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Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.

they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.

All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

n vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

A large test of the Novavax COVID-19 vaccine's effectiveness, conducted in tens of thousands of volunteers in the United States and Mexico, is about to wrap up. Dr. Gregory Glenn, president of research and development for Novavax, told an audience at a recent webinar hosted by the International Society for Vaccines that "we anticipate filing for authorization in the U.K., U.S. and Europe in the third quarter."

To make the virus protein, Novavax uses giant vats of cells grown in the lab. But there's another way to make the protein: Get plants in a greenhouse to do it.

"Especially in elderly individuals in that study, it was not as immunogenic as it should be," says Dr. Paul Goepfert at the University of Alabama at Birmingham, who was one of the researchers involved in those early studies. He says the issue turned out to be an incorrect calculation of the dose of vaccine being delivered."So instead of giving 10 micrograms of the dose, they were actually giving one microgram," Goepfert says.

Early studies suggest Medicago's candidate vaccine does just that, and the company is confident enough in those findings that it's already begun a large study in people that could involve as many as 30,000 volunteers in 11 countries.

Another latecomer that's coming is the pharmaceutical giant Sanofi. Its protein subunit vaccine against the coronavirus is also grown in cells in the lab.

Late last year the company was getting ready to mount a large study of the vaccine's effectiveness when the early results in a smaller group of people showed it did not seem to be inducing the immune response that would be protective.

The plants used are related to the tobacco plant, and have been modified to contain the genetic instructions to make the viral protein.The plants do something very valuable — they make a lipid shell that surrounds a bunch of the viral proteins, with the proteins sticking out.

Goepfert says it'll be a good thing if all these vaccines make it to consumers. But that alone isn't going to solve the problem of getting people vaccinated.Why? "Because the vaccines that we have now are just beyond our wildest dreams kind of effective," he says. "And I'm living in a state right now where it just frustrates me how slow our vaccine uptake is."

This more diminutive antibody can access tinier pockets and crevices on spike proteins — the proteins that allow viruses like the novel coronavirus to break into host cells and infect us — that human antibodies cannot. That can make it more effective in neutralizing viruses.

The llama’s antibody still forms a Y, but its arms are much shorter because it doesn’t have any light-chain proteins.

Humans produce only one kind of antibody, made of two types of protein chains — heavy and light — that together form a Y shape. Heavy-chain proteins span the entire Y, while light-chain proteins touch only the Y’s arms. Llamas, on the other hand, produce two types of antibodies

They can be linked or fused with other antibodies, including human antibodies, and remain stable despite those manipulations.

Llamas’ antibodies are also easily manipulated

researchers looked to llamas — and, specifically, Winter — to find a smaller llama antibody “that could broadly neutralize many different types of coronavirus,” Dr. McLellan said.

They injected Winter with spike proteins from the virus that caused the 2002-03 SARS epidemic as well as MERS, then tested a sample of her blood. And while they couldn’t isolate a single llama antibody that worked against both viruses, they found two potent antibodies that each fought separately against MERS and SARS.

They immediately realized that the smaller llama antibodies “that could neutralize SARS would very likely also recognize the Covid-19 virus,” Dr. Saelens said.

It did, the researchers found, effectively inhibiting the coronavirus in cell cultures.

While the treatment’s protection would be immediate, its effects wouldn’t be permanent, lasting only a month or two without additional injections.

This proactive approach is at least several months away, but the researchers are moving toward clinical trials. Additional studies may also be needed to verify the safety of injecting a llama’s antibodies into human patients.

Experts think the UK or "Kent" strain emerged in September and may be up to 70% more transmissible or infectious, although latest research by Public Health England puts it between 30% and 50%.

The South Africa variant emerged in October, and it has more potentially important changes in the spike protein than the UK variant. It has one of the same mutations as the UK one, plus two more that scientists think may interfere more with vaccine effectiveness. One of these may help the virus evade parts of the immune system called antibodies.The UK has imposed a ban on direct flights from South Africa and restrictions on flights to the country.

The Brazil variant emerged in July and has three key mutations in the spike protein that make it similar to the South Africa one.

The current vaccines were designed around earlier variants, but scientists are confident that they should still work against the new ones, although perhaps not quite as well.

Vaccines train the body to attack several parts of the virus, however, not just these sections of the spike protein. Variants could emerge in the future that are more different again.Even in the worst case scenario, the vaccines could be redesigned and tweaked to be a better match - in a matter or weeks or months, if necessary,

As with flu vaccines, where a new shot is given each year to account for any changes in circulating flu viruses, something similar could happen for coronavirus.

There is currently no evidence to suggest that any of them cause more serious illness.Measures such as washing your hands, keeping your distance from other people and wearing a face covering will still help prevent infections, and because the new variants spread more easily it is important to be extra vigilant.

Scientists around the world are on the look-out and any new variants will be closely studied and monitored. Researchers at the Kenya Medical Research Institute say they are analysing a new variant that is different to the UK and South Africa strains, for example. The UK's vaccine development minster Nadhim Zahawi says measures have already been put in place to produce another wave of vaccines if needed.

The split suggests that Moderna’s vaccine doesn’t just block the virus in most cases, but also shields the people who do get sick from the worst outcomes of the disease. It also eases concerns that a vaccine for Covid-19 may make the disease worse, not better.

Pfizer’s outside board of experts analyzed 94 volunteers and estimated that the effectiveness of its vaccine was over 90 percent. They did not specify how many people who got sick had received the vaccine or the placebo.

The Pfizer and Moderna vaccines are similar not only because they use mRNA but also because they coax our cells to make the same viral protein, called spike. Other vaccines that don’t use mRNA also make the spike protein their target. The success of Moderna and Pfizer may bode well for them as well.

AstraZeneca and Johnson & Johnson are also conducting Phase 3 trials on adenoviruses that carry the spike protein gene. And other companies, including Novavax and Medicago, are running advanced trials on vaccines that deliver the spike protein itself, or pieces of it, to the body.

While scientists have investigated mRNA vaccines for years, no vaccine has yet been licensed as safe and effective to use in people.

It’s possible that the distribution of one or both vaccines will begin by the end of the year.

“This is not going to dig us out of what’s ahead this next month,” Natalie Dean, a biostatistician at the University of Florida, warned about Thanksgiving and the coming holiday season.

Public health experts also point out that there’s much we don’t know about how foods nourish us. Stripping out and recombining a food’s constituent parts or growing it in a petri dish is unlikely to replicate all the benefits.

High-tech food entrepreneurs, mostly white, well-educated young men who have spent much of their lives fueling up on fast food, say they want to provide more convenience and better taste.

Instead of centrifuging out plant proteins, “Why not just eat the vegetables?”

ike sex, food is fraught with emotional, psychological, social, cultural, gender and religious associations. Sharing a meal is how we establish and maintain relationships. It is how we celebrate and mourn. Some attach their identity to the food they eat. Others use it to exert or lose control. These unpredictable and perhaps intransigent views and expectations may be Food 2.0’s most daunting challenge.

the story of the golden calf also reminds us that without rules we quickly become slaves to our passions—and there’s nothing freeing about that.

And the story suggests something more: unchaperoned, and left to our own untutored judgment, we are quick to aim low and worship qualities that are beneath us—in this case, an artificial animal that brings out our own animal instincts in a completely unregulated way.

Similarly, in this book Professor Peterson doesn’t just propose his twelve rules, he tells stories, too, bringing to bear his knowledge of many fields as he illustrates and explains why the best rules do not ultimately restrict us but instead facilitate our goals and make for fuller, freer lives.

Peterson wasn’t really an “eccentric”; he had sufficient conventional chops, had been a Harvard professor, was a gentleman (as cowboys can be) though he did say damn and bloody a lot, in a rural 1950s sort of way. But everyone listened, with fascination on their faces, because he was in fact addressing questions of concern to everyone at the table.

unlike many academics who take the floor and hold it, if someone challenged or corrected him he really seemed to like it. He didn’t rear up and neigh. He’d say, in a kind of folksy way, “Yeah,” and bow his head involuntarily, wag it if he had overlooked something, laughing at himself for overgeneralizing. He appreciated being shown another side of an issue, and it became clear that thinking through a problem was, for him, a dialogic process.

for an egghead Peterson was extremely practical. His examples were filled with applications to everyday life: business management, how to make furniture (he made much of his own), designing a simple house, making a room beautiful (now an internet meme) or in another, specific case related to education, creating an online writing project that kept minority students from dropping out of school by getting them to do a kind of psychoanalytic exercise on themselves,

These Westerners were different: self-made, unentitled, hands on, neighbourly and less precious than many of their big-city peers, who increasingly spend their lives indoors, manipulating symbols on computers. This cowboy psychologist seemed to care about a thought only if it might, in some way, be helpful to someone.

