Jennifer Doudna Quotes

The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.

Never do something that a thousand other people are doing.

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.

Hypocrisy in search of social acceptance erodes your self-respect.

Men ought not to play God before they learn to be men.

The beauty of nature and the joy that comes from unstructured human engagement is a powerful combination.

just because we are not ready for scientific progress does not mean it won’t happen.

The disjunction between scientific consensus and public opinion on the topic of GMOs is disturbing, to say the least.

Great inventions come from understanding basic science. Nature is beautiful that way.

I think my blunt and contrary nature helps my science, because I don’t simply accept things just because other people believe it,

How do we distinguish between traits that are true disabilities and ones that are disabilities mainly because society is not good at adapting for them?

The first half of the twentieth century, beginning with Albert Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics.

A full 8 percent of the human genome—over 250 million letters of DNA—is a remnant of ancient retroviruses that infected ancestors of our species millennia ago.

Just as bacteria have spent millennia evolving ways to develop immunity to viruses, perhaps we humans should use our ingenuity to do the same.

Ingenuity without wisdom is dangerous.

Does empathy depend on believing that but for the grace of God, or the randomness of the natural lottery, we could have been born with a different set of endowments?

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.

The second half of the twentieth century was an information-technology era, based on the idea that all information could be encoded by binary digits—known as bits—and all logical processes could be performed by circuits with on-off switches.

Nature is beautiful.

After more than three billion years of evolution of life on this planet, one species (us) had developed the talent and temerity to grab control of its own genetic future. There

The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions

This overall flow of genetic information—from DNA to RNA to protein—is known as the central dogma of molecular biology, and it is the language used to communicate and express life.

Even gene variants implicated in neurodegenerative diseases like Alzheimer’s may have benefits: E. S. Lander, “Brave New Genome,” New England Journal of Medicine 373 (2015): 5–8.

We had to determine structures, because structures, the folds and shapes, are conserved over a longer evolutionary period than the nucleic acid sequences.

The scientist does not study nature because it is useful. He studies it because he takes pleasure in it, and he takes pleasure in it because it is beautiful.

have no doubt, this technology will — someday, somewhere — be used to change the genome of our own species in ways that are heritable, forever altering the genetic composition of human kind.

The evolutionary process cares little about what happens to us after we have children and get them to a safe age, so there are a whole bunch of middle-aged maladies, including Huntington’s and most forms of cancer, that we humans would want to eliminate, even though nature sees no need to.

I once asked Steve Jobs what his best product was, thinking he would say the Macintosh or iPhone. Instead he said that creating great products is important, but what’s even more important is creating a team that can continually make such products.

We all see nature's wonders every day, whether it be a plant that moves or a sunset that reaches with pink fingers into a sky of deep blue. The key to true curiosity is pausing to ponder the causes. What makes a sky blue or a sunset pink or a leaf of sleeping grass curl?

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.

Much of the attention paid to CRISPR these days involves its potential to make inheritable (germline) edits in humans that will be passed along to all the cells of all of our future descendants and have the potential to alter our species. These edits are done in reproductive cells or early-stage embryos. This is what occurred with the CRISPR baby twins in China in 2018, and it is the controversial topic that I will discuss later in this book.

It was a bad day for viruses,” Moderna’s chair Afeyan says about the Sunday in November 2020 when he got the first word of the clinical trial results. “There was a sudden shift in the evolutionary balance between what human technology can do and what viruses can do. We may never have a pandemic again.

TOMATOES THAT CAN sit in the pantry slowly ripening for months without rotting. Plants that can better weather climate change. Mosquitoes that are unable to transmit malaria. Ultra-muscular dogs that make fearsome partners for police and soldiers. Cows that no longer grow horns. These organisms might sound far-fetched, but in fact, they already exist, thanks to gene editing. And they’re only the beginning. As I write this, the world around us is being revolutionized by CRISPR, whether we’re ready for it or not.

how a piece of RNA could pair up with its phage DNA counterpart and cause that DNA to be destroyed.

En fin, la naturaleza esconde un montón de secretos asombrosos —dice.[8]

Figuring out if and when to edit our genes will be one of the most consequential questions of the twenty-first century,

seriously

researchers at the height of the coronavirus crisis were posting more than a hundred papers a day on preprint servers, such as medRxiv and bioRxiv, that were free and open

A looming ethical issue, everyone at the table agrees, is that gene editing could exacerbate, and even encode, inequality in society.

