The Code Breaker by Walter Isaacson

This is a book about some of the most competitive people in science.

It’s a joint biography of Jennifer Doudna (who in 2020 won the Nobel prize together with Emanuelle Charpentier) and the CRISPR method for gene editing.

The former is significantly less interesting than the latter. Isaacson does his best to wring a few drops of controversy or adversity out of Doudna’s life, but despite growing up white in Hawaii, she seems to have led a rather nice middle-class existence with nice supportive parents.

Prior to reading the book, I thought CRISPR (“Clustered regularly interspaced short palindromic repeats”) was an acronym for a special technique. In fact CRISPR refers to repetitive DNA sequences (first observed in bacteria, notable because they exactly match to sequences in viruses). It was subsequently discovered that bacteria transcribe these DNA elements to RNA upon viral infection. The RNA activates a sequence that cuts the DNA, providing protection against the virus. Through Processes Too Complicated To Explain, this enables editing of genes and thus the creation of “designer” organisms.

The liveliest bits are when Doudna (based at Berkeley) fights with other scientists. (Doudna doesn’t seem especially belligerent – fighting seems to be par for the course in this field of science). The fights with Feng Zhang of the Broad Institute led to one of the most epic patent battles of all time: who owns CRISPR? Spoiler alert: Doudna and Charpentier got the Nobel prize, but in March 2022 the Broad Institute defeated the Berkeley patent in a ruling by the US Patent office. Apparently the wrangling will continue for years, and the result has led to some absurd situations. In order for companies to create therapies and products using CRISPR, they had to license the technology from its inventors. Presumably because of the Nobel glow, most companies licensed from Berkeley. Will these companies need to re-negotiate new licensing deals with the Broad institute? I don’t know – I stopped following the plot: it’s a bit ridiculous at this point. By the time the legal bickering is over, the 20-year patent monopoly will have expired and CRISPR will have been supplanted by the Next Hot Thing in molecular biology.

I do recall that when CRISPR first emerged, it was meant to cure everything. Needless to say, that hasn’t happened; it never does with the latest flashy discovery in science (remember how buckyballs were the material of the future?), but this detracts nothing from how remarkable and versatile CRISPR is as a technique.

It struck me that a lot of the unsung, early pioneering work was done by scientists who are very nearly anonymous . The Broad Institute publishes a “CRISPR timeline” that pointedly downplays Doudna’s contributions. The term CRISPR was coined by a researcher at the University of Alicante in Spain, Prof. Mojica, who noticed these repeating sequences in bacteria and theorized that they were part of an immune response system. One of the other seminal contributions was made by scientists at Danisco in France (the makers of Danone yoghurt!!), who showed experimentally that CRISPR systems are indeed an adaptive immune system; they integrate new phage DNA into the CRISPR array, which allows them to fight off the next wave of attacking phages.

Truly new and pioneering work is often done at decidedly un-glamorous institutions (Charpentier worked at the even-rather-obscure-for-Sweden Umea University). My own theory is that at great big sparkly institutions with enormous names, where half the faculty publishes a Nature paper every other week, the pressure to publish in hot new fields actually suppresses creativity.

In conclusion, I enjoyed the bit where Doudna had a dream about Hitler with the face of a pig, lecturing Doudna about the “implications of this amazing technology you’ve developed”. The saga of He Jiankui is told in great and dramatic detail (spoiler: CRISPR babies were birthed). Poor fellow almost certainly worked with the direct or covert support of the Chinese government, but when the international community looked ill upon the work, viewing it as an ethically crossed line, Jiankui was sent to prison. He was released early in 2022.

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