Curiosity, Cell Death and Caspases: One Researcher’S Journey to Big Discoveries

Health & Medicine ︱ Professor Vishva Dixit Curiosity, cell death and caspases: One researcher’s journey to big discoveries All comic book superheroes have isii, Kenya, the mid-1950s. Valley, and at the heart of the African tea an intriguing ‘origins story’; and The East African country is still industry. Nestled in the mountains 7000 in the case of science superman K a British colony, and there is feet above sea level, and surrounded Professor Vishva Dixit he has strong cultural and societal demarcation by the lush green of tea plantations, one too. Beginning in Kenya and of ethnicities, with separate schools, this must have seemed a world away Vishva and his wife, Manjul, on a recent visit ending in California, this is the hospital and civic centres depending from the bleak and arid landscape of to the Laikipia anti-poaching unit in Kenya. story of a researcher who asked on race. Vishva Dixit was born into this the frontier. Perhaps aptly, one theory big questions of himself and the discordant atmosphere a decade after for the etymology of the name of the world, and went on to pioneer a his physician parents were sent to Kenya town ‘Kericho’ is that it derives from the lecturer, Professor Hettiaratchi, left a that a career in public health was not for his medical degree recognised in the field of research into cell death, from India on colonial service. Initially, Kipsigis word for hospital, ‘kerichek’; so particular impression; revealing to the him. He felt that as a physician, he could United States, and following a good word caspases and apoptosis. Dixit’s mother and father had been posted called because it was where the region’s eager student the foundational logic of make little impact on such largescale from his brother, a resident in Internal to the ‘Northern Frontier District’ close first hospital was set up. In 1963, Kenya medical science. As well as being inspired, problems. However, his childhood desire Medicine, Vishva was admitted to the to the Somali border to run the clinic achieved independence, and segregation Vishva was also exposed to the tragically for scientific discovery and fascination Department of Pathology at Washington associated with a British prison camp policies in the country came to an end; high levels of infant mortality in the with death remained, and it became University, St. Louis. there. The area was a veritable desert, the young Vishva Dixit was able to attend country during the 1970s. Poverty-stricken clear to him that a career in biomedical troubled by scorpions and bandits, and the previously ‘European’ school. parents could only afford to bring their research (pathology specifically) would What was it like moving from the over- Dixit’s father recalls having to surgically children to the hospital in the city when be better suited to his interests and skills. crowded and under-staffed Kenyatta remove the severed head of a hyena A CURIOUS CHILD conditions were far advanced; by the time The lack of resources and funding in National Hospital to the state-of-the-art from the forearm of a man who had been With parents busy at house calls most the doctors saw them, there was often Kenya meant that he would have to look Barnes Hospital in St. Louis? The contrast attacked while wandering in scrubland evenings, ten-year-old Dixit kept himself little they could do. must have been nearby. After leaving the colonial service, busy with a series of science books Towards the end monumental. In his first Dixit’s parents set up private practice in bought for him by his mother and father. of his study period …even at that young age he was year of clinical training a number of small towns before settling He reminisces that even at that young Dixit experienced in laboratory medicine, in Kericho, on the edge of the Kenyan Rift age he was fascinated by the idea that the futility of trying fascinated by the idea that the tools of Dixit rotated through the tools of science can allow one to to treat a disease the various topics be an explorer. He also notes that he without knowing science can allow one to be an explorer. that make up the was particularly intrigued by one book its cause or name discipline, including on forensic-pathology, beginning a – whilst working in the tropical medicine for opportunities overseas if he wanted blood banking and microbiology. Weekly lifelong preoccupation with death, and unit Dixit and his tutor Dr Philip Rees to realise this dream; Dr Dixit began to presentation meetings known among deciding there and then that when he began to see many patients with the same look at the possibility of making the move residents as the ‘shark tank’ taught him grew up he wanted to be a scientist. Not symptoms, famished and skeletal looking, to the United States. to question perceived wisdom in a long after this, the Dixit family moved with a ‘fever