Abstract
I became exposed to Gobind's discoveries in genetics and nucleic acids in a chapter of my high school biochemistry textbook. Who knew then that one day I would be able to meet Gobind in person, and not only that, but pursue a research career in nucleic acids? It was in 1985 when I met Gobind face-to-face in the corridors of New Hall, at the University of Cambridge, where he was looking for directions to the dining hall. As we walked, he immediately inquired about my research, which I was pursuing in Mike Gait's lab at the Laboratory of Molecular Biology in Cambridge. Mike had spent time in Gobind's lab and had organized a symposium entitled “Har Gobind Khorana Symposium” to celebrate Gobind's 60th birthday, and it was attended by most who had spent time in Gobind's lab. For a young researcher like me, it was an opportunity to see the respect and admiration the attendees had for Gobind.
Gobind unraveled the trinucleotide code, in which the 4 nucleotides that comprise DNA combine to form the 64 “3-letter words” that each code for a specific amino acid or function as a start or stop signal to guide the translation of mRNA into a peptide strand. Even once this mechanism was uncovered, Gobind and colleagues worked to solve the mystery of the redundancy in coding, in which more than one codon could represent an individual amino acid. It was this body of research, which he carried out at the University of Wisconsin–Madison, which led to his selection as a Nobel Prize recipient.
Gobind led the chemical synthesis of the first gene in 1970, followed by the demonstration in 1979 that it was functional in a bacterium, creating a landmark in genetics. This work used short strands of oligonucleotides in vitro to assemble the gene.
Gobind was introduced to the importance of education from a young age. His interest and aptitude for learning and for science in particular were rewarded early on, as he received a scholarship from the government of India to study chemistry at the University of Punjab, Lahore, Pakistan where he completed both a bachelor's and master's degree. In 1945 Gobind traveled to the University of Liverpool, England, under a government of India fellowship to pursue his graduate studies. After obtaining his doctorate in 1948 in organic chemistry, Gobind traveled to Switzerland and spent 11 months at the Federal Institute of Technology in Zurich. In 1949 he returned to England to work with Alexander Todd at Cambridge University, where he began to focus his work on the chemistry of nucleic acids.
In 1952 Gobind moved to Vancouver to start his own research group at the British Columbia Research Council at the University of British Columbia. During that time, he is credited with developing a cost-efficient chemical method for synthesizing coenzyme A. The next stop along his career path took Gobind to the University of Wisconsin–Madison, Wisconsin. Those were highly productive years, and the outstanding research done in his lab earned Gobind both a Nobel Prize and a Lasker Award in 1968. Shortly thereafter, in 1970, he moved to MIT, where he retired in 2007 as the Alfred P. Sloan Professor of Biology and Chemistry emeritus. In 1987 he was awarded the National Medal of Science.
Gobind shared his love of education, science, and research with the hundreds of students he taught and mentored during his career. He gave of himself unselfishly to his many students, colleagues, and friends throughout his long and illustrious life. Mike Gait always spoke glowingly about Gobind. “Working in Gobind's lab in the early 1970s was both exhilarating and awe-inspiring for a young postdoc like myself. I learned how Gobind's outstanding vision for tackling a complex but important biological goal, namely the expression of a single functional synthetic gene, required the harnessing of both pioneering chemical and biological techniques. This was ‘Chemical Biology’ well before the term was invented. It also needed both persistence and dedication to inspire a large group of scientists to work very hard together towards a common goal. The camaraderie was tremendous and the learning experience unparalleled. I made lifelong friends with many of my contemporaries as well as numerous others of the ‘Khorana mafia,’ as this became known. I also scientifically ‘grew up’ in Gobind's lab and took inspiration from this time for my own subsequent career.”
When I came to Cambridge, Massachusetts, to work in the laboratory of Paul Zamecnik, I became closer to Gobind, as he and Paul had been colleagues and friends for many years. As I did so, my appreciation and admiration for his insights and vision continued to grow stronger. Over the years, as Paul and I were developing antisense technology, Gobind's advice and suggestions were particularly insightful and helped us clarify a path forward.
I clearly remember him stating that synthetic oligonucleotides could trigger unwanted reactions by the host as a defense mechanism. It was, in fact, so true that the administration of these oligonucleotides led to the observation of immune activation and created a whole new path of potential therapies that could exploit this immune response in a positive way. When Paul and I formed the company Hybridon (now Idera), Gobind served as an advisor and his help was invaluable. His thoughts, as always, were crystal clear and his perspectives illuminating. His guidance was especially valuable in helping us analyze the data we were generating. It was always great to have him visit; when Gobind was in the room, everyone else there became infected with his enthusiasm and energy.
Gobind was an inspiration, a teacher, and a mentor to me and to all his colleagues. He will be greatly missed.