How mRNA Could Revolutionize Medicine
In November 2020, messenger RNA catapulted into the public consciousness when the first COVID-19 vaccines were authorized for emergency use. Around the same time, an equally groundbreaking yet relatively unheralded application of mRNA technology was taking place at a London hospital.
Over the past two decades, there's been increasing interest in harnessing mRNA — molecules present in all of our cells that act like digital tape recorders, copying instructions from DNA in the cell nucleus and carrying them to the protein-making structures — to create a whole new class of therapeutics.
Scientists realized that artificial mRNA, designed in the lab, could be used to instruct our cells to produce certain antibodies, turning our bodies into vaccine-making factories, or to recognize and attack tumors. More recently, researchers recognized that mRNA could also be used to make another groundbreaking technology far more accessible to more patients: gene editing. The gene-editing tool CRISPR has generated plenty of hype for its potential to cure inherited diseases. But delivering CRISPR to the body is complicated and costly.
"Most gene editing involves taking cells out of the patient, treating them and then giving them back, which is an extremely expensive process," explains Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the COVID-19 vaccines.
But last November, a Massachusetts-based biotech company called Intellia Therapeutics showed it was possible to use mRNA to make the CRISPR system inside the body, eliminating the need to extract cells out of the body and edit them in a lab. Just as mRNA can instruct our cells to produce antibodies against a viral infection, it can also teach them to produce one of the two components that make up CRISPR — a cutting protein that snips out a problem gene.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies."
In Intellia's London-based clinical trial, the company applied this for the first time in a patient with a rare inherited liver disease known as hereditary transthyretin amyloidosis with polyneuropathy. The disease causes a toxic protein to build up in a person's organs and is typically fatal. In a company press release, Intellia's president and CEO John Leonard swiftly declared that its mRNA-based CRISPR therapy could usher in a "new era of potential genome editing cures."
Weissman predicts that turning CRISPR into an affordable therapy will become the next major frontier for mRNA over the coming decade. His lab is currently working on an mRNA-based CRISPR treatment for sickle cell disease. More than 300,000 babies are born with sickle cell every year, mainly in lower income nations.
"There is a FDA-approved cure, but it involves taking the bone marrow out of the person, and then giving it back which is prohibitively expensive," he says. It also requires a patient to have a matched bone marrow done. "We give an intravenous injection of mRNA lipid nanoparticles that target CRISPR to the bone marrow stem cells in the patient, which is easy, and much less expensive."
Cancer Immunotherapy
Meanwhile, the overwhelming success of the COVID-19 vaccines has focused attention on other ways of using mRNA to bolster the immune system against threats ranging from other infectious diseases to cancer.
The practicality of mRNA vaccines – relatively small quantities are required to induce an antibody response – coupled with their adaptable design, mean companies like Moderna are now targeting pathogens like Zika, chikungunya and cytomegalovirus, or CMV, which previously considered commercially unviable for vaccine developers. This is because outbreaks have been relatively sporadic, and these viruses mainly affect people in low-income nations who can't afford to pay premium prices for a vaccine. But mRNA technology means that jabs could be produced on a flexible basis, when required, at relatively low cost.
Other scientists suggest that mRNA could even provide a means of developing a universal influenza vaccine, a goal that's long been the Holy Grail for vaccinologists around the world.
"The mRNA technology allows you to pick out bits of the virus that you want to induce immunity to," says Michael Mulqueen, vice president of business development at eTheRNA, a Belgium-based biotech that's developing mRNA-based vaccines for malaria and HIV, as well as various forms of cancer. "This means you can get the immune system primed to the bits of the virus that don't vary so much between strains. So you could actually have a single vaccine that protects against a whole raft of different variants of the same virus, offering more universal coverage."
Before mRNA became synonymous with vaccines, its biggest potential was for cancer treatments. BioNTech, the German biotech company that collaborated with Pfizer to develop the first authorized COVID-19 vaccine, was initially founded to utilize mRNA for personalized cancer treatments, and the company remains interested in cancers ranging from melanoma to breast cancer.
One of the major hurdles in treating cancer has been the fact that tumors can look very different from one person to the next. It's why conventional approaches, such as chemotherapy or radiation, don't work for every patient. But weaponizing mRNA against cancer primes the immune cells with the tumor's specific genetic sequence, training the patient's body to attack their own unique type of cancer.