In-person interactions are especially important in the initial brainstorming of new ideas and the forging of personal bonds.

Most of us someday will have detection devices in our home that will allow us to check for viruses and many other conditions.

Someday we may consider it unethical not to use germline editing to alleviate human suffering.

The Ethics of Genetic Control. “As we learn to direct mutations medically, we should do so. Not to control when we can is immoral.

the microchip, the computer, and the internet. When these three innovations were combined, the digital revolution was born.

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.

Don’t fight over divvying up the proceeds until you finish robbing the stagecoach.

We have 100,000 people in the U.S. affected by sickle cell,” one senator pointed out. “How are we going to afford that if it’s $1 million per patient? That just breaks the bank.

Conferences can have consequences

It’s good to have strong opinions about gene engineering in humans, but it’s even better if you know what a gene is.

She had succeeded where the other technician had failed. “It was an incredible moment, and it made me think I could do science.

The most controversial player was the wild and abrasive Craig Venter, who had worked in a U.S. Navy field hospital as a draftee during the Tet Offensive of the Vietnam War,

RNA, on the other hand, actually goes out and does real work. Instead of just sitting at home curating information, it makes real products, such as proteins.

four bases in DNA: adenine, thymine, guanine, and cytosine, now commonly known by the letters A, T, G, and C.

Jack Szostak, who admitted to not being a visual thinker or expert in structural biology.

Thomas Cech (pronounced “check”) of the University of Colorado in Boulder, who was using X-ray crystallography in order to explore each nook and cranny of the structure of RNA.

I'd recently co-founded an institute in the Bay Area called the Innovative Genomics Institute (ICI) with the goal of advancing gene-editing technologies.

with a DNA molecule mimicking the genome of a phage.

Armed with the complete CRISPR toolkit, scientists can now exert nearly complete control over both the composition of the genome and its output.

CRISPR offers the greatest hope to treat monogenic genetic diseases—those caused by a single mutated gene.

human gene editing would almost assuredly never have the same catastrophic consequences as the detonation of a nuclear weapon

Mojica was driving home from his lab one evening when he came up with the name CRISPR, for “clustered regularly interspaced short palindromic repeats.

phages,” which was short for “bacteriophages,” meaning bacteria-eaters.

Ah, that picture, it will always haunt me,” he says, then pauses and smiles his impish grin. “But she never figured out it was a helix.”1

A few decades from now, if it becomes possible and safe, should we allow parents to enhance the IQ and muscles of their kids? Should we let them decide eye color? Skin color? Height?

some forms of RNA could likewise be enzymes. Specifically, they found that some RNA molecules can split themselves by sparking a chemical reaction. They dubbed these catalytic RNAs “ribozymes,

is an amazing revelation for those who are interested in uncovering the fundamental secrets of life. It is the way that chemistry—the study of how atoms bond to create molecules—becomes biology.

For his doctorate, he went to the University of Pennsylvania, where he figured out how non-coding regions of our genome, previously described as “junk DNA,” could play a role in disease progression.

DNA doesn’t do much work. It mainly stays at home in the nucleus of our cells, not venturing forth. Its primary activity is protecting the information it encodes and occasionally replicating itself.

RNA (ribonucleic acid) is a molecule in living cells that is similar to DNA (deoxyribonucleic acid), but it has one more oxygen atom in its sugar-phosphate backbone and a difference in one of its four bases.

Doudna’s mission when she arrived at the University of Colorado as a postdoc was to map the intron that Cech had discovered could be a self-splicing piece of RNA, showing all of its atoms, bonds, and shapes.

Asilomar’s lack of focus on ethical issues bothered many religious leaders. That prompted a letter to President Jimmy Carter signed by the heads of three major religious organizations: the National Council of Churches, the Synagogue Council of America, and the U.S. Catholic Conference. “We are rapidly moving into a new era of fundamental danger triggered by the rapid growth of genetic engineering,” they wrote. “Who shall determine how human good is best served when new life forms are being engineered?”13 These decisions should not be left to scientists, the trio argued. “There will always be those who believe it appropriate to ‘correct’ our mental and social structures by genetic means. This becomes more dangerous when the basic tools to do so are finally at hand. Those who would play God will be tempted as never before.

But 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.

Instead of injecting a weakened or partial version of the dangerous virus into humans, these new vaccines deliver a gene or piece of genetic coding that will guide human cells to produce, on their own, components of the virus.

