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Interview

From Auld Reekie to the City of Angels, and all the Meccano in between: A Glimpse into the Life and Mind of Sir Fraser Stoddart

Dr. Fraser Stoddart, Professor of Chemistry and Biochemistry at UCLA, is the Fred Kavli Chair

of NanoSystems Sciences and Director of the California NanoSystems Institute (CNSI). Dr. Stoddart received his B. Sc., Ph. D., and D. Sc. degrees from Edinburgh University in 1964, 1966, and 1980, respectively. He is internationally renowned for his pioneering work in chemistry and molecular nanotechnology. Stoddart has featured and popularized the mechanical bond in the making of compounds he calls catenanes and rotaxanes. Bistable variants of these compounds have been employed as molecular switches and motor-molecules. Sir Fraser Stoddart has employed his natural tendency towards creativity over the past few decades to promote the field of NanoElectroMechanical Systems (NEMS), as it relates to molecular computing and health care.

Alex N. Capecelatro

“There is a lot of room for creativity to be expressed in chemistry by someone who is bent on wanting to be inventive and make discoveries.”

Sir Fraser Stoddart

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Unique childhood experiences help people blossom into distinct individuals. From lawyers to doctors to car salesmen, everyone develops a distinctive passion for life. Regardless of their chosen career, individuals often have the opportunity to succeed because of these experiences, which have often taught them to set goals and achieve them. Truly great men, as exemplified by Sir Fraser Stoddart, not only succeed but repeatedly persevere in any situation.

Fraser Stoddart was born on Victoria Day (May 24) in 1942 in Edinburgh, Scotland. The son of a tenant farmer, he grew up in a home without electricity or any modern day conveniences. While Stoddart was an only child, supportive parents and an abundance of puzzles and toys sparked a yearning in him for knowledge. Although he showed prodigious ambition at an early age, his parents never imagined how successful he was to become.

Dr. Stoddart explains that his mother, however, always “had some sort of intuitive feeling that her only son would accomplish something worthwhile.” He was the apple of her eye. She expected him to leave Scotland with a good education and go out into the world and do something reputable. The fact that both his parents were “extremely supportive” was the key to his being able to build a good foundation for his future. “If you don’t have that [support] from your family, forging out a career in science will be an up-hill battle. The process is challenging enough. I was

lucky. It is important that you get off to a good early start in life,” Stoddart reflected.

With his parents’ full blessing, he went to Edinburgh University in 1960 and quickly discovered a path of creative, intellectual endeavors. Stoddart recalled, “I started off at Edinburgh with the feeling that my future, like many young Scots bought up on farms before me, would be in medicine. The path to get into medicine involved interacting closely with the sciences and so I started off by studying chemistry, physics, and mathematics. Soon, I became more and more interested in the sciences, and medicine started to pale into insignificance in my mind. While I reckoned I could possibly help people more directly if I were in the medical profession, I became concerned that I would not be able to pursue my passion for research, which had already started to develop inside me. I found the challenge of tackling problems in research that no one knows the answer to beforehand as increasingly rewarding. I was captivated by the wonder of making discoveries. I wanted to achieve on a scale that would not only reflect well on me, but might also produce some benefits for society in the fullness of time. I was soon to realize that among the sciences, chemistry would give me, by far, the biggest opportunity to be creative. As a chemist, just as if you are an artist, you can create an object that no one has made before and then study it for its properties and functions. More than in any other science, chemistry gives you that feeling of being able to pose problems and solve them. That aspect of chemistry appealed to me, for growing up on a farm in the lowlands of Scotland in the 1950s had been all about solving problems: it was all about being creative against the clock with limited resources to hand.”

Stoddart continued to develop his passion for research, which he had begun as an undergraduate student, during his graduate studies in chemistry at Edinburgh. His passion for research reached extraordinary heights. He published his first paper in 1964 and earned his Ph. D. two years later under Sir Edmund Hirst, before spending three years in Canada at Queen’s University as a postdoctoral researcher.