I was drawn to him because here was a clinician who also had given himself a great books education, and who not only loved soulful Russian novels, philosophy and ancient mythology, but who also seemed to treat them as his most treasured inheritance. But he also did illuminating statistical research on personality and temperament, and had studied neuroscience. Though trained as a behaviourist, he was powerfully drawn to psychoanalysis with its focus on dreams, archetypes, the persistence of childhood conflicts in the adult, and the role of defences and rationalization in everyday life. He was also an outlier in being the only member of the research-oriented Department of Psychology at the University of Toronto who also kept a clinical practice.

Maps of Meaning, published nearly two decades ago, shows Jordan’s wide-ranging approach to understanding how human beings and the human brain deal with the archetypal situation that arises whenever we, in our daily lives, must face something we do not understand.

The brilliance of the book is in his demonstration of how rooted this situation is in evolution, our DNA, our brains and our most ancient stories. And he shows that these stories have survived because they still provide guidance in dealing with uncertainty, and the unavoidable unknown.

this is why many of the rules in this book, being based on Maps of Meaning, have an element of universality to them.

We are ambivalent about rules, even when we know they are good for us. If we are spirited souls, if we have character, rules seem restrictive, an affront to our sense of agency and our pride in working out our own lives. Why should we be judged according to another’s rule?

And he felt he had to understand the ideologies that drove totalitarian regimes to a variant of that same behaviour: killing their own citizens.

Ideologies are simple ideas, disguised as science or philosophy, that purport to explain the complexity of the world and offer remedies that will perfect it.

Ideologues are people who pretend they know how to “make the world a better place” before they’ve taken care of their own chaos within.

Ideologies are substitutes for true knowledge, and ideologues are always dangerous when they come to power, because a simple-minded I-know-it-all approach is no match for the complexity of existence.

To understand ideology, Jordan read extensively about not only the Soviet gulag, but also the Holocaust and the rise of Nazism. I had never before met a person, born Christian and of my generation, who was so utterly tormented by what happened in Europe to the Jews, and who had worked so hard to understand how it could have occurred.

I saw what now millions have seen online: a brilliant, often dazzling public speaker who was at his best riffing like a jazz artist; at times he resembled an ardent Prairie preacher (not in evangelizing, but in his passion, in his ability to tell stories that convey the life-stakes that go with believing or disbelieving various ideas). Then he’d just as easily switch to do a breathtakingly systematic summary of a series of scientific studies. He was a master at helping students become more reflective, and take themselves and their futures seriously. He taught them to respect many of the greatest books ever written. He gave vivid examples from clinical practice, was (appropriately) self-revealing, even of his own vulnerabilities, and made fascinating links between evolution, the brain and religious stories.

Above all, he alerted his students to topics rarely discussed in university, such as the simple fact that all the ancients, from Buddha to the biblical authors, knew what every slightly worn-out adult knows, that life is suffering.

chances are, if you or someone you love is not suffering now, they will be within five years, unless you are freakishly lucky. Rearing kids is hard, work is hard, aging, sickness and death are hard, and Jordan emphasized that doing all that totally on your own, without the benefit of a loving relationship, or wisdom, or the psychological insights of the greatest psychologists, only makes it harder.

focused on triumphant heroes. In all these triumph stories, the hero has to go into the unknown, into an unexplored territory, and deal with a new great challenge and take great risks. In the process, something of himself has to die, or be given up, so he can be reborn and meet the challenge. This requires courage, something rarely discussed in a psychology class or textbook.

Jordan

views of his first YouTube statements quickly numbered in the hundreds of thousands. But people have kept listening because what he is saying meets a deep and unarticulated need. And that is because alongside our wish to be free of rules, we all search for structure.

the first generation to have been so thoroughly taught two seemingly contradictory ideas about morality, simultaneously—at their schools, colleges and universities, by many in my own generation. This contradiction has left them at times disoriented and uncertain, without guidance and, more tragically, deprived of riches they don’t even know exist.

morality and the rules associated with it are just a matter of personal opinion or happenstance, “relative to” or “related to” a particular framework, such as one’s ethnicity, one’s upbringing, or the culture or historical…

The first idea or teaching is that morality is relative, at best a…

So, the decent thing to do—once it becomes apparent how arbitrary your, and your society’s, “moral values” are—is to show tolerance for people who think differently, and…

for many people one of the worst character flaws a person can have is to be “judgmental.”* And, since we don’t know right from wrong, or what is good, just about the most inappropriate thing an adult can…

That emphasis on tolerance is so paramount that for many people one of the worst character flaws a person can have is to be “judgmental.”* And, since we don’t know right from wrong, or what is good, just about the most inappropriate thing an…

And so a generation has been raised untutored in what was once called, aptly, “practical wisdom,” which guided previous generations. Millennials, often told they have received the finest education available anywhere, have actually…

professors, chose to devalue thousands of years of human knowledge about how to acquire virtue, dismissing it as passé, “…

They were so successful at it that the very word “virtue” sounds out of date, and someone using it appears…

The study of virtue is not quite the same as the study of morals (right and wrong, good and evil). Aristotle defined the virtues simply as the ways of behaving that are most conducive to happiness in life. Vice was…

Cultivating judgment about the difference between virtue and vice is the beginning of wisdom, something…

By contrast, our modern relativism begins by asserting that making judgments about how to live is impossible, because there is no real good, and no…

Thus relativism’s closest approximation to “virtue” is “tolerance.” Only tolerance will provide social cohesion between different groups, and save us from harming each other. On Facebook and other forms of social media, therefore, you signal your so-called…

Intolerance of others’ views (no matter how ignorant or incoherent they may be) is not simply wrong; in a world where there is no right or wrong, it is worse: it is a sign you are…

But it turns out that many people cannot tolerate the vacuum—the chaos—which is inherent in life, but made worse by this moral relativism; they cannot live without a moral compass,…

So, right alongside relativism, we find the spread of nihilism and despair, and also the opposite of moral relativism: the blind certainty offered by ideologies…

Dr. Norman Doidge, MD, is the author of The Brain That Changes Itself

so we arrive at the second teaching that millennials have been bombarded with. They sign up for a humanities course, to study the greatest books ever written. But they’re not assigned the books; instead they are given…

(But the idea that we can easily separate facts and values was and remains naive; to some extent, one’s values determine what one will pay…

For the ancients, the discovery that different people have different ideas about how, practically, to live, did not paralyze them; it deepened their understanding of humanity and led to some of the most satisfying conversations human beings have ever had, about how life might be lived.

Modern moral relativism has many sources. As we in the West learned more history, we understood that different epochs had different moral codes. As we travelled the seas and explored the globe, we learned of far-flung tribes on different continents whose different moral codes made sense relative to, or within the framework of, their societies. Science played a role, too, by attacking the religious view of the world, and thus undermining the religious grounds for ethics and rules. Materialist social science implied that we could divide the world into facts (which all could observe, and were objective and “real”) and values (…

it seems that all human beings are, by some kind of biological endowment, so ineradicably concerned with morality that we create a structure of laws and rules wherever we are. The idea that human life can be free of moral concerns is a fantasy.

given that we are moral animals, what must be the effect of our simplistic modern relativism upon us? It means we are hobbling ourselves by pretending to be something we are not. It is a mask, but a strange one, for it mostly deceives the one who wears it.

Far better to integrate the best of what we are now learning with the books human beings saw fit to preserve over millennia, and with the stories that have survived, against all odds, time’s tendency to obliterate.

these really are rules. And the foremost rule is that you must take responsibility for your own life. Period.

Jordan’s message that each individual has ultimate responsibility to bear; that if one wants to live a full life, one first sets one’s own house in order; and only then can one sensibly aim to take on bigger responsibilities.

if it’s uncertain that our ideals are attainable, why do we bother reaching in the first place? Because if you don’t reach for them, it is certain you will never feel that your life has meaning.

And perhaps because, as unfamiliar and strange as it sounds, in the deepest part of our psyche, we all want to be judged.

