The partisan divide in coronavirus vaccinations is widening

One hesitates to elevate obviously bad arguments, even to point out how bad they are. This is a conundrum that comes up a lot these days, as members of the media measure the utility of reporting on bad faith, disingenuous or simply bizarre claims.

If someone were to insist, for example, that they were not going to get the coronavirus vaccine solely to spite the political left, should that claim be elevated? Can we simply point out how deranged it is to refuse a vaccine that will almost certainly end an international pandemic simply because people with whom you disagree think that maybe this is a good route to end that pandemic? If someone were to write such a thing at some attention-thirsty website, we certainly wouldn’t want to link to it, leaving our own readers having to figure out where it might be found should they choose to do so.

In this case, it’s worth elevating this argument (which, to be clear, is actually floating out there) to point out one of the myriad ways in which the effort to vaccinate as many adults as possible has become interlaced with partisan politics. As the weeks pass and demand for the vaccine has tapered off, the gap between Democratic and Republican interest in being vaccinated seems to be widening — meaning that the end to the pandemic is likely to move that much further into the future.

Consider, for example, the rate of completed vaccinations by county, according to data compiled by CovidActNow. You can see a slight correlation between how a county voted in 2020 — the horizontal axis — and the density of completed vaccinations, shown on the vertical. There’s a greater density of completed vaccinations on the left side of the graph than on the right.

If we shift to the percentage of the population that’s received even one dose of the vaccine, the effect is much more obvious.

This is a relatively recent development. At the beginning of the month, the density of the population that had received only one dose resulted in a graph that looked much like the current density of completed doses.

If we animate those two graphs, the effect is obvious. In the past few weeks, the density of first doses has increased much faster in more-Democratic counties.

If we group the results of the 2020 presidential contest into 20-point buckets, the pattern is again obvious.

It’s not a new observation that Republicans are less willing to get the vaccine; we’ve reported on it repeatedly. What’s relatively new is how that hesitance is showing up in the actual vaccination data.

A Post-ABC News poll released on Monday showed that this response to the vaccine holds even when considering age groups. We’ve known for a while that older Americans, who are more at risk from the virus, have been more likely to seek the vaccine. But even among seniors, Republicans are significantly more hesitant to receive the vaccine than are Democrats.

This is a particularly dangerous example of partisanship. People 65 or older have made up 14 percent of coronavirus infections, according to federal data, but 81 percent of deaths. That’s among those for whom ages are known, a subset (though a large majority) of overall cases. While about 1.8 percent of that overall group has died, the figure for those aged 65 and over is above 10 percent.

As vaccines have been rolled out across the country, you can see how more-heavily-blue counties have a higher density of vaccinations in many states.

This is not a universal truth, of course. Some heavily Republican counties have above-average vaccination rates. (About 40 percent of counties that preferred former president Donald Trump last year are above the average in the CovidActNow data. The rate among Democratic counties is closer to 80 percent.) But it is the case that there is a correlation between how a county voted and how many of its residents have been vaccinated. It is also the case that the gap between red and blue counties is widening.

Given all of that, it probably makes sense to point out that an argument against vaccines based on nothing more than “lol libs will hate this” is an embarrassing argument to make.

COVID-19 Is Still Devastating the World—Especially India

The pandemic won’t end for anyone until it ends for everyone. That sentiment has been repeated so many times, by so many people, it’s easy to forget it’s not just a cliche—particularly if you live in one of the wealthy countries, like the U.S. and Israel, that has made significant moves toward what feels like an end to the COVID-19 era.

Israel, for example, has fully vaccinated more than half of its population and about 90% of its adults 50 and older are now immune to the virus—enough that the country is “busting loose” and “partying like it’s 2019,” as the Washington Post put it last week. The U.S. is a bit further behind, with nearly 30% of its population fully vaccinated, but the possibility of a post-pandemic reality is already coming into focus. While daily case counts remain high, they are far lower than they were even a few months ago—about 32,000 diagnoses were reported on April 25, compared to daily tallies well above 250,000 in January. Deaths have also trended downward for most of 2021. The U.S. Centers for Disease Control and Prevention has relaxed its guidance on travel and indoor gatherings, and some states have repealed mask mandates and other disease precautions.

