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But only a handful of cancers—of the breast, lung, colon and cervix—have screening tests recommended by the U.S. Preventive Services Task Force

Many companies are developing blood tests that can detect cancer signals before symptoms occur, and Grail’s is the most advanced. A study found it can identify more than 50 types of cancer 52% of the time and the 12 deadliest cancers in Stages I through III 68% of the time.

There’s a hitch. The test costs $949 and isn’t covered by Medicare or most private insurance.

The trouble is that this cancer is almost never caught early. There’s no routine screening for it, and symptoms don’t develop until it is advanced. Mr. Royse, 64, had no idea he was sick until he took a blood test called Galleri, produced by the Menlo Park, Calif., startup Grail. He had surgery and chemotherapy and is now cancer-free.

Mr. Royse visited Grail’s website, which referred him to a telemedicine provider who ordered a test. Another telemedicine doctor walked him through his results, which showed a cancer signal likely emanating from the pancreas, gallbladder, stomach or esophagus.

An MRI revealed a suspicious mass on his pancreas, which a biopsy confirmed was cancerous. Mr. Royse had three months of chemotherapy, surgery and another three months of chemotherapy, which ended last February. Because pancreatic cancer often recurs, he gets CT and MRI scans every three months. In addition, he has signed up for startup Natera’s Signatera customized blood test, which checks DNA specific to the patient’s cancer and can signal its return before signs are visible on the scans

Grail’s test likewise looks for DNA shed by cancer cells, which is tagged by molecules called methyl groups that are specific to a cancer’s origin. Grail uses genetic sequencing and machine learning to recognize links between DNA methyl groups and particular cancers

The test “is based on how much DNA is being shed by tumor,” Grail’s president, Josh Ofman, says. “Some tumors shed a lot of DNA. Some shed almost none.

ut slow-growing tumors typically aren’t shedding a lot of DNA.” That reduces the probability that Grail’s test will identify indolent cancers that pose no immediate danger.

Grail’s test has a roughly 0.5% false-positive rate, meaning 1 in 200 patients who don’t have cancer will get a positive signal

Its positive predictive value is 43%, so that of every 100 patients with a positive signal, 43 actually have cancer

the legislation’s price tag could reduce political support. According to one private company’s estimate, the test could cost the government $39 billion to $145 billion over a decade. Mr. Goldman counters that analysts usually overestimate the costs and underestimate the benefits of medical interventions.

Because Grail uses machine learning to detect DNA-methylation cancer linkages, the Grail test’s accuracy should improve as more tests and patient data are collected

regulators may balk at approving the test, and insurers at covering it, until it becomes cheaper and more reliable.

How would the FDA weigh the risk that a false positive on a test like Grail’s could require invasive follow-up testing against the dire but hard-to-quantify risk that a deadly cancer wouldn’t be caught until it’s much harder to treat? It’s unclear.

some experts urge the FDA to require large randomized controlled trials before approving blood cancer tests. “Multicancer screening would entail tremendous costs and potentially substantial harms,” H. Gilbert Welch and Tanujit Dey of Brigham and Women’s Hospital wrote

Dr. Welch and Mr. Dey also suggested that companies should be required to prove their tests reduce overall mortality, even though the FDA doesn’t require drugmakers to prove their products reduce deaths or extend life. Clinical trials for the mRNA Covid vaccines didn’t show they reduced deaths.

One alternative is to rely on real-world studies, which Grail is already doing. One study of patients 50 and older without signs of cancer showed that the test doubled the number of cancers detected.

One recurring problem he has seen: “Epidemiologists are always getting cancer wrong,” he says. “Epidemiologists a decade ago said U.S. overtreats cancers. Well, no, the EU undertreats cancer.”

A 2012 study that he co-authored found that the higher U.S. spending on cancer care relative to Europe between 1983 and 1999 resulted in significantly higher survival rates for American patients than for those in Europe

By his study’s calculation, U.S. spending on cancer treatments during that period resulted in $556 billion in net benefits owing to reduced mortality.

He expects Galleri and other multicancer early-detection tests to reduce deaths and produce public-health and economic benefits that exceed their monetary costs

Expanding access to multicancer early-detection tests could also help solve the chicken-and-egg problem of drug development. Because few patients are diagnosed at early stages of some cancers, it’s hard to develop treatments for them

the positive predictive value for some recommended cancer screenings is far lower. Fewer than 1 in 10 women with an abnormal finding on a mammogram are diagnosed with breast cancer.

Mr. Royse makes the same point with personal force. “I would be dead right now if not for multicancer early-detection testing,” Mr. Royse told an FDA advisory committee last fall. “The longer the FDA waits, the more people are going to die. It’s that simple.”

"To imagine that we will find a simple solution to this doesn't do service to the true complexity of the problem," explains Siddhartha Mukherjee

Overall, Archer points out, the language around cancer in general desperately lags behind the current scientific understanding of the disease — and that has implications for cancer patients and their families.

The psychological effects of cancer are in fact so widespread that the American College of Surgeons recently required all accredited cancer centers to screen for the level of cancer distress in new patients and then offer psychosocial care to match patients' needs.

From testing a drop of blood, researchers could determine the type, whether it had spread into other parts of the body and where the tumor was in the body.

