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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.

“That amount of memory would likely prevent the vast majority of people from getting hospitalized disease, severe disease, for many years,” said Shane Crotty, a virologist at the La Jolla Institute of Immunology who co-led the new study.

A study published last week also found that people who have recovered from Covid-19 have powerful and protective killer immune cells even when antibodies are not detectable.

These studies “are all by and large painting the same picture, which is that once you get past those first few critical weeks, the rest of the response looks pretty conventional,” said Deepta Bhattacharya, an immunologist at the University of Arizona

A small number of infected people in the new study did not have long-lasting immunity after recovery, perhaps because of differences in the amounts of coronavirus they were exposed to.

Although antibodies in the blood are needed to block the virus and forestall a second infection — a condition known as sterilizing immunity — immune cells that “remember” the virus more often are responsible for preventing serious illness.

More often, people become infected a second time with a particular pathogen, and the immune system recognizes the invader and quickly extinguishes the infection. The coronavirus in particular is slow to do harm, giving the immune system plenty of time to kick into gear.

“It may be terminated fast enough that not only are you not experiencing any symptoms but you are not infectious,” Dr. Sette said.

Dr. Sette and his colleagues recruited 185 men and women, aged 19 to 81, who had recovered from Covid-19. The majority had mild symptoms not requiring hospitalization

The team tracked four components of the immune system: antibodies, B cells that make more antibodies as needed; and two types of T cells that kill other infected cells.

He and his colleagues found that antibodies were durable, with modest declines at six to eight months after infection, although there was a 200-fold difference in the levels among the participants.

The study is the first to chart the immune response to a virus in such granular detail, experts said. “For sure, we have no priors here,” Dr. Gommerman said. “We’re learning, I think for the first time, about some of the dynamics of these populations through time.”

Exactly how long immunity lasts is hard to predict, because scientists don’t yet know what levels of various immune cells are needed to protect from the virus. But studies so far have suggested that even small numbers of antibodies or T and B cells may be enough to shield those who have recovered.

The challenge is that unlike some of our other organs, like the skin and liver, the heart has a very limited ability to self-heal. Heart muscle cells replicate at a rate of just 0.5% a year, not sufficient to repair any significant damage. Instead, the dead cells are replaced by thick layers of tough, rigid scar tissue, meaning that sections of the heart simply cease to function.

But along with a team of stem cell biologists at the University of Cambridge’s Stem Cell Institute, Sinha is working on a slightly different idea: heart patches.

One of the main challenges with this approach is how to electrically integrate the new patch with the heart to ensure that both beat in synchrony. Any defective electrical connections could stimulate an abnormal heart rhythm.

So in recent years, scientists started creating structures that resemble human embryos in the lab by using chemical signals to coax cells into forming themselves into entities that look like very primitive human embryos.

Now, Wu's team and another international team of scientists have gone further than ever before. They created hollow balls of cells that closely resemble embryos at the stage when they usually implant in the womb, which are known as blastocysts. The new laboratory-made embryos have been dubbed "blastoids."

Now with this technique we can make hundreds of these structures. So this will allow us to scale up our understanding of very early human development. We think this will be very important." Some other scientists are hailing the research.

The goal of the experiments is to gain important insights into early human development and find new ways to prevent birth defects and miscarriages and treat fertility problems.But the research, which was published in two separate papers Wednesday in the journal Nature Portfolio, raises sensitive moral and ethical concerns.

The two experiments started with different cells to get similar results. Wu's group created his blastoids from human embryonic stem cells, and from "induced pluripotent stem cells," which are made from adult cells. Polo's group started with adult skin cells.

Hyun agrees the research is very important and could lead to a many other advances. But Hyun says it's important to come up with clear guidelines about how scientists can responsibly be permitted to pursue this kind of research.

Hyun favors revising a guideline known as the 14-day rule, which prohibits experiments on human embryos in the lab beyond two weeks of their existence. Hyun says exceptions should be allowed under certain carefully reviewed conditions.

But others worry about easing the 14-day rule.That could mean "we could just keep growing these sort-of humans in a test tube and not even considering the fact that they're so close to being human, right?"