"It means you're able to think about personalizing cancer treatments down to specific subgroups of patients," says Mulqueen. "For example, eTheRNA are developing a renal cell carcinoma treatment which will be targeted at around 20% of these patients, who have specific tumor types. We're hoping to take that to human trials next year, but the challenge is trying to identify the right patients for the treatment at an early stage."
Repairing Damaged mRNA
While hopes are high that mRNA could usher in new cancer treatments and make CRISPR more accessible, a growing number of companies are also exploring an alternative to gene editing, known as RNA editing.
In genetic disorders, the mRNA in certain cells is impaired due to a rogue gene defect, and so the body ceases to produce a particular vital protein. Instead of permanently deleting the problem gene with CRISPR, the idea behind RNA editing is to inject small pieces of synthetic mRNA to repair the existing mRNA. Scientists think this approach will allow normal protein production to resume.
Over the past few years, this approach has gathered momentum, as some researchers have recognized that it holds certain key advantages over CRISPR. Companies from Belgium to Japan are now looking at RNA editing to treat all kinds of disorders, from Huntingdon's disease, to amyotrophic lateral sclerosis, or ALS, and certain types of cancer.
"With RNA editing, you don't need to make any changes to the DNA," explains Daniel de Boer, CEO of Dutch biotech ProQR, which is looking to treat rare genetic disorders that cause blindness. "Changes to the DNA are permanent, so if something goes wrong, that may not be desirable. With RNA editing, it's a temporary change, so we dose patients with our drugs once or twice a year."
Last month, ProQR reported a landmark case study, in which a patient with a rare form of blindness called Leber congenital amaurosis, which affects the retina at the back of the eye, recovered vision after three months of treatment.
"We have seen that this RNA therapy restores vision in people that were completely blind for a year or so," says de Boer. "They were able to see again, to read again. We think there are a large number of other genetic diseases we could go after with this technology. There are thousands of different mutations that can lead to blindness, and we think this technology can target approximately 25% of them."
Ultimately, there's likely to be a role for both RNA editing and CRISPR, depending on the disease. "I think CRISPR is ideally suited for illnesses where you would like to permanently correct a genetic defect," says Joshua Rosenthal of the Marine Biology Laboratory in Chicago. "Whereas RNA editing could be used to treat things like pain, where you might want to reset a neural circuit temporarily over a shorter period of time."
Much of this research has been accelerated by the COVID-19 pandemic, which has played a major role in bringing mRNA to the forefront of people's minds as a therapeutic.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies," says Mulqueen. "In the future, I would not be surprised if many of the top pharma products are mRNA derived."
Individuals seeking funding for experimental therapies may enroll in legitimate clinical trials -- or fall prey to snake oil.
Nearly a decade ago, Jamie Anderson hit his highest weight ever: 618 pounds. Depression drove him to eat and eat. He tried all kinds of diets, losing and regaining weight again and again. Then, four years ago, a friend nudged him to join a gym, and with a trainer's guidance, he embarked on a life-altering path.
Ethicists become particularly alarmed when medical crowdfunding appeals are for scientifically unfounded and potentially harmful interventions.
"The big catalyst for all of this is, I was diagnosed as a diabetic," says Anderson, a 46-year-old sales associate in the auto care department at Walmart. Within three years, he was down to 276 pounds but left with excess skin, which sagged from his belly to his mid-thighs.
Plastic surgery would cost $4,000 more than the sum his health insurance approved. That's when Anderson, who lives in Cabot, Arkansas, a suburb outside of Little Rock, turned to online crowdfunding to raise money. In a few months last year, current and former co-workers and friends of friends came up with that amount, covering the remaining expenses for the tummy tuck and overnight hospital stay.
The crowdfunding site that he used, CoFund Health, aimed to give his donors some peace of mind about where their money was going. Unlike GoFundMe and other platforms that don't restrict how donations are spent, Anderson's funds were loaded on a debit card that only worked at health care providers, so the donors "were assured that it was for medical bills only," he says.
CoFund Health was started in January 2019 in response to concerns about the legitimacy of many medical crowdfunding campaigns. As crowdfunding for health-related expenses has gained more traction on social media sites, with countless campaigns seeking to subsidize the high costs of care, it has given rise to some questionable transactions and legitimate ethical concerns.