The researchers note that some cancers were easier to detect, such as intestinal cancers, while brain cancers were harder to find (the rate of reliable detection dropped by 11%). The reason for the latter, the researchers suspect, is because of the blood-brain barrier, which reduces accuracy. Still, this detection method is better than anything they'd tried previously.

having such a minimally invasive procedure capable of early detection could mean stopping an enormous amount of potentially fatal cancer diagnoses — many of which are discovered too late to be stopped.

Beyond Crispr and Covid vaccines, there are countless potential applications of mRNA tools for other diseases; a new frontier for immunotherapy and next-generation cancer treatment; a whole new world of weight-loss drugs; new insights and drug-development pathways to chase with the help of machine learning; and vaccines heralded as game-changing for some of the world’s most intractable infectious diseases.

“You cannot imagine what you’re going to see over the next 30 years. The pace of advancement is in an exponential phase right now.”

the mRNA sequence of the first shot was designed in a weekend, and the finished vaccines arrived within months, an accelerated timeline that saved perhaps several million American lives and tens of millions worldwide — numbers that are probably larger than the cumulative global death toll of the disease.

As the first of their kind to be approved by the Food and Drug Administration, they brought with them a very long list of potential future mRNA applications: H.I.V., tuberculosis, Zika, respiratory syncytial virus (R.S.V.), cancers of various and brutal kinds.

A Nobel laureate, Doudna is known primarily for Crispr, the gene-editing Swiss Army knife that has been called “a word processor” for the human genome and that she herself describes as “a technology that literally enables the rewriting of the code of life.”

A couple of decades later, it looks like a golden age for new treatments. New trials of breast-cancer drugs have led to survival rates hailed in The Times as “unheard-of,” and a new treatment for postoperative lung-cancer patients may cut mortality by more than half. Another new treatment, for rectal cancer, turned every single member of a small group of cases into cancer-free survivors.

many of their back stories do rhyme, often stretching back several decades through the time of the Human Genome Project, which was completed in 2003, and the near-concurrent near-doubling of the National Institutes of Health’s budget, which helped unleash what Donna Shalala, President Bill Clinton’s secretary for health and human services, last year called “a golden age of biomedical research.”

Ozempic and Wegovy have already changed the landscape for obesity in America

although the very first person to receive Crispr gene therapy in the United States received it just four years ago, for sickle-cell disease, it has since been rolled out for testing on congenital blindness, heart disease, diabetes, cancer and H.I.V

all told, some 400 million people worldwide are afflicted by one or more diseases arising from single-gene mutations that would be theoretically simple for Crispr to fix.

in theory, inserting a kind of genetic prophylaxis against Alzheimer’s or dementia.

In January, a much-talked-about paper in Nature suggested that the rate of what the authors called disruptive scientific breakthroughs was steadily declining over time — that, partly as a result of dysfunctional academic pressures, researchers are more narrowly specialized than in the past and often tinkering around the margins of well-understood science.

when it comes to the arrival of new vaccines and treatments, the opposite story seems more true: whole branches of research, cultivated across decades, finally bearing real fruit

Does this mean we are riding an exponential curve upward toward radical life extension and the total elimination of cancer? No. The advances are more piecemeal and scattered than tha

“The biology and the science that we need is already in place,” he says. “The question now to me is: Can we actually do it?”

Sometimes these things just take a little time.

The chemicals were traced back to an out-of-use chemical manufacturing facility, last held by the Olin Chemical Corporation in 1980, though now in the hands of the Environmental Protection Agency, which has a proposed a $48 million clean-up plan.

"Wilmington’s public drinking water is no longer contaminated with NDMA or TCE and currently poses no known risk to public health,"

Fox, who lived in Birmingham, Alabama, claimed she used Baby Powder and Shower to Shower for feminine hygiene for more than 35 years before being diagnosed three years ago with ovarian cancer. She died in October at age 62.

Jurors found Johnson & Johnson liable for fraud, negligence and conspiracy, the family's lawyers said. Deliberations lasted four hours, following a three-week trial.

Trials in several other talc lawsuits have been set for later this year, according to Danielle Mason, who also represented Fox's family at trial.

In October 2013, a federal jury in Sioux Falls, South Dakota found that plaintiff Deane Berg's use of Johnson & Johnson's body powder products was a factor in her developing ovarian cancer. Nevertheless, it awarded no damages, court records show.

"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."

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.

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.

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.

"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.

Greene quickly shot back on Twitter, asserting that "the real cancer for the Republican Party is weak Republicans who only know how to lose gracefully. This is why we are losing our country."

Greene has faced backlash since a CNN KFile report last week found that she had repeatedly indicated support for executing prominent Democratic politicians in 2018 and 2019 before being elected to Congress.

The freshman congresswoman has a track record of incendiary rhetoric, including past comments using Islamophobic and anti-Semitic tropes, as well as ties to the baseless and thoroughly debunked QAnon conspiracy theory.

Greene now faces potentially serious consequences in light of her prior comments, with House Democrats moving expeditiously to remove her from her committee assignments.

CNN previously reported that McCarthy is slated to meet with Greene this week, as many House Republicans have been silent about her newly resurfaced incendiary comments.

McConnell's short but pointed rebuke Monday night came the same day the Kentucky Republican waded publicly into another controversy threatening party unity.

In a separate statement to CNN, he expressed support for Republican Rep. Liz Cheney's vote to impeach President Donald Trump as some Trump loyalists seek to remove her from leadership.

Senate Republican leader Mitch McConnell on Monday issued a tacit rebuke of controversial Rep. Marjorie Taylor Greene, slamming the Georgia Republican's "loony lies and conspiracy theories" as a "cancer" for the party.

