If you think the digital revolution is having profound effects on human society, buckle up because the biotech revolution is just getting underway and it will redefine, even redesign, our species.
Ever since the early 1950’s when James Watson and Francis Crick first mapped out the structure of DNA, the famous double helix that makes up the genes of every living organism, scientists have begun to understand the deep biochemistry at the heart of life. Progress has been incredibly swift. Mapping of the human genome was completed by 2003. And in 2012 scientists developed the first technique for editing genes.
Walter Isaacson captures the personalities, the science, the drama, and the moral dilemmas of these developments in his latest book The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race.
The Code Breaker
By Walter Isaacson
Simon & Schuster, New York, 2021
Isaacson is a professor of history at Tulane University in New Orleans. He’s a former editor of Time magazine and a former CEO of the Aspen Institute, a think tank. I’ve read a couple of Isaacson’s previous books including his biographies of Steve Jobs, and Leonardo da Vinci which I reviewed here.
The Code Breaker is centered on the life and work of Jennifer Doudna who won the 2020 Nobel Prize in chemistry along with Emmanuelle Charpentier for developing a method of genome editing. But the book isn’t a biography in the conventional sense. It’s more like, well, a double helix.
One strand of the book concerns people, starting with Doudna and including dozens of other scientists who inspired, contributed to, competed with, or built upon her work. The other strand is about CRISPR which are fragments of DNA found in most forms of bacteria. Doudna and Charpentier developed a way to use CRISPR in combination with an enzyme called Cas9 to edit genes including human genes. These two strands twist around each other throughout the book.
Jennifer Doudna grew up in Hilo, Hawaii. One day her father left a copy of James Watson’s book The Double Helix on her bed. It inspired her to study biology and become a scientist. As a graduate student she studied RNA and later began her pioneering work on CRISPR.
CRISPR stands for “clustered regularly interspaced short palindromic repeats.” Clear as mud, right? Well, scientists discovered repeating occurrences of short sequences of DNA in the genes of various bacteria and gave them the cute acronym CRISPR. Their purpose was a mystery. Spaced between these repeating CRISPR sequences were other bits of seemingly random DNA that also had no discernable purpose.
Eventually, scientist learned that the seemingly random spacer DNA segments were actually snippets of the DNA of viruses which at some point in history had attacked the bacteria. Surviving bacteria stashed chunks of viral DNA within their own DNA, surrounded by CRISPR sequences. In effect, bacteria are keeping a catalog of mug shots of viruses. Whenever one of them is recognized, CRISPR springs into action, causing RNA – DNA’s cousin – to seek and destroy the invading virus. It’s a bacterial immune system.
I know I’m doing a terrible job explaining this. There’s a lot of complexity and detail here that I don’t understand. Isaacson tries to give a high level view of how it all works, but frankly, if you’re looking for a crash course in DNA, genetics, or gene editing, you’ll be disappointed by this book. Isaacson provides just enough scientific scaffolding for the story he’s telling about the people and the discoveries, but it left me with many, many questions. (If anyone can recommend a good introductory book on genetics, please leave a comment.)
He does much better exploring the moral dilemmas surrounding gene editing.
There are basically two types of gene editing: somatic and germline. Somatic gene editing involves making changes to the body’s non-reproductive or somatic cells. For example, doctors are working on ways to treat sickle cell anemia, a hereditary blood disease, by using CRISPR-based drugs to edit the DNA of a patient’s blood cells. Germline gene editing, on the other hand, is used to edit reproductive cells – sperm, egg, and embryo cells – to make permanent and inheritable changes to an organism’s DNA. Using germline editing to treat sickle cell anemia would cure not just the patient but their descendants too.
Sounds great, doesn’t it? We could rid the world of sickle cell and other terrible genetic diseases much like we’ve used vaccines to eliminate smallpox. In fact, how could we not do this?
Using germline gene editing on humans is highly controversial. (There’s less argument about somatic gene editing). That’s because it will change the human genome forever. You might remember the story of “CRISPR babies” from China a couple of years ago. A Chinese scientist, He Jiankui, edited the embryonic genes of twin Chinese girls going against standard safety and ethical guidelines.
Isaacson covers this case and other moral questions in detail, and it’s well worth the attention.
You see it’s one thing to cure genetic diseases like sickle cell, Huntington’s, or Tay-Sachs disease. But what if you want your children to be six inches taller than you? Or twenty IQ points smarter? What if you want them to be blond-haired and blue-eyed?
And who will have access to this kind of procedure? It’s going to be expensive, so does this mean only the rich will be able to afford it? Is it OK to give the children of wealthy people not just financial advantages but genetic ones too? And not just advantages for them, but for their offspring?
We don’t yet have strict rules for this. And as usual the technology is advancing much faster than the ethics and policies around using it. Isaacson notes one possibility: restricting germline editing to medically necessary treatments, as opposed to elective enhancements. But the line between treatment and enhancement is grey and fuzzy.
I think Isaacson’s focus on these ethical questions is the most important part of the book.
Isaacson is a great story-teller. Although his scientific explanations are less detailed than I would have liked, he conveys the drama and the excitement really well. The book is on the longish side – 481 pages, but for the most part it moves quickly. One exception: I thought there was way too much attention given to the patent wars between Doudna’s lab and another group of scientists in Boston.
As with Leonardo da Vinci, Isaacson is very much present in The Code Breaker. This time his subjects are alive, he’s interviewed them, many times in some cases. He’s attended their conferences, even edited DNA in a lab (under close supervision). He was a volunteer participant in clinical trials of the Pfizer BioNTech COVID-19 vaccine. You can feel his enthusiasm for curiosity-driven research and his excitement at the possibilities it opens up.
Another important theme in the book is the role of women in science. Isaacson deliberately chose Doudna as the focal point of his book, and throughout The Code Breaker he tells the stories of many women who played a part and how they got inspired to become scientists. This culminates in the awarding of the 2020 Nobel Prize to two women, Doudna and Charpentier. I hope the book inspires more women to make a career in science.
One thing that struck me about the story Isaacson tells is the naiveté of the scientific community. Doudna and her contemporaries professed to be “shocked” by He Jiankui’s CRISPR babies, yet the genie was well out of the bottle. Few of them want a moratorium, much less a permanent ban, on germline gene editing. Even a Nobel laureate does not have much influence over the pace of technological adoption, let alone the fractious political process of policy making.
In my view, it’s a virtual certainty that germline gene editing of human embryos is happening secretly in labs around the world, most likely in places with fewer scruples or fewer laws than the US or Europe. I bet there are more children alive today, somewhere, who have had their embryonic cells edited using CRISPR-Cas9 technology.
Historian Noah Yuval Harari wrote in his fabulous 2015 book Sapiens, which I reviewed here, that the days of Homo sapiens are rapidly coming to an end. He said that unless a nuclear or environmental disaster destroys us first, technological advancements will lead to the replacement of Homo sapiens with a new and dramatically different species. The Code Breaker shows how that day is already upon us.
Thanks for reading.
A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity
By Martin Jinek, Krzysztof Chylinski, Ines Fonfara, Michael Hauer, Jennifer A. Doudna, Emmanuelle Charpentier
This is the paper which describes the CRISPR-Cas9 mechanism for gene editing. Published online June 28, 2012, in Science.
A prudent path forward for genomic engineering and germline gene modification
A paper co-authored by Jennifer Doudna proposing a framework for discussing the moral issues and guidelines around germline gene editing. Published June 3, 2015, in Science.