Famous Chemists and the Nobel Prize

As a boy growing up in Eugene in the 40's, the notion that you could meet a 'famous person' seemed quite remote to me.  How did I know who the famous people were?  Mainly by going to a Saturday matinee at one of our local movie theaters, and by watching a newsreel prior to the featured movie.  A newsreel was a form of a short documentary film, in black and white, that was the source of news, current affairs, and entertainment.  At a time when there was no TV, this was my first opportunity to see what presidents, generals, top athletes, and movie stars, looked like in 'real life'.  People like President Truman, General Eisenhower, Jesse Owens, Clark Gable, and Elizabeth Taylor, come to mind.

Of course at school, we heard about many famous people in our lessons, and by reading our Weekly Reader.  Weekly Reader was a weekly newspaper for elementary school children.  It was first published by the American Education Press of Columbus, Ohio, in 1928.  By 1950 it had a circulation of nearly 5 million!  At Stella Magladry School it was handed out each Friday afternoon by our teacher.  It featured current events, and had a many pictures to go with the articles.  It was our own copy that could be taken home for further reading.


In grade school, I think that the most famous scientist that I knew about was Albert Einstein.  We were told that he was a genius, and I was quite sure that this was a very special attribute.  I imagined that any genius would have hair that was uncombed, and I didn't run into anyone that had a hairdo quite like that of Albert Einstein!  We learned that Einstein received a Nobel Prize in physics, and developed the general theory of relativity.  I didn't know what this theory really meant, but I did know that he came up with his well-known equation, E = mc(2).

At a young age, I learned that a Nobel Prize was given for outstanding work in medicine, physics, chemistry, literature or peace.  In 1984, our family traveled to Sweden, and we visited our friend, Klas Nyberg in Karlskoga, which is a town of 25,000 about 150 miles west of Stockholm.  Alfred Nobel was forced to relocate his explosives company after a serious explosion at his factory in Stockholm.  Klas showed us the beautiful two-story home where Nobel lived in Karlskoga the late 1800's, after he moved his company to the country.  Money from his estate has funded Nobel Prize winners since 1901.  When I was a child, the prize was worth around $50,000 dollars, and today it's $1.2 million.  That's in addition to the gold medal.  What an interesting legacy for the man that invented dynamite!

As I studied chemistry, first in high school, and then in college and graduate school, I began to learn about a number of chemists that won a Nobel Prize.  In some cases, they were well know before they won the prize, but more often they became famous after they won such a prestigious honor.  My first organic chemistry textbook, by Louis and Mary Fieser from Harvard, cited Nobel Prize winners in reference to their work.

Over the years, I would hear 12 Nobel laureates present chemistry lectures, and see four others at chemistry seminars.  One of the most notable lectures was by Linus Pauling in 1966 at the chemistry department of UCLA.  At the time, Pauling was 65 years old and had already won the Nobel Prize in Chemistry (1954) and the Nobel Peace Prize (1962).  I was most eager to hear him speak, knowing that he was born in Portland, and had graduated from Oregon State.  Without a doubt he was the most famous scientist Oregon had ever produced.  He gave an engaging talk about how he conceived the idea of the alpha helix for protein structures.  He was at home, ill with a cold, when he built some simple molecular models made of newspapers and magazines while recovering in bed, which over a short time would lead him to yet another amazing chemical discovery in 1951.

Soon after I heard Pauling's lecture, he made headline news when he proposed taking 3 grams of vitamin C daily for the common cold.  His work on vitamin C generated even more controversy when he advocated high doses for the treatment of cancer.  As a peace activist, Pauling was an outspoken opponent of the Vietnam War, and in 1968 he led a demonstration against the war in downtown Los Angeles.  My friend and colleague, Peter van Konynenburg, and I attended the rally.  We were among the nearly 10,000 people marching down Broadway Blvd.  Needless to say, I wasn't able to get a glimpse of Pauling at the head of the line.

During my career, I knew two chemists that won the Nobel Prize later in life.  Donald Cram, one of my graduate school professors at UCLA in 1965, was awarded the prize in 1987, at age 68. I first heard Cram give a seminar at the University of Washington, when I was an undergraduate at nearby PLU.  My undergraduate advisor, Bill Giddings, took me to Seattle so that we could hear Cram present his research. I was using Cram's well known organic chemistry textbook, co-written with George Hammond at Cal Tech, and this was the first time that I had such an experience, i.e., meeting a top scientist and textbook author. This opportunity was very influential in my decision to apply to UCLA for graduate school.

At UCLA I found Cram to be a very friendly guy, with a boyish grin and hearty laugh. He routinely wore one one of his 150 'trademark' bow ties. He would bring his guitar to the last day of class so that he could sing to his students!  Whenever I talked to him in his office, I noticed that his surf board was always upright in the corner so that he could head to Santa Monica Beach for some surfing on a moments notice.  Little did I know that Cram would one day win a Nobel Prize!  This was exciting news, and I wrote him a congratulation note shortly after the announcement.  He then sent me a nice thank you card that featured the structure of one of his interesting organic molecules.  My final visit with Cram, who was born and raised in Chester, Vermont, was at Wesleyan U. in Middletown, Connecticut, where he gave an excellent seminar on his Nobel Prize winning research in 1990.  I never met another chemistry professor with a personality quite like Donald Cram.