Instead of despairing about these differences in moral codes, Aristotle argued that though specific rules, laws and customs differed from place to place, what does not differ is that in all places human beings, by their nature, have a proclivity to make rules, laws and customs.

Freud never argued (as do some who want all culture to become one huge group therapy session) that one can live one’s entire life without ever making judgments, or without morality. In fact, his point in Civilization and Its Discontents is that civilization only arises when some restraining rules and morality are in place.

Aleksandr Solzhenitsyn, the great documenter of the slave-labour-camp horrors of the latter, once wrote that the “pitiful ideology” holding that “human beings are created for happiness” was an ideology “done in by the first blow of the work assigner’s cudgel.”1 In a crisis, the inevitable suffering that life entails can rapidly make a mockery of the idea that happiness is the proper pursuit of the individual. On the radio show, I suggested, instead, that a deeper meaning was required. I noted that the nature of such meaning was constantly re-presented in the great stories of the past, and that it had more to do with developing character in the face of suffering than with happiness.

I proposed in Maps of Meaning that the great myths and religious stories of the past, particularly those derived from an earlier, oral tradition, were moral in their intent, rather than descriptive. Thus, they did not concern themselves with what the world was, as a scientist might have it, but with how a human being should act.

I suggested that our ancestors portrayed the world as a stage—a drama—instead of a place of objects. I described how I had come

to believe that the constituent elements of the world as drama were order and chaos, and not material things.

Order is where the people around you act according to well-understood social norms, and remain predictable and cooperative. It’s the world of social structure, explored territory, and familiarity. The state of Order is typically portrayed, symbolically—imaginatively—as masculine.

Chaos, by contrast, is where—or when—something unexpected happens.

As the antithesis of symbolically masculine order, it’s presented imaginatively as feminine. It’s the new and unpredictable suddenly emerging in the midst of the commonplace familiar. It’s Creation and Destruction,

Order is the white, masculine serpent; Chaos, its black, feminine counterpart. The black dot in the white—and the white in the black—indicate the possibility of transformation: just when things seem secure, the unknown can loom, unexpectedly and large. Conversely, just when everything seems lost, new order can emerge from catastrophe and chaos.

For the Taoists, meaning is to be found on the border between the ever-entwined pair. To walk that border is to stay on the path of life, the divine Way. And that’s much better than happiness.

trying to address a perplexing problem: the reason or reasons for the nuclear standoff of the Cold War. I couldn’t understand how belief systems could be so important to people that they were willing to risk the destruction of the world to protect them. I came to realize that shared belief systems made people intelligible to one another—and that the systems weren’t just about belief.

People who live by the same code are rendered mutually predictable to one another. They act in keeping with each other’s expectations and desires. They can cooperate. They can even compete peacefully, because everyone knows what to expect from everyone else.

Shared beliefs simplify the world, as well, because people who know what to expect from one another can act together to tame the world. There is perhaps nothing more important than the maintenance of this organization—this simplification. If it’s threatened, the great ship of state rocks.

It isn’t precisely that people will fight for what they believe. They will fight, instead, to maintain the match between what they believe, what they expect, and what they desire. They will fight to maintain the match between what they expect and how everyone is acting. It is precisely the maintenance of that match that enables everyone

There’s more to it, too. A shared cultural system stabilizes human interaction, but is also a system of value—a hierarchy of value, where some things are given priority and importance and others are not. In the absence of such a system of value, people simply cannot act. In fact, they can’t even perceive, because both action and perception require a goal, and a valid goal is, by necessity, something valued.

We experience much of our positive emotion in relation to goals. We are not happy, technically speaking, unless we see ourselves progressing—and the very idea of progression implies value.

Worse yet is the fact that the meaning of life without positive value is not simply neutral. Because we are vulnerable and mortal, pain and anxiety are an integral part of human existence. We must have something to set against the suffering that is intrinsic to Being.*2 We must have the meaning inherent in a profound system of value or the horror of existence rapidly becomes paramount. Then, nihilism beckons, with its hopelessness and despair.

So: no value, no meaning. Between value systems, however, there is the possibility of conflict. We are thus eternally caught between the most diamantine rock and the hardest of places:

loss of group-centred belief renders life chaotic, miserable, intolerable; presence of group-centred belief makes conflict with other groups inevitable.

In the West, we have been withdrawing from our tradition-, religion- and even nation-centred cultures, partly to decrease the danger of group conflict. But we are increasingly falling prey to the desperation of meaninglessness, and that is no improvement at all.

While writing Maps of Meaning, I was (also) driven by the realization that we can no longer afford conflict—certainly not on the scale of the world conflagrations of the twentieth century.

I came to a more complete, personal realization of what the great stories of the past continually insist upon: the centre is occupied by the individual.

It is possible to transcend slavish adherence to the group and its doctrines and, simultaneously, to avoid the pitfalls of its opposite extreme, nihilism. It is possible, instead, to find sufficient meaning in individual consciousness and experience.

How could the world be freed from the terrible dilemma of conflict, on the one hand, and psychological and social dissolution, on the other? The answer was this: through the elevation and development of the individual, and through the willingness of everyone to shoulder the burden of Being and to take the heroic path. We must each adopt as much responsibility as possible for individual life, society and the world.

We must each tell the truth and repair what is in disrepair and break down and recreate what is old and outdated. It is in this manner that we can and must reduce the suffering that poisons the world. It’s asking a lot. It’s asking for everything.

the alternative—the horror of authoritarian belief, the chaos of the collapsed state, the tragic catastrophe of the unbridled natural world, the existential angst and weakness of the purposeless

individual—is clearly worse.

a title: 12 Rules for Life: An Antidote to Chaos. Why did that one rise up above all others? First and foremost, because of its simplicity. It indicates clearly that people need ordering principles, and that chaos otherwise beckons.

We require rules, standards, values—alone and together. We’re pack animals, beasts of burden. We must bear a load, to justify our miserable existence. We require routine and tradition. That’s order. Order can become excessive, and that’s not good, but chaos can swamp us, so we drown—and that is also not good. We need to stay on the straight and narrow path.

I hope that these rules and their accompanying essays will help people understand what they already know: that the soul of the individual eternally hungers for the heroism of genuine Being, and that the willingness to take on that responsibility is identical to the decision to live a meaningful life.

RULE 1   STAND UP STRAIGHT WITH YOUR SHOULDERS BACK

Because territory matters, and because the best locales are always in short supply, territory-seeking among animals produces conflict. Conflict, in turn, produces another problem: how to win or lose without the disagreeing parties incurring too great a cost.

It’s winner-take-all in the lobster world, just as it is in human societies, where the top 1 percent have as much loot as the bottom 50 percent11—and where the richest eighty-five people have as much as the bottom three and a half billion.

This principle is sometimes known as Price’s law, after Derek J. de Solla Price,13 the researcher who discovered its application in science in 1963. It can be modelled using an approximately L-shaped graph, with number of people on the vertical axis, and productivity or resources on the horizontal.

Instead of undertaking the computationally difficult task of identifying the best man, the females outsource the problem to the machine-like calculations of the dominance hierarchy. They let the males fight it out and peel their paramours from the top.

The dominant male, with his upright and confident posture, not only gets the prime real estate and easiest access to the best hunting grounds. He also gets all the girls. It is exponentially more worthwhile to be successful, if you are a lobster, and male.

dominance hierarchies have been an essentially permanent feature of the environment to which all complex life has adapted. A third of a billion years ago, brains and nervous systems were comparatively simple. Nonetheless, they already had the structure and neurochemistry necessary to process information about status and society. The importance of this fact can hardly be overstated.

evolution works, in large part, through variation and natural selection. Variation exists for many reasons, including gene-shuffling (to put it simply) and random mutation. Individuals vary within a species for such reasons. Nature chooses from among them, across time. That theory, as stated, appears to account for the continual alteration of life-forms over the eons.

But there’s an additional question lurking under the surface: what exactly is the “nature” in “natural selection”? What exactly is “the environment” to which animals adapt?

Nature “selects.” The idea of selects contains implicitly nested within it the idea of fitness. It is “fitness” that is “selected.” Fitness, roughly speaking, is the probability that a given organism will leave offspring (will propagate its genes through time). The “fit” in “fitness” is therefore the matching of organismal attribute to environmental demand.

But nature, the selecting agent, is not a static selector—not in any simple sense.

