3 major health items included in Biden’s budget request

President Joe Biden proposed an ambitious budget for the next federal fiscal year that includes more money for fighting the opioid epidemic, bolstering public health and several other healthcare items.

The budget request to Congress, released Friday, acts as essentially a wish list of priorities for the administration for the next year.

It is doubtful how much would get approved by Congress but sends a message of what the administration prioritizes.

Here are three healthcare priorities outlined in the request:

  • The opioid epidemic: $10.7 billion was requested for fighting the opioid epidemic, $3.9 billion over the 2021 enacted level. The money will help support research, prevention and recovery services. The administration also is calling for targeted investments for “populations with unique needs, including Native Americans, older Americans and rural populations,” according to a release from the Office of Management and Budget on Friday.
     
  • Public health infrastructure: $8.7 billion was requested for the Centers for Disease Control and Prevention to boost public health capacity in states and territories. OMB calls the budget increase the largest in nearly two decades for the agency at the frontlines of combating COVID-19. The Biden administration hopes to use the new money to train new epidemiologists and public health experts and “build international capacity to detect, prepare for and respond to emerging global threats.” A letter sent Friday to congressional leaders from the White House said that CDC funding was 10% lower than the previous decade after adjusting for inflation.
     
  • Research funding boosts: $6.5 billion to launch a new agency called the Advanced Research Projects Agency for Health. The new agency would provide major increases in federal research and development spending on cancer and other diseases such as diabetes and Alzheimer’s. The goal of the investment is to “drive transformational innovation in health research and speed application and implementation of health breakthroughs,” OMB’s letter to Congress said. The funding is rolled into a $51 billion request for funding to the National Institutes of Health.

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.

No, children are not “basically vaccinated”

https://mailchi.mp/d88637d819ee/the-weekly-gist-march-19-2021?e=d1e747d2d8

Seven ways to talk to anti-vaxxers (that might actually change their minds)  - Healthy Debate

A new piece in the Atlantic sparked debate this week about the risk of ongoing COVID exposure to children as the country navigates toward the end of the pandemic. Brown University economist Emily Oster equated a child’s risk of serious illness from the coronavirus to that of their vaccinated grandmother. If grandma receives the Pfizer vaccine, her risk of serious illness is decreased by 95 percent. According to Oster, the condition of “being a child” aged 0-17 is 98 percent protective against hospitalization—so go ahead, plan that family summer vacation!

Oster cites no clinical or scientific experts in her piece, but some doctors were quick to respond that the comparisons are not equivalent (and also provide ready-made scripting for the “anti-vaxx” movement, which could claim that kids are already “basically vaccinated”).

But the article does bring up a real question that millions of families will soon facewhat can we do when grandma and grandpa (and hopefully mom and dad) are vaccinated, but the kids are not? Given the pace of clinical trials, teens could be eligible for vaccination as soon as late summer, but COVID vaccines might not be approved for younger children until months later—and this generational vaccine divide will likely linger into 2022.

Undoubtedly children are at lower risk from COVID than adults, and likely transmit the disease less frequently (although much of the data supporting the latter comes from studies in schools, where social distancing and masking are enforced). And we’re not out of the woods yet: as COVID cases surge again in Michigan, schools there have seen a spike in outbreaks as well. 

As families look at conflicting data and messages in the media, they need clear, coordinated guidance from state and federal officials to help them gauge safety as they navigate their second “pandemic summer”.

A stark global vaccine divide

The vaccine divide: Wealthy nations have 23 jabs for every one in a poorer  country | World News | Sky News

Wealthy nations — including the U.S., the U.K. and the EU — have vaccinated their citizens at a rate of one person per second over the last month, while most developing countries still haven’t administered a single shot, according to the People’s Vaccine Alliance.

Why it matters: As higher-income countries aim to achieve herd immunity in a matter of months, most of the world’s vulnerable people will remain unprotected.

  • Experts say that mutations that may arise while the virus spreads could be a danger to us all, vaccinated or not.

The big picture: Even though more vaccines will arrive in developing nations soon, only 3% of people in those countries are likely to be vaccinated by mid-2021.

  • At best, only a fifth of their population will be vaccinated by the end of the year, per the People’s Vaccine Alliance.

What we’re watching: Three dozen countries have bought several times the amount of vaccine that they’ll need to vaccinate their entire population.

