Chris Mehlin, Project Violet

Small compounds derived from organisms: a big promise for cancer treatment

by Graciela Matrajt

The scientific world is full of fascinating people. Many are sensitive individuals, particularly those who work in tough diseases like cancer. This is the case of Chris Mehlin, a chemist who has worked in drug discovery for 15 years and who recently joined Jim Olson's group at the Fred Hutchinson Cancer Research Center.

Chris was interested in science from an early age. Attracted by the sense of philosophy that his grandfather, an astronomer, transmitted to him, he started reading Isaac Asimov's books and soon realized that he had an aptitude for science. 

As he advanced in his high school years, he dedicated himself to deepening his scientific knowledge. Chris wanted to help improve people’s health, so he went into drug discovery, first as a chemist at the University of Illinois and later at the Department of Pathobiology at the University of Washington (UW), where he received his Ph.D.

When Chris was a graduate student, his sister, whom he was very close to, was diagnosed with a type of blood cancer called Hodgkin's disease. This event sparked Chris’s sensitivity, making him realize he could use his scientific background to develop treatments for tough diseases. 

For several years, Chris worked in a structural genomics lab at the University of Washington, where he focused his efforts in finding drug targets to fight malaria, a devastating disease. Then, he moved to the biotech sector where he searched for drug targets using antibodies, a class of proteins involved in immunity. But Chris believed that a better approach to fight disease was through the use of small compounds –called “peptides”- which are smaller than antibodies but larger than most conventional drugs. 

And as it happens with love, which brings two similar people together, so it happens with science, which brings bright minds together. One day, Jim Olson, who had heard about Chris’ expertise and leadership strengths, invited Chris to meet with him to talk about working together on peptide drugs. 

Indeed, for years both of them had been working independently on the properties of natural compounds with a potential therapeutic: Chris was working with Cyclosporine, a compound secreted by a fungus, while Jim was working with a compound extracted from scorpions called Chlorotoxin. 

Both Chlorotoxin and Cyclosporine are mid-sized molecules that act inside cells. By combining the qualities of small and large-molecule drugs, they show immense promise in treating diseases in a new way. A remarkable particularity is that Chlorotoxin can cross the blood-brain barrier, something that antibodies cannot do, meaning that it can be used to deliver treatment targeted to a very particular type of cancer for which treatment is not available: brain cancer. 

Jim’s research mission, which is highly oriented toward fighting brain cancer, particularly in children, was a source of inspiration to Chris, who shortly after joined Jim's group. “I knew that working in a Research Center was an extraordinary opportunity to do high breakthrough science and that I could make a drug that helps people, my number one goal in life,” says Chris. 

Chris and Jim started the Peptide Drug Discovery Initiative, for which Chris is the director. So far it has been very successful, as they have already found several molecules with structures similar to Chlorotoxin and Cyclosporine, derived from a variety of organisms: bacteria, potatoes, and West African berries.

These molecules are all peptides, and in the lab Chris and colleagues look to create an optimized synthetic form of these peptides, to make their properties more optimal to treat cancer. They are known as “Optides”, from optimized peptide, and they have a lot of potential as therapeutic drugs. “I am happy to have joined this group. I feel that here I can change the world” admits Chris.

Thanks to the similarities between fungi and scorpions, today two bright scientists are working on a very innovative and promising route to fight brain cancer. Follow their track and watch out for poisonous scorpions and fungi in your next hike, as they may bear the secrets against this, and other diseases.