At the end of November 2021, the caseload was six million. More than 300,000 cases have been waiting for more than a year for planned care. A decade ago, there were fewer than 500.

Macmillan Cancer Support, a charity, estimates that some 50,000 people across Britain have not yet been diagnosed with some form of cancer that should have been caught earlier, in a direct result of the pandemic’s hindering screenings and referrals. The number of women being diagnosed with Stage 4 breast cancer — which means that the disease is advanced and very dangerous — has jumped by 48 percent in recent months.

PFASs are “a poster child” for what’s wrong with chemical regulation in America, says John Peterson Myers, chief scientist of Environmental Health Science

PFASs are just about indestructible, so, for eons to come, they will poison our blood, our household dust, our water and the breast milk our babies drink.

Warnings of health risks from PFASs go back half a century and are growing more ominous. In May, more than 200 scientists released a Madrid Statement warning of PFAS’s severe health risks. It was published in Environmental Health Perspectives, a peer-reviewed journal backed by the National Institutes of Health.

Arlene Blum is a chemist whose warnings about carcinogens have proved prophetic. In recent years, she has waged an increasingly successful campaign against modern flame-retardant chemicals because of evidence that they also cause cancer, but she told me that PFASs “are even a bigger problem than flame retardants.”

Americans expect that chemicals used in consumer products have been tested for safety. Not so. The vast majority of the 80,000 chemicals available for sale in the United States have never been tested for effects on our health.

Any testing is being done on all of us. We’re the guinea pigs.

Congress may finally pass new legislation regulating toxic chemicals, but it’s so weak a bill that the chemical industry has embraced it. The Senate version is better than nothing, but, astonishingly, it provides for assessing high-priority chemicals at a rate of about only five a year, and it’s not clear that the House will go that far.

Yes, of countless toxicants suspected of increasing the risk of cancer, obesity, epigenetic damage and reproductive problems, the United States would commit to testing five each year. And that would actually be progress.

For safety reasons, Europe and Canada already restrict hundreds of chemicals routinely used in the United States. Perhaps the danger of tainted brands and lost sales abroad — not the risk to Americans — will motivate American companies to adopt overseas limits.

Scientists are already taking precautions and weighing trade-offs in their personal lives. R. Thomas Zoeller, a biology professor at the University of Massachusetts, Amherst, says he now avoids buying nonstick pans. Rainer Lohmann, an oceanographer at the University of Rhode Island, told me that he is replacing carpets in his house with wood floors in part to reduce PFASs.

Simona Balan, a senior scientist at the Green Science Policy Institute, avoids microwave popcorn and stain-resistant furniture.

Dr. Blum says she avoids buying certain nonstick products and waterproof products

Some brands, including Levi’s, Benetton and Victoria’s Secret, are pledging to avoid PFASs. Evaluations of the safety of products are available free at the GoodGuide and Skin Deep websites.

. The Supreme Court, though it ruled 5-4 in the 2008 Heller case that an individual has the right to own a gun unconnected to service in a militia, has left the door open to sensible regulation.“Like most rights, the Second Amendment right is not unlimited,” the court wrote in that case. “It is not a right to keep and carry any weapon whatsoever in any manner whatsoever for whatever purpose.”

The disgraced former cable pundit Bill O’Reilly said all the recent carnage is “the price of freedom.” But it’s not the price of freedom in Canada or Japan or England. It’s the price of freedom only in the United States, where mass killings have surged. In every other free country, sanity has prevailed.

It’s a no-brainer to pass a law designed to keep people from turning their AKs into machine guns with the so-called bump stocks. But it was also a no-brainer to restrict people on terrorism watch lists from buying guns, as was proposed after the Orlando slaughter of 49 people last year. It failed.

I had other doubts, too. It seemed hubristic, or worse, to make multitrillion-dollar policy bets based on computer models trying to forecast climate patterns decades into the future. Climate activists kept promoting policies based on technologies that were either far from mature (solar energy) or sometimes actively harmful (biofuels).

Expensive efforts to curb greenhouse gas emissions in Europe and North America seemed particularly fruitless when China, India and other developing countries weren’t about to curb their own appetite for fossil fuels

just how fast is Greenland’s ice melting right now? Is this an emergency for our time, or is it a problem for the future?

His pitch was simple: The coastline we have taken for granted for thousands of years of human history changed rapidly in the past on account of natural forces — and would soon be changing rapidly and disastrously by man-made ones. A trip to Greenland, which holds one-eighth of the world’s ice on land (most of the rest is in Antarctica) would show me just how drastic those changes have been. Would I join him?

Greenland is about the size of Alaska and California combined and, except at its coasts, is covered by ice that in places is nearly two miles thick. Even that’s only a fraction of the ice in Antarctica, which is more than six times as large

Greenland’s ice also poses a nearer-term risk because it is melting faster. If all its ice were to melt, global sea levels would rise by some 24 feet. That would be more than enough to inundate hundreds of coastal cities in scores of nations, from Jakarta and Bangkok to Copenhagen and Amsterdam to Miami and New Orleans.

There was also a millenarian fervor that bothered me about climate activism, with its apocalyptic imagery (the Statue of Liberty underwater) and threats of doom unless we were willing to live far more frugally.