Common examples of alleged fraud have involved misusing the donations for nonmedical purposes, feigning or embellishing the story of one's own unfortunate plight or that of another person, or impersonating someone else with an illness. Ethicists become particularly alarmed when medical crowdfunding appeals are for scientifically unfounded and potentially harmful interventions.
About 20 percent of American adults reported giving to a crowdfunding campaign for medical bills or treatments, according to a survey by AmeriSpeak Spotlight on Health from NORC, formerly called the National Opinion Research Center, a non-partisan research institution at the University of Chicago. The self-funded poll, conducted in November 2019, included 1,020 interviews with a representative sample of U.S. households. Researchers cited a 2019 City University of New York-Harvard study, which noted that medical bills are the most common basis for declaring personal bankruptcy.
Some experts contend that crowdfunding platforms should serve as gatekeepers in prohibiting campaigns for unproven treatments. Facing a dire diagnosis, individuals may go out on a limb to try anything and everything to prolong and improve the quality of their lives.
They may enroll in well-designed clinical trials, or they could fall prey "to snake oil being sold by people out there just making a buck," says Jeremy Snyder, a health sciences professor at Simon Fraser University in British Columbia, Canada, and the lead author of a December 2019 article in The Hastings Report about crowdfunding for dubious treatments.
For instance, crowdfunding campaigns have sought donations for homeopathic healing for cancer, unapproved stem cell therapy for central nervous system injury, and extended antibiotic use for chronic Lyme disease, according to an October 2018 report in the Journal of the American Medical Association.
Ford Vox, the lead author and an Atlanta-based physician specializing in brain injury, maintains that a repository should exist to monitor the outcomes of experimental treatments. "At the very least, there ought to be some tracking of what happens to the people the funds are being raised for," he says. "It would be great for an independent organization to do so."
"Even if it appears like a good cause, consumers should still do some research before donating to a crowdfunding campaign."
The Federal Trade Commission, the national consumer watchdog, cautions online that "it might be impossible for you to know if the cause is real and if the money actually gets to the intended recipient." Another caveat: Donors can't deduct contributions to individuals on tax returns.
"Even if it appears like a good cause, consumers should still do some research before donating to a crowdfunding campaign," says Malini Mithal, associate director of financial practices at the FTC. "Don't assume all medical treatments are tested and safe."
Before making any donation, it would be wise to check whether a crowdfunding site offers some sort of guarantee if a campaign ends up being fraudulent, says Kristin Judge, chief executive and founder of the Cybercrime Support Network, a Michigan-based nonprofit that serves victims before, during, and after an incident. They should know how the campaign organizer is related to the intended recipient and note whether any direct family members and friends have given funds and left supportive comments.
Donating to vetted charities offers more assurance than crowdfunding that the money will be channeled toward helping someone in need, says Daniel Billingsley, vice president of external affairs for the Oklahoma Center of Nonprofits. "Otherwise, you could be putting money into all sorts of scams." There is "zero accountability" for the crowdfunding site or the recipient to provide proof that the dollars were indeed funneled into health-related expenses.
Even if donors may have limited recourse against scammers, the "platforms have an ethical obligation to protect the people using their site from fraud," says Bryanna Moore, a postdoctoral fellow at Baylor College of Medicine's Center for Medical Ethics and Health Policy. "It's easy to take advantage of people who want to be charitable."
There are "different layers of deception" on a broad spectrum of fraud, ranging from "outright lying for a self-serving reason" to publicizing an imaginary illness to collect money genuinely needed for basic living expenses. With medical campaigns being a top category among crowdfunding appeals, it's "a lot of money that's exchanging hands," Moore says.
The advent of crowdfunding "reveals and, in some ways, reinforces a health care system that is totally broken," says Jessica Pierce, a faculty affiliate in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus in Denver. "The fact that people have to scrounge for money to get life-saving treatment is unethical."
Crowdfunding also highlights socioeconomic and racial disparities by giving an unfair advantage to those who are social-media savvy and capable of crafting a compelling narrative that attracts donors. Privacy issues enter into the picture as well, because telling that narrative entails revealing personal details, Pierce says, particularly when it comes to children, "who may not be able to consent at a really informed level."
CoFund Health, the crowdfunding site on which Anderson raised the money for his plastic surgery, offers to help people write their campaigns and copy edit for proper language, says Matthew Martin, co-founder and chief executive officer. Like other crowdfunding sites, it retains a few percent of the donations for each campaign. Martin is the husband of Anderson's acquaintance from high school.
