David MacMillan: “Organic stuff just makes sense”

The MacMillan family lived in the small town of Bellshill, Scotland, and David MacMillan’s older brother was the first in the neighborhood to go to college, where he studied physics. After graduating, he got a job making more money than the boys’ father, who promptly sent young David to college to study physics as well.

He found his calling

At the stately and nearly ancient University of Glasgow  – founded in 1451 – physics was taught early in the morning in a cold room with a leaky roof.  MacMillan also signed up for a chemistry class, which was taught later in the day in a building with heat and an intact roof. Then he took organic chemistry and found his calling. ”It was one of the few things I could read and understand immediately,” he says. “Organic stuff just makes sense.”

”It was one of the few things I could read and understand immediately.”

So began MacMillan’s life’s work, which culminated in him winning half the 2021 Nobel Prize in Chemistry for the development of asymmetric organocatalysts, which produces organic, carbon-based molecules that are mirror images of one another and can drive chemical reactions. MacMillan, who currently is the James S. McDonnell Distinguished University Professor and Director of the Merck Center for Catalysis at Princeton University in the U.S., shared the Prize with German scientist Benjamin List, who was working with organocatalysis on his own.

It took several tries for MacMillan to get the news that he had won a Nobel Prize.  When a colleague called MacMillan early on an October morning to tell him he was a Nobel laureate, he thought it was a prank, hung up and went back to sleep. Later he got up, went to get coffee and saw an artist’s rendering of himself in the New York Times, accompanying a story on Nobel Prize winners.

More accessible

The organocatalysts produced in the work by MacMillan and others can be used in the creation of pharmaceuticals, perfumes and even clothing and shampoo. They are less expensive to create than metal catalysts, which are often toxic. The organocatalysts also can break down plastics so they can be recycled.

MacMillan started looking for alternatives after several years of the cumbersome process of working with metal catalysts. “I had to make catalysts and I had to use big boxes,” he says. Scientists cannot handle metal catalysts and must manipulate them in a box while wearing gloves.

“I was working in this box for two years, and I wanted to use organic molecules. I wanted to stay away from metals, because organic molecules are more sustainable and better for the environment.”

“I was working in this box for two years, and I wanted to use organic molecules. I wanted to stay away from metals, because organic molecules are more sustainable and better for the environment,” McMillan says.

He created his first organocatalyst by combining an amino acid from an artificial sweetener with nail polish remover. “The first one was so cheap,” MacMillan says. The use of organic material “democratizes” this research, he says, because the organic catalysts are more affordable. “These make the process more accessible to people. When you make tiny changes (in organocatalysts), you can go from something smelling incredibly bad to sweet. It amazes me to this day.”

One of the biggest applications of organocatalysts is in the development of pharmaceuticals. This is where the process of asymmetric organocatalysis comes in, creating molecules that are mirror images of each other. Frequently, scientists only want to use one of the molecules, since the two versions can have different properties, and asymmetric organocatalysis produces them efficiently.

“When you make mirror images for medicines, have to be able to make one and not the other,” according to MacMillan. “You have to use the right one.”

The importance of early education

MacMillan began working with catalysts in 1999 when he was doing a post-doctoral program at Harvard University. The story of how he came to the U.S. to study also is a bit quirky. MacMillan was inspired by his passion for the National Football League (NFL) in the U.S. “I was doing my undergraduate work in Scotland, and I loved the NFL, so I wrote to 19 universities in the U.S. about getting into their PhD. programs,” he says. “The University of California at Irvine was the only one that accepted me.”

Multiple people, both in and outside the science field, influenced MacMillan on his career path. Among them were Larry Overman, with whom he worked on his PhD; Dave Evans with whom he did his post-doctoral work at Harvard  – “he thinks about chemistry in a different way” – and Scottish comedian Billy Connelly. “He came from working-class Scotland and was able to go off and see the work using his communication skills, having a great relationship with people.”

“Teachers worked hard to make sure everyone had a high level of education. I would not have won a Nobel Prize without these teachers.”

MacMillan also cited the importance of his early education in his home country. “When I was in elementary and high school in Scotland, there was a huge premium on education,” he says. “Teachers worked hard to make sure everyone had a high level of education. I would not have won a Nobel Prize without these teachers.”

MacMillan also is well-known in the field of photoredox catalysis, which employs visible light to separate and reconnect atomic bonds.

To jettison science, makes no sense

For ten years MacMillan says he worked with visible light, developing ways of mapping cells and devising ways for light to enter cells with the catalysts, enabling scientists to see inside cells while diseases are happening. “This technology tells you what cells are nearby and tells you how to go after new targets for different diseases,” says MacMillan.*

As he continues to pursue different problems in chemistry, MacMillan says he worries about how some of the current attitudes towards science will impact future research.

“To jettison science, makes no sense. Without science we have nothing. We have to get back to trust and faith.”

“A lot of people lost faith in science,” he says. “In the past, we had faith in science and it was apolitical. What every single person in society doesn’t realize is that we wouldn’t have the world we have without science. To jettison science, makes no sense. Without science we have nothing. We have to get back to trust and faith.”

about the author

Ellen R. Delisio is a US-based freelance journalist and editor. Since 2010 she has written numerous articles, including several Nobel Prize interviews, for NLS magazine.