E. J. Corey of Harvard was a consultant at Pfizer for over 50 years.  He would take the train from Boston to New London about once a month in order to discuss our chemistry problems.  I first met him in 1973.  I would usually see him over his lunch hour, which he chose to spend in the consulting room.  I would stop by and ask him what he would like for lunch from the cafeteria.  Each and every time it was the same, a tuna sandwich and a chocolate milk!  Fortunately, he took interest in my synthetic work, particularly when we were looking for new routes to bicyclomycin and indolmycin.  The news that Corey won the Nobel Prize in 1990 was very exciting.  More than 250 molecules have been synthesized in the Corey Group since 1950.  His 1969 total syntheses of of several prostaglandlins are considered classics. I was pleased when E.J. made reference to the synthesis of indolmycin that Dave Clark, Scott Hecker, and I published in the Journal of Organic Chemistry in his book 'The Logic of Chemical Synthesis' in 1991.

In the field of organic chemistry, I do not believe than any scientist gave a more impressive seminar than Robert B. Woodward of Harvard, who won the Nobel Prize in 1965.  He is considered by many to be the preeminent organic chemist of the 20th century, having made many key contributions to the subject, especially in the synthesis of complex natural products and the determination of their molecular structure.  I became familiar with his work while I was a graduate student at UCLA, and my research professor, Saul Winstein, knew Woodward very well from their collaborative studies at Harvard in the early 1950's.  While I was at UCLA, Winstein showed me an amusing photo of Woodward all dressed up for a backyard barbecue in sunny California.  Woodward wore a chef's hat and apron as he stood in front of the grill, ready to do some serious cooking.  This seemed quite out of character for a fellow that almost always wore a blue suit and a blue tie.

In 1972, I was introduced to Woodward in Middletown, Connecticut by Jerome Berson, my Yale postdoctoral advisor.  I mentioned the photo to Woodward, and he broke into laughter recalling the scene in Winstein's backyard.  Woodward was about to present a lecture at Wesleyan U., on his collaborative synthesis of vitamin B12, which had just been finished.  Albert Eschenmoser of the ETH in Zurich, Switzerland, and Woodward, together with 99 graduate and postdoctoral students, had worked for 11 years to complete this monumental task.

Woodward started his talk by placing a country flag, about six inches tall, on the cabinet counter top at the front of the auditorium, for each country that was represented by his coworkers.  After all of the flags were carefully lined up on bench top, I counted a total of 11 different countries!  He didn't say a word.  Woodward then lay out two large white handkerchiefs on the bench top.  Upon one he placed five colors of chalk, all new pieces.  On the other handkerchief he placed an impressive number of cigarettes.  In an age when most formal lectures were presented using slides, Woodward proceeded to give one of his famous chalk talks, in which he painstakingly drew all structures on a large chalk board using these five colors of chalk.  He lit his first cigarette, and just when it got to the end, he used it to light the next one.  His chain-smoking continued throughout his talk. One of the key steps near the end of the synthesis was performed by my friend, Helmut Hamberger from Austria, who had been a postdoc with Winstein at UCLA before he went to Harvard to work with Woodward.  The several hundred  scientists and I, which were packed into this 'full house' performance, remained spell bound for the entire three hour lecture.  I remember this fine afternoon like it was yesterday.

I had an interesting encounter with a 'future Nobel Prize winner' in 1972.  I was making a connection in Chicago at O'Hare Airport, when I recognized Herbert Brown of Purdue University and realized that he was waiting for the same flight.  My graduate work at UCLA with Winstein on 'nonclassical ions' was highly contested by Brown in the chemistry literature, since he believed that 'classical ions' were rapidly equilibrating, and did not have a delocalized charge as had been proposed by Winstein in 1949.  I heard Brown give a lecture on his work at UC Riverside in 1967.  I introduced myself, and he was immediately friendly toward me.  We discussed my published results, and he was eager to know why Winstein, who had died unexpectedly in 1969, had remained so opposed to his theories.  It was a great opportunity for me to defend our research results with him.

A few years later George Olah, who pioneered the use of 'superacids' to generate carbocations in the 1960's at Dow Chemical in Ontario and Case Western Reserve University, was able to directly observe the delocalized charge in the same molecular structure that I studied in my thesis work, using low temperature nuclear magnetic resonance (NMR).  I was very excited to read Olah's published data, which gave further support to the nonclassical ion theory originally proposed by Winstein.  In 1968, my friend and colleague, Maurice 'Brook' Brookhart, in his Ph.D. work with Winstein and Professor Frank Anet, interpreted some NMR signals in 'superacids' that proved to be useful in Olah's studies.  Olah received the Nobel Prize in 1994.

