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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 Through epic poems and historical documents, many Icelanders can trace their ancestry back to the nation’s earliest arrivals.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.)

World Health Organization data published in September showed there were twice as many cholera cases in 2022 than in 2021. Outbreaks were recorded in countries where cholera had been under control for years, including Yemen and Lebanon.

2. Mosquitoes on the march

Rising temperatures and frequent floods also unlock new places where disease-carrying insects thrive. The mosquitoes that carry the viruses that cause dengue fever and mala

Nor is the disease confined to developing countries. There are fears that it is spreading in southern Europe, partly owing to the warm weather. More than 8 billion people could be at risk of malaria and dengue fever by 2080, scientists have warned.

3. Human-animal contact

Many existing diseases will get more dangerous, but new illnesses could also emerge as people are increasingly forced into areas where there is wildlife. Diseases can jump from animals to humans. These diseases, such as Ebola, avian flu and Sars, are called “zoonoses” and they make up the majority of new illnesses.

Scientists have found that the climate crisis is helping to circulate diseases between species that previously did not encounter each other. As the planet heats up, many animal species are forced to move into new areas to find suitable conditions.

It has been estimated that zoonoses are responsible for as many as 2.5bn cases of human illness and 2.7m human deaths worldwide each year, and that animals have played a major part in nearly every major disease outbreak since 1970.

4. Severe weather events

Although governments are getting better at preparing for severe weather events, nine out of 10 deaths linked to weather disasters since 1970 happened in small island nations and developing countries in Africa, Asia and South America.

5. The air that we breathe

Outside air pollution has been linked to numerous cancers and diseases and is estimated to be responsible for more than 4m premature deaths globally each year.

Changing weather patterns are expected to make this already bad situation worse as more dust, rain and wildfire smoke are added to the mix. Children are especially likely to get sick from air pollution because their brains, lungs and other organs are still developing.

6. The psychological cost

Environmental deterioration has a knock-on effect on the economic and social systems that keep society productive and happy, setting in motion a downward spiral of psychological hardship.

If crops are destroyed during extreme weather events, children may get less nutritious food, the consumption of which is linked to psychological conditions such as anxiety and depression.

When people can’t get the help they need, they may self-medicate with alcohol or drugs, which in turn makes them more likely to engage in risky behaviour (such as unprotected sex) that could result in infections such as HIV, or illnesses that can result from spending time in crowded places, such as tuberculosis.

In 2021, scientists studying evidence of a potential link between heat exposure and mental health found a 2.2% increase in mental health-related mortality per 1C rise in temperature.

7. Salty water and perilous pregnancies

Drinking water is becoming saltier. One reason for this is that sea levels are rising, so there is more sea water flowing into rivers and other sources of fresh water during floods and tropical storms.

Taking in too much salt can lead to high blood pressure (hypertension). Over time, this condition damages the body’s veins, arteries and major organs (including the brain, heart, kidneys and eyes) since they’re working so much harder overall.

Hypertension is doubly dangerous for pregnant women and their babies

8. Food insecurity

More frequent and severe droughts and floods make it harder to grow the grains, fruit and vegetables that people need to eat to stay healthy. Small island states in the Caribbean, Atlantic, Pacific and Indian Ocean bear the brunt of the effects of the crisis, in part because most people live close to sea level.

As a result, people who live in one of the 39 small island nations are the most likely to die from one of the four main NCDs: cancer, diabetes, heart disease and lung disease.

9. The stress of extreme heat

The scorching temperatures this year broke records in Europe, China and North America. Heat is one of the most dangerous effects of the climate crisis and the top cause of weather-related deaths in the U

When it gets too hot, the body’s temperature rises faster than it can cool itself down, less blood flows to other organs, and the kidneys have to work harder. This puts strain on the heart and can lead to organ failure. Heatstroke is the most serious heat-related illness.

In particular, people whose jobs require long hours of physical labour in the sun face an increased risk of kidney disease as temperatures rise, research suggests. Repeated instances of heat stress can lead to permanent damage and chronic kidney disease.

In June, the Guardian revealed how young migrant workers were returning to Nepal with chronic kidney disease after working in extreme heat conditions in the Gulf and Malaysia. “One factor highlighted again and again is heat. Prolonged exposure to h

10. Millions on the move

It’s hard to predict exactly how many people will be on the move because of the climate crisis, but extreme weather events are likely to make conditions worse for the more than 100 million displaced people around the world.

If nothing changes, the number of people who need humanitarian aid to recover from floods, storms and droughts could double by 2050,

That means more than 200 million people will need aid annually. The displacement of millions of people also means cramped and often unsanitary living. For example, more than 900,000 Rohingya refugees live in makeshift shelters in Bangladesh, often built on unstable ground that’s prone to landslides.

until now, the planet’s natural defense systems were better at fighting them off.

Today, climate warming is demolishing those defense systems, driving a catastrophic loss in biodiversity that, when coupled with reckless deforestation and aggressive conversion of wildland for economic development, pushes farms and people closer to the wild and opens the gates for the spread of disease.

ignoring how climate and rapid land development were putting disease-carrying animals in a squeeze was akin to playing Russian roulette.

the virus is believed to have originated with the horseshoe bat, part of a genus that’s been roaming the forests of the planet for 40 million years and thrives in the remote jungles of south China, even that remains uncertain.

China for years and warning that swift climate and environmental change there — in both loss of biodiversity and encroachment by civilization — was going to help new viruses jump to people.

. Roughly 60% of new pathogens come from animals — including those pressured by diversity loss — and roughly one-third of those can be directly attributed to changes in human land use, meaning deforestation, the introduction of farming, development or resource extraction in otherwise natural settings

Vector-borne diseases — those carried by insects like mosquitoes and ticks and transferred in the blood of infected people — are also on the rise as warming weather and erratic precipitation vastly expand the geographic regions vulnerable to contagion.

Climate is even bringing old viruses back from the dead, thawing zombie contagions like the anthrax released from a frozen reindeer in 2016, which can come down from the arctic and haunt us from the past.

It is demonstrating in real time the enormous and undeniable power that nature has over civilization and even over its politics.

it also makes clear that climate policy today is indivisible from efforts to prevent new infectious outbreaks, or, as Bernstein put it, the notion that climate and health and environmental policy might not be related is “a ​dangerous delusion.”

The warming of the climate is one of the principal drivers of the greatest — and fastest — loss of species diversity in the history of the planet, as shifting climate patterns force species to change habitats, push them into new regions or threaten their food and water supplies

What’s known as biodiversity is critical because the natural variety of plants and animals lends each species greater resiliency against threat and together offers a delicately balanced safety net for natural systems

As diversity wanes, the balance is upset, and remaining species are both more vulnerable to human influences and, according to a landmark 2010 study in the journal Nature, more likely to pass along powerful pathogens.

even incremental and seemingly manageable injuries to local environments — say, the construction of a livestock farm adjacent to stressed natural forest — can add up to outsized consequences.

Coronaviruses like COVID-19 aren’t likely to be carried by insects — they don’t leave enough infected virus cells in the blood. But one in five other viruses transmitted from animals to people are vector-borne

the number of species on the planet has already dropped by 20% and that more than a million animal and plant species now face extinction.

Americans have been experiencing this phenomenon directly in recent years as migratory birds have become less diverse and the threat posed by West Nile encephalitis has spread. It turns out that the birds that host the disease happen to also be the tough ones that prevail amid a thinned population

as larger mammals suffer declines at the hands of hunters or loggers or shifting climate patterns, smaller species, including bats, rats and other rodents, are thriving, either because they are more resilient to the degraded environment or they are able to live better among people.

It is these small animals, the ones that manage to find food in garbage cans or build nests in the eaves of buildings, that are proving most adaptable to human interference and also happen to spread disease.

Warmer temperatures and higher rainfall associated with climate change — coupled with the loss of predators — are bound to make the rodent problem worse, with calamitous implications.

As much as weather changes can drive changes in species, so does altering the landscape for new farms and new cities. In fact, researchers attribute a full 30% of emerging contagion to what they call “land use change.”

As the global population surges to 10 billion over the next 35 years, and the capacity to farm food is stressed further again by the warming climate, the demand for land will only get more intense.

Already, more than one-third of the planet’s land surface, and three-quarters of all of its fresh water, go toward the cultivation of crops and raising of livestock. These are the places where infectious diseases spread most often.

