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Alumnus worked in lab of Distinguished Professor Marvin Caruthers assisting in the development of pioneering technology

Second-generation CU Buff and Boulder native Lincoln McBride helped pioneer technology used to test for the novel coronavirus, COVID-19, and he credits his success in part to scientists at his alma mater.

McBride earned a doctorate in chemistry from the University of Colorado Boulder in 1985 and worked in the lab of Distinguished Professor Marvin Caruthers, the founder of Amgen (one of the world’s largest biotechnology companies) and one of four CU professors to have won the National Medal of Science.

Recently, McBride learned that the FDA had approved COVID-19 testing using technology he pioneered while working at Applied Biosystems Inc. (ABI). He founded and led that technology program from 1991 to 1997.

His team shipped its first prototype in 1995 to Genentech (Roche). The Model 7700 TaqMan Real-Time Polymerase Chain Reaction Sequence Detection System was then commercialized in 1997. This technology allowed scientists to detect and quantify the presence of minute amounts of genetic material with unmatched speed, sensitivity and accuracy. 

The latest generation of this technology is proving invaluable worldwide for COVID-19 testing during this pandemic, McBride said. 

He recently answered questions about his work and his time at CU Boulder. The questions and answers follow:

What did you work on in Marvin Caruthers’ laboratory while at CU?

I helped identify and develop methods for structural optimization, synthesis and purification of phosphoramidites, the key building blocks for solid-supported, automated DNA synthesis, which has helped fuel the biotech revolution.

How do you best describe the technology that you worked on at Applied Biosystems?

The University of Colorado granted ABI the licenses to the Caruthers group’s phosphoramidite DNA synthesis patents. ABI recruited me with my understanding that I would define and develop new products. Unexpectedly, my first months at ABI were spent frantically solving a crisis with their existing phosphoramidite manufacturing. As a new research and development employee, I was quickly initiated by introduction to a highly commissioned and desperate sales force.

Eventually, my dream was fulfilled at ABI to define and lead a new product line aimed toward DNA diagnostics. The short pieces of synthetic DNA made by phophoramidite chemistry invented in Dr. Caruthers’ lab in the early 1980s were, and still are, used worldwide for inventing and performing myriad revolutionary biotechnology applications. 

One of which, Polymerase Chain Reaction (PCR), makes millions of copies of any short genetic target. This amplification takes place in a few drops of buffered water containing, most importantly, Taq Polymerase as well as two short pieces of synthetic DNA designed to uniquely stick or “prime” to a target’s unique DNA sequence. This “cocktail” is put in a small vapor-tight container and placed on a rapidly heating and cooling plate called a thermal cycler. 

Taq polymerase is an enzyme that not only survives, but also makes copies of DNA at the elevated temperatures required for thermal cycling. The two synthetic “primers” direct the polymerase to the target to be copied.

Each time the thermal cycler completes one heating and cooling cycle, taking about a minute, the number of target copies made doubles. So, 20 minutes later, as many as 2 to the power of 20—or 1 million—copies of the original genetic target are made. Hypothetically, if a given test sample originally contained two virus particles, 20 cycles of PCR amplification would produce as many as 2 million copies of the targeted DNA fragment. 

Real-Time PCR technology places an integrated fluorescence detector over the thermal cycler to detect in real time the copies being made during PCR amplification. Fluorescence is made possible by adding a synthetic fluorescent DNA probe to the PCR cocktail. We made our fluorescent “TaqMan” probes with the DNA synthesis chemistry invented in Marv’s lab. ABI’s fluorescence technology originally was developed in the late 1980s for their DNA Sequencers that were used to sequence the first human genome. 

Many of us at ABI were so enthused by the promise of fluorescent probe-based real-time PCR for both research and diagnostics that we agreed to merge with Perkin Elmer as their junior partner in order to have their rights for key PCR patents. Immediately after the merger, I formed and led the combined ABI and Perkin Elmer product team through commercialization. The Model 7700 led to a multi-billion-dollar product line for ABI.

How is that technology now being used to fight COVID-19? 

Twenty-five years after shipping our first prototype, my team and ABI as a whole can still be proud. For a virus as a detection target, fluorescence, probe-based real-time PCR has proved to be the most sensitive and rapid way to measure its presence in myriad sample types. 

The latest generation of this technology commercialized by Thermo Fisher, which now owns the ABI brand, was recently granted emergency permission by the FDA to test for this coronavirus. More recently, Roche and Abbott have been also granted emergency permission for their current product versions of real-time PCR. 

What were some of your experiences while at CU?

Sharing these memories with teammates at ABI and key instructors has been more rewarding than any bonus or promotion ever was. Writing here to thank the University of Colorado and professors for my education is equally gratifying. 

Professor Barney Ellison, a physical organic chemist, was our freshman chemistry graduate class “shepherd.” We freshmen needed to commit to a thesis advisor by Christmas. I was recruited by CU as a physical organic chemist presumably because of my affinity for math and hands-on organic chemistry experience. 

Christmastime came, and I had cold feet, unable to choose. I remember like it was yesterday the knot in my stomach when meeting with Professor Ellison where he offered, “I don’t see a big O (for organic chemistry) branded on your forehead. Go over to MCDB (molecular, cellular and developmental biology) or walk up to the third floor and talk to the biochemistry groups.” How selfless was that! 

So, thanks to Professor Ellison, and my deceased chemistry Professor Kurt Kaufman at Kalamazoo College, that I stumbled upon my great thesis advisor, Marvin Caruthers and his group’s revolutionary work on solid supported DNA synthesis. 

Who at CU made a significant impact on your career?

Over the years I’ve tried to pinpoint the qualities that make Marv so successful. Of course, he has good ideas and intuition, but what sets him apart is that he was an amazing leader, ahead of his time. 

I believe it’s a badge of honor for him to have assembled such talented, diverse and even somewhat unruly teams. He’s stated to me on several occasions that this style creates the most. He’s not afraid of failure, nor afraid of brainstorming where even one of his latest ideas may initially seem silly, risking loss of credibility with some technical folks.

During my stay, he led our “primordial soup” group with a soft touch and profound results. In my estimation, he’s a strong candidate as a modern-age Nobel laureate, notably for all the far-reaching contributions his technical leadership style has given us.

Where do you live, and what do you do in your current line of work?

I’ve retired from the corporate world and have spent many years raising our sons Max and Leo while renovating our homes, including where Claire and I now live in Belmont, California.

Is there anything else you’d like to share with our readers?

My parents were CU undergrads, and I was born in Boulder. My father, William R. McBride, graduated in 1958 with an electrical engineering degree, and it’s my understanding he was an All-American gymnast and performer and president of CU’s high-flying gymnastics and juggling traveling show called the Pentagon. 

My parents moved to Michigan where my father invented the first fully automated coin sorters, counters and wrappers in the 1960s. My mom, Sharon K. Zubler, had me in February of her sophomore year. She was valedictorian of her 1956 class at Monticello High School in Iowa. Her major was a brand new one at CU—physical therapy. She dropped out in 1958 to take care of me when my parents moved to Michigan. She would have made an amazing healthcare CEO. 

For more information, contact Lincoln McBride at Lincolnclaire2018@gmail.com.