Arguing About Vaccines Doesn’t Usually Work — But This Might
Ethan Lindenberger, the Ohio teenager who sought out vaccinations after he was denied them as a child, recently testified before Congress about why his parents became anti-vaxxers. The trouble, he believes, stems from the pervasiveness of misinformation online.
There is evidence that 'educating' people with facts about the benefits of vaccination may not be effective.
"For my mother, her love and affection and care as a parent was used to push an agenda to create a false distress," he told the Senate Committee. His mother read posts on social media saying vaccines are dangerous, and that was enough to persuade her against them.
His story is an example of how widespread and harmful the current discourse on vaccinations is—and more importantly—how traditional strategies to convince people about the merits of vaccination have largely failed.
As responsible members of society, all of us have implicitly signed on to what ethicists call the "Social Contract" -- we agree to abide by certain moral and political rules of behavior. This is what our societal values, norms, and often governments are based upon. However, with the unprecedented rise of social media, alternative facts, and fake news, it is evident that our understanding—and application—of the social contract must also evolve.
Nowhere is this breakdown of societal norms more visible than in the failure to contain the spread of vaccine-preventable diseases like measles. What started off as unexplained episodes in New York City last October, mostly in communities that are under-vaccinated, has exploded into a national epidemic: 880 cases of measles across 24 states in 2019, according to the CDC (as of May 17, 2019). In fact, the Unites States is only eight months away from losing its "measles free" status, joining Venezuela as the second country out of North and South America with that status.
The U.S. is not the only country facing this growing problem. Such constant and perilous reemergence of measles and other vaccine-preventable diseases in various parts of the world raises doubts about the efficacy of current vaccination policies. In addition to the loss of valuable life, these outbreaks lead to loss of millions of dollars in unnecessary expenditure of scarce healthcare resources. While we may be living through an age of information, we are also navigating an era whose hallmark is a massive onslaught on truth.
There is ample evidence on how these outbreaks start: low-vaccination rates. At the same time, there is evidence that 'educating' people with facts about the benefits of vaccination may not be effective. Indeed, human reasoning has a limit, and facts alone rarely change a person's opinion. In a fascinating report by researchers from the University of Pennsylvania, a small experiment revealed how "behavioral nudges" could inform policy decisions around vaccination.
In the reported experiment, the vaccination rate for employees of a company increased by 1.5 percent when they were prompted to name the date when they planned to get their flu shot. In the same experiment, when employees were prompted to name both a date and a time for their planned flu shot, vaccination rate increased by 4 percent.
A randomized trial revealed the subtle power of "announcements" – direct, brief, assertive statements by physicians that assumed parents were ready to vaccinate their children.
This experiment is a part of an emerging field of behavioral economics—a scientific undertaking that uses insights from psychology to understand human decision-making. The field was born from a humbling realization that humans probably do not possess an unlimited capacity for processing information. Work in this field could inform how we can formulate vaccination policy that is effective, conserves healthcare resources, and is applicable to current societal norms.
Take, for instance, the case of Human Papilloma Virus (HPV) that can cause several types of cancers in both men and women. Research into the quality of physician communication has repeatedly revealed how lukewarm recommendations for HPV vaccination by primary care physicians likely contributes to under-immunization of eligible adolescents and can cause confusion for parents.
A randomized trial revealed the subtle power of "announcements" – direct, brief, assertive statements by physicians that assumed parents were ready to vaccinate their children. These announcements increased vaccination rates by 5.4 percent. Lengthy, open-ended dialogues demonstrated no benefit in vaccination rates. It seems that uncertainty from the physician translates to unwillingness from a parent.
Choice architecture is another compelling concept. The premise is simple: We hardly make any of our decisions in vacuum; the environment in which these decisions are made has an influence. If health systems were designed with these insights in mind, people would be more likely to make better choices—without being forced.
This theory, proposed by Richard Thaler, who won the 2017 Nobel Prize in Economics, was put to the test by physicians at the University of Pennsylvania. In their study, flu vaccination rates at primary care practices increased by 9.5 percent all because the staff implemented "active choice intervention" in their electronic health records—a prompt that nudged doctors and nurses to ask patients if they'd gotten the vaccine yet. This study illustrated how an intervention as simple as a reminder can save lives.
To be sure, some bioethicists do worry about implementing these policies. Are behavioral nudges akin to increased scrutiny or a burden for the disadvantaged? For example, would incentives to quit smoking unfairly target the poor, who are more likely to receive criticism for bad choices?
The measles outbreak is a sober reminder of how devastating it can be when the social contract breaks down.
While this is a valid concern, behavioral economics offers one of the only ethical solutions to increasing vaccination rates by addressing the most critical—and often legal—challenge to universal vaccinations: mandates. Choice architecture and other interventions encourage and inform a choice, allowing an individual to retain his or her right to refuse unwanted treatment. This distinction is especially important, as evidence suggests that people who refuse vaccinations often do so as a result of cognitive biases – systematic errors in thinking resulting from emotional attachment or a lack of information.
