“I had synthesized a new molecule, and I was asking someone else in the lab where I could find a picture of what it should look like,” MacMillan recalls. “I was told there was no such picture because the molecule had never existed before.”
Groundbreaking work has been MacMillan’s hallmark ever since, and he has been recognized with the field’s most prestigious awards, including the American Chemical Society’s Arthur C. Cope Scholar Award, the Thieme-International Union of Pure and Applied Chemistry Prize in Synthetic Organic Chemistry, and, most recently, the 2021 Nobel Prize in chemistry.
A good part of this acclaim is for his role in pioneering a new method for creating organic molecules, an area of research called organic synthesis. As MacMillan explains, in organic synthesis, chemists work to create new molecules that have the capacity to bind to different sites in the body. The new molecules must be designed to fit into biological receptor sites like a key in a lock. The research has an enormous impact on pharmacology; these new molecules can be used in the development of new drugs.
MacMillan’s research group made its breakthrough searching for a method for organic synthesis that would replace the metals usually used in the process — which were expensive, toxic and unstable — with safer, cheaper, organic compounds. The new process they invented has since been used by researchers all over the world to create hundreds of new molecules.
It's that ability to reinvent the world of organic chemistry through work in the lab that MacMillan loves best about his field. “It's like playing chess,” he explains. “You learn all the theory, but then the excitement comes from how you put the elements together. You aren't just observing; your work requires creativity as much as knowledge.”
For students who think they might like to explore the world of organic chemistry, MacMillan has some straightforward advice: Get to a lab. “Sure, students should learn the theory and read their textbooks, but as fast as possible they should get involved in laboratory research.” According to MacMillan, in this field, it's remarkable how quickly students can begin doing work at the forefront of research. “Right away you can create a piece of matter that's never existed before,” he says.
It's an opportunity MacMillan offers to the students who join his research group. “Students gain a lot in my group. They are exposed to researchers from all over the world,” he says. “Moreover, they'll get to work on real projects, not just do prep work for other people’s research. They'll be designing new chemical reactions. It is such an exciting thing to know that there will be immediate applications for their work.”