Ensuring genetic well-being of all is the core of Prof Thelma's research
A renowned geneticist and genomics expert, Professor BK Thelma’s research is driven by the overarching vision of P4 (predictive, preventive, personalised and participatory) medicine, a new paradigm in the healthcare sector. Her laboratory at the University of Delhi South Campus (UDSC) works tirelessly not only to uncover the genetic bases of genetic disorders, but also to undertake functional analyses to yield either diagnostics or therapeutics that directly benefit the patients and empower the clinicians.
While the single gene disorders show clear-cut patterns of inheritance within families, they make up only 6 to 8% of the total patients with genetic diseases. Intellectual disabilities and Parkinson’s disease come under this category. The second kind of gene disorders are the more rampant lifestyle disorders or complex disorders, the cause of which are multiple genetic loci and non-genetic factors, making them more difficult to study. Cardiovascular diseases, diabetes and rheumatoid arthritis are some examples. Undeterred by the difficulty of the questions, Prof Thelma, now 68, and her army of students have discovered contributing genetic variants for many diseases.
Spearheading research
Her independent research began with intellectual disability linked to the fragile-X syndrome, the genetic diagnosis of which was done by means of a tedious procedure called the southern blot then. To date, molecular diagnosis of fragile-X syndrome is one of the services her lab renders to any clinician or patient knocking on its door, though the process has become simpler with the advent of next generation sequencing (NGS). The causal gene of intellectual disability was found to be MID2 — the first discovery of a disease-causing gene mutation through NGS in India.
Soon, clinicians and genetic counsellors brought more patients to uncover causes of many more diseases. Parkinson’s disease, schizophrenia, irritable bowel syndrome, celiac disease and rheumatoid arthritis are only a few of Thelma’s focus areas.
Thelma in office checking manuscripts
Despite the tragic impact of genetic disorders on families, India is a genetic research goldmine with extended family trees of affected individuals providing a unique advantage for discovery genomics studies. Prof Thelma leverages this edge for risk prediction and disease prevention. Recently, she entered into pharmacogenetics, seeking drug candidates for genetic disorders.
Thelma’s lab explores Ayurveda principles for deep phenotyping — a potent way to investigate medical implications of genetic variations. Additionally, she holds prominent positions, including as co-chair of the UMMID (Unique Methods of Management and treatment of Inherited Disorders) programme of the Department of Biotechnology.
Thelma’s tryst with research began with a PhD in zoology from the University of Delhi in 1982. After a short stint as a postdoctoral fellow in Switzerland, she returned to her alma mater as a research associate in the zoology department. In 1987, she joined the genetics department as a lecturer. She was elevated to the position of a senior lecturer in 1993, reader in 1998, professor (zoology) in 2003 and finally professor in the genetics department in 2006.
“Thelma stayed nights on end in the lab… She was working on fragile-X [then], and patients would turn up in long queues… Accommodation was not quite in place [at UDSC] then, and we all struggled with it. She never complained, she just stayed back [overnight in the lab],” says Professor PK Burma, a long-standing colleague and friend.
She is always the first to reach her lab and the last to leave. “Lack of basic infrastructure and housing were the greatest challenges during my career — no hostels for women postdocs and young scientists, imagine in the 1980s,” Thelma concurs. “Everything else is a part and parcel of a research career.”
Thelma always counts her blessings and does what she can. ‘Begin where you are and do not give up’ is her mantra for young women in research. When she could not join medical college, she graduated in science; when she did not get physiology for specialisation, she accepted cytology and finally, became a medical geneticist. With countless collaborators, she investigated the role of genetics in many diseases . After retirement too, she is unstoppable, pushing to get newborn screening for genetic diseases termed ‘inborn errors of metabolism’ integrated into the national health and welfare policy.
