“Chance favors the prepared mind.” Louis Pasteur

I couldn’t help but think about this quote last Wednesday, as I sat in on a panel discussion at the Harvard Business School of a recently completed case study of Moderna, whose Covid vaccine is taking the world by storm (together with that of Pfizer). Unlike Pfizer, though, the Moderna vaccine is the company’s first commercial product ever, and it’s helping bring down illnesses and deaths so dramatically that it’s now possible to begin seeing the end of the Covid-19 pandemic.

The Pasteur quote came to mind as the panelists reviewed the extensive history of Moderna, which is based in Cambridge, MA, and produces much of its vaccine from a manufacturing facility in nearby Norwood, MA. Moderna was founded 11 years ago, in 2010, and has been working to commercialize more than a dozen products since; the Covid vaccine opportunity just appeared in early 2020, and Moderna exploited it so quickly and expertly that it astounded the scientific community.  (Company case studies are the primary teaching tool at Harvard Business School. The 15-30-page documents are copyrighted and available for sale from Harvard Business School.)

An aside: I’ve not written much on vaccines over the years because I’ve felt less than completely informed about the diametrically opposing views. After following developments on the Covid vaccine front, and especially with release of the HBS case on the Moderna vaccine, I feel comfortable that the progress illustrated by Moderna is real, and important. However, I know many readers of this blog are anti-vaccine of any sort, so you may not want to read further if you’re upset by evidence of vaccine success.

Vaccines have always been about using the immune system to fight disease. Many anti-vaxxers have objected to artificially boosting the immune system via use of weakened viruses. They’ve also objected to the use of preservatives common in traditional vaccines. A big part of what is so exciting about the Moderna vaccine (and I presume Pfizer and Johnson & Johnson vaccines) is that they don’t use either weakened viruses or preservatives to maintain the vaccines. I don’t want to make an argument about long-term safety, because there is no long-term track record for any of these vaccines, but all studies suggest they are much safer than simply continuing to allow the coronavirus to spread and mutate and expect naturally induced herd immunity or vitamins to end it.

What I found most fascinating about last week’s Harvard Business School session (attended by some 2,400 alums and staff) was the lengthy startup process for Moderna, a nearly unheard-of luxury in the world of business, even businesses heavily funded by venture capital and other investment, as Moderna was. That luxury was judged acceptable, and necessary, because Moderna was embarking on use of an entirely new technology for stimulating the immune system. This excerpt from the case study explains it well: “To produce a protein, the body used the information contained in DNA (i.e., genes). Each cell contained only two copies of each DNA gene, but the body needs many more copies to make a protein. When a body needed to produce a particular protein, it made many copies of that protein’s gene, in the form of RNA. These temporary RNA copies, called messenger RNAs, or mRNAs, move out of the cell’s nucleus and into the cytoplasm, where they instruct the cell’s ribosomes (the small particles that serve as protein factories) to produce the desired protein. Melissa Moore, chief scientific officer of platform research at Moderna said, ‘mRNA is basically a template that holds a code, or instructions, for a cell on how to manufacture proteins. It doesn’t have anything to do with gene editing, because it doesn’t function in the nucleus, so doesn’t touch the DNA. But it does get the cell to behave in a certain way.’

“Moderna, and other companies that followed, took the use of mRNA to the next level by turning it into a drug. Following this logic, once an externally manufactured mRNA was injected into the body as a drug, the ribosomes in the cells read the injected mRNA like a code and made the protein the mRNA instructed them to make, thus leveraging the power of mRNA for the targeted production of proteins needed to fight diseases. mRNA functioned like a software instruction manual, instructing the body how to produce its own drugs.

“LNPs were also important for the development of Moderna’s drugs. LNPs served as the ‘delivery vehicles’ for mRNA, clothing the mRNA in fats to ensure proper delivery into the human body. ‘mRNA is the software and LNPs are the hardware needed to make our therapeutics work,’ Moore said. ‘So we are not just an mRNA company; we are also a delivery company.’ If Moderna could prove that its approach worked in one single drug, it would work for all others as well. ‘mRNA is a platform like the iPhone,” she added. “The individual drugs—preventative vaccines or therapeutic treatments— are like apps. If we get the platform to work, many, many apps can be developed on our platform.’ “

While Moderna had the luxury of operating for 11 years without offering a product for sale, it’s not as if the company was just sitting around waiting for Covid19 to appear. As the case puts it: “By early 2020, Moderna was running 23 programs for various drugs, of which 11 were in Phase 1, and one was in Phase 2. The programs included 11 vaccines, including nine prophylactic vaccines and two cancer vaccines. The latest addition of vaccines included one against the novel coronavirus, though other vaccines had been in the pipeline for much longer. Besides vaccines, Moderna also had several therapeutics, including against cancer, autoimmune disorders and heart failure….”

But all its earlier scientific development enabled Moderna to move at unheard of speeds once the Chinese released the virus’ genetic blueprint. in early 2020. From the case: “Moderna shifted into high gear when the first death was announced. Over the weekend of January 11 and 12, the Chinese authorities posted the genome sequence of the virus online for everybody to access…. By February 7, the team at Moderna had manufactured the first clinical batch for the vaccine, on which they then ran quality control. On February 24—a mere 42 days after first getting access to the virus genome sequence—they sent their vaccine to the NIH. On March 16, the first inoculation happened: the first dose of Moderna’s vaccine was injected into a human volunteer in Seattle, Washington. This meant the company had moved from the viral genome sequence to a human trial in just over two months.  Stephane Bancel., the company’s CEO, called it “groundbreaking.”

Indeed, it was. I remember well awaiting development of a polio vaccine in the 1950s, when American cities were being ravaged by polio’s spread, mostly in children. It took Jonas Salk two-and-a-half years of intensive work to complete development of a vaccine in 1955–a vaccine on which work had started in the 1930s– leading finally to the end of a long nightmare.

Moderna is trying hard to differentiate itself from traditional Big Pharma companies, which work in linear fashion to develop vaccines and therapies. “We’re a technology company that happens to do biology,” says CEO Bancel. “We are changing the game. Covid accelerated (Moderna)  by three years. We got lucky, but we were prepared,” he said last week. And, oh yes, Moderna could see something approaching $35 billion in new revenue before the Covid crisis is over.