Your Excellency Mr. President of the Republic,
Your Beatitude – Your Grace,
Your Excellency Mr. President Vassiliou,
Your Excellencies Mr. Ministers – Distinguished guests,

In accepting the great honor that comes with the Nemitsas Prize, I wish to thank the selection committee and the Board of the Nemitsas Foundation, especially Mr. Takis and Mrs. Louki Nemitsas for the great honor that bears their name and which brought me this evening in front of this distinguished audience. I sincerely thank you Mr. President and Makariotate for your presence here tonight, which makes this ceremony so much more magnificent and meaningful to all of us. I would also like to thank Professor Marios Mavronicolas, Vice Rector of the University of Cyprus for his nice words about me, and I hasten to add that I share this honor with my family for their unconditional love and support and my students for their contributions.

My speech will include remarks about my family and upbringing in Cyprus and my subsequent adventures around the world as I endeavored to establish my career abroad, and together with my wife, Georgette, create my own family in the United States, but never forgetting, of course, our Greek Cypriot origins and culture.

My Family, Education and Career

Born in Karavas, a town in the now occupied part of Cyprus, I was not exactly poised for a scientific career in chemistry, certainly not one that would bring me to this podium this evening. My grandfathers were both small farmers, cultivating their small patches of land to feed their families and earn enough money for their most basic needs. My father could only become a mason, having attended schooling no further than third grade. His wish for me was to become an architect, but I was more fascinated about the stars and the universe. While my father was thinking about my future, my mother was lovingly involved with my everyday needs and those of my younger brother Nicolis and younger sisters Despo, Vaso, Rita and Yianna, but not without working in the fields to earn additional monies for the family’s needs. Needless to say we all had to work from a young age as part of our duties to contribute to our upkeeping.

I attended primary schools at Karavas and first grade at the Lapithos Gymnasium before my father arranged for me to enroll at the Pancyprian Gymnasium in Nicosia, where I received the rest of my high school education while I was living with my uncle John and his family and working in his pastry shop in Ayios Dhometios. At the Pancyprian I had the good fortune of encountering incredible teachers, including Dr. Telemachos Charalambous, my chemistry teacher, who identified my talent in chemistry and inspired me to follow it with passion. I was also fortunate to be one of the generation of students that was inspired by J. F. Kennedy, who interestingly made his famous speech standing on the grounds of Rice University where I currently teach and do research in chemistry after my long voyage from Cyprus to Houston, Texas. This was indeed an enriching and rewarding journey, “full of adventure, full of knowledge” as C. P. Cavafy wrote in his well-known poem, “Ithaca.”

After graduation and at the age of 18, I traveled to England where I studied chemistry at Bedford College (BSc) and University College London (PhD) with Franz Sondheimer and Peter J. Garratt, but not before working in a sausage factory, a rubber factory and several Fish & Chips shops while learning English and preparing for my examinations to enter the University. It was in London where I made my biggest discovery, Georgette, now my beloved wife for more than four decades.

My next stop was Columbia University, New York City where I carried out postdoctoral studies with Thomas J. Katz and then Harvard University, where I worked under the mentorship of E.J. Corey (Nobel Laureate, 1990). My first appointment was as an Assistant Professor at the University of Pennsylvania, Philadelphia where I rose through the ranks to become the Rhodes Thompson Professor of Chemistry. In 1989, I was appointed as the Founding Chairman of the newly established Chemistry Department at The Scripps Research Institute in San Diego, California where I held the Darlene Shiley Chair in Chemistry, and jointly the position of Distinguished Professor of Chemistry at the University of California, San Diego until 2013, when I moved to Rice University, where I currently hold the Harry and Olga Wiess Chair in Chemistry. In 2004, I was recruited by A*STAR, Singapore to establish the Chemical Synthesis Laboratory where I held, concurrently with my other appointments, the position of Director until 2010.

My Science and Its Impact on Society

Chemistry has been called the central science, for it stretches between physics and biology. Its centrality and power derives from its ability to analyze and synthesize molecules that make up all things we can see, touch, smell and taste. Chemists create these molecules from atoms or groups of atoms through the art and science of chemical synthesis. The latter practice is of extreme importance because through it we discover and produce some of our most precious items such as medicines, diagnostics, cosmetics, dyes, fibers, polymers, plastics, agricultural chemicals, and high tech materials for all intents and purposes. A particular branch of synthesis called organic synthesis is that of constructing molecules, natural or designed, whose primary element is carbon. It is from such molecules that living creatures like us are made of. The ability of man to replicate the molecules of living nature and create others like them in the laboratory is one of the most profound developments in the history of humankind, for it changed our way of life and shaped our world as we know it today. Among the many molecules that changed the world, those of aspirin, penicillin, Taxol, and the antibody drug conjugates (ADCs), stand out for their huge impact on society.