  • The U.S. alone has ordered more than a billion extra dosesScience Magazine reports. Global health leaders are saying it’s time to figure out where all of these excess doses will go.
  • “Over the next year or two, U.S. surplus doses and those from other countries could add up to enough to immunize everyone in the many poorer nations that lack any secured COVID-19 vaccine,” Science writes.

America’s nightmarish year is finally ending

America's nightmare year of COVID is finally ending

One year after the World Health Organization declared COVID-19 a pandemic, the end of that pandemic is within reach.

The big picture: The death and suffering caused by the coronavirus have been much worse than many people expected a year ago — but the vaccines have been much better.

Flashback“Bottom line, it’s going to get worse,” Anthony Fauci told a congressional panel on March 11, 2020, the day the WHO formally declared COVID-19 to be a global pandemic.

  • A year ago today, the U.S. had confirmed 1,000 coronavirus infections. Now we’re approaching 30 million.
  • In the earliest days of the pandemic, Americans were terrified by the White House’s projections — informed by well-respected modeling — that 100,000 to 240,000 Americans could die from the virus. That actual number now sits at just under 530,000.
  • Many models at the time thought the virus would peak last May. It was nowhere close to its height by then. The deadliest month of the pandemic was January.

Yes, but: Last March, even the sunniest optimists didn’t expect the U.S. to have a vaccine by now.

  • They certainly didn’t anticipate that over 300 million shots would already be in arms worldwide, and they didn’t think the eventual vaccines, whenever they arrived, would be anywhere near as effective as these shots turned out to be.

Where it stands: President Biden has said every American adult who wants a vaccine will be able to get one by the end of May, and the country is on track to meet that target.

  • The U.S. is administering over 2 million shots per day, on average. Roughly 25% of the adult population has gotten at least one shot.
  • The federal government has purchased more doses than this country will be able to use: 300 million from Pfizer, 300 million from Moderna and 200 million from Johnson & Johnson.
  • The Pfizer and Moderna orders alone would be more than enough to fully vaccinate every American adult. (The vaccines aren’t yet authorized for use in children.)

Yes, millions of Americans are still anxiously awaiting their first shot — and navigating signup websites that are often frustrating and awful.

  • But the supply of available vaccines is expected to surge this month, and the companies say the bulk of those doses should be available by the end of May.
  • Cases, hospitalizations and deaths are all falling sharply at the same time vaccinations are ramping up.

The bottom line: Measured in death, loss, isolation and financial ruin, one year has felt like an eternity. Measured as the time between the declaration of a pandemic and vaccinating 60 million Americans, one year is an instant.

  • The virus hasn’t been defeated, and may never fully go away. Getting back to “normal” will be a moving target. Nothing’s over yet. But the end of the worst of it — the long, brutal nightmare of death and suffering — is getting close.

The pandemic’s coming new normal

Photo illustration of the Freedom from Want image by Norman Rockwell with all the participants of the dinner wearing surgical masks.

As both vaccinations and acquired immunity spread, life will likely settle into a new normal that will resemble pre-COVID-19 days— with some major twists.

The big picture: While hospitalizations and deaths are tamped down, the novel coronavirus should recede as a mortal threat to the world. But a lingering pool of unvaccinated people — and the virus’ own ability to mutate — will ensure SARS-CoV-2 keeps circulating at some level, meaning some precautions will be kept in place for years.

Driving the news: On Tuesday, Johnson & Johnson CEO Alex Gorsky told CNBC that people might well need a new coronavirus vaccine annually in the years ahead, much as they do now for the flu.

  • Gorsky’s comments were one of the clearest signals that even as the number of vaccinated people rises, the mutability of SARS-CoV-2 means the virus will almost certainly be with us in some form for years to come.

Be smartThat sounds like bad news — and indeed, it’s much less ideal than a world in which vaccination or infection conferred close to lifelong immunity and SARS-CoV-2 could be definitively conquered like smallpox.

  • With more contagious variants spreading rapidly, “the next 12 weeks are likely to be the darkest days of the pandemic,” says Michael Osterholm, the director of the University of Minnesota’s Center for Infectious Disease Research and Policy.
  • But the apparent effectiveness of the vaccines in preventing hospitalizations and death from COVID-19 — even in the face of new variants — points the way toward a milder future for the pandemic, albeit one that may be experienced very differently around the world.

