent female scientists have come from our group, the most well-known being Jennifer Doudna, who is now at the University of California, Berkeley. She has made great contributions to CRISPR gene editing and is a fantastic person. She did excellent work in our laboratory and has done spectacularly well in her career, making her a great role model. Besides her, there are four female alumni (PhD’s and post-docs) from my laboratory who are now in the National Academy of Sciences. It makes me really happy to see my students thrive :)


Did your parents have a major impact on your interest and were you interested in any other careers as well?


My father was a pilot who then studied aeronautical engineering at Imperial College London. My mother became a librarian for a chemical company. Back in those days, she used to bring home chemicals and I conducted experiments in a makeshift lab in our basement! Although my parents did set up an environment very conducive for me to study science, neither really pushed me to study it. They encouraged me to pursue whatever I was interested in, which, from an early age, was maths and science.


Have you ever had entrepreneurial ventures spring out of your research?


In my lab, I try to look at fundamental questions. However, I also really enjoy applied sciences to see how our research translates into real life solutions. This is the work I do in collaboration with companies.

One example is a technology our lab developed for evolving proteins and peptides. This was little over 20 years ago and was purely an attempt to answer a fundamental science question at the beginning. However, over the years, more and more people started working with our technology and companies actually developed drugs based on it. These drugs are now in clinical trials! So, in research, you can go all the way from fundamental science to practical applications, but it does take a long time! Apart from that, I co-founded a company called Ra Pharma six to seven years ago. There is also a company called Moderna Therapeutics, where I am the Chairman of the Scientific Advisory Board. It employs a new and innovative approach to cure diseases by using mRNA as a drug.


In the most general sense, what do you work on, and how does it benefit humanity?


In our lab, we are currently working on trying to understand how life emerged from the chemistry and physics of the early earth around four billion years ago. It is a very engaging subject, because we have now discovered many other planets which may actually be able to support life, we don’t know if they actually do.

The overarching aim is to understand the step-by step process by which we went from planet formation, to simple chemicals, which then gradually turned into more complex molecules and how they assembled into cells to finally start Darwinian evolution. We focus on the step in the middle, where the correct molecules were available and then they somehow advanced into cells, which then grew and divided. This is particularly fascinating, because it involves many different aspects of chemistry, physics and even geology.


All cells have a boundary, called the cell membrane. We have worked for quite a while to try and understand how these membranes assemble from very simple molecules and how they grow and divide without any of the complicated biochemical machinery now present in cells. This is because, at the very beginning, cells were very basic and their specialised machinery developed over time. We understand parts of the process well and think we know the steps by which primitive cell membranes could grow and divide in reasonable conditions on early earth.


However, what we don’t yet know is how genetic material, like RNA or DNA could replicate, before we actually had any enzymes to manage it. We are trying to ascertain the chemistry behind these genetic molecules, their replication mechanism and how these basic cells could selectively pass on beneficial genetic information from generation to generation at that time. It is a very complicated and interesting chemical problem. We’ve solved many of the steps, but there are still several more challenges to overcome! It is a really fun puzzle.


How big is your research group? What are their backgrounds?


20 people work in my lab. We have around eight PhD students and 12 post-docs. It is a reasonably big group with people from all over the world and with a variety of scientific backgrounds. Some researchers do crystallography, some do organic synthesis, some do membrane biophysics, and a few do molecular biology. Since we are trying to tackle our research problems from many different angles, this interdisciplinary approach is crucial for our lab. Everyone needs to be able to exchange and communicate their ideas and collaborate.



You have done research in different areas and are currently working on the very fundamental question of the origin of life on earth. What has prompted you to focus on different scientific problems over the years? What drives/motivates you/your academic journey?


Years ago, when I was still a post-doc and then later when I started my own lab, I was doing a lot of biology related work on DNA repair and telomeres (Protective caps of our DNA). It was a fascinating research area and I enjoyed working in it for many years. However, after a while, I spent a couple of years thinking about what else to work on.  As a person I don’t like hyper-competitive research areas. I prefer areas which are interesting but only few people are working on. So I switched to RNA.


Tom Cech and Sid Altman had discovered that RNA molecules could act like enzymes, which fascinated me and I got into that field. One thing led to another and we realised nature wasn’t giving us ribozymes that could do the chemistry we wanted, so we learned how to evolve our own ribozymes. After working on the directed evolution of molecules for 10-15 years, I got more and more interested into how evolution started all by itself. It is one thing to evolve molecules in the lab, where you have the tools, chemicals, enzymes, good students and so on, but the same process somehow spontaneously happened on early earth. This captivated my interest and now the whole lab is focused on it.



