# Bibudhendra Sarkar

Bibudhendra (Amu) Sarkar CM (born August 2, 1935) is a Canadian biochemist best known for his research on copper-histidine in human blood, leading to the first treatments for Menkes disease. He served as head of the Division of Biochemistry Research at the Sick Kids Research Institute in Toronto from 1990-2002, where he established the Department of Structural Biology Research in 1990.

## Early life and education

Bibudhendra Sarkar was born on August 2, 1935 in Kushtia, Bengal, British India (now Bangladesh). His father, Surendra Nath Sarkar, was a lawyer and mother, Sucheta Sarkar (née Chaki), a homemaker who died when he was one year old. He attended Kushtia Mission School, a Catholic school for his kindergarten and primary education.
Following the Partition of India in 1947, his family was forced to leave behind everything and migrated to Calcutta. He studied in City College School and City College, Kolkata. He obtained his Matriculation and Intermediate Science Certification from the University of Calcutta. He then enrolled in the Banaras Hindu University, Uttar Pradesh where he received B. Pharm and M. Pharm degrees specializing in the chemistry of natural products. During his studies in BHU he was a regular summer student in the Central Drug Research Institute in Lucknow where he was mentored by Manojit Mohan Dhar. Dhar encouraged Sarkar to do his graduate studies in the USA or Europe. Sarkar then travelled to the USA to do his graduate studies in biochemistry in the University of Southern California, under the supervision of Paul Saltman. Sarkar was influenced by several scientists while at USC: Sydney Benson in chemical kinetics, Arthur Adamson in physical chemistry and Bo Malmström in metal-activated enzyme chemistry. Sarkar graduated with a PhD in biochemistry in 1964.

## Career

In early 1964 Sarkar was presenting his PhD work at the Federation of American Societies for Experimental Biology (FASEB) meeting in Chicago where Andrew Sass-Kortsak, a clinician specialist in Wilson’s disease at the Hospital for Sick Children in Toronto, Canada came to listen. Sass-Kortsak was leading the Genetic Metabolic Program of the Hospital for Sick Children and was looking for a young basic scientist to join in his program. Sass-Kortsak offered Sarkar a Staff Scientist’s position in the Genetic Metabolic Research Program with start-up funds and his own laboratory in a newly built wing in SickKids. Soon thereafter he was cross-appointed to the Department of Biochemistry at the University of Toronto.
Sarkar began attending Grand Rounds with Sass-Kortsak and went to the wards to visit Wilson’s disease patients. Because of his interest in the biophysical aspects of metal protein interactions and metal transport, Sarkar’s research turned to metal-related diseases. He pioneered multidisciplinary research in SickKids in association with Sass-Kortsak by crossing the boundaries between basic science and clinical medicine and creating a collaborative environment in SickKids. In 1990 he was appointed Head of the Division of Biochemistry Research in SickKids.

## Research

Sarkar discovered copper-histidine in human blood. He invented the treatment of Menkes disease by copper-histidine. He discovered the amino terminal Cu (II)- and Ni (II)- binding (ATCUN) motif of proteins. This motif has been used to cleave DNA, applied as a paramagnetic probe and used to kill Ehrlich cells. His laboratory identified and characterized the six copper-binding sites of copper-ATPase that is defective in Wilson’s disease. He pioneered the development of metalloproteomics, a subdiscipline of proteomics that attempts to identify and characterize all metal-associated proteins in a well-defined system. He also contributed to global health research in Bangladesh, India, Nepal, and Myanmar, where tens of thousands of people are exposed to naturally occurring arsenic and other toxic metals in drinking water from underground wells Sarkar is considered a pioneer in establishing inorganic biochemistry through his research in the early 1960s. He organized the first international meeting of Biological Inorganic Chemistry in the Board Room of the Hospital for Sick Children in 1972. This initiative was followed by the 56th Nobel Symposium in Inorganic Biochemistry held in Sweden under the auspices of the Nobel Foundation in 1982 where Sarkar was an invited speaker. He has published extensively in scientific journals, organized many series of international symposia on metals and genetics, edited several books on metals in biology, genetics, and environment. He was a founding member as well as a member of the first Editorial Board of Metallomics published by the Royal Society of Chemistry, UK.

### The discovery of copper-histidine in human blood and invention of Menkes disease treatment

Sarkar discovered copper-histidine in human blood in 1966 and recognized it as a biological form by which copper, an essential element to sustain life, is transported in blood. In 1976, Sarkar proposed that a baby with Menkes disease receive copper-histidine via subcutaneous injection. This was the world’s first Menkes patient to receive copper-histidine therapy. Children with this disease are now living longer and reaching adulthood with copper-histidine treatment. Sarkar did not patent copper-histidine; he intended that it be readily available to Menkes patients at a reasonable cost. The formulation and detailed compounding procedure for the preparation of copper-histidine is freely available by SickKids Pharmacy to physicians and hospital pharmacies around the world upon request. Sarkar also helped make copper-histidine formulation for Menkes disease in other countries including NIH Clinical Center, Bethesda, Md. USA, India, and Mexico.

### Molecular structure of Cu(II)-histidine and ATCUN Motif

Sarkar solved the structure of the copper(II)-histidine molecule used for the treatment of Menkes disease. He discovered the ATCUN (Amino terminal Cu(II), Ni(II) binding) motif of proteins and peptides.