Although his successes were already considerable, Stoddart still had a lot to learn about the world around him when he landed his first academic position in England in Sheffield University in 1970. He reflected, “I was ill-equipped to deal with senior colleagues who were devious in their dealings with me and envious of my achievements in research. I had come from a community of farmers in Scotland who had been extremely supportive of each other. It never occurred to me that, because I was successful and [would be] soon doing research that was receiving international attention, this level of accomplishment would become a focal point for envy and resentment and all the discomfort that follows in their wake. The 1970s was a stressful decade for me and it was only after taking a three-year sabbatical at Imperial Chemical Industries (ICI) Corporate Laboratory in Runcorn that I was able to make the necessary personal

Stoddart, at age three, pushing a wheelbarrow at his childhood farmhouse.

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Sir Fraser Stoddart

adjustments. I had to cast off a reserved and serene demeanor and become much more aggressive and combative.”

So Stoddart had to change from having a shy, retiring demeanor, to displaying an authoritative, assertive one. His future successes were to rely heavily on adopting this proactive mindset. He exemplified this when he “started to write to the national press and put my arguments forward publicly for reform of the UK academic system. I challenged the fact that most British academics were too ready to whine about a perceived lack of funding as an excuse for their lack of research productivity. I was not popular for breaking out on the scene saying, ‘No, it’s not a question of there not being enough money, it’s a question of the waste of money after it is handed out far too easily.’ I called for a more competitive funding strategy. My stance was far from a popular one. I made a lot of enemies. The outcome was that I was not appointed to a full professorship [at Birmingham University] until aged 49.

“My fortunes were completely transformed by my move to the chemistry department at Birmingham University in 1990,” Stoddart added. “I only accepted the Chair of Organic Chemistry

after asking for start-up funds that were unheard of in the UK at the time. I thought the university would turn me down but they gave me all I asked for! There was again some local resentment but I had learnt by this time how to confront it. The Birmingham era was a highly productive one, during which time the size and stature of my research group rose rapidly and the department was almost completely refurbished into the bargain. The transformation had a huge impact on the rest of the UK community in chemistry. Chairs in other chemistry departments could point to what Birmingham had done for Stoddart and insist that it should happen in their university, and, in most cases, it did! There was a lot of satisfaction to be had at the end of the day, but it was a pretty hard 27 years I had to hoe to prove my point.”

Tough as those years in the UK were, Stoddart reflects that he wouldn’t have had it any other way, now in retrospect. He comments, “It proved to me that I could always get round adversity in life by asking how to turn a difficult set of circumstances to my advantage. I came out of it a lot wiser and with increased confidence in my own abilities. My creative talents had also been enhanced by always having to be one step ahead of my

A timeline of Stoddart’s work from 1978-1994.

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protagonists, or to be able to outflank them if I wasn’t.”After his ultimately successful tussle with the academic

system in the UK, Stoddart started to set his sights on coming to the United States. He did so to UCLA in 1997. Stoddart recalled, “When I first arrived, I held the Saul Winstein Chair in Organic Chemistry. Winstein had been the intellectual leader in physical organic chemistry through the 40s, 50s, and 60s.

“Many people at UCLA believed Winstein was in line to receive the Nobel Prize in Chemistry when he died tragically in his swimming pool from a heart attack at a relatively young age in 1969. Some time after his death, a chair was endowed in his name and, Don Cram, one of his younger colleagues, became its first holder. When Don started to downsize his research effort in the 1990s, I was offered the chair. By accepting it, I immediately put myself under a lot of pressure. Don Cram was a legend in his time and had been awarded the Nobel Prize in Chemistry in 1987. The double act of Winstein and Cram was a particularly challenging one for me to follow.”

