Book Review The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race By Walter Isaacson New York: Simon & Schuster, 2021
This comes just in time for an age when baffled and agitated citizens are questioning the value of medical science, and particularly government regulations based on this expertise. It centers on the work of Jennifer Doudna, a biochemist RNA specialist, who was the first to discover the structure of the RNA molecule, and through this how RNA could replicate itself, and thus be the origin of all life on earth. She was also a pioneer in CRISPR gene editing, and Nobel Prize winner in chemistry (2020). Not too many women scientists make it like this; she’s the only that grew up in Hilo, Hawaii, where her father taught literature at the University of Hawaii, and gave Jennifer a moral perspective on science that served her well.
But it's not just a biography of one person, because biology is a team effort today. The author shows how these teams come together, break up, recombine, compete, and cooperate, drawing in multidisciplinary expertise from academia, government, nonprofits, and profit making business.
As the author goes through the various teams, discoveries, publications and applications, he dispels many myths about science. First, while there are a few "Oh my God" moments in science, it is mainly a series of many small steps forward and backwards. Each small step is the work of a team, typically drawing on experiments and thinking of one or two junior researchers, guided by a mentor like Doudna. Two or more teams may be doing very similar work at the same time, and the key is to get published first in a peer reviewed journal.
The links between basic science and practical application are not always linear. Sometimes the former leads to the latter, sometimes it works in reverse. CRISPR was first discovered by scientists who saw it as an important advancement in knowledge (how bacteria survived viruses over billions of years) but of little practical value. Doudna and teams like hers found the practical uses and then worked backward to better understand how an easily programmed RNA molecule could target specific genes and change them. Some biochemists like Doudna started at the molecular level looking at results in test tubes, while others went first to living cells and tested what would work, without first understanding the molecular story of what was going on. Along the way, traditional dogma was upended. For example, it was once thought that information only traveled from DNA to RNA, but then science found that viruses containing RNA, like COVID19, insert their genetic material into the DNA of host cells.
Some scientists cash in by taking their work to private business. Others try that route and don't like it. Doudna, for example, leaves Berkeley for a couple of months to join Genentech, but can't stand the focus on getting more corporate power and status so goes back to academia. On the other hand, she helps set up many startups as a way of retaining patents on discoveries by her teams, and keeping them out of the hands of patent trawls who may take out patents and then block their use. She and her teammates are highly motivated mainly by the joy of discovery, and by the practical applications of scientific breakthroughs. For the practical side, business provides the way forward, but the process can be bumpy. Doudna went through a multiyear patent battle with another lab over who made key discoveries first; her lawyer admitted at the end that it would have been better to share the patents rather than fight for them.
The last section of the book covers the work of Doudna's teams and others on COVID19, including CRISPR use for testing, and development and testing of mRNA vaccines. Because of the urgency of controlling the pandemic, all her team's work, and that of other teams, was made public, and published on preprint servers. Peer reviewing was crowd sourced.
The testing team develops CRISPR based home testing kits (where are they now when we need them?) that are thought to be an early foundation for home medical services that will transform medicine like PCs and cell phones transformed computing. The book also covers bio-hacking: individuals investing and testing equivalents of Linux and open source in the IT field; and the risks of bio-terrorism, altered genes accidently escaping into the wild, and the need for safeguards and self-regulation to prevent bad stuff from happening, without stifling the good stuff, agreed at the Asilomar II conference of Feb 1975. Teams are working on a CRISPR based COVID vaccine where a scissors-like enzyme is used to chop up the genetic material of an RNA-based virus, without having to use the person's immune system.
Also, there is a provocative section on designer babies, AKA germ-line gene editing (of DNA of sperm, eggs, early stage embryo) to make them resistant to genetic disease and disorders like HIV AIDS and Sickle Cell Anemia, and aspects like skin and eye color, height, weight, musculature, IQ and lots more. The ethics of this are complicated due to religion, political economy and other concerns, particularly when the editing changes DNA for the baby and its descendants. The author points out that advances in ethical understanding are as important as scientific breakthroughs. How can we avoid a science-fictional world where the privileged evolve into a super intelligent elite of Olympian strength, and prevail over the under enhanced masses? Doudna dreams that she is being interviewed by Hitler, who wants this technology to perfect his Aryan man. So far, the international gene community have agreed not to do germ line, inheritable editing until we understand more about the tradeoffs. A Chinese scientist does it anyway, apparently successfully, and is punished by his government.
Overall, bioscience and biotechnology will lead to changes in our lives for generations to come even greater than the changes wrought by information technology in the recent past. The uses of these ideas significantly changes the balance of power in favor of humans against viruses as long as humans agree to follow scientific protocols. Gene editing, including edits that are inheritable, can also be a powerful force to eliminate genetic diseases, but needs to be carefully understood and regulated to ensure we avoid unintended negative consequences. Government leaders need to draw on topflight scientific and ethical advice to make wise decisions. Building on this, they need to instill strong understanding and support by citizens for how these developments should be managed going forward.
Clay Wescott,President, International Public Management Network and member of international Advisory Board at Centre for Governance Studies (CGS).