Breakthrough infections might not be a big transmission risk. Here’s the evidence

Conventional wisdom says that if you’re vaccinated and you get a breakthrough infection with the coronavirus, you can transmit that infection to someone else and make that person sick.

But new evidence suggests that even though that may happen on occasion, breakthrough infections might not represent the threat to others that scientists originally thought.

Ross Kedl, an immunologist at the University of Colorado School of Medicine, will point out to anyone who cares to listen that basic immunology suggests the virus of a vaccinated person who gets infected will be different from the virus of an infected unvaccinated person.

That’s because vaccinated people have already made antibodies to the coronavirus. Even if those antibodies don’t prevent infection, they still “should be coating that virus with antibody and therefore helping prevent excessive downstream transmission,” Kedl says. And a virus coated with antibodies won’t be as infectious as a virus not coated in antibodies.

Scant evidence for easy transmission of breakthrough infections

In Provincetown, Mass., this summer, a lot of vaccinated people got infected with the coronavirus, leading many to assume that this was an example of vaccinated people with breakthrough infections giving their infection to other vaccinated people.

Kedl isn’t convinced.

“In all these cases where you have these big breakthrough infections, there’s always unvaccinated people in the room,” he says.

In a recent study from Israel of breakthrough infections among health care workers, the researchers report that in “all 37 case patients for whom data were available regarding the source of infection, the suspected source was an unvaccinated person.”

It’s hard to prove that an infected vaccinated person actually was responsible for transmitting their infection to someone else.

“I have seen no one report actually trying to trace whether or not the people who were vaccinated who got infected are downstream — and certainly only could be downstream — of another vaccinated person,” Kedl says.

There’s new laboratory evidence supporting Kedl’s supposition. Initially, most vaccine experts predicted that mRNA vaccines like the ones made by Pfizer and Moderna that are injected into someone’s arm muscle would generate only the kinds of antibodies that circulate throughout the body.

But that might not be the whole story.

“I think what was the big surprise here is that the mRNA vaccines are going beyond that,” says Michal Caspi Tal, until recently an instructor at Stanford University’s Institute for Stem Cell Biology and Regenerative Medicine and now a visiting scientist at the Massachusetts Institute of Technology.

What Tal has found is that in addition to the circulating antibodies, there was a surprisingly large amount of antibodies in mucosal membranes in the nose and mouth, two of the primary entry points for the coronavirus.

The vaccinated aren’t “sitting ducks”

Immunologist Jennifer Gommerman of the University of Toronto found this as well.

“This is the first example where we can show that a local mucosal immune response is made, even though the person got the vaccine in an intramuscular delivery,” Gommerman says.

If there are antibodies in the mucosal membranes, they would likely be coating any virus that got into the nose or throat. So any virus that was exhaled by a sneeze or a cough would likely be less infectious.

Gommerman says that until now, it seemed likely that a vaccine that was delivered directly to the mucosal tissue was the only way to generate antibodies in the nose or throat.

“Obviously a mucosal vaccination would be great too. But at least we’re not sitting ducks,” Gommerman says. “Otherwise everyone would be getting breakthrough infection.”

Now, these studies by Gommerman and Tal have yet to undergo peer review, and some have already suggested that the antibodies they have described may not confer true mucosal immunity.

But there’s other evidence that a vaccinated person’s breakthrough infection may not transmit efficiently to others.

Marion Pepper, an immunologist at the University of Washington, says a recent study from the Netherlands looked at how well virus from vaccinated people could infect cells in the lab.

Pepper says the answer was not well.

“If you actually isolate virus from people who are getting a secondary infection after being vaccinated, that virus is less good at infecting cells,” Pepper says. “It’s not known why. Is it covered with an antibody? Maybe. Has it been hit by some other kind of immune mediators, cytokines, things like that? Maybe. Nobody really knows. But the virus does seem to be less viable coming from a vaccinated person.”