“We haven’t had a good positive mass balance year since the late 1990s,” he told me in a follow-on email when I asked him to explain the data for me. The losses can vary sharply by year. The annualized average over the past 30 years, he added, is 170 gigatons per year. That’s the equivalent of about 5,400 tons of ice loss per second. That “suggests that Greenland ice loss has been tracking the I.P.P.C. worse-case, highest-carbon-emission scenario.

The data shows unmistakably that Greenland’s ice is not in balance. It is losing far more than it is gaining.

scientists have been drilling ice-core samples from Greenland for decades, giving them a very good idea of climatic changes stretching back thousands of years. Better yet, a pair of satellites that detect anomalies in Earth’s gravity fields have been taking measurements of the sheet regularly for nearly 20 years, giving scientists a much more precise idea of what is happening.

it’s hard to forecast with any precision what that means. “Anyone who says they know what the sea level is going to be in 2100 is giving you an educated guess,” said NASA’s Willis. “The fact is, we’re seeing these big ice sheets melt for the first time in history, and we don’t really know how fast they can go.”

His own educated guess: “By 2100, we are probably looking at more than a foot or two and hopefully less than seven or eight feet. But we are struggling to figure out just how fast the ice sheets can melt. So the upper end of range is still not well known.”

On the face of it, that sounds manageable. Even if sea levels rise by eight feet, won’t the world have nearly 80 years to come to grips with the problem, during which technologies that help us mitigate the effects of climate change while adapting to its consequences are likely to make dramatic advances?

Won’t the world — including countries that today are poor — become far richer and thus more capable of weathering the floods, surges and superstorms?

The average rate at which sea level is rising around the world, he estimates, has more than tripled over the past three decades, to five millimeters a year from 1.5 millimeters. That may still seem minute, yet as the world learned during the pandemic, exponential increases have a way of hitting hard.

“When something is on a straight line or a smooth curve, you can plot its trajectory,” Englander said. “But sea level, like earthquakes and mudslides, is something that happens irregularly and can change rather quickly and surprise us. The point is, you can no longer predict the future by the recent past.”

In The Wall Street Journal’s editorial pages, where I used to work, the theoretical physicist Steven Koonin, a former under secretary for science in the Obama administration’s Energy Department, cast doubt on the threat from Thwaites in a voice that could have once been mine. He also thinks the risks associated with Greenland’s melting are less a product of human-induced global warming than of natural cycles in North Atlantic currents and temperatures, which over time have a way of regressing to the mean.

Even the poorest countries, while still unacceptably vulnerable, are suffering far fewer human and economic losses to climate-related disasters.

Another climate nonalarmist is Roger Pielke Jr., a professor of environmental studies at the University of Colorado Boulder. I call Pielke a nonalarmist rather than a skeptic because he readily acknowledges that the challenges associated with climate change, including sea-level rise, are real, serious and probably unstoppable, at least for many decades.

“If we have to have a problem,” he told me when I reached him by phone, “we probably want one with a slow onset that we can see coming. It’s not like an asteroid coming from space.”

“Since the 1940s, the impact of floods as a proportion of U.S. gross domestic product has dropped by 70 percent-plus,” Pielke said. “We see this around the world, across phenomena. The story is that fewer people are dying and we are having less damage proportional to G.D.P.”

“Much climate reporting today highlights short-term changes when they fit the narrative of a broken climate but then ignores or plays down changes when they don’t, often dismissing them as ‘just weather,’” he wrote in February.

Global warming is real and getting worse, Pielke said, yet still it’s possible that humanity will be able to adapt to, and compensate for, its effects.

A few years ago, I would have found voices like Koonin’s and Pielke’s persuasive. Now I’m less sure. What intervened was a pandemic.

That’s what I thought until the spring of 2020, when, along with everyone else, I experienced how swiftly and implacably nature can overwhelm even the richest and most technologically advanced societies. It was a lesson in the sort of intellectual humility I recommended for others

It was also a lesson in thinking about risk, especially those in the category known as high-impact, low-probability events that seem to be hitting us with such regularity in this century: the attacks of Sept. 11, 2001; the tsunamis of 2004 and 2011, the mass upheavals in the Arab world

What if the past does nothing to predict the future? What if climate risks do not evolve gradually and relatively predictably but instead suddenly soar uncontrollably? How much lead time is required to deal with something like sea-level rise? How do we weigh the risks of underreacting to climate change against the risks of overreacting to it?

I called Seth Klarman, one of the world’s most successful hedge-fund managers, to think through questions of risk. While he’s not an expert on climate change, he has spent decades thinking deeply about every manner of risk

And we will almost certainly have to do it from sources other than Russia, China, the Democratic Republic of Congo and other places that pose unacceptable strategic, environmental or humanitarian risks

“If you face something that is potentially existential,” he explained, “existential for nations, even for life as we know it, even if you thought the risk is, say, 5 percent, you’d want to hedge against it.”

“One thing we try to do,” he said, “is we buy protection when it’s really inexpensive, even when we think we may well not need it.” The forces contributing to climate change, he noted, echoing Englander, “might be irreversible sooner than the damage from climate change has become fully apparent. You can’t say it’s far off and wait when, if you had acted sooner, you might have dealt with it better and at less cost. We have to act now.”

In other words, an ounce of prevention is worth a pound of cure. That’s particularly true if climate change is akin to cancer — manageable or curable in its earlier stages, disastrous in its later ones.

As I’ve always believed, knowing there is grave risk to future generations — and expecting current ones to make immediate sacrifices for it — defies most of what we know about human nature. So I began to think more deeply about that challenge, and others.