As the environment supporting a species transforms and changes, the features that make a given individual successful in surviving and reproducing also transform and change. Thus, the theory of natural selection does not posit creatures matching themselves ever more precisely to a template specified by the world. It is more that creatures are in a dance with nature, albeit one that is deadly.

Nature is not simply dynamic, either. Some things change quickly, but they are nested within other things that change less quickly (music

It’s chaos, within order, within chaos, within higher order. The order that is most real is the order that is most unchanging—and that is not necessarily the order that is most easily seen. The leaf, when perceived, might blind the observer to the tree. The tree can blind him to the forest.

It is also a mistake to conceptualize nature romantically.

Unfortunately, “the environment” is also elephantiasis and guinea worms (don’t ask), anopheles mosquitoes and malaria, starvation-level droughts, AIDS and the Black Plague.

It is because of the existence of such things, of course, that we attempt to modify our surroundings, protecting our children, building cities and transportation systems and growing food and generating power.

this brings us to a third erroneous concept: that nature is something strictly segregated from the cultural constructs that have emerged within it.

It does not matter whether that feature is physical and biological, or social and cultural. All that matters, from a Darwinian perspective, is permanence—and the dominance hierarchy, however social or cultural it might appear, has been around for some half a billion years.

The dominance hierarchy is not capitalism. It’s not communism, either, for that matter. It’s not the military-industrial complex. It’s not the patriarchy—that disposable, malleable, arbitrary cultural artefact. It’s not even a human creation; not in the most profound sense. It is instead a near-eternal aspect of the environment, and much of what is blamed on these more ephemeral manifestations is a consequence of its unchanging existence.

We were struggling for position before we had skin, or hands, or lungs, or bones. There is little more natural than culture. Dominance hierarchies are older than trees.

The part of our brain that keeps track of our position in the dominance hierarchy is therefore exceptionally ancient and fundamental.17 It is a master control system, modulating our perceptions, values, emotions, thoughts and actions. It powerfully affects every aspect of our Being, conscious and unconscious alike.

The ancient part of your brain specialized for assessing dominance watches how you are treated by other people. On that evidence, it renders a determination of your value and assigns you a status. If you are judged by your peers as of little worth, the counter restricts serotonin availability. That makes you much more physically and psychologically reactive to any circumstance or event that might produce emotion, particularly if it is negative. You need that reactivity. Emergencies are common at the bottom, and you must be ready to survive. Unfortunately, that physical hyper-response, that constant alertness, burns up a lot of precious energy and physical resources.

It will leave you far more likely to live, or die, carelessly, for a rare opportunity at pleasure, when it manifests itself. The physical demands of emergency preparedness will wear you down in every way.21

If you have a high status, on the other hand, the counter’s cold, pre-reptilian mechanics assume that your niche is secure, productive

You can delay gratification, without forgoing it forever. You can afford to be a reliable and thoughtful citizen.

Sometimes, however, the counter mechanism can go wrong. Erratic habits of sleeping and eating can interfere with its function. Uncertainty can throw it for a loop. The body, with its various parts,

needs

to function like a well-rehearsed orchestra. Every system must play its role properly, and at exactly the right time, or noise and chaos ensue. It is for this reason that routine is so necessary. The acts of life we repeat every day need to be automatized. They must be turned into stable and reliable habits, so they lose their complexity and gain predictability and simplicity.

It is for such reasons that I always ask my clinical clients first about sleep. Do they wake up in the morning at approximately the time the typical person wakes up, and at the same time every day?

The next thing I ask about is breakfast. I counsel my clients to eat a fat and protein-heavy breakfast as soon as possible after they awaken (no simple carbohydrates, no sugars,

I have had many clients whose anxiety was reduced to subclinical levels merely because they started to sleep on a predictable schedule and eat breakfast.

Other bad habits can also interfere with the counter’s accuracy.

There are many systems of interaction between brain, body and social world that can get caught in positive feedback loops. Depressed people, for example, can start feeling useless and burdensome, as well as grief-stricken and pained. This makes them withdraw from contact with friends and family. Then the withdrawal makes them more lonesome and isolated, and more likely to feel useless and burdensome. Then they withdraw more. In this manner, depression spirals and amplifies.

If someone is badly hurt at some point in life—traumatized—the dominance counter can transform in a manner that makes additional hurt more rather than less likely. This often happens in the case of people, now adults, who were viciously bullied during childhood or adolescence. They become anxious and easily upset. They shield themselves with a defensive crouch, and avoid the direct eye contact interpretable as a dominance challenge.

With their capacity for aggression strait-jacketed within a too-narrow morality, those who are only or merely compassionate and self-sacrificing (and naïve and exploitable) cannot call forth the genuinely righteous and appropriately self-protective anger necessary to defend themselves. If you can bite, you generally don’t have to. When skillfully integrated, the ability to respond with aggression and violence decreases rather than increases the probability that actual aggression will become necessary.

Naive, harmless people usually guide their perceptions and actions with a few simple axioms: people are basically good; no one really wants to hurt anyone else; the threat (and, certainly, the use) of force, physical or otherwise, is wrong. These axioms collapse, or worse, in the presence of

individuals who are genuinely malevolent.27

I have had clients who were terrified into literally years of daily hysterical convulsions by the sheer look of malevolence on their attackers’ faces. Such individuals typically come from hyper-sheltered families, where nothing

terrible is allowed to exist, and everything is fairyland wonderful (or else).

When the wakening occurs—when once-naïve people recognize in themselves the seeds of evil and monstrosity, and see themselves as dangerous (at least potentially)— their fear decreases. They develop more self-respect. Then, perhaps, they begin to resist oppression. They see that they have the ability to withstand, because they are terrible too. They see they can and must stand up, because they begin to understand how genuinely monstrous they will become, otherwise,

There is very little difference between the capacity for mayhem and destruction, integrated, and strength of character. This is one of the most difficult lessons of life.

even if you came by your poor posture honestly—even if you were unpopular or bullied at home or in grade school28—it’s not necessarily appropriate now. Circumstances change. If you slump around, with the same bearing that characterizes a defeated lobster, people will assign you a lower status, and the old counter that you share with crustaceans, sitting at the very base of your brain, will assign you a low dominance number.

the other, far more optimistic lesson of Price’s law and the Pareto distribution: those who start to have will probably get more.

Some of these upwardly moving loops can occur in your own private, subjective space.

If you are asked to move the muscles one by one into a position that looks happy, you will report feeling happier. Emotion is partly bodily expression, and can be amplified (or dampened) by that expression.29

To stand up straight with your shoulders back is to accept the terrible responsibility of life, with eyes wide open.

It means deciding to voluntarily transform the chaos of potential into the realities of habitable order. It means adopting the burden of self-conscious vulnerability, and accepting the end of the unconscious paradise of childhood, where finitude and mortality are only dimly comprehended. It means willingly undertaking the sacrifices necessary to generate a productive and meaningful reality (it means acting to please God, in the ancient language).

So, attend carefully to your posture. Quit drooping and hunching around. Speak your mind. Put your desires forward, as if you had a right to them—at least the same right as others. Walk tall and gaze forthrightly ahead. Dare to be dangerous. Encourage the serotonin to flow plentifully through the neural pathways desperate for its calming influence.

Thus emboldened, you will embark on the voyage of your life, let your light shine, so to speak, on the heavenly hill, and pursue your rightful destiny. Then the meaning of your life may be sufficient to keep the corrupting influence of mortal despair at bay. Then you may be able to accept the terrible burden of the World, and find joy.

RULE 2   TREAT YOURSELF LIKE SOMEONE YOU ARE RESPONSIBLE FOR HELPING

People are better at filling and properly administering prescription medication to their pets than to themselves. That

It is difficult to conclude anything from this set of facts except that people appear to love their dogs, cats, ferrets and birds (and maybe even their lizards) more than themselves. How horrible is that? How much shame must exist, for something like that to be true? What could it be about people that makes them prefer their pets to themselves?

To understand Genesis 1, the Priestly story, with its insistence on speech as the fundamental creative force, it is first necessary to review a few fundamental, ancient assumptions (these are markedly different in type and intent from the assumptions of science, which are, historically speaking, quite novel).

those who existed during the distant time in which the foundational epics of our culture emerged were much more concerned with the actions that dictated survival (and with interpreting the world in a manner commensurate with that goal) than with anything approximating what we now understand as objective truth.