Can you tell us more about your contributions to the human genome project? What are its aims, applications and how does benefit humanity?


My contributions have been somewhat exaggerated! We were studying telomeres and had learned how to assemble artificial chromosomes in yeast, since we had all the bits and pieces necessary to make them. They turned out to be useful cloning vectors for big chunks of DNA. So, for a very short while, yeast artificial chromosomes or YACS were used in studying the human genome. This was because having long sequences of DNA made it easy to get overlaps. Soon after, people switched over to using artificial bacterial chromosomes because they are easier to handle.


Why did you stay in academia and not go into industry? How can we keep more graduates in academic/doing active research? What is the beauty of the academic world?


Depending on the academic institution, or the company, you can do great work in both environments. Some people even manage to switch back and forth. I feel I was extremely lucky to get my first independent job at a good institution. It was relatively easy to raise money to support the lab back then. It is much harder and more competitive these days. I’ve been very fortunate to have spent my career at great places, with lots of resources, inspiring colleagues, and students. These circumstances had a very positive impact on the quality of my academic work.


I enjoy working on very fundamental problems in an academic environment. However, it is also satisfying to address more applied problems. That is why I also work as a scientific advisor for several companies and have co-founded a couple of ventures.

In my lab, some of the researchers stay in academia, but many go into industry. These days, you have to be really driven to find and build an environment where you can study fundamental science. The academic world is very competitive and it is also unfortunately very difficult to get grants to help support your research and lab. Even in industry, you could spend a large fraction of your time trying to marshal the funds needed to actually carry out your project since there is a lot of internal competition.


Are there people who inspired you and shaped the way you think? And do/did you have a mentor?


My PhD and post-doc advisor (Ray Wu) was a huge influence. I have tried to model my lab on the way he ran his. Everyone in his lab was really independent and worked on different things within a certain research area. He was always there to talk to people when they needed him. I don’t like to micromanage people and I don’t think you can become an independent scientist if your advisor is telling you what to do all the time.

Instead, I like to walk through the lab and ask what’s new. Of course, people are always welcome to come to my office and talk to me.


How has your life changed after receiving the Nobel prize? How did it feel? Have you received more attention for your work, especially with regard to the public? Do you speak a lot in public about your work?


When you work on an interesting problem, you just feel that you really want to solve it and share your results. The Nobel Prize is the highest level of scientific recognition from other scientists, so being awarded one in 2009 is incredibly satisfying.


My life hasn’t changed a lot after the Prize. I was already travelling a lot, and delivering lectures across the globe. My main activity is still doing science. People might think it is much easier for me now to get grants or publish papers. In fact, it is not. People often hold you to a higher standard.


What has definitely changed after receiving the Nobel Prize are my outreach activities. The Prize has enabled me to participate in more outreach activities to promote science. It provides a platform for supporting science and encouraging especially young people to go into science, which is great.


What is your secret to academic success? What do you still want to achieve? How do you deal with failure?


My big remaining scientific goal is to really understand how the first cells evolved, how they functioned and how evolution began.


The most difficult time of my life was during my first three years of graduate school. Everything I did failed. I was miserable and very close to just giving up. However, my advisor seemed to have faith in me, and supported me. He was fantastic and eventually things luckily started to work.


When you run a lab and have lots of ideas, most of them don’t work. As long as a certain fraction of those do work, it is okay. That is why really good people always have two to three different projects, and it’s good to have more than one thing going on.


What do you do outside of academia/work? Any other passions?


Yes, I have a family and children. I love spending time with them, going on family vacations, and hiking. There are lots of fun things to do outside of science.


Are your children into science?


No, not at all. They are more interested in literature, philosophy and politics. But that is also great. They should pursue what they love. Maybe it is also a good idea not to be in the same profession if your father has won a Nobel Prize!


What do you think is the next big breakthrough/idea in science?


There are so many! In medicine, the problems associated with ageing are of particular interest, which includes the research on telomeres I did at the early stage of my academic career. In the area of bioengineering, the understanding of soft materials, tissue growth and assembly at higher levels are hot topics.



More information on Prof Jack Szostak can be found here. His research group can be found here.



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