For instance, people are prone to "confirmation bias," or a tendency to selectively believe in information that confirms their preexisting theories, rather than the available evidence. At the same time, people do not like mandates. In such situations, choice architecture provides a useful option: people are nudged to make the right choice via the design of health delivery systems, without needing policies that rely on force.
The measles outbreak is a sober reminder of how devastating it can be when the social contract breaks down and people fall prey to misinformation. But all is not lost. As we fight a larger societal battle against alternative facts, we now have another option in the trenches to subtly encourage people to make better choices.
Using insights from research in decision-making, we can all contribute meaningfully in controversial conversations with family, friends, neighbors, colleagues, and our representatives — and push for policies that protect those we care about. A little more than a hundred years ago, thousands of lives were routinely lost to preventive illnesses. We've come too far to let ignorance destroy us now.
Meet Dr. Renee Wegrzyn, the first Director of President Biden's new health agency, ARPA-H
In today’s podcast episode, I talk with Renee Wegrzyn, appointed by President Biden as the first director of a federal agency created last year called the Advanced Research Projects Agency for Health, or ARPA-H. It’s inspired by DARPA, the agency that develops innovations for the Defense department and has been credited with hatching world changing technologies such as ARPANET, which became the internet.
Time will tell if ARPA-H will lead to similar achievements in the realm of health. That’s what President Biden and Congress expect in return for funding ARPA-H at 2.5 billion dollars over three years.
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How will the agency figure out which projects to take on, especially with so many patient advocates for different diseases demanding moonshot funding for rapid progress.
I talked with Dr. Wegrzyn about the opportunities and challenges, what lessons ARPA-H is borrowing from Operation Warp Speed, how she decided on the first ARPA-H project which was just announced recently, why a separate agency was needed instead of trying to reform HHS and the National Institutes of Health to be better at innovation, and how ARPA-H will make progress on disease prevention in addition to treatments for cancer, Alzheimer’s and diabetes, among many other health priorities.
Dr. Wegrzyn’s resume is filled with experience for her important role. She was a program manager at DARPA where she focused on applying gene editing and synthetic biology to the goal of improving biosecurity. For her work there, she was given the Superior Public Service Medal and, just in case that wasn’t enough ARPA experience, she also worked at another ARPA that leads advanced projects in intelligence, called I-ARPA. Before that, she was in charge of technical teams in the private sector working on gene therapies and disease diagnostics, among other areas. She has been a vice president of business development at Gingko Bioworks and headed innovation at Concentric by Gingko. Her training and education includes a PhD and undergraduate degree in applied biology from the Georgia Institute of Technology and she did her postdoc as an Alexander von Humboldt Fellow in Heidelberg, Germany.
As Dr. Wegrzyn told me, she’s “in the hot seat” - the pressure is on for ARPA-H especially after the need and potential for health innovation was spot lit by the pandemic and the unprecedented speed of vaccine development. We'll soon find out if ARPA-H can produce something in health that’s equivalent to DARPA’s creation of the internet.
ARPA-H - https://arpa-h.gov/
Dr. Wegrzyn profile - https://arpa-h.gov/people/renee-wegrzyn/
Dr. Wegrzyn Twitter - https://twitter.com/rwegrzyn?lang=en
President Biden Announces Dr. Wegrzyn's appointment - https://www.whitehouse.gov/briefing-room/statement...
Leaps.org coverage of ARPA-H - https://leaps.org/arpa/
ARPA-H program for joints to heal themselves - https://arpa-h.gov/news/nitro/ -
ARPA-H virtual talent search - https://arpa-h.gov/news/aco-talent-search/
Matt Fuchs is the editor-in-chief of Leaps.org and Making Sense of Science. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him @fuchswriter.
Tiny, tough “water bears” may help bring new vaccines and medicines to sub-Saharan Africa
Microscopic tardigrades, widely considered to be some of the toughest animals on earth, can survive for decades without oxygen or water and are thought to have lived through a crash-landing on the moon. Also known as water bears, they survive by fully dehydrating and later rehydrating themselves – a feat only a few animals can accomplish. Now scientists are harnessing tardigrades’ talents to make medicines that can be dried and stored at ambient temperatures and later rehydrated for use—instead of being kept refrigerated or frozen.
Many biologics—pharmaceutical products made by using living cells or synthesized from biological sources—require refrigeration, which isn’t always available in many remote locales or places with unreliable electricity. These products include mRNA and other vaccines, monoclonal antibodies and immuno-therapies for cancer, rheumatoid arthritis and other conditions. Cooling is also needed for medicines for blood clotting disorders like hemophilia and for trauma patients.
Formulating biologics to withstand drying and hot temperatures has been the holy grail for pharmaceutical researchers for decades. It’s a hard feat to manage. “Biologic pharmaceuticals are highly efficacious, but many are inherently unstable,” says Thomas Boothby, assistant professor of molecular biology at University of Wyoming. Therefore, during storage and shipping, they must be refrigerated at 2 to 8 degrees Celsius (35 to 46 degrees Fahrenheit). Some must be frozen, typically at -20 degrees Celsius, but sometimes as low -90 degrees Celsius as was the case with the Pfizer Covid vaccine.
For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
The costly cold chain
The logistics network that ensures those temperature requirements are met from production to administration is called the cold chain. This cold chain network is often unreliable or entirely lacking in remote, rural areas in developing nations that have malfunctioning electrical grids. “Almost all routine vaccines require a cold chain,” says Christopher Fox, senior vice president of formulations at the Access to Advanced Health Institute. But when the power goes out, so does refrigeration, putting refrigerated or frozen medical products at risk. Consequently, the mRNA vaccines developed for Covid-19 and other conditions, as well as more traditional vaccines for cholera, tetanus and other diseases, often can’t be delivered to the most remote parts of the world.
To understand the scope of the challenge, consider this: In the U.S., more than 984 million doses of Covid-19 vaccine have been distributed so far. Each one needed refrigeration that, even in the U.S., proved challenging. Now extrapolate to all vaccines and the entire world. For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
Globally, the cold chain packaging market is valued at over $15 billion and is expected to exceed $60 billion by 2033.
Freeze-drying, also called lyophilization, which is common for many vaccines, isn’t always an option. Many freeze-dried vaccines still need refrigeration, and even medicines approved for storage at ambient temperatures break down in the heat of sub-Saharan Africa. “Even in a freeze-dried state, biologics often will undergo partial rehydration and dehydration, which can be extremely damaging,” Boothby explains.
The cold chain is also very expensive to maintain. The global pharmaceutical cold chain packaging market is valued at more than $15 billion, and is expected to exceed $60 billion by 2033, according to a report by Future Market Insights. This cost is only expected to grow. According to the consulting company Accenture, the number of medicines that require the cold chain are expected to grow by 48 percent, compared to only 21 percent for non-cold-chain therapies.
Tardigrades to the rescue
Tardigrades are only about a millimeter long – with four legs and claws, and they lumber around like bears, thus their nickname – but could provide a big solution. “Tardigrades are unique in the animal kingdom, in that they’re able to survive a vast array of environmental insults,” says Boothby, the Wyoming professor. “They can be dried out, frozen, heated past the boiling point of water and irradiated at levels that are thousands of times more than you or I could survive.” So, his team is gradually unlocking tardigrades’ survival secrets and applying them to biologic pharmaceuticals to make them withstand both extreme heat and desiccation without losing efficacy.
Boothby’s team is focusing on blood clotting factor VIII, which, as the name implies, causes blood to clot. Currently, Boothby is concentrating on the so-called cytoplasmic abundant heat soluble (CAHS) protein family, which is found only in tardigrades, protecting them when they dry out. “We showed we can desiccate a biologic (blood clotting factor VIII, a key clotting component) in the presence of tardigrade proteins,” he says—without losing any of its effectiveness.
The researchers mixed the tardigrade protein with the blood clotting factor and then dried and rehydrated that substance six times without damaging the latter. This suggests that biologics protected with tardigrade proteins can withstand real-world fluctuations in humidity.
Furthermore, Boothby’s team found that when the blood clotting factor was dried and stabilized with tardigrade proteins, it retained its efficacy at temperatures as high as 95 degrees Celsius. That’s over 200 degrees Fahrenheit, much hotter than the 58 degrees Celsius that the World Meteorological Organization lists as the hottest recorded air temperature on earth. In contrast, without the protein, the blood clotting factor degraded significantly. The team published their findings in the journal Nature in March.
Although tardigrades rarely live more than 2.5 years, they have survived in a desiccated state for up to two decades, according to Animal Diversity Web. This suggests that tardigrades’ CAHS protein can protect biologic pharmaceuticals nearly indefinitely without refrigeration or freezing, which makes it significantly easier to deliver them in locations where refrigeration is unreliable or doesn’t exist.
The tricks of the tardigrades
Besides the CAHS proteins, tardigrades rely on a type of sugar called trehalose and some other protectants. So, rather than drying up, their cells solidify into rigid, glass-like structures. As that happens, viscosity between cells increases, thereby slowing their biological functions so much that they all but stop.
Now Boothby is combining CAHS D, one of the proteins in the CAHS family, with trehalose. He found that CAHS D and trehalose each protected proteins through repeated drying and rehydrating cycles. They also work synergistically, which means that together they might stabilize biologics under a variety of dry storage conditions.
“We’re finding the protective effect is not just additive but actually is synergistic,” he says. “We’re keen to see if something like that also holds true with different protein combinations.” If so, combinations could possibly protect against a variety of conditions.
Before any stabilization technology for biologics can be commercialized, it first must be approved by the appropriate regulators. In the U.S., that’s the U.S. Food and Drug Administration. Developing a new formulation would require clinical testing and vast numbers of participants. So existing vaccines and biologics likely won’t be re-formulated for dry storage. “Many were developed decades ago,” says Fox. “They‘re not going to be reformulated into thermo-stable vaccines overnight,” if ever, he predicts.
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits.
Instead, this technