Note on the cultish status of organic synthesis: Part 1

When I was in graduate school, a friend and I used to joke that the most egotistical elitists are to be predominantly found in two fields: particle physics and the total synthesis of complex organic molecules. As with most jokes and exaggerations, this one had a shred of truth in it. We had read about the hubris arising from a belief in strict reductionism to be found among particle physicists, and we had heard of similar hubris arising from a sense of mastery over nature found among synthetic organic chemists. What physicist has not heard Paul Dirac's quote that quantum mechanics would explain "all of chemistry", and what organic chemist does not like to gossip about slave-driving synthetic chemists who think they are doing other chemists a favor by contributing to what they have proclaimed to be the highest calling in their field? There is little doubt that more than many other branches of chemistry, organic chemistry and synthesis in particular enjoy (or is it suffer from?) a cultish status.

More recently, a few comments on the "greatest chemists" post at The Skeptical Chymist again struck a chord. The writers of the post wondered whether "organic chemists are just a little insular and think that their bit of the chemistry kingdom is the only one that matters?". Another commenter reaffirmed this sentiment by saying that more than other fields of chemistry, "organic chemists have a culture of legend-making".

I agree with both these statements and I think there are three main reasons why organic synthesis has lent itself to cult-making. A major reason is the personalities, their exquisite language and metaphors, their harnessing of armies of graduate students and postdocs and the stories they loved to weave around their science. The second reason is simply the great practical utility of organic chemistry in improving the quality of life. The last and perhaps the most important reason is the continued perception of organic synthesis as the ultimate chemical science which has lifted the great veil of nature and allowed man to wrest Nature's deepest secrets from her; there is something stupendous in having a mere mortal synthesize chlorophyll from scratch. The three reasons are connected, but each brings a distinct flavor to the argument. In this post I will dwell on the perceived cult of personality in organic synthesis, and will leave the rest of the discussion for another post.

So let's talk about the personalities. At the outset let's make it clear that not all organic chemists revel in showmanship, and such generalizations can be flawed. There are of course dozens of brilliant chemists who are extremely unassuming, letting their colleagues put on the shows in papers and in lectures. Yet as we all know, belief depends as much on perception as on reality, and there is a very distinct feeling in the chemical community that synthetic organic chemists love to perform more than others.

Is this true? Well, more than most other chemists, organic chemists have surrounded themselves with stories reminiscent of tales of great human adventures, exploits, triumphs and follies. Myth-making has contributed somewhat uniquely to organic chemistry. Part of the myth-making and legend-building was engendered by a happy accident of history that inadvertently did some harm to the perception of the field- the name of this happy accident was Robert Burns Woodward. So much has been said about him that it's not worth repeating. But there was no comparable chemist in any field during his time, and as long as he lived, Woodward achieved feats that almost defied belief. It's hard to see how organic synthesis would have turned into a mythical endeavor had it not been for this singular man. Others like Corey, Djerassi, Danishefsky, Nicolaou etc. simply carried on the tradition. Harvard became the mecca of organic synthesis, and Woodward and Corey's laboratories turned into Plato's academies through which every budding intellectual in the field had to pass in order to get a stamp of respect. Even today it's remarkable how many top synthetic organic chemists in the world have trained with one of these masters. The students in turn have carried forward the legend-making and perpetuated the reputation of the field, like Homer's portraits of Hector, Achilles and the great wars they fought in.

A corollary to the legend-making is the language and the metaphors. Look up some of the most famous total synthesis papers and the authors make them sound less like synthesis and more like a combination of Tenzing and Hillary's conquest of Everest and Michelangelo's painting of the Sistine Chapel. For instance, a review on the synthesis of the CP molecules begins with stories and portraits of Thesus's pursuit of the fearsome Minotaur. Organic synthesis is portrayed as the ultimate art and adventure and organic chemists are intrepid explorers venturing into the unknown. There is no doubt that synthesis is an art and that synthetic chemists are explorers, but so are other scientists. In fact, protein crystallography probably lends itself to the mountain-climbing metaphor even more since crystallographers sometimes stake their entire careers on the relentless chase of a single structure. Yet it's organic synthesis and not other branches of chemistry which claims to be the epitome of art, science, adventure and determination. I suspect that is partly because unlike synthesis, crystallography is a more interdisciplinary activity that cannot be easily labeled as chemical.

Again, one has to inevitably partly blame Woodward. For instance, consider this masterpiece from his colchicine synthesis which makes us feel like we are reading not Woodward but Tolkien:

"Our investigation now entered a phase which was tinged with melancholy. Our isothiazole ring had served admirably in every anticipated capacity and some others as well...it had mobilised its special directive and reactive capacities dutifully, and had not once obtruded a willful and diverting reactivity of its own. Now it must discharge but one more responsibility- to permit itself gracefully to be dismantled, not to be used again until someone might see another opportunity to adopt so useful a companion on another synthetic adventure. And perform this final act of grace it did."

A more exquisite paean to a five-membered ring containing carbon, nitrogen and sulfur was never penned. No wonder synthesis acquired the status of a highly-refined art form. One wonders how the field would have been perceived had it not been for the flourishing phrases, the allusions to mountain-climbing and Greek classics and the romantic metaphors. Not everyone does this of course, but it seems to be widely prevalent among top synthetic chemists.

The power of personality also extends to power over other human beings, and this has always been a sensitive topic that has contributed to the field's reputation. In the latter half of the twentieth century, the ability to synthesize increasingly complex molecules translated to the need to amass armies of students and postdocs. Woodward's collaboration with Swiss master Albert Eschenmoser on the stunning synthesis of Vitamin-B12 is a telling example; the synthesis involved dozens of graduate students and postdocs in a kind of trans-Atlantic relay that spanned 12 years and almost a hundred steps. Who would not be swayed by such overarching ability to attract personnel, resources, time and funding? Other total synthesis chemists also typically command such a glut of labor. For a long time, organic synthesis was regarded as the ultimate character-building experience. Hard work is of course essential to success in any science, but organic synthesis seemed to require a particularly intense combination of the ability to constantly bounce back from failure and the cheerful stamina of a marathon runner. This is perhaps one of the reasons why total synthesis students in my department appeared darker and more self preoccupied than others, and it could also contribute to the perceived sense of hubris among synthetic chemists. But that is also one of the reasons why total synthesis students are highly sought-after in both academia and industry, not just for their technical abilities but for their doggedness.

Nonetheless, while synthetic activity continues to be regarded as a character-building experience, the reputation of synthetic chemists has suffered in recent years because of their reliance on cheap labor and the unusually harsh working hours that synthesis students have to endure. Synthetic chemists have been held up as slave-drivers who care little about their students' education and simply need them to serve as automatons who plug one step's intermediate into the next. There have even been rumors of students forced to compete against each other for the quickest route to the product, with the "loser" not making it to the authors' list on the paper. New students are being advised not to spend five years working in a high-profile total synthesis group if they want to have a life outside graduate school. Stories of student suicides have done nothing to improve the situation, although one wonders if such stories are also not to be found in other disciplines and are simply being highlighted because of the high-profile nature of the groups. Is this reputation deserved? I don't know, but it certainly seems to contribute to an unfavorable view of total synthesis.

Yet this view has not generally colored the status of the field. Total synthesis still commands the attention of first-rate blogs, synthesis papers still make it to highly-cited lists, and total syntheses are still enthusiastically lauded as the works of art which they undoubtedly are. While the reputation of synthesis may have suffered because of myriad factors, the power of personality and the artistic metaphors have guaranteed it a special place in the minds and souls of chemists. The ghost of Robert Burns Woodward lives on in more than one way.