Ted Taylor and the Butterfly Effect

Editor’s note: Chemistry professor emeritus Edward C. “Ted” Taylor, one of Princeton’s best-known faculty members, died Nov. 22 in St. Paul, Minn., at the age of 94. Following are remarks delivered by Tom Muir, chair of the University’s chemistry department, at Taylor’s funeral service.

Good afternoon — my name is Tom Muir, and I have the honor of serving as chair of the Princeton chemistry department, a department that Ted Taylor was associated with for some 63 years. I am here today to say a few words about Ted’s scientific accomplishments, academic career, and, of course, his contributions to society. Let me begin by stating that it is simply impossible to do justice to Ted’s professional life in any reasonable amount of time – I would literally need a week. The man was blessed with incredible energy and vigor that extended to the very end of his life, as did his almost childlike curiosity of the world around him – we should all be so lucky. As but one metric of his professional output, Ted published 450 scientific papers, edited some 90 scholarly books, and was awarded 52 patents. In case you are wondering – this is a lot, even by the over-achieving standards of a place like Princeton. So what follows is but a mere sampling of his numerous and lasting contributions to science and the academy.

The butterfly effect is defined as “small, seemingly random events that can have larger effects in the world.” As I will attempt to convince you, this concept is particularly relevant to Ted’s career, in more ways than one. Indeed, that Ted even decided to pursue chemistry as a major in college can be traced to such a random event, in this case a simple toss of the coin. For as Ted told me a few years back, giddy-eyed as always, this was exactly the basis on which he decided to major in chemistry while an undergraduate at Hamilton College and later Cornell – he always loved the subject but needed this act of Providence to send him on the right path. In hindsight, it is a little scary to think that the lives of countless people were so positively affected by such a seemingly nonchalant decision!

The second butterfly effect literally involved butterflies. It is now well known, to point of lore in the chemistry community, that way back in 1946 Ted read a chemistry publication while in graduate school about an organic molecule found in the pigments of butterfly wings that looked similar in structure (its chemical shape) to a molecule just isolated from plants and from the livers of animals. This liver molecule turned out to be folic acid, or folate, an essential vitamin required in the biosynthesis of DNA and RNA. This early work had a visceral effect on Ted, setting him off on a lifelong love affair with a class of organic molecules known as heterocycles, of which folate is but one example, albeit a really important one. Now I can see some folks eyes beginning to glaze over on hearing this “chemistry speak,” so let me briefly describe to you what heterocycles are and why you, like Ted before you, should care about them.

Life on our planet is carbon based – we all know this. But carbon, in and of itself, is not enough to build even the simplest life form, it needs some chemical “seasoning”  in the form of what we chemists call heteroatoms. Now you have all heard of these; nitrogen, oxygen, and sulfur are examples of heteroatoms. Many of these elements are in the air around us, but almost miraculously they make it into essentially all of the molecules of life. Now a heterocycle refers to a ring of mostly carbon atoms that contains one or more nitrogen, oxygen, or sulfur atoms typically – imagine six Scotsmen standing in a circle holding hands, now kick one of them out and replace him with an Englishman – voila, a heterocycle. See, it is not so hard. And let me tell you, it is hard to think of a class of molecule more important than heterocycles. They are the key components in the molecules of life; found within the amino acid building blocks of proteins, the nucleoside building blocks of DNA and RNA, and even the carbohydrate building blocks in sugars. Moreover, the vast majority of pharmaceutical drugs contain heterocycles. Put simply, a world without heterocycles would be a grim place indeed.

Ted set out to become an expert in heterocyclic chemistry, learning their chemical properties and how to make them, first as a graduate student in Cornell and then as a postdoc and junior faculty member at Illinois. So by the time he arrived in Princeton in 1954, he was already gaining a reputation as one of the rising young stars in this field of organic chemistry.

Ted thrived at Princeton, both personally and professionally. In recognition of the latter, he was appointed the A. Barton Hepburn Professor of Organic Chemistry in 1966, a position he held through his retirement in 1997. Indeed, by the 1970s he had established himself as probably the leading heterocyclic chemist in the world. He made many important contributions to the field of organic chemistry. He was among the first chemists to explore the utility of metals, specifically thallium, in the synthesis of complex organic molecules such as heterocycles – helping to establish the important field we now call organometallic chemistry. He developed ingenious ways to assemble heterocyclic molecules, many of them of therapeutic value. Admittedly, this sometimes got him into hot water, like when he and his students figured out a clever way to make the active ingredient of marijuana – a heterocycle called a cannabinoid, or THC. Apparently, this led to part of his lab being closed down for a while by the U.S. Department of the Treasury, although he did apparently get his photo into Life magazine.