In fact, another team of scientists at the Weizmann Institute of Science in Israel figured out how to grow mouse embryos outside the womb — a step toward creating an "artificial womb," according to report published Wednesday in the journal Nature.

“Whether the Delta variant is already at that plateau, or whether there’s going to be further increases before it gets to that plateau, I can’t say. But I do think that plateau exists.”

Antibodies, which can prevent the virus from entering our cells, are engineered to latch onto specific molecules on the surface of the virus, snapping into place like puzzle pieces. But genetic mutations in the virus can change the shape of those binding sites.

“If you change that shape, you can make it impossible for an antibody to do its job,”

But as more people acquire antibodies against the virus, mutations that allow the virus to slip past these antibodies will become even more advantageous.

The good news is that there are many different kinds of antibodies, and a variant with a few new mutations is unlikely to escape them all, experts said.

its sleeve to counteract the evolution of the virus,” Dr. Pepper said. “Knowing that there is this complex level of diversity in the immune system allows me to sleep better at night.”

“It’s a lot harder to evade T cell responses than antibody responses,”

And then there are B cells, which generate our army of antibodies. Even after we clear the infection, the body keeps churning out B cells for a while, deliberately introducing small genetic mutations. The result is an enormously diverse collection of B cells producing an array of antibodies, some of which might be a good match for the next variant that comes along.

Whether the virus will become more virulent — that is, whether it will cause more serious disease — is the hardest to predict,

Unlike transmissibility or immune evasion, virulence has no inherent evolutionary advantage.

Some scientists predict that the virus will ultimately be much like the flu, which can still cause serious illness and death, especially during seasonal surges.

“The virus has no interest in killing us,” Dr. Metcalf said. “Virulence only matters for the virus if it works for transmission.”

It is too early to say whether SARS-CoV-2 will change in virulence over the long-term. There could certainly be trade-offs between virulence and transmission; variants that make people too sick too quickly may not spread very far.

Then again, this virus spreads before people become severely ill. As long as that remains true, the virus could become more virulent without sacrificing transmissibility.

Moreover, the same thing that makes the virus more infectious — faster replication or tighter binding to our cells — could also make it more virulent.

Although many possible paths remain open to us, what is certain is that SARS-CoV-2 will not stop evolving — and that the arms race between the virus and us is just beginning.

We lost the first few rounds, by allowing the virus to spread unchecked, but we still have powerful weapons to bring to the fight. The most notable are highly effective vaccines, developed at record speed. “I think there is hope in the fact that the SARS-CoV-2 vaccines at this point are more effective than flu vaccines have probably ever been,”

“I have great faith that we can sort any detrimental evolutionary trajectories out by improving our current or next generation vaccines,”

be you have a re-infection, but it’s relatively mild, which also boosts your immunity,”

rising vaccination rates may already be suppressing new mutations.And the evolution rate could also slow down as the virus becomes better adapted to humans.

“There’s low-hanging fruit,” Dr. Lauring said. “So there are certain ways it can evolve and make big improvements, but after a while there aren’t areas to improve — it’s figured out all the easy ways to improve.”

Eventually, as viral evolution slows down and our immune systems catch up, we will reach an uneasy equilibrium with the virus, scientists predict. We will never extinguish it, but it will smolder rather than rage.

So far, studies suggest that our antibody, T cell and B cell responses are all working as expected when it comes to SARS-CoV-2. “This virus is mostly playing by immunological rules we understand,”

Others are more optimistic. “My guess is that one day this is going to be another cause of the common cold,”

There are four other coronaviruses that have become endemic in human populations. We are exposed to them early and often, and all four mostly cause run-of-the-mill colds.

much of the world remains unvaccinated, and this virus has already proved capable of surprising us. “We should be somewhat cautious and humble about trying to predict what it is capable of doing in the future,”

While we can’t guard against every eventuality, we can tip the odds in our favor by expanding viral surveillance, speeding up global vaccine distribution and tamping down transmission until more people can be vaccinated

The future, he said, “depends much, much more on what humans do than on what the virus does.”

