September 12, 2018

By Elizabeth Thomson

Jasmine Corbin’s career as a UC Davis graduate student—she is scheduled to receive her Ph.D. in chemical engineering this fall—should be an inspiration for graduate students everywhere.

After years in the lab, her hard work is on track to what could be a spectacular payoff: the production of an affordable drug against organophosphorus nerve agents like sarin gas, the chemical weapon infamous for its use in Syria.

In two published papers and a third that’s being written, Corbin and colleagues describe how they coaxed rice cells to create butyrylcholinesterase (BChE), a human protein that binds up nerve agents in the body before they can hurt soldiers and others. Importantly, it works well after exposure, but can also provide advance protection when injected before exposure.

“It’s a really great drug, but we don’t have a good way to produce it cheaply,” said Corbin, who worked in the laboratory of Professor Karen McDonald at UC Davis. Today a single dose of BChE produced by purification from human plasma costs about $20,000. Over the last 20 years, scientists have worked on many alternative ways to produce the drug, said Corbin, “but none of them has really been the Holy Grail that gives something effective and inexpensive.”

Thanks to genetic engineering and innovations including a unique processing system, Corbin expects that her approach could bring the cost per dose down to less than $300. “That’s almost a 100-fold decrease in price,” she said with a hint of awe.

There were many challenges along the way. For example, in addition to creating cultures of rice cells containing the gene for BChE, Corbin added an extra genetic element that “allows you to turn on and off the production of the drug using a specific trigger, sugar starvation.” Give the cells sugar and they grow; take away the sugar and they start producing the drug. The result is a semi-continuous process that alternates between these two phases of growth and production. “It allows you to re-use your cells rather than harvesting the drug from them, throwing them away, and starting the process all over again.” And that can save a lot of money.

Corbin also developed a cost-effective way to purify BChE from the rice cells. Then, working with collaborators at the US Army Medical Research Institute for Chemical Defense, she compared the rice-derived drug’s effectiveness to the version derived from human plasma. The results, based on tests in test tubes, “were very exciting,” Corbin said. “We expect that our drug should be able to provide protection.”

The next step is to make lots of the new drug and test it in animal models, work that another graduate student in the McDonald lab will take over. Corbin herself has accepted a job at Allakos, a biotech company in the Bay Area.

Two mentors at UC Davis and one program were key to Corbin’s graduate career. Through Professor McDonald, “I matured a lot both as a scientist and a person.” She also notes the support of Dr. Somen Nandi, an adjunct professor in the McDonald lab. The UC Davis Biotechnology Program “really characterized my entire experience at UC Davis. It gave me a community of like-minded people and taught me the skills needed in the industry, thanks in part to a required internship that was a privilege to hold.”

Over her years in the lab, “I often felt like I was doing everything wrong,” Corbin said. “For every experiment that works and turns into a publication, you have some 30 that fail. So it was really rewarding the first time I saw the number for the estimated cost per dose of our drug. Hopefully I did something that will help people.”