Before the dawn of the scientific worldview, reality was construed differently. Being was understood as a place of action, not a place of things.31 It was understood as something more akin to story or drama. That story or drama was lived, subjective experience, as it manifested itself moment to moment in the consciousness of every living person.

subjective pain. That’s something so real no argument can stand against it. Everyone acts as if their pain is real—ultimately, finally real. Pain matters, more than matter matters. It is for this reason, I believe, that so many of the world’s traditions regard the suffering attendant upon existence as the irreducible truth of Being.

In any case, that which we subjectively experience can be likened much more to a novel or a movie than to a scientific description of physical reality.

The Domain, Not of Matter, but of What Matters

the world of experience has primal constituents, as well. These are the necessary elements whose interactions define drama and fiction. One of these is chaos. Another is order. The third (as there are three) is the process that mediates between the two, which appears identical to what modern people call consciousness.

Chaos is the domain of ignorance itself. It’s unexplored territory. Chaos is what extends, eternally and without limit, beyond the boundaries of all states, all ideas, and all disciplines. It’s the foreigner, the stranger, the member of another gang, the rustle in the bushes in the night-time,

It is, in short, all those things and situations we neither know nor understand.

Chaos is also the formless potential from which the God of Genesis 1 called forth order using language at the beginning of time. It’s the same potential from which we, made in that Image, call forth the novel and ever-changing moments of our lives. And Chaos is freedom, dreadful freedom, too.

Order, by contrast, is explored territory. That’s the hundreds-of-millions-of-years-old hierarchy of place, position and authority. That’s the structure of society. It’s the structure provided by biology, too—particularly insofar as you are adapted, as you are, to the structure of society. Order is tribe, religion, hearth, home and country.

Order is the public façade we’re called upon to wear, the politeness of a gathering of civilized strangers, and the thin ice on which we all skate. Order is the place where the behavior of the world matches our expectations and our desires; the place where all things turn out the way we want them to.

But order is sometimes tyranny and stultification, as well, when the demand for certainty and uniformity and purity becomes too one-sided.

In order, we’re able to think about things in the long term. There, things work, and we’re stable, calm and competent. We seldom leave places we

understand—geographical or conceptual—for that reason, and we certainly do not like it when we are compelled to or when it happens accidentally.

When the same person betrays you, sells you out, you move from the daytime world of clarity and light to the dark underworld of chaos, confusion and despair. That’s the same move you make, and the same place you visit, when the company you work for starts to fail and your job is placed in doubt.

Before the Twin Towers fell—that was order. Chaos manifested itself afterward. Everyone felt it. The very air became uncertain. What exactly was it that fell? Wrong question. What exactly remained standing? That was the issue at hand.

Chaos is the deep ocean bottom to which Pinocchio voyaged to rescue his father from Monstro, whale and fire-breathing dragon. That journey into darkness and rescue is the most difficult thing a puppet must do, if he wants to be real; if he wants to extract himself from the temptations of deceit and acting and victimization and impulsive pleasure and totalitarian subjugation; if he wants to take his place as a genuine Being in the world.

Chaos is the new place and time that emerges when tragedy strikes suddenly, or malevolence reveals its paralyzing visage, even in the confines of your own home. Something unexpected or undesired can always make its appearance, when a plan is being laid out, regardless of how familiar the circumstances.

Our brains respond instantly when chaos appears, with simple, hyper-fast circuits maintained from the ancient days, when our ancestors dwelled in trees, and snakes struck in a flash.32 After that nigh-instantaneous, deeply reflexive bodily response comes the later-evolving, more complex but slower responses of emotions—and, after that, comes thinking, of the higher order, which can extend over seconds, minutes or years. All that response is instinctive, in some sense—but the faster the response, the more instinctive.

Things or objects are part of the objective world. They’re inanimate; spiritless. They’re dead. This is not true of chaos and order. Those are perceived, experienced and understood (to the degree that they are understood at all) as personalities—and that is just as true of the perceptions, experiences and understanding of modern people as their ancient forebears. It’s just that moderners don’t notice.

Perception of things as entities with personality also occurs before perception of things as things. This is particularly true of the action of others,34 living others, but we also see the non-living “objective world” as animated, with purpose and intent.

This is because of the operation of what psychologists have called “the hyperactive agency detector” within us.35 We evolved, over millennia, within intensely social circumstances. This means that the most significant elements of our environment of origin were personalities, not things, objects or situations.

The personalities we have evolved to perceive have been around, in predictable form, and in typical, hierarchical configurations, forever, for all intents and purposes. They have been…

the category of “parent” and/or “child” has been around for 200 million years. That’s longer than birds have existed. That’s longer than flowers have grown. It’s not a billion years, but it’s still a very long time. It’s plenty long enough for male and female and parent and child to serve as vital and fundamental parts of the environment to which we have adapted. This means that male and female and parent and child are…

Our brains are deeply social. Other creatures (particularly, other humans) were crucially important to us as we lived, mated and evolved. Those creatures were…

From a Darwinian perspective, nature—reality itself; the environment, itself—is what selects. The environment cannot be defined in any more fundamental manner. It is not mere inert matter. Reality itself is whatever we contend with when we are striving to survive and reproduce. A…

as our brain capacity increased and we developed curiosity to spare, we became increasingly aware of and curious about the nature of the world—what we eventually conceptualized as the objective…

“outside” is not merely unexplored physical territory. Outside is outside of what we currently understand—and understanding is dealing with and coping with…

when we first began to perceive the unknown, chaotic, non-animal world, we used categories that had originally evolved to represent the pre-human animal social world. Our minds are far older than mere…

Our most…

category—as old, in some sense, as the sexual act itself—appears to be that of sex, male and female. We appear to have taken that primordial knowledge of structured, creative opposition and…

Order, the known, appears symbolically associated with masculinity (as illustrated in the aforementioned yang of the Taoist yin-yang symbol). This is perhaps because the primary…

Chaos—the unknown—is symbolically associated with the feminine. This is partly because all the things we have come to know were born, originally, of the unknown, just as all beings we encounter were born of mothers. Chaos is mater, origin, source, mother; materia, the substance from which all things are made.

In its positive guise, chaos is possibility itself, the source of ideas, the mysterious realm of gestation and birth. As a negative force, it’s the impenetrable darkness of a cave and the accident by the side of the road.

Chaos, the eternal feminine, is also the crushing force of sexual selection.

Most men do not meet female human standards. It is for this reason that women on dating sites rate 85 percent of men as below average in attractiveness.40

Women’s proclivity to say no, more than any other force, has shaped our evolution into the creative, industrious, upright, large-brained (competitive, aggressive, domineering) creatures that we are.42 It is Nature as Woman who says, “Well, bucko, you’re good enough for a friend, but my experience of you so far has not indicated the suitability of your genetic material for continued propagation.”

Many things begin to fall into place when you begin to consciously understand the world in this manner. It’s as if the knowledge of your body and soul falls into alignment with the knowledge of your intellect.

And there’s more: such knowledge is proscriptive, as well as descriptive. This is the kind of knowing what that helps you know how. This is the kind of is from which you can derive an ought. The Taoist juxtaposition of yin and yang, for example, doesn’t simply portray chaos and order as the fundamental elements of Being—it also tells you how to act.

The Way, the Taoist path of life, is represented by (or exists on) the border between the twin serpents. The Way is the path of proper Being. It’s the same Way as that referred to by Christ in John 14:6: I am the way, and the truth and the life. The same idea is expressed in Matthew 7:14: Because strait is the gate, and narrow is the way, which leadeth unto life, and few there be that find it.

We eternally inhabit order, surrounded by chaos. We eternally occupy known territory, surrounded by the unknown. We experience meaningful engagement when we mediate appropriately between them. We are adapted, in the deepest Darwinian sense, not to the world of objects, but to the meta-realities of order and chaos, yang and yin. Chaos and order make up the eternal, transcendent environment of the living.

To straddle that fundamental duality is to be balanced: to have one foot firmly planted in order and security, and the other in chaos, possibility, growth and adventure.

Chaos and order are fundamental elements because every lived situation (even every conceivable lived situation) is made up of both.

you need to place one foot in what you have mastered and understood and the other in what you are currently exploring and mastering. Then you have positioned yourself where the terror of existence is under control and you are secure, but where you are also alert and engaged. That is where there is something new to master and some way that you can be improved. That is where meaning is to be found.

