INTERVIEW

Mandavilli Gourie-Devi

Interviewed by John Bonner

This article also appears in BioMedNet's Conference Reporter.

Posted July 6, 2001 · Issue 106

Background

Biography
Mandavilli Gourie-Devi is professor of neurology and director of the National Institute of Mental Health and Neuroscience (NIMHANS) in Bangalore, India. After qualifying in medicine from Andhra Medical College and the All India Institute of Medical Sciences in New Delhi, she studied neurology under the tutelage of "Papa Neuron," the great Indian neurologist Baldev Singh. Her interest in neuromuscular disorders led to her 1977 appointment at NIMHANS, where has combined her clinical duties with extensive research on motor neuron disease and related conditions. She holds visiting professorships at 24 institutions around the world. In 1999 she was awarded the Indian government's prestigious Shri Om Prakah Basin Award for outstanding contributions in the health and medical sciences.

What event or person inspired to take up a career in clinical research?

A very inspiring teacher, Professor Baldev Singh, who sadly died two years ago at the age of 95. He was India's first neurologist and joined the All India Institute of Medical Sciences in 1965, just as I was finishing my internal medicine postgraduate training and beginning work as a registrar. He combined a knowledge of modern science with ancient Indian wisdom. The higher brain functions - consciousness, memory - are all very well described in the ancient literature. He was a very benevolent person and students loved and admired him. At the same time he was a very hard taskmaster, so this combination of qualities attracted me to the field. This was a time when women doctors in India were unlikely to choose internal medicine, they would go into gynecology, obstetrics, or pediatrics. So my choice of career was considered strange at the time. I felt that neurology was much less well understood than some of the other branches of medicine - so it was a challenge and an enigma.

What was your first major research project?

Working in India, we see a lot of patients with neurological infections, particularly tuberculous meningitis. I came across patients with a complication of tuberculous meningitis called spinal arachnoiditis. In this condition, the meninges surrounding the spinal cord become adherent to the spinal cord and prevent the flow of cerebrospinal fluid, leading to paralysis. In 1975 I was working at a hospital in Delhi and was seeing a patient with the condition who was prepared to travel from Agra, three hours away on the train. How he managed this journey as a paraplegic I do not know. He was very upset with his condition and he told me I could do anything I could to bring him some relief. The only treatment available at the time was to give steroids intrathecally, into the spinal space. That didn't work because the movement of the fluid was totally blocked. Then I remembered something from my earlier training in which we gave the enzyme hyaluronidase to small babies before administering fluids, to help absorption. I did some research and found that this enzyme had been used to dissolve adhesions in the abdomen, and so I thought I would try it. After four weekly treatments there was some improvement, but I realized that his condition was too well established to hope for much more. However, I began giving the same treatment to people at an earlier stage. The project expanded after I came to Bangalore, and the first study was published in 1979.

What was the most exciting moment of your research career?

Cyclophosphamide is one of the few treatments available for motor neuron disease, although it only gives a temporary improvement for a few months. We published one of the early papers on this treatment and later developed an in vitro model to investigate the effects of cyclophosphamide on neurofilament phosphorylation. It was very satisfying for me, as a clinician, to produce experimental evidence to back up the findings from clinical practice. You have to remember that the picture for patients with this disease is so gloomy that any progress we can make is very important. In a developing country it is also essential that we provide treatments that are affordable, and this is not an expensive drug.

What was the most disappointing moment of your career?

Again, that was the work on cyclophosphamide. I would have wished that it benefited more patients - only 52 percent of our study of 44 patients showed slight changes. The improvement was small as far as I was concerned, but the patients felt happy because they weren't expecting anything at all.

What are your current research interests?

As well as my research on motor neuron disease, I retain my interest in neurological infections such as neurotuberculosis, Japanese encephalitis, and now AIDS. Our institution is an apex center - taking referral patients with neurological signs of AIDS from the Karnataka and the surrounding states. We are also the main center in India for neuroepidemiological studies.

What, in your view, is the greatest unanswered scientific question?

The fundamental question in neurology is what causes cell death in neurons, because if you know the mechanisms then there is hope for regeneration. In my particular field I am concerned with the anterior horn cell, which is affected in a range of motor neuron disorders from a very severe and rapidly progressing disease in infants, spinal muscular atrophy type 1, to the very mild form, monomelic atrophy [about which Gourie-Devi spoke at this congress]. Why does this neuron degenerate in certain people at certain periods of their lives, and why is the clinical picture so different?

Which scientist, living or dead, would you most like to have worked with?

The 1960s was a very interesting time with the work of Carleton Gajdusek on kuru, and the Icelandic veterinary scientist Bjorn Sigurdsson on maedi-visna in sheep. Their studies were showing that conditions which were previously believed to be degenerative diseases were actually caused by slow acting infections. I was very impressed with how a total disease concept was being overturned. I would have liked to have been able to switch over from my clinical work to laboratory studies, but that was not possible at that time. I did meet Gajdusek when he visited NIMHANS in the early 1980s, but by then it was too late to change.

What do you feel are the essential personal qualities in a good researcher?

I think the most critical quality is clarity of thought, to be able to identify the problem and the range of possible solutions. There are bound to be a number of alternative strategies, and one should not be discouraged if there are failures along the way. But while doggedness in pursuing a particular line of inquiry is important, it is also essential to remain open to fresh ideas. The wisdom of a good researcher is in knowing when to pick up a good idea and when to drop a bad one.

Are there any scientific discoveries that should never have been made?

There are no discoveries that are bad. A discovery means finding something that is already there, you are revealing the secrets of nature. How people use that discovery it what really matters.

Where do you expect to be in five years' time?

I hope to continue my work on motor neuron diseases because there is still much to be done. I shall be looking particularly at the two forms of the disease found in India that are rare in other parts of the world. So far we do not have any idea of the causes, whether there is a genetic or an environmental influence.

John Bonner is a freelance science journalist based in London. He writes for a range of publications but has a particular interest in veterinary medicine. He is a former news editor of a weekly journal called the Veterinary Record.