But while people in certain affluent countries celebrate a return to vacations and parties, COVID-19 remains a dire threat in many nations around the world—nowhere more so than India. For five days in a row, the country has set and reset the global record for new cases in a single day, tallying about 353,000 on April 26.

By official counts, about 2,000 people in India are dying from COVID-19 every day as hospitals grow overtaxed and oxygen supplies run short. Experts say the true toll is likely even higher than that. People are dying as they desperately seek treatment, and crematoriums nationwide are overwhelmed.

It can be difficult to grapple with that devastating reality when people in countries like the U.S. are reuniting with loved ones and cautiously emerging from lockdown. How can both scenarios be happening at once? The answer, as it often has during the pandemic, lies in disparity. As of April 26, 83% of vaccinations worldwide had been given in high- and upper-middle-income countries, according to a New York Times data analysis. In the developing world, many countries are preparing for the reality that it could take until 2022 or even 2023 to reach vaccination levels already achieved by richer countries today. Even in India, one of the world’s leading vaccine manufacturers, fewer than 10% of people have gotten a vaccine—a cruel irony, as people in India die in the streets while those thousands of miles away celebrate receiving their second doses.

To truly defeat COVID-19, we must reckon with that cognitive dissonance, says Dr. Rahel Nardos, who is originally from Ethiopia and now works in the University of Minnesota’s Center for Global Health and Social Responsibility. As an immigrant and global health physician who lives in the U.S., Nardos says she inhabits two worlds: one in which the U.S. may feasibly vaccinate at least 70% of its population this year, and another in which many countries struggle to inoculate even 20% of their residents in the same time frame.

“It’s a huge disparity,” Nardos says. “We need to get out of our silos and start talking to each other and hearing each other.”

That’s imperative, first and foremost because it could save lives. More than 13,000 people around the world died from COVID-19 on April 24. Remaining vigilant about disease prevention and monitoring, and working to distribute vaccines in countries that desperately need them to fight back COVID-19 surges, could help prevent more deaths in the future. That’s especially critical for developing countries, many of which are so overwhelmed by COVID-19 that nearly all other aspects of health care have suffered. “We may be looking at five, 10 years before they can get back to their baseline, which wasn’t that great to begin with,” Nardos says.

There’s also a global health argument for distributing vaccines more equitably. Infectious diseases do not respect borders. If even one country remains vulnerable to COVID-19, that could allow the virus to keep spreading and mutating, potentially evolving to such a point that it could infect people who are vaccinated against original strains of the disease. Already, vaccine makers are exploring the possibility of booster shots to add extra protection against the more transmissible variants currently circulating in various parts of the world.

We aren’t at that point yet; currently authorized vaccines appear to hold up well against these variants. But if the virus keeps spreading for years in some areas, there’s no telling what will happen, says Jonna Mazet, an epidemiologist and emerging infectious disease expert at the University of California, Davis.

Evolution of those new strains could go into multiple directions. They may evolve to cause more severe or less severe disease. Some of the variants [could be] more concerning for young people,” Mazet says. “The whole dynamics of the disease change.”

And if the virus is mutating somewhere, chances are good it will eventually keep spreading in multiple areas, Mazet says. “Unless or until we have a major shift, we are still going to have large parts of every country that have a susceptible population,” she says. “The virus is going to find a way.”

The only way to stop a virus from mutating is to stop giving it new hosts, and vaccines help provide that protection. COVAX—a joint initiative of the World Health Organization; Gavi, the Vaccine Alliance; the Coalition for Epidemic Preparedness Innovations; and UNICEF—was meant to ensure that people in low-income countries could get vaccinated at the same time as people in wealthier ones. COVAX is providing free vaccines to middle- and low-income countries, using funds gained through purchase agreements and donations from richer countries. But supply and funding shortages have made it difficult for the initiative to distribute vaccines as quickly as it intended to. Many of the doses it planned to disseminate were supposed to have come from the Serum Institute of India, which delayed exporting doses in March and April as India focused on domestic vaccine rollout to combat its COVID-19 surge at home.

In the meanwhile, many poorer countries have been unable to vaccinate anywhere close to as many people as would be required to reach herd immunity. That will almost surely improve as new vaccines are authorized for use by regulators around the world, and as manufacturers scale up production, but those moves may be months away.