More studies are emerging that suggest there’s something different about the virus coming from a vaccinated person, something that may help prevent transmission.

Whatever it is, the University of Colorado’s Kedl says it’s one more reason that getting vaccinated is a good idea.

“Because you’re going to be even more protected yourself. And you’re going to be better off protecting other people.”

Kedl says that’s what you call a win-win situation.

How Merck’s antiviral pill could change the game for COVID-19

https://www.nationalgeographic.com/science/article/how-mercks-antiviral-pill-could-change-the-game-for-covid-19?cmpid=org=ngp::mc=crm-email::src=ngp::cmp=editorial::add=SpecialEdition_20211001::rid=C1D3D2601560EDF454552B245D039020

Coronavirus: 'Game-changing' oral pill molnupiravir reduces COVID-19  hospitalisations by half in trial | Newshub

A new drug by Merck significantly reduces the risk of hospitalization and death in people who take it early in the course of their COVID-19 illness, according to the interim results of a major study released today. It is the first oral antiviral found to be effective against this coronavirus.

People who took this drug, called molnupiravir—four pills twice a day for five days—within five days of showing symptoms were about half as likely to be hospitalized as those taking the placebo. They were also less likely to die, with eight deaths in the placebo group reported within a month of treatment and none in those who received the medicine.

“Having a pill that would be easy for people to take at home would be terrific. If this was available through a drug store, more people could get it,” says Albert Shaw, an infectious diseases specialist at Yale Medicine in New Haven, Connecticut, who was not involved with the research. All of the antiviral medicines available today, including remdesivir and the monoclonal antibodies, must be administered through an IV in a medical setting. Monoclonal antibodies are much more effective against COVID-19 and cut the risk of hospitalization and death by up to 85 percent, but this treatment costs almost three times as much as molnupiravir.

How the antiviral works

Antiviral drugs are used against many viruses, including for herpes and the flu. These drugs take advantage of the fact that viruses need to replicate inside a person’s cells in order to sicken them. Antivirals stop the replication process so the illness doesn’t progress.

The Merck drug works by introducing RNA-like building blocks into the virus’s genome as it multiplies, which creates numerous mutations, disrupts replication, and kills the virus.

Keeping the virus from multiplying is important because the more it replicates, destroying cell after cell, the sicker a person usually becomes, says Waleed Javaid, an epidemiologist and director of infection prevention and control at Mount Sinai Downtown in New York, who was not involved in the study. Additionally, when enough virus is inside the body the immune system may go into overdrive. “At a certain point the body detects a virus it has never seen and will throw everything against it, like a tank coming at a small target.” he says. This helps the body eliminate the virus but can cause sometimes deadly collateral damage throughout the body in its wake.

The research, which was conducted in numerous sites around the world, was stopped early because the results were so promising, Merck says. The drug was even effective against variants like Delta and Mu. Based on this interim analysis in 775 people, the company plans to submit an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration as well as regulatory bodies in other countries in hopes the drug can be made available. When that will happen is not clear, but the U.S. government has already agreed to purchase 1.7 million courses of treatment at $700 each, Merck notes.

Who can get the drug?

It’s also not known who would ultimately be authorized to take the medicine. The study included only people who were sick and unvaccinated and had at least one risk factor for developing a severe case of COVID-19, says Aaron Weinberg, national director of clinical research at Carbon Health, a for-profit provider of primary and urgent care, and a principal investigator of the study. This includes people who are older than 60, obese, immunocompromised from another condition, or have underlying heart or pulmonary disease, among others.

If the FDA does authorize the drug, it could limit who gets it to people like those in the research, Javaid says.

Although this drug looks promising, it’s a treatment but not a prophylactic like the vaccine. The medicine does not negate the need for unvaccinated people to get their shot, Shaw says. Some people taking the pills still got sick enough to be hospitalized. And while side effects in this study were mild—generally gastrointestinal issues, Weinberg says, and at comparable rates in the treatment and placebo groups—safety issues might emerge when the drug is given more broadly, Shaw says. Meanwhile, hundreds of millions of people have already gotten the vaccines with no major consequences.

