A Romance with the Power of Evolution

Caltech, MIT and Stanford alumnus, M.G. Finn, also GTPT Chief Science Officer, shares his life science journey, insights on opportunity and advice for those aspiring to a possible career in chemistry and the life sciences

The faculty at Georgia Tech include many of the finest, most accomplished researchers, scientists, scholars and engineers in the world. The Georgia Tech Pediatric Technology Chief Scientific Officer M.G. Finn, Ph.D., is one of them.

M.G. Finn

He currently holds the James A. Carlos Family Chair for Pediatric Technology and is Chair of the School of Chemistry and Biochemistry. His group conducts their research in two buildings on the Georgia Tech campus, befitting a dual focus on synthetic chemicals and biomolecular systems.

M.G. and his group were instrumental in developing the science honored by the 2022 Nobel Prize in Chemistry for “Click chemistry,” which is changing the world “by making it possible for scientists from many different areas to create new functional molecules or molecular systems.” (You can hear him talk about this subject in a public lecture given to the Georgia Tech community at https://www.youtube.com/watch?v=SdkPDW8brY0.)

In parallel to a recent Georgia Tech “Faces of Research” article, we are most pleased to share more about M.G.’s career pathway, his work and life science insights in the following Q&A.

Tell us about your career’s journey

“Mine is a career path of extraordinary good luck in its intersections with extraordinary people. I started with a B.Sc. in Chemistry at Caltech, then went to MIT for a Ph.D., where I worked with Barry Sharpless, whom readers may recognize as the winner of his second Nobel Prize this year.

“In the Sharpless lab, I helped work out the mechanism of the chemical reaction that won Prof. Sharpless his first Nobel Prize, thus starting my life-long affinity for the details of chemical reactivity. After postdoctoral research at Stanford in organometallic chemistry, I started my independent academic career at the University of Virginia in 1988. This was another stroke of good fortune, as UVA came through with an offer just before I was set to take a job in the pharmaceutical industry – an exciting path, to be sure, but one that would have been much less suited to my lack of sustained attention span, and almost certainly less rewarding.

“After six years doing research in my previous comfort zone of transition metal-mediated reactions (and barely doing well enough to earn promotion and tenure), I made a sharp turn to the field of combinatorial chemistry for catalysis. We weren’t all that successful in that endeavor, but it led to a dramatic change in my life and career when I did a sabbatical at The Scripps Research Institute in 1996. Scripps was and remains a research powerhouse in the biological sciences, and it was there that I started to learn about biological molecules, systems, and how to manipulate them. In this, I was hugely aided by the peerless Carlos Barbas and Richard Lerner, both of whom are sadly gone, but whose visionary work remains.

“Richard’s influence on me was also immediate and practical: as the president of Scripps, he hired me in 1998. I soon met the structural virologist Jack Johnson, who was looking for a chemistry partner to work with viruses. I was immediately captured by the beauty and potential utility of these particles, which Nature provides in wonderful abundance and limitless variation.

“At the same time, I was reunited with Barry Sharpless who had moved to Scripps several years earlier, and we started talking about his vision of something called ‘click chemistry.’ These interests came together in a new research program to use viruses as molecular building blocks. That, in turn, led to a deep dive – again with the help of wonderful colleagues who were willing to explain things to an ignoramus like me – into the world of immunology, because our immune systems exist, in part, to deal with things that look like viruses.

“After 14 years at Scripps, I came to Georgia Tech in 2013, in part to expand my research to the world of materials science and engineering, and to continue our immunology efforts in new ways.

“While it won’t be apparent to most, a romance with the power of evolution underpins everything that I’ve tried to do since our early combinatorial chemistry days. Evolution is Nature’s way of developing new things, it uses combinatorial mechanisms, and these are most obviously relevant in the functioning of the immune system. And Georgia Tech is perhaps the country’s foremost institution for the study and use of evolution in a variety of ways.”

How did this journey lead you to your role with Georgia Tech Pediatric Technologies?