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

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

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

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

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

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

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

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

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

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

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

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

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

that would be on par with what we experience with flu viruses, which scientists estimate hit us about every two to five years, less often in adulthood. It also matches up well with the documented cadence of the four other coronaviruses that seasonally trouble humans, and cause common colds.

For now, every infection, and every subsequent reinfection, remains a toss of the dice. “Really, it’s a gamble,” says Ziyad Al-Aly, a clinical epidemiologist and long-COVID researcher at Washington University in St. Louis. Vaccination and infection-induced immunity may load the dice against landing on severe disease, but that danger will never go away completely, and scientists don’t yet know what happens to people who contract “mild” COVID over and over again

Or maybe not. This virus seems capable of tangling into just about every tissue in the body, affecting organs such as the heart, brain, liver, kidneys, and gut; it has already claimed the lives of millions, while saddling countless others with symptoms that can linger for months or years.

considering our current baseline, “less dangerous” could still be terrible—and it’s not clear exactly where we’re headed. When it comes to reinfection, we “just don’t know enough,”

Perhaps, as several experts have posited since the pandemic’s early days, SARS-CoV-2 will just become the fifth cold-causing coronavirus.

Bodies, wised up to the virus’s quirks, can now react more quickly, clobbering it with sharper and speedier strikes.

Future versions of SARS-CoV-2 could continue to shape-shift out of existing antibodies’ reach, as coronaviruses often do. But the body is flush with other fighters that are much tougher to bamboozle—among them, B cells and T cells that can quash a growing infection before it spirals out of control

Those protections tend to build iteratively, as people see pathogens or vaccines more often. People vaccinated three times over, for instance, seem especially well equipped to duke it out with all sorts of SARS-CoV-2 variants, including Omicron and its offshoots.

promising patterns: Second infections and post-vaccination infections “are significantly less severe,” she told me, sometimes to the point where people don’t notice them at all

A third or fourth bout might be more muted still; the burden of individual diseases may be headed toward an asymptote of mildness that holds for many years

Gordon and Swartz are both hopeful that the slow accumulation of immunity will also slash people’s chances of developing long COVID.

Immunity, though, is neither binary nor permanent. Even if SARS-CoV-2’s assaults are blunted over time, there are no guarantees about the degree to which that happens, or how long it lasts.

A slew of factors could end up weighting the dice toward severe disease—among them, a person’s genetics, age, underlying medical conditions, health-care access, and frequency or magnitude of exposure to the virus.

for everyone else, no amount of viral dampening can totally eliminate the chance, however small it may be, of getting very sick.

Long COVID, too, might remain a possibility with every discrete bout of illness. Or maybe the effects of a slow-but-steady trickle of minor, fast-resolving infections would sum together, and bring about the condition.

Every time the body’s defenses are engaged, it “takes a lot of energy, and causes tissue damage,” Thomas told me. Should that become a near-constant barrage, “that’s probably not great for you.”

Bodies are resilient, especially when they’re offered time to rest, and she doubts that reinfection with a typically ephemeral virus such as SARS-CoV-2 would cause mounting damage. “The cumulative effect is more likely to be protective than detrimental,” she said, because of the immunity that’s laid down each time.

people who have caught the virus twice or thrice may be more likely to become long-haulers than those who have had it just once.

Some other microbes, when they reinvade us, can fire up the immune system in unhelpful ways, driving bad bouts of inflammation that burn through the body, or duping certain defensive molecules into aiding, rather than blocking, the virus’s siege. Researchers don’t think SARS-CoV-2 will do the same. But this pathogen is “much more formidable than even someone working on coronaviruses would have expected,

Seasonal encounters with pathogens other than SARS-CoV-2 don’t often worry us—but perhaps that’s because we’re still working to understand their toll. “Have we been underestimating long-term consequences from other repeat infections?” Thomas said. “The answer is probably, almost certainly, yes.”

the rhythm of reinfection isn’t just about the durability of immunity or the pace of viral evolution. It’s also about our actions and policies, and whether they allow the pathogen to transmit and evolve. Strategies to avoid infection—to make it as infrequent as possible, for as many people as possible—remain options, in the form of vaccination, masking, ventilation, paid sick leave, and more.