Still, the results of this study should be celebrated, Javaid says. “Saving eight lives is huge, as is halving hospitalization,” he says. Perhaps another drug being studied will later prove to be more effective, reducing hospitalization by 80 or even 100 percent, he says. “But this is better than any oral antivirals we have right now, which is none,” he says.

A new antiviral pill shows promise, as do vaccine mandates

https://mailchi.mp/a2cd96a48c9b/the-weekly-gist-october-1-2021?e=d1e747d2d8

Everything we know about the covid-19 coronavirus

Two pieces of hopeful news on the COVID front this week.

First, pharmaceutical manufacturer Merck announced this morning that molnupiravir, the oral antiviral drug it developed along with Ridgeback Biotherapeutics, reduced hospitalizations among newly diagnosed COVID patients by 50 percent. A five-day course of the drug was so successful in Merck’s clinical study that an independent monitoring group recommended halting the study and submitting the pill to the Food and Drug Administration (FDA) for emergency use authorization. Molnupiravir is activated by metabolism, and upon entering human cells, is converted into RNA-like building blocks, causing mutations in the COVID virus’s RNA genome and interfering with its replication. For that reason, the drug is unlikely to be prescribed during pregnancy, but otherwise the therapy seems to hold great promise in adding to the limited armamentarium available to fight the pandemic. One possible concern: the drug’s price tag. The federal government has agreed to purchase 1.7M courses of the drug at $700 per course, and with most insurance companies having returned to normal cost-sharing for COVID treatments, the drug may be out of reach for some patients. Still, a major clinical development to be celebrated, and more to come as Merck’s drug is vetted by the FDA.
 
At $20 to $40 per dose, with costs fully absorbed by the federal government, and remarkable effectiveness at preventing severe disease, hospitalizations, and deaths, vaccines remain far and away our best frontline weapon for fighting the COVID pandemic. Promising, then, that the much-debated vaccine mandates have begun to demonstrate success in increasing vaccination rates, even among those who have thus far resisted getting the shot.

Despite concerns about massive staffing shortages among hospitals resulting from the implementation of its mandate, the state of New York found that 92 percent of healthcare workers had been vaccinated by Monday, when the mandate went into effect. That was a 10-percentage-point increase from a week earlier, holding promise that the Biden administration’s planned federal mandate for healthcare workers could have the desired effect.

California’s mandate for healthcare workers went into effect yesterday, and was credited with boosting vaccination rates to 90 percent at many of the state’s health systems. Among private employers considering mandates, the experience of United Airlines may also be instructive: its employee mandate led to the vaccination of more than 99 percent of its workers, resulting in the termination of only 700 of its 67,000 employees. Of course, everyone prefers carrots to sticks, but sweepstakes and bonuses have only gotten so far in encouraging people to get vaccinated—now it appears mandates have a useful role to play as well.

With 56 percent of the population fully vaccinated, the US now ranks 43rd among nations, just ahead of Saudi Arabia and far behind most of Europe. In the next few days we’ll reach the grim milestone of 700,000 COVID deaths in this country—anything that helps stop that number from growing further should be welcome news.

Drug companies on verge of sinking longtime Democratic priority

https://thehill.com/business-a-lobbying/business-a-lobbying/572841-drug-companies-on-verge-of-sinking-longtime

The pharmaceutical industry is on the verge of defeating a major Democratic proposal that would allow the federal government to negotiate drug prices.

Speaker Nancy Pelosi (D-Calif.) can afford only three defections when the House votes on a sweeping $3.5 trillion spending package, but Reps. Scott Peters (D-Calif.), Kurt Schrader (D-Ore.) and Kathleen Rice (D-N.Y.) last week voted to block the drug pricing bill from advancing out of the Energy and Commerce Committee. Rep. Stephanie Murphy (D-Fla.) voted against advancing the tax portion of the legislation in the House Ways and Means Committee.

