Tuesday, May 11, 2021

The Code Breaker by Walter Isaacson

The Code Breaker by Walter Isaacson is a great book that’s subtitled Jennifer Doudna, Gene Editing, and the Future of the Human Race

Isaacson writes about CRISPR, genetic engineering, and the fight against COVID-19, which the book was conceived of prior to, but features prominently in the introduction and the final section. All of this is covered well by Isaacson through the lens of the main character, Nobel Prize-winning scientist Jennifer Doudna. Early in the book there’s a story of her in the sixth grade reading The Double Helix by James Watson about his co-discovery of DNA. Doudna was fascinated by how science could be exciting and full of mystery and it led her to want to work in the field. She had to overcome skeptics who didn’t believe girls should aspire to a career in science and as a graduate student in chemistry, she focused on RNA, the molecule in a cell that copies instructions coded by DNA and uses them to build proteins. Her mapping out the structure of RNA was very akin to what Watson and Francis Crick did in discovering the double-helix structure of DNA in 1953. 

DNA is what contains genetic information in cells and Doudna and her collaborators in 2012 found that some bacteria developed clustered repeated sequences, or CRISPR, in their DNA. It was found that these sequences were an immune system that bacteria adapted when attacked by a new type of virus. Doudna and her team discovered that along with RNA, these sequences could be engineered to edit DNA. The way it works is: 1. A Cas9 protein joins with RNA and guides it to a DNA sequence, 2. The Cas9 cuts into the DNA, likely chopping out a gene, 3. A newly programmed piece of DNA with a preferred gene gets inserted where the cut was made. Watson found that the DNA holds genetic information, Doudna how to edit that by using RNA. 

Isaacson notes that figuring out when to edit our genes will be one of the most consequential questions of the twenty-first century. The first half of the twentieth century was based on the atom and creating a nuclear age, the second half on the bit and creating the information technology era, and now we’ve entered the life-science revolution centered around the gene. There's a difference between non-inheritable, or somatic, gene editing and gene editing that crosses the germline. In the non-inheritable version, you're changing a genome in someone, and in germline editing you're engineering a change that will be inherited by all future descendants.

CRISPR gene editing is now being used to treat sickle-cell anemia, cancers, and blindness, and last year Doudna and her team explored how CRISPR technology could detect the coronavirus, and hopefully in the future play a role in fending off future pandemic-causing viruses. The book starts by noting it as a way to potentially engineer inheritable edits in humans that would make our children, and all of our descendants, less vulnerable to virus infections like we’ve had with COVID-19. This sounds like a good thing, but there are very legitimate concerns about genetic engineering, or germline editing. There’s the treatment vs. enhancement question, or continuum conundrum. Fending off a pandemic is a worthwhile endeavor, as is perhaps eliminating maladies like Huntington’s disease, but what about other things ranging from HIV-susceptibility, to deafness, IQ, and height? Additionally, should you cross the germline to accomplish something that could be done another way? In 2018, a young Chinese scientist used CRISPR to edit embryos and remove a gene that produces a receptor for HIV, which led to the birth of twin girls and the world’s first designer babies. It was crossing a threshold; one the scientific community had held back from to that point, and in this case of trying to get children less likely to contract HIV later in life, there’s less drastic steps that could have been taken. Also, making this type of genetic engineering a choice that parents can readily make would have the impact of increasing inequities in society as well as likely limiting diversity and understanding of differences in people. 

There’s also interesting content in the book about competition in the field, both friendly and not so friendly, and about biological hackers, people doing for life sciences the same type of tinkering that was done with personal computing, putting power in the hands of the people. The last portion of the book is about the reaction to COVID-19 and Isaacson covers the collaboration when scientists responding to the pandemic. The genetic sequence of the virus was posted online by Chinese researchers on January 9, 2020. On Mar 13, Doudna convened a meeting of top doctors to figure out what they would work on, with many of the efforts around developing tests for the virus given the limited Federal response. Doudna’s lab did its first COVID tests, of Berkeley firefighters, on April 6. Also covered is how the Pfizer and Moderna vaccines injects a snippet of RNA rather than a weakened version of the virus; it’s a genetic vaccine that guides cells to produce components of the virus. This knowledge of RNA and what it could do helped the vaccines get produced in record time, and will also be helpful in responding to future viruses.