Book review: “The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race” by Walter Isaacson

Scientists analyzing DNA helix and editing genome within organisms, CRISPR technology.

Long gone are the days when genetically engineered humans solely existed in science fiction. Mary Shelley’s “Frankenstein: or, The Modern Prometheus,” H.G. Wells’ “The Time Machine”, and Aldous Huxley’s “Brave New World,” all posited ideas of human-like scientific experiments and how humanity might progress given the power of genetic engineering. Over the past few decades, those ideas from fiction have gradually become more real. Like a story unfolding, American biochemist Jennifer Doudna, a hero behind the Crispr-cas9 technique, takes center stage. 

In “The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race,” the famous historian Walter Isaacson follows the steps of Doudna on her journey to uncover the secrets of the genetic code and the moral questions resulting from tampering with human life. 

After Isaacson has established himself thoroughly as a historian and journalist with his biographies on Albert Einstein, Steve Jobs, Benjamin Franklin, and other men, he now shares the story of Doudna, one of the women behind the pioneering work in the field of gene editing. 

Her technique relies on Crispr, an acronym for the “clustered regularly interspaced palindromic repeats,” found in the bacteria in everyone’s DNA, that lets scientists edit parts of the genome with precision and versatility. With the associated protein Cas9, an enzyme that uses Crispr sequences to select and remove specific parts of the DNA, Doudna’s Crispr-cas9 technique would prove its usefulness in letting scientists edit genomes in vivo, or right in place in a living organism. 

Put in the hands of amazing scientists, Doudna and her team at Berkeley hope to use Crispr-cas9 to “engineer inheritable edits in humans that will make our descendants less vulnerable to virus infections.” Such a powerful technology could change the human race as we know it. 

Coming at no time more opportune than the pandemic, the creation of effective vaccines for the COVID-19 has brought the need for Crispr-cas9. And, when Doudna earned the Nobel Prize in chemistry last year alongside French microbiologist Emmanuelle Charpentier, the story ends with events unfolding in the news today. When you close the cover of the book at the end, the next chapter continues before your eyes. 

Isaacson’s biography wasn’t just history: it was reality. Reading the book feels like watching a movie with everything we’ve witnessed in Crispr-Cas9 research leading up to these momentous events we’ve read about in the news only recently. 

In 2012, the two women, Charpentier and Doudna, published their manuscript on the first use of the technique, using Crispr RNAs to provide adaptive immunity to bacteria and archaea. Eight years later, they won the Nobel Prize for their groundbreaking work. Their story involves a race between scientists competing against one another for publications and patents while questions of how the technology will shape the future take the stage. 

The power of genetic engineering has raised questions of how scientists should use it for decades. American biochemists Stanley N. Cohen and Herbert W. Boyer pioneered recombinant DNA technology, letting scientists cut DNA into fragments and rejoin them to create and insert new sequences at their will in the early 1970s. When 150 physicians and biologists gathered at the Asilomar conference in 1975 to debate what sort of restraints should be placed on these new genetic engineering technologies, Stanford biochemist Paul Berg set the stage by describing the science behind it: recombinant DNA technology, formed from different organisms, has made it “ridiculously simple” to create new genes. Berg claimed that, given its risks were so difficult to determine, the technology should be banned. Others dissented, including MIT biologist David Baltimore, who argued for a solution that would restrict the use of recombinant DNA to “crippled” viruses so they wouldn’t spread. 

Using Crispr-Cas9 to get rid of sickle cell anemia, cancer, Huntington’s disease, or COVID-19 may sound amazing already, but, given the power to change the genome, why not use it to change other things about who we are? With the technology to change our height or make us smarter, the questions of what right we have to do so arise. Isaacson goes into the deep moral questions that the technique poses. Why not engineer a child to be the perfect athlete, the perfect student, or the perfect scientist? 

