“Coronavirus and the economic dislocations to come will certainly be one of the most significant financial events of our lifetimes. But more important than financial difficulties, it could very well become a tragic health episode for many of us in the coming weeks. Hopefully citizens and the politicians who represent us will rise to the occasion.”
— The Surreal Weekend, March 15, 2020
Our memories can play tricks on us. As we live through a tumultuous period of history and process incoming information over weeks, months, and years, we begin to subconsciously reconstruct our recollection of the early days of a crisis to conform with subsequent events. If we are not careful, we can quite easily allow ourselves to recollect a history that bears little resemblance to objective reality or to what we were actually thinking at the time. For this reason, it is very helpful to write down your thoughts in a private journal or, better yet, publish your thoughts online for the world to see.
As we passed the two year anniversary of the start of the pandemic, I looked back at what I wrote during the dark days of March 2020. In Thoughts on the Coronavirus Correction, Coping With Market Meltdowns II, and Berkshire Hathaway and the Coronavirus Crash, I focused on the financial implications of the government mandated shutdowns. The Surreal Weekend and The World Has No Pause Button attempted to take a broader societal perspective. Writing helped me to process the incoming information and cope with the uncertainty, both financially and in my personal life, and it makes it harder to fool myself retrospectively.
From what I wrote publicly and in my personal journal entries, I was both too optimistic and too pessimistic, although in different areas. As the full impact of the crisis materialized, my examination of the financial implications gave me the confidence to remain invested although I never expected markets to reach record highs again so quickly. From a societal standpoint, I did not expect the level of discord to become so extreme. Rather than unifying in a time of crisis, the country divided into ideological camps that hardened their views over time. Almost all politicians chose to fuel the flames of discord rather than act as unifiers. Social media, especially Twitter, threw gasoline on an already tense situation and the level of dystopian vitriol reached unbelievable levels that remain to this day.
It is easy to become a cynic in this type of environment, but we should try as hard as possible to resist that temptation because cynicism often leads to hatred which leads inevitably to ruin. We need to learn to look at the bright side, and in the context of the pandemic, the bright side is well represented by the major advances in scientific knowledge that led to vaccines.
At the beginning of the pandemic, few thought that it would be possible to have vaccines available for the public in a matter of months rather than years, but that’s precisely what happened. The story of how it happened is the subject of Gregory Zuckerman’s latest book, A Shot to Save the World: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine. Many readers will be familiar with Mr. Zuckerman’s work as a reporter for the Wall Street Journal. His previous books include The Man Who Solved the Market, a biography of Jim Simons that I reviewed in 2019. Writing a book about a scientific topic intended for the general public is a very tough job, and this is particularly true when the subject is very complicated and the technological advances culminating in success span multiple decades. Mr. Zuckerman succeeds in delivering an important and timely book that can be understood by any intelligent reader.
The underlying science that made the COVID-19 vaccines possible is the product of decades of painstaking research undertaken by scientists on various missions. In many cases, the research began as efforts to develop vaccines for AIDS and therapies for various forms of cancer.
The first several chapters of the book focus on examining incremental advances through the lives and careers of the scientists who doggedly pursued their studies even amid serious setbacks. I found most of the stories of individual scientists compelling. While each of the scientists had different backgrounds, interests, and motivations, one gets the feeling that all of them were on missions to improve public health rather than to strike it rich personally. I found Katalin Karikó’s journey to be the most inspiring one in the book.
Katalin Karikó arrived in the United States in 1985, a thirty year old immigrant from Hungary who knew hardly any English. She smuggled $1,200, her family’s entire savings, by carving a hole into the stomach of her two-year-old daughter’s teddy bear, which was enough concealment to evade the communist-era restrictions that prohibited citizens from leaving the country with hard currency.
Despite holding a PhD in biochemistry from a top Hungarian university, Karikó had trouble finding steady employment in the United States, finally ending up in a $17,000 per year position in the biochemistry department at Temple University School of Medicine. Karikó’s job involved working on AIDS, a major priority of medical research in the 1980s given the lack of treatments for the disease at the time. Despite the low pay and difficult conditions her family faced, Karikó was happy to be working at Temple University because it allowed her to focus on her main area of interest, mRNA.
Let’s take a brief detour into the basics of vaccines before we continue with Karikó’s work with mRNA.
Vaccines work by training the human body’s immune system to recognize a pathogen and fight it off. There are a number of ways in which the body can be trained to do this, and scientists have been exploring different methods for a surprisingly long time.
One of the most primitive methods is variolation, which was used to inoculate people against smallpox. In order to avoid a virulent case of smallpox transmitted through the air, eighteenth century physicians experimented with purposely using material from smallpox scabs to deliberately infect patients via superficial cuts in the skin. Benjamin Franklin’s son died of smallpox in 1736, leading Franklin to become an advocate of variolation. Late in the eighteenth century, Edward Jenner discovered that a far less harmful cowpox infection could reduce the risk of death when people are exposed to smallpox. Inoculation using the cowpox virus became a viable way to protect people against the devastating effects of smallpox.