All told, the number of House Democrats who have concerns about the drug pricing bill is in the double digits, and several Democrats in the 50-50 Senate would not vote for the measure in its current form, according to industry lobbyists.

The holdouts mark a sharp contrast to just two years ago, when every House Democrat voted for the same drug pricing bill, underscoring the inroads pharmaceutical manufacturers have made with the caucus on a measure that would narrow corporate profit margins.

“The House markups on health care demonstrate there are real concerns with Speaker Pelosi’s extreme drug pricing plan and those concerns are shared by thoughtful lawmakers on both sides of the aisle,” the Pharmaceutical Research and Manufacturers of America (PhRMA), the industry’s top trade group, said in a statement following the committee votes.

The reversal follows the industry’s multimillion-dollar ad campaigns opposing the bill, timely political donations and an extensive lobbying effort stressing drugmakers’ success in swiftly developing lifesaving COVID-19 vaccines.

The bill at the center of the fight, H.R. 3, would allow Medicare to negotiate the price of prescription drugs by tying them to the lower prices paid by other high-income countries. The measure is projected to free up around $700 billion through the money it saves on drug purchases — covering a big chunk of the Democrats’ $3.5 trillion spending plan.

Drugmakers say the measure would reduce innovation, pointing to a Congressional Budget Office estimate that found it would lead to nearly 60 fewer new drugs over the next three decades.

Peters and other Democrats have proposed an alternative bill that would limit price negotiation to a fraction of the prescription drugs included in H.R. 3, focusing instead on drugs like insulin, the diabetes treatment that has seen its price rise dramatically over the last decade. The alternative measure also would set a yearly out-of-pocket spending limit for lower-income Medicare recipients.

The proposal foreshadows a less aggressive drug pricing compromise that uneasy Senate Democrats are more likely to get behind.

“You’re going to see something pass, but it probably won’t be H.R. 3,” said a lobbyist who represents pharmaceutical companies.

Pharmaceutical manufacturers oppose any efforts to control the price of prescription drugs, but the alternative bill is more favorable to the industry than the broader Democratic bill.

“Any kind of artificial price controls will have an impact on both new scientific investment as well as access to medicines,” said Rich Masters, chief public affairs and advocacy officer at the Biotechnology Innovation Organization, a trade group that represents pharmaceutical giants such as Sanofi, Merck and Johnson & Johnson.

“We appreciate the focus on patient out of pocket costs, which we know is a critical component to any reform efforts and something that BIO and our member companies have long supported,” he added.

Progressive lawmakers, who have long bemoaned rising drug prices, blasted the three House Democrats who voted to block H.R. 3, saying they succumbed to industry donations and lobbying efforts.

“What the pharmaceutical industry has done, year after year, is pour huge amounts of money into lobbying and campaign contributions … the result is that they can raise their prices to any level they want,” Sen. Bernie Sanders (I-Vt.) said in a video message Friday.

The pharmaceutical industry spent $171 million on lobbying through the first half of the year, more than any other industry, to deploy nearly 1,500 lobbyists, according to money-in-politics watchdog OpenSecrets. That’s up from around $160 million at the same point last year, when the industry broke its own lobbying spending record.

Peters announced his opposition to Pelosi’s drug pricing proposal in May and shortly after was showered with donations from pharmaceutical industry executives and lobbyists, STAT News reported.

Peters is the No. 1 House recipient of pharmaceutical industry donations this year, bringing in $88,550 from pharmaceutical executives and PACs, according to OpenSecrets. Over his congressional career, Peters has received in excess of $860,000 from drugmakers, more than any other private industry.