The innovative success in pushing the boundaries of how closely and thoroughly Crispr scientists can change the genome has also raised questions of how much one should tamper with what makes us human. Isaacson doesn’t stop at the science, though. His writing on the theories of justice by philosophers John Rawls and Robert Nozicke that relate to the ethics of Crispr would help readers understand methods of philosophical reasoning that can be used to define and provide a framework for hot topic issues such as eugenics and pre-implantation genetic diagnosis. 

Even the issues of how unequal access to the technology could consolidate disadvantaged and marginalized subjects and groups, the way human life is treated through motives and methods of reasoning, such as the justification of giving priority to patients who need an organ immediately to prevent death, even if there is a utilitarian motive for giving the organ to a healthier patient, all depend upon the essential questions of human life that Crispr raises. 

It’s difficult to downplay the sexism Doudna faces on her journey to own her own research. Isaacson’s story brings light to these subtle ways men overshadow and overlook the work of women in science with notable similarities to the treatment of Rosalind Franklin. When Eric Lander, biologist at MIT and Harvard’s Broad Institute, published his essay “The Heroes of CRISPR,” in the journal Cell in January 2016, he concluded that, “the narrative underscores that scientific breakthroughs are rarely eureka moments. They are typically ensemble acts, played out over a decade or more, in which the cast becomes part of something greater than what any one of them could do alone. It’s a wonderful lesson for the general public, as well as for a young person contemplating a life in science.” Though it may seem noble to praise the scientists behind Crispr this way, what wasn’t said revealed the misogynistic undertones. 

In her Jezebel article “How One Man Tried to Write Women Out of Crispr, the Biggest Biotech Innovation in Decades” writer Joanna Rothkopf pointed out that Lander failed to mention the billion-dollar patent battle between his institute and Doudna and Charpentier. “Not only did the Cell paper fail to disclose the potential conflict of interest, it significantly minimized the role of Doudna’s lab in advancing the technology,” Rothkopf wrote. Such a manipulative method of subtly ignoring the work of women spoke to larger systemic issues of sexism in science. Similarly, the patent battle only epitomized the greater, more universal competition that pitted scientists against one another throughout Isaacson’s book.

And what a war it was. Isaacson emphasizes the nature of scientific research as competition with individuals racing to discover the blueprints of the genetic code. Through bitter rivalries and battles, each combatant with their own motives and research techniques, the book feels like a series of duels between scientists in a culture that rewards national competitiveness and firsts. The reader is left to wonder whether the fault for misconduct and discrimination lies with the decisions the individual makes or with the culture that glorifies provocative research and celebrity status. 

Like a mystery story unraveling, Doudna’s journey is all about finding the clue that leads to the next step, one by one, with each step getting closer to fighting against disease. One finds a noble cause among Crispr scientists searching for truth and answers for the greater good, showing the worth of their character. Echoing what Lander wrote, the young person contemplating a “life in science” should understand how grand narratives emerge out of ensemble acts that play out over decades. Indeed, one should hope that life in science would be determined by the actions of the scientist herself, not by her DNA. 

Explaining Hidden Markov Models (HMMs) using Pac-Man!

The DNA Pac-Man game (https://github.com/HussainAther/dnapacman) can represent how protein sequences are generated (using Hidden Markov Models). We can draw an analogy of how HMMs work in the context of generating protein sequences using the Pac-Man. The next token/letter you eat is the next letter in the sequence of generating a sequence of protein amino acids.

Essentially, if we organize regions of the Pac-Man board representing different hidden states in a Markov Model, then the next letter that Pac-Man eats can represent the next state an HMM selects. We can change the probabilities a certain letter may appear and, when Pac-Man enters the hidden state, then the probabilities would change.

We can observe how the probability for different states changes as people play based on which letter they choose next. We can compare the HMM of Pac-Man to the HMMs in modeling eukaryotic genes following the methods of this manuscript “Hidden Markov Models and their Applications in Biological Sequence Analysis”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766791/

Full post here: https://github.com/HussainAther/DNAPacManHMM

Political Virtue of a Virus

A cell infected with a virus in the show “Cells at Work!” Metaphors for a disease can teach us more about them.