Details: From studying what happened after new viruses emerged in the past, scientists predict SARS-CoV-2 will eventually become endemic, most likely in a seasonal pattern similar to the kind of coronaviruses that cause the common cold.

  • That’s nothing to sneeze at — literally, it will make us sneeze — but as immunity levels accumulate throughout the population, our experience of the virus will attenuate, and we’ll be highly unlikely to experience the severe death tolls and overloaded hospitals that marked much of the past year.

Yes, but: The existence of a stubborn pool of Americans who say they won’t get vaccinated — as well as the fact that it may take far longer for children, whom the vaccines have yet to be tested on, to get coverage — will give the virus longer legs than it would otherwise have.

  • “This will be with us forever,” says Osterholm. “That’s not even a debate at this point.”

What’s next: This means we can expect the K-shaped recovery that has marked the pandemic to continue, says Ben Pring, who leads Cognizant’s Center for the Future of Work.

  • With the virus likely to remain a threat, even if a diminished one, “those who are more stuck in the analog world are really going to continue to struggle,” he says.
  • Health security will also become a more ingrained part of daily life and work, which means temperature checks, masks, frequent COVID-19 testing and even vaccine passports for travel are here to stay.

The catch: That’s not all bad — the measures put in place to slow COVID-19 have stomped the flu and other seasonal respiratory viruses, and if we can hold onto some of those benefits in the future, we can save tens of thousands of lives and billions of dollars.

  • If the inequalities seen in the early phase of the vaccine rollout persist, COVID-19 could become a disease of the poor and disadvantaged, argues Mark Sendak, the co-founder and scientific adviser for Greenlight Ready, a COVID-19 resilience system that grew out of Duke Health.
  • Sendak points to the example of HIV, a disease that is entirely controllable with drugs but continues to exert a disproportionate toll on Black Americans, who take pre-exposure prophylactic medicine at much lower rates.

“If we go back to ‘normal,’ then we have failed.”

— Mark Sendak

What to watch: Whether the vaccine rollout can be adapted to reach hard to find and hard to persuade populations.

  • The Biden administration announced yesterday that it will start delivering vaccines directly to community health centers next week in an effort to promote more equity in the vaccine distribution process.
  • As the administration rolls out new COVID-19 plans, it needs to “invest in the community health care personnel” who can ensure that no one is left behind, says Sendak.

The bottom line: While SARS-CoV-2 has proven it can adapt to a changing environment, so can we. But we have to do so in a way that is fairer than our experience of the pandemic has been so far.

What happens after a year without the flu?

https://mailchi.mp/85f08f5211a4/the-weekly-gist-february-5-2021?e=d1e747d2d8

Image result for What happens after a year without the flu?

Doctors and scientists have been relieved that the dreaded “twindemic”—the usual winter spike of seasonal influenza superimposed on the COVID pandemic—did not materialize.

In fact, flu cases are at one of the lowest levels ever recorded, with just 155 flu-related hospitalizations this season (compared to over 490K in 2019). A new piece in the Atlantic looks at the long-term ramifications of a year without the flu. 

Public health measures like masking and handwashing have surely lowered flu transmission, but scientists remain uncertain why flu cases have flatlined as COVID-19, which spreads via the same mechanisms, surged.

Children are a much greater vector for influenza, and reduced mingling in schools and childcare likely slowed spread. Perhaps the shutdown in travel slowed the viruses’ ability to hop a ride from continent to continent, and the cancellation of gatherings further dampened transmission.

Nor are scientists sure what to expect next year. Optimists hope that record-low levels of flu could take a strain out of circulation. But others warn that flu could return with a vengeance, as the virus continues to mutate while population immunity declines. 

Researchers developing next year’s vaccines, meanwhile, face a lack of data on what strains and mutations to target—although many hope the mRNA technologies that proved effective for COVID will enable more agile flu vaccine development in the future. 

Regardless, renewed vigilance in flu prevention and vaccination next fall will be essential, as a COVID-fatigued population will be inclined to breathe a sigh of relief as the current pandemic comes under control.

Turning the tide in the battle against the virus

https://mailchi.mp/85f08f5211a4/the-weekly-gist-february-5-2021?e=d1e747d2d8

Image result for Turning the tide

The national COVID indicators all continued to move in the right direction this week, with new cases down 16 percent, hospitalizations down 26 percent, and deaths (while still alarmingly high at more than 3,000 per day) down 6 percent from the week prior.