“There are still very good reasons” to keep exposures few and far between, Landon, of the University of Chicago, told me. Putting off reinfection creates fewer opportunities for harm: The dice are less likely to land on severe disease (or chronic illness) when they’re rolled less often overall. It also buys us time to enhance our understanding of the virus, and improve our tools to fight it.

The outlooks of the experts I spoke with spanned the range from optimism to pessimism, though all agreed that uncertainty loomed. Until we know more, none were keen to gamble with the virus—or with their own health. Any reinfection will likely still pose a threat, “even if it’s not the worst-case scenario,” Abdool Karim told me. “I wouldn’t want to put myself in that position.”

Curley, a lawyer and former Army colonel, oversees the police officers at the building. She is best known to the public as the person who chants, "Oyez! Oyez! Oyez!" at the beginning of the justices' oral argument sessions. The marshal's office would not normally examine the details of cell phone data or engage in a broad-scale investigation of personnel.The investigation comes at the busiest time in the court's annual term, when relations among the justices are already taut. Assisted by their law clerks, the justices are pressing toward late June deadlines, trying to resolve differences in the toughest cases, all with new pressures and public scrutiny.

The draft opinion in the case of Dobbs v. Jackson Women's Health Organization was written by Justice Samuel Alito and appeared to have a five-justice majority to completely reverse the 1973 Roe v. Wade decision. That landmark ruling made abortion legal nationwide and buttressed other privacy interests not expressly stated in the Constitution. Some law professors have warned that if Roe is reversed, the Supreme Court's 2015 decision declaring a constitutional right to same-sex marriage could be in jeopardy.

As the justices continue their secret negotiations, the scrutiny of the law clerks is heating up.The clerks have been the subject of much of the outside speculation over who might have disclosed the draft, but they are not the only insiders who had access. Alito's opinion, labeled a first draft and dated February 10, would have been circulated to the nine justices, their clerks, and key staffers within each justice's chambers and select administrative offices.

Cell phones, of course, hold an enormous amount of information, related to personal interactions, involving all manner of content, texts and images, as well as apps used. It is uncertain whether details linked only to calls would be sought or whether a broader retrieval would occur.

Court officials are secretive even in normal times. No progress reports related to the leak investigation have been made public, and it is not clear whether any report from the probe will ever be released.

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

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

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

Llamas’ antibodies are also easily manipulated

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

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

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

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

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

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

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

"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.

even if his role in leading the protest onto the highway was negligent, it couldn't make him personally liable for the actions of an individual whose only association to him was attendance at the protest.

On Monday, the Supreme Court threw out the suit for now, declaring that the 5th Circuit's interpretation of state law "is too uncertain a premise on which to address" the question currently at issue.

any reasonable officer should have realized that Taylor's conditions of confinement offended the Constitution,

whether Louisiana would permit such a suit.

In a second case — involving cruel and unusual punishment of a prisoner — the justices also repudiated a 5th Circuit decision.

the prison officers responsible for this treatment could not be sued because the law "wasn't clearly established" that "prisoners "couldn't be housed in cells teaming with human waste" "for only six days." Thus, the 5th Circuit granted the officers qualified immunity from being sued.

The constitutional question — namely whether such a suit violated the First Amendment guarantee of free speech — is only raised if Louisiana law in fact permits such a suit in the first place,

The telephone format allows each justice only a few minutes to ask questions so there was no way to compare Barrett's questioning with other newbies in recent years.

New Supreme Court Justice Amy Coney Barrett heard her first oral arguments at the Supreme Court on Monday. Participating by phone with the other justices

Barrett could well be forgiven for bowing out of the court's work last week, with six days to prep before her Monday debut. But Chief Justice John Roberts also had just six days to prepare in 2005

Barrett's choice to forgo participating last week meant she did not vote in two significant cases decided by the court in opinions released Monday.

In an important First Amendment case involving a Black Lives Matter protest, the court sided with activist DeRay Mckesson in his effort to avoid a lawsuit by a police officer who was severely injured by an unknown assailant.