The U.S. Centers for Disease Control and Prevention says that fully three-quarters of all new viruses have emerged from animals

Almost every major epidemic we know of over the past couple of decades — SARS, COVID-19, Ebola and Nipah virus — jumped to people from wildlife enduring extreme climate and habitat strain, and still, “we’re naive to them,” she said. “That puts us in a dangerous place.”

A 2008 study in the journal Nature found nearly one-third of emerging infectious diseases over the past 10 years were vector-borne, and that the jumps matched unusual changes in the climate

Ticks and mosquitoes now thrive in places they’d never ventured before. As tropical species move northward, they are bringing dangerous pathogens with them.

by 2050, disease-carrying mosquitoes will ultimately reach 500 million more people than they do today, including some 55 million more Americans.

In 2013, dengue fever — an affliction affecting nearly 400 million people a year, but normally associated with the poorest regions of Africa — was transmitted locally in New York for the first time.

“The long-term risk from dengue may be much higher than COVID,

only 15% of the planet’s forests remain intact. The rest have been cut down, degraded or fragmented to the point that they disrupt the natural ecosystems that depend on them.

it’s only a matter of time before other exotic animal-driven pathogens are driven from the forests of the global tropics to the United States or Canada or Europe because of the warming climate.

it will also shape how easily we get sick. According to a 2013 study in the journal PLOS Currents Influenza, warm winters were predictors of the most severe flu seasons in the following year

Even harsh swings from hot to cold, or sudden storms — exactly the kinds of climate-induced patterns we’re already seeing — make people more likely to get sick.

The chance of a flu epidemic in America’s most populated cities will increase by as much as 50% this century, and flu-related deaths in Europe could also jump by 50%.

Slow action on climate has made dramatic warming and large-scale environmental changes inevitable, he said, “and I think that increases in disease are going to come along with it.”

By late 2018, epidemiologists there were bracing for what they call “spillover,” or the failure to keep a virus locally contained as it jumped from the bats and villages of Yunnan into the wider world.

In late 2018, the Trump administration, as part of a sweeping effort to bring U.S. programs in China to a halt, abruptly shut down the research — and its efforts to intercept the spread of a new novel coronavirus along with it. “We got a cease and desist,” said Dennis Carroll, who founded the PREDICT program and has been instrumental in global work to address the risks from emerging viruses. By late 2019, USAID had cut the program’s global funding.

The loss is immense. The researchers believed they were on the cusp of a breakthrough, racing to sequence the genes of the coronaviruses they’d extracted from the horseshoe bat and to begin work on vaccines.

They’d campaigned for years for policymakers to fully consider what they’d learned about how land development and climate changes were driving the spread of disease, and they thought their research could literally provide governments a map to the hot spots most likely to spawn the next pandemic.

They also hoped the genetic material they’d collected could lead to a vaccine not just for one lethal variation of COVID, but perhaps — like a missile defense shield for the biosphere — to address a whole family of viruses at once

Carroll said knowledge of the virus genomes had the potential “to totally transform how we think about future biomedical interventions before there’s an emergence.

PREDICT’s staff and advisers have pushed the U.S. government to consider how welding public health policy with environmental and climate science could help stem the spread of contagions.

Since Donald Trump was elected, the group hasn’t been invited back.

What Daszak really wants — in addition to restored funding to continue his work — is the public and leaders to understand that it’s human behavior driving the rise in disease, just as it drives the climate crisis

“We turn a blind eye to the fact that our behavior is driving this,” he said. “We get cheap goods through Walmart, and then we pay for it forever through the rise in pandemics. It’s upside down.”

No one knows exactly how many people died from influenza in 1918; estimates range from 15 million to 100 million globally. Historians estimate that the virus killed about 675,000 people in the United States across three waves of the pandemic

confirmed cases. But in this global crisis, both the numerator and the denominator are fuzzy.

the rising rate may reflect the disease’s gradual progression, combined with discoveries of additional deaths.

The “virulence” of the virus — its ability to cause illness — has been steadily coming into focus.

One scholarly estimate finds that the 1918-1920 pandemic killed 218 out of every 100,000 people living in the world at that time

In Spain, the death toll already stands at 41 out of 100,000 people; in Belgium the number is 45. In New York state, it is 63, and that number rises even higher if you consider the “probable” death toll in New York City.

So is the coronavirus as deadly? “This depends on how long this continues,”

The disease is far more likely to cause severe outcomes in older people, with the oldest cohorts the most vulnerable. That said, in every age group — even 85-plus — most people who contract the disease will recover.

But more than a month later, the WHO number has gone even higher: On April 16, the WHO showed a global fatality rate of 6.6 percent among confirmed cases.

Preliminary research indicates that the virus is not mutating significantly as it spreads, and so there is no evidence that some countries are dealing with a more virulent strain of SARS-CoV-2.

the median age of patients in Italy is 63 or 64 years; the median age of patients in Germany is 47. The mortality is much lower [in Germany] because they avoided having the older population affected.”

The other major factor in mortality is chronic disease. Most people hospitalized with severe cases of covid-19 have chronic health conditions such as diabetes, lung disease and heart disease. Where there is a high percentage of noncommunicable diseases like high blood pressure, the coronavirus will also be more deadly

“We saw it everyday. African Americans have three times the rate of chronic kidney disease that Caucasians have, and 25 percent higher heart disease. They’ve got higher rates of diabetes, hypertension and asthma,” Duggan said. “I fully expect that when people are hit hard and they are on a ventilator to breathe and their body needs to fight the infection, that people who already have compromised hearts or kidneys or lungs are that much more in jeopardy.”

Also critical is the nature, and robustness, of the national health system. For instance, Japan, where the current case fatality rate is 1.6 percent, and Singapore are reporting extremely high rates of hospitalization for coronavirus patients, at 80 percent and higher, figures that are unheard of in the United States. But this probably helps improve treatment and also reduces disease spread by isolating patients. The result is fewer deaths.

Several of the countries with low fatality rates — Germany, South Korea, Norway — have very high rates of coronavirus testing. This gave them a better look at the disease within their borders.

San Francisco General Hospital, noted that the hospital nearly tripled the capacity of its intensive care unit by adding doctors, nurses and technicians while the city adopted social distancing measures shortly ahead of New York.

“We were ready for a surge that never happened,” Balmes said. “They’re every bit as good as we are in intensive care in New York, but the system was overwhelmed. We did physical distancing just a few days earlier than New York, but it was a few days to the good.”

in a news conference that the global case fatality rate was 3.4 percent. That was treated as a revelation about the innate deadliness of the disease, but in fact was simply the WHO’s crude mortality ratio for confirmed covid-19 cases up to that point in time.

“If, in fact, the case fatality rate is higher than the 1918 flu, then this one has the potential to kill even more people,

A new study from researchers at Stanford, not yet peer-reviewed, looked for coronavirus antibodies in a sample population in Santa Clara County, Calif., and concluded that the actual infection rate in the county by early April was 50 to 85 times greater than the rate of confirmed cases.

“The story of this virus is turning out to be more about its contagiousness and less about its case fatality rate,” said David Rubin, director of PolicyLab at Children’s Hospital of Philadelphia and a University of Pennsylvania professor of pediatrics. “It’s less fatal than we thought, but it’s more contagious.”

Where extensive testing has been done, estimates for the case fatality rate are often below 1 percent, The Post has found, suggesting these countries are getting closer to a rate that takes into account all infections

In Iceland, which has tested over 10 percent of the population, vastly more than other countries, the fatality rate is just 0.5 percent.

Harvard epidemiologist Marc Lipsitch has written that he and most experts suspect the fatality rate is about 1 to 2 percent for symptomatic cases. A 1 percent fatality rate is 10 times the average fatality rate for seasonal flu.

“It’s probably about an order of magnitude higher for covid-19,” said Viboud, the NIH epidemiologist. “It’s more severe in terms of mortality than the pandemics we’ve seen since 1918.”

But for those hoping that 25 percent represents a true ceiling for pandemic spread in a given community, well, it almost certainly does not, considering that recent serological surveys have shown that perhaps 93 percent of the population of Iquitos, Peru, has contracted the disease; as have more than half of those living in Indian slums; and as many as 68 percent in particular neighborhoods of New York City

overshoot of that scale would seem unlikely if the “true” threshold were as low as 20 or 25 percent.

