Jennifer Walters Quotes

You only get one heart", Walter said to his daughter after the second one ended. He seemed sad, but not regretful. " I gave mine to your mother the day I met her. And she still has it.

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.

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

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

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

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

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

Feel free to start using Walter Jackson Freeman II as an insult directed toward people you hate. Almost no one will get the reference, but if I am in the room we’ll high-five and it will be awesome.

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

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.

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

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?

Ingenuity without wisdom is dangerous.

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.

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.

What drives people to do good things is recognition.

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?

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

Nature is beautiful.

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 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 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.

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 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.

He named these “CRISPR-associated,” or Cas, enzymes.

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.

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.

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.

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

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

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.

it folded and twisted, which would reveal how it interacted with other molecules.5

the sequence of letters in the DNA did not reveal how it worked; what was important was

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.

I don’t think that I would be me if I didn’t have sickle cell.

peripatetic

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

In explaining the amazing mechanisms of life, little things matter. And very little things matter a lot.

consensus

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

too

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.

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

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

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?

She felt at home in the lab. It was a quiet temple for individual persistence and contemplation. She could be creative and independent as she pursued a path toward her own discoveries.

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.

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.

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.

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.

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.

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.

What made the single-guide system particularly significant—from both a scientific and an intellectual property standpoint—was that it was an actual human-made invention, not merely a discovery of a natural phenomenon.

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.

Almost from the beginning of life on this planet, there’s been an intense arms race between bacteria, which developed elaborate methods of defending against viruses, and the ever-evolving viruses, which sought ways to thwart those defenses.

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.

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.

The next day they had lunch, followed by a stroll along the cobblestone streets of old San Juan. When the discussion turned to Cas9, Charpentier became excited. “We have to figure out exactly how it works,” she urged Doudna. “What’s the exact mechanism it uses to cut DNA?

I mention “mosaic,” a term often used in biology. “That’s a better description than grayscale,” she says. “And frankly that’s true for all of us. All of us, if we’re honest with ourselves, know that we have things that we’re great at and things that we’re not so great at.

An interesting example is found in an article by Dr. Jennifer Roback titled “The Political Economy of Segregation: The Case of Segregated Streetcars,” in the Journal of Economic History (1986). During the late 1800s, private streetcar companies in Augusta, Houston, Jacksonville, Mobile, Montgomery, and Memphis were not segregated, but by the early 1900s, they were. Why? City ordinances forced them to segregate black and white passengers. Numerous Jim Crow laws ruled the day throughout the South mandating segregation in public accommodations.

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.

I think this is going to trigger ‘Sputnik 2.0,’ a biomedical duel on progress between China and the United States,” said Carl June, a noted cancer researcher at the University of Pennsylvania who at the time was still struggling to get regulatory approval for a similar clinical trial.

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

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.

The dark side of our new information technology is not that it allows government repression of free speech but just the opposite: it permits anyone to spread, with little risk of being held accountable, any idea, conspiracy, lie, hatred, scam, or scheme, with the result that societies become less civil and governable.

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.

Zhang was at Harvard at the same time as Mark Zuckerberg, and it’s interesting to speculate on which of them will end up having the most impact on the world. It’s a proxy for the larger question, which future historians will answer, of whether the digital revolution or the life-science revolution will end up being the more important.

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.

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

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.

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.

[Walter Lippmann] applied the term “stereotype” to what he called “the pictures in our heads”—impressions that reflect subjective perceptions but stand in for objective reality. The word comes from the old typesetting process, in which a mold of a message is cast on a metal plate and replicated in the printing process again and again—mimicking the unchecked spread of ideas that we only presume to be true. Those ideas then dictate how we interpret what we see.

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.

He and his colleagues were finally able to get their trial underway and reported preliminary results in 2020. Their method, used in three late-stage cancer patients, was more sophisticated than the one used in China. They knocked out the PD-1 gene and also inserted into the T cells a gene that targeted the patients’ tumors. Although the patients were not cured, the trials showed that the technique was safe. Doudna and one of her postdoctoral students published an article in Science explaining the Penn results.

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.