For the world to achieve the net-zero goal for carbon dioxide emissions by 2050, according to the International Energy Agency, we will have to mine, by 2040, six times the current amounts of critical minerals — nickel, cobalt, copper, lithium, manganese, graphite, chromium, rare earths and other minerals and elements — needed for electric vehicles, wind turbines and solar panels.

The poster child for this kind of magical thinking is Germany, which undertook a historic Energiewende — “energy revolution” — only to come up short. At the turn of the century, Germany got about 85 percent of its primary energy from fossil fuels. Now it gets about 78 percent, a puny reduction, considering that the country has spent massive sums on renewables to increase the share of electricity it generates from them.

As in everything else in life, so too with the environment: There is no such thing as a free lunch. Whether it’s nuclear, biofuels, natural gas, hydroelectric or, yes, wind and solar, there will always be serious environmental downsides to any form of energy when used on a massive scale. A single industrial-size wind turbine, for instance, typically requires about a ton of rare earth metals as well as three metric tons of copper, which is notoriously destructive and dirty to mine.

no “clean energy” solution will easily liberate us from our overwhelming and, for now, inescapable dependence on fossil fuels.

Nobody brings the point home better than Vaclav Smil, the Canadian polymath whose most recent book, “How the World Really Works,” should be required reading for policymakers and anyone else interested in a serious discussion about potential climate solutions.

“I’ve talked to so many experts and seen so much evidence,” he told me over Zoom, “I’m convinced the climate is changing, and addressing climate change has become a philanthropic priority of mine.”

Things could turn a corner once scientists finally figure out a technical solution to the energy storage problem. Or when governments and local actors get over their NIMBYism when it comes to permitting and building a large energy grid to move electricity from Germany’s windy north to its energy-hungry south. Or when thoughtful environmental activists finally come to grips with the necessity of nuclear energy

Till then, even as I’ve come to accept the danger we face, I think it’s worth extending the cancer metaphor a little further: Just as cancer treatments, when they work at all, can have terrible side effects, much the same can be said of climate treatments: The gap between an accurate diagnosis and effective treatment remains dismayingly wide

Only when countries like Vietnam and China turned to a different model, of largely bottom-up, market-driven development, did hundreds of millions of people get lifted out of destitution.

the most important transformation has come in agriculture, which uses about 70 percent of the world’s freshwater supply.

Farmers gradually adopted sprinkler and drip irrigation systems, rather than more wasteful flood irrigation, not to conserve water but because the technology provided higher crop yields and larger profit margins.

Water shortages “will spur a revolutionary, aggressive approach to getting rid of flood irrigation,” said Seth Siegel, the chief sustainability officer of the Israeli AgTech company N-Drip. “Most of this innovation will be driven by free-market capitalism, with important incentives from government and NGOs.

meaningful environmental progress has been made through market forces. In this century, America’s carbon dioxide emissions across fuel types have fallen to well below 5,000 million metric tons per year, from a peak of about 6,000 million in 2007, even as our inflation-adjusted G.D.P. has grown by over 50 percent and total population by about 17 percent.

1) Engagement with critics is vital. Insults and stridency are never good tools of persuasion, and trying to cow or censor climate skeptics into silence rarely works

the biggest single driver in emissions reductions from 2005 to 2017 was the switch from coal to natural gas for power generation, since gas produces roughly half the carbon dioxide as coal. This, in turn, was the result of a fracking revolution in the past decade, fiercely resisted by many environmental activists, that made the United States the world’s largest gas producer.

In the long run, we are likelier to make progress when we adopt partial solutions that work with the grain of human nature, not big ones that work against it

Renewables, particularly wind power, played a role. So did efficiency mandates.

The problem with our civilization isn’t overconfidence. It’s polarization, paralysis and a profound lack of trust in all institutions, including the scientific one

Devising effective climate policies begins with recognizing the reality of the social and political landscape in which all policy operates. Some thoughts on how we might do better:

They may not be directly related to climate change but can nonetheless have a positive impact on it. And they probably won’t come in the form of One Big Idea but in thousands of little ones whose cumulative impacts add up.

2) Separate facts from predictions and predictions from policy. Global warming is a fact. So is the human contribution to it. So are observed increases in temperature and sea levels. So are continued increases if we continue to do more of the same. But the rate of those increases is difficult to predict even with the most sophisticated computer modeling

3) Don’t allow climate to become a mainly left-of-center concern. One reason the topic of climate has become so anathema to many conservatives is that so many of the proposed solutions have the flavor, and often the price tag, of old-fashioned statism

4) Be honest about the nature of the challenge. Talk of an imminent climate catastrophe is probably misleading, at least in the way most people understand “imminent.”

A more accurate description of the challenge might be a “potentially imminent tipping point,” meaning the worst consequences of climate change can still be far off but our ability to reverse them is drawing near. Again, the metaphor of cancer — never safe to ignore and always better to deal with at Stage 2 than at Stage 4 — can be helpful.

5) Be humble about the nature of the solutions. The larger the political and financial investment in a “big fix” response to climate change on the scale of the Energiewende, the greater the loss in time, capital and (crucially) public trust when it doesn’t work as planned

6) Begin solving problems our great-grandchildren will face. Start with sea-level rise

We can also stop providing incentives for building in flood-prone areas by raising the price of federal flood insurance to reflect the increased risk more accurately.