The UDSC genetics department
Thelma understands varied points of view, holding her own ground simultaneously. “We do not agree on a lot of things, but it has never soured our personal relations,” says Burma. Thelma played an integral role in setting up the UDSC genetics department along with Prof Sheela Srivastava, Prof MV Rajam, Prof Deepak Pentel and Prof Burma.
“Do you know, she makes excellent coffee,” Burma says. “She made it for everyone in the department. Its aroma used to fill the entire corridor. Herself a frugal eater, she can cook elaborate scrumptious meals for others. Her caramel custard is our favourite. She is very kind and compassionate, always sharing.”
Thelma with her sister Tanuja
Thelma would to date share her sequencers and freezers the same way she would share the only air-conditioned room in the entire department during the initial days of UDSC, which housed one of the first PCR machines of the time — a Perkin-Elmer — and a microscope.
“We had to go out to find mole rats, our model organism [Nesokia indica]. We would flood their burrows with water and catch them as they escaped,” recalls Sudha Babu, senior director, CMC Regulatory Affairs, Kriya Therapeutics, Philadelphia, USA, one of the first students of Thelma working on the fragile-X syndrome. “We were like family. She gave us a firm foundation, not just for our careers, but for life.”
“I was just an MSc dissertation trainee, but she sat with me until 9.30 pm to look at my presentation! The day was still not over for her, PhD students continued discussions afterwards,” recalls Gaura Chaturvedi, a past trainee in Thelma’s lab. “She gives her all to the students. There was once a fellow who did not have a place to stay and she offered him space right inside her home!” Perhaps because she herself knew the pain of the lack of housing.
“She is a tough taskmaster. Because she is devoted, she expects maximum effort from the students also. You have to earn her trust and your place in the lab,” says Gurvisha Sandhu, one of Thelma’s most recently graduated PhD students. Thelma also alludes to arguments and tussles between students and herself, but finds it a necessary element of their growth trajectory rather than a problem.
Thelma is a career woman, thorough researcher, counsellor, mentor and a family person, all rolled into one. An ardent yoga practitioner, she does not use any social media, WhatsApp or a smartphone. But her promptness over emails is remarkable. Building resources for the department and winning substantial grants in a university setup are no small feats.
There is a compelling story behind her strength of character. Thelma’s early life was spent in the humble abode of her maternal grandparents in Coorg, Karnataka, since her father had a transferable job. It was an atypical joint family setup with her mother, five aunts and two siblings. Her grandfather was an ex-Army man, a strict disciplinarian who became a drawing teacher after retirement, while her grandmother looked after the household. Mother was in the government administration.
“Her visit to the families of those with intellectual disabilities in North Delhi inspired similar efforts in other projects. I learnt that to be a successful researcher, one should go beyond one’s comfort zone,” says Dr Neerja Gupta, a 15-year-long collaborator of Thelma and Additional Professor, Division of Genetics, All India Institute of Medical Sciences (AIIMS), New Delhi.
“She is so dedicated to her work ethics and professionalism that the project is bound to succeed,”says Prof Ashok Kumar, Head (Rheumatology), Fortis Vasant Kunj.
Dr Madhulika Kabra, Professor and Head of Department, Medical Genetics, AIIMS, New Delhi, reminisces the career-long association with Prof Thelma. “Since the beginning, she was meticulous, organised, clear and willing to solve the core issue of disease prevention. Empathetic towards the families, she is a wonderful communicator, but she never interfered with the role of the clinician, letting them shine in their own right.”
Prof Thelma fosters a collaborative mindset central to the academic-entrepreneurial partnerships, such as her latest one with Pankaj Sharma, managing director and co-founder, LeadInvent Pharma Inc. While LeadInventwas housed at the UDSC, they shared knowledge and ideas, ultimately collaborating to work on rheumatoid arthritis. “She is very down-to-earth and approachable. She always focuses on the goal and not the contractual relationship that startups or companies generally have with academicians. It is rather an enablement of the entrepreneur’s pursuit,” he says.
Thelma in 1964 with her family