On Monday, the Supreme Court threw out the suit for now, declaring that the 5th Circuit's interpretation of state law "is too uncertain a premise on which to address"

Acknowledging these "exceptional circumstances," the high court, in essence, then asked the Louisiana Supreme Court to decide what the state law actually is — in short, whether Louisiana would permit such a suit.

This one involved a Texas state prisoner, Trent Taylor, who alleged that for six days in 2013 he was held in what the court called "shockingly unsanitary cells."

Taylor did not eat or drink for nearly four days. Correctional officers then moved Taylor to a second, frigidly cold cell, which was equipped with only a clogged drain in the floor to dispose of bodily wastes.

Because the cell lacked a bunk, and because Taylor was confined without clothing, he was left to sleep naked in sewage."

the Supreme Court noted that the 5th Circuit "properly held that such conditions ... violate the Eighth Amendment's prohibition on cruel and unusual punishment."

went on to say that the prison officers responsible for this treatment could not be sued because the law "wasn't clearly established" that "prisoners "couldn't be housed in cells teaming with human waste" "for only six days."

Dr. Gallo is leading the charge to test the O.P.V. live polio vaccine as a treatment for coronavirus.

B.C.G. may actually be able to ramp up the body’s initial immune response in ways that reduce the amount of virus in the body, such that an inflammatory response never occurs.

ey might eventually grow human organs in such animals for transplantation.

Another concern is that using human cells in this way could produce animals that have human sperm or eggs.

The notion of using organs from animals for transplants has also long raised concerns about spreading viruses from animals to humans. So, if the current research comes to fruition, steps would have to be taken to reduce that infection risk, scientists said, such as carefully sequestering animals used for that purpose and screening any organs used for transplantation.

This rapid radical reduction in the price of PV solar is a story about Chinese industrial might backed by American capital, fanned by European political sensibilities and made possible largely thanks to the pioneering work of an Australian research team.

“We’ve got to the point where solar is the cheapest source of energy in the world in most places. This means we’ve been trying to model a situation where the grid looks totally different today.”

Every time you double producing capacity, you reduce the cost of PV solar by 28%

In the very early years of the industry, the received wisdom had been that a 20% conversion rate marked the hard limit of what was possible from PV solar cells. Green, however, disagreed in a paper published in 1984.A year later, his team built the first cell that pushed past that limit, and in 1989 built the first full solar panel capable of running at 20% efficiency.

It was a moment that opened up what was possible from the industry, and the new upper limit was “set” at 25% – another barrier Green and his team would smash in 2008. In 2015, they built the world’s most efficient solar cell, achieving a 40.6% conversion rate using focused light reflected off a mirror.

“The first reaction was: that’s the future. Everybody said that’s the future. But they also said it was one step too early. What they meant was that there was no market for it yet. In China at the time, if you mentioned solar, people thought of solar hot water.”

All that would change when Germany passed new laws encouraging the uptake of solar power. Quickly it became clear there was a massive global demand and the world’s manufacturers were struggling to keep up with supply.

Spying an opportunity for investment, a consortium that included Actis Capital and Goldman Sachs came knocking to pitch Shi on taking the company public. When the company listed on the New York Stock Exchange in 2005, it raised $420m and made Shi an instant billionaire. A year later he would be worth an estimated $3bn and crowned the richest man in China, earning him the moniker “the Sun King”.

Around 2012 the world market was flooded with solar panels, sending the price plummeting through the floor, leaving SunTech vulnerable. Already under intense financial pressure, disaster struck when an internal investigation found a takeover bid it had launched had been guaranteed by €560m in fake German government bonds.

In a quirk of history, what had begun as an American drive to wean itself off oil was eventually taken up by China, which made solar power dirt cheap in the process.“The Chinese approach to renewables is all about energy security,” Mathews says. “At the scale from which they’re building new industries, they would need colossal imports of conventional fossil fuels, which would cripple them economically.

“They can get around that problem, which is a geopolitical obstacle, by manufacturing their own energy equipment.”