But, of course, that threshold may not be the same in all places, across all populations, and is surely affected, to some degree, by the social behavior taken to protect against the spread of the disease.

we probably err when we conceive of group immunity in simplistically binary terms. While herd immunity is a technical term referring to a particular threshold at which point the disease can no longer spread, some amount of community protection against that spread begins almost as soon as the first people are exposed, with each case reducing the number of unexposed and vulnerable potential cases in the community by one

you would not expect a disease to spread in a purely exponential way until the point of herd immunity, at which time the spread would suddenly stop. Instead, you would expect that growth to slow as more people in the community were exposed to the disease, with most of them emerging relatively quickly with some immune response. Add to that the effects of even modest, commonplace protections — intuitive social distancing, some amount of mask-wearing — and you could expect to get an infection curve that tapers off well shy of 60 percent exposure.

Looking at the data, we see that transmissions in many severely impacted states began to slow down in July, despite limited interventions. This is especially notable in states like Arizona, Florida, and Texas. While we believe that changes in human behavior and changes in policy (such as mask mandates and closing of bars/nightclubs) certainly contributed to the decrease in transmission, it seems unlikely that these were the primary drivers behind the decrease. We believe that many regions obtained a certain degree of temporary herd immunity after reaching 10-35 percent prevalence under the current conditions. We call this 10-35 percent threshold the effective herd immunity threshold.

Indeed, that is more or less what was recently found by Youyang Gu, to date the best modeler of pandemic spread in the U.S

he cautioned again that he did not mean to imply that the natural herd-immunity level was as low as 10 percent, or even 35 percent. Instead, he suggested it was a plateau determined in part by better collective understanding of the disease and what precautions to take

Gu estimates national prevalence as just below 20 percent (i.e., right in the middle of his range of effective herd immunity), it still counts, I think, as encouraging — even if people in hard-hit communities won’t truly breathe a sigh of relief until vaccines arrive.

If you can get real protection starting at 35 percent, it means that even a mediocre vaccine, administered much more haphazardly to a population with some meaningful share of vaccination skeptics, could still achieve community protection pretty quickly. And that is really significant — making both the total lack of national coordination on rollout and the likely “vaccine wars” much less consequential.

At least 20 percent of the public, and perhaps 50 percent, had some preexisting, cross-protective T-cell response to SARS-CoV-2, according to one much-discussed recent paper. An earlier paper had put the figure at between 40 and 60 percent. And a third had found an even higher prevalence: 81 percent.

The T-cell story is similarly encouraging in its big-picture implications without being necessarily paradigm-changing

These numbers suggest their own heterogeneity — that different populations, with different demographics, would likely exhibit different levels of cross-reactive T-cell immune response

The most optimistic interpretation of the data was given to me by Francois Balloux, a somewhat contrarian disease geneticist and the director of the University College of London’s Genetics Institute

According to him, a cross-reactive T-cell response wouldn’t prevent infection, but would probably mean a faster immune response, a shorter period of infection, and a “massively” reduced risk of severe illness — meaning, he guessed, that somewhere between a third and three-quarters of the population carried into the epidemic significant protection against its scariest outcomes

the distribution of this T-cell response could explain at least some, and perhaps quite a lot, of COVID-19’s age skew when it comes to disease severity and mortality, since the young are the most exposed to other coronaviruses, and the protection tapers as you get older and spend less time in environments, like schools, where these viruses spread so promiscuously.

Balloux told me he believed it was also possible that the heterogeneous distribution of T-cell protection also explains some amount of the apparent decline in disease severity over time within countries on different pandemic timelines — a phenomenon that is more conventionally attributed to infection spreading more among the young, better treatment, and more effective protection of the most vulnerable (especially the old).

Going back to Youyang Gu’s analysis, what he calls the “implied infection fatality rate” — essentially an estimated ratio based on his modeling of untested cases — has fallen for the country as a whole from about one percent in March to about 0.8 percent in mid-April, 0.6 percent in May, and down to about 0.25 percent today.

even as we have seemed to reach a second peak of coronavirus deaths, the rate of death from COVID-19 infection has continued to decline — total deaths have gone up, but much less than the number of cases

In other words, at the population level, the lethality of the disease in America has fallen by about three-quarters since its peak. This is, despite everything that is genuinely horrible about the pandemic and the American response to it, rather fantastic.

there may be some possible “mortality displacement,” whereby the most severe cases show up first, in the most susceptible people, leaving behind a relatively protected population whose experience overall would be more mild, and that T-cell response may play a significant role in determining that susceptibility.

That, again, is Balloux’s interpretation — the most expansive assessment of the T-cell data offered to me

The most conservative assessment came from Sarah Fortune, the chair of Harvard’s Department of Immunology

Fortune cautioned not to assume that cross-protection was playing a significant role in determining severity of illness in a given patient. Those with such a T-cell response, she told me, would likely see a faster onset of robust response, yes, but that may or may not yield a shorter period of infection and viral shedding

Most of the scientists, doctors, epidemiologists, and immunologists I spoke to fell between those two poles, suggesting the T-cell cross-immunity findings were significant without necessarily being determinative — that they may help explain some of the shape of pandemic spread through particular populations, but only some of the dynamics of that spread.

he told me he believed, in the absence of that data, that T-cell cross-immunity from exposure to previous coronaviruses “might explain different disease severity in different people,” and “could certainly be part of the explanation for the age skew, especially for why the very young fare so well.”

the headline finding was quite clear and explicitly stated: that preexisting T-cell response came primarily via the variety of T-cells called CD4 T-cells, and that this dynamic was consistent with the hypothesis that the mechanism was inherited from previous exposure to a few different “common cold” coronaviruses

“This potential preexisting cross-reactive T-cell immunity to SARS-CoV-2 has broad implications,” the authors wrote, “as it could explain aspects of differential COVID-19 clinical outcomes, influence epidemiological models of herd immunity, or affect the performance of COVID-19 candidate vaccines.”

“This is at present highly speculative,” they cautioned.

For the study, Dr. Robert Abbott of the Shiga University of Medical Science in Otsu, Japan, and colleagues studied 449 Japanese-American men living in Hawaii who were taking part in a larger study of aging. They gave details of how much milk they drank as part of a larger survey, and they donated their brains for study after they died.

The researchers also looked for the pesticide heptachlor, which was taken off the market for most uses in the U.S. in 1988.

"Among those who drank the most milk, residues of heptachlor epoxide were found in nine of 10 brains as compared to 63.4 percent for those who consumed no milk," the researchers wrote.

"The researchers could not test whether the milk the men drank was contaminated with pesticides (heptachlor, in this case), and no one knows how long or how widespread the contamination was before being detected," the Parkinson's Disease Foundation said in a statement on its website.

"This study is unique because it brings together two critical but different pieces of information — environmental exposure and physical changes in the brain — to understand potential contributors of Parkinson's disease," James Beck, vice president of scientific affairs at the Parkinson's Disease Foundation, said in a statement.

The Parkinson's Disease Foundation estimates that 1 million Americans have the condition, marked by tremor, rigid muscles and problems with movement. There is no cure, although early treatment can delay the worst symptoms.

The rate of firearm homicides was 20 times higher in the United States than in the other countries, according to the report, which cited a 2011 study of 23 countries. And though suicide rates were lower in the United States, firearm suicide rates were six times higher.

Panelists were surprised at just how consistently Americans ended up at the bottom of the rankings. The United States had the second-highest death rate from the most common form of heart disease, the kind that causes heart attacks, and the second-highest death rate from lung disease, a legacy of high smoking rates in past decades. American adults also have the highest diabetes rates.

Youths fared no better. The United States has the highest infant mortality rate among these countries, and its young people have the highest rates of sexually transmitted diseases, teen pregnancy and deaths from car crashes. Americans lose more years of life before age 50 to alcohol and drug abuse than people in any of the other countries.

The United States is a bigger, more heterogeneous society with greater levels of economic inequality, and comparing its health outcomes to those in countries like Sweden or France may seem lopsided. B

the U.S. ranked near and at the bottom in almost every heath indicator. That stunned us.”

The panel sought to explain the poor performance. It noted the United States has a highly fragmented health care system, with limited primary care resources and a large uninsured population. It has the highest rates of poverty among the countries studied.

In the other countries, more generous social safety nets buffer families from the health consequences of poverty, the report said.