I wish it need not have happened in my time,” said Frodo. “So do I,” said Gandalf, “and so do all who live to see such times. But that is not for them to decide. All we have to decide is what to do with the time that is given us.

Throughout human history, we have been subjected to wave after wave of viral and bacterial plagues. The first known one was the Babylon flu epidemic around 1200 BC. The plague of Athens in 429 BC killed close to 100,000 people, the Antonine plague in the second century killed ten million, the plague of Justinian in the sixth century killed fifty million, and the Black Death of the fourteenth century took almost 200 million lives, close to half of Europe’s population.

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.

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.

But as we grope for a set of principles to include in our moral calculus, the distinction does point to a factor we should consider: favoring enhancements that would benefit all of society over those that would give the recipient a positional advantage.

A small segment of DNA that encodes a gene is transcribed into a snippet of RNA, which then travels to the manufacturing region of the cell. There this “messenger RNA” facilitates the assembly of the proper sequence of amino acids to make a specified protein.

Indeed, phage viruses are by far the most plentiful biological entity on earth. There are 1031 of them—a trillion phages for every grain of sand, and more than all organisms (including bacteria) combined. In one milliliter (0.03 ounces) of seawater there can be as many as 900 million of these viruses.7

You have to be self-sufficient,” he told Wilson. “If you’re not self-motivated, Jennifer is not going to help you much or do the work for you. At times she will seem disengaged. But if you’re a self-starter, she will give you the chance to take risks, provide really smart guidance, and be there when you need her.

The gene-editing tool that Doudna and others developed in 2012 is based on a virus-fighting trick used by bacteria, which have been battling viruses for more than a billion years. In their DNA, bacteria develop clustered repeated sequences, known as CRISPRs, that can remember and then destroy viruses that attack them.

It turns out that tracrRNA performs two important tasks. First, it facilitates the making of the crRNA, the sequence that carries the memory of a virus that previously attacked the bacteria. Then it serves as a handle to latch on to the invading virus so that the crRNA can target the right spot for the Cas9 enzyme to chop.

Developers and entrepreneurs may someday be able to use CRISPR-based home testing kits as platforms on which to build a variety of biomedical apps: virus detection, disease diagnosis, cancer screening, nutritional analyses, microbiome assessments, and genetic tests. “We can get people in their homes to check if they have the flu or just a cold,” says Zhang.

American spy agencies seemed rattled by the experiments too. I was shocked when the next Worldwide Threat Assessment — the annual report presented by the U.S. intelligence community to the Senate Armed Services Committee — described genome editing as one of the six weapons of mass destruction and proliferation that nation-states might try to develop, at great risk to America.

Wielding imaging techniques such as X-ray crystallography, which is what Rosalind Franklin used to find evidence of the structure of DNA, structural biologists try to discover the three-dimensional shape of molecules. Linus Pauling worked out the spiral structure of proteins in the early 1950s, which was followed by Watson and Crick’s paper on the double-helix structure of DNA.

RNA interference operates by deploying an enzyme known as “Dicer.” Dicer snips a long piece of RNA into short fragments. These little fragments can then embark on a search-and-destroy mission: they seek out a messenger RNA molecule that has matching letters, then they use a scissors-like enzyme to chop it up. The genetic information carried by that messenger RNA is thus silenced.

Doudna wrote in a scholarly publication back in 2013, researchers hoped to find ways to use RNA interference to protect humans from infections.6 Two papers published in Science that year gave strong evidence that it might work. The hope then was that drugs based on RNA interference might someday be a good option for treating severe viral infections, including those from new coronaviruses

There are other star players in the field of gene editing. Most of them deserve to be the focus of biographies or perhaps even movies. (The elevator pitch: A Beautiful Mind meets Jurassic Park.) They play important roles in this book, because I want to show that science is a team sport. But I also want to show the impact that a persistent, sharply inquisitive, stubborn, and edgily competitive player can have. With a smile that sometimes (but not always) masks the wariness in her eyes, Jennifer Doudna turned out to be a great central character. She has the instincts to be collaborative, as any scientist must, but ingrained in her character is a competitive streak, which most great innovators have. With her emotions usually carefully controlled, she wears her star status lightly.

It was fitting that a virus-fighting team would be led by a CRISPR pioneer. The gene-editing tool that Doudna and others developed in 2012 is based on a virus-fighting trick used by bacteria, which have been battling viruses for more than a billion years. In their DNA, bacteria develop clustered repeated sequences, known as CRISPRs, that can remember and then destroy viruses that attack them.