More good news: both nationally and globallythe number of people vaccinated against COVID now exceeds the total number of people infected with the virus, at least according to official statistics—the actual number of coronavirus infections is likely several times higher.

On the vaccine front, Johnson & Johnson filed with the Food and Drug Administration (FDA) for an Emergency Use Authorization for its single-dose COVID vaccine, which could become the third vaccine approved for use in the US following government review later this month. The J&J vaccine is reportedly 85 percent effective at preventing severe COVID disease, although it is less effective at preventing infection than the Pfizer and Moderna shots.

Elsewhere, TheLancet reported interim Phase III results for Russia’s Sputnik V vaccine trials, showing it to be 91 percent effective at preventing infection, and a new study found the Oxford-AstraZeneca vaccine to be 75 percent effective against the more-contagious UK virus variant.

Amid the positive vaccine news, the Biden administration moved to accelerate the vaccination campaigninvoking the Defense Production Act to boost production and initiating shipments directly to retail pharmacies. With the House and Senate starting the budget reconciliation process that could eventually lead to as much as $1.9T in stimulus funding, including billions more for vaccines and testing, it feels as though the tide may be finally turning in the battle against coronavirus.

While the key indicators are still worrisome—we’re only back to Thanksgiving-week levels of new cases—and emerging variants are cause for concern, it’s worth celebrating a week that brought more good news than bad.

Best to follow Dr. Fauci’s advice for this Super Bowl weekend, however: “Just lay low and cool it.”

Cartoon – Specimens used for Covid-19 Testing and Experimentation

Letters to editor for Wednesday, Aug. 5, 2020

mRNA Technology Gave Us the First COVID-19 Vaccines. It Could Also Upend the Drug Industry

https://time.com/5927342/mrna-covid-vaccine/?fbclid=IwAR1wC2ZhNbrGepu9WiPIsYMFWwA_VNgwppCQQCwzb_wQYt4EXBNF3wd2s40

How mRNA Technology Gave Us the First COVID-19 Vaccines | Time

“No!” The doctor snapped. “Look at me!”

I had been staring her in the eyes, as she had ordered, but when a doctor on my other side began jabbing me with a needle, I started to turn my head. “Don’t look at it,” the first doctor said. I obeyed.

This was in early August in New Orleans, where I had signed up to be a participant in the clinical trial for the Pfizer-BioNTech COVID-19 vaccine. It was a blind study, which meant I was not supposed to know whether I had gotten the placebo or the real vaccine. I asked the doctor if I would really been able to tell by looking at the syringe. “Probably not,” she answered, “but we want to be careful. This is very important to get right.”

I became a vaccine guinea pig because, in addition to wanting to be useful, I had a deep interest in the wondrous new roles now being played by RNA, the genetic material that is at the heart of new types of vaccines, cancer treatments and gene-editing tools. I was writing a book on the Berkeley biochemist Jennifer Doudna. She was a pioneer in determining the structure of RNA, which helped her and her doctoral adviser figure out how it could be the origin of all life on this planet. Then she and a colleague invented an RNA-guided gene-editing tool, which won them the 2020 Nobel Prize in Chemistry.

The tool is based on a system that bacteria use to fight viruses. Bacteria develop clustered repeated sequences in their DNA, known as CRISPRs, that can remember dangerous viruses and then deploy RNA-guided scissors to destroy them. In other words, it’s an immune system that can adapt itself to fight each new wave of viruses—just what we humans need. Now, with the recently approved Pfizer-BioNTech vaccine and a similar one from Moderna being slowly rolled out across the U.S. and Europe, RNA has been deployed to make a whole new type of vaccine that will, when it reaches enough people, change the course of the pandemic.

Drs. Ugur Sahin and Ozlem Tureci, Co-founders, BioNTech. In January 2020, before many in the Western world were paying attention to a new virus spreading in China, Dr. Ugur Sahin was convinced it would spur a pandemic. Sahin, who in 2008 co-founded the German biotech company BioNTech with his wife Dr. Ozlem Tureci, went to work on a vaccine and by March called his contact at Pfizer, a much larger pharmaceutical company with which BioNTech had previously worked on an influenza vaccine using mRNA. Less than a year later, the Pfizer-BioNTech COVID-19 vaccine became the first ever mRNA vaccine available for widespread use. Even so, Sahin, BioNTech’s CEO, and Tureci, its chief medical officer, maintain that BioNTech is not an mRNA company but rather an immunotherapy company. Much of the couple’s work—both at BioNTech and at their previous venture, Ganymed—has focused on treating cancer. But it is mRNA, and the COVID-19 vaccine made possible by the technology, that has pushed the famously hardworking couple into the ­limelight—and helped them become one of the richest pairs in Germany, though they reportedly still bicycle to work and live in a modest apartment near their office.

