The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

by Walter Isaacson

As she stood in front of the room to rally them, Doudna displayed an intensity that she usually kept masked by a calm façade. “This is not something that academics typically do,” she told them. “We need to step up.”

It was fitting that a virus-fighting team would be led by a CRISPR pioneer.

In their DNA, bacteria develop clustered repeated sequences, known as CRISPRs, that can remember and then destroy viruses that attack them.

What none of the participants discussed was a longer-range prospect: using CRISPR to engineer inheritable edits in humans that would make our children, and all of our descendants, less vulnerable to virus infections. These genetic improvements could permanently alter the human race.

If these offerings at the genetic supermarket aren’t free (and they won’t be), will that greatly increase inequality—and indeed encode it permanently in the human race?

The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.

Now we have entered a third and even more momentous era, a life-science revolution. Children who study digital coding will be joined by those who study genetic code.

she became more interested in DNA’s less-celebrated sibling, RNA. It’s the molecule that actually does the work in a cell by copying some of the instructions coded by the DNA and using them to build proteins.

in 2012 Doudna and others figured out a more earth-shattering use: how to turn CRISPR into a tool to edit genes.

CRISPR is now being used to treat sickle-cell anemia, cancers, and blindness.

2020, Doudna and her teams began exploring how CRISPR could detect and de...

“CRISPR evolved in bacteria because of their long-running wa...

Her work also illustrates, as Leonardo da Vinci’s did, that the key to innovation is connecting a curiosity about basic science to the practical work of devising tools that can be applied to our lives—moving discoveries from lab bench to bedside.

Most of all, I want to convey the importance of basic science, meaning quests that are curiosity-driven rather than application-oriented. Curiosity-driven research into the wonders of nature plants the seeds, sometimes in unpredictable ways, for later innovations.

Many creative people—including most of those I have chronicled, such as Leonardo da Vinci, Albert Einstein, Henry Kissinger, and Steve Jobs—grew up feeling alienated from their surroundings.

“I was really, really alone and isolated at school,”

“I’ve looked for opportunities where I can fill a niche where there aren’t too many other people with the same skill sets.”

Doudna’s father was a voracious reader who would check out a stack of books from the local library each Saturday and finish them by the following weekend.

Doudna’s career would be shaped by the insight that is at the core of The Double Helix: the shape and structure of a chemical molecule determine what biological role it can play.

The beaks of Darwin’s finches and the traits of Mendel’s peas gave birth to the idea of the gene, an entity inside of living organisms that carries the code of heredity.

He knew that horses and cows near his childhood home in rural England were occasionally born with slight variations, and over the years breeders would select the best to produce herds with more desirable traits. Perhaps nature did the same thing. He called it “natural selection.”

“Under these circumstances, favorable variations would tend to be preserved, and unfavorable ones to be destroyed,” he wrote. “The results of this would be the formation of a new species.”

Darwin was hesitant to publish his theory because it was so heretical, but competition acted as a spur,

Darwin and Wallace had a key trait that is a catalyst for creativity: they had wide-ranging interests and were able to make connections between different disciplines.

“An Essay on the Principle of Population” by Thomas Malthus, an English economist. Malthus argued that the human population was likely to grow faster than the food supply. The resulting overpopulation would lead to famine that would weed out the weaker and poorer people.

As the science fiction writer and biochemistry professor Isaac Asimov later noted concerning the genesis of evolutionary theory, “What you needed was someone who studied species, read Malthus, and had the ability to make a cross-connection.”

What his experiments showed was momentous, given what Darwin was writing at the time. There was no blending of traits.

Instead, all the offspring of a tall and a short plant were tall. The offspring from purple flowers crossbred with white flowers produced only purple flowers. Mendel called these the dominant traits; the ones that did not prevail he called recessive.

in this second generation, the dominant trait was displayed in three out of four cases, with the recessive trait appearing once.

The findings of Mendel and these subsequent scientists led to the concept of a unit of heredity, what a Danish botanist named Wilhelm Johannsen in 1905 dubbed a “gene.” There was, apparently, some molecule that encoded bits of hereditary information.

