Long before anyone knew anything about COVID-19, scientists studying an obscure enzyme at Brookhaven National Laboratory stumbled upon one of the key building blocks of two vaccines that today are saving potentially millions of lives, Newsday has learned.
The discovery nearly four decades ago of the so-called T7 expression system by a Brookhaven team led by senior biophysicist F. William Studier initially was of little interest to the general public. But scientists quickly grasped it could be used to study molecules and develop cancer treatments — and pharmaceutical giants Pfizer and Moderna incorporated the process into the vaccines that so far have been used in more than 250 million injections in the United States.
And it was all an accident. Studier had no idea he would help to fight a deadly disease when he began studying a virus that infects E. coli, a bacteria known as the scourge of the agricultural industry. It was simply the kind of routine scientific research that he and others at the Upton lab conducted every day.
"He was just studying how the virus worked," said John Shanklin, chair of Brookhaven’s biology department. "And he then just realized that he had, kind of, the puzzle pieces to put something together that would be uniquely useful."
Brookhaven’s research is one of the reasons Moderna and Pfizer were able to manufacture their vaccines in such enormous quantities, and so much faster than what would have been possible previously, said Venki Ramakrishnan, a Nobel Prize-winning biologist with the Medical Research Council Laboratory of Molecular Biology in Cambridge, Great Britain.
What to know
- The so-called T7 expression system was discovered by a Brookhaven team in 1983 and is a key component in the production of the coronavirus vaccine
- In an exquisite piece of scientific subterfuge, a senior BNL biophysicist realized that T7 could be tricked into copying good kinds of protein — like the kind that helps fight human diseases
- BNL's 38-year-old discovery will help Pfizer and Moderna develop new versions of the vaccine as the coronavirus mutates into different variants
Studier's 38-year-old discovery also will help those companies swiftly and efficiently develop new versions of the vaccine as the coronavirus mutates into different variants, he said.
"It’s a very powerful tool," Ramakrishnan said in a telephone interview. "Of course, a lot of things went into it, but I would say the Brookhaven element is an essential component of what is needed to make this vaccine. … It made something possible that would not have been possible before."
Roots in gene-cloning
Pfizer and Moderna, in separate emails to Newsday, acknowledged their vaccines used the technology pioneered by the Brookhaven lab. Both companies declined to comment further.
The research leading to the T7 expression system had its roots in the 1970s gene-cloning craze, when scientists around the world were looking into copying genes of living things as small as cells and as large as sheep.
Studier had been studying bacteriophage T7, a virus that infects E. coli, since his graduate school days in the early 1960s. He continued the research at Brookhaven, where he worked with senior researcher Alan Rosenberg, the late John Dunn, graduate student Barbara Moffatt and postdoctoral fellow Parichehre Davanloo.
Their research involved studies of molecular mysteries such as messenger RNA, or mRNA, the scientific marvel that helps convert DNA into proteins.
E. coli is a common bacteria that dwells in humans, other warm-blooded animals and some foods. Some forms can cause illnesses such as diarrhea and urinary tract infections.
But E. coli has a natural enemy in T7, which kills the bacteria by infecting it and rapidly replicating its own proteins.
In an exquisite piece of scientific subterfuge, Studier realized that T7 could be tricked into copying good kinds of protein — like the kind that helps fight human diseases.
"It turned out by luck," Rosenberg said in a phone interview, "that T7 had elements that if you put them together in the right fashion, what you could do is fashion a system to [create] large amounts of messenger RNA or any protein you desired to have large amounts of."
The Brookhaven team eventually figured out how to redirect T7 toward using its powers for good instead of evil. But first they had to learn how to clone the little varmint — something that no other lab had done.
"Our group accomplished this in 1983," Studier, 84 and retired, wrote in an email from his home in Pleasanton, California. "This enabled the T7 expression system, which has been widely used for making almost any proteins. As it happens, it also enables obtaining large amounts of mRNAs for vaccines."
Studier said the result, nearly 40 years later, is enormously satisfying.
"I feel very good that our early work is helping to save so many lives," he wrote.
Shanklin said the genius of Studier’s discovery was that he found he could substitute the gene of any living thing in E. coli, and then by adding components of the T7 virus, "He could trick the E. coli into essentially copying only that one protein."
The discovery revolutionized science by simplifying things that once had been laborious, Shanklin said.
"It just changed everything about the way everyone did everything," he said. "It made it really simple."
Speeds vaccine production
Brookhaven officials said Studier’s discovery is the most successful technology in the lab’s history.
"T7 is still the go-to system for biochemists everywhere," lab officials said in a news release.
Brookhaven once held patents to the system, but they expired in 2014, lab officials said. Over the 24-year patent period, the lab was paid $70 million in royalties by hundreds of companies that used the technology.
The technique also helped to speed development of the Moderna and Pfizer vaccines by providing crucial shortcuts.
First, the technology enables swift mass production of the vaccines. Then, once injected into human arms, the mRNA in the vaccine prompts our own cells to manufacture a "spike" protein, which in turn sends our immune systems into action to fight the COVID-19 virus.
"Your cell makes the protein for you, and then you get the immunity from the protein that you made yourself," Shanklin said.
Combined with the ability to quickly alter the vaccine formula to fight COVID-19 variants, "the cumulative effect of those two things is we’ll save millions of lives worldwide," Shanklin said.
"We’re all really happy," Shanklin added. "And also we’re happy because Bill Studier is … a model scientist and a model gentleman. I don’t think there’s anyone at Brookhaven National Lab who’s met Bill who doesn’t have tremendous respect for him. He lives and breathes science and does it in the best community-benefit way that he can."
Getting vaccinated, Shanklin said, should be thought of as "a civic duty" that will help the world defeat one of the worst pandemics in history.
"Once we get to this herd immunity, that is the single thing that will get this under control and get rid of it," he said.
A previous version of this story misstated what then-senior BNL biophysicist F. William Studier was studying when his team discovered the T7 expression system; the role the T7 expression system plays in the coronavirus vaccine; and T7’s effects on E. coli bacteria.