7) Stop viewing economic growth as a problem. Industrialization may be the leading cause of climate change. But we cannot and will not reverse it through some form of deindustrialization, which would send the world into poverty and deprivation

8) Get serious about the environmental trade-offs that come with clean energy. You cannot support wind farms but hinder the transmission lines needed to bring their power to the markets where they are needed.

9) A problem for the future is, by its very nature, a moral one. A conservative movement that claims to care about what we owe the future has the twin responsibility of setting an example for its children and at the same time preparing for that future.

The low-income, middle-income and high-income health systems have extremely different problems. You know, in low-income countries, getting to a health post is hard. It’s very expensive. Whereas in rich countries, yes, you can get to your doctor. In low-income countries, the main problems you have is infectious diseases. We’re dealing with countries that in the worst case where kids have death rates of 20 percent and that’s all infectious disease. And nothing else. In the U.S., in terms of kids under 5, other than premature birth, you really don’t have big problems. Kids just don’t die of infectious disease.

in the U.S., what do people die of? From age 5 till age 50, you’ve got suicide, you’ve got traffic accidents. There’s very little cancer and heart disease before age 50.

what’s a year of life worth? They call it a disability-adjusted life year (DALY). When you’re running a poor country health-care system, you can’t treat a year of life as being worth more than, say, $200, $300 or else you’ll bankrupt your health system immediately. So, with very few exceptions, you do nothing for cancer. If you get cancer, you’re going to die. And so none of the stuff that’s going on in the U.S. about $300,000 a year chemotherapy drugs is relevant.

If you spend the less than 2 percent of what the rich countries spend, but you spend it on vaccinations and antibiotics, you get over half of all that healthcare does to extend life. So you spend 2 percent and you get 50 percent. If you spend another 80 percent you’re at over 90 percent.

in rich-world health, innovation is both your friend and your enemy. Innovation is inventing organ replacement, joint replacement. We’re inventing ways of doing new things that cost $300,000 and take people in their 70s and, on average, give them an extra, say, two or three years of life. And then you have to say, given finite resources, should we fire two or three teachers to do this operation? And with chemotherapies, we’ve got things where we’ll spend our dollars on treatments where you’re valuing a life here at over $10 to $20 million. Really big, big numbers, which if you were infinitely rich, of course that would be fine. So most innovations, unfortunately, actually increase the net costs of the healthcare system. There’s a few, particularly having to do with chronic diseases, that are an exception. If you could cure Alzheimer’s, if you could avoid diabetes — those are gigantic in terms of saving money. But the incentive regime doesn’t favor them.

We’re very uncomfortable putting a value on human life. The way I see our health system is we’ve chosen to pay a huge premium in order to avoid these questions. A prerequisite for the kind of cost-cutting innovations you’re talking about it is being willing to make judgments about what a human life is worth, or even what a few months of a human life are worth. Because if you can’t decide that, then of course you just pay for everything. But if you start trying to make those choices, or even get people to think about those choices, people cry “death panels!”

BG. Yes, someone in the society has to deal with the reality that there are finite resources and we’re making trade-offs, and be explicit about that. When the car companies were found to have a memo that actually said, “This safety feature costs X and saved Y lives,” the very existence of that memo was considered damning. It was “Oh, you think human life is only a bank account.” Or when you made it reimbursable for a doctor to ask, “Do you want heroic care at the end-of-life,” that was a death panel. No, it wasn’t a death panel! It was asking somebody to make a decision.

Gloves and soap have vanished from some hospitals. Often, cancer medicines are found only on the black market. There is so little electricity that the government works only two days a week to save what energy is left.

At the University of the Andes Hospital in the mountain city of Mérida, there was not enough water to wash blood from the operating table. Doctors preparing for surgery cleaned their hands with bottles of seltzer water.

The hospital has no fully functioning X-ray or kidney dialysis machines because they broke long ago. And because there are no open beds, some patients lie on the floor in pools of their blood.

This nation has the largest oil reserves in the world, yet the government saved little money for hard times when oil prices were high.

So without water, gloves, soap or antibiotics, a group of surgeons prepared to remove an appendix that was about to burst, even though the operating room was still covered in another patient’s blood.

In April, the authorities arrested its director, Aquiles Martínez, and removed him from his post. Local news reports said he was accused of stealing equipment meant for the hospital, including machines to treat people with respiratory illnesses, as well as intravenous solutions and 127 boxes of medicine.

In a supply room, cockroaches fled as the door swung open.

Ms. Parucho, a diabetic, was unable to receive kidney dialysis because the machines were broken. An infection had spread to her feet, which were black that night. She was going into septic shock.

A holiday had been declared by the government to save electricity, and the blood bank took donations only on workdays.

For the past two and a half months, the hospital has not had a way to print X-rays. So patients must use a smartphone to take a picture of their scans and take them to the proper doctor.

Near him, a handwritten sign read, “We sell antibiotics — negotiable.” A black-market seller’s number was listed.

The ninth floor of the hospital is the maternity ward, where the seven babies had died the day before. A room at the end of the hall was filled with broken incubators.

The day of the power blackout, Dr. Rodríguez said, the hospital staff tried turning on the generator, but it did not work.

Last month, it eclipsed Walmart as the most valuable retailer in the country, with a market valuation of $250 billion, and Forbes deemed Mr. Bezos the fifth-wealthiest person on earth.

Others who cycled in and out of the company said that what they learned in their brief stints helped their careers take off. And more than a few who fled said they later realized they had become addicted to Amazon’s way of working.

