It’s a David v Goliath story and probably one of the biggest medical inventions of our time—mRNA vaccine technology. The road, like most medical inventions, was littered with frustration and multiple dead ends. In a fascinating race, with the world held hostage by an unknown virus, two small companies—Moderna and BioNtech (combined market cap of $10 billion) with the help of Pfizer—beat giants like J&J, AstraZeneca and Merck—all with market caps of over $150 billion. The old adage of size doesn’t matter was right again.
The story of mRNA is linked to one woman—Katalin Karikò, an immigrant from Hungary—who came up with the idea in 2005. Like most geniuses, her idea to use synthetic mRNA to instruct the body cells to become a factory to whatever protein you wanted it to produce was mocked. She was demoted at work and her grant applications were turned down. However, her work was noted by Harvard researchers, who built on her work and founded the company Moderna (which has mRNA in its name) in 2010.
Over the next 10 years, Moderna promised investors the moon with mRNA technology—from cancer treatment to treating virtually any chronic disease—raising millions of dollars in the process. The long and short of it was that nothing worked.
In the same timeframe, on the other side of the Atlantic, in Germany, a physician couple began researching the body’s immune system to fight disease. They formed the company BioNTech, and, in 2013, a frustrated Karikò joined the company, after being denied a faculty position at UPenn.
Both companies struggled with mRNA due to two major issues—the body was sensing synthetic mRNA was foreign and was destroying it. Karikò collaborated with another scientist, Drew Weissman (they met at a photocopying machine), and found a method of tweaking the synthetic mRNA to fool the body into thinking it was natural. Both scientists hold the patent for this technology. The second issue was delivering the mRNA into the cell—this was achieved by suspending the mRNA in a fat molecule to allow it to enter the cell. Robert Langer at Moderna developed this technology.
When the pandemic hit, the mRNA companies were ahead of the game. BioNTech partnered with Pfizer, while Moderna partnered with the US government for funding. They didn’t need to cultivate the virus; they just needed the genetic code. Covid was first identified in Wuhan at the end of December 2019. Chinese researchers, in breath-taking speed, identified the virus and posted the genetic code online. The rest, as they say, is history—the first mRNA vaccine was made within 42 days of the genetic code being released, and trials were underway.
Pfizer-BioNTech won the race narrowly, being granted emergency approval in the UK and the US in early December, followed by Moderna. Both vaccines showed a striking 95 per cent efficacy rate in preventing disease. The adenovirus platforms by the big companies like J&J and AstraZeneca have an efficacy of 66 per cent and 76 per cent, respectively. AstraZeneca is still not approved in the US, while J&J was recently restarted after being paused for issues with blood clots.
As we move into the present, Pfizer-BioNTech recently announced six-month data, which showed a 100 per cent efficacy against severe disease and a 100 per cent efficacy against the South Africa variant with the B.1.351 lineage. They are also 97 per cent efficacious against the B.1.1.7 variant found originally in the UK. This is true of all vaccines; they are felt to be very efficacious in preventing severe disease and hospitalisation. The infection rate and hospitalisation in the US has been dramatically falling, and the country is limping back to normalcy.
Which brings us to India and the notorious B.1.617 strain, which has two mutations. While things do look dire in India, the current rate of infection is still less than 2 per cent of the Indian population, as opposed to the US at 9 per cent of the population. Approximately 8 per cent of the Indian population has already been vaccinated. In essence, 90 per cent of the population of India is at risk, and if the percentage of cases increases, the health care systems will be in further jeopardy.
The CEO of BioNTech feels that the vaccine will be effective against the Indian variant, as similar double mutations were studied with the current vaccine. Both mRNA vaccines will likely need booster doses as immunity wanes in about eight months. The booster will include future mutations. The world needs to coordinate vaccine delivery to this huge, vulnerable population in India. Recently Moderna said its vaccine can now be stored at refrigerator temperature for up to three months—this data still needs FDA approval.
Pfizer-BioNTech vaccine trials have now started in India, and we will have more data shortly. The mRNA technology is a major breakthrough in the medical field and hopefully this experience translates into other disease states. Heroes never wear capes; they are ordinary people like Karikò and Langer, who achieve extraordinary results in times of critical need. The world is indebted to all those unsung heroes who made this medical miracle possible.
dinarab@yahoo.com