The Code Breaker by Walter Isaacson
A review.
By Razaq Khazi-Syed
The Code Breaker is a very interesting and timely read. Walter Isaacson brings interesting perspectives on how we stand on the cusp of monumental changes in our understanding of the human genome and how we can potentially edit the blueprint of human life itself in the not-too-distant future. Mother Nature has taken billions of years to fine tune life as we know it, but within a few years or a decade or two at the most, man will likely be able to alter life in unimaginable ways.
First a bit of a side bar… for far too long, women in science have been given short shrift. Isaacson changes that in some small measure by squarely focusing on Jennifer Doudna, the professor from UC Berkeley instrumental in development of gene editing technology that has proven to be extraordinarily effective in humanity’s fight against the COVID-19 pandemic. Given the proper recognition of the importance of her work, Doudna has shown the world emphatically that, in fact, “girls and women can do science!” That is a great accomplishment in itself.
Historically, this has not always been the case… Rosalind Franklin was one of those women who eminently deserved recognition (perhaps even a Nobel prize) during her own lifetime for her contributions to the discovery of DNA, but did not. For those that may not be familiar, Rosalind’s work was used (some might even say that it was done in an underhanded way) by Francis Crick and James Watson on their way to the discovery of DNA, The Double Helix 🧬, the code of life itself.
When the Nobel Foundation decided to recognize the groundbreaking work on DNA, Rosalind’s contributions should have been considered seriously. That would have put the foundation in a bind because Rosalind would have been the fourth person in addition to Crick, Watson, and Rosalind’s boss, vying for the prize. I did not know this until I read this book, but a Nobel prize can only be shared by up to three individuals. Quite possibly to the Nobel Foundation’s relief, Rosalind was out of the way – she passed away at the far too young age of 38 of cancer (there is speculation that excessive exposure to X-Ray radiation in the lab was to blame), when the Nobel was awarded for the discovery of DNA. And unfortunately, Nobel prizes are not awarded posthumously, so poor Rosalind will never be duly recognized with a Nobel prize.
Thankfully, we have come a long way from the days of Rosalind. Jennifer Doudna, the titular Code Breaker did win a Nobel prize jointly with Emmanuelle Charpentier for their work on CRISPR, which is a system for editing the human genome. Doudna and Charpentier figured out a way to use RNA guide molecules to precisely target DNA sequences and snip them away using a CRISPR-Cas9 system – a CRISPR system working in conjunction with CRISPR-associated proteins (this is modeled after how bacteria destroy viruses).
Like many advances in science, Doudna and Charpentier’s work is a build on work by many other brilliant scientists, including the work of a Spanish scientist, Francisco Mojica, who was intrigued by the way bacteria outmaneuver viruses and kill them. The battle between viruses and bacteria has been going on from times immemorial (billions of years!). Mojica was especially keen to understand the way bacteria activate their defenses against viruses… how bacteria expertly chop up the RNA of viruses to destroy them. In fact, Mojica is the inventor of the name CRISPR, which stands for – Clustered Regularly Interspaced Short Palindromic Repeats. In lay person-speak, CRISPR is a set of repeating sequences within bacterial DNA that bacteria use to attack and destroy infectious viruses.
This book is in many ways about several people who have been driven by this fact (bacteria are great at defeating viruses, but how exactly do they do it?) and went out to figure out how techniques developed by bacteria for self-defense can be harnessed to target viruses that infect human beings. As Mojica once humbly said, “I am one in 100 or 1,000. Many people have been involved in CRISPR.”
A Lithuanian scientist and researcher Virginijus Šikšnys independently developed the same ideas and concepts as Doudna/Charpentier did around CRISPR-Cas9. Unfortunately, his paper outlining this work was not accepted for publication. Doudna/Chapentier’s paper was accepted and published by Science magazine a couple of months after Virginijus’ rejection.
Another scientist who deserves a mention here is Feng Zhang, an immigrant Chinese American whiz kid and a Harvard/MIT product who focused his attention on using CRISPR-Cas systems on eukaryotic cells, as opposed to bacteria. This work opened all sorts of possibilities for using gene editing for human beings. Eukaryotic cells make up all kinds of life forms on Earth including human beings.