### Wilson’s disease ATPase

Sarkar’s laboratory identified six copper-binding sites of Wilson’s disease ATPase with all six copper atoms binding ATPase in +1-oxidation state. Based on nuclear magnetic resonance (NMR) studies, Sarkar’s team proposed that copper transfer to and between the N-terminal domains of the Wilson ATPase occurs via protein interactions that are facilitated by the flexibility of the linkers and the motional freedom of the domains with respect to each other.

### Metalloproteomics

Sarkar along with his colleague Eve Roberts, a hepatologist and Wilson’s disease specialist, pioneered the development of metalloproteomics. He first presented the concept and findings of metalloproetomics relating to copper in 2002.

### Global health research

Sarkar led a team of international scientists investigating naturally occurring arsenic and other toxic metals throughout South- and Southeast Asia. In his early research in Bangladesh, Sarkar identified a small child with advanced signs of arsenic poisoning, an observation that motivated extensive research in this region. Discovery Canada Television produced an hour-long documentary focusing on Sarkar’s work on this devastating health crisis in Bangladesh. Sarkar’s team discovered that arsenic is not the only toxic metal contaminating the groundwater; other toxic metals such as, manganese, lead, chromium, and uranium are also present in groundwater. They produced heat maps of arsenic and other toxic metals in Bangladesh and West Bengal (India) groundwater, identifying areas where contamination is of special concern. Their investigation was further extended to the neighboring country of Myanmar (Burma), which has a similar geology, and where they found high concentrations of many of the same toxic metals in groundwater. Sarkar’s team also carried out field work in Kathmandu, Nepal in 2015. In addition, the team called for the WHO to re-evaluate its guidelines for many toxic substances in drinking water based on their health hazards. Sarkar’s team stressed that multiple metal contamination of groundwater is an issue of global concern, and the risks may be further magnified by climate change.

### Inorganic Biochemistry

Sarkar organized and chaired the first international meeting of Inorganic Biochemistry in the Board Room of SickKids with 35 participants in 1972 which included among others, R J P Williams (Oxford), Gerhard Schrauzer (University of California, San Diego), David R. Williams (Saint Andrews University, UK), David A Brown (University College Dublin) and Barry Lever (York University). To acknowledge this new discipline the 56th Nobel Symposium introducing Inorganic Biochemistry was held in Sweden under the auspices of the Nobel Foundation in 1982 where Sarkar was an invited speaker. He organized various series of Symposia on Metals and Genetics beginning in 1994 and edited several books on metals in biology, metal-related diseases, and metals in the environment. He was a member of the committee to establish terminology relating to -omics and metals under the auspices of the International Union of Pure and Applied Chemistry (IUPAC). He was a founding member as well as a member of the first Editorial Board of Metallomics published by the Royal Society of Chemistry, UK.

## Personal life

He was married to Dipti Sarkar (née Dutt) (b. 1944 – d. 1985), an Indian classical dancer, choreographer, and historian. He has a son and a daughter.

## Awards and honours

* 2024: Order of Canada
* 2020: Sarkar Symposium, a celebration honoring Sarkar’s 55 year career at SickKids.
* 2010: Fellow of the Royal Society of Chemistry, U.K. (FRSC (UK)).
* 2010: Fellow of IUPAC (International Union of Pure and Applied Chemistry).
* 2008: Visiting Professor, University of Hong Kong, Hong Kong.
* 2006: Priyadaranjan Ray Memorial Award from the Indian Chemical Society.
* 2005: “Annual Sarkar Lecture” was established in Sarkar’s honor to invite distinguished scientists to give lectures in the Research Institute of SickKids.
* 2004: Received R. C. Mehrotra Award for Science from the Vice President of India at the International Conference on Chemistry Biology Interface: Synergistic New Frontiers, New Delhi, India.
* 2003: Research Institute (SickKids) Citizenship Award of the Year.
* 2002: Visiting Professor, National University of Singapore, Singapore.
* 2000: Visiting Professor (European Union) University of Ioannina, Greece.
* 1998: Honorary Professor, Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India.
* 1996: Commencement Speaker, Akdeniz University, Antalya (Turkey).
* 1988: Chinese Academy of Sciences invitation to lecture in Academies/Universities in Beijing, Guiyang and Hangzhou as Visiting Professor.
* 1986: Elected Fellow of the Chemical Institute of Canada (FCIC).
* 1984 : Visiting Professor : Université de Paris Nord, Paris, France.
* 1982: Invited to speak at the 56th Nobel Symposium on Inorganic Biochemistry under the auspices of the Nobel Foundation, Sweden.
* 1981–1982: Chairman: Biological Chemistry Division, Chemical Institute of Canada.
* 1977: Member of the High Table, King’s College, University of Cambridge, U.K.
* 1977: Nuffield Foundation Award, U.K.
* 1977: USSR Academy of Sciences invitation to lecture in Academies/Universities in Moscow, Pouschino, Novosibirsk, Tashkent, and Leningrad as a visiting professor.
* 1965–1970: Medical Research Scholar Award (Canada).
* 1964: Blue Key Award: University of Southern California, Los Angeles, USA.