COVAX is also developing a mechanism through which developed countries could donate vaccine doses they don’t need. Some wealthy countries, including the U.S. and Canada, have contracts to purchase more than enough doses to vaccinate their entire populations, and have signaled their intent to eventually donate unneeded supplies—but timing is everything. That is, these countries will likely only donate once they are sure their own populations have been vaccinated at a level that ensures herd immunity.

On April 25, the Biden Administration said the U.S. would provide India with raw supplies for making AstraZeneca’s vaccine, as well as COVID-19 tests and treatments, ventilators, personal protective equipment, and funding. That’s a significant shift, since the export of raw vaccine materials was previously banned, but it still doesn’t provide India with ready-to-go vaccines. That step may be next, though. The U.S. will export as many as 60 million doses of AstraZeneca’s vaccine once the shot clears federal safety reviews, the Associated Press reports.

Gian Gandhi, UNICEF’s COVAX coordinator for supply, says he fears many wealthy countries’ vaccine donations may not come until late in 2021, just when global supply is expected to ramp up. That may cause a bottleneck effect: all doses may come in at once, rather than at a slow-but-steady pace that allows countries with smaller health care networks to distribute them. “We need doses now, when we’re not able to access them via other means,” Gandhi says.

The global situation is also critical now. Worldwide, more than 5.2 million cases and 83,000 deaths were reported during the week leading up to April 18. Indian hospitals are so overrun, crowds have formed outside their doors and desperate families are trying to source their own oxygen. Hospitals in Brazil are reportedly running out of sedatives. Iran last week broke daily case count records three days in a row. Countries across Europe remain under various forms of lockdown. Vaccines won’t change those realities immediately—but without them, the global community stands little chance of containing COVID-19 worldwide.

Entering a new phase of the vaccine rollout

https://mailchi.mp/da8db2c9bc41/the-weekly-gist-april-23-2021?e=d1e747d2d8

Why some Americans are hesitant to receive the COVID-19 vaccine - Vital  Record

With more than 222M Americans having received at least one dose of COVID vaccine, and 27.5 percent of the population now fully vaccinated, we are now nearing a point at which vaccine supply will exceed demand, signaling a new phase of the rollout.

This week, for the first time since February, the daily rate of vaccinations slowed substantially, down about 11 percent from last week on a seven-day rolling average. Several states and counties are dialing back requests for new vaccine shipments, and the New York Times reported that some local health departments are beginning to shutter mass vaccination sites as appointment slots go unfilled.

On Friday, the White House’s COVID response coordinator, Jeff Zients, said that the Biden administration now expects “daily vaccination rates will fluctuate and moderate,” after several weeks of accelerating pace. In every state, everyone over the age of 16 is now eligible to be vaccinated, but experts expect that demand from the “vaccine-eager” population will run out over the next two weeksnecessitating a more aggressive campaign to distribute vaccines in hard-to-reach populations, and to convince vaccine skeptics to get the shot.

Vaccine hesitancy, like so many other issues related to the COVID pandemic, has now become starkly politicized—one recent survey found that 43 percent of Republicans “likely will never get” the vaccine, as opposed to only 5 percent of Democrats. Another 12 percent of those surveyed, regardless of party identification, say they plan to “see how it goes” before getting the vaccine, a subset that will surely be unnerved by continued doubts about the safety of the Johnson & Johnson (J&J) vaccine.

An expert advisory panel on Friday recommended that use of the J&J shot be resumed, but advised that a warning be included about potential risk of rare blood clots in women under 50. The first three months of the COVID vaccination campaign have been a staggering success—but getting from 27 percent fully vaccinated to the 80 percent needed for “herd immunity” will likely be a much tougher slog.

U.S. lifts pause on Johnson & Johnson’s coronavirus vaccine

The CDC and FDA on Friday lifted the recommended pause on use of Johnson & Johnson’s coronavirus vaccine, saying the benefits of the shot outweigh the risk of a rare blood clot disorder.

Why it matters: The move clears the way for states to immediately resume administering the one-shot vaccine.

  • The Johnson & Johnson shot had been seen as an important tool to fill gaps in the U.S. vaccination effort. But between the pause in its use and repeated manufacturing problems, its role in that effort is shrinking.

Driving the news: J&J shots have been paused for about two weeks, in response to reports that they may have caused serious blood clots in a small number of patients.

  • Only six people had experienced those blood clots at the time of the pause. The CDC said Friday that there have been nine additional cases.
  • Regulators said the number is small enough to safely resume the use of J&J’s vaccine.