Herbert Brown did all right, too.  Even though he was on the 'wrong side' of history in the nonclassical ion controversy, he did receive the 1979 Nobel Prize in Chemistry for his development of boron compounds into important reagents in organic synthesis.  In fact, I used his hydroboration reaction to my benefit in my work at UCLA, and also at the University of Lund, Sweden.  When I mentioned this to Brown, he was extremely pleased to know that I had such great success using his reactions.  Winstein told me more than once that Brown should have 'stuck to synthetic chemistry', and not engaged him in what became one of the greatest academic feuds in physical organic chemistry, a controversy that would last nearly 20 years by the time Winstein died.  Many leading scientists published work that would claim to support, or refute, the nonclassical ion theory.  Entire book chapters were written on this one subject alone!

Perhaps no one lost more in the nonclassical ion controversy than Saul Winstein.  I first met Winstein in 1965, shortly after I started graduate school at UCLA.  Winstein was 53, and had been a full professor since he was 35 years old.  I talked with four professors, including Winstein and Cram, before I decided that I wished Winstein to be my Ph.D. advisor.  His research group numbered 28 graduate and postdoctoral students, nearly half of whom were from Europe.  His work was exciting, and he was brilliant.  I knew that Winstein was a very demanding guy, but I thought that 'I could take it' for four years.  I recall that I worked 23 consecutive days between Thanksgiving and Christmas in 1967. Winstein wanted to submit my latest results to the Journal of the American Chemical Society before I went home for Christmas, and he was determined not to get 'scooped'.  I was more than eager to get my first paper from UCLA, and so I worked as hard as possible to make it happen.  Fortunately we did it!  About a month later, in January, Winstein stopped by my lab late one afternoon and asked me if I could use his tickets to the UCLA Bruins basketball game against Oregon State.  I did indeed!  I took this offer as a thank you for a job well done, although he never actually said those words.

Winstein conducted a weekly seminar, dubbed 'The Thursday Night Seminar', that would start at 8 pm, and would sometimes go well beyond midnight!  One professor from UC San Diego was given such a 'bad time' by the penetrating questions that Winstein posed about his research, that he vowed never again to return to UCLA.  Over time, these seminars became known world wide among organic and physical organic chemists. Years later while I was studying with Berson at Yale, he told me that when he began his academic career as an assistant professor at USC, he would make the hour drive to UCLA to attend these seminars each week.  He felt that the scientific rigor of these talks were second to none when it came to a discussion of the presented work, and that it was like 'obtaining a 2nd Ph.D'.  Winstein told me that the key to debating scientific issues is to be seated at the front row as he was, and have the speaker, or 'opponent' standing at the blackboard, where they must 'think on their feet'.  He said that this is always more difficult to do.  As you have probably have guessed by now, Winstein was eager to compete in the field of chemistry.  I had no idea that when he signed my completed Ph.D. thesis on October 2, 1969 that I would be his last graduate student.  I was one of seventy-two students that obtained their Ph.D. under his supervision.  He died suddenly six weeks later on November 23rd.

The following year when I was studying in Sweden, I met an Uppsala University chemistry professor at a meeting near Stockholm.  He was a member of the Nobel Prize in Chemistry nominating committee.  He told me that the committee had seriously considered Winstein as their top choice for the prize, but ultimately recommended a much older scientist since posthumous nominations are not permitted.  He felt certain the Winstein would have won the Nobel Prize the following year, if only he had lived.  How sad, as this achievement would have been one of Winstein's proudest moments in his illustrious career.  His work contributed mightily to the maturing of physical organic chemistry as a discipline. Winstein's discoveries of neighboring group involvement in cation formation, which was an outgrowth of his studies on nonclassical ions, became an integral part in the understanding of many important biochemical reactions.  As I recall my years at UCLA, I can still hear Winstein say 'how goes it?' as he would each and every time when he walked into my lab.  He would go to our lab blackboard, and we would discuss my latest progress by drawing structures, reactions, and tabulating any new kinetic chemistry results.  If it happened to be a Friday afternoon, he would always say 'I'll stop by tomorrow and see what's new'.  Needless to say, we worked most Saturdays in the Winstein Group.

As scientists, our discoveries are built on those that come before us.  Richard Heck, who received his Ph.D. degree at UCLA in 1954, initiated his physical organic chemistry career under the supervision of Winstein.  Heck then went to work for Hercules Powder Co. in Wilmington, Delaware, where he developed the 'Heck Reaction' that uses palladium to catalyze organic chemical reactions that couple aryl halides with alkenes.  He performed his early work single-handedly, without a research team commonly found in academia.  This reaction was used to couple fluorescent dyes to DNA bases, allowing the automation of DNA sequencing and the examination of the human genome!

Winstein's last consulting trip was to Hercules, just a week before he died, and I imagine that he met with Heck during his stay.  At the time, they were collaborating on a palladium catalyzed chemistry project, which was being performed by my Winstein Group colleague, Jack McCaskie.  In 2010, Heck won the Nobel Prize in Chemistry, and I am certain that Winstein would have been extremely proud of his former student.  I regret that I never had the opportunity to meet Heck.  However, it's quite remarkable how many amazing scientists I was able to know, or come in contact with, as I pursued my own career in chemistry.