Amazon may be singular but perhaps not quite as peculiar as it claims. It has just been quicker in responding to changes that the rest of the work world is now experiencing: data that allows individual performance to be measured continuously, come-and-go relationships between employers and employees, and global competition in which empires rise and fall overnight. Amazon is in the vanguard of where technology wants to take the modern office: more nimble and more productive, but harsher and less forgiving.

“Organizations are turning up the dial, pushing their teams to do more for less money, either to keep up with the competition or just stay ahead of the executioner’s blade,”

At its best, some employees said, Amazon can feel like the Bezos vision come to life, a place willing to embrace risk and strengthen ideas by stress test. Employees often say their co-workers are the sharpest, most committed colleagues they have ever met, taking to heart instructions in the leadership principles like “never settle” and “no task is beneath them.”

In contrast to companies where declarations about their philosophy amount to vague platitudes, Amazon has rules that are part of its daily language and rituals, used in hiring, cited at meetings and quoted in food-truck lines at lunchtime

“You can work long, hard or smart, but at Amazon.com you can’t choose two out of three,” Mr. Bezos wrote in his 1997 letter to shareholders

mazon, though, offers no pretense that catering to employees is a priority. Compensation

As the company has grown, Mr. Bezos has become more committed to his original ideas, viewing them in almost moral terms, those who have worked closely with him say. “My main job today: I work hard at helping to maintain the culture,”

perhaps the most distinctive is his belief that harmony is often overvalued in the workplace — that it can stifle honest critique and encourage polite praise for flawed ideas. Instead, Amazonians are instructed to “disagree and commit” (

According to early executives and employees, Mr. Bezos was determined almost from the moment he founded Amazon in 1994 to resist the forces he thought sapped businesses over time — bureaucracy, profligate spending, lack of rigor. As the company grew, he wanted to codify his ideas about the workplace, some of them proudly counterintuitive, into instructions simple enough for a new worker to understand, general enough to apply to the nearly limitless number of businesses he wanted to enter and stringent enough to stave off the mediocrity he feared.

Company veterans often say the genius of Amazon is the way it drives them to drive themselves. “If you’re a good Amazonian, you become an Amabot,” said one employee, using a term that means you have become at one with the system.

But in its offices, Amazon uses a self-reinforcing set of management, data and psychological tools to spur its tens of thousands of white-collar employees to do more and more. “The company is running a continual performance improvement algorithm on its staff,” said Amy Michaels, a former Kindle marketer.

As the newcomers acclimate, they often feel dazzled, flattered and intimidated by how much responsibility the company puts on their shoulders and how directly Amazon links their performance to the success of their assigned projects

Every aspect of the Amazon system amplifies the others to motivate and discipline the company’s marketers, engineers and finance specialists: the leadership principles; rigorous, continuing feedback on performance; and the competition among peers who fear missing a potential problem or improvement and race to answer an email before anyone else.

many others said the culture stoked their willingness to erode work-life boundaries, castigate themselves for shortcomings (being “vocally self-critical” is included in the description of the leadership principles) and try to impress a company that can often feel like an insatiable taskmaster.

“One time I didn’t sleep for four days straight,” said Dina Vaccari, who joined in 2008 to sell Amazon gift cards to other companies and once used her own money, without asking for approval, to pay a freelancer in India to enter data so she could get more done. “These businesses were my babies, and I did whatever I could to make them successful.”

To prod employees, Amazon has a powerful lever: more data than any retail operation in history. Its perpetual flow of real-time, ultradetailed metrics allows the company to measure nearly everything its customers do:

Amazon employees are held accountable for a staggering array of metrics, a process that unfolds in what can be anxiety-provoking sessions called business reviews, held weekly or monthly among various teams. A day or two before the meetings, employees receive printouts, sometimes up to 50 or 60 pages long, several workers said. At the reviews, employees are cold-called and pop-quizzed on any one of those thousands of numbers.

Ms. Willet’s co-workers strafed her through the Anytime Feedback Tool, the widget in the company directory that allows employees to send praise or criticism about colleagues to management. (While bosses know who sends the comments, their identities are not typically shared with the subjects of the remarks.) Because team members are ranked, and those at the bottom eliminated every year, it is in everyone’s interest to outperform everyone else.

many workers called it a river of intrigue and scheming. They described making quiet pacts with colleagues to bury the same person at once, or to praise one another lavishly. Many others, along with Ms. Willet, described feeling sabotaged by negative comments from unidentified colleagues with whom they could not argue

The rivalries at Amazon extend beyond behind-the-back comments. Employees say that the Bezos ideal, a meritocracy in which people and ideas compete and the best win, where co-workers challenge one another “even when doing so is uncomfortable or exhausting,” as the leadership principles note, has turned into a world of frequent combat

Resources are sometimes hoarded. That includes promising job candidates, who are especially precious at a company with a high number of open positions. To get new team members, one veteran said, sometimes “you drown someone in the deep end of the pool,” then take his or her subordinates. Ideas are critiqued so harshly in meetings at times that some workers fear speaking up.

David Loftesness, a senior developer, said he admired the customer focus but could not tolerate the hostile language used in many meetings, a comment echoed by many others.