The California Democrat told The Hill last week that accusations of his vote being guided by donations are “flat wrong” and noted that his San Diego congressional district employs roughly 27,000 pharmaceutical industry workers consisting mostly of researchers.

“It’s always going to be the attack because it’s simple and it’s easier than engaging on the merits,” he said.

Schrader received nearly $615,000 from the industry. He inherited a fortune from his grandfather, a former top executive at Pfizer, and had between $50,000 and $100,000 invested in Pfizer, in addition to other pharmaceutical holdings as of last year, according to his most recent annual financial disclosure.

Schrader tweeted last week that he is “committed to lowering prescription drug costs,” while arguing that the House bill would not pass the Senate in its current form.

Rep. Lou Correa (D-Calif.) another supporter of Peters’s more industry friendly bill, received an influx of pharmaceutical donations in recent months, including a $2,000 check from Pfizer’s PAC in mid-August, according to Federal Election Commission filings.

In meetings with lawmakers, lobbyists have argued that now is not the time to go after drugmakers, which developed highly effective COVID-19 vaccines and are developing booster shots and other treatments to fight the virus.

The U.S. Chamber of Commerce, which represents several major pharmaceutical manufacturers, said last month that Democratic drug pricing efforts will leave the U.S. “unprepared for the next public health crisis.”

PhRMA last week launched a seven-figure ad campaign to oppose H.R. 3. That’s after pharmaceutical groups and conservative organizations bankrolled by drugmakers spent $18 million on ads attacking the proposal through late August, according to an analysis from Patients for Affordable Drugs, a group that launched its own ads backing H.R. 3 last week.

The ad buys are meant to sway both lawmakers and the general public. A June Kaiser Family Foundation poll found that 90 percent of Americans approve of the drug pricing measure, but that support dropped to 32 percent when they were told that the proposal “could lead to less research and development of new drugs.”

The Research on Ivermectin and Covid-19

Interest in the antiparasitic drug Ivermectin has increased drastically as of late thanks to the belief that it can help to prevent and/or treat Covid-19. In today’s episode we examine recent data on the efficacy of Ivermectin as an antiviral and discuss the history behind how it gained this reputation.

Recognizing the importance of aerosol transmission

https://mailchi.mp/13ef4dd36d77/the-weekly-gist-august-27-2021?e=d1e747d2d8

Droplets vs Aerosols: What's More Important in COVID-19 Spread? | MedPage  Today

Droplets, fomites, aerosols…these terms describing the kinds of particles which can spread virus particles rose to the top of our lexicon last year. Initially we focused on fomites, infectious particles deposited on surfaces, and worried that touching our groceries and mail could spread the coronavirus.

Scientists were convinced that most COVID transmission occurred via droplets, large respiratory particles exhaled in a cough or a sneeze that traveled only a short distance from an infected person, which led to the guidance that staying six feet apart would keep us safe. But worrisome case reports of a single individual passing the virus to a roomful of people, and the mitigating effects of ventilation, began to hint at aerosol transmission, a much more insidious type of spread in which the virus is transmitted through much smaller particles, which travel longer distances and can linger in the air for hours.

Aerosol spread is not only worrisome because it makes a pathogen more contagious, but smaller aerosol particles can be inhaled more deeply into the lungs, potentially causing more severe illness. A new review in Science evaluates the current data on COVID transmission and the advances made over the past year in understanding airflow and aerosol spread, making the bold statement that aerosol transmission is not only the main mechanism for COVID-19 spread, but is likely the primary mode of transmission for the vast majority of respiratory diseases.
 
Today, our lack of attention to ventilation, air purification and other means to reduce aerosol spread means that we are woefully unprepared for children to return to school—and underscores the need for extensive masking to mitigate transmission. But in the long run, better understanding the mechanisms for preventing airborne transmission could allow us to reduce susceptibility to a host of respiratory diseases. Take complications from asthma, which dropped dramatically during the pandemic—leading researchers to posit that viral infections, rather than environmental triggers, could be the more common cause behind exacerbations. 

Harnessing this new knowledge will require further research to quantify the effects of spread and mitigation—and the willingness to invest in preventive measures in schools and other public spaces, yet another domain in which bolstering public health could have a meaningful long-term impact on our lives.

Delta spreads 225% faster than original virus — this may be why

Why The Delta Variant Is So Contagious: A New Study Sheds Light : Goats and  Soda : NPR

Mounting evidence suggests the delta variant is the most contagious strain in the world, spreading about 225 percent faster than the original version of the virus. A small study published online July 7 may help explain why, NPR reported.

The delta variant, first identified in India, grows faster in people’s respiratory tracts and to much higher levels, according to researchers at the Guangdong Provincial Center for Disease Control and Prevention in China.

They analyzed virus levels in 62 people infected during China’s first delta variant outbreak between May 21 and June 18. They compared their findings to virus levels in 63 patients infected in 2020 by an earlier version of the virus.

On average, viral load was about 1,000 times higher for people infected with delta, compared to those infected with the earlier strain, researchers found. It also took about four days on average for delta to reach detectable levels in study participants, compared to six days for the other strain. This finding suggests people with delta likely become infectious sooner and are spreading the virus earlier in the course of their infection, researchers said. 

To view the full study, click here.

Benjamin Franklin’s fight against a deadly virus: Colonial America was divided over smallpox inoculation, but he championed science to skeptics

Benjamin Franklin's fight against a deadly virus: Colonial America was divided  over smallpox inoculation, but he championed science to skeptics

Exactly 300 years ago, in 1721, Benjamin Franklin and his fellow American colonists faced a deadly smallpox outbreak. Their varying responses constitute an eerily prescient object lesson for today’s world, similarly devastated by a virus and divided over vaccination three centuries later.

As a microbiologist and a Franklin scholar, we see some parallels between then and now that could help governments, journalists and the rest of us cope with the coronavirus pandemic and future threats.

Smallpox strikes Boston

Smallpox was nothing new in 1721. Known to have affected people for at least 3,000 years, it ran rampant in Boston, eventually striking more than half the city’s population. The virus killed about 1 in 13 residents – but the death toll was probably more, since the lack of sophisticated epidemiology made it impossible to identify the cause of all deaths.

What was new, at least to Boston, was a simple procedure that could protect people from the disease. It was known as “variolation” or “inoculation,” and involved deliberately exposing someone to the smallpox “matter” from a victim’s scabs or pus, injecting the material into the skin using a needle. This approach typically caused a mild disease and induced a state of “immunity” against smallpox.

Even today, the exact mechanism is poorly understood and not much research on variolation has been done. Inoculation through the skin seems to activate an immune response that leads to milder symptoms and less transmission, possibly because of the route of infection and the lower dose. Since it relies on activating the immune response with live smallpox variola virus, inoculation is different from the modern vaccination that eradicated smallpox using the much less harmful but related vaccinia virus.

The inoculation treatment, which originated in Asia and Africa, came to be known in Boston thanks to a man named Onesimus. By 1721, Onesimus was enslaved, owned by the most influential man in all of Boston, the Rev. Cotton Mather.

etching of an 18th century man in white wig
Cotton Mather heard about variolation from an enslaved West African man in his household named Onesimus. Bettman via Getty Images

Known primarily as a Congregational minister, Mather was also a scientist with a special interest in biology. He paid attention when Onesimus told him “he had undergone an operation, which had given him something of the smallpox and would forever preserve him from it; adding that it was often used” in West Africa, where he was from.

Inspired by this information from Onesimus, Mather teamed up with a Boston physician, Zabdiel Boylston, to conduct a scientific study of inoculation’s effectiveness worthy of 21st-century praise. They found that of the approximately 300 people Boylston had inoculated, 2% had died, compared with almost 15% of those who contracted smallpox from nature.

