Something in the water

Interview: Something in the water
From Metallomics, 24 February 2010

Bibudhendra Sarkar talks to May Copsey about metalloenzymes, helping sick children and hunting for toxic metals in the environment Bibudhendra Sarkar is an Emeritus Professor at The University of Toronto and the Hospital for Sick Children, Toronto, Canada. His major research interests are in the area of metal-related genetic diseases with a special emphasis on Wilson and Menkes diseases and studying the effects of toxic metals in the environment and their impact on human health. He is also a member of the Metallomics editorial board.

How did your career in science start?
While I was an undergraduate in India, a scientist called Babul Dhar encouraged me to study abroad so I went to the University of Southern California, Los Angeles, US, to do a PhD.

That was the time when Dorothy Hodgkin had just discovered the structure of vitamin B12, which has cobalt in it. Her work inspired me to study the metalloenzyme structure. It was the late 1950s, and the term inorganic biochemistry was not yet recognised. There was no link between inorganic chemists and nutritionists.

Even in my graduate days I still remember that many biochemists did not realise that enzymes contained metal centres which were an integral part of the protein, and many believed that it was metal-contamination.

How did your move to The Hospital for Sick Children, in Toronto come about?
I had been asked to give a seminar at the hospital which is affiliated with the University of Toronto, where they were setting up a major research institute and wanted to develop the area of metal-related diseases. Then I was offered the position of an assistant professor.

When I first arrived, I didn't think it would last six months. I had come from southern California where it hardly rains to a place with lots of snow!

What was your first area of research?
We focussed on genetic metabolic disorders with a particular interest in Wilson and Menkes diseases. I was surrounded by many sick children and I thought that whatever I do, it must lead from bench to bedside so I can see the results.

What do you consider as your greatest discovery?
The Menkes disease treatment discovery is one of the greatest satisfactions that I have had in my lifetime; that a child who would have died at the age of three years lived to be 22. Copper-histidine was prepared in my lab, and now it is used all over the world to treat the disease. It is not a cure, Menkes is a genetic disease, but you can improve it.

What is currently hot in the field of metal-proteins?
The discovery of even more metal-binding proteins is a rather recent development in my work. The old paradigm of one protein to one gene is not true anymore and in eukaryotic cells, the situation is more like six to eight proteins per gene. So there are an enormous number of proteins to find, once splice site variation and post-translational modifications are considered. The challenge is to separate, enrich and then analyse them.

Once we get this set of proteins, and find out what they all do in metal transport and in the metal disease field, it will ultimately help in the identification of biomarkers to improve clinical diagnosis and to develop new therapies.

One area of interest to you is environmental metallomics, can you explain more about this?
My interest started about 13 years ago when I was invited to talk about Menkes disease at the Indian Science Congress in Delhi. After the talk, I was asked, as a metals expert, whether I was aware of the catastrophe in the Bengal Delta, where it looked as though people had arsenic poisoning from the drinking water in wells. I went to several villages to see for myself and the experience was unbelievable. The awful cases of melanosis and advanced gangrene cases were terrible, and the sufferers were treated as social outcasts.

In 1998, I was the first person to report the effects of arsenic in an 8-year-old child. This was strange as arsenic poisoning normally takes time to develop, it is normally a slow poison. After seeing this child, I formed an international, multidisciplinary team of volunteer scientists, known as Scientists Without Borders. Our first major work was a national-scale mapping of not only arsenic but 29 other metals. Anyone can now go and look at the map that we produced to see the most contaminated areas. The next job was to develop a very inexpensive method by which you can routinely measure arsenic in water which goes below 10 micrograms per litre.

We found that it is not just arsenic but other toxic metals such as antimony coming from the underground water that can enhance arsenic toxicity. Recently we found uranium and manganese in the drinking water. Uranium can cause kidney and bone diseases and manganese can cause Parkinsonian disorders and neurological problems. All this work is one example of what environmental metallomics has to offer the scientific and global community.

Related Links:
Bibudhendra Sarkar's homepage
University of Toronto