The serpent in Eden therefore means the same thing as the black dot in the yin side of the Taoist yin/yang symbol of totality—that is, the possibility of the unknown and revolutionary suddenly manifesting itself where everything appears calm.

The outside, chaos, always sneaks into the inside, because nothing can be completely walled off from the rest of reality. So even the ultimate in safe spaces inevitably harbours a snake.

We have seen the enemy, after all, and he is us. The snake inhabits each of our souls.

The worst of all possible snakes is the eternal human proclivity for evil. The worst of all possible snakes is psychological, spiritual, personal, internal. No walls, however tall, will keep that out. Even if the fortress were thick enough, in principle, to keep everything bad whatsoever outside, it would immediately appear again within.

I have learned that these old stories contain nothing superfluous. Anything accidental—anything that does not serve the plot—has long been forgotten in the telling. As the Russian playwright Anton Chekhov advised, “If there is a rifle hanging on the wall in act one, it must be fired in the next act. Otherwise it has no

business being there.”50

Eve immediately shares the fruit with Adam. That makes him self-conscious. Little has changed. Women have been making men self-conscious since the beginning of time. They do this primarily by rejecting them—but they also do it by shaming them, if men do not take responsibility. Since women bear the primary burden of reproduction, it’s no wonder. It is very hard to see how it could be otherwise. But the capacity of women to shame men and render them self-conscious is still a primal force of nature.

What does it mean to know yourself naked

Naked means vulnerable and easily damaged. Naked means subject to judgment for beauty and health. Naked means unprotected and unarmed in the jungle of nature and man. This is why Adam and Eve became ashamed, immediately after their eyes were opened. They could see—and what they first saw was themselves.

In their vulnerability, now fully realized, they felt unworthy to stand before God.

Beauty shames the ugly. Strength shames the weak. Death shames the living—and the Ideal shames us all.

He tells the woman that she will now bring forth children in sorrow, and desire an unworthy, sometimes resentful man, who will in consequence lord her biological fate over her, permanently. What might this mean? It could just mean that God is a patriarchal tyrant, as politically motivated interpretations of the ancient story insist. I think it’s merely descriptive.

women pay a high price for pregnancy and child-rearing, particularly in the early stages, and that one of the inevitable consequences is increased dependence upon the sometimes unreliable and always problematic good graces of men.

then God banishes the first man and the first woman from Paradise, out of infancy, out of the unconscious animal world, into the horrors of history itself. And then He puts cherubim and a flaming sword at the gate of Eden, just to stop them from eating the Fruit of the Tree of Life.

Perhaps Heaven is something you must build, and immortality something you must earn.

so we return to our original query: Why would someone buy prescription medication for his dog, and then so carefully administer it, when he would not do the same for himself?

Why should anyone take care of anything as naked, ugly, ashamed, frightened, worthless, cowardly, resentful, defensive and accusatory as a descendant of Adam? Even if that thing, that being, is himself?

We know how we are naked, and how that nakedness can be exploited—and that means we know how others are naked, and how they can be exploited. We can terrify other people, consciously. We can hurt and humiliate them for faults we understand only too well. We can torture them—literally—slowly, artfully and terribly. That’s far more than predation. That’s a qualitative shift in understanding. That’s a cataclysm as large as the development of self-consciousness itself. That’s the entry of the knowledge of Good and Evil into the world.

Only man could conceive of the rack, the iron maiden and the thumbscrew. Only man will inflict suffering for the sake of suffering. That is the best definition of evil I have been able to formulate.

with this realization we have well-nigh full legitimization of the idea, very unpopular in modern intellectual circles, of Original Sin.

Human beings have a great capacity for wrongdoing. It’s an attribute that is unique in the world of life. We can and do make things worse, voluntarily, with full knowledge of what we are doing (as well as accidentally, and carelessly, and in a manner that is willfully blind). Given that terrible capacity, that proclivity for malevolent actions, is it any wonder we have a hard time taking care of ourselves, or others—or even that we doubt the value of the entire human enterprise?

The juxtaposition of Genesis 1 with Genesis 2 & 3 (the latter two chapters outlining the fall of man, describing why our lot is so tragedy-ridden and ethically torturous) produces a narrative sequence almost unbearable in its profundity. The moral of Genesis 1 is that Being brought into existence through true speech is Good.

The original Man and Woman, existing in unbroken unity with their Creator, did not appear conscious (and certainly not self-conscious). Their eyes were not open. But, in their perfection, they were also less, not more, than their post-Fall counterparts. Their goodness was something bestowed, rather than deserved or earned.

Maybe, even in some cosmic sense (assuming that consciousness itself is a phenomenon of cosmic significance), free choice matters.

here’s a proposition: perhaps it is not simply the emergence of self-consciousness and the rise of our moral knowledge of Death and the Fall that besets us and makes us doubt our own worth. Perhaps it is instead our unwillingness—reflected in Adam’s shamed hiding—to walk with God, despite our fragility and propensity for evil.

The entire Bible is structured so that everything after the Fall—the history of Israel, the prophets, the coming of Christ—is presented as a remedy for that Fall, a way out of evil. The beginning of conscious history, the rise of the state and all its pathologies of pride and rigidity, the emergence of great moral figures who try to set things right, culminating in the Messiah Himself—that is all part of humanity’s attempt, God willing, to set itself right. And what would that mean?

And this is an amazing thing: the answer is already implicit in Genesis 1: to embody the Image of God—to speak out of chaos the Being that is Good—but to do so consciously, of our own free choice.

Back is the way forward—as T. S. Eliot so rightly insisted

We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know the place for the first time.

If we wish to take care of ourselves properly, we would have to respect ourselves—but we don’t, because we are—not least in our own eyes—fallen creatures.

If we lived in Truth; if we spoke the Truth—then we could walk with God once again, and respect ourselves, and others, and the world. Then we might treat ourselves like people we cared for.

We might strive to set the world straight. We might orient it toward Heaven, where we would want people we cared for to dwell, instead of Hell, where our resentment and hatred would eternally sentence everyone.

Then, the primary moral issue confronting society was control of violent, impulsive selfishness and the mindless greed and brutality that accompanies it.

It is easy to believe that people are arrogant, and egotistical, and always looking out for themselves. The cynicism that makes that opinion a universal truism is widespread and fashionable.

But such an orientation to the world is not at all characteristic of many people. They have the opposite problem: they shoulder intolerable burdens of self-disgust, self-contempt, shame and self-consciousness. Thus, instead of narcissistically inflating their own importance, they don’t value themselves at all, and they don’t take care of themselves with attention and skill.

Christ’s archetypal death exists as an example of how to accept finitude, betrayal and tyranny heroically—how to walk with God despite the tragedy of self-conscious knowledge—and not as a directive to victimize ourselves in the service of others.

To sacrifice ourselves to God (to the highest good, if you like) does not mean to suffer silently and willingly when some person or organization demands more from us, consistently, than is offered in return. That means we are supporting tyranny, and allowing ourselves to be treated like slaves.

I learned two very important lessons from Carl Jung, the famous Swiss depth psychologist, about “doing unto others as you would have them do unto you” or “loving your neighbour as yourself.”

The first lesson was that neither of these statements has anything to do with being nice. The second was that both are equations, rather than injunctions.

If I am someone’s friend, family member, or lover, then I am morally obliged to bargain as hard on my own behalf as they are on theirs.

there is little difference between standing up and speaking for yourself, when you are being bullied or otherwise tormented and enslaved, and standing up and speaking for someone else.

you do not simply belong to yourself. You are not simply your own possession to torture and mistreat. This is partly because your Being is inexorably tied up with that of others, and your mistreatment of yourself can have catastrophic consequences for others.

metaphorically speaking, there is also this: you have a spark of the divine in you, which belongs not to you, but to God. We are, after all—according to Genesis—made in His image.

We can make order from chaos—and vice versa—in our way, with our words. So, we may not exactly be God, but we’re not exactly nothing, either.

In my own periods of darkness, in the underworld of the soul, I find myself frequently overcome and amazed by the ability of people to befriend each other, to love their intimate partners and parents and children, and to do what they must do to keep the machinery of the world running.

It is this sympathy that should be the proper medicament for self-conscious self-contempt, which has its justification, but is only half the full and proper story. Hatred for self and mankind must be balanced with gratefulness for tradition and the state and astonishment at what normal, everyday people accomplish

You have some vital role to play in the unfolding destiny of the world. You are, therefore, morally obliged to take care of yourself.