of unknown origin’. All tests thoughtful, precise and rigorous manner. again, this time to Nairobi, Kenya’s capital carried out returned negative results, A NEW CHAPTER city. Vishva has described his high school and the patients gradually wasted away, IN THE NEW WORLD years as ‘turbulent’. With the hustle and eventually succumbing to the mystery With his siblings already based stateside, bustle of the city as a backdrop, young condition. Looking back, Dixit realises Dixit began in earnest to work towards Dixit ‘muddled’ through his teenage years that this was the beginning of the AIDS the move. With his medical degree from in the knowledge that ‘come hell or high epidemic, and he has commented that Nairobi (‘hardly a hotbed of biomedical water’ he would go on to study medicine, for him it ‘underscored the helplessness research’), Dixit knew he would have as his parents insisted he should. of ignorance’. to prove he had the appetite and ability to gain admission onto a residency at THE TRAINEE These experiences taught Dixit that in a an American institution, so he set about For the young adult Vishva Dixit, medical country like Kenya, where infant mortality getting some of his recent research school was a revelation. Some of stood at 120 in 1000 and the AIDS crisis published. Once he had articles published the teachers Dixit encountered during was just beginning, public health was in Developmental Medicine and Child Vishva and his wife with one of their adopted his time passed on not just knowledge a political problem, and disillusioned Neurology and The Lancet, Dixit also baby elephants at Sheldrick Wildlife Trust but new ways of thinking. A physiology by the scale of the tragedies he knew took the examinations necessary to get Orphanage, Nairobi, Kenya. www.researchoutreach.org www.researchoutreach.org the Cell Biology meeting, each describing Vishva with Barack the rhino at Ol Pejeta, Kenya. a modest advance.’ Dixit was frustrated, his curiosity stalled, and he was desperate Behind the Research to do work that would get him noticed, to make a real difference and to carry out research that would make up textbooks. Professor Vishva Dixit The child who had wanted to be a science explorer was still a huge part of who E: [email protected] T: +1 (650) 225-1312 W: https://www.gene.com/scientists/our-scientists/vishva-dixit Assistant Professor Dixit was and he felt he had no choice; Vishva switched fields. Research Objectives Personal Response A FRESH START AND CELL DEATH After reading an article in Scientific Professor Dixit has played a pivotal role in the advancement What is your proudest achievement of your career so far? American that briefly mentioned cell of apoptosis research. death, Dixit realised this could be the Being able to implant the seed of curiosity in the gap he was looking for. Cell cycle was many trainees who have worked with me over the years – the ‘hot topic’ of the time, and no one and, seeing their careers blossom. Also, the satisfaction else at Michigan was studying cell death; of being able to pursue my dreams and in my own small way open up “Tutankhamun’s tomb” to see the absolute Dixit knew it would be make or break. Detail splendour and beauty of the executioner machinery His funding was for research in another Vishva M. Dixit M.D. responsible for cell death, a process of such fundamental topic, and if he came to the end of the Genentech, Inc. importance, that without it, life on our planet would not have grant period and he had nothing to show 1 DNA Way been possible. he would lose his job. This pressure was Mail Stop #40 exciting though, and for the first time South San Francisco Can you tell us a bit more about the research in years Dixit felt galvanised. The gamble CA 94080, USA you are undertaking currently at Genentech? paid off; Dixit’s lab became famous We are actively exploring how cells undergo a form for its work on caspases, apoptosis and Bio of pro-inflammatory death referred to as sterile necrosis. This what actually happens during cell death. Professor Vishva Dixit is Vice President at Genentech, Inc., process, that happens in the absence of infection (hence the Landmark papers were published. Dixit’s a leading pharmaceutical company. Member of the National term “sterile”), generates persistent tissue damage that drives lab identified each stage of the cell death Academy of Sciences, National Academy of Medicine, the chronic diseases such as stroke, heart attacks and Alzheimers, The gauntlet of probing questions from significant in how it made him feel about pathway, and determined how they were American Academy of Arts and Sciences, and a Foreign responsible for much of the morbidity and mortality that tutors and peers began to change Dixit’s his personal contribution to cell and all connected, and in 1997 Dixit was Member of the European Molecular Biology Organization.

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