The Code Breaker – Jennifer Doudna, Gene Editing and The Future of The Human Race by Walter Isaacson
‘”We decant our babies as socialized human beings, as Alphas or Epsilons, as future sewage workers or future…” He was going to say “future World controllers,” but correcting himself, said “future Directors of Hatcheries.”‘ – Aldous Huxley, Brave New World (as quoted in The Code Breaker)
As of the writing of this review, it has been fifteen long, isolating months since my family and I have been in the perpetual Groundhog Day that is Coronavirus lockdown. We haven’t hugged our families, there have been no birthday parties in the backyard, no friends over to play. But we have kept the roof over our heads, our bellies are full, and we fiercely love each other – possibly more now than ever before – as we continue to forge our path through this crazy labyrinth of plague and despair. It is the journey through said maze that has led me to The Code Breaker, as I try to understand what direction is best chosen for my family.
I have never been against vaccination, and can safely say that everyone in my house is fully immunized for all the standard diseases. That said, after having heard that there was a new type of technology being used for the Corona shots, a type of injection that would change my DNA and insert a microchip in my body (Whoa!), I was quick to put on the brakes. I then pondered that it may be time to delete a few of my YouTube subscriptions.
To be clear, I don’t have a tendency to get my science from conspiracy hypotheses, memes, or my friend Sarah who flunked out of grade eleven biology; I like to make informed decisions. Not to knock Sarah, though, because I have no postsecondary science knowledge to draw on, myself. I do, however, like to read, so I thought the best place to start would be to try and understand what the mRNA vaccines were about. I can somewhat confidently say that after having read about the revolutionary CRISPR technology, and Jennifer Doudna and her colleagues’ discoveries in Walter Isaacson’s extremely thought-provoking and enlightening book, I am not going to win any Nobel prize for scientific comprehension, but I think I have a handle on the basics. I’m essentially saying that I no longer feel like the machines are trying to take over… at least not yet.
This almost 500-page book was not like reading a textbook, where if you aren’t passionate about the subject, it just drones on and you have to pry your eyelids open with your fingers – or maybe that was just me in college, but I digress. Not only a story about the fascinating life of Doudna, and the crazy ride through competition and innovation that she and her collaborators and opponents lived through over the past few decades, we are also invited to question how we feel about these new frontiers that humanity is being dragged into with the advent of somatic and germline gene editing.
From the first chapter, I had an emotional connection to the story, as I felt grateful that Doudna had the internal fortitude not to listen to the many teachers who in various different ways insisted that “Girls don’t do science.” She shares that at the time it was hurtful to her, but it also stiffened her resolve and caused her to focus on her goals. She remembered telling herself “I will show you. If I want to do science, I am going to do it.”
Doudna, under the tutelage of Jack Szostak, was a pioneer in the research of RNA as a major player in the origins of life, monstrously widening the scope from how it had once been considered a dull intermediary to the proteins doing the lion’s share of the work in human cells. Ever the valorous adventurer, she gave into curiosity and took the risk of doing her doctoral research in this ground-breaking area of study, while other biochemists were choosing to focus on the sequencing research for DNA with regard to The Human Genome Project.
She credits Jack for sharing his guiding principle: Never do something that a thousand other people are doing. She said, “I learned from Jack that there was more of a risk but also more of a reward if you ventured into a new arena.”
In 1989 Doudna received her PhD from Harvard. She then went on to do her postdoctoral studies in Colorado, with Tom Chech, a man that she both respected and admired, namely for his discovery of self-splicing introns, and for leading the very best RNA biochemistry lab, at the time.
On the heels of Doudna and her future husband – then workmate in Chech’s lab – Jamie Cate, unveiling their grand discovery of the three-dimensional structure of RNA, she suffered the news that she would lose her father to melanoma. Sadly, the cancer had metastasized to his brain, and he was given only a short time to live. He was her biggest champion, and in the last months of his life she regaled him with the details of their massive breakthrough.
“It was only after he died that I realized how influential he was in my decision to become a scientist.”
As sad as those days were for her, their groundbreaking findings were the catalyst to Doudna and her colleagues putting in place the tools that could edit genes. During a TV interview for a science news show, when explaining what the implications of such technology could be, she said, “One possibility is that we might be able to cure or treat people who have genetic defects.”