Here’s to the crazy ones. The misfits. The rebels. The troublemakers. The round pegs in the square holes. The ones who see things differently. They’re not fond of rules. And they have no respect for the status quo. You can quote them, disagree with them, glorify or vilify them. About the only thing you can’t do is ignore them. Because they change things. They push the human race forward. And while some may see them as the crazy ones, we see genius. Because the people who are crazy enough to think they can change the world are the ones who do. —Steve Jobs, Apple’s “Think Different” ad, 1997

In-person meetings can produce ideas in ways that conference calls and Zoom meetings can’t. That had happened in Puerto Rico, and it did so again when the four researchers got together for the first time in Berkeley. There they were able to brainstorm a strategy for figuring out exactly what molecules were necessary for a CRISPR system to cut DNA. Physical meetings are especially useful when a project is in an early phase. “There’s nothing like sitting in a room with people and seeing their reactions to things and having a chance to bat around ideas face to face,” Doudna says. “That’s been a cornerstone to every collaboration that we’ve had, even those where we are conducting a lot of the work by electronic communication.

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.

As World War II was ending, the great engineer and public official Vannevar Bush argued that America’s innovation engine would require a three-way partnership of government, business, and academia. He was uniquely qualified to envision that triangle, because he had a foot in all three camps. He had been dean of engineering at MIT, a founder of Raytheon, and the chief government science administrator overseeing, among other projects, the building of the atom bomb.4 Bush’s recommendation was that government should not build big research labs of its own, as it had done with the atomic bomb project, but instead should fund research at universities and corporate labs. This government-business-university partnership produced the great innovations that propelled the U.S. economy in the postwar period, including transistors, microchips, computers, graphical user interfaces, GPS, lasers, the internet, and search engines.

His tone was odd, a mixture of restraint and subtle conviction. He did not make light of the question, nor did he attempt to couch his words in chivalrous courtesy. “He wants you, Marian.” She sighed. “So he says, when it is the lands he wants—” “No.” He cut her off. “DeLacey wants you.” She grimaced. “Because of what I have—” “Because of what you are.” She scowled at him. “What am I, then? Sir Hugh FitzWalter’s daughter, ward to King Richard—” “Marian.” His face was stripped free of the mask. What she saw now was blazing, naked emotion. “What you are is a woman he wants very badly in bed. And I think he would do anything to make sure he gets you there.” Her shocked denial was instantaneous. “Oh no—” “Oh yes.” She stared at him, undone by his conviction. This was nothing she had anticipated, this brutal, male truth. “I—don’t understand ...” And she didn’t, not really, not fully. She was only beginning to, and it frightened her very badly. His smile was wintry. “I am not the one to explain in elaborate detail why a man, any man, might feel as deLacey does.” Why not?” Robin sighed. “Helen of Troy.” It baffled her utterly. “What?” “Helen of Troy. Have you no knowledge of the classics?” “Of course I do; I was told all the stories. Helen was married to Menelaus of Sparta, until Paris of Troy cast his eyes upon her and fell in love with her at once. He stole her and took her to Troy. Agamemnon and Menelaus followed to get her back, and Troy was destroyed.” Robin nodded. “For the love of a beautiful woman.” “Yes, but—” She stopped. “Oh no--” “Yes.” “But—I’m not—” “Ask any man,” he said.

As time passed, I learned more and more about the culture that comes with beign an injured veteran. There are a lot of really wonderful people and organizations to help veterans returning from war. Right about the time I started to really move forward in my recovery, two women came by and introduced themselves. They explained that they raise money to help injured veterans with various needs. They asked if there was anything I or my family needed. I said, “No thank you, I’m all good.” But my sisters piped up and said, “He needs clothes. He doesn’t have anything.” The women smiled and said they’d be back. They came back with some sweatpants and a shirt and then announced that they were taking us to the mall. This would be my first time leaving the campus of Walter Reed, my first real trip out of the hospital. We were all excited. Leaving the hospital was a big step for me but my poor sisters had been cooped up much of the time with me in there as well. I was a little nervous, but I owed it to them to push aside my anxiety. We decided that the electric wheelchair would be too heavy and too much trouble to get in and out of the car, so Jennifer wheeled me down to the front door where the ladies were waiting in their car. With very little assistance, Jennifer was able to get me for that chair into the car and we were off to the mall. When we arrived, my sisters pulled the wheelchair out of the trunk and placed it next to the car door. They opened the door and Jennifer leaned down and with one swift motion lifted me up like a nearly weightless child and placed me in the chair. I laughed it off. “My sister’s strong. She’s really strong,” I boasted on her behalf. Sara, Katherine, and Jennifer were laughing the whole time because I didn’t realize how scrawny I was, how much weight I had lost. Jennifer could pick me up with no problem because I practically weighed nothing at all. But through the laughter, I felt a pang of guilt. I am the brother of three sisters. It was my job to protect and care for them. Yet here I was, barely able to take care of myself.