Up until last year, vaccines had not changed very much, at least in concept, for more than two centuries. Most have been modeled on the discovery made in 1796 by the English doctor Edward Jenner, who noticed that many milkmaids were immune to smallpox. They had all been infected by a form of pox that afflicts cows but is relatively harmless to humans, and Jenner surmised that the cowpox had given them immunity to smallpox. So he took some pus from a cowpox blister, rubbed it into scratches he made in the arm of his gardener’s 8-year-old son and then (this was in the days before bioethics panels) exposed the kid to smallpox. He didn’t become ill.

Before then, inoculations were done by giving patients a small dose of the actual smallpox virus, hoping that they would get a mild case and then be immune. Jenner’s great advance was to use a related but relatively harmless virus. Ever since, vaccinations have been based on the idea of exposing a patient to a safe facsimile of a dangerous virus or other germ. This is intended to kick the person’s adaptive immune system into gear. When it works, the body produces antibodies that will, sometimes for many years, fend off any infection if the real germ attacks.

One approach is to inject a safely weakened version of the virus. These can be good teachers, because they look very much like the real thing. The body responds by making antibodies for fighting them, and the immunity can last a lifetime. Albert Sabin used this approach for the oral polio vaccine in the 1950s, and that’s the way we now fend off measles, mumps, rubella and chicken pox.

At the same time Sabin was trying to develop a vaccine based on a weakened polio virus, Jonas Salk succeeded with a safer approach: using a killed or inactivated virus. This type of vaccine can still teach a person’s immune system how to fight off the live virus but is less likely to cause serious side effects. Two Chinese companies, Sinopharm and Sinovac, have used this approach to develop vaccines for COVID-19 that are now in limited use in China, the UAE and Indonesia.

Another traditional approach is to inject a subunit of the virus, such as one of the proteins that are on the virus’s coat. The immune system will then remember these, allowing the body to mount a quick and robust response when it encounters the actual virus. The vaccine against the hepatitis B virus, for example, works this way. Using only a fragment of the virus means that they are safer to inject into a patient and easier to produce, but they are often not as good at producing long-term immunity. The Maryland-based biotech Novavax is in late-stage clinical trials for a COVID-19 vaccine using this approach, and it is the basis for one of the two vaccines already being rolled out in Russia.

The plague year of 2020 will be remembered as the time when these traditional vaccines were supplanted by something fundamentally new: genetic vaccines, which deliver a gene or piece of genetic code into human cells. The genetic instructions then cause the cells to produce, on their own, safe components of the target virus in order to stimulate the patient’s immune system.

For SARS-CoV-2—the virus that causes COVID-19—the target component is its spike protein, which studs the outer envelope of the virus and enables it to infiltrate human cells. One method for doing this is by inserting the desired gene, using a technique known as recombinant DNA, into a harmless virus that can deliver the gene into human cells. To make a COVID vaccine, a gene that contains instructions for building part of a coronavirus spike protein is edited into the DNA of a weakened virus like an adenovirus, which can cause the common cold. The idea is that the re-engineered adenovirus will worm its way into human cells, where the new gene will cause the cells to make lots of these spike proteins. As a result, the person’s immune system will be primed to respond rapidly if the real coronavirus strikes.

This approach led to one of the earliest COVID vaccine candidates, developed at the aptly named Jenner Institute of the University of Oxford. Scientists there engineered the spike-protein gene into an adenovirus that causes the common cold in chimpanzees, but is relatively harmless in humans.

The lead researcher at Oxford is Sarah Gilbert. She worked on developing a vaccine for Middle East respiratory syndrome (MERS) using the same chimp adenovirus. That epidemic waned before her vaccine could be deployed, but it gave her a head start when COVID-19 struck. She already knew that the chimp adenovirus had successfully delivered into humans the gene for the spike protein of MERS. As soon as the Chinese published the genetic sequence of the new coronavirus in January 2020, she began engineering its spike-protein gene into the chimp virus, waking each day at 4 a.m.