What they’re saying: Safety is our top priority. This pause was an example of our extensive safety monitoring working as they were designed to work — identifying even these small number of cases,” said acting FDA Commissioner Janet Woodcock.

  • “We’ve lifted the pause based on the FDA and CDC’s review of all available data and in consultation with medical experts and based on recommendations from the CDC’s Advisory Committee on Immunization Practices,” she said.
  • “We are confident that this vaccine continues to meet our standards for safety, effectiveness and quality.”

What’s next: Regulators said health care providers administering the shot and vaccine recipients should review revised fact sheets about the J&J vaccine, which includes information about the rare blood clot disorder.

  • That heightened attention is important because the standard treatment for blood clots can make this particular type of clot worse.

Yes, but: J&J was already a relatively small part of the overall domestic vaccination effort, in part because the company missed some of its early manufacturing targets.

  • Multiple problems have since emerged at a Baltimore facility that makes a key ingredient for the vaccine, which could sideline production for weeks.

Blood Clots, FDA Approval, and the AstraZeneca Covid Vaccine

Blood Clots, FDA Approval, and the AstraZeneca Covid Vaccine - YouTube

There’s a lot of anxiety about the AstraZeneca vaccine thanks to recent reports of incomplete data, as well as reports on blood clot risks. Let’s take a look at both issues in context, understanding the efficacy data before and after numbers were updated, and understanding blood clot risk in relation to other common situations where blood clots are a potential concern.

India’s devastating outbreak is driving the global coronavirus surge

India's covid surge is bringing its healthcare system to the brink -  Washington Post

NEW DELHI — More than a year after the pandemic began, infections worldwide have surpassed their previous peak. The average number of coronavirus cases reported each day is now higher than it has ever been.

“Cases and deaths are continuing to increase at worrying rates,” said World Health Organization chief Tedros Adhanom Ghebreyesus on Friday.

A major reason for the increase: the ferocity of India’s second wave. The country accounts for about one in three of all new cases.

It wasn’t supposed to happen like this. Earlier this year, India appeared to be weathering the pandemic. The number of daily cases dropped below 10,000 and the government launched a vaccination drive powered by locally made vaccines.

But experts say that changes in behavior and the influence of new variants have combined to produce a tidal wave of new cases.

India is adding more than 250,000 new infections a day — and if current trends continue, that figure could soar to 500,000 within a month, said Bhramar Mukherjee, a biostatistician at the University of Michigan.

While infections are rising around the country, some places are bearing the brunt of the surge. Six states and Delhi, the nation’s capital, account for about two-thirds of new daily cases. Maharashtra, home to India’s financial hub, Mumbai, represents about a quarter of the nation’s total.

Mohammad Shahzad, a 40-year-old accountant, was one of many desperately seeking care. He developed a fever and grew breathless on the afternoon of April 15. His wife, Shazia, rushed him to the nearest hospital. It was full, but staffers checked his oxygen level: 62, dangerously low.

For three hours, they went from hospital to hospital trying to get him admitted, with no luck. She took him home. At 3:30 a.m., with Shahzad struggling to breathe, she called an ambulance. When the driver arrived, he asked if Shahzad truly needed oxygen — otherwise he would save it for the most serious patients.

The scene at the hospital was “harrowing,” said Shazia: a line of ambulances, people crying and pleading, a man barely breathing. Shahzad finally found a bed. Now Shazia and her two children, 8 and 6, have also developed covid-19 symptoms.

From early morning until late at night, Prafulla Gudadhe’s phone does not stop ringing. Each call is from a constituent and each call is the same: Can he help to arrange a hospital bed for a loved one?

Gudadhe is a municipal official in Nagpur, a city in the interior of Maharashtra. “We tell them we will try, but there are no beds,” he said. About 10 people in his ward have died at home in recent days after they couldn’t get admitted to hospitals, Gudadhe said, his voice weary. “I am helpless.”

Kamlesh Sailor knows how bad it is. Worse than the previous wave of the pandemic, like nothing he’s ever seen.

Sailor is the president of a crematorium trust in the city of Surat. Last week, the steel pipes in two of the facility’s six chimneys melted from constant use. Where the facility used to receive about 20 bodies a day, he said, now it is receiving 100.

“We try to control our emotions,” he said. “But it is unbearable.”