Aspirin. The story of Aspirin goes back to ancient Egypt where it was known that the willow and related trees contained an ingredient that relieved pain and fever. Hippocrates, the Father of Modern Medicine, prescribed willow bark to patients for the same purposes in Ancient Greece. But it was not until chemistry became of age in the nineteenth century that scientists discovered the active ingredient from the willow, salicin, a natural product that exhibited the pain and fever relieving properties attributed to this tree. Chemists at the Bayer company in Germany made a simpler version of salicin that had better pharmacological properties and launched Aspirin in 1899 as the first pure substance to be used as medicine. It became the most successful medication of all time and continues to be indispensible to us today. Made possible through chemistry, the discovery of Aspirin marks the beginning of the pharmaceutical industry and modern medicine.

Penicillin . Penicillin was discovered by the Englishman Alexander Fleming in 1928 from a simple mold and was developed as an antibiotic during the second World War through an urgent project to save the lives of dying soldiers in the battlefield from infections. Involving thousands of scientists and medical doctors, this so called Anglo-American Project gave humanity a tremendous edge in its battle over bacteria and inspired myriad of discoveries that led to a new generation of miracle drugs from nature (i.e. from microbes, plants, marine creatures, etc.). The advent of penicillin and other antibiotics such as vancomycin, synthesized in our laboratory in 1999, almost doubled the average lifespan of people in Europe and around the world. However, we must still remain vigilant against drug resistant bacteria which continue to menace society today. Overuse of antibiotics contribute to this continuing battle against bacteria, with scientists constantly searching for new antibiotics to replace old ones as they become obsolete due to the continuous emergence of drug resistant bacterial strains.

Taxol. Taxol is one of the most, if not the most, widely used anticancer drugs today. It was discovered from the Pacific Yew tree in 1971, but its development as a drug was delayed due to its low solubility and scarcity. Because of its great promise as a new anticancer agent, Taxol became a “celebrity” molecule with many groups around the world racing to synthesize it in the laboratory. The total synthesis of Taxol was published first by our group in 1994. In the meantime, the discovery of its plentiful relative, and precursor, 10-deacetylbaccatin III, from the European Yew tree made it feasible to produce Taxol on a large scale. These discoveries facilitated the development of Taxol and related compounds as anticancer drugs. Today, these drugs are used against a variety of cancers, either alone or in combination with other drugs.

Antibody Drug Conjugates (ADCs). Antibody drug conjugates (CADs) represent a new paradigm in cancer chemotherapy. They are targeted drugs against different types of cancers characterized with higher efficacy and lower toxicity than traditional anticancer drugs. They can be compared to a guided missile (or a magic bullet) possessing a delivery system (i.e. the antibody), a payload (i.e. the drug or cytotoxic agent), and a chemical linker through which the drug is attached to the delivery system. ADCs are designed to selectively target and destroy cancer cells without collateral damage of healthy cells, unlike many of the conventional anticancer drugs, the latter being associated with serious side effects. Calicheamicin, a rare naturally occurring substance first synthesized in our laboratory in 1992, was the first cytotoxic agent to be placed on an approved antibody drug conjugate and continues to be in demand today for such purposes. A number of other potent, but scarce cytotoxic agents have been discovered from nature and proved to be uniquely suitable as payloads. Today, chemists, biologists and clinicians endeavor to develop new types of ADCs for treating cancer patients on a personalized basis by identifying biomarkers and using them to design specific antibodies onto which powerful anticancer drugs can be attached as payloads. In collaboration with pharmaceutical and biotechnology companies, our group is at the forefront of this exciting new field of investigation.

Acknowledgements

In closing, I wish to express my sincere thanks and appreciation to my students for their brilliant contributions to the work described in our publications. I also wish to thank the various agencies, companies and benefactors for supporting our research programs over the years. I am indebted to my parents and grandparents, uncle John and aunt Aphroditi, brother Nicolis and sisters Despina, Vaso, Margarita and Yianna for their love and support as I was growing up and since. I also wish to express my appreciation and respect to my teachers and mentors for their guidance and inspiration during my studies and career. Last but not least and with all my love, I wish to thank my wife Georgette, daughter Colette, sons Alex, Christopher and Paul (PJ), and my grandson Nicolas and granddaughter Georgia for their unconditional love and support. And once again, I thank Mr. and Mrs. Takis and Louki Nemitsas and the Nemitsas Foundation for the Nemitsas Prize 2014.