As RNA discoveries continued to flourish, so did the significance and necessity such findings would have in the future of vaccines. Spanish Molecular Biologist Francis Mojica discovered palindrome-like, repeating segments of DNA, in the 90s, and ended up creating the defining acronym – CRISPR (clustered regularly interspaced short palindromic repeats), which was excepted on November 21, 2001 as the appropriate moniker.
‘Mojica found that bacteria with CRISPR spacer sequences seemed 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 with emotion at this realization that he got tears in his eyes. The beauty of nature can sometimes do that to you.’
After marriage and the birth of their son, Doudna and Cate were both offered a professorship at UC Berkley. Part of Doudna’s genius was her ability as an effective leader. The emphasis she put on assembling a team in her lab that had chemistry (pardon the pun), so that ideas would collaborate and flow instead of egos or combative competition causing objectives to be stifled, was cherished by her underlings.
‘The camaraderie in the lab was not an accident: in hiring, Doudna placed as much emphasis on making sure someone was a good fit as she did assessing their research accomplishments.’
While she preferred and encouraged her team to be self-sufficient and independently driven, she still offered guidance and had a knack for asking creative questions, that lead to big ideas and new projects. She offered the right amount of challenge to inspire her team to be bold and brave in their endeavours. Her engagement in a project would increase when it came nearer to completion, as her excitement would see her wanting a competitive edge over other labs who may beat hers to a discovery.
The truly revolutionising work came when Jennifer Doudna and Martin Jinek collaborated with Emmanuelle Charpentier and Krzysztof Chylinski, as they attempted to figure out the mechanisms of the CRISPR-Cas9 enzyme. It was determined that – as Jinek informed Doudna – “Without the tracrRNA, the crRNA guide does not bind to the Cas9 enzyme.” Doudna would go on to win the Nobel Prize with Charpentier in 2020, for their pioneering work in CRISPR gene editing.
‘This amazing little system, it quickly became clear, had a truly momentous potential application: the crRNA guide could be modified to target any DNA sequence you might wish to cut. It was programmable. It could become an editing tool.’
The race to prove that CRISPR-Cas9 could work in human cells became fierce, and was realised in roughly six months in five different labs within the scientific community. Although, admittedly, the scientific and technical jargon became difficult to follow at times, there was often an under thread of competition and excitement that kept me reading. It almost became a sport, and I was in the stands rooting for my team to be first to the finish.
Doudna’s most direct opponent in the field of CRISPR research and technology appeared to be Feng Zhang. Although healthy competition can inspire innovation and unleash creativity, I couldn’t help but wonder how much ego and competitiveness had slowed progress of this very important research. They seemed to have differing skill sets, and that had they worked together in the race to turn CRISPR into a human gene-editing tool, things may have happened smoother and/or sooner. Putting a practical need for alliances aside, intellectual property disputes and competition for patents and prizes made for an interesting and sometimes even thrilling journey throughout The Code Breaker.
Somatic editing – changes that are made in targeted cells of a living patient and do not affect reproductive cells – is currently being used for gene editing, and is helping to eliminate blood disorders such as sickle cell anemia, aiding in the detection and treatment of cancer, as well as assisting in a cure for a form of congenital blindness. While it is true that I am no expert in … well, anything really, (except maybe crochet,) I can see nothing wrong ethically with carrying out these kinds of treatments, most certainly if funding can be made available through all socioeconomic communities. With insurance companies being as lucrative as they are, is it naive of me to think that with government regulation this could be attainable? If the incidence of lengthy and expensive diseases were minimised within the population, and therefore are not bogging down the healthcare system, are expensive price tags for somatic gene editing not worth it in the long run? Or maybe pharmaceutical companies that pull in billions on the backs of said diseases would have a complaint that governments and the lobbyists couldn’t ignore.
While somatic gene editing gets a pass with me until I can be convinced otherwise, germline editing – inheritable changes made through reproductive cells – on the other hand, has me in full-force hypervigilance mode. As amazing as these new heights being reached by CRISPR were, like any great technology, there is the possibility that it could be weaponised and used for nefarious reasons. This was when the book started to weigh heavy on my psyche, and I found myself putting it down to discuss the ethics with my husband. I couldn’t shake the nagging feeling that these advances would be in the same vein as the splitting of the atom, or the proliferation of the internet. How does one truly feel about such important and life changing technologies that could also be the authors of the world’s destruction?
