The “fittest sterol” - origin mysteries still fascinate

As a graduate student, I ended my PhD work on this very topic with van Tamelen. My experience on the cyclase^[1] project greatly influenced my views of chemistry and the chemistry of life itself, and it still does today. I think of this bizarre process discovered by life, as it got to cholesterol, as one of the greatest stories to alert humankind that we are deluded in our aims to discover life’s most profound, even just physics and chemistry mysteries, let alone our endless, fanciful worries^[2,3].

Returning to direct comments on Krief et al.^[4] work here, I found it fascinating and profound scientifically. More than most other chemists, except for Hisashi Yamamoto, I can say how tough synthetic chemistry stands behind this work^[5,6]. Not only are the steps fraught with steps that never give perfect yields, but they are also deep into overlapping physical properties of the product mixtures, and then they need to get each component of mixtures separated and then on very small scales assigned unambiguously.

This takes concentration and effort beyond any challenges I have taken on since graduate school. This is important scientific research that has been conducted without taking any shortcuts. The scholarship is superb. The paper is illuminating, thought-provoking, and its methodology is a model for others to follow.

Chemical Synthesis is so fortunate that its debut motivated Prof. Krief and his associate to revive this research. Moreover, I would like to close now by giving the authors my most sincere and highest congratulations!