The convoluted path of innovation: the COVID-19 vaccine

The general perception of drug development is as close to the linear model of innovation as any process can be. Starting with basic the research on a new compound, then turning that compound into a drug to combat a specific disease, then testing and certification by the FDA, and finally scaling up mass production.

A look at the example of using synthetic messenger RNA (mRNA) to fight COVID-19 reveals how convoluted drug development really can be.

The following is from Damian Garde and Jonathan Saltzman, “The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race.”

The story starts with an idea by Dr. Katalin Karikơ, working with her collaborator Dr. Drew Weissman, on how that mRNA could be used to trigger cells to manufacture certain proteins — including antibodies to fight infection. That work, itself, built upon years of work by other researchers on DNA, going back of course to Watson and Crick (and Franklin) and the discovery of the DNA Double Helix, which built on work even further in the past.

For Karikơ and Weissman, it was years of grant rejections and frustration until they came up with a way to prevent the injected mRNA from triggering a massive immune response and making matters worse.

The idea was then picked up by Dr. Derrick Rossi as a focus of his work on a replacement for embryonic stem cells. That work came to the attention of Dr. Robert Langer – who recognized its potential for creating vaccines, among other uses. Langer contacted the venture capital firm Flagship Ventures which lead to the creation of Moderna.

As Moderna was pursuing its research, two scientists in Germany, Dr. Ugur Sahin and Dr. Özlem Türeci, were also working with mRNA technology. The established a company in the US, BioNTech, and even hired Dr. Karikơ. Meanwhile, Moderna ran into technical problems with the general use of mRNA for multiple conditions and focused instead on vaccines. As Garde and Saltzman tell it, the two companies took different directions.

Then the pandemic hit – and the rest is history. Moderna tailored a mRNA vaccine to the coronavirus. BioNTech partnered with Pfizer on its own vaccine.

Which brings the technology almost back to the starting point. With all the subsequent high-level attention, mRNA technology is now being touted as newest breakthrough for multiple uses – as envisioned by Karikơ, Weissman, Rossi and others.

So, when the newest mRNA-based therapy for some disease is announced in the future, remember that the road from at-the-time-ignored research in the 1990s to medical breakthroughs today has been a long and convoluted path.

[And note, the Garde and Saltzman article says little about the role of the government in the process – especially in the latter stages. For a description of that, see this article in today’s Washington Post on Operation Warp Speed – “How the ‘deep state’ scientists vilified by Trump helped him deliver an unprecedented achievement”]

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