‘…in 2016 when James Clapper, the U.S. Director of National Intelligence, issued the agency’s annual “Worldwide Threat Assessment” and it included for the first time “genome editing” as a potential weapon of mass destruction.’
Moral and ethical questions concerning the usage of genetic engineering to produce children of specific qualifications and lacking undesirable features, leaves a lot for discussion and thought. Although one may be inclined to feel that gene modification and selection is playing God and should be left to chance, another may think it cruel and unusual not to use every tool in the workbench to make sure all living beings have a fair chance at a good life. Imagine for a moment being able to eliminate schizophrenia from the gene pool.
Another important factor to consider is the ability for germline editing to further erode equality of opportunity within society. Could the expense of the technology, and differing regulatory standards in certain countries lead to genetic tourism? If you have the money, just travel to one of the countries that offer the procedure and design your genetically modified little human. How could any governing body or judicial system possibly regulate such a thing?
The thought that I kept coming back to as Isaacson was weighing out the pros and cons was what would be the dreaded possible unintended consequences… What would happen to: personal drive, empathy, humility, sense of accomplishment through grit and determination, sacrifice, tolerating discomfort, personal responsibility, or healthy living? If we don’t seriously consider all that could come from this, do we deserve whatever we get? It felt as though there should have been an international referendum on this, but as documented in the case of the CRISPR twins in China – which you’ll find chronicled in the book – the cat was already out of the bag.
“Ingenuity without wisdom is dangerous.”
It’s hard to imagine how a gene supermarket, with price points only affordable to the already rich and privileged, would result in anything other than a super-elite class. Those unable to keep up would merely be serfs whose only existence would be to serve the master class. Bio-techno-feudalism, as it were. That is not the world I want to live in.
Doudna: “We could create a gene gap that would get wider with each new generation,” she says. “If you think we face inequalities now, imagine what it would be like if society became genetically tiered along economic lines and we transcribed our financial inequality into our genetic code.”
‘By limiting gene edits to those that are truly “medically necessary,” she says, we can make it less likely that parents could seek to “enhance” their children, which she feels is morally and socially wrong.’
Speaking of supermarkets, as an aside, one of my favourite questions laid out in the book references genetically modified food and one of its unintended consequences: ‘Will we become less flavorful, like our tomatoes?’ Maybe if more people are fed, and fewer left starving, the taste is less important? … If only it were that black and white.
Nearing the end of the book we reach the vaccination information. It was heartening to see a shift in the behaviour amongst the CRISPR scientists when they became less worried about competition and were willing to share their work, as they became impassioned by the urgency to defeat the coronavirus. The fundamental breakdown of what the mRNA vaccine technology can do for humanity and the future of plague and disease in the world is nothing short of miraculous. I am truly amazed by what these genius scientists have uncovered to help to defend mankind, and how their hard work could see us not locked down in our homes every time a novel corona virus comes on the scene.
‘…basic function that RNA performs in the central dogma of biology: serving as a messenger RNA (mRNA) that carries genetic instructions from DNA, which is bunkered inside a cell’s nucleus, to the manufacturing region of the cell, where it directs what proteins to make. In the case of the COVID vaccine, the mRNA instructs cells to make part of the spike protein that is on the surface of a coronavirus.’
I’m really glad that I took the time to wrestle with The Code Breaker and its big questions, and I would recommend that others do the same if they are interested, as this is the world we live in now, like it or lump it. You don’t have to be science minded to follow, as long as you give yourself the space to not understand everything to the T… cell (haha), and who knows, you may just find you’ve learned something. Upwards of 90% success rate or not, for my family I am inclined to think that more time is needed to see how these vaccines will react to people’s immune systems in the long-term, especially those with autoimmune disorders, as we have in our household. The data collected regarding their use in humans is obviously very limited in scope, given they have been in use for under a year at this point. With time and confidence this could truly be the thing to save us, and as long as the technology stays in the right hands, it won’t be the thing to destroy us.
What are your thoughts on the gene editing possibilities that this technology offers humanity? Do you trust in the world to use this revolutionary science fairly, or will it be manipulated and weaponised by the fortunate few against the masses?
A bookmark representing a spike protein, that I had fun creating after reading The Code Breaker.