Remembering Ray Salemme

It was a year ago last week, while I was having dinner with my family at the idyllic Limeni bay in the Mani peninsula in southern Peloponnese, when I received the dreadful call from my former 3DP colleague Rich Soll letting me know that our mentor and founder of 3-Dimensional Pharmaceuticals (3DP), Ray Salemme, had passed away. We all feared that that moment could come but refused to lose hope – we were accustomed to Ray recovering from setbacks and beating the odds that even cancer, we believed, would be no match for him.

Ray was a remarkable man by any measure: a brilliant scientist, an inventive engineer, a visionary leader, an expert team builder – perpetually curious, relentlessly enterprising, incurably optimistic, unfailingly inspiring – a restless mind who combined a passion for science and technology with dogged perseverance and resilience, and a discerning eye for talent and character.

Ray was a loving and devoted husband and parent. His admiration and affection for his wife Patricia (Pat) and their sons Patrick and Bruno was boundless. I witnessed it the first day I met him during my interview, which took place at the Longwood Gardens in the former DuPont estate. That evening Pat had a car accident and we ended up cutting our dinner short, visiting her together at the hospital, and driving her home after her discharge. I could see how worried he was about her, yet they both insisted that I spent the night at their house. Ray treated his employees like a second family. He felt a deep sense of responsibility to them and their families who depended on his judgement and leadership for their livelihoods. That responsibility weighed heavily on his shoulders.

Ray commanded great respect, trust and followership. He made you feel valued and important, but also kept you grounded; he would absorb the shocks and shield you from problems beyond your control that could demoralize or distract you; he would not mislead or abandon you in difficult times; he would take personal accountability and not lay blame when things did not go as expected; he would remove obstacles and help you find solutions; and when you did, he would sing your praises more than anyone else I have ever known. His leadership was instinctive and came straight from the heart.

His interest and support had no expiration date. He took pride and joy in our successes, and supported each one of us personally long after 3DP ceased to exist as an independent entity and our careers diverged. He just cared about us.

Ray always considered 3DP to be his crowning achievement. He was proud of the team he had assembled in that microcosm of drug discovery and the pioneering work that was done under his guidance in so many areas – from combinatorial and medicinal chemistry to structural biology, biophysics, computational chemistry, informatics, and engineering – which he chronicled on his personal website with the precision, objectivity and self-reflection of a dutiful historian.

It is hard to identify the inflection points in one’s life, the exact moments when things take a decidedly different turn, but my decision to join 3DP was definitely one of those moments that set my career on a trajectory that I could never have imagined.

It was there where I came of age as a scientist, published my first independent papers, had my most creative ideas, and wrote my most inventive code.

It was there where I built some of my strongest professional bonds and closest friendships that would endure through distance and time.

It was there where I learned how to lead a group, hired my first teammates, and watched them grow into independent researchers, engineers and professionals, making their own mark.

It was there where I experienced life’s full range of hopes and anxieties, breakthroughs and setbacks, celebrations and defeats – from not knowing whether we could make payroll the next month to having one of Y2K’s most successful biotech IPOs; from frustrating experiments to important discoveries; from joyful family picnics and holiday parties to heartbreaking personal stories that kept reminding us all of the fragile and unpredictable nature of the human existence.

It was also during those years when my second daughter was born and when I learned of my father’s diagnosis with terminal cancer – life’s highest ups and lowest downs.

And so it was in this most magical and peaceful of settings, surrounded by the people I loved the most, that I experienced once again that strange mix of emotions – a deep sadness for my mentor’s loss with a profound gratitude for all he had done for me, for the wonderful life that he helped me built. It is the same sadness and gratitude that I feel every year when I visit my father in his resting place and I am reminded that the secret to living a worthy and fulfilled life is being of help to others.

It was with these thoughts and with the voice of Nikos Xylouris singing Kostas Karyotakis’ melancholic verses echoing constantly inside my head – in the language and sounds that have defined me – that I spent the rest of that summer remembering Ray’s worthy life and mourning his untimely loss:

You are, my soul, like a maiden who is being extinguished

by a bitter love

who was forgotten looking back at the bygones

never to return.

Alone in a corner, like her,

you are abandoned by people, by time

you would be just another one among the dead

had the dead not found their peace.

I hope Ray has found his.

____________

Photo: A picture from a mini 3DP founders reunion taken on September 15, 2016 in Yardley, PA. Shown from left to right are Victor Lobanov, myself, Roger Bone, Ray, and Scott Horvitz. Ray is holding the first 3DP annual report following the IPO.

Ray’s biography:

Francis Raymond (Ray) Salemme (born on 8 June 1945 in Norwood, MA, USA) was a prominent structural biologist and successful American entrepreneur. He was best known for his pioneering work in protein crystallography and the founding of 3-Dimensional Pharmaceuticals, a Nasdaq-listed biotechnology company that developed several ground-breaking technologies for precision and high-throughput drug discovery and was acquired by Johnson & Johnson in 2003.