One odd result of allowing super-enhancements could be that children will become like iPhones: a new version will come out every few years with better features and apps. Will children as they age feel that they are becoming obsolete? That their eyes don’t have the cool triple-lens enhancements that are engineered into the latest version of kids? Fortunately, these are questions we can ask for amusement but not for an answer.

Before getting into CRISPR, Zayner tried a variety of synthetic biology experiments, including on himself. To treat his gastrointestinal problems, he performed a fecal transplant (don’t ask) to transform his gut’s microbiome. He did the procedure in a hotel room with two filmmakers documenting the scene, and (in case you really do want to know how it works) it became a short documentary called Gut Hack that can be found online.2

Genetic vaccines The plague year of 2020 is likely to be remembered as the time when these traditional vaccines began to be supplanted by genetic vaccines. Instead of injecting a weakened or partial version of the dangerous virus into humans, these new vaccines deliver a gene or piece of genetic coding that will guide human cells to produce, on their own, components of the virus. The goal is for these components to stimulate the patient’s immune system.

Scholars and journalists have already started dreaming that CRISPR might be used to create mythical creatures like winged dragons by editing the genes of Komodo dragons,70 noting in a prominent bioethics journal that, while basic physics would prevent them from breathing fire, “a very large reptile that looks at least somewhat like the European or Asian dragon (perhaps even with flappable if not flyable wings) could be someone’s target of opportunity.”71

Michael Sandel uses this thought experiment: Suppose a parent comes to a doctor and says, “My child is going to be born deaf, but I want you to do something to make her able to hear.” The doctor should try, right? But now suppose a parent says, “My child is going to be born able to hear, but I want you to do something to her to make sure she is born deaf.” I think most of us would recoil if the doctor agreed. Our natural instinct is to consider deafness a disability.

These proteins come in many types. Fibrous proteins, for example, form structures such as bones, tissues, muscles, hair, fingernails, tendons, and skin cells. Membrane proteins relay signals within cells. Above all is the most fascinating type of proteins: enzymes. They serve as catalysts. They spark and accelerate and modulate the chemical reactions in all living things. Almost every action that takes place in a cell needs to be catalyzed by an enzyme. Pay attention to enzymes

Doudna deeply enjoyed being a bench scientist, a researcher who gets to the lab early, puts on latex gloves and a white coat, and begins working with pipettes and Petri dishes. For the first few years after setting up her lab at Berkeley, she was able to work at the bench half her time. “I didn’t want to give that up,” she says. “I think I was a pretty good experimenter. That’s how my mind works. I can see experiments in my mind, especially when I am working myself.” But by 2009, after her return from Genentech, Doudna realized that she had to spend more time cultivating her lab rather than her bacterial cultures. This transition from player to coach happens in many fields. Writers become editors, engineers become managers. When bench scientists become lab heads their new managerial duties include hiring the right young researchers, mentoring them, going over their results, suggesting new experiments, and offering up the insights that come from having been there.

The CRISPR-based tests developed by Mammoth and Sherlock are cheaper and faster than conventional PCR tests. They also have an advantage over antigen tests, such as the one developed by Abbott Labs that was approved in August of the plague year. The CRISPR-based tests can detect the presence of the RNA of a virus as soon as a person has been infected. But the antigen tests, which detect the presence of proteins that exist on the surface of the virus, are most accurate only after a patient has become highly infectious to others.

The idea that germline editing was “unnatural” began to recede in her thinking. All medical advances attempt to correct something that happened “naturally,” she realized. “Sometimes nature does things that are downright cruel, and there are many mutations that cause enormous suffering, so the idea that germline editing was unnatural began to carry less weight for me,” she says. “I am not sure how to make a sharp distinction in medicine between what is natural and what is unnatural, and I think it’s dangerous to use that dichotomy to block something that could alleviate suffering and disability.

He became the only person I’ve ever encountered who moved from France to North Carolina in order to learn more about food. He enrolled at North Carolina State in Raleigh and got his master’s degree in the science of pickle and sauerkraut fermentation. He went on to get his doctorate there, married a food scientist he met in class, and followed her to Madison, Wisconsin, when she went to work at the Oscar Mayer meat company. Madison is also home to a Danisco unit that produces hundreds of megatons of bacteria cultures for fermented dairy products, including yogurt. Barrangou took a job there as a research director in 2005.3