Scientific Creativity and Responsibility

Scientific creativity can be defined many ways - as applied to chemistry, I think of it as the application of a sense of fantasy to generate a carefully crafted piece of research. I believe fantasy arises from the collision of ideas or groups of ideas or mental pictures that contain elements of similarity, but which are mainly unrelated. One group of ideas or mental pictures is stored in the brain, while the other is usually undergoing conscious examination. Let me illustrate. We have the following chemical terms - ethyl, barbituric acid, amyl, ester, half acid - half ester. Whenever I use these terms in a lecture, the girls I have known named Ethel, Barbara, and Esther, and the boys I have known named Emile come to mind. This cross-referencing of elements of similarity between essentially dissimilar phenomena is confusing - the conscious mind is constantly having to reject the nonuseful fantasies. If it fails, trouble arises. For example, I flunked an exam at Harvard because I substituted the word Amyl for Emile in the name of organic chemistry's greatest investigator - Emile Fisher, the second Nobel Prize winner in chemistry. Occasionally, two mental pictures that initially appear incongruent when placed side by side tend to merge to form a single, much more complete and lovely picture, a new one, whose components in retrospect have "cried out" to be fitted to one another. Dreams are composed of these "almost completely" unrelated mind picture sequences.

A disciplined mind discriminates between the mental images that "knock at the door" of consciousness, allowing attention to be given only to those that are useful, which is a fraction of one percent. When I have been stimulated by a sequence of related fits, some very tenuous, the relationships between the "new" fitted picture are examined for utility as hypotheses that can be verbalized - often the act of verbalization initiates a whole new line of mental pictures waiting to be merged.

Organic chemistry is largely empirical - the distance between observation and governing theory is very short. How can the investigator in organic chemistry initiate novel new thought patterns. He or she can do it by looking at the body of literature, noting gaps in it, and asking himself or herself questions about those gaps. The surrounding area can be scrutinized to look for small projections that line the gaps. This kind of thinking was used in geophysics when the idea of continental drift was born and tested. The moment maps of the world were drawn certain people looking at the bulges and depressions along the edges of the continents noticed that they had complementary shapes - that they could be roughly fitted together to make a single landmass. Those who pushed the idea further tested this theory by examining the geological-chemical history of hypothetical points of ancient contact. They matched very well. Many other questions were asked and answered. The theory of continental drift resulted.

In my field of organic chemistry, there are two general branches of research that have evolved side by side - the study of evolutionary organic compounds that compose the material world, and the design and synthesis of compounds that probably have not existed on this planet, but like a circuit board can be the product of the human mind and hands. The first kind of work involves discovering what nature has provided in the way of compounds, and the laws that govern their existence. The second kind involves the application of those laws to designing and producing "new compositions of matter." The number of naturally occurring organic compounds is undoubtedly well over a million, but no one yet can do other than make an estimate. The number of synthetic compounds now known is over seven million. Organic reactions useful for converting compounds into one another number a little over two thousand. Over half of the synthetic compounds now known have been prepared during my lifetime - my students and I have prepared an estimated 15,000-20,000 of them involving some 400 man years of effort and a cost of an estimated $40,000,000 in today's dollars.

Let me point to one research theme that we have been pursuing recently. About 10 years ago, I asked myself the question, can we design and synthesize a closed surface, sphere-like compound with a large enough hole in it to imprison other molecules or ions (charged part molecules). After thinking about the problem for about four years, a few viable approaches came to mind. Within the last three years we have synthesized three such compounds. The last step in the synthesis of each of these compounds involves four reactions, which tie two bowls together at their rims. The reactions were conducted in solution, and the components of the medium were imprisoned during the shell closure. Thus far we have imprisoned in our "molecular cell" the following components - Cs+, Na+, F-, DMF, DMA, and THF (simple organic compounds). We are tailoring the compounds to make them useful. Possible uses range from molecular light switches to radioactive delivery systems for cancer chemotherapy.

We have recently completed a research effort that started out with the question: "Can we design a system to complex specifically Na+ ion in the presence of K+ and change color, and a second system to complex specifically K+ ion in the presence of Na+ and change color? These compounds are now in commercial production for use in the colorimetric measurement of Na+ and K+ ions in blood and urine.