Variolation, Innoculation, and Vaccination: A History, Part I

Who Invented Vaccines? A History of Variolation and Innoculation - YouTube

Part one of our six-part series on vaccinations, supported by the National Institute for Health Care Management Foundation, dives into the history of variolation, exploring the beginning of the long road that led to vaccines as we know them today.

Vaccine Development, Covid-19, and mRNA vaccines

Vaccine Development, Covid-19, and mRNA vaccines | The Incidental Economist

In this last episode of our six-part series on vaccinations, supported by the National Institute for Health Care Management Foundation, we cover vaccine development – particularly in the context of the current global pandemic. We discuss the timeline of Covid-19 vaccine development and the mRNA vaccine approach.

Kati Kariko Helped Shield the World From the Coronavirus

Katalin Kariko at her home in Jenkintown, Pa., in February. Dr. Kariko’s early research into mRNA eventually led to development of the Moderna and Pfizer-BioNTech vaccines.Credit.

She grew up in Hungary, daughter of a butcher. She decided she wanted to be a scientist, although she had never met one. She moved to the United States in her 20s, but for decades never found a permanent position, instead clinging to the fringes of academia.

Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr. Drew Weissman of the University of Pennsylvania, laid the foundation for the stunningly successful vaccines made by Pfizer-BioNTech and Moderna.

For her entire career, Dr. Kariko has focused on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.

But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year.

By all accounts intense and single-minded, Dr. Kariko lives for “the bench” — the spot in the lab where she works. She cares little for fame. “The bench is there, the science is good,” she shrugged in a recent interview. “Who cares?”

Dr. Anthony Fauci, director of the National Institutes of Allergy and infectious Diseases, knows Dr. Kariko’s work. “She was, in a positive sense, kind of obsessed with the concept of messenger RNA,” he said.

Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded.

“When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer, a neurosurgeon who has worked with Dr. Kariko.

Dr. Kariko’s ideas about mRNA were definitely unorthodox. Increasingly, they also seem to have been prescient.

“It’s going to be transforming,” Dr. Fauci said of mRNA research. “It is already transforming for Covid-19, but also for other vaccines. H.I.V. — people in the field are already excited. Influenza, malaria.”

For Dr. Kariko, most every day was a day in the lab. “You are not going to work — you are going to have fun,” her husband, Bela Francia, manager of an apartment complex, used to tell her as she dashed back to the office on evenings and weekends. He once calculated that her endless workdays meant she was earning about a dollar an hour.

For many scientists, a new discovery is followed by a plan to make money, to form a company and get a patent. But not for Dr. Kariko. “That’s the furthest thing from Kate’s mind,” Dr. Langer said.

She grew up in the small Hungarian town of Kisujszallas. She earned a Ph.D. at the University of Szeged and worked as a postdoctoral fellow at its Biological Research Center.

In 1985, when the university’s research program ran out of money, Dr. Kariko, her husband, and 2-year-old daughter, Susan, moved to Philadelphia for a job as a postdoctoral student at Temple University. Because the Hungarian government only allowed them to take $100 out of the country, she and her husband sewed £900 (roughly $1,246 today) into Susan’s teddy bear. (Susan grew up to be a two-time Olympic gold medal winner in rowing.)

When Dr. Kariko started, it was early days in the mRNA field. Even the most basic tasks were difficult, if not impossible. How do you make RNA molecules in a lab? How do you get mRNA into cells of the body?

In 1989, she landed a job with Dr. Elliot Barnathan, then a cardiologist at the University of Pennsylvania. It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position. She was supposed to be supported by grant money, but none came in.

She and Dr. Barnathan planned to insert mRNA into cells, inducing them to make new proteins. In one of the first experiments, they hoped to use the strategy to instruct cells to make a protein called the urokinase receptor. If the experiment worked, they would detect the new protein with a radioactive molecule that would be drawn to the receptor.

“Most people laughed at us,” Dr. Barnathan said.

One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data.

Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein, at will.

“I felt like a god,” Dr. Kariko recalled.

She and Dr. Barnathan were on fire with ideas. Maybe they could use mRNA to improve blood vessels for heart bypass surgery. Perhaps they could even use the procedure to extend the life span of human cells.

Dr. Barnathan, though, soon left the university, accepting a position at a biotech firm, and Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.

Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” and at that point “mRNA was more of an idea,” he said.

But Dr. Langer knew Dr. Kariko from his days as a medical resident, when he had worked in Dr. Barnathan’s lab. Dr. Langer urged the head of the neurosurgery department to give Dr. Kariko’s research a chance. “He saved me,” she said.

Dr. Langer thinks it was Dr. Kariko who saved him — from the kind of thinking that dooms so many scientists.

Working with her, he realized that one key to real scientific understanding is to design experiments that always tell you something, even if it is something you don’t want to hear. The crucial data often come from the control, he learned — the part of the experiment that involves a dummy substance for comparison.

“There’s a tendency when scientists are looking at data to try to validate their own idea,” Dr. Langer said. “The best scientists try to prove themselves wrong. Kate’s genius was a willingness to accept failure and keep trying, and her ability to answer questions people were not smart enough to ask.”

Dr. Langer hoped to use mRNA to treat patients who developed blood clots following brain surgery, often resulting in strokes. His idea was to get cells in blood vessels to make nitric oxide, a substance that dilates blood vessels, but has a half-life of milliseconds. Doctors can’t just inject patients with it.

He and Dr. Kariko tried their mRNA on isolated blood vessels used to study strokes. It failed. They trudged through snow in Buffalo, N.Y., to try it in a laboratory with rabbits prone to strokes. Failure again.

And then Dr. Langer left the university, and the department chairman said he was leaving as well. Dr. Kariko again was without a lab and without funds for research.

A meeting at a photocopying machine changed that. Dr. Weissman happened by, and she struck up a conversation. “I said, ‘I am an RNA scientist — I can make anything with mRNA,’” Dr. Kariko recalled.

Dr. Weissman told her he wanted to make a vaccine against H.I.V. “I said, ‘Yeah, yeah, I can do it,’” Dr. Kariko said.

Despite her bravado, her research on mRNA had stalled. She could make mRNA molecules that instructed cells in petri dishes to make the protein of her choice. But the mRNA did not work in living mice.

“Nobody knew why,” Dr. Weissman said. “All we knew was that the mice got sick. Their fur got ruffled, they hunched up, they stopped eating, they stopped running.”

It turned out that the immune system recognizes invading microbes by detecting their mRNA and responding with inflammation. The scientists’ mRNA injections looked to the immune system like an invasion of pathogens.

But with that answer came another puzzle. Every cell in every person’s body makes mRNA, and the immune system turns a blind eye. “Why is the mRNA I made different?Dr. Kariko wondered.

A control in an experiment finally provided a clue. Dr. Kariko and Dr. Weissman noticed their mRNA caused an immune overreaction. But the control molecules, another form of RNA in the human body — so-called transfer RNA, or tRNA — did not.

A molecule called pseudouridine in tRNA allowed it to evade the immune response. As it turned out, naturally occurring human mRNA also contains the molecule.

Added to the mRNA made by Dr. Kariko and Dr. Weissman, the molecule did the same — and also made the mRNA much more powerful, directing the synthesis of 10 times as much protein in each cell.

The idea that adding pseudouridine to mRNA protected it from the body’s immune system was a basic scientific discovery with a wide range of thrilling applications. It meant that mRNA could be used to alter the functions of cells without prompting an immune system attack.

“We both started writing grants,” Dr. Weissman said. “We didn’t get most of them. People were not interested in mRNA. The people who reviewed the grants said mRNA will not be a good therapeutic, so don’t bother.’”

Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention.

Dr. Weissman and Dr. Kariko then showed they could induce an animal — a monkey — to make a protein they had selected. In this case, they injected monkeys with mRNA for erythropoietin, a protein that stimulates the body to make red blood cells. The animals’ red blood cell counts soared.

The scientists thought the same method could be used to prompt the body to make any protein drug, like insulin or other hormones or some of the new diabetes drugs. Crucially, mRNA also could be used to make vaccines unlike any seen before.

Instead of injecting a piece of a virus into the body, doctors could inject mRNA that would instruct cells to briefly make that part of the virus.

“We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.”

Eventually, though, two biotech companies took notice of the work: Moderna, in the United States, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Dr. Weissman’s lab.

Soon clinical trials of an mRNA flu vaccine were underway, and there were efforts to build new vaccines against cytomegalovirus and the Zika virus, among others. Then came the coronavirus.