“Immunology was the conduit. Our work with viruses – Nature’s nanoparticles – connected me to the Center for Pediatric Nanomedicine (CPN), which was created in the earliest days of the partnership between Georgia Tech and Children’s Healthcare of Atlanta.  I had no familiarity with CHOA, nor with the special challenges of pediatric biomedicine, but kids are the primary recipients of vaccines, so I was certainly ready to engage. Gang Bao was the director of CPN, and when Gang left Tech I was asked to take his place. CPN was later folded into the larger structure of the partnership, an organization which eventually became Georgia Tech Pediatric Technologies.

“Most importantly, during this part of my journey, I came to understand some of the unique aspects of pediatric biomedicine. Researchers in this field are fond of saying that kids are not little adults, meaning that medicines, diagnostics, instruments, and techniques that are developed for adult medicine are usually not directly applicable to children. There needs to be much more attention paid to kid-specific biomedical questions, and of course nothing is more rewarding than helping children lead healthier and better lives.”

Image credit: The Finn Lab.

In lay terms, what does the Finn Lab do?

“We develop and use highly reliable methods to make and break chemical bonds. This sounds quite far from pediatrics, or indeed from any application, but that’s not true. Controlling the making and breaking of chemical bonds is required to do almost anything useful in identifying and treating disease. So if [you] are willing to use those skills in the service of collaborative work with experts in other areas, it can take you to a lot of interesting places.

“We therefore find ourselves pursuing five main avenues of research and development in our lab: new immunogens and vaccines, new ways to release drug molecules into the body, effective methods to find and enter cells, new materials and surfaces with desired properties, and new ways to evolve functional molecules and materials.”

What is ‘click chemistry?’

“Click chemistry are chemical reactions that make bonds with the highest degree of reliability and generality. Since chemistry is uniquely a science that creates new matter, click chemistry is also a philosophy or style in which such reactions are used as much as possible, thereby making it easier to find new molecules with desired functions, and to produce them on large scale.”

 

How does it translate into pediatric technologies?

“By enabling the reliable assembly of molecules from almost any type of building block, click chemistry makes it easier to make things that address problems in pediatric medicine. In our case, we use click reactions to create materials such as medical tubing or implants that resist bacterial contamination (an important problem in the long-term care of babies in the hospital) and to create vaccines for kids.”

What are you most proud of, especially tied closely to GTPT projects?

“Our vaccine and immunology work. We have a very promising candidate for a vaccine against leishmaniasis and Chagas disease, caused by related parasites and affecting millions of people around the world, mostly in developing countries. There’s a long way to go to get this to the clinic, but it’s an exciting road to take. I am also very proud of our work with the Centers for Disease Control and Prevention during the COVID pandemic; we helped them develop antibodies early on that were used throughout the agency as standards for virus detection.”

Where do you think the greatest opportunities are for accelerating translational research? 

“As a general matter, translational impact always starts with basic research, lots and lots of it. But there’s also room for improvement in how we translate discoveries to the clinic. There are tremendous opportunities here for targeted philanthropic funding to make an outsized contribution – we need to set up better ways of evaluating the practical potential of new knowledge and inventions, and then pushing the best over the finish line.

“As for fields, I am of course biased towards immunology as an area of great impact – the immune system is our best defense against disease, and we are really only beginning to learn how to enhance and control it for such purposes. Immunotherapy has a very bright future. Also, the loud buzz about artificial intelligence, data analytics, and machine learning is not a fad: these techniques will dramatically change everything from research to diagnostics to treatment. This will go hand-in-hand with the development of more and more devices for home use, making expert medical care more accessible to underserved populations.”

What advice would you give your 20-years-ago-self?

“Make that 30+ years ago, and my advice would be to be even less reluctant to change fields, and be more knowledgeable about how money works in science. Good advice to any researcher starting on an independent career.”

What advice would you give others who might aspire to work in an environment like your lab at some point in their own journey?

“My current students will recognize this one: don’t look for your “passion.” Instead, look for what you’re willing (or eager) to work hard at. Then you can find the environment that will allow you to do so.”

The team at Georgia Tech Pediatric Technologies congratulates M.G. and his team’s phenomenal accomplishments, punctuated most recently by his contributions to Dr. Sharpless’ et. als.’ 2022 Nobel Prize. And we thank them for their contributions that help advance our mission: to accelerate development, regulatory approval, and clinical utility of new medical technologies for pediatric patients.

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