I believe that the most noble and important thrust of world culture in the last 200 hundred years has been in science. The fact that society supports scientists to do research demands certain behavior from scientists. Above all things, the scientist must be scrupulously honest in the reporting of his results.
REMARKS ON THE SIXTH DAY AFTER FORTY YEARS

In a car with R. B. Woodward driving to Brussels after a three-day IUPAC meeting.
Woodward: "Don, you gave a nice talk on Thursday, but I doubt if your research is what people are going to remember about you from this meeting."
Cram: "How so?"
Woodward: "What they will remember is that after the banquet you sat on a chair on top of a table, playing the guitar and singing to them in that foghorn voice of yours, with me holding your microphone in place."
This snippet of dialogue sets the tone for the remainder of my remarks here this happy afternoon. Ted Cairnes, the former director of research at DuPont once told me that "chemistry is not funny." My reply was "true enough, but chemistry is fun, and chemists are, on occasion, funny." What is true is that I have greatly enjoyed my teaching and research over my past forty years at UCLA, and am looking forward to some more of the same. In my view, the teaching of how to think about and execute research is the most noble of ventures in this twentieth century, and will likely be for the twenty-first. What a privilege I have enjoyed in growing up with UCLA. When I was a young man, UCLA was a young campus. Now that I am approaching late middle age, UCLA is just beginning to mature.
My concept of the values exercised in our Department over my forty years here are as follows. We have believed above all else in excellence, and in those organizational and human arrangements that breed excellence. For example, I believe in the principle of minimum governance. However, such a principle can work only if first-class staff are retained. I believe in challenge - principally that provided by research problems, but also that provided by co-workers and colleagues and, occasionally, that provided by our higher administration and the granting agencies. I believe in amity - in knowing how to lose with grace and how to win without arrogance. My training for the former has been more thorough than for the latter. I am currently in training for the latter, and the grades are not yet in.
Last Wednesday at 6:45 a.m., my good friend, George Olah from USC, called me. After listening to ten or so rings of the telephone, I thought it should be answered - it passed through my mind that someone might have died! George, in his unmistakable voice, said, "Wake up, Don, you have a big day ahead of you." I said, "What do you mean, George?" He said, "You have just won the Nobel Prize." I said, still half asleep, "How do you know?", a favorite expression of mine. He said, "I just heard it on the radio." I said, "You are pulling my leg!" He said, "This is pretty powerful medicine!" I said, "Thanks, George, but I still can't believe it", and hung up. I went back to bed without waking Jane, and had the stupid idea of catching a little more sleep. Then the telephone rang again, but I didn't answer it. I lay in bed, wondering what was afoot. The telephone stopped ringing, and then started again. I answered it, and some lady from KNX Radio asked if I wanted to make a statement as one of three Nobel Prize winners in Chemistry. By this time, I thought I had better wake Jane. So I shook her, and said, "Wake up Jane, I am going to need help - it appears that we might have won the Nobel Prize." By eight a.m., the television crews had arrived at the house. In about an hour, I went from scientist to celebrity. My hope is to return to my former status as soon as possible. Mel Calvin at Berkeley told me later that my life would never be the same. I am determined to go on enjoying my life much as it has been.
My fine wife, Jane, and I are just starting to get close enough to the ground to begin to enjoy ourselves. Here are some interesting facts: I have classroom taught about 8,000 ± 2,000 undergraduates at UCLA; have supervised the thesis work of about 110 graduate students, and the postdoctoral work of some 100 co-workers. I have consulted at Upjohn for 35 years, at Union Carbide for 20 years, and at Kodak for 6 years. What a great debt I owe to society, to UCLA, to my chairmen, to my colleagues, to my co-workers, and to my fine secretary and friend, June Hendrix. My longtime co-worker, Roger Helgeson, has been splendid. My wife has been my most constant critic and foil, and has frequently given me the right advice.
One last vignette - a Japanese co-worker had been working hard for three years to synthesize a hoped for strong binder of Li+ and Na+ ions, the first spherand. He was finally successful. About a week later he asked me, "How many times did you consider abandoning this project?" I told him I had never considered abandoning the project. After a minute, I said, "Taki, how many times did you so consider?" He answered, "once a week." Apparently Taki had faith in my faith. Research will be ever thus!
Science and Responsibility