To treat yourself as if you were someone you are responsible for helping is, instead, to consider what would be truly good for you. This is not “what you want.” It is also not “what would make you happy.”

You must help a child become a virtuous, responsible, awake being, capable of full reciprocity—able to take care of himself and others, and to thrive while doing so. Why would you think it acceptable to do anything less for yourself?

You need to know who you are, so that you understand your armament and bolster yourself in respect to your limitations. You need to know where you are going, so that you can limit the extent of chaos in your life, restructure order, and bring the divine force of Hope to bear on the world.

You need to determine how to act toward yourself so that you are most likely to become and to stay a good person.

Don’t underestimate the power of vision and direction. These are irresistible forces, able to transform what might appear to be unconquerable obstacles into traversable pathways and expanding opportunities.

Once having understood Hell, researched it, so to speak—particularly your

own individual Hell—you could decide against going there or creating that.

You could, in fact, devote your life to this. That would give you a Meaning, with a capital M. That would justify your miserable existence.

That would atone for your sinful nature, and replace your shame and self-consciousness with the natural pride and forthright confidence of someone who has learned once again to walk with God in the Garden.

RULE 3   MAKE FRIENDS WITH PEOPLE WHO WANT THE BEST FOR YOU

It would be more romantic, I suppose, to suggest that we would have all jumped at the chance for something more productive, bored out of our skulls as we were. But it’s not true. We were all too prematurely cynical and world-weary and leery of responsibility to stick to the debating clubs and Air Cadets and school sports that the adults around us tried to organize. Doing anything wasn’t cool.

When you move, everything is up in the air, at least for a while. It’s stressful, but in the chaos there are new possibilities. People, including you, can’t hem you in with their old notions. You get shaken out of your ruts. You can make new, better ruts, with people aiming at better things. I thought this was just a natural development. I thought that every person who moved would have—and want—the same phoenix-like experience.

What was it that made Chris and Carl and Ed unable (or, worse, perhaps, unwilling) to move or to change their friendships and improve the circumstances of their lives? Was it inevitable—a consequence of their own limitations, nascent illnesses and traumas of the past?

Why did he—like his cousin, like my other friends—continually choose people who, and places that, were not good for him?

perhaps, they don’t want the trouble of better. Freud called this a “repetition compulsion.” He thought of it as an unconscious drive to repeat the horrors of the past

People create their worlds with the tools they have directly at hand. Faulty tools produce faulty results. Repeated use of the same faulty tools produces the same faulty results.

It is in this manner that those who fail to learn from the past doom themselves to repeat it. It’s partly fate. It’s partly inability. It’s partly…unwillingness to learn? Refusal to learn? Motivated refusal to learn?

People choose friends who aren’t good for them for other reasons, too. Sometimes it’s because they want to rescue someone.

it is not easy to distinguish between someone truly wanting and needing help and someone who is merely exploiting a willing helper. The distinction is difficult even for the person who is wanting and needing and possibly exploiting.

When it’s not just naïveté, the attempt to rescue someone is often fuelled by vanity and narcissism.

But Christ himself, you might object, befriended tax-collectors and prostitutes. How dare I cast aspersions on the motives of those who are trying to help? But Christ was the archetypal perfect man. And you’re you.

How do you know that your attempts to pull someone up won’t instead bring them—or you—further down?

The same thing happens when well-meaning counsellors place a delinquent teen among comparatively civilized peers. The delinquency spreads, not the stability.65 Down is a lot easier than up.

maybe you’re saving someone because you want to convince yourself that the strength of your character is more than just a side effect of your luck and birthplace. Or maybe it’s because it’s easier to look virtuous when standing alongside someone utterly irresponsible.

Or maybe you have no plan, genuine or otherwise, to rescue anybody. You’re associating with people who are bad for you not because it’s better for anyone, but because it’s easier.

You know it. Your friends know it. You’re all bound by an implicit contract—one aimed at nihilism, and failure, and suffering of the stupidest sort.

Before you help someone, you should find out why that person is in trouble. You shouldn’t merely assume that he or she is a noble victim of unjust circumstances and exploitation. It’s the most unlikely explanation, not the most probable.

Besides, if you buy the story that everything terrible just happened on its own, with no personal responsibility on the part of the victim, you deny that person all agency in the past (and, by implication, in the present and future, as well).

It is far more likely that a given individual has just decided to reject the path upward, because of its difficulty. Perhaps that should even be your default assumption, when faced with such a situation.

failure is easy to understand. No explanation for its existence is required. In the same manner, fear, hatred, addiction, promiscuity, betrayal and deception require no explanation. It’s not the existence of vice, or the indulgence in it, that requires explanation. Vice is easy.

Failure is easy, too. It’s easier not to shoulder a burden. It’s easier not to think, and not to do, and not to care. It’s easier to put off until tomorrow what needs to be done today,

Success: that’s the mystery. Virtue: that’s what’s inexplicable. To fail, you merely have to cultivate a few bad habits. You just have to bide your time. And once someone has spent enough time cultivating bad habits and biding their time, they are much diminished.

I am not saying that there is no hope of redemption. But it is much harder to extract someone

from a chasm than to lift him from a ditch. And some chasms are very deep. And there’s not much left of the body at the bottom.

Carl Rogers, the famous humanistic psychologist, believed it was impossible to start a therapeutic relationship if the person seeking help did not want to improve.67 Rogers believed it was impossible to convince someone to change for the better. The

none of this is a justification for abandoning those in real need to pursue your narrow, blind ambition, in case it has to be said.

Here’s something to consider: If you have a friend whose friendship you wouldn’t recommend to your sister, or your father, or your son, why would you have such a friend for yourself?

You are not morally obliged to support someone who is making the world a worse place. Quite the opposite. You should choose people who want things to be better, not worse. It’s a good thing, not a selfish thing, to choose people who are good for you.

It is for this reason that every good example is a fateful challenge, and every hero, a judge. Michelangelo’s great perfect marble David cries out to its observer: “You could be more than you are.”

Don’t think that it is easier to surround yourself with good healthy people than with bad unhealthy people. It’s not. A good, healthy person is an ideal. It requires strength and daring to stand up near such a person.

RULE 4   COMPARE YOURSELF TO WHO YOU WERE YESTERDAY, NOT TO WHO SOMEONE ELSE IS TODAY

IT WAS EASIER FOR PEOPLE to be good at something when more of us lived in small, rural communities. Someone could be homecoming queen. Someone else could be spelling-bee champ, math whiz or basketball star. There were only one or two mechanics and a couple of teachers. In each of their domains, these local heroes had the opportunity to enjoy the serotonin-fuelled confidence of the victor.

Our hierarchies of accomplishment are now dizzyingly vertical.

No matter how good you are at something, or how you rank your accomplishments, there is someone out there who makes you look incompetent.

We are not equal in ability or outcome, and never will be. A very small number of people produce very much of everything.

People are unhappy at the bottom. They get sick there, and remain unknown and unloved. They waste their lives there. They die there. In consequence, the self-denigrating voice in the minds of people weaves a devastating tale. Life is a zero-sum game. Worthlessness is the default condition.

It is for such reasons that a whole generation of social psychologists recommended “positive illusions” as the only reliable route to mental health.69 Their credo? Let a lie be your umbrella. A more dismal, wretched, pessimistic philosophy can hardly be imagined:

Here is an alternative approach (and one that requires no illusions). If the cards are always stacked against you, perhaps the game you are playing is somehow rigged (perhaps by you, unbeknownst to yourself). If the internal voice makes you doubt the value of your endeavours—or your life, or life itself—perhaps you should stop listening.

There will always be people better than you—that’s a cliché of nihilism, like the phrase, In a million years, who’s going to know the difference? The proper response to that statement is not, Well, then, everything is meaningless. It’s, Any idiot can choose a frame of time within which nothing matters.

Standards of better or worse are not illusory or unnecessary. If you hadn’t decided that what you are doing right now was better than the alternatives, you wouldn’t be doing it. The idea of a value-free choice is a contradiction in terms. Value judgments are a precondition for action.

Furthermore, every activity, once chosen, comes with its own internal standards of accomplishment. If something can be done at all, it can be done better or worse. To do anything at all is therefore to play a game with a defined and valued end, which can always be reached more or less efficiently and elegantly.