Coronavirus has become something else. Analogies of COVID-19 being like an evil force of nature, on the edge of life and death just as a virus would be. As alluring as it is to use grandiose metaphors and contemplate their meaning, it’s hard to separate truth from fiction. Any metaphor that lets us understand a deeper or hidden similarity we couldn’t otherwise explain runs the risk of straying from what something actually is. Still, a global pandemic that overturns notions of morality, reality, politics, and everything else can’t be explained without resorting to analogies. With that, the coronavirus is an experimental hypothesis of ethics. It’s a test to our character and morality in how we fight a virus as though it were something evil.

The politics of globalization and communication, like the anonymous force that spreads a viral video spreading, are at their end for this era. The promise of rising living standards and faith in government authority will fall along with them. With them, the experiment of liberalism, in forming unity and common bonds between people, has ended. The virus becomes a test of what can best answer the issues raised by these losses with the mistrust and tension between individualism and collectivism it brings.

When 19th-century Austrian physician Ignaz Semmelweis realized washing hands would prevent the high death rate among pregnant women due to post-partum infections, he was ostracized and sent to a mental asylum where he he would die. Just as Aristotle in Politics described the “exceptional man” who could sing better than the others in the chorus and, as a result, become ostracized by them, we can determine which exceptions we can’t afford to ignore through methods like washing hands and vaccinations.

When philosopher Michel Foucault wrote that modern sovereign power was biopolitical, expressed through the production, management, and administration of “life,” philosopher Giorgio Agamben responded that there was a “state of exception” in which an authority could exercise power in areas law had not otherwise granted to it. During the emergency of the pandemic, we find ourselves in this state. Knowledge itself has become a privilege. Only some voices are valued. Those who choose to spread knowledge and let ideas flourish would be virtuous during this time.

The virus invites us to reflect and meditate upon the world. We are mortal, finite, contingent, lacking, wanting, and many other things. These ideals have been true and will always be, but the virus only further reveals them. Philosopher Baruch Spinoza ridiculed how other thinkers put humans above nature, the idea that man, in nature, is a dominion within a dominion. The coronavirus breaks down solidarity between humans and creates walls between them. It sows divisions and prevents information and righteousness from reaching one another, much the way we self-isolate and quarantine. We must, then, find common solutions that can overcome these obstacles.

We may see the fall of postmodernism. Though nature may seem sinister with how threatening the virus is, we can’t address these issues and help one another without turning to nature. With the rise of “red zone” hotspots, domestic seclusion, and militarized territories, “neighbors” can be “anyone.” Turning to nature for answers and seeking unifying, grand narratives to unite people among one another would bring about a return to modernist ideals. Even fighting against fascism, an ideology that would otherwise welcome barricaded borders and segregation from superior groups, means coming to terms with the idea that the enemy is not some foreigner or outsider. As Agamben wrote, on coronavirus, “The enemy is not outside, it is within us.” Blocking communication with other nations, as sovereignists like Trump may want, won’t solve the problem. Conspiracy theories that Asian individuals or 5G are to blame may also show this xenophobia that attempts to remedy our anxieties.

With certainty, I believe the virus has made politics more of a morality test. There’s a political “virtue” in how we react to it with wisdom and resilience. If the political virtue abandons the “human, all too human,” illusion that we can appropriate nature like a dominion in a dominion, then the morality test of politics means we must learn how to govern nature, not control it. The Greeks would have called political “cybernetic” or nautical, and, like a sailor fighting against a stormy sea, politics means caring about the crew to survive.

Much like the coronavirus was named “corona” for its crown-shape, the authority, legitimacy, and power of individuals who rule nations come into question. Like a virus, neither dead nor alive, we find ourselves in a state of motionless solitude during isolation and quarantine. Teetering on the brink of despair, we have to regain our balance. When governments and economies begin starting up again, we can only fight against the virus so it doesn’t retain its power.