“We think a 40% module, rather than the 22% you can do nowadays with PERC, is what the industry will be doing once we perfect this stacking approach,” Green says. “We’re just trying to find a new cell that will have all the qualities of silicon that we can stack on top of silicon.

“The International Energy Agency now says solar is providing the cheapest energy the world has ever seen. But we’re headed towards a future of insanely cheap energy.“It’s a fundamentally different world we’re moving into.”

In severe cases, however, the clash between the virus and the immune system rages much longer. Other parts of the body, including those not directly affected by the virus, become collateral damage, prompting serious and potentially life-threatening symptoms

On Friday, the president received an experimental antibody cocktail developed by drug maker Regeneron. The next day he began a course of the antiviral remdesivir. Experts say such treatments might be best administered early in infection, to rein in the virus before it runs amok.

A typical immune response launches its defense in two phases. First, a cadre of fast-acting fighters rushes to the site of infection and attempts to corral the invader. This so-called innate response buys the rest of the immune system time to mount a second, more tailored attack, called the adaptive response, which kicks in about a week later, around the time the first wave begins to wane.

Eventually, a second wave of immune cells and molecules arrives, more targeted than their early counterparts and able to home in on the coronavirus and the cells it infects.

If the innate immune system makes early progress against the virus, the infection may be mild. But if the body’s defenses flag, the coronavirus may continue replicating, ratcheting up the viral load. Faced with a growing threat, innate immune cells will continue to call for help, fueling a vicious cycle of recruitment and destruction. Prolonged, excessive inflammation can cause life-threatening damage to vital organs like the heart, kidneys and lungs.

On Sunday, President Trump’s doctors reported that he had also received a course of dexamethasone, a steroid that broadly blunts the immune response by curbing the activity of several cytokines. Dexamethasone has been shown to reduce death rates in hospitalized Covid-19 patients who are ill enough to require ventilation or supplemental oxygen. But it is far less likely to help and may even harm patients at an earlier stage of infection, or those who have milder disease. Experts say that administering dexamethasone inappropriately, or too soon, could undermine a helpful immune response, allowing the virus to ravage the body.

At 74 years old and about 240 pounds, Mr. Trump occupies a high-risk age group and verges on obesity, a condition that can exacerbate the severity of Covid-19. Men also tend to have a poorer disease prognosis.

Dogged by skepticism and inconsistent funding, these coronavirus researchers were stymied from developing treatments and vaccines for SARS—many of which could have been helpful in the current crisis.

Another similarly affected researcher was Brenda Hogue, a virologist at Arizona State University in Tempe. Hogue had devoted her career to studying coronaviruses, focusing on the protein machinery that drives their assembly. After SARS, she and her colleagues turned part of their attention toward developing a vaccine. But when the funding dropped off in 2008, she said, the vaccine went into limbo “and we put our efforts into other directions.”

to some experts whose business it is to hunt potential pathogens before they spill over into human populations, the many years spent not girding for a serious coronavirus outbreak were tragically—and unnecessarily—wasted.

“We were out there on the ground after SARS, working on coronaviruses with Chinese colleagues in collaboration,” said Peter Daszak, president of the EcoHealth Alliance, a New York–based nonprofit group that took part in a large federally funded effort, called Predict, to hunt for new pandemic viruses in wildlife in 31 countries, including China. That program was famously defunded last fall, just before the SARS-CoV-2 outbreak began.

“But we were the only group of western scientists,” Daszak added. “How can we be the only people looking for these viruses when there was such a clear and present danger?”

when SARS emerged in late 2002, there was initially “general disbelief among medical people that a coronavirus could be the basis of such a huge outbreak.”