Each year, the internal competition culminates at an extended semi-open tournament called an Organization Level Review, where managers debate subordinates’ rankings, assigning and reassigning names to boxes in a matrix projected on the wall. In recent years, other large companies, including Microsoft, General Electric and Accenture Consulting, have dropped the practice — often called stack ranking, or “rank and yank” — in part because it can force managers to get rid of valuable talent just to meet quotas.

Molly Jay, an early member of the Kindle team, said she received high ratings for years. But when she began traveling to care for her father, who was suffering from cancer, and cut back working on nights and weekends, her status changed. She was blocked from transferring to a less pressure-filled job, she said, and her boss told her she was “a problem.” As her father was dying, she took unpaid leave to care for him and never returned to Amazon.

“When you’re not able to give your absolute all, 80 hours a week, they see it as a major weakness,” she said.

A woman who had thyroid cancer was given a low performance rating after she returned from treatment. She says her manager explained that while she was out, her peers were accomplishing a great deal. Another employee who miscarried twins left for a business trip the day after she had surgery. “I’m sorry, the work is still going to need to get done,” she said her boss told her. “From where you are in life, trying to start a family, I don’t know if this is the right place for you.”

A woman who had breast cancer was told that she was put on a “performance improvement plan” — Amazon code for “you’re in danger of being fired” — because “difficulties” in her “personal life” had interfered with fulfilling her work goals. Their accounts echoed others from workers who had suffered health crises and felt they had also been judged harshly instead of being given time to recover.

Amazon retains new workers in part by requiring them to repay a part of their signing bonus if they leave within a year, and a portion of their hefty relocation fees if they leave within two years.

In interviews, 40-year-old men were convinced Amazon would replace them with 30-year-olds who could put in more hours, and 30-year-olds were sure that the company preferred to hire 20-somethings who would outwork them. A

A 2013 survey by PayScale, a salary analysis firm, put the median employee tenure at one year, among the briefest in the Fortune 500

Recruiters, though, also say that other businesses are sometimes cautious about bringing in Amazon workers, because they have been trained to be so combative. The derisive local nickname for Amazon employees is “Amholes” — pugnacious and work-obsessed.

By the time the dust settles in three years, Amazon will have enough space for 50,000 employees or so, more than triple what it had as recently as 2013.

just as Jeff Bezos was able to see the future of e-commerce before anyone else, she added, he was able to envision a new kind of workplace: fluid but tough, with employees staying only a short time and employers demanding the maximum.

“Amazon is driven by data,” said Ms. Pearce, who now runs her own Seattle software company, which is well stocked with ex-Amazonians. “It will only change if the data says it must — when the entire way of hiring and working and firing stops making economic sense.”

While some diseases, like cystic fibrosis, are caused by a single genetic mutation, the most common ones are not. Instead, mutations to a number of different genes can each raise the risk of getting, say, heart disease or breast cancer. Discovering these mutations can shed light on these diseases and point to potential treatments. But many of them are rare, making it necessary to search large groups of people to find them.

The wealth of data created in Iceland may enable scientists to begin doing that

For example, they found eight people in Iceland who shared a mutation on a gene called MYL4. Medical records showed that they also have early onset atrial fibrillation, a type of irregular heartbeat.

they identified a gene called ABCA7 as a risk factor for Alzheimer’s disease.Previous studies had suggested a gene in the genetic neighborhood of ABCA7 was associated with the disease.But the Icelandic study pinpointed the gene itself — and even the specific mutation involved.

Since Dr. Stefansson and his colleagues submitted their initial results for publication, they have continued gathering DNA from Icelanders.The scientists now have full genomes from about 10,000 Icelanders and partial genetic information on 150,000 more.

Dr. Stefansson said that means that his firm could generate a report for genetic disease on every person in Iceland

Iceland is a particularly fertile country for doing genetics research. It was founded by a small number of settlers from Europe arriving about 1,100 years ago. Between 8,000 and 20,000 people came mainly from Scandinavia, Ireland and Scotland.

The country remained isolated for the next thousand years, and so living Icelanders have a relatively low level of genetic diversity. This makes it easier for scientists to detect genetic variants that raise the risk of disease, because there are fewer of them to examine.

celand also has impressive genealogical records. Through epic poems and historical documents, many Icelanders can trace their ancestry back to the nation’s earliest arrivals. Geneticists use national genealogy databases to look for diseases that are unusually common in relatives — a sign that they share a mutation.

the company is now investigating a gene, found by Decode, with a strong link to cardiovascular disease in Iceland. (He declined to name the gene.)

We ask not whether a given chemical might cause cancer but whether we’re certain that it does. Since it’s unethical to test the effects of new chemicals and food additives on humans, we rely on the indirect expedient of extensive and expensive animal testing

t the job of the F.D.A. should be to guarantee a reasonable expectation of protection from danger, not to wait until people become sick before taking products off the market

Even now, when it’s clear that more research must be done to determine to what degree glyphosate may be carcinogenic, it’s not clear whose responsibility it is to conduct that research.

Or — here’s an idea — how about Monsanto, which has made billions of dollars selling glyphosate and the associated seed technology.

While we’re at it, let’s finally start labeling products made with genetically engineered food

If G.M.O.s were largely beneficial to eaters, manufacturers would proudly boast of products containing them. The fact is that they have not.

We don’t need better, smarter chemicals along with crops that can tolerate them; we need fewer chemicals. And it’s been adequately demonstrated that crop rotation, the use of organic fertilizers, interplanting of varieties of crops, and other ecologically informed techniques commonly grouped together under the term “agroecology” can effectively reduce the use of chemicals.