Using a live virus to confer protection against an even worse virus is not without risk. In the centuries following Jenner’s discovery, scientists developed safer and more effective methods of vaccination. Prior to the development of mRNA vaccines, traditional vaccines typically contained weakened or dead versions of the virus that the vaccine was intended to protect against. While the injected virus in the vaccine is deactivated and harmless, the body’s immune system nonetheless recognizes it and, in healthy individuals, antibodies are created to fight it off. When a person exposed to this harmless virus via inoculation later encounters the real and dangerous virus, the immune system recognizes the virus and is able to fight it off.
Katalin Karikó was not the first researcher to investigate potential uses of mRNA. Scientists at California Institution of Technology discovered messenger RNA in 1961. mRNA is responsible for carrying a copy of the genetic instructions found in DNA into the cytoplasm where the instructions are used to generate proteins essential for life. However, researchers had long been stymied in efforts to use mRNA due to the fact that it is short-lived. However, Karikó had a crucial insight: the fact that mRNA is short-lived and dissolves after making the necessary proteins could be desirable. Rather than attempting to modify DNA, which would be a permeant genetic change, using mRNA to instruct the body to make proteins could be a safer approach.
“Karikó had heard all the complaints and criticisms, but she had trained herself to find positives when others saw problems. To her, mRNA was the perfect molecule — it only needed to get into the cell’s cytoplasm to create proteins, not all the way into the nucleus, like DNA. She agreed that mRNA was a short-lived molecule, but she thought that might be a good thing. Many illnesses and ailments didn’t seem to require the introduction of new genes, which can produce permanent changes in the body, as her colleagues were hoping to do with DNA. Sometimes the body just needs a short-term boost or improvement, not a long-term alteration.”A shot to save the world, p. 73-74
Karikó and her colleague, Drew Weissman, eventually came up with the technology needed to develop synthetic mRNA that could be used in mice and monkeys to create desired proteins. However, she had trouble obtaining funding at her position at the University of Pennsylvania to explore ways to use mRNA molecules to develop human therapeutics. In 2013, she was asked to vacate her lab and move to a lesser facility she characterized as a “virtual gulag” for serious researchers. Unwilling to work under such conditions, Karikó decided to move to Mainz, a city in Germany where she joined a relatively unknown firm named BioNTech.
When a strange respiratory disease emerged in China in late 2019, alarm bells went off in the medical community and work began immediately to discover the genetic sequence of the new pathogen. Scientists sequenced the genome of the COVID-19 virus in record time and were soon working on potential vaccines. The speed of these developments was not widely reported at first and the conventional wisdom was that it would take well over a year before vaccine candidates could be developed, to say nothing of navigating the complex process needed to gain regulatory approval.
In the United States, two vaccines based on mRNA technologies were approved for the general public in December 2020, just nine months after the gravity of the situation caused much of the country to grind to a halt. The FDA issued an emergency use authorization for the Pfizer/BioNTech vaccine on December 11, 2020 which was soon followed by approval of the Moderna vaccine on December 18, 2020.
The road to approval of these vaccines was not a straight line of success and many scientists other than Katalin Karikó played instrumental roles. Nor was mRNA the only technology used to develop vaccines for COVID-19. Mr. Zuckerman surveys the entire field in the book, providing the origins of each of the vaccine approaches and good explanations of the science behind them, all accessible from a layman’s perspective.
It is unfortunate that COVID-19 vaccines have become mired in controversy over the past year. While all vaccines have the potential for side-effects, all of which should be considered and discussed, there was a great deal of outright misinformation regarding the mRNA shots in particular. Conspiracy theories about mRNA vaccines, inducing allegations of permanent changes to human DNA, became common despite the fact that mRNA vaccines cannot possibly alter human DNA. Even wilder conspiracies about microchips being implanted via the shots would be amusing under more benign circumstances.
I’m as close to a free speech absolutist as one can get, and I also believe that vaccination should never be forced on citizens in a free society. I do not advocate suppression of viewpoints, even ridiculous viewpoints, not just because it violates our Constitutional right to freedom of speech but because suppression often fuels the very conspiracy theories that censors seek to suppress. However, with our rights also come responsibilities to be well informed. Too many people fell for conspiracy theories who had the capacity to try to understand vaccine technology. While complex, vaccines can be understood by any intelligent person.
Mr. Zuckerman’s book does a good job1 of providing the background needed to understand how vaccines in general, and mRNA vaccines in particular, work to protect against disease. The book was published in October 2021 and does not cover the rise of breakthrough infections that occurred in the Omicron wave of the pandemic which began later in the year. In many ways, COVID-19 is a moving target.
The virus mutates over time, but scientists have the tools to quickly respond which is reason for optimism. In a troubled world in which it is easy to fall into cynicism, it was great to read about the heroic efforts of scientists like Katalin Karikó. Politicians may have failed to rise to the occasion, but these scientists did not. Their tireless efforts spanning many decades paid off. We owe them a debt of gratitude.
- One criticism of the book is that it lacks an index. This made it much harder to write this review and it also reduces the utility of the book as a reference. Why are so many books these days published without an index? [↩]