As that epidemic spread, an influx of new researchers crowded the field. More grants were awarded, and funding started to climb. “Everyone wanted to know where the virus had come from,” said Ralph Baric, a microbiologist at the University of North Carolina’s Gillings School of Global Public Health. Initial findings pointed to wild civets and raccoon dogs sold for meat and pelts, respectively, in Chinese markets. Later evidence began to implicate horseshoe bats as the original source of the infections. Some researchers whose pre-SARS careers had been grounded in basic coronavirus biology began working on therapies and vaccines—and they made steady progress for several years.

funding declines hobbled individual investigators who weren’t part of these larger consortia. Pharmaceutical companies that develop vaccines and therapies scaled back on coronavirus research, too. Within a few years after the SARS outbreak, public health funding agencies both in the United States and abroad “no longer regarded coronaviruses as a high public health threat compared to other diseases,” Saif wrote in an email.

Then on May 12, The Wall Street Journal reported that the Chinese government was responding in kind, “by stalling international efforts to find the source of the [SARS-CoV-2] virus amid an escalating U.S. push to blame China for the pandemic.”

To demonstrate that a particular virus is actually harmful to people, scientists need to isolate and culture the microbe and show it infects human cells in the lab

Led by virologist Zheng-Li Shi, the Wuhan team reported in 2013 that this particular virus, called WIV1, binds with ACE2 in civet and human cells, and then replicates efficiently inside them. “That was the red flag,” Saif said. Earlier evidence suggested that direct contact with these bats could lead to viral spillover in humans. “Now there was proof of that.”

hen cases of those diseases fell off, public-health responders shifted to other viral emergencies such as Ebola and Zika, and coronavirus research funding dropped sharply.

They created a hybrid microbe by attaching the spike protein from SHC014 to the genetic backbone of a SARS-like virus that was previously adapted to grow in mice. Called a chimera—an organism containing cells with more than one genotype—this lab-made microbe had no problem binding with ACE2 and infecting human cells. Baric’s research team concluded that like WIV1, any SARS-like viruses outfitted with the SHC014 spike could pose cross-species threats to people.

Baric acknowledged the risky nature of the research but emphasized the safety protocols. “In general, we don’t know the transmissibility or virulence potential of any bat viruses or chimeras,” Baric said in an email message. “Hence it’s best to keep and work with them under biosafety level 3 laboratory conditions to maximize safety.”

Baric also pointed out that a chimera would display a genetic signature “that says what it is.” The adjoining parts of a chimera segregate discreetly in a logical pattern.

A genetic analysis of the chimera produced in his lab, for instance, “would come out to be mouse-adapted SARS everywhere but the spike, which is SHC014.” Similar logical patterns are absent in SARS-CoV-2, indicating that the virus that causes COVID-19 evolved naturally.

ven as Baric and others were generating lab evidence that more SARS-like viruses were poised for human emergence, another outbreak—in pigs, not people—provided another strong and recent signal: Some 25,000 piglets were killed by a coronavirus in the Guangdong province of China, starting in 2016. That virus, too, was found in horseshoe bats, and Buchmeier described the outbreak as both a major cross-species spillover and a warning shot that was never really picked up by the broader public-health community.

The EcoHealth Alliance, which had been part of the Predict effort, maintained its own collaboration with the Wuhan Institute of Virology using funds supplied by the National Institutes of Health. But on April 24, the Trump administration—which is investigating whether SARS-CoV-2 escaped accidentally from the Wuhan Institute, an allegation that’s been broadly discredited—directed the NIH to cut off that support.

The bats had been trapped in a cave in Kunming, the capital of the Yunnan province. At least seven other SARS-like strains were present in that same colony, leading the researchers to speculate that bat coronaviruses remained “a substantial global threat to public health.”

To disease experts, the bickering is a worrying—perhaps even astonishing—indicator that at least some global leaders still aren’t hearing what they have to say about the threat of coronaviruses, and Baric asserted that the ongoing pandemic exposes the need for better communication between countries, not less. “That is absolutely key,” he said. “Critical information needs to be passed as quickly as possible.”

Many other warnings would follow.Indeed, evidence of a looming and more deadly coronavirus pandemic had been building for years. Yet experts who specialize in coronaviruses—a large family of pathogens, found especially in birds and mammals, that can cross over to humans from other mammals and cause varying degrees of illness—struggled to convince a broader audience of the risk

the number of coronavirus-research grants funded by the National Institutes of Health—which had increased from a low of 28 in 2002 to a peak of 103 in 2008—went into a tailspin.