Could cultural factors like individualism and dislike of government interference play a role? Americans are less likely to wear seat belts and more likely to ride motorcycles without helmets.  

Americans also had the lowest probability over all of surviving to the age of 50. The report’s second chapter details health indicators for youths where the United States ranks near or at the bottom. There are so many that the list takes up four pages.

the panelists point out that this country spends more on health care than any other in the survey. And as recently as the 1950s, Americans scored better in life expectancy and disease than many of the other countries in the current study.

“Never before have so many opportunities existed for pathogens to pass from wild and domestic animals to people,” she told the Guardian, explaining that 75% of all emerging infectious diseases come from wildlife.“Our continued erosion of wild spaces has brought us uncomfortably close to animals and plants that harbour diseases that can jump to humans.”

“There are too many pressures at the same time on our natural systems and something has to give,” she added. “We are intimately interconnected with nature, whether we like it or not. If we don’t take care of nature, we can’t take care of ourselves. And as we hurtle towards a population of 10 billion people on this planet, we need to go into this future armed with nature as our strongest ally.”

Human infectious disease outbreaks are rising and in recent years there have been Ebola, bird flu, Middle East respiratory syndrome (Mers), Rift Valley fever, sudden acute respiratory syndrome (Sars), West Nile virus and Zika virus all cross from animals to humans.

Cunningham said other diseases from wildlife had much higher fatality rates in people, such as 50% for Ebola and 60%-75% for Nipah virus, transmitted from bats in south Asia. “Although, you might not think it at the moment, we’ve probably got a bit lucky with [Covid-19],” he said. “So I think we should be taking this as a clear warning shot. It’s a throw of the dice.”

“The animals have been transported over large distances and are crammed together into cages. They are stressed and immunosuppressed and excreting whatever pathogens they have in them,” he said. “With people in large numbers in the market and in intimate contact with the body fluids of these animals, you have an ideal mixing bowl for [disease] emergence. If you wanted a scenario to maximise the chances of [transmission], I couldn’t think of a much better way of doing it.”

Aaron Bernstein, at the Harvard School of Public Health in the US, said the destruction of natural places drives wildlife to live close to people and that climate change was also forcing animals to move: “That creates an opportunity for pathogens to get into new hosts.”

The billion-dollar illegal wildlife trade is another part of the problem, said John Scanlon, the former secretary general of the Convention on International Trade of Endangered Species of Wild Fauna and Flora.

The Covid-19 crisis may provide an opportunity for change, but Cunningham is not convinced it will be taken: “I thought things would have changed after Sars, which was a massive wake up call – the biggest economic impact of any emerging disease to that date,” he said.

Last year, a Chinese scientist he worked with published a specific forecast: “It is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China.”

Humans today are exposed to more deadly new pathogens than ever. They typically come from animals, as global travel, trade and economic development, such as meat production and deforestation, push people, livestock and wildlife closer together

Scientists knew infectious disease outbreaks were becoming more common, with 2010 having more than six times the outbreaks of pathogens from animal origins than in 1980, according to data in a study by Brown University researchers.

Yet plenty was left undone, in areas including funding, early-warning systems, the role of the WHO and coordination with China. A big chunk of U.S. funding went toward protecting Americans against a bioterror attack. Government funding for pandemics has come largely in emergency, one-time packages to stop an ongoing outbreak.

She said a better solution would be to fund public health more like national defense, with much more guaranteed money, year in, year out.

“Will there be another human influenza pandemic?” Dr. Webster asked in a paper presented at an NIH meeting in 1995. “The certainty is that there will be.”

Experts including Dr. Webster were particularly concerned about the potential for spillover in southern China, where large, densely populated cities were expanding rapidly into forests and agricultural lands, bringing people into closer contact with animals. Two of the three influenza pandemics of the 20th century are thought to have originated in China.

Dr. Webster and others warned it could re-emerge or mutate into something more contagious. With U.S. funding, he set up an animal influenza surveillance center in Hong Kong. The WHO, which hadn’t planned for pandemics before, started compiling protocols for a large-scale outbreak, including contingency plans for vaccines.

At a dinner back in the U.S., he remembers one guest saying, “Oh, you really needed to have someone in the U.S. to be impacted to really galvanize the government.”

That “drove home the reality in my own mind of globalization,” said Dr. Fukuda. SARS showed that viruses can crisscross the globe by plane in hours, making a local epidemic much more dangerous.

The WHO’s director-general, Gro Harlem Brundtland, publicly criticized China. The government under new leaders reversed course. It implemented draconian quarantines and sanitized cities, including a reported 80 million people enlisted to clean streets in Guangdong.

By May 2003, the number of new SARS cases was dwindling. It infected around 8,000 people world-wide, killing nearly 10%.

After SARS, China expanded epidemiologist training and increased budgets for new laboratories. It started working more closely in public health with the U.S., the world’s leader. The U.S. CDC opened an office in Beijing to share expertise and make sure coverups never happened again. U.S. CDC officials visiting a new China CDC campus planted a friendship tree.

In Washington in 2005, a powerful player started driving U.S. efforts to become more prepared. President George W. Bush had read author John M. Barry’s “The Great Influenza,” a history of the 1918 flu pandemic

Mr. Bush leaned toward the group of 10 or so officials and said, “I want to see a plan,” according to Dr. Venkayya. “He had been asking questions and not getting answers,” recalled Dr. Venkayya, now president of Takeda Pharmaceutical Co. ’s global vaccine business unit. “He wanted people to see this as a national threat.”

Mr. Bush launched the strategy in November, and Congress approved $6.1 billion in one-time funding.

The CDC began exercises enacting pandemic scenarios and expanded research. The government created the Biomedical Advanced Research and Development Authority to fund companies to develop diagnostics, drugs and vaccines.

A team of researchers also dug into archives of the 1918 pandemic to develop guidelines for mitigating the spread when vaccines aren’t available. The tactics included social distancing, canceling large public gatherings and closing schools—steps adopted this year when Covid-19 struck, though at the time they didn’t include wide-scale lockdowns.

A year after the plan was released, a progress report called for more real-time disease surveillance and preparations for a medical surge to care for large numbers of patients, and stressed strong, coordinated federal planning.

A European vaccine makers’ association said its members had spent around $4 billion on pandemic vaccine research and manufacturing adjustments by 2008.

The $6.1 billion Congress appropriated for Mr. Bush’s pandemic plan was spent mostly to make and stockpile medicines and flu vaccines and to train public-health department staff. The money wasn’t renewed. “The reality is that for any leader it’s really hard to maintain a focus on low-probability high-consequence events, particularly in the health arena,” Dr. Venkayya said.

In the U.S., President Barack Obama’s administration put Mr. Bush’s new plan into action for the first time. By mid-June, swine flu, as it was dubbed, had jumped to 74 countries. The WHO officially labeled it a pandemic, despite some evidence suggesting the sickness was pretty mild in most people.

That put in motion a host of measures, including some “sleeping” contracts with pharmaceutical companies to begin vaccine manufacturing—contracts that countries like the United Kingdom had negotiated ahead of time so they wouldn’t have to scramble during an outbreak.

In August, a panel of scientific advisers to Mr. Obama published a scenario in which as many as 120 million Americans, 40% of the population, could be infected that year, and up to 90,000 people could die.

H1N1 turned out to be much milder. Although it eventually infected more than 60 million Americans, it killed less than 13,000. In Europe, fewer than 5,000 deaths were reported.

The WHO came under fire for labeling the outbreak a pandemic too soon. European lawmakers, health professionals and others suggested the organization may have been pressured by the pharmaceutical industry.

France ordered 94 million doses, but had logged only 1,334 serious cases and 312 deaths as of April 2010. It managed to cancel 50 million doses and sell some to other countries, but it was still stuck with a €365 million tab, or about $520 million at the time, and 25 million extra doses.

The WHO had raised scares for SARS, mad-cow disease, bird flu and now swine flu, and it had been wrong each time, said Paul Flynn, a member of the Council of Europe’s Parliamentary Assembly and a British lawmaker, at a 2010 health committee hearing in Strasbourg.

Ultimately, an investigation by the council’s committee accused the WHO and public-health officials of jumping the gun, wasting money, provoking “unjustified fear” among Europeans and creating risks through vaccines and medications that might not have been sufficiently tested.