Researchers had known for 20 years that the crucial feature of any coronavirus is the spike protein sitting on its surface, which allows the virus to inject itself into human cells. It was a fat target for an mRNA vaccine.

Chinese scientists posted the genetic sequence of the virus ravaging Wuhan in January 2020, and researchers everywhere went to work. BioNTech designed its mRNA vaccine in hours; Moderna designed its in two days.

The idea for both vaccines was to introduce mRNA into the body that would briefly instruct human cells to produce the coronavirus’s spike protein. The immune system would see the protein, recognize it as alien, and learn to attack the coronavirus if it ever appeared in the body.

The vaccines, though, needed a lipid bubble to encase the mRNA and carry it to the cells that it would enter. The vehicle came quickly, based on 25 years of work by multiple scientists, including Pieter Cullis of the University of British Columbia.

Scientists also needed to isolate the virus’s spike protein from the bounty of genetic data provided by Chinese researchers. Dr. Barney Graham, of the National Institutes of Health, and Jason McClellan, of the University of Texas at Austin, solved that problem in short order.

Testing the quickly designed vaccines required a monumental effort by companies and the National Institutes of Health. But Dr. Kariko had no doubts.

On Nov. 8, the first results of the Pfizer-BioNTech study came in, showing that the mRNA vaccine offered powerful immunity to the new virus. Dr. Kariko turned to her husband. “Oh, it works,” she said. “I thought so.”

To celebrate, she ate an entire box of Goobers chocolate-covered peanuts. By herself.

Dr. Weissman celebrated with his family, ordering takeout dinner from an Italian restaurant, “with wine,” he said. Deep down, he was awed.

“My dream was always that we develop something in the lab that helps people,” Dr. Weissman said. “I’ve satisfied my life’s dream.”

Dr. Kariko and Dr. Weissman were vaccinated on Dec. 18 at the University of Pennsylvania. Their inoculations turned into a press event, and as the cameras flashed, she began to feel uncharacteristically overwhelmed.

A senior administrator told the doctors and nurses rolling up their sleeves for shots that the scientists whose research made the vaccine possible were present, and they all clapped. Dr. Kariko wept.

Things could have gone so differently, for the scientists and for the world, Dr. Langer said. “There are probably many people like her who failed,” he said.

How basic research leads to future job growth

https://www.axios.com/basic-science-research-fuels-job-growth-fcf7723b-b701-4ed2-8b2b-699d28dd1fbd.html

Illustration of a hand in a medical glove holding a beaker full of liquid

A new report out later today concludes that basic scientific research plays an essential role in creating companies that later produce thousands of jobs and billions in economic value.

Why it mattersThe report uses the pandemic — and especially the rapid development of new mRNA vaccines — to show how basic research funding from the government lays the necessary groundwork for economically valuable companies down the road.

By the numbers: The Science Coalition — a nonprofit group that represents 50 of the nation’s top private and public research universities — identified 53 companies that have spun off from federally funded university research.

  • Those companies — which range from pharmaceutical startups to agriculture firms — have contributed more than $1.3 billion to U.S. GDP between 2015 and 2019, while supporting the creation of more than 100,000 jobs.

What they’re saying: “The COVID-19 pandemic has shown that the need for the federal government to continue investing in fundamental research is far from theoretical,” says John Latini, president of the Science Coalition. “Consistent, sustained, robust federal funding is how science evolves.”

DetailsLatini praised the Biden administration’s first budget proposal to Congress, released last week, which includes what would be a $9 billion funding boost for the National Institutes of Health (NIH) — the country’s single biggest science research funding agency.

  • The National Oceanic and Atmospheric Administration would see its budget rise to a record high of $6.9 billion, including $800 million reserved for climate research.

The catch: The Biden budget proposal is just that, and it will ultimately be up to Congress to decide how much to allocate to research agencies.

Context: Government research funding is vital because private money tends to go to applied research. But without basic research — the lifeblood of science — the U.S. risks missing out on potentially world-changing innovations in the future.

  • The long-term value of that funding can be seen in the story of Katalin Kariko, an obscure biomedical researcher who labored for years on mRNA with little reward — until the pandemic, when her work helped provide the foundation for mRNA COVID-19 vaccines.

The bottom line: Because its ultimate payoff might lay years in the future, it’s easy to see basic research funding as a waste — until the day comes when we need it.