Her 21-year-old triplets, all of whom were studying biochemistry, volunteered to be early testers, getting the vaccine and seeing if they developed the desired antibodies. (They did.) Trials in monkeys conducted at a Montana primate center in March also produced promising results.

Bill Gates, whose foundation provided much of the funding, pushed Oxford to team up with a major company that could test, manufacture and distribute the vaccine. So Oxford forged a partnership with AstraZeneca, the British-Swedish pharmaceutical company. Unfortunately, the clinical trials turned out to be sloppy, with the wrong doses given to some participants, which led to delays. Britain authorized it for emergency use at the end of December, and the U.S. is likely to do so in the next two months.

Johnson & Johnson is testing a similar vaccine that uses a human adenovirus, rather than a chimpanzee one, as the delivery mechanism to carry a gene that codes for making part of the spike protein. It’s a method that has shown promise in the past, but it could have the disadvantage that humans who have already been exposed to that adenovirus may have some immunity to it. Results from its clinical trial are expected later this month.

In addition, two other vaccines based on genetically engineered adenoviruses are now in limited distribution: one made by CanSino Biologics and being used on the military in China and another named Sputnik V from the Russian ministry of health.

There is another way to get genetic material into a human cell and cause it to produce the components of a dangerous virus, such as the spike proteins, that can stimulate the immune system. Instead of engineering the gene for the component into an adenovirus, you can simply inject the genetic code for the component into humans as DNA or RNA.

Let’s start with DNA vaccines. Researchers at Inovio Pharmaceuticals and a handful of other companies in 2020 created a little circle of DNA that coded for parts of the coronavirus spike protein. The idea was that if it could get inside the nucleus of a cell, the DNA could very efficiently churn out instructions for the production of the spike-protein parts, which serve to train the immune system to react to the real thing.

The big challenge facing a DNA vaccine is delivery. How can you get the little ring of DNA not only into a human cell but into the nucleus of the cell? Injecting a lot of the DNA vaccine into a patient’s arm will cause some of the DNA to get into cells, but it’s not very efficient.

Some of the developers of DNA vaccines, including Inovio, tried to facilitate the delivery into human cells through a method called electroporation, which delivers electrical shock pulses to the patient at the site of the injection. That opens pores in the cell membranes and allows the DNA to get in. The electric pulse guns have lots of tiny needles and are unnerving to behold. It’s not hard to see why this technique is unpopular, especially with those on the receiving end. So far, no easy and reliable delivery mechanism has been developed for getting DNA vaccines into the nucleus of human cells.

That leads us to the molecule that has proven victorious in the COVID vaccine race and deserves the title of TIME magazine’s Molecule of the Year: RNA. Its sibling DNA is more famous. But like many famous siblings, DNA doesn’t do much work. It mainly stays bunkered down in the nucleus of our cells, protecting the information it encodes. RNA, on the other hand, actually goes out and gets things done. The genes encoded by our DNA are transcribed into snippets of RNA that venture out from the nucleus of our cells into the protein-manufacturing region. There, this messenger RNA (mRNA) oversees the assembly of the specified protein. In other words, instead of just sitting at home curating information, it makes real products.

Scientists including Sydney Brenner at Cambridge and James Watson at Harvard first identified and isolated mRNA molecules in 1961. But it was hard to harness them to do our bidding, because the body’s immune system often destroyed the mRNA that researchers engineered and attempted to introduce into the body. Then in 2005, a pair of researchers at the University of Pennsylvania, Katalin Kariko and Drew Weissman, showed how to tweak a synthetic mRNA molecule so it could get into human cells without being attacked by the body’s immune system.

Stéphane Bancel, CEO, Moderna. Moderna’s COVID-19 vaccine was first tested in humans less than three months after news of the novel virus broke. But that lightning-fast development process belies the years of work that got Moderna to where it is today. The startup was founded in 2010 with the belief that mRNA technology, then still fairly new, could help treat any number of ailments. CEO Stéphane Bancel, pictured above, joined a year later. Moderna wasn’t originally focused on vaccines, but over time, its scientists began working toward vaccines against several infectious diseases as well as some forms of cancer. That experience came in handy when the COVID-19 pandemic arrived, leaving the world clamoring for a vaccine that could fight the deadly virus—and fast. Bancel’s company took the challenge in stride, using its mRNA platform to develop a vaccine around 95% effective at protecting against COVID-19 disease in less than a year.