Now, as the director of the CNSI, Stoddart has broadened the scope of his research from a predominantly chemistry base to include more and more molecular nanotechnology. When asked if he had any advice for someone wanting to follow in his tradition of doing research, Stoddart replied, “There are now lots of opportunities to do ground-breaking research in chemistry that addresses areas of complexity and emergent phenomena and how they can contribute to molecular nanotechnology in a fundamental manner. There is a lot of room for creativity to be expressed in chemistry by someone who is bent on wanting to be inventive and make discoveries. If, as an undergraduate student, the opportunity arises to spend time in a faculty member’s research laboratory, then this experience is one to grasp quickly. It is what I did myself. Although course work is important for acquiring a basic fundamental knowledge in chemistry, the real excitement is to be had in the research laboratory. Just get in there, roll up your sleeves and find out if going down the path of doing something new gives satisfaction. I got involved in research very quickly as an undergraduate student and I was soon engaged in experiments that I had thought up and designed myself. Ownership of research is important. I knew I was at the cusp of having the opportunity to invent and make discoveries. I found the whole experience to be additive. It became difficult to drag myself away from the lab.” Stoddart has worked in and around a lab since 1962.

All these years later, he has delivered almost a thousand lectures about his research at different venues all around the world. Between January 1996 and June 2006 alone, he published 309 papers which have chalked up no less than 13,567 citations. These metrics leave Stoddart, according to the Institute for Scientific Information, as the third most highly cited researcher in chemistry in the world today. When asked about this ranking, Stoddart commented, “I have in the region of 800 publications out there in the scientific literature which is probably too many!” But then in defense of this large number, he added, “As time

goes by they are less important for me and more important for the young people who have done their research in my lab.” Stoddart believes quite strongly that young scientists, who are going to succeed, need to register their productivity in research and their ability to write papers before they pursue independent academic careers. Creativity is doing research that has not been done before, and doing it over and over again. He cites Mozart and Beethoven as good examples of creative individuals due to their contributions to classical music.

Dr. Stoddart is credited with playing a major role in introducing a new type of bond into chemistry, the mechanical bond. He takes advantage of molecular recognition and self-assembly processes in order to make mechanically interlocked molecular compounds called catenanes and rotaxanes. A catenane is a molecule composed of two or more interlocked rings. It derives its name from the Latin word catena, meaning chain. The simplest rotaxane has a dumbbell component with a ring encircling it that is prevented from escaping because of the stoppers at the ends of the dumbbell. Rota comes from the Latin words, rota, meaning wheel, and axis, which means axle. These mechanically interlocked molecular compounds are unique because they create different topologies, depending on the orientations and linkages between the rings and dumbbells. The Borromean rings, which have long been a symbol of interest to artists and mathematicians, was first made in its molecular form in Stoddart’s group in 2004. The molecular Solomon’s knot followed in 2006.

As suggested by his artistic rendering of molecules, Stoddart looks at his laboratory as a blank canvas, ready to be painted upon. Commenting on the field in which he has devoted a lifetime of study, Stoddart said, “The one thing you have got to appreciate about chemistry is that it’s not a mathematical science; it’s not black and white but rather many different shades of grey.”

Stoddart’s research on “Molecular Meccano,” as he calls it, could have far-reaching implications for molecular computing. He reflected on how it all began back in the late 60s when he was a postdoctoral fellow in Canada by reminiscing, “As far as learning the art of designed molecular recognition and self-assembly, that started for me in 1967 with a seminal publication from the DuPont Laboratories by Charles Pedersen, another of the [three] Nobel Laureates in Chemistry in 1987. He had used the weak interactions that exist between hard metal ions, like sodium and potassium ions, to assemble large rings under the templating influence of the ions. I realized that the chemistry associated with these interactions provided the chemist with a completely new way of making chemical compounds which would be very difficult to make by any other means. Templation is a concept that I knew pervaded both architecture and biology and so why shouldn’t it be a concept that could be used in a chemical context? And so my chemistry became, like much of biology, that of molecular recognition and self-assembly processes in support of template-directed synthesis. Simply by transferring a

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concept from biology into chemistry, we ended up by creating compounds which contain mechanical bonds. And what’s more, the chemistry is highly modular. All the ingredients were in place to build artificial molecular machines, so that’s what we did. As somebody who had tinkered with a lot of machinery at a very basic level on a farm during an era when automobiles and tractors were very easy to take apart and put together again, I was fortunate to come face-to-face with a similar kind of activity in chemistry. To begin with, it was an activity that interested very few chemists, and so there was a great opportunity in the early days to develop a new area of chemistry, along with no more than half-a-dozen other people in the world.”