1. Accurate, thorough, reportable results that are reported. Difficult to cheat - if work is insignificant or obscure, it might be years before checked. If important, then rapidly self-defeating. Science is an institution relatively untouched by the "something-for-nothing" side of human nature. It is open-ended -depends only on you - lends itself as a creative medium - good bookkeeping - can look up how great minds were occupied over the years. Has the nobility and legitimacy of removing or moderating the harshness of the human condition. Honor plays an important role. Two poles - academic and industrial. Each has its advantages. Academic freedom - still the marketplace for results is granting agencies with their peer review system. For example - personal history - research, teaching research, classroom teaching.

Everything that
We know and do
In times gone by
Was wild and new
A lot of good people have died by overstriving to stay alive!

Congratulations for my Nobel Prize came to me from the white house nine days after the announcement of my award, but just after the announcement the last of the awards was made. I know the white house has been trying to economize, and am glad to have first-hand evidence of their efficiency in getting all of the congratulatory messages out at the same time.

Rumors - unequal prizes
Nobel Peach Prize in Chemistry -
Chemists are on the warpath"
Statement to Academic Senate

If I told you I was a barefoot boy from Vermont, you would not believe me, although there is some truth in the statement. Explain. My hour-long Ascension to Scientific Sainthood has been rather exhilarating - now I must find some means of coming back to earth, where I am more comfortable. Further, I must resist the temptation to become an instant seer, prophet, priest, or authority on every subject under the sun. Thanks for listening.
I have never been caught without a statement!
Glenn Seaborg got the Nobel Prize as a young man. I am getting the Nobel Prize in late middle age. For my tastes, temperament, and durability, the timing of my prize is ideal. However, unlike Glenn Seaborg's prize, Uncle Sam is a corecipient of my award. But then, I do owe much to my country for supporting my forty-five years of basic research, 40 years of which have been at UCLA.
Dear President Gardner:
Recall our meeting one another last October the day after my selection as the 1987 Nobel Prize Winner in Chemistry when you invited me to address the Board of Regents meeting at UCLA. We again met in Sacramento on March 9 at your reception for UC alumni, a group to which you asked both Professor Y. Lee of Berkeley and me to say a few words.
After forty-one years of continuity at UCLA, I am writing because of the uncertainty as to my status in the university in the short and longer range future. I was born April 22, 1919, and am subject to normal mandatory retirement on July 1, 1989. However, my chairman told me recently that in the latter part of June, a nomination of me for a University Professorship by the appropriate committees, and individuals at UCLA was sent to your office for further consideration. I currently raise and account for about $500,000 a year from federal granting agencies, which supports a research group of eleven coworkers. A variety of personal, personnel, and grant application decisions must be made which are tied to whether or not I will retire July 1, 1989. The longer the lead time for these decisions, the greater the wisdom and humanity I can apply to them. Accordingly,. I am hoping that you can expedite the deliberations on my nomination, and can tell me when a final decision might be made.
Cordially yours,

/s/Donald J. Cram
S. Winstein Professor of Chemistry
Scientific Creativity and Responsibility
Governed sense of fantasy applied to a carefully crafted piece of research. Successful research is a process in which a large gamble becomes less of one as results appear. Faith - confidence - any damn fool. Two kinds of research in the physical sciences - both ultimately limited by physical law. One is the study of nature - the evolutionary patterns of nature (e.g., the universe, or matter at the molecular level, or at the biological level). The other is the invention of compositions of matter that probably have never existed in nature. Nakagawa and the immune system (a study of nature - Nakagawa and the immune system (a study of nature - Nakagawa is a modern naturalist). New compositions of matter can be invented in the cyclotron, or in the organic chemist's laboratory, or in the shop of a maker of circuit boards.