When the COVID-19 pandemic hit a year ago, two innovative young pharmaceutical companies decided to try to harness this role played by messenger RNA: the German company BioNTech, which formed a partnership with the U.S. company Pfizer; and Moderna, based in Cambridge, Mass. Their mission was to engineer messenger RNA carrying the code letters to make part of the coronavirus spike protein—a string that begins CCUCGGCGGGCA … —and to deploy it in human cells.

BioNTech was founded in 2008 by the husband-and-wife team of Ugur Sahin and Ozlem Tureci, who met when they were training to be doctors in Germany in the early 1990s. Both were from Turkish immigrant families, and they shared a passion for medical research, so much so that they spent part of their wedding day working in the lab. They founded BioNTech with the goal of creating therapies that stimulate the immune system to fight cancerous cells. It also soon became a leader in devising medicines that use mRNA in vaccines against viruses.

In January 2020, Sahin read an article in the medical journal Lancet about a new coronavirus in China. After discussing it with his wife over breakfast, he sent an email to the other members of the BioNTech board saying that it was wrong to believe that this virus would come and go as easily as MERS and SARS. “This time it is different,” he told them.

BioNTech launched a crash project to devise a vaccine based on RNA sequences, which Sahin was able to write within days, that would cause human cells to make versions of the coronavirus’s spike protein. Once it looked promising, Sahin called Kathrin Jansen, the head of vaccine research and development at Pfizer. The two companies had been working together since 2018 to develop flu vaccines using mRNA technology, and he asked her whether Pfizer would want to enter a similar partnership for a COVID vaccine. “I was just about to call you and propose the same thing,” Jansen replied. The deal was signed in March.

By then, a similar mRNA vaccine was being developed by Moderna, a much smaller company with only 800 employees. Its chair and co-founder, Noubar Afeyan, a Beirut-born Armenian who immigrated to the U.S., had become fascinated by mRNA in 2010, when he heard a pitch from a group of Harvard and MIT researchers. Together they formed Moderna, which initially focused on using mRNA to try to develop personalized cancer treatments, but soon began experimenting with using the technique to make vaccines against viruses.

In January 2020, Afeyan took one of his daughters to a restaurant near his office in Cambridge to celebrate her birthday. In the middle of the meal, he got an urgent text message from the CEO of his company, Stéphane Bancel, in Switzerland. So he rushed outside in the freezing temperature, forgetting to grab his coat, to call him back.

Bancel said that he wanted to launch a project to use mRNA to attempt a vaccine against the new coronavirus. At that point, Moderna had more than 20 drugs in development but none had even reached the final stage of clinical trials. Nevertheless, Afeyan instantly authorized him to start work. “Don’t worry about the board,” he said. “Just get moving.” Lacking Pfizer’s resources, Moderna had to depend on funding from the U.S. government. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, was supportive. “Go for it,” he declared. “Whatever it costs, don’t worry about it.”

It took Bancel and his Moderna team only two days to create the RNA sequences that would produce the spike protein, and 41 days later, it shipped the first box of vials to the National Institutes of Health to begin early trials. Afeyan keeps a picture of that box on his cell phone.

An mRNA vaccine has certain advantages over a DNA vaccine, which has to use a re-engineered virus or other delivery mechanism to make it through the membrane that protects the nucleus of a cell. The RNA does not need to get into the nucleus. It simply needs to be delivered into the more-accessible outer region of cells, the cytoplasm, which is where proteins are constructed.

The Pfizer-BioNTech and Moderna vaccines do so by encapsulating the mRNA in tiny oily capsules, known as lipid nanoparticles. Moderna had been working for 10 years to improve its nanoparticles. This gave it one advantage over Pfizer-BioNTech: its particles were more stable and did not have to be stored at extremely low temperatures.