“I thought you might have uttered a word of regret or an apology,” Mr. Flynn told Dr. Fukuda, who as a representative of the WHO had been called to testify.

Back in Washington, scientist Dennis Carroll, at the U.S. Agency for International Development, was also convinced that flu wasn’t the only major pandemic threat. In early 2008, Dr. Carroll was intrigued by Dr. Daszak’s newly published research that said viruses from wildlife were a growing threat, and would emerge most frequently where development was bringing people closer to animals.

If most of these viruses spilled over to humans in just a few places, including southern China, USAID could more easily fund an early warning system.

“You didn’t have to look everywhere,” he said he realized. “You could target certain places.” He launched a new USAID effort focused on emerging pandemic threats. One program called Predict had funding of about $20 million a year to identify pathogens in wildlife that have the potential to infect people.

Drs. Daszak, Shi and Wang, supported by funds from Predict, the NIH and China, shifted their focus to Yunnan, a relatively wild and mountainous province that borders Myanmar, Laos and Vietnam.

One key discovery: a coronavirus resembling SARS that lab tests showed could infect human cells. It was the first proof that SARS-like coronaviruses circulating in southern China could hop from bats to people. The scientists warned of their findings in a study published in the journal Nature in 2013.

Evidence grew that showed people in the area were being exposed to coronaviruses. One survey turned up hundreds of villagers who said they recently showed symptoms such as trouble breathing and a fever, suggesting a possible viral infection.

Over the next several years, governments in the U.S. and elsewhere found themselves constantly on the defensive from global viral outbreaks. Time and again, preparedness plans proved insufficient. One, which started sickening people in Saudi Arabia and nearby

On a weekend morning in January 2013, more than a dozen senior Obama administration officials met in a basement family room in the suburban home of a senior National Security Council official. They were brainstorming how to help other countries upgrade their epidemic response capabilities, fueled by bagels and coffee. Emerging disease threats were growing, yet more than 80% of the world’s countries hadn’t met a 2012 International Health Regulations deadline to be able to detect and respond to epidemics.

The session led to the Global Health Security Agenda, launched by the U.S., the WHO and about 30 partners in early 2014, to help nations improve their capabilities within five years.

Money was tight. The U.S. was recovering from the 2008-09 financial crisis, and federal funding to help U.S. states and cities prepare and train for health emergencies was declining. Public-health departments had cut thousands of jobs, and outdated data systems weren’t replaced.

“It was a Hail Mary pass,” said Tom Frieden, who was director of the CDC from 2009 to 2017 and a force behind the creation of the GHSA. “We didn’t have any money.”

At the WHO, Dr. Fukuda was in charge of health security. When the Ebola outbreak was found in March 2014, he and his colleagues were already stretched, after budget cuts and amid other crises.

The United Nations created a special Ebola response mission that assumed the role normally played by the WHO. Mr. Obama sent the U.S. military to Liberia, underscoring the inability of international organizations to fully handle the problem.

It took the WHO until August to raise an international alarm about Ebola. By then, the epidemic was raging. It would become the largest Ebola epidemic in history, with at least 28,600 people infected, and more than 11,300 dead in 10 countries. The largest outbreak before that, in Uganda, had involved 425 cases.

Congress passed a $5.4 billion package in supplemental funds over five years, with about $1 billion going to the GHSA. The flood of money, along with aggressive contact tracing and other steps, helped bring the epidemic to a halt, though it took until mid-2016.

Global health experts and authorities called for changes at the WHO to strengthen epidemic response, and it created an emergencies program. The National Security Council warned that globalization and population growth “will lead to more pandemics,” and called for the U.S. to do more.

r. Carroll of USAID, who had visited West Africa during the crisis, and saw some health workers wrap themselves in garbage bags for protection, started conceiving of a Global Virome Project, to detect and sequence all the unknown viral species in mammals and avian populations on the planet.

Billionaire Bill Gates warned in a TED talk that an infectious disease pandemic posed a greater threat to the world than nuclear war, and urged world leaders to invest more in preparing for one. The Bill & Melinda Gates Foundation helped form a new initiative to finance vaccines for emerging infections, the Coalition for Epidemic Preparedness Innovations.

Congress established a permanent Infectious Diseases Rapid Response Fund for the CDC in fiscal 2019, with $50 million for that year and $85 million in fiscal 2020.

In May 2018, John Bolton, then President Trump’s national security adviser, dismantled an NSC unit that had focused on global health security and biodefense, with staff going to other units. The senior director of the unit left.

It pushed emerging disease threats down one level in the NSC hierarchy, making pandemics compete for attention with issues such as North Korea, said Beth Cameron, a previous senior director of the unit. She is now vice president for global biological policy and programs at the Nuclear Threat Initiative.

Deteriorating relations with China reduced Washington’s activities there just as researchers were becoming more certain of the threat from coronaviruses.

Dr. Carroll had earlier been ordered to suspend his emerging pandemic threats program in China.

Dr. Carroll pitched to USAID his Global Virome Project. USAID wasn’t interested, he said. He left USAID last year. A meeting that Dr. Carroll planned for last August with the Chinese CDC and Chinese Academy of Sciences to form a Chinese National Virome Project was postponed due to a bureaucratic hang-up. Plans to meet are now on hold, due to Covid-19.

But I do think it’s going to be a while before this virus becomes completely normal. And I’ve never been convinced that this current generation of elderly people will ever get to a place where it is completely normal. If you’re 65 or 75 or even older — it’s really hard to teach an immune system new tricks if you’re that age

And so while we may see excess mortality in the elderly decline somewhat, I don’t think we’ll see it ever disappear for this generation who was already old when the pandemic hit. Many will never develop that robust, long-term immunological memory we would want to see — and which happens naturally to someone who’s been exposed hundreds of times since they were a little baby.

With Covid, when it infects you, it can land in your upper respiratory tract and it just start replicating right there. Immediately, it’s present and replicating in your lungs and in your nose. And that alone elicits enough of an immune response to cause us to feel really crappy and even cause us to feel disease.

Is it really the case that, as babies, we are fighting off those viruses hundreds of times?The short answer is yeah. We start seeing viruses when we’re 2 months old, when we’re a month old. And a lot of these viruses we’ve seen literally tens, if not hundreds of times for some people by the time we’re adults. People tend to think that immunity is binary — you’re either immune or you’re not. That couldn’t be farther from the truth. It’s a gradient, and your protection gets stronger the more times you see a virus.

We used to think we just had this spectacular immune response when we first encountered the virus at, say, age 6, and that the immune response lasted until we were 70. But actually what we were seeing was the effect of an immune system being retrained every time it came into contact with the virus after the initial infection — at 6, and 7, and 8, and so on. Every time your friend got chickenpox, or your neighbor, you got a massive boost. You were re-upping your immune response and diversifying your immunological tools — potentially multiple times a year, a kind of natural booster.

But now, in America, kids get chickenpox vaccines. So you don’t have kids in America getting chickenpox today, and never will. But that means that older Americans, who did get it as kids, are not being exposed again — certainly not multiple times each year. And it turns out that, in the absence of routine re-exposures, that first exposure alone isn’t nearly as good at driving lifelong immunity and warding off shingles until your immune system begins to fall apart in old age — it can last until you’re in your 30s, for example but not until your 70s.

There’s a similar story with measles. There is no routine later-life sequelae, like shingles, for measles. But what we do see is that, in measles outbreaks today, there are some people who were vaccinated who get it anyway. Maybe 5 to 15 percent of cases are not immunologically naïve people, but vaccinated people.

But we could have just set the narrative better at the beginning: Look, you might get sick again, but your risk of landing in the hospital is going to be really low, and if you get a booster, you might still get sick again, but your risk of landing in the hospital is going to be even lower. That’s something I think humans can deal with, and I think the public could have understood it.

But it’s why we don’t see the severe disease as much, with a second exposure or an exposure after vaccination: For most people, it’s not getting into the heart and the liver and stuff nearly as easily.

But it doesn’t have to. It’s still causing symptomatic disease. And maybe mucosal vaccines could stop this, but without them we’re likely to continue seeing infections and even symptomatic infections.

through most of 2020 and into 2021, though. Back then, I think the conventional wisdom was that a single exposure — through infection or vaccination — would be the end of the pandemic for you. If this is basic virology and immunology, how did we get that so wrong?

