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| The Code Breaker, by Walter Isaacson |
My favorite authors are Simon Winchester, David Quammen, and Walter Isaacson. This week I read Isaacson’s latest book: The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. I would place it alongside The Eighth Day of Creation and The Making of the Atomic Bomb as one of the best books about the history of science.
In his introduction, Isaacson writes
The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.Early in the book, Isaacson describes Francisco Mojica’s discovery that bacteria have “CRISPR spacer sequences”: strands of DNA that serve as an immune system protecting them from viruses.
The first half of the twentieth century, beginning with Albert Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics. In the five decades following his miracle year, his theories led to atom bombs and nuclear power, transistors and spaceships, lasers and radar.
The second half of the twentieth century was an information-technology era, based on the idea that all information could be encoded by binary digits—known as bits—and all logical processes could be performed by circuits with on-off switches. In the 1950s, this led to the development of the microchip, the computer, and the internet. When these three innovations were combined, the digital revolution was born.
Now we have entered a third and even more momentous era, a life-science revolution. Children who study digital coding will be joined by those who study genetic code.
As we humans struggle to fight off novel strains of viruses, it’s useful to note that bacteria have been doing this for about three billion years, give or take a few million centuries. Almost from the beginning of life on this planet, there’s been an intense arms race between bacteria, which developed elaborate methods of defending against viruses, and the ever-evolving viruses, which sought ways to thwart those defenses.
Mojica found that bacteria with CRISPR space sequences seems to be immune from infection by a virus that had the same sequence. But bacteria without the spacer did get infected. It was a pretty ingenious defense system, but there was something even cooler: it appeared to adapt to new threats. When new viruses came along, the bacteria that survived were able to incorporate some of that virus’s DNA and thus create, in its progeny, an acquired immunity to that new virus. Mojica recalls being so overcome by emotion at this realization that he got tears in his eyes. The beauty of nature can sometimes do that to you.
The Code Breaker focuses on the life and work of Jennifer Doudna, who won the 2020 Nobel Prize in Chemistry. However, the star of the book is not Doudna, nor Emmanuelle Charpentier (who shared the prize with Doudna), nor Mojica, nor any of the other scientific heroes. The star is RNA, the molecule that carries genetic information from DNA in the nucleus to the cytoplasm where proteins are produced.
By 2008, scientists had discovered a handful of enzymes produced by genes that are adjacent to the CRISPR sequences in a bacteria’s DNA. These CRISPR-associated (Cas) enzymes enable the system to cut and paste new memories of viruses that attack the bacteria. They also create short segments of RNA, known as CRISPR RNA (crRNA), that can guide a scissors-like enzyme to a dangerous virus and cut up its genetic material. Presto! That’s how the wily bacteria create an adaptive immune system!Doudna and Charpentier’s Nobel Prize resulted from their developing the CRISPR-Cas9 system into a powerful technique for gene editing.
The study of CRISPR would become a vivid example of the call-and-response duet between basic science and translational medicine. At the beginning it was driven by the pure curiosity of microbe-hunters who wanted to explain an oddity they had stumbled upon when sequencing the DNA of offbeat bacteria. Then it was studied in an effort to protect the bacteria in yogurt cultures from attacking viruses. That led to a basic discovery about the fundamental workings of biology. Now a biochemical analysis was pointing the way to the invention of a tool with potential practical uses. “Once we figured out the components of the CRISPR-Cas9 assembly, we realized that we could program it on our own,” Doudna says. “In other words, we could add a different crRNA and get it to cut any different DNA sequence we chose.”
Several other themes appear throughout The Code Breaker:
- The role of competition and collaboration in science,
- How industry partnerships and intellectual property affect scientific discovery,
- The ethics of gene editing, and
- The epic scientific response to the COVID-19 pandemic.
I’m amazed that Isaacson’s book is so up-to-date. I received my second dose of the Pfizer-BioNTech vaccine last Saturday and then read The Code Breaker in a three-day marathon. My arm was still sore while reading the chapter near the end of the book about RNA Covid vaccines like Pfizer’s.
There’s a lot of biology and medicine in The Code Breaker, but not much physics. Yet, some of the topics discussed in Intermediate Physics for Medicine and Biology appear briefly. Doudna uses x-ray diffraction to decipher the structure of RNA. Electroporation helps get vaccines and drugs into cells. Electrophoresis, microfluidics, and electron microscopy are mentioned. I wonder if injecting more physics and math into this field would supercharge its progress.
CRISPR isn’t the first gene-editing tool, but it increases the precision of the technique. As Winchester noted in The Perfectionists, precision is a hallmark of technology in the modern world. Quammen’s book Spillover suggests that humanity may be doomed by an endless flood of viral pandemics, but The Code Breaker offers hope that science will provide the tools needed to prevail over the viruses.
I will close with my favorite passage from The Code Breaker: Isaacson’s paean to curiosity-driven scientific research.
The invention of easily reprogrammable RNA vaccines was a lightning-fast triumph of human ingenuity, but it was based on decades of curiosity-driven research into one of the most fundamental aspects of life on planet earth: how genes encoded by DNA are transcribed into snippets of RNA that tell cells what proteins to assemble. Likewise, CRISPR gene-editing technology came from understanding the way that bacteria use snippets of RNA to guide enzymes to chop up dangerous viruses. Great inventions come from understanding basic science. Nature is beautiful that way.
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