Katalin Kariko, Senior vice president, BioNTech. In 1995, after years of struggle, Hungarian-born Katalin Kariko was pushed off the path to full professorship at the University of Pennsylvania. Her work on mRNA, molecules she believed could fundamentally change the way humans treat disease, had stalled. Then, in 1997, she met and began working with immunologist Drew Weissman. In 2005, they published a study describing a modified form of artificial ­mRNA—a discovery, they argued, that opened the door to mRNA’s use in vaccines and other therapies. Eventually, Kariko and Weissman licensed their technology to the German company BioNTech, where Kariko, shown here in a portrait shot by a photographer working remotely, is now a senior vice president. Her patience paid off this year. The mRNA-based Pfizer-­BioNTech corona­virus vaccine, which Kariko helped develop, has been shown to be 95% effective at preventing COVID-19.
Katalin Kariko, Senior vice president, BioNTech. In 1995, after years of struggle, Hungarian-born Katalin Kariko was pushed off the path to full professorship at the University of Pennsylvania. Her work on mRNA, molecules she believed could fundamentally change the way humans treat disease, had stalled. Then, in 1997, she met and began working with immunologist Drew Weissman. In 2005, they published a study describing a modified form of artificial ­mRNA—a discovery, they argued, that opened the door to mRNA’s use in vaccines and other therapies. Eventually, Kariko and Weissman licensed their technology to the German company BioNTech, where Kariko, shown here in a portrait shot by a photographer working remotely, is now a senior vice president. Her patience paid off this year. The mRNA-based Pfizer-­BioNTech corona­virus vaccine, which Kariko helped develop, has been shown to be 95% effective at preventing COVID-19.

By November, the results of the Pfizer-BioNTech and Moderna late-stage trials came back with resounding findings: both vaccines were more than 90% effective. A few weeks later, with COVID-19 once again surging throughout much of the world, they received emergency authorization from the U.S. Food and Drug Administration and became the vanguard of the biotech effort to beat back the pandemic.

The ability to code messenger RNA to do our bidding will transform medicine. As with the COVID vaccines, we can instruct mRNA to cause our cells to make antigens—molecules that stimulate our immune system—that could protect us against many viruses, bacteria, or other pathogens that cause infectious disease. In addition, mRNA could in the future be used, as BioNTech and Moderna are pioneering, to fight cancer. Harnessing a process called immunotherapy, the mRNA can be coded to produce molecules that will cause the body’s immune system to identify and kill cancer cells.

RNA can also be engineered, as Jennifer Doudna and others discovered, to target genes for editing. Using the CRISPR system adapted from bacteria, RNA can guide scissors-like enzymes to specific sequences of DNA in order to eliminate or edit a gene. This technique has already been used in trials to cure sickle cell anemia. Now it is also being used in the war against COVID. Doudna and others have created RNA-guided enzymes that can directly detect SARS-CoV-2 and eventually could be used to destroy it.

More controversially, CRISPR could be used to create “designer babies” with inheritable genetic changes. In 2018, a young Chinese doctor used CRISPR to engineer twin girls so they did not have the receptor for the virus that causes AIDS. There was an immediate outburst of awe and then shock. The doctor was denounced, and there were calls for an international moratorium on inheritable gene edits. But in the wake of the pandemic, RNA-guided genetic editing to make our species less receptive to viruses may someday begin to seem more acceptable.

Throughout human history, we have been subjected to wave after wave of viral and bacterial plagues. One of the earliest known was the Babylon flu epidemic around 1200 B.C. The plague of Athens in 429 B.C. killed close to 100,000 people, the Antonine plague in the 2nd century killed 5 million, the plague of Justinian in the 6th century killed 50 million, and the Black Death of the 14th century took almost 200 million lives, close to half of Europe’s population.

The COVID-19 pandemic that killed more than 1.8 million people in 2020 will not be the final plague. However, thanks to the new RNA technology, our defenses against most future plagues are likely to be immensely faster and more effective. As new viruses come along, or as the current coronavirus mutates, researchers can quickly recode a vaccine’s mRNA to target the new threats. “It was a bad day for viruses,” Moderna’s chair Afeyan says about the Sunday when he got the first word of his company’s clinical trial results. “There was a sudden shift in the evolutionary balance between what human technology can do and what viruses can do. We may never have a pandemic again.”

The invention of easily reprogrammable RNA vaccines was a lightning-fast triumph of human ingenuity, but it was based on decades of curiosity-driven research into one of the most fundamental aspects of life on planet earth: how genes are transcribed into RNA that tell cells what proteins to assemble. Likewise, CRISPR gene-editing technology came from understanding the way that bacteria use snippets of RNA to guide enzymes to destroy viruses. Great inventions come from understanding basic science. Nature is beautiful that way.