The findings seemed clear: Inoculation could help in the fight against smallpox. Science won out in this clergyman’s mind. But others were not convinced.

Stirring up controversy

A local newspaper editor named James Franklin had his own affliction – namely an insatiable hunger for controversy. Franklin, who was no fan of Mather, set about attacking inoculation in his newspaper, The New-England Courant.

frontpage of a 1721 newspaper
From its first edition, The New-England Courant covered inoculation. Wikimedia Commons

One article from August 1721 tried to guilt readers into resisting inoculation. If someone gets inoculated and then spreads the disease to someone else, who in turn dies of it, the article asked, “at whose hands shall their Blood be required?” The same article went on to say that “Epidemeal Distempers” such as smallpox come “as Judgments from an angry and displeased God.”

In contrast to Mather and Boylston’s research, the Courant’s articles were designed not to discover, but to sow doubt and distrust. The argument that inoculation might help to spread the disease posits something that was theoretically possible – at least if simple precautions were not taken – but it seems beside the point. If inoculation worked, wouldn’t it be worth this small risk, especially since widespread inoculations would dramatically decrease the likelihood that one person would infect another?

Franklin, the Courant’s editor, had a kid brother apprenticed to him at the time – a teenager by the name of Benjamin.

Historians don’t know which side the younger Franklin took in 1721 – or whether he took a side at all – but his subsequent approach to inoculation years later has lessons for the world’s current encounter with a deadly virus and a divided response to a vaccine.

Independent thought

You might expect that James’ little brother would have been inclined to oppose inoculation as well. After all, thinking like family members and others you identify with is a common human tendency.

That he was capable of overcoming this inclination shows Benjamin Franklin’s capacity for independent thought, an asset that would serve him well throughout his life as a writer, scientist and statesman. While sticking with social expectations confers certain advantages in certain settings, being able to shake off these norms when they are dangerous is also valuable. We believe the most successful people are the ones who, like Franklin, have the intellectual flexibility to choose between adherence and independence.

Truth, not victory

etching of Franklin standing at a table in a lab
Franklin matured into a well-known scientist and statesman, with many successes aided by his open mind. Universal History Archive/Universal Images Group via Getty Images

What happened next shows that Franklin, unlike his brother – and plenty of pundits and politicians in the 21st century – was more interested in discovering the truth than in proving he was right.

Perhaps the inoculation controversy of 1721 had helped him to understand an unfortunate phenomenon that continues to plague the U.S. in 2021: When people take sides, progress suffersTribes, whether long-standing or newly formed around an issue, can devote their energies to demonizing the other side and rallying their own. Instead of attacking the problem, they attack each other.

Franklin, in fact, became convinced that inoculation was a sound approach to preventing smallpox. Years later he intended to have his son Francis inoculated after recovering from a case of diarrhea. But before inoculation took place, the 4-year-old boy contracted smallpox and died in 1736. Citing a rumor that Francis had died because of inoculation and noting that such a rumor might deter parents from exposing their children to this procedure, Franklin made a point of setting the record straight, explaining that the child had “receiv’d the Distemper in the common Way of Infection.”

Writing his autobiography in 1771, Franklin reflected on the tragedy and used it to advocate for inoculation. He explained that he “regretted bitterly and still regret” not inoculating the boy, adding, “This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.”

A scientific perspective

A final lesson from 1721 has to do with the importance of a truly scientific perspective, one that embraces science, facts and objectivity.

19th-century photo of a smallpox patient
Smallpox was characterized by fever and aches and pustules all over the body. Before eradication, the virus killed about 30% of those it infected, according to the U.S. Centers for Disease Control and Prevention. Sepia Times/Universal Images Group via Getty Images

Inoculation was a relatively new procedure for Bostonians in 1721, and this lifesaving method was not without deadly risks. To address this paradox, several physicians meticulously collected data and compared the number of those who died because of natural smallpox with deaths after smallpox inoculation. Boylston essentially carried out what today’s researchers would call a clinical study on the efficacy of inoculation. Knowing he needed to demonstrate the usefulness of inoculation in a diverse population, he reported in a short book how he inoculated nearly 300 individuals and carefully noted their symptoms and conditions over days and weeks.