Salemme was admitted at Yale University as a high school junior at the age of 16, where he studied Molecular Biophysics, receiving his B.A. with exceptional distinction in 1967. During his undergraduate studies, he spent a year as a shipboard scientist and able-bodied seaman aboard the oceanographic research vessel USNS Robert D. Conrad where he circumnavigated the earth (~70,000 nautical miles) to map tectonic plate boundaries and perform seismic profiling and deep core sampling of geological features on the ocean floor.

Upon his graduation from Yale, he moved to the University of California, San_Diego (UCSD) where he received his Ph.D. in Chemistry under the direction of Joseph Kraut in 1972. His doctoral work resulted in the determination of the crystal structure of cytochrome c2, one of the first protein structures to be determined at near atomic resolution using X-ray crystallography.

From 1972 to 1973, he was a postdoctoral fellow at UCSD with M. D. Kamen studying electron transport mechanisms, while simultaneously designing and constructing the UCSD steam-powered car for the CalTech-MIT coast-to-coast clear air car race, along with Stanley Miller and Rodney Burton.

Following his postdoctoral training, Salemme joined the faculty at the University of Arizona in 1973 as an Assistant Professor of Biochemistry, eventually rising to the rank of Full Professor in 1982. While at Arizona, he determined several protein crystal structures using X-ray techniques, authored high-impact papers on biological electron transfer mechanisms, principles of protein architecture, and the role of dynamics in protein function, and built a digital coordinate measuring machine to replace the plumb bob.

In 1983, Salemme left academia and joined Genex Corporation as Director of the Protein Engineering department, one of the first integrated research teams in the biotechnology industry to successfully engineer proteins using a combination of protein crystallography and computer-aided design methods. At Genex, he developed ground-breaking technology for rapid protein structure determination using 2-dimensional X-ray area detectors, designed and engineered the first single-chain Fv antibodies for diagnostic and therapeutic applications, and developed advanced computer programs for protein engineering to produce improved catalysts with properties suitable for industrial process environments.

In 1985, Salemme moved to DuPont Central Research and Development and then DuPont Merck Pharmaceuticals where he built and supervised a multidisciplinary group of biophysicists, crystallographers, computational chemists, and applied mathematicians, oversaw the crystal structure determination of several therapeutically relevant proteins such as streptavidin, protocatechuate dioxygenase, interleukin 1?, phospholipase A2 and several retroviral proteases, and developed and commercialized the first robotic system for protein crystallization.

In 1991, he joined Sterling Winthrop Pharmaceuticals as Senior Director of Biophysics and Computational Chemistry, where he established and directed a new department that consolidated technical resources for structure-based drug discovery and rational drug design across the company.

In 1993, Salemme left Sterling Winthrop to found 3-Dimensional Pharmaceuticals (3DP), a biopharmaceutical company that focused on the development of novel technologies on the interface of structure-based drug design, combinatorial chemistry, high-throughput screening, and computing, and the discovery of drugs for cardiovascular disease and cancer. As 3DP’s President and Chief Scientific Officer, Salemme raised over $40 million in equity-backed capital, assembled a Scientific Advisory Board comprised of prominent life scientists including the 2013 Nobel Laureate Michael Levitt from Stanford, the late Lasker Award winner Don Wiley from Harvard, the former Editor of Science, NIH NIGMS Director and Johns Hopkins University professor Jeremy Berg, and now retired Princeton University professor Clarence Schutt, developed an aggressive intellectual property strategy, formed collaborations and licensing agreements with several biopharmaceutical companies, and secured an ~$85 million investment in its initial public offering in August 2000 (NASDAQ:DDDP), which valued the company at ~$335 million. The technologies that Salemme pioneered at 3DP include ThemoFluor?, an integrated software and instrumentation solution for label-free drug screening and related applications requiring thermodynamic measurements of protein stability; DirectedDiversity?, an AI-driven adaptive drug optimization process control technology that enabled directed exploration of chemical space using machine intelligence and robotic parallel synthesis and biological screening; and DisoverWorks?, an integrated data management and analytics platform designed to increase the productivity of the drug discovery process and enable scientists to optimize drug candidates. The computational and cheminformatics codes developed at 3DP became the foundation of Johnson & Johnson’s ABCD discovery informatics platform, which has been in continuous use since 2005 to enable every drug discovery program at the world’s leading healthcare company.

Following 3DP’s acquisition by Johnson & Johnson in 2003, Salemme joined Redpoint Bio Corporation as Chief Executive Officer, where he developed its strategic and technical plans and led the discovery of chemosensation modulators, allowing the use of reduced quantities of sugar in food and beverage applications, and the modulation of incretin secretion for diabetes and obesity.

In 2004, and while at Redpoint Bio, Salemme co-founded with his wife Patricia Weber Imiplex, a nanotechnology company focused on the development of specialized computer codes for engineering nanostructures for life and material science applications, where he served as President until 2019. He passed away on July 24, 2019 at the age of 74.

Salemme was the author of 100 peer-reviewed publications and book chapters and co-inventor of 42 patents. He had an h-index of 48 and more than 10,000 citations to his work.

He received the Camille Dreyfus Teacher-Scholar Award in 1978 and the Ernst and Young Greater Philadelphia Emerging Entrepreneur Award in 1998.