So far, the site, which is based in Raleigh, North Carolina, has hosted about 600 crowdfunding campaigns, some completed and some still in progress. Campaigns have raised as little as $300 to cover immediate dental expenses and as much as $12,000 for cancer treatments, Martin says, but most have set a goal between $5,000 and $10,000.
Whether or not someone's campaign is based on fact or fiction remains for prospective donors to decide.
The services could be cosmetic—for example, a breast enhancement or reduction, laser procedures for the eyes or skin, and chiropractic care. A number of campaigns have sought funding for transgender surgeries, which many insurers consider optional, he says.
In July 2019, a second site was hatched out of pet owners' requests for assistance with their dogs' and cats' medical expenses. Money raised on CoFund My Pet can only be used at veterinary clinics. Martin says the debit card would be declined at other merchants, just as its CoFund Health counterpart for humans will be rejected at places other than health care facilities, dental and vision providers, and pharmacies.
Whether or not someone's campaign is based on fact or fiction remains for prospective donors to decide. If a donor were to regret a transaction, he says the site would reach out to the campaign's owner but ultimately couldn't force a refund, Martin explains, because "it's hard to chase down fraud without having access to people's health records."
In some crowdfunding campaigns, the individual needs some or all the donated resources to pay for travel and lodging at faraway destinations to receive care, says Snyder, the health sciences professor and crowdfunding report author. He suggests people only give to recipients they know personally.
"That may change the calculus a little bit," tipping the decision in favor of donating, he says. As long as the treatment isn't harmful, the funds are a small gesture of support. "There's some value in that for preserving hope or just showing them that you care."
Coronavirus Misinformation: How You Can Fight Back
Turn yourself into a source of coronavirus facts and a bulwark against the fake, misleading and fraudulent.
When it comes to fighting the new coronavirus threat, the truth is one of the few things more crucial than a gallon of hand sanitizer. But these days, both can be hard to find if you don't know where to look.
"Humans are wired to respond to emotional triggers and share misinformation if it reinforces existing beliefs and prejudices."
While it's only been around for a few months, COVID-19 has already produced an ever-expanding universe of conspiracy theories about its origins, its spread, and the danger it poses. Meanwhile, fraudulent cures and myths about treatments threaten to upend public health efforts to contain the epidemic.
But ordinary citizens aren't helpless. Research offers insight into why we're susceptible to misinformation, and armies of fact-checkers can tell us what's real and what isn't. Meanwhile, experts are offering tips about how we can effectively promote facts whether we're chatting with a stranger at the post office or challenging a cousin on Facebook.
Here a four-part strategy to help you fight back against the Coronavirus Misinformation Industrial Complex:
Understand How Bogus Beliefs Work
That crank on the Internet may be your neighbor. Or maybe even you.
According to a 2014 study published in JAMA Internal Medicine, nearly half of American surveyed said they believed in at least one grand medical conspiracy theory. Twenty percent agreed, for example, that cell phones cause cancer but officials won't do anything because of corporate pressure, and 37 percent believed an elaborate conspiracy theory about the suppression of natural cancer cures. "Although it is common to disparage adherents of conspiracy theories as a delusional fringe of paranoid cranks, our data suggest that medical conspiracy theories are widely known, broadly endorsed, and highly predictive of many common health behaviors," the study authors write.
In an interview with leapsmag, study lead author Eric Oliver said we're drawn to "conspiracy theories that correspond with our intuitions."
"In the case of medicine, I think there are three big factors: Fears of Big Pharma -- a large percentage of Americans have a distorted sense of what pharmaceutical companies are capable of -- fears of government, and fears of contagion," said Oliver, a political scientist at the University of Chicago.
Why does it matter if people believe in conspiracy theories about coronavirus? As Oliver's study notes, conspiracy theorists are less likely to rely on traditional medicine, get flu shots, or go to annual check-ups. They could be especially susceptible to disease and inappropriate treatment.
Joseph Uscinski, a professor of political science at the University of Miami who studies conspiracies, elaborated on how this works. "You could have people who think coronavirus is fake and say, 'I'm not going to wash my hand or take preventive action. This is the media making something up, or this is just a plot for the pharmaceutical companies to sell a vaccine.' If you have a lot of people acting that way, that increases the ability of the virus to spread."
Get the Facts from the Experts
How can you avoid being a misinformation source? Educate yourself to make sure you're not spouting fake facts yourself with the instant ease that the Internet allows. "Humans are wired to respond to emotional triggers and share misinformation if it reinforces existing beliefs and prejudices," writes misinformation scholar Claire Wardle in a 2019 Scientific American commentary. That means you too.
For coronavirus facts, experts recommend looking to the websites of government agencies (such as the CDC, World Health Organization and National Institutes of Health) and top-tier medical organizations (Mayo Clinic, Infectious Disease Society of America).
Respected mainstream news outlets such as The New York Times and National Public Radio offer extensive original reporting on the coronavirus threat. While some news outlets still require users to pay to get full access to stories, others have dropped their paywalls and made coronavirus content free to all. These include the Seattle Times, Bloomberg News and the medical news site Stat.
Locally, look to your region's public health department, news outlets, and medical organizations such as hospitals and health plans.
The Poynter Institute, a journalism watchdog outfit, offers a helpful guide to evaluating what you read about coronavirus. And a paid service called NewsGuard offers a browser plug-in that provides a "trust rating" for popular news sites. "Our goal is to teach news literacy–and we hope all websites will earn green ratings and be generally reliable to consumers," the NewsGuard site says.
"As we combat misinformation, we also need to be mindful of the fact that we're dealing with a lot of uncertainty."
Remember, however, that scientists and physicians are learning more about the coronavirus each day. Assumptions about the virus will change as more information comes in, and there are still many questions about crucial topics like its fatality rate and the ways the virus spreads. You should expect that reliable sources – and experts – may provide conflicting information.
"As we combat misinformation, we also need to be mindful of the fact that we're dealing with a lot of uncertainty," says Boston cardiologist and author Dr. Haider Warraich of Brigham and Women's Hospital.
Double-Check Suspicious Information
No, the coronavirus wasn't created in a Winnipeg laboratory. You can't kill it by drinking bleach or frolicking in snow. And, as the French Health Ministry helpfully advised on Twitter, "Non, La cocaïne NE protège PAS contre le #COVID19" – "No, cocaine does NOT prevent Covid-19."
Facebook, YouTube and Twitter are all trying to remove fake or misleading coronavirus content, The New York Times reported, and "all said they were making efforts to point people back to reliable sources of medical information." Still, as the Times reports, bogus cures and conspiracy theories are rampant across social media and beyond.
Fortunately, there are many fact-checking resources. Turn to them for ammunition before you amplify – or challenge -- a coronavirus claim that seems suspicious.
Helpful myth-busting resources include:
** The venerable fact-checking site Snopes.com, which has checked multiple coronavirus claims. (Example: No, garlic water won't cure coronavirus.)
** The World Health Organization. (Example: No, mosquito bites can't transmit coronavirus)
** FactCheck.org. (Example: No, a disgraced Harvard scientist wasn't arrested for creating the coronavirus.)
** PolitiFact.org. (Example: No, the coronavirus is not just "the common cold.")
** The International Fact-Checking Network, accessible via the social-media hashtags #CoronaVirusFacts and #DatosCoronaVirus.
Correct Others With Caution
On social media, anger and sarcasm make up a kind of common tongue. But sick burns won't force misinformed people see the light. Instead, try a gentler approach.
"The most important thing would be to first acknowledge their anxieties rather than first trying to rationalize away their misbeliefs," said the University of Chicago's Oliver. "People embrace misinformation and conspiracy theories because they are afraid and trying to make sense of the world. Their beliefs serve a strong emotional function and will be defended as such. Trying to rationalize with them or argue with them may be counterproductive if one can't first put them at some ease."
Turn yourself into a source of coronavirus facts and a bulwark against the fake, misleading, and fraudulent.
So what can you do? "There will never be a magic bullet," the University of Miami's Uscinski said, but one approach is to highlight reliable information from sources that the person trusts, such as news outlets (think MSNBC or Fox News) or politicians.
However, don't waste your time. "If you have people who are believing in the craziest thing, they're probably not going to offer a rational conversation," he said. And, he added, there's an alternative to correcting others: Turn yourself into a source of coronavirus facts and a bulwark against the fake, misleading, and fraudulent. "We can be preventive and inoculate people against these beliefs," he said, "by flooding the information environment with proper information as much as possible."