The recent emergency-use authorization of mRNA-based and viral-vector vaccines for COVID-19 has produced a vast array of hoaxes, false claims and conspiracy theories, especially in various social media. Like 18th-century inoculations, these vaccines represent new scientific approaches to vaccination, but ones that are based on decades of scientific research and clinical studies.

We suspect that if he were alive today, Benjamin Franklin would want his example to guide modern scientists, politicians, journalists and everyone else making personal health decisions. Like Mather and Boylston, Franklin was a scientist with a respect for evidence and ultimately for truth.

When it comes to a deadly virus and a divided response to a preventive treatment, Franklin was clear what he would do. It doesn’t take a visionary like Franklin to accept the evidence of medical science today.

CRISPR Shows Promise in Gene-Editing Therapy During Clinical Trial

CRISPR-Cas9 Gene Therapy Shows Promise in Angelman Mouse Model

Scientists at UCL National Amyloidosis Centre at the Royal Free Hospital, London are hoping their gene editing therapy using CRISPR will be a breakthrough for patients suffering from hereditary transthyretin (ATTR) amyloidosis. In a phase 1 clinical trial, the first six patients have shown positive interim results for gene-editing treatment.

The CRISPR breakthrough comes in treating transthyretin amyloidosis, a mutation in the transthyretin (TTR) gene. Those with this mutation produce an abnormal protein, which gradually builds up in the heart and nerves. Symptoms can include numbness in the hands and feet, loss of control of the bowel and bladder, and loss of mobility.

Hereditary transthyretin amyloidosis gets progressively worse and is fatal. Up until this point, most of the treatment options available to patients have included management of the symptoms and prevention of progression.

Those taking part in the trial have received a molecule knows as CRISPR/Cas9 via one-off infusion. The purpose of this is to deactivate the incorrect gene within the liver cell.

“With the gene no longer active in the liver, it is expected that the patient will only produce negligible levels of the harmful transthyretin protein,” UCL stated in a press release

Scientists saw in the first six patients a reduced production of the harmful transthyretin protein by up to 96 percent, 28 days after the treatment. Additionally, there were no serious adverse effects witnessed. This data was published in the New England Journal of Medicine.

“As the trial progresses, patients will be given higher doses of the gene editing therapy with the hope that will drive the levels of toxic protein even lower,” UCL explained. 

CRISPR/Cas9, a Nobel Prize-winning technology, has been used to edit cells outside the body in the past. However, UCL is presenting the first clinical data which CRISPR/Cas9 is being used as medicine itself for a potential therapy.

“This is wonderful news for patients with this condition. If this trial continues to be successful, the treatment may permit patients who are diagnosed early in the course of the disease to lead completely normal lives without the need for ongoing therapy,” Professor Julian Gillmore, the trial lead, of the UCL National Amyloidosis Centre, part of the UCL Centre for Amyloidosis and Acute Phase Proteins said in a press release.

“Until very recently, the majority of treatments we have been able to offer patients with this condition have had limited success. If this trial continues to go well, it will mean we can offer real hope and the prospect of meaningful clinical improvement to patients who suffer from this condition,” Gillmore continued.

The global trial includes patients from the Royal Free London and a hospital located in Auckland, New Zealand. The investigational therapy, designated NTLA-2001, is being developed by Intellia Therapeutics; a biotechnology company based in the United States.

 This could be a big step forward in using CRISPR as gene therapy. Typically, the therapy is injected into the site of illness. However, this newest approach injects CRISPR directly into the bloodstream, which could revolutionize how clinicians treat certain illnesses.