Doudna and Charpentier thus nipped a few other worthy contenders in the quest for CRISPR glory, but not without incurring some costs themselves. Some of the competition later devolved into knock-out-and-drag-down patent fights for CRISPR-based technologies. Especially between Doudna and Zhang.
Isaacson does a good job of showing that scientists are human beings too – they have their own motivations for why they do what they do, and like other human beings they are competitive and desire to win and to be recognized as the first to do something – a new discovery, a new technology, a patent, a new company built on the promise of an exciting and groundbreaking idea, a cure for a previously untreatable disease and so on.
And this sort of thing happens not only between overt competitors (for example, between Doudna and Zhang, scientists from rival schools/labs) and even collaborators, over time (for example, between Doudna and Charpentier, who jointly won the Nobel prize for their collaborative work on CRISPR gene-editing).
The promise of gene editing or human germline editing as it is called is very tantalizing and offers seemingly infinite possibilities. The human genome was mapped more than 3 decades ago, but only now we can precisely edit genes so that someone’s genetic makeup becomes not just luck of the draw – it can be carefully controlled to eliminate pre-disposition to potentially deadly diseases.
Sickle cell anemia is a debilitating disease that affects millions of African Americans and Africans – it can lead to chronic pain and suffering and often result in early death. There are early-stage efforts underway to create gene therapies to cure people suffering from this disease. There are also efforts to create heritable genomes using gene editing to prevent sickle cell anemia in future generations. Even in this happy scenario, there is an important caveat – we can excise away l genes that cause individuals to be pre-disposed toward sickle cell anemia, but when we do that, we also do away with genes that offer protection to these individuals against malaria. The benefit of eliminating or minimizing sickle cell anemia may be well worth a reduction in protection against malaria! Especially now that a malaria vaccine has just been announced.
Human germline editing capability confers on human beings the power to make changes to genomes that are heritable – changes that could go well beyond eliminating deadly diseases. What if someone wanted their children and their children’s children and beyond to have blue eyes, blond hair, and fair skin? What if they wanted them to be tall, fast, and strong? How about superhuman eyesight? An increase in IQ? More? Who gets to benefit from these technologies first? Will this lead to a nightmarish scenario where humans are genetically and permanently codified into classes – upper, lower, and other? What happens then? Who is to be held responsible?
Isacsson paints a sobering picture of the ethical minefield that these exciting advances present. When there are so many possibilities and rewards, it is only logical that someone somewhere will try to take advantage of the unsettled situation and do something with gene editing that is truly beyond the pale. There is a well-publicized case of a Chinese scientist who created twin designer babies for an HIV-positive couple, ostensibly to protect the infants from contracting HIV from their parents. But Doudna and many other scientists and bioethicists strongly believe that gene editing was not necessary in this case, and that there were other available methods that would have provided the children adequate protection against contracting HIV.
Isaacson describes the benefits of human gene editing at length in the book. He also talks about the all-too-real challenges that humanity will face when it comes to figuring out how this superpower will be used. Scientists like Doudna and Zhang and others have shied away from putting too many controls over the development and use of this technology for fear that it will stifle innovation, but we must be clear-headed about what this all means, and where it might potentially lead. While scientists and bioethicists may argue amongst each other and even come up with a rigorous regime of self-policing, what is to prevent for-profit entities from trying to benefit from this technology or rogue regimes/scientists from developing even more extreme use cases for this technology. It behooves all of us to be well informed on these developments and voice our opinions.
There is untold promise, but there is also a lot left to figure out. Let me end this review/summary on a positive note… if there is one well-known and well-understood benefit that CRISPR has yielded to humanity, it is the speed at which RNA rapid-tests and vaccines have been developed in the fight against COVID-19. It is in this realm that Isaacson shows that relationships between scientists mirror other human relationships in important ways – rivals can rise to the occasion and come together when the occasion demands it – Doudna, Zhang and many other scientists and labs collaborated when COVID-19 went from being a potential problem in way-out-there Wuhan to a global pandemic in a matter of weeks. Rival labs and companies licensed patented technologies and techniques to each other easily and freely to speed up the development of tests and vaccines for COVID-19, and for this the whole world can be grateful.
