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Bibudhendra Sarkar Recipient “Order of Canada” | |
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Born | |
Nationality | Indian (former) Canadian |
Alma mater | Calcutta University Banaras Hindu University University of Southern California |
Known for | Inventor of Menkes disease treatment by copper-histidine |
Spouse | Dipti Dutt (d. 1985) |
Children | 2 |
Scientific career | |
Fields |
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Institutions | Hospital For Sick Children and University of Toronto |
Thesis | Studies on the transport, metabolism and chemistry of iron-sugar chelates (1964) |
Doctoral advisor | Paul Saltman |
Bibudhendra Sarkar CM (born August 2, 1935), commonly known as Amu Sarkar, is an Indian-born Canadian biochemist known for his research on copper-histidine therapy in human blood, which led to one of the first effective treatments for Menkes disease. From 1990 to 2002, he served as Head of the Division of Biochemistry Research at the Hospital for Sick Children Research Institute in Toronto. During his tenure, he founded the institute's Department of Structural Biology Research in 1990. [1]
Bibudhendra Sarkar was born on August 2, 1935, in Kushtia, Bengal, British India (now Bangladesh). [2] [3] His father, Surendra Nath Sarkar, was a lawyer, and his mother, Sucheta Sarkar (née Chaki), a homemaker, died when he was one year old. [2] He completed his kindergarten and primary education at Kushtia Mission School, a Catholic institution. [2]
Following the Partition of India in 1947, Sarkar's family relocated to Calcutta after losing their possessions. [2] He attended City College School and later City College, Kolkata, earning his Matriculation and Intermediate Science certifications from the University of Calcutta. [2] [3] [4] He pursued higher education at Banaras Hindu University in Uttar Pradesh, [2] specializing in the chemistry of natural products and earning Bachelor of Pharmacy (B.Pharm) and Master of Pharmacy (M.Pharm) degrees. [2]
During his undergraduate studies, Sarkar worked as a summer researcher at the Central Drug Research Institute in Lucknow, under the mentorship of Manojit Mohan Dhar, who encouraged him to pursue graduate studies abroad. [2] He subsequently moved to the United States, completing a PhD in biochemistry at the University of Southern California in 1964 under the supervision of Paul Saltman. [2] [5] At USC, his work was influenced by chemists Sydney Benson (chemical kinetics), Arthur Adamson (physical chemistry), and Bo Malmström (metal-activated enzyme chemistry). [2]
In early 1964, Sarkar presented his PhD research at the Federation of American Societies for Experimental Biology (FASEB) meeting in Chicago, where he was approached by Andrew Sass-Kortsak, a clinician specializing in Wilson’s disease at Toronto's Hospital for Sick Children. [2] [6] Sass-Kortsak, then leading the hospital's Genetic Metabolic Program, sought a basic scientist to join his team and offered Sarkar a staff scientist position. This role included start-up funding and a dedicated laboratory in a newly constructed wing of the hospital. [2] [6] Shortly after, Sarkar received a cross-appointment to the University of Toronto's Department of Biochemistry. [1]
Sarkar began attending clinical Grand Rounds with Sass-Kortsak and visited Wilson's disease patients in hospital wards. [2] His research shifted toward metal-related disorders, driven by his expertise in biophysical studies of metal-protein interactions and metal transport. Collaborating with Sass-Kortsak, Sarkar pioneered multidisciplinary research at SickKids, bridging basic science and clinical medicine to foster a collaborative institutional environment. [6] In 1990, he was appointed Head of the Division of Biochemistry Research at SickKids. [1]
Sarkar discovered copper-histidine in human blood. [7] He invented the treatment of Menkes disease by copper-histidine. [8] [9] He discovered the amino terminal Cu (II)- and Ni (II)- binding (ATCUN) motif of proteins. [10] [11] This motif has been used to cleave DNA, [12] [13] [14] applied as a paramagnetic probe [15] and used to kill Ehrlich cells. [16] His laboratory identified and characterized the six copper-binding sites of copper-ATPase [17] that is defective in Wilson’s disease. [18] 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. [19] [20] [21] [22] [23] [24] 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 [25] [26] [27] [28] [29] [30] [31] [32] [33] 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. [34] 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. [35] 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. [36] [37] [38] [39] 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. [40]
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. [7] In 1976, Sarkar proposed that a baby with Menkes disease receive copper-histidine via subcutaneous injection. [6] This was the world’s first Menkes patient to receive copper-histidine therapy. [6] [7] [8] [41] Children with this disease are now living longer and reaching adulthood with copper-histidine treatment. [8] [9] [41] [42] [43] Sarkar did not patent copper-histidine; he intended that it be readily available to Menkes patients at a reasonable cost. [6] [41] 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. [6] [41] Sarkar also helped make copper-histidine formulation for Menkes disease in other countries including NIH Clinical Center, Bethesda, Md. USA, [44] India, [45] and Mexico. [46]
Sarkar solved the structure of the copper(II)-histidine molecule used for the treatment of Menkes disease. [47] He discovered the ATCUN (Amino terminal Cu(II), Ni(II) binding) motif of proteins and peptides. [10] [11]
Sarkar’s laboratory identified six copper-binding sites of Wilson’s disease ATPase with all six copper atoms binding ATPase in +1-oxidation state. [17] 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. [18]
Sarkar along with his colleague Eve Roberts, a hepatologist and Wilson’s disease specialist, pioneered the development of metalloproteomics. [20] [21] [22] [23] [24] He first presented the concept and findings of metalloproetomics relating to copper in 2002. [19] [20]
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. [48] [49] [50] Discovery Canada Television produced an hour-long documentary focusing on Sarkar’s work on this devastating health crisis in Bangladesh. [26] [27] 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. [28] [29] 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. [30] Sarkar’s team also carried out field work in Kathmandu, Nepal in 2015. [31] 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. [32] 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. [33]
Sarkar organized and chaired the first international meeting of Inorganic Biochemistry in the Board Room of SickKids with 35 participants in 1972 [34] 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. [35] 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. [36] [37] [38] [39] 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). [51] 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. [40]
He was married to Dipti Sarkar (née Dutt) (b. 1944 – d. 1985), an Indian classical dancer, choreographer, and historian. [52] He has a son and a daughter. [52]