So all of this meant that Ted was perfectly primed to take on the professional challenge of his life, which brings us back to the butterflies. If you remember, the butterfly pigment looked similar to folic acid. By the early 1970s it was already recognized that mimicking folic acid was a powerful way to block the synthesis of DNA/RNA, which in turn stops cells from dividing – a good thing in, say, cancer. Indeed, there were at that time drugs on the market, for example methotrexate, that mimicked folates and hence inhibited enzymes that used this vitamin in the biosynthesis of nucleic acid building blocks. But these existing drugs are very toxic and not suitable for many medical indications.

Ted entered the fray in the mid-1970s with the view of making a series of slightly modified versions of folic acid, what medicinal chemists call analogs, that might more selectively inhibit metabolic enzymes that utilize the vitamin to make key heterocycles needed for the generation of DNA and RNA – these are called purines and thymidylate. As part of this campaign, and one cannot overstate the importance of this, Ted was able to tap into his connections in the pharmaceutical industry – specifically Eli Lilly and Co., where Ted had been a consultant for many years. Thus, an unprecedented and now famous academia/industry collaboration was set in motion, whereby the Princeton group would lead up the chemistry effort on the synthesis of the analogs, while the biochemistry and pharmacology testing of these molecules would be carried out in Indianapolis. The eventual success of this collaboration, which remains a model of its kind, rested on the deep respect the two groups of scientists had for each other, allowing unfettered exchange of ideas, and I must say by the remarkable flexibility that the scientists at each institution were given to work on this long-term project. Ted told me more than once that he doubts such a lengthy collaboration would be possible now, and I fear he may be right.

Be that as it may, the Princeton/Lilly collaboration was a resounding success. Of course, it involved a tremendous amount of work on all sides, including the synthesis and evaluation of some 800 compounds, but eventually the team arrived at an optimized molecule, known by its trade name pemetrexed, which acted as a potent and selective inhibitor of the folate-dependent enzymes in their crosshairs. Amazingly, pemetrexed was a slight variation on one of the very first compounds Ted had designed back in the 1970s – talk about insight. By 2004, this drug, marketed as Alimta, had been approved for the treatment of malignant mesothelioma, and thereafter, other devastating lung cancers. This blockbuster medicine has extended and improved the lives of countless cancer patients around the world. Altogether, a remarkable contribution to society. On a more local level, royalties from Alimta, paid to Princeton by Lilly, financed the incredible new chemistry building my colleagues and I are all so privileged to work in – certainly the best facility of its kind anywhere (and I have been most places). So all and all, if this isn’t the world’s best example of the butterfly effect, then I do not know what is.

Ted rightly received an enormous amount of recognition for his research achievements, both basic and applied. He was the recipient of a very, very long list of prestigious awards and prizes from a host of learned societies and top universities around the world. This list is way too long for me to recite, something I know Ted would have just hated me to do anyway. Basically, Ted won nearly everything. I will mention only two since I think they speak to the impact of his work and the esteem with which he was held, namely: He was named a Hero of Chemistry by the American Chemical Society in 2006, and in 2013 he received the National Academy of Sciences Award for Chemistry in the Service to Society.

Despite all this fame, Ted remained the consummate academic, a conscientious colleague who served in various leadership roles at Princeton University and beyond, including as chair of the chemistry department for most of the 1970s. Ted was also a dedicated teacher who taught organic chemistry to legions of undergraduate and graduate students at Princeton, his exuberance for the field no doubt inspiring many to pursue the subject as a career. But what I think Ted was most proud of in his career are the hundreds of students and postdoctorals who trained in his laboratory and who then went on to do great things in the world. Ted was by all accounts an amazing mentor, and I would posit that this, as much as anything, is his most lasting professional legacy, particularly when one considers all the folks that this immediate cohort have themselves gone on and trained – a multiplier effect, rather than a butterfly effect. At this point, I would be terribly remiss if I didn’t say that Ted will continue to shape new generations of scientists at Princeton, thanks his remarkable generosity and that of the family. Of his many gifts to the academic community, I will mention just one since it is near and dear to my own heart, namely the Taylor Chemistry Graduate Student Fellowship program that was established last year. This will have a lasting impact on science at Princeton, and is something that I know that other schools are now trying to emulate. Working with Ted on the development of this idea was a joy from beginning to end – I got to witness the man in action; a force of nature to be sure.

So to conclude, Ted was an incredible human being. His joie de vivre, fueled by a piercing intellect and an unshakable hopefulness for the future, was a rare thing indeed, as was his remarkable generosity. Altogether he leaves an amazing legacy and provides a shining example of a life well lived. He will be greatly missed by everyone fortunate to have met him. So on behalf of everyone at Princeton, an institute packed full of his friends, let me conclude by offering my heartfelt condolences to the Taylor family on your loss. Thank you for sharing this wonderful man with us.