Stoddart’s work, although ground-breaking and well-documented in the top chemistry journals, was not accepted as being of any real importance by the chemistry community in the early days. He commented, “Our initial research on catenanes and rotaxanes was seen by many as being ‘cute’ but they questioned if it had any use at all. It was nice but would probably never find a niche was the popular opinion. Well, these comments were all I needed. They acted as a spur and also made me turn my

thoughts more seriously to moving to the US.” Very soon after Stoddart left the United Kingdom to come to California, he found that the opportunities for collaboration at UCLA were more than he and his group could embrace all at once. They were spoilt for choice. His research, which had started out at a fundamental level, was now ready to become application driven, in part at least.

Stoddart observed, “I don’t believe there’s any other culture in science and engineering, other than here in the US, that is quite as focused on the challenge of taking fundamental discoveries and inventions into a situation where they are almost ready to be taken into the marketplace. This is a country which has devised the mechanisms of funding and nurtured the minds of academics to think in a particular way when it comes to benefiting society at large.” By coming to UCLA, the opportunity was suddenly there to work collaboratively with a colleague, Jim Heath, on the construction of a molecular computer, and, in more recent times, with another colleague, Jeff Zink, on the fabrication of functioning nanovalves operated by motor-molecules for applications in health care. Both these lines of research

A timeline of Stoddart’s work, from 2001 to present, including catenanes (A, E)

Sir Fraser Stoddart

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depend heavily on the design and construction of switchable catenanes and rotaxanes. Stoddart emphasized, “We were greatly encouraged by the potential applications of the research in the design and evaluation of these molecular switches. All that has happened at UCLA was anticipated for me by Don Cram back in early 1997, before I arrived in the US. I remember sitting down with Don and asking him what chances our molecular switches would have of finding applications in devices if I were to come to UCLA and he responded right away, saying, ‘You will find that in a very short period of time you will have many more opportunities to collaborate than you will have the time or the energy to give to the collaborations.’ He was right.” Stoddart continued, “Once we had the basic building blocks in place and we had some identifiable functions in mind, we realized we were standing at the entrances to several gold mines. This situation is an ideal one from which to launch vigorous collaborative research programs.”

When asked why his fundamental work was ripe for exploitation on his arrival at UCLA, Stoddart speculated, “We were able to bring something to the table which was quite unique. That uniqueness centers round the chemistry of the mechanical bond. We were not only able to present the mechanical bond as having form, but also function when the catenanes and rotaxanes were rendered bistable, that is capable of existing in two states. We could use the fact that the most stable configurations of the molecules can be switched to less stable configurations by, for example, using redox reagents to carry out reductions and oxidations on the molecules. Such molecules are said to be redox-active; by taking electrons away and putting them back again, we can even make them switch, one component with respect to the other. The redox chemistry can be done with chemicals, or with electricity in an electrochemical cell, or we can use light to stimulate the supply of electrons in appropriately designed molecules.”

On December 30, 2006, Fraser Stoddart was made a knight bachelor by Queen Elizabeth II for his services to chemistry and molecular nanotechnology. Dr. Stoddart’s humble disposition is demonstrated by his request that no one in the United States address him as “Sir”. Although he has received numerous prizes and awards throughout his professional career, he cares little for personal recognition. He insists, “Any pleasure I feel is because of the recognition they bring to my research group and the different institutions that have supported me over the years. I am in no way egocentric. I am not living for the next piece of recognition to happen, for I am not. If it happens, then so be it. Gongs [awards] are not high on my pecking order of what’s important in life.” He added, “But they are important for my students, both past and present. They need to become calibrated as to how significant their research is in the world at large. Awards to me are awards to them for it calibrates them and raises their visibility. They act as a tremendous fillip to my whole research group, urging its members on to even greater levels of achievement. They also

