Fifty Years After Huxley: The Roadmap of Reproductive Medicine Revisited and Updated: The 2015 SRI-Pardi Distinguished Scientist Plenary Lecture of the Society for Reproductive Investigation.

President Bulun, Members of the SRI, Friends, What a pleasure it is to be back. It has been 15 years since I had the privilege of presiding over this society then known as the Society for Gynecologic Investigation (SGI). I am especially pleased to see President Bulun at the helm. The society could not have done better. I also wish to take this opportunity to thank the society for this vote of recognition. I am deeply honored. Among my distinguished predecessors, I wish to single out Robert B. Jaffe, the 1973 president of this society who made this city his home (Figure 1). This presentation is dedicated in his honor. Aldous Leonard Huxley, a liberal humanist and one of the preeminent intellectuals of his time, died at the age of 69 in Los Angeles in 1963 (Figure 2). Were he to rejoin us today, 50 years hence, he would hardly be surprised. By now, sex without reproduction and reproduction without sex have become commonplace in a manner he long ago envisaged. Equal equanimity would likely have been accorded to some of the improbable scientific breakthroughs of the day most if not all of which he has prefigured. The grandson of a celebrated zoologist, Thomas Huxley, the brother of an evolutionary biologist, Julian Huxley, and the half-brother of a Nobel Prize-wining physiologist and biophysicist, Andrew Huxley, Aldous never suffered from want of scientific enlightenment (Figure 3). His hopes of becoming a physician, however, were dashed early on by compromised eyesight. Instead, he threw himself with abandon into a life of literary excellence. Still, it is safe to assume that young Aldous was suffused with the science of the day. For all we know, his keen foresight may well have been informed by no more auspicious a source than conversations around the family dinner table. That said, John Haldane’s 1924 essay, Dedalus, or Science and the Future, was probably just as pivotal. 1 Brave New World, Huxley’s bleak satirical masterpiece, written in all of 3 months, was all about a sinister dystopian future gone off the deep totalitarian end. Set in London of 2540, the plot as such it is revolves around a regime bent on reproductive and social engineering, with the view of keeping the masses at bay through endless mindless bliss. Sex was recreational, love was obsolete, and the notion of a family obscene. Unexpectedly, however, in an all too brief an opening chapter, we are being treated to a profound display of clairvoyance in which Huxley literally lays out the future of reproductive medicine. The setting by any other name is a familiar one. The so-called Central London Hatchery, replete with its ‘‘Fertilizing Room,’’ incubators, work tables, slides, test tubes, bottles, and microscopes, could readily pass for today’s embryology laboratory. Eggs are secured via ex vivo cultures of whole ovaries. Embryos in turn are secured via, imagine, in vitro fertilization only to be followed by in vitro gestation that is ectogenesis. Even genome editing and human cloning receive some mention. Clearly, the arc of Huxley’s vision went well beyond the present state of the art. Hard as we might try, we are still catching up to him. The realization of in vitro fertilization (IVF) by Edwards and Steptoe constituted a remarkable indeed disruptive innovation. Life thereafter was never the same again. Many of us were fortunate enough to witness this breakthrough in our lifetime. Huxley, regrettably, passed on 15 years earlier. Recognized by a Nobel Prize in physiology and medicine (Figure 4), IVF all but vanquished the scourge of infertility. No less important, IVF gave rise to multiple often improbable therapeutic and diagnostic breakthroughs, many of which could not have been foreseen by its originators let alone Huxley. Astoundingly, IVF, remarkable a feat as it was, could well be supplanted before too long by a literal watershed of unprecedented breakthroughs which are materializing at a far more ferocious clip than ever before. With your indulgence, let me expand some on this latter point. Examined in hindsight, the