Congo compounds

An integral part of science is detecting hitherto unforseen connections. The path of research is not straightforward. There are often twists, forks and junctions along the way. While working on a couple of stories at La Trobe University, Archimedes was struck by the connections which can lead to significant outcomes in research. Then the stories merged ...

The first story begins when Lorenz Gran, a Norwegian doctor working with the Red Cross in the Congo in the 1960s, observed a tendency for the contractions of women in labour to accelerate after being visited by relatives. He soon tracked down the cause—a traditional medicinal tea brewed from a local weedy plant smuggled into the women. On his return to Norway, Gran extracted the active ingredient. It was a small protein, but he was unable to unscramble its structure. Twenty years later, Prof David Craik, now at the Institute for Molecular Bioscience at the University of Queensland, used nuclear magnetic resonance (NMR) to solve the problem.

Craik found a complete ring of about 30 amino acids, tied into a pretzel-shaped knot by cross linkages between sulphur atoms. He named the compounds cyclotides. Not only is their structure tiny for a protein, it is also exceptionally stable and resists boiling. So, Craik reasoned, they could pass through the digestive system without being broken down. Yet they were so small, they should be easily absorbed. In short they could form a useful platform for oral drug delivery.

Concurrently, cyclotide compounds were found to be widespread in plants though their natural function was a mystery. ‘We thought anything produced in such abundance in leaves—where you get 20 to 30 different types produced by one plant—probably had something to do with plant defence’, said Dr Marilyn Anderson of the La Trobe Department of Biochemistry. She was right. When Anderson and her research team fed a diet containing the compounds to an important pest of cotton and corn, the insects did not grow, and nearly half died within a fortnight of hatching, leading to the possibility of a new class of insecticides.

But there’s another strange link—multiple sclerosis. MS is a degenerative disease of the nerves of the spinal cord and brain that, since the eradication of polio, is the most common cause of paralysis in Western countries. La Trobe has a research group working in the area, headed by Prof Claude Bernard.

Until recently, MS was thought to be associated solely with inflammation of the fatty (myelin) sheath surrounding the spinal nerves. Following recent work in the US and at La Trobe, many neuroscientists now believe the condition actually involves damage to the nerves themselves.

Now, the La Trobe group has published evidence in British journal Nature Neuroscience establishing a link in mice between an MS-like condition and nerve damage, providing possibilities for treating MS by applying new techniques for repairing spinal cord injury.

The connection to the cyclotides? Professors Craik and Bernard are now exploring the potential of the protein from the plant in central Africa to treat MS.

These stories provide support for open access to scientific knowledge. How else can researchers become aware of obscure medicinal plants in the Congo? Today, commercial and security interests restrict the flow of scientific information. The end result could be to choke the life blood out of science. 

Tim Thwaites is a freelance science writer



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