help to raise UCLA’s standing and visibility. If an individual receives a major prize [Dr. Stoddart very recently won the King Faisal International Prize in Science] then the institutions with which that individual is identified gain considerable kudos.” Stoddart went on, “In my case, I hope the CNSI will be a major beneficiary and that UCLA is also put on the map as a result. It is all part of the synergy to attract good faculty to come and join your department, to entice the very best postdoctoral scholars to come and work in your research group, and to encourage highly talented graduate and undergraduate students to choose to come to UCLA. In the pursuit of excellence, gongs are much more about the institutions than they are about the glorification of an individual. The one thing I have learned by this stage in my life is that our time on the planet is finite and people tend to forget about you quite quickly after you are no longer around. Science is more important than any one scientist. We should not be blinded by our own self-importance. I often say that, if you were to stop a man or woman in the street and ask them to name five leading scientists in the last century, many people would have difficulty identifying five. So let’s keep our feet on the ground and not get carried away by our achievements, however great we might think they are.”

Stoddart has always held his students to the high level of excellence to which he holds himself. He strives everyday for perfection, pointing out that in order to be a successful academic in the sciences, “You need the strength of a horse, the hide of an elephant, and the work ethic of a honey bee.” He motivates others to achieve the best of their abilities. Stoddart commented, “One of the challenges I put before my very best postdocs and students comes after they have been a little time in my group and are doing well by any stretch of the imagination, I will say

Stoddart research group, 2007, forming a rotaxane molecule.

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to them, ‘Right, you are doing well but do you know you could do 200 times better,’ and I expect them to raise their game in response to my raising the bar. If they look surprised, I just say, ‘You are so talented, you can do a lot more with your talents. I am going to make your life hell on earth until you reach a level of achievement and productivity that commensurates with your knowledge base and innate ability.’ I don’t think there has ever been someone who has not risen to the challenge of the 200 factor. In fact, at the end of it all, the young person usually comes back to me, recalls the challenge, and thanks me for issuing it. Too many young people underachieve because they have never discovered the pleasure of becoming an overachiever.”

Dr. Stoddart continually praises the excellence of his collaborators and students. He admits very readily that his achievements are a result of the many individuals who have shared his vision and passion over the years. They have been not only colleagues, but have been friends of his for life as well. He added, “There are close on 300 graduate students and postdoctoral scholars that have played a huge role in our success as a group. The youngsters, as I often call them, are the people who have driven me on from day to day. I have always looked upon the opportunity to interact with young people between the ages of 18 and 28, many of them blessed with an incredible amount of talent, as a real privilege indeed. It certainly keeps you on your toes.”

Dr. Stoddart has been successful in part because he is always willing to ask for help. He insists that he learns something new every day. He never stops asking questions. He is so capable and creative because he has that innate ability to admit to his faults

and to ask for help. Stoddart reflected, “To be successful you have got to be able to look at yourself and say what’s going to have to be learned today, accepting that you still have a lot to learn. You have got to be constantly reinventing yourself and also to be prepared to maybe go to basics if everything else fails. You cannot entertain the fear of failure. I am forever quoting the impresario, Noel Coward, who said, ‘The secret of success is the capacity to survive failure.’ All of us live lives that are full of failures and disappointments. The things that you would like to happen to you don’t always happen, so it’s how you respond to failures and disappointments that ultimately decides your level of achievement. If at first you don’t succeed, try, try, try again.”

Stoddart concluded by offering a few final words of wisdom about becoming successful, “My father used to say, ‘Son, stick in until you stick out.’ Whether it’s passing examinations when you are a student, obtaining an academic position, getting grant applications funded, or publishing articles in the best journals, you just have to hang in there until it works out for the best. You will have your setbacks, and it’s how you respond to them that will determine who you will become.”

Clearly, Fraser Stoddart overcame setbacks. He grew up on a remote farm, worked his way up to positions of influence, and succeeded where so many others have failed. Stoddart’s positive mindset and strong work ethic have set an example from which even the very best can learn. A professor to plenty, a friend to many, and a collaborator to a few, Sir Fraser is an exceptional man who is influencing the way in which science and scientists develop in the future.

Sir Fraser Stoddart