We might start by considering the all-too-black-and-white words themselves: “success” or “failure.” You are either a success, a comprehensive, singular, over-all good thing, or its opposite, a failure, a comprehensive, singular, irredeemably bad thing.

There are vital degrees and gradations of value obliterated by this binary system, and the consequences are not good.

there is not just one game at which to succeed or fail. There are many games and, more specifically, many good games—

if changing games does not work, you can invent a new one. I

and athletic pursuits. You might consider judging your success across all the games you play.

When we are very young we are neither individual nor informed. We have not had the time nor gained the wisdom to develop our own standards. In consequence, we must compare ourselves to others, because standards are necessary.

As we mature we become, by contrast, increasingly individual and unique. The conditions of our lives become more and more personal and less and less comparable with those of others. Symbolically speaking, this means we must leave the house ruled by our father, and confront the chaos of our individual Being.

We must then rediscover the values of our culture—veiled from us by our ignorance, hidden in the dusty treasure-trove of the past—rescue them, and integrate them into our own lives. This is what gives existence its full and necessary meaning.

What is it that you actually love? What is it that you genuinely want? Before you can articulate your own standards of value, you must see yourself as a stranger—and then you must get to know yourself. What

Dare to be truthful. Dare to articulate yourself, and express (or at least become aware of) what would really justify your life.

Consult your resentment. It’s a revelatory emotion, for all its pathology. It’s part of an evil triad: arrogance, deceit, and resentment. Nothing causes more harm than this underworld Trinity. But resentment always means one of two things. Either the resentful person is immature, in which case he or she should shut up, quit whining, and get on with it, or there is tyranny afoot—in which case the person subjugated has a moral obligation to speak up.

Be cautious when you’re comparing yourself to others. You’re a singular being, once you’re an adult. You have your own particular, specific problems—financial, intimate, psychological, and otherwise.

Those are embedded in the unique broader context of your existence. Your career or job works for you in a personal manner, or it does not, and it does so in a unique interplay with the other specifics of your life.

We must see, but to see, we must aim, so we are always aiming. Our minds are built on the hunting-and-gathering platforms of our bodies. To hunt is to specify a target, track it, and throw at it.

We live within a framework that defines the present as eternally lacking and the future as eternally better. If we did not see things this way, we would not act at all. We wouldn’t even be able to see, because to see we must focus, and to focus we must pick one thing above all else on which to focus.

The disadvantage to all this foresight and creativity is chronic unease and discomfort. Because we always contrast what is with what could be, we have to aim at what could be.

The present is eternally flawed. But where you start might not be as important as the direction you are heading. Perhaps happiness is always to be found in the journey uphill, and not in the fleeting sense of satisfaction awaiting at the next peak.

Called upon properly, the internal critic will suggest something to set in order, which you could set in order, which you would set in order—voluntarily, without resentment, even with pleasure.

“Excuse me,” you might say to yourself, without irony or sarcasm. “I’m trying to reduce some of the unnecessary suffering around here. I could use some help.” Keep the derision at bay. “I’m wondering if there is anything that you would be willing to do? I’d be very grateful for your service.” Ask honestly and with humility. That’s no simple matter.

The COVID-19 vaccine that Vaxart is developing is similar to Johnson & Johnson's in that it uses a harmless virus to deliver instructions to cells to make proteins that will prompt an immune response to the coronavirus.

But instead of putting the delivery virus in a liquid, Vaxart freeze-dries it, turning into a powder that can be formulated into a pill that can be stored at room temperature.

Another vaccine that could be self-administered is a nasal spray vaccine.

By contrast, an intranasal vaccine induces two kinds of immunity, Lund says. You still get the systemic protection, she says, "but you will also get immunity directly at the site where you put that vaccine." That makes it harder for the coronavirus to sneak in through the nose.

One way of doing that is to modify something called the spike protein, which prompts the immune response to the coronavirus.

Another possible improvement is the way the spike protein is packaged for delivery in a vaccine.

The immune system of the person receiving the vaccine will react as if it has encountered the real virus when actually it has encountered a harmless mimic. That's the whole trick behind vaccines — getting the body's immune system ready if the real thing comes along.

He says there's some evidence that starting with one kind of vaccine and then switching to another may give better immunity than a single vaccine could do on its own.

In the end, among the most important qualities a new vaccine should have are that it should be able to be made and modified quickly in response to variants, as well as be distributed quickly.

Lurie says it's virtually certain the world will face new and dangerous microbes that will necessitate vaccines that are "safe and effective, fast, easy to use, preferably a single dose."

That way, she says, "when the next one comes, we're much closer to the starting gate than we even were for this one."

Gray is the first person in the United States to be successfully treated for a genetic disorder with the help of CRISPR, a revolutionary gene-editing technique that makes it much easier to make very precise changes in DNA.

The treatment boosted levels of a protein in the study subjects' blood known as fetal hemoglobin. The scientists believe that protein is compensating for defective adult hemoglobin that their bodies produce because of a genetic defect they were born with.

The New England Journal of Medicine published online this month the first peer-reviewed research paper from the study, focusing on Gray and the first beta thalassemia patient who was treated.

"I'm very excited to see these results," says Jennifer Doudna of the University of California, Berkeley, who shared the Nobel Prize this year for her role in the development of CRISPR

But the results from the first 10 patients "represent an important scientific and medical milestone," says Dr. David Altshuler, Vertex's chief scientific officer.

All the patients appear to have responded well. The only side effects have been from the intense chemotherapy they've had to undergo before getting the billions of edited cells infused into their bodies.

showed the gene-edited cells had persisted the full year — a promising indication that the approach has permanently altered her DNA and could last a lifetime.

"This gives us great confidence that this can be a one-time therapy that can be a cure for life," says Samarth Kulkarni, the CEO of CRISPR Therapeutics.

Gray has also been able to wean off the powerful pain medications she'd needed most of her life.

haven't needed the regular blood transfusions that had been required to keep them alive.

For the treatment, doctors remove stem cells from the patients' bone marrow and use CRISPR to edit a gene in the cells, activating the production of fetal hemoglobin. That protein is produced by fetuses in the womb but usually shuts off shortly after birth. The patients then undergo a grueling round of chemotherapy to destroy most of their bone marrow to make room for the gene-edited cells, billions of which are then infused into their bodies.

Doctors have already started trying to use CRISPR to treat cancer and to restore vision to people blinded by a genetic disease. They hope to try it for many other diseases as well, including heart disease and AIDS.

"This is really a life-changer for me," she says. "It's magnificent."

"If you want to make a new influenza vaccine using the traditional methods, you have to isolate the virus, learn how to grow it, learn how to inactivate it, and purify it. That takes months. With RNA, you only need the sequence,"

"When the Chinese released the sequence of the SARS-CoV-2 virus, we started the process of making RNA the next day. A couple weeks later, we were injecting animals with the vaccine."

Weissman's lab is now working on a universal coronavirus vaccine that would protect against Covid-19, SARS, MERS, coronavirus that cause the common cold -- and future strains.

"We started working on a pan-coronavirus vaccine last spring," Weissman said. "There have been three coronavirus epidemics in the past 20 years. There are going to be more."

Another obvious use for mRNA technology is to fight cancer. The human body fights off cancer every day, and using mRNA could help it do so even better.

Different tumor cell types have various, recognizable structures on the outside that the immune system can recognize. "You can imagine being able to inject someone with an mRNA that encodes an antibody that specifically targets that receptor," McLellan said.

"We identify mutations found on a patient's cancer cells," the company says on its website. Computer algorithms predict the 20 most common mutations. "We then create a vaccine that encodes for each of these mutations and load them onto a single mRNA molecule," Moderna says.

BioNtech has been working with academic researchers to use mRNA to treat mice genetically engineered to develop a disease similar to multiple sclerosis -- an autoimmune disease that starts when the immune system mistakenly attacks the myelin, a fatty covering of the nerve cells.In the mice, the treatment appeared to help stop the attack, while keeping the rest of the immune system intact.

The idea behind gene therapy is to replace a defective gene with one that works properly.

The mRNA approach promises to send instructions for making the healthy version of a protein, and Weissman sees special promise in treating sickle cell disease, in particular.

"It's gene therapy without the half a million dollar price tag," he added. "It should be just an IV injection and that's it."

"The idea there is if you are immune to tick saliva proteins, when the tick bites you, the body produces inflammation and the tick falls off," Weissman said.