Thesis Christ: Synthesizing Strychnine with Lucas Forshee

The thesis is a way for seniors to leave their mark in the history of both their discipline and Reed’s institutional memory, which Lucas Forshee ‘25 understands particularly well from his thesis’ combination of chemical and historical analysis. Forshee is conducting historical research on the place of strychnine within the development of chemistry alongside his own synthesis of strychnine, working with Visiting Assistant Professor of Chemistry Bobby O’Brien. 

As Forshee explained, strychnine has been a critical chemical throughout history, with uses in everything from assassinations to tests of groundbreaking chemical analyses. Strychnine is notable as the first chemical to be isolated as an organic base, which is significant as previously chemists “organized chemicals based off of what plants or animals they isolated them from” and “could not conceive of a basic plant chemical.” 

After this development, chemical research began to order chemicals based on atomic composition, rather than physical characteristics. Forshee explained, “Chemistry was more about the physical structure of molecules around this time and strychnine, having one of the most complicated structures of all time, became this forefronting molecule of how far we can push the technology of analytical structural determination of chemicals.”

Speaking on strychnine’s historic role, Forshee said, “People are still synthesizing it today. I decided I wanted to be a part of that little history and I devised my own route.” Forshee is carrying on the spirit of these previous chemists’ breakthroughs by conducting his own synthesis of strychnine. Forshee is operating within the discipline of total synthesis, in which chemists build “more complicated organic compounds using only chemicals that you can buy that are available for purchase very cheap online.”

In doing so, Forshee is working with Bobby O’Brien using a method known as “convergent synthesis, where you build multiple little parts up and then you connect them all in one big step.” Forshee is currently five steps into the sixteen-part process of synthesis, and does not intend to complete a full synthesis of strychnine, which is a lengthy endeavor that can take years of work. Still, Forshee believes his analysis will be valuable in supporting future chemists, saying “I’m kind of here to set the stage for research in the future in the [Bobby] O’Brien lab.”

After working with O’Brien over the summer, Forshee was driven to pursue strychnine synthesis for his thesis after finding an earlier synthesis of strychnine conducted using the same type of reaction. He modeled his synthesis on this synthesis from 2005, modifying it with the new techniques that have become available in the years of research since then. Forshee explained his motivation, saying “I identified that this was something I could improve on, using the chemistry that we developed over the summer.”

In his quest to add to the history of strychnine, Forshee’s thesis has not been without its fair share of challenges, in the synthesis as well as the research. From a practical standpoint, Forshee related how he has to contend with limited lab space and time constraints. Describing the realities of doing a chemistry thesis, Forshee stated, “The amount of research you can get done is directly proportional to the amount of time you spend in lab,” although “trying to manage it with my other classes has been difficult just because I want to do as much as I can.”

“It was difficult in the beginning to really find a foothold in it because [the] history of chemistry doesn’t have the largest body of research around it and it’s not exactly centralized in any specific school or anything,” explained Forshee. As a result, he has had to comb through a limited number of sources to find unexpected connections in the references of papers. By contributing to this legacy, Forshee hopes his own thesis research will become “the newest footnote in the history of strychnine.”

After graduation, Forshee hopes to get a Fulbright scholarship to conduct research into science communications in Indonesia. If this opportunity works out, Forshee will split his time between a research lab studying the genetics of coffee plants and out in the fields working with coffee farmers. “I want to see how information about the fungal diseases that bring blight upon coffee production… is disseminated to someone who works in a genetics lab compared to someone who works actually cultivating the coffee and how the power dynamics work within that,” said Forshee.

Apart from recommending that future chemistry seniors apply to work with O’Brien, Forshee advised anyone thesising now or in the future, “See it as something that is your research and make it your own. I think this is a very unique opportunity that we have where we have the ability to look at whatever we want to look at. To be able to do research is a gift and a privilege in itself.”