In the spring of 1964, biochemist Bibudhendra (Amu) Sarkar gave a conference talk that would change his life. It would also change the lives of countless children born with a rare neurodegenerative condition called Menkes disease that typically kills by the age of three.
Today, Dr. Sarkar is a senior scientist emeritus at the Research Institute of the Hospital for Sick Children and professor emeritus in the department of biochemistry at the University of Toronto. In June, he was appointed a member of the Order of Canada in recognition of his work advancing medical research in Canada and abroad, including bridging scientific research and clinical care at SickKids where he worked for 60 years.
But on that day in 1964, he was a freshly-minted University of Southern California PhD presenting his dissertation on the transport, metabolism and chemistry of iron-sugar chelates at the Federation of American Societies for Experimental Biology meeting in Chicago.
Unbeknownst to him, sitting in the front row was Dr. Andrew Sass-Kortsak, a clinician and expert in metabolic genetics at SickKids who was scouting for a young basic scientist to join the hospital’s genetic metabolic program. Impressed by the talk, Sass-Kortsak invited Sarkar to dinner.
“I didn’t understand why he wanted to talk to me,” recalls Sarkar. At the time, most medical research was applied, not basic. “My whole thrust was chemistry and physics and I’m very mathematically inclined.”
But during dinner, he agreed to give a talk later that year at SickKids.
“I was winding down my PhD thesis work in L.A and I had never been to Canada – although I’d heard about Canadian winters,” says Sarkar. Curious about the country and SickKids, he came, spoke, and was promptly offered a research position with his own lab, staff and start-up funds.
Sarkar said he would think about it and went back to L.A. where colleagues advised him to turn down the job. He had other offers after all. But Sass-Kortsak had taken Sarkar on rounds to meet his young patients, and he couldn’t stop thinking about those children.
“I felt a human connection with those kids, who were sick but still smiled,” he recalled. “I knew I could never feel that within the boundaries of my laboratory.”
The rest, as they say, is history.
Sass-Kortsak, whose clinical expertise was in diseases stemming from too much or too little metal, had a hunch his new recruit’s interest in interactions between metals and proteins would be important.
One day, he and Sarkar were talking about a patient with Wilson disease, a rare degenerative disorder that affects how the body handles copper, a metal vital to our survival. In the case of those with Wilson disease, copper deposits build up in the liver, brain and other tissues.
Sass-Kortsak made a passing reference to how copper that is not bound to proteins would be moving about freely in the blood. But Sarkar knew copper had a strong affinity for nitrogen and felt it would bind to another nitrogen compound in the blood rather than float about.
So he went back to his lab where he began to experiment with his own blood. It took some time, but Sarkar was able to prove copper binds to an amino acid in the blood called histidine. That in turn led him to turn his attention to other diseases caused by abnormal copper absorption, including Menkes disease which is caused by a lack of copper.
“Wilson disease results in too much copper, kids with Menkes do not have enough,” says Sarkar.
When Sass-Kortsak diagnosed SickKids’ first Menkes patient in 1976, Sarkar’s discovery that copper-histidine was biologically available in human blood would turn out to be key. Because it was a fatal disease with no known treatment, Sarkar suggested an injection of copper-histidine. The family and the hospital’s ethics board both agreed.
The baby’s copper levels began to slowly rise and everyone breathed a sigh of relief. “By three years old he was climbing stairs and growing normally,” recalls Sarkar.
Copper-histidine isn’t a cure – the oldest surviving Menkes patient was 37 – but if treated very early it can have a significant impact on growth, brain development and life expectancy.
Sarkar, who refused to patent his discovery, worked with a SickKids pharmacist to create a recommended dosage and clinical protocol and it has since become the standard treatment for Menkes disease.
“When I discovered copper-histidine in human blood, I really didn’t know what it was,” he says. “But I followed my curiosity and when you do that, science has tentacles.”