The short answer is that epidemiologists are not immunologists and immunologists are not virologists and virologists are not epidemiologists. And, in general, physicians don’t know anything about the details.

But this failure had some pretty concrete impacts. When reinfections first began popping up, people were surprised, they were scared, and then, to some degree, they lost trust in vaccines. And the people they were turning to for guidance — not only did they not warn us about that, they were slow to acknowledge it, as well.

It had dramatic impacts and ripple effects that will last for years to limit our ability to get populations properly vaccinated.

For babies born today, though, I really think they’re not going to view Covid as any different than other viruses. By the time they are 20, it will be like any other virus to them. Because their immune systems will have grown up with it.

And now, there’s a huge number of people questioning, do these vaccines even do anything?

the worst thing we can do during a pandemic is set inappropriately high expectations. These vaccines are incredible, they’ve had an enormously positive impact on mortality, but they were never going to end the pandemic.

Instead, we set society up for failure, since people feel like the government failed everyone, that biology failed us, and that this was a crazy virus that has broken all the rules of our immune system, when it’s just doing what we’ve always known it would do.

The really hard part of answering that question is there’s just not enough data on the frequency of long-term effects, because nothing like this has ever happened at such scale. It’s like everyone in Europe and North America suddenly traveled to a country where malaria was endemic.

To say that this is a textbook virus, it doesn’t mean that it’s not killing people. Objectively, it’s still killing more people than any other infectious disease

What it means is that we could’ve taken action based on what we knew, rather than waiting around to prove everything and publish papers in Nature and Science talking about things we already knew.

We could have prepared for November and December of 2020 and then for November and December of 2021. But everyone kept saying, we don’t know if it’s going to come back. We knew it was going to come back and it makes me want to cry to think about it. We did nothing and hundreds of thousands of people died. We didn’t prepare nursing homes because we all got to the summer of 2020 and we said, cross our fingers.

We knew how tests worked. We knew about serial testing and why it was important for a public health approach. We knew that vaccines could have really good impacts once they were around. And if you were looking through the correct lens, we even knew that they weren’t going to stop transmission.

We didn’t have to live in a world where we were flying blind. We could have lived in a world where we’re knowledgeable. But instead, we chose almost across the board to will ourselves into this state of fear and anxiety.

And that really started in the earliest days. Almost the first experience I had was a lot like that movie with Jennifer Lawrence —Don’t Look Up.

none of this was complicated. You just had to ask a simple question: what would happen if you took away all immunity from an adult? Well, once you control for no immunity, adults are going to get very, very sick.

Of course, by and large, babies didn’t get very sick from this disease.Babies are immunologically naïve, but they are also resilient. A virus can tear up a baby, but a baby can repair its tissue so fast. Adults don’t have that. It’s just like a baby getting a cut. They’ll heal really quick

An adult getting a cut — you go by age, and every decade of age that you are, it’s going to take exponentially longer for that wound to heal. Eventually get to 80 or 90 and the wound can’t even heal. In the immunology world, this is called “tolerance.”

why are all these organ systems getting damaged when other viruses don’t seem to do that? It’s natural to think, it’s Covid — this is a weird disease. But it’s much more a story about immunity and how it develops than about the virus or the disease. None of our organ systems had any immune defenses around to help them out. And I think that the majority of post-acute sequelae and multi-organ complications and long Covid — they are not the result of the virus being a crazy different virus, but are a result of this virus replicating in an environment where there were such absent or exceedingly low defenses.

Is it the same whenever we encounter a virus for the first time?Think about travelers. Travelers get way more sick from a local disease than people who grew up with that virus. If you get malaria as a traveler, you’re much more likely to get really sick. You don’t see everyone in Nicaragua taking chloroquine every day. But you definitely see travelers taking it, because malaria can be deadly for adults.

What about, not severity, but post-acute complications — do we have long malaria? Do we have liver complications from dengue?

How do you wish we had messaged things differently? What would it have meant to communicate early and clearly that Covid was a textbook virus, as you say?I think the biggest thing would have been just to say, we understand the enemy.

Or think about H.I.V. It essentially kills your immune system, and once the immune barriers are down, other viruses that used to infect humans would get into tissues that we didn’t like them to get into. If there wasn’t such a clear signal of a loss of CD-4 T cells to explain it, people might still be scratching their heads and going, man, I wonder why all these patients are getting fungal infections. Well, there’s a virus there that’s depleting their immune system.

Covid is absolutely waking the world up to this — to the fact that there are really weird long-term sequelae to viruses when they infect organ systems that would normally be protected. And I think we’re going to find that more and more cancers are being attributed to viral infections.

It wasn’t that long ago that we first learned that most cases of cervical cancer were caused by H.P.V. — I think the 1980s. And now we have a vaccine for H.P.V. and rates of cervical cancer have fallen by two-thirds.

what about incidence? We’ve talked at a few points about how important it is to think about all of these questions in terms of the scale. What is the right scale for thinking about future long Covid, for instance, or other post-acute sequelae?

I think the absolute risk, per infection, is going down and down and down. That’s just true.

he U.K.’s Office of National Statistics, which shows a much lower risk of developing long Covid now, from reinfection, than from an initial infection earlier in the pandemic.

the worst is definitely behind us, which is a good thing, especially for people who worry that the problems will keep building and a lot of people — or even everyone — will get long Covid symptoms. I don’t think there’s a world where we’re looking at the babies of today dealing with long Covid at any meaningful scale.

a lot of the fear right now comes from the worst cases, and there’s a lot of worst cases. Even one of the people that I know well, I know in their mind they’re worried that they’ll never recover, but I think objectively they are recovering slowly. It might not be an eight month course. It might be a year and a half. But they will get better. Most of us will.

Researchers expected the details in the study to dispel doubts about the likelihood that many years of head trauma can lead to C.T.E. The growing connections between head trauma and contact sports, though, have led some nervous parents and coaches to assume that any concussion could lead to long-term impairment. Some doctors say that oversimplifies matters. Rather, the total amount of head trauma, including smaller subconcussive hits, as well as how they were treated, must be considered

But the F.D.A. advisory committee, along with an independent think tank and several prominent experts — including some Alzheimer’s doctors who worked on the aducanumab clinical trials — said the evidence raised significant doubts about whether the drug is effective.

The F.D.A. authorized the drug under a program called accelerated approval, which has been applied to therapies for some cancers and other serious diseases for which there are few, if any, treatments.

The risks with aducanumab involve brain swelling or bleeding experienced by about 40 percent of Phase 3 trial participants receiving the high dose. Most were either asymptomatic or had headaches, dizziness or nausea. But such effects prompted 6 percent of high-dose recipients to discontinue. No Phase 3 participants died from the effects, but one safety trial participant did.

About two million Americans may fit the description of the patients the drug was tested on: people in the early stages of Alzheimer’s or the stage just before that, Alzheimer’s-related mild cognitive impairment. About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages.

The crux of the controversy over aducanumab involved two Phase 3 trials with results that contradicted each other: One suggested the drug slightly slowed cognitive decline while the other trial showed no benefit. The trials were stopped early by a data monitoring committee that found aducanumab didn’t appear to be showing any benefit. Consequently, over a third of the 3,285 participants in those trials were never able to complete them.

Aducanumab, a monoclonal antibody, targets a protein, amyloid, that clumps into plaques in the brains of Alzheimer’s patients and is considered a biomarker of the disease. One thing both critics and supporters of approval agree on is that the drug substantially reduces levels of amyloid, and the F.D.A. said that the drug’s effect on a biomarker qualified it for the accelerated approval program.

He estimates 25 to 40 percent of the clinic’s roughly 3,000 patients might be eligible, but it doesn’t have enough neurologists.

Such information would allow detection of so-called Mendelian disorders, like cystic fibrosis, Tay-Sachs disease and Marfan syndrome, which are caused by mutations in a single gene.

Outbreaks can be influenced by seasonal weather conditions, which affect the numbers of the virus's natural host - the multimammate rat.

Most people catch Lassa fever from anything contaminated with rat urine, faeces, blood or saliva - through eating, drinking or simply handling contaminated objects in the home.

It is likely that a vaccine could be found for Lassa - reducing the possibility of an outbreak becoming a global health emergency - but as with other epidemic diseases that mainly affect poorer countries, progress has stalled.

Vaccine development is a long, complex and costly process. This is especially true for emerging epidemic diseases, where a prototype vaccine can usually only be tested where there is an outbreak.

what the administration should have been doing in January to prepare us for today.

She cites the delay on tests, without which “cases go undetected and people continue to circulate” as a leading issue along with other missed federal government responses—many of which are still not fully operational

The prescient recommendations from experts across disciplines in the period before COVID-19 reached American shores—about testing, equipment, and distancing—make clear that more than any single factor, it was Trump’s squandering of out lead-time which should have been used to prepare for the pandemic that has exacerbated this crisis.

What follows is an annotated timeline revealing the warning signs the administration received and showing how slow the administration was to act on these recommendations.

The Early Years: Warnings Ignored

2017: Trump administrations officials are briefed on an intelligence document titled “Playbook for Early Response to High-Consequence Emerging Infectious Disease Threats and Biological Incidents.” That’s right. The administration literally had an actual playbook for what to do in the early stages of a pandemic

February 2018: The Washington Post writes “CDC to cut by 80 percent efforts to prevent global disease outbreak.” The meat of the story is “Countries where the CDC is planning to scale back include some of the world’s hot spots for emerging infectious disease, such as China, Pakistan, Haiti, Rwanda and Congo.”

May 2018: At an event marking the 100 year anniversary of the 1918 pandemic, Borio says “pandemic flu” is the “number 1 health security issue” and that the U.S. is not ready to respond.

One day later her boss, Rear Adm. Timothy Ziemer is pushed out of the administration and the global health security team is disbanded

Beth Cameron, former senior director for global health security on the National Security Council adds: “It is unclear in his absence who at the White House would be in charge of a pandemic,” Cameron said, calling it “a situation that should be immediately rectified.” Note: It was not

January 2019: The director of National Intelligence issues the U.S. Intelligence Community’s assessment of threats to national security. Among its findings:

A novel strain of a virulent microbe that is easily transmissible between humans continues to be a major threat, with pathogens such as H5N1 and H7N9 influenza and Middle East Respiratory Syndrome Coronavirus having pandemic potential if they were to acquire efficient human-to-human transmissibility.”

Page 21: “We assess that the United States and the world will remain vulnerable to the next flu pandemic or large scale outbreak of a contagious disease that could lead to massive rates of death and disability, severely affect the world economy, strain international resources, and increase calls on the United States for support.”

September, 2019: The Trump Administration ended the pandemic early warning program, PREDICT, which trained scientists in China and other countries to identify viruses that had the potential to turn into pandemics. According to the Los Angeles Times, “field work ceased when funding ran out in September,” two months before COVID-19 emerged in Wuhan Province, China.

2020: COVID-19 Arrives

anuary 3, 2020: The CDC is first alerted to a public health event in Wuhan, China

January 6, 2020: The CDC issues a travel notice for Wuhan due to the spreading coronavirus

Note: The Trump campaign claims that this marks the beginning of the federal government disease control experts becoming aware of the virus. It was 10 weeks from this point until the week of March 16 when Trump began to change his tone on the threat.

January 10, 2020: Former Trump Homeland Security Advisor Tom Bossert warns that we shouldn’t “jerk around with ego politics” because “we face a global health threat…Coordinate!”

January 18, 2020: After two weeks of attempts, HHS Secretary Alex Azar finally gets the chance to speak to Trump about the virus. The president redirects the conversation to vaping, according to the Washington Post. 

January 21, 2020: Dr. Nancy Messonnier, the director of the National Center for Immunization and Respiratory Disease at the CDC tells reporters, “We do expect additional cases in the United States.”

January 27, 2020: Top White House aides meet with Chief of Staff Mick Mulvaney to encourage greater focus on the threat from the virus. Joe Grogan, head of the White House Domestic Policy Council warns that “dealing with the virus was likely to dominate life in the United States for many months.”

January 28, 2020: Two former Trump administration officials—Gottlieb and Borio—publish an op-ed in the Wall Street Journal imploring the president to “Act Now to Prevent an American Epidemic.” They advocate a 4-point plan to address the coming crisis:

(1) Expand testing to identify and isolate cases. Note: This did not happen for many weeks. The first time more than 2,000 tests were deployed in a single day was not until almost six weeks later, on March 11.

(3) Prepare hospital units for isolation with more gowns and masks. Note: There was no dramatic ramp-up in the production of critical supplies undertaken. As a result, many hospitals quickly experienced shortages of critical PPE materials. Federal agencies waited until Mid-March to begin bulk orders of N95 masks.

January 29, 2020: Trump trade advisor Peter Navarro circulates an internal memo warning that America is “defenseless” in the face of an outbreak which “elevates the risk of the coronavirus evolving into a full-blown pandemic, imperiling the lives of millions of Americans.”

January 30, 2020: Dr. James Hamblin publishes another warning about critical PPE materials in the Atlantic, titled “We Don’t Have Enough Masks.”

January 29, 2020: Republican Senator Tom Cotton reaches out to President Trump in private to encourage him to take the virus seriously.

Late January, 2020:  HHS sends a letter asking to use its transfer authority to shift $136 million of department funds into pools that could be tapped for combating the coronavirus. White House budget hawks argued that appropriating too much money at once when there were only a few U.S. cases would be viewed as alarmist.

Trump’s Chinese travel ban only banned “foreign nationals who had been in China in the last 14 days.” This wording did not—at all—stop people from arriving in America from China. In fact, for much of the crisis, flights from China landed in America almost daily filled with people who had been in China, but did not fit the category as Trump’s “travel ban” defined it.

January 31, 2020: On the same day Trump was enacting his fake travel ban, Foreign Policy reports that face masks and latex gloves are sold out on Amazon and at leading stores in New York City and suggests the surge in masks being sold to other countries needs “refereeing” in the face of the coming crisis.

February 4, 2020: Gottlieb and Borio take to the WSJ again, this time to warn the president that “a pandemic seems inevitable” and call on the administration to dramatically expand testing, expand the number of labs for reviewing tests, and change the rules to allow for tests of people even if they don’t have a clear known risk factor.

Note: Some of these recommendations were eventually implemented—25 days later.

February 5, 2020: HHS Secretary Alex Azar requests $2 billion to “buy respirator masks and other supplies for a depleted federal stockpile of emergency medical equipment.” He is rebuffed by Trump and the White House OMB who eventually send Congress a $500 million request weeks later.

February 4 or 5, 2020: Robert Kadlec, the assistant secretary for preparedness and response, and other intelligence officials brief the Senate Intelligence Committee that the virus poses a “serious” threat and that “Americans would need to take actions that could disrupt their daily lives.”

February 5, 2020: Senator Chris Murphy tweets: Just left the Administration briefing on Coronavirus. Bottom line: they aren't taking this seriously enough. Notably, no request for ANY emergency funding, which is a big mistake. Local health systems need supplies, training, screening staff etc. And they need it now.

February 9, 2020: The Washington Post reports that a group of governors participated in a jarring meeting with Dr. Anthony Fauci and Dr. Robert Redfield that was much more alarmist than what they were hearing from Trump. “The doctors and the scientists, they were telling us then exactly what they are saying now,” Maryland Gov. Larry Hogan (R) said.

the administration lifted CDC restrictions on tests. This is a factually true statement. But it elides that fact that they did so on March 3—two critical weeks after the third Borio/Gottlieb op-ed on the topic, during which time the window for intervention had shrunk to a pinhole.

February 20, 2020: Borio and Gottlieb write in the Wall Street Journal that tests must be ramped up immediately “while we can intervene to stop spread.”

February 23, 2020: Harvard School of Public Health professor issues warning on lack of test capability: “As of today, the US remains extremely limited in#COVID19 testing. Only 3 of ~100 public health labs haveCDC test kits working and CDC is not sharing what went wrong with the kits. How to know if COVID19 is spreading here if we are not looking for it.

February 24, 2020: The Trump administration sends a letter to Congress requesting a small dollar amount—between $1.8 billion and $2.5 billion—to help combat the spread of the coronavirus. This is, of course, a pittance

February 25, 2020: Messonier says she expects “community spread” of the virus in the United States and that “disruption to everyday life might be severe.” Trump is reportedly furious and Messonier’s warnings are curtailed in the ensuing weeks.

Trump mocks Congress in a White House briefing, saying “If Congress wants to give us the money so easy—it wasn’t very easy for the wall, but we got that one done. If they want to give us the money, we’ll take the money.”

February 26, 2020: Congress, recognizing the coming threat, offers to give the administration $6 billion more than Trump asked for in order to prepare for the virus.

February 27, 2020: In a leaked audio recording Sen. Richard Burr, chairman of the Intelligence Committee and author of the Pandemic and All-Hazards Preparedness Act (PAHPA) and the Pandemic and All-Hazards Preparedness and Advancing Innovation Act (reauthorization of PAHPA), was telling people that COVID-19 “is probably more akin to the 1918 pandemic.”

March 4, 2020: HHS says they only have 1 percent of respirator masks needed if the virus became a “full-blown pandemic.”

March 3, 2020: Vice President Pence is asked about legislation encouraging companies to produce more masks. He says the Trump administration is “looking at it.”

March 7, 2020: Fox News host Tucker Carlson, flies to Mar-a-Lago to implore Trump to take the virus seriously in private rather than embarrass him on TV. Even after the private meeting, Trump continued to downplay the crisis

March 9, 2020: Tom Bossert, Trump’s former Homeland Security adviser, publishes an op-ed saying it is “now or never” to act. He advocates for social distancing and school closures to slow the spread of the contagion.

Trump says that developments are “good for the consumer” and compares COVID-19 favorably to the common flu.

March 17, 2020: Facing continued shortages of the PPE equipment needed to prevent healthcare providers from succumbing to the virus, Oregon Senators Jeff Merkeley and Ron Wyden call on Trump to use the Defense Production Act to expand supply of medical equipment

March 18, 2020: Trump signs the executive order to activate the Defense Production Act, but declines to use it

At the White House briefing he is asked about Senator Chuck Schumer’s call to urgently produce medical supplies and ventilators. Trump responds: “Well we’re going to know whether or not it’s urgent.” Note: At this point 118 Americans had died from COVID-19.

March 20, 2020: At an April 2nd White House Press Conference, President Trump’s son-in-law Jared Kushner who was made ad hoc point man for the coronavirus response said that on this date he began working with Rear Admiral John Polowczyk to “build a team” that would handle the logistics and supply chain for providing medical supplies to the states. This suggestion was first made by former Trump Administration officials January 28th

March 22, 2020: Six days after calling for a 15-day period of distancing, Trump tweets that this approach “may be worse than the problem itself.”

March 24, 2020: Trump tells Fox News that he wants the country opened up by Easter Sunday (April 12)

As Trump was speaking to Fox, there were 52,145 confirmed cases in the United States and the doubling time for daily new cases was roughly four days.

Aviation is safe in large part because it learns from its disasters. Investigators from the U.S. National Transportation Safety Board go immediately to accident sites to begin assessing evidence. After months or even years of research, their detailed reports try to lay out the “accident chain” and explain what went wrong

with respect to the coronavirus pandemic, it has suffered by far the largest number of fatalities, about one-quarter of the global total, despite having less than one-20th of the world’s population.

What if the NTSB were brought in to look at the Trump administration’s handling of the pandemic? What would its investigation conclude?

This was a journey straight into a mountainside, with countless missed opportunities to turn away. A system was in place to save lives and contain disaster. The people in charge of the system could not be bothered to avoid the doomed course.

Timelines of aviation disasters typically start long before the passengers or even the flight crew knew anything was wrong, with problems in the design of the airplane, the procedures of the maintenance crew, the route, or the conditions into which the captain decided to fly. In the worst cases, those decisions doomed the flight even before it took off. My focus here is similarly on conditions and decisions that may have doomed the country even before the first COVID-19 death had been recorded on U.S. soil.

What happened once the disease began spreading in this country was a federal disaster in its own right: Katrina on a national scale, Chernobyl minus the radiation. It involved the failure to test; the failure to trace; the shortage of equipment; the dismissal of masks; the silencing or sidelining of professional scientists; the stream of conflicting, misleading, callous, and recklessly ignorant statements by those who did speak on the national government’s behalf

As late as February 26, Donald Trump notoriously said of the infection rate, “You have 15 people, and the 15 within a couple of days is going to be down close to zero.” What happened after that—when those 15 cases became 15,000, and then more than 2 million, en route to a total no one can foretell—will be a central part of the history of our times.

1. The Flight Plan

the most important event was the H5N1 “bird flu” outbreak, in 2005. It originated in Asia and was mainly confined there, as the SARS outbreak had been two years earlier. Bush-administration officials viewed H5N1 as an extremely close call. “

Shortly before Barack Obama left office, his administration’s Pandemic Prediction and Forecasting Science and Technology Working Group—yes, that was a thing—released a report reflecting the progress that had been made in applying remote-sensing and AI tools since the early days of Global Argus. The report is freely available online and notes pointedly that recent technological advances “provide opportunities to mitigate large-scale outbreaks by predicting more accurately when and where outbreaks are likely to occur, and how they will progress.”

“Absolutely nothing that has happened has been a surprise. We saw it coming. Not only did we see it, we ran the models and the gaming exercises. We had every bit of the structure in place. We’ve been talking about a biohazard risk like this for years. Anyone who says we did not see this coming has their head in the sand, or is lying through their teeth.”

The system the government set up was designed to warn not about improbable “black swan” events but rather about what are sometimes called “gray rhinos.” These are the large, obvious dangers that will sooner or later emerge but whose exact timing is unknown.

other U.S. leaders had dealt with foreign cover-ups, including by China in the early stages of the SARS outbreak in 2002. Washington knew enough, soon enough, in this case to act while there still was time.

During the Obama administration, the U.S. had negotiated to have its observers stationed in many cities across China, through a program called Predict. But the Trump administration did not fill those positions, including in Wuhan. This meant that no one was on site to learn about, for instance, the unexplained closure on January 1 of the city’s main downtown Huanan Seafood Wholesale Market, a so-called wet market

“It was in the briefings by the beginning of January,” a person involved in preparing the president’s briefing book told me. “On that there is no dispute.” This person went on: “But knowing it is in the briefing book is different from knowing whether the president saw it.” He didn’t need to spell out his point, which was: Of course this president did not.

To sum up: The weather forecast showed a dangerous storm ahead, and the warning came in plenty of time. At the start of January, the total number of people infected with the virus was probably less than 1,000. All or nearly all of them were in China. Not a single case or fatality had been reported in the United States.

2. The Air Traffic Controllers

In cases of disease outbreak, U.S. leadership and coordination of the international response was as well established and taken for granted as the role of air traffic controllers in directing flights through their sectors

in normal circumstances, its location in China would have been a plus. Whatever the ups and downs of political relations over the past two decades, Chinese and American scientists and public-health officials have worked together frequently, and positively, on health crises ranging from SARS during George W. Bush’s administration to the H1N1 and Ebola outbreaks during Barack Obama’s.

One U.S. official recalled the Predict program: “Getting Chinese agreement to American monitors throughout their territory—that was something.” But then the Trump administration zeroed out that program.

“We had cooperated with China on every public-health threat until now,” Susan Shirk, a former State Department official and longtime scholar of Chinese affairs at UC San Diego, told me. “SARS, AIDS, Ebola in Africa, H1N1—no matter what other disputes were going on in the relationship, we managed to carve out health, and work together quite professionally. So this case is just so anomalous and so tragic.” A significant comparison, she said, is the way the United States and the Soviet Union had worked together to eliminate smallpox around the world, despite their Cold War tensions. But now, she said, “people have definitely died because the U.S. and China have been unable to cooperate.”

What did the breakdown in U.S.-Chinese cooperation mean in practice? That the U.S. knew less than it would have otherwise, and knew it later; that its actions brought out the worst (rather than the merely bad) in China’s own approach to the disease, which was essentially to cover it up internally and stall in allowing international access to emerging data; that the Trump administration lost what leverage it might have had over Chinese President Xi Jinping and his officials; and that the chance to keep the disease within the confines of a single country was forever lost.

In addition to America’s destruction of its own advance-warning system, by removing CDC and Predict observers, the Trump administration’s bellicose tone toward China had an effect. Many U.S. officials stressed that a vicious cycle of blame and recrimination made public health an additional source of friction between the countries, rather than a sustained point of cooperation, as it had been for so many years.

“The state of the relationship meant that every U.S. request was met with distrust on the Chinese side, and every Chinese response was seen on the American side as one more attempt to cover up,”