Though support for coronavirus research spiked a bit with the MERS outbreak in 2012, the increase was short-lived. Since that outbreak was quickly contained, the disease didn’t raise wider concerns and grant opportunities declined further.

Ironically, just as funding for drugs and vaccines was drying up, evidence that other coronavirus threats lurked in wildlife was only getting stronger

Ten years would pass, however, before researchers could show there were other SARS-like viruses in nature that also bind with ACE2. The evidence came from a team based at the Wuhan Institute of Virology

Just two blocks away, a big order of tacos was picked up after midnight on Jan. 8 by a man driving a white van, like the one believed to be driven by Mr. Guzmán’s associates, witnesses said.

Hours later, on a highway heading out of town, the authorities finally got Mr. Guzmán, arguably the most powerful drug dealer in the history of the trade, for the third time since 1993.

Mr. Guzmán’s capture — described using information from interviews with witnesses and government officials, police reports, military video and Mexican news reports confirmed by officials — brings to a close, for now, one of the most exhaustive manhunts the Mexican government has conducted, an endeavor that drew in more than 2,500 people across the nation.

As the head of the Sinaloa cartel, Mr. Guzmán is the embodiment of an identity the country has fought to shed for decades.

Either way, Mr. Guzmán represents a deep crisis for Mexico’s leaders as they struggle to define the country’s image.

His daring escape from prison last July, in view of the video camera in his cell, cast a lurid spotlight on the incompetence and corruption that has long dogged the Mexican state, driving many to view the government on a par with criminals.

El Chapo’s image, by contrast, seemed only to grow after his escapes. Perhaps more than the infamy he gained as a cartel chief — responsible for shipping tons of drugs to more than 50 countries around the world, with a wider reach than even Pablo Escobar in his heyday — Mr. Guzmán has earned a reputation as the world’s pre-eminent escape artist.

During the 17 months Mr. Guzmán was locked up, he met often with associates, not only to plan his legal defense, but also to plot his escape, Mexican officials said. His men purchased land within sight of the prison, constructing an outer wall and an unfinished building on the site. From there, a mile away, the digging began.

The Mexican authorities were monitoring the phones of Mr. Guzmán and his accomplices, reading the odd and unexpectedly tender exchanges between him and the actress. Mr. Guzmán promised to protect Ms. del Castillo as he would his own eyes, an affectionate phrase Mexican parents often say of their children.

Six days later, a detachment of marines swept in to capture Mr. Guzmán on his ranch, acting with information from American authorities. During the raid, Mr. Guzmán, who always took his two cooks with him wherever he went, darted into a gully as he fled, injuring his face and leg.

In the following weeks, operations continued in and around areas under Mr. Guzmán’s control. The brutal weather of an approaching winter also concerned the cartel leader — Culiacán, the capital of Sinaloa, where life could be more comfortable, was under constant surveillance. He needed to go somewhere outside his traditional zone of influence.

The government, aware that Mr. Guzmán was planning a trip to an urban center, followed one of his associates to a house in Los Mochis, on a busy road with a movie theater, restaurants and shopping nearby.

A commander ordered one of the marines to toss a grenade in front of one of the many doors blocking their advance. As the mission continued, two marines advanced down another hallway, pressing cautiously toward a staircase used by the surviving gunmen to escape to the roof, drawing fire away from the interior of the house.

After the marines arrived, Mr. Guzmán was taken to Mexico City in a helicopter, the capture finally over. Soon everyone was gone, leaving behind just one thing: an unpaid bill, according to an employee of the hotel.

To keep him locked up this time, the authorities said they would rotate his cells, never allowing him to stay anywhere long enough to burrow his way out again. Vigilance would be enhanced, with more officers and round-the-clock surveillance from extra cameras.

But to many, the longer the drug lord remains in prison in Mexico, the higher the risk of flight. His imprisonment could drag on for a year, perhaps longer, given the numerous — and creative — injunctions filed by his team of lawyers to fight his extradition to the United States, where he faces federal indictments on charges that include narcotics trafficking and murder.