A story of human ingenuity crossing decades

This article by Michael Helmstetter, Ph.D., first appeared July 6, 2021 at Forbes

In my last article, I made a case for betting on the power of human ingenuity. Coming from a family of scientists, I have some firsthand experience in understanding how a simple question can drive inventions, even decades later.

What’s at the core of ingenuity?

Most definitions of ingenuity describe a condition of being clever, original, or inventive. The etymology of word itself is intertwined with dual meanings – from the French referring to a trait that is “inborn or freeborn,” and from Latin with links to “the mind” and “intellect.” Significantly, it’s also connected to the Latin root of the verb “to engineer.”

In modern culture, ingenuity describes the creation of a solution to a dilemma or problem. It is tied closely to uncovering truth and demonstrating novel or unusual approaches to achieve a solution. Google shows use of the word waning since a high point around 1789, but in my world of scientific research, it remains a constant presence – as does the search for truth.

A recent example: Covid-19 vaccine

When I received my Covid-19 vaccination, I understood how it worked in human body. As a scientist, I was confident in the research and the knowledge it led us to – a way to use messenger RNA (or mRNA) to train our immune system to recognize and fight off coronavirus. In agricultural biotechnology and in some animal health areas, my company TechAccel is using a similar approach through RNA interference (RNAi) to create safe and insect specific biopesticides, vaccines for diseases in animal health, and other applications.
My father, Charles Helmstetter, Ph.D, on the left, and my uncle, Bill Studier, Ph.D., in a friendly (but fierce) competition from the 1960s with rubber suction darts. Their ingenuity in basic research contributed to discoveries to make the world a better place. (Photo Credit: Author Collection)
Later, after my vaccination, in family chatter that started with my updates on our RNAi insect field trials and stitched in discussion of the mRNA vaccines, I learned a fascinating footnote: My sole uncle’s research some 40 years earlier had delivered a critical step in the manufacturing of the mRNA vaccines developed by Moderna and Pfizer/BioNTech. Bill Studier, Ph.D., who I’ve highlighted in a previous article, spent 51 years at Brookhaven National Lab and retired in 2015 with the title senior biophysicist emeritus.

While performing basic research at Brookhaven, Dr. Studier developed a way to harness the molecular machinery of E.coli, through the T7 bacteriophage, highlighted in a recent article by the Brookhaven National Lab. The article explains: “T7 is a virus that infects E.coli and commandeers those cells to make copies of the virus.”

Dr. Studier and his team then “direct(ed) T7’s prolific copying capability toward making things other than T7s.” The process involves cloning T7 polymerase, an enzyme that transcribes DNA genes into messenger RNA, which instructs cells how to build a particular protein (just as occurs in the mRNA Covid-19 vaccines). Combining the T7 polymerase with a T7 promoter, the team found a way to produce large amounts of RNA from almost any gene.

This expression system was patented and is now noted as Brookhaven’s most successful technology, licensed to more than 800 companies and earning the laboratory – not my uncle – more than $72 million. The T7 system has earned Brookhaven “much of its royalty income over the years,” notes a April 11, 2001 article and a Dec. 11, 2018 article.

And now, Brookhaven reports this system is used by the companies that make the mRNA Covid-19 vaccines. The Science Behind the Shot explains how it is used in vaccine manufacturing in an animation; The New York Times also detailed the Pfizer process for manufacturing its mRNA Covid 19 vaccine, explaining the T7 procedure in steps 9, 10, 13 and 14.  

Different rewards

My uncle is now 85 and lives with his wife, Sue, in Pleasanton, CA, importantly close to family and wineries. They’re celebrating 59 years together. I remember many unique attributes about my uncle: His obsession with the most difficult math or structural puzzles, his highly competitive nature and borderline-scary way to intimidate rival poker players (including even me in my teens), and, maybe most importantly, his ability to tie science to almost everything we do. I remember quite fondly while I was an aspiring high school baseball pitcher with a mean curve ball, there in my backyard, he taught me the physics of how it worked. My curve was even better from that day on.

Yet with all that genius-level knowledge, he lived modestly. For example, he drove a base model Toyota Camry for 300,000-plus miles before trading it in for yet another base model Toyota Camry. A recent article from his hometown newspaper (he is a native of Waverly, Iowa), used the word “humble” four times in describing him. 

I can recall conversations between my uncle and my father, Charles Helmstetter, Ph.D., a retired Florida Institute of Technology and Roswell Park Comprehensive Cancer Center cell biologist. They often spoke about basic research, a shared passion. I’ve written before about my father, one of the most prolific and successful recipients of National Institutes of Health funding. He made many discoveries throughout his 46-year career, the most significant being a system to produce “synchronized” bacterial cells all of the same age for cancer and other studies.

In one recent exchange, while the two were sharing war stories about grant writing, my father expressed his irritation at grants that ask, “How will your research help humanity?” He pounded the table: “You can’t answer, you don’t know. If you make up an answer, it’s not basic research.”

There is a simple motivation in basic research. It is exploration, learning at each step. Knowledge for knowledge’s sake. Basic research doesn’t start with a specific goal, rather a hypothesis; and you may not know where it will lead you. My uncle had no idea that the basic research he was doing decades ago would play such a pivotal role in addressing a major global pandemic.

“I had wondered casually if T7 RNA polymerase might be involved in making the RNA vaccines,” my uncle recently commented in a Brookhaven article. “Basic research is almost always useful and I’m pleased that my work has been helpful in obtaining powerful vaccines against this pandemic.”

Back to ingenuity

This is why we do basic research and why it is critical that we -- government, industry and academia – continue to invest in basic research. You can think of knowledge like a fine dust that slowly builds and accumulates over time. Sometimes a new bit of understanding may produce tectonic plate shift, opening up a whole new landscape. Sometimes, you may not realize the impact of a learning for decades.

Curiosity drives research: Why? Why not? How? Answering the basic questions leads to the knowledge and its application. That’s the magic part. That’s the spark of ingenuity. That’s why I first became a scientist.

“The invention of easily programmable RNA vaccines was a lightning-fast triumph of human ingenuity, but it was based on decades of curiosity-driven research into one of the most fundamental aspects of life on planet earth: how genes encoded by DNA are transcribed into snippets of RNA that tell cells what proteins to assemble,” says Walter Isaacson in his latest book, “The Code Breaker, Jennifer Doudna, Gene Editing and the Future of the Human Race.

He continues: “Great inventions come from understanding basic science. Nature is beautiful that way.”

The motivation is not wealth or fame, but a far nobler mission. As Isaacson puts it, the motivation is “the chance to unlock the mysteries of nature and use those discoveries to make the world a better place.” 

Just like my uncle and my dad have done and so many before and after.
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