Scientists initially assumed that genes are carried by proteins. After all, proteins do most of the important tasks in organisms. They eventually figured out, however, that it is another common substance in living cells, nucleic acids, that are the workhorses of heredity.

They come in two varieties: ribonucleic acid (RNA) and a similar molecule that lacks one oxygen atom and thus is called deoxyribonucleic acid (DNA).

From an evolutionary perspective, both the simplest coronavirus and the most complex human are essentially protein-wrapped packages that contain and seek to replicate the genetic material encoded by their nucleic acids.

He later said that one of the most important lessons his parents taught him was “Hypocrisy in search of social acceptance erodes your self-respect.”

With Luria as his PhD advisor, Watson studied viruses. These tiny packets of genetic material are essentially lifeless on their own, but when they invade a living cell, they hijack its machinery and multiply themselves. The easiest of these viruses to study are the ones that attack bacteria, and they were dubbed (remember the term, for it will reappear when we discuss the discovery of CRISPR) “phages,” which was short for “bacteriophages,” meaning bacteria-eaters.

By then Watson and Crick had a pretty good idea of DNA’s structure. It had two sugar-phosphate strands that twisted and spiraled to form a double-stranded helix. Protruding from these were the four bases in DNA: adenine, thymine, guanine, and cytosine, now commonly known by the letters A, T, G, and C. They came to agree with Franklin that the backbones were on the outside and the bases pointed inward, like a twisted ladder or spiral staircase.

There was an exciting consequence of this structure: when the two strands split apart, they could perfectly replicate, because any half-rung would attract its natural partner.

such a structure would permit the molecule to replicate itself and pass along the information encoded in its sequences.

“Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.” The solution was too beautiful not to be true. The structure was perfect for the molecule’s function. It could carry a code that it could replicate.

“It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

Two revolutions coincided in the 1950s. Mathematicians, including Claude Shannon and Alan Turing, showed that all information could be encoded by binary digits, known as bits. This led to a digital revolution powered by circuits with on-off switches that processed information. Simultaneously, Watson and Crick discovered how instructions for building every cell in every form of life were encoded by the four-letter sequences of DNA. Thus was born an information age based on digital coding (0100110111001…) and genetic coding (ACTGGTAGATTACA…). The flow of history is accelerated when two rivers converge.

Life was made up of molecules. The chemical components and structure of these molecules governed what they would do.

He was using electron microscopy to investigate the movement of chemicals inside cells. “Jennifer was fascinated by the ability to look inside cells and study what all the small particles were doing,” he recalled.

Panasenko was studying a topic that aligned with Doudna’s interest in the mechanisms of living cells: how some bacteria found in soil are able to communicate so that they can join together when they are starved for nutrients. They form a commune called a “fruiting body.” Millions of the bacteria figure out how to aggregate by sending out chemical signals. Panasenko enlisted Doudna to help figure out how those chemical signals worked.

His lab was international, with many of the researchers from Spain or Latin America, and Doudna was struck by how young and politically active they were.

Her experiments gave her a glimpse of how basic science can be turned into applied science. Yeast cells are very efficient at taking up pieces of DNA and integrating them into their genetic makeup.

She engineered strands of DNA that ended with a sequence that matched a sequence in the yeast. With a little electric shock, she opened up tiny passageways in the cell wall of the yeast, allowing the DNA that she made to wriggle inside. It then recombined into the yeast’s DNA. She had made a tool that could edit the genes of yeast.

It was called the Human Genome Project, and its goal was to figure out the sequence of the three billion base pairs in our DNA and map the more than twenty thousand genes that these base pairs encode.

“My wife and I hoped when he was young we could set up the right environment for him to succeed. But I soon realized that his troubles lay in his genes. That drove me to lead the Human Genome Project. The only way I could understand our son and help him live at a normal level was to decipher the genome.”

“In an achievement that represents a pinnacle of human self-knowledge, two rival groups of scientists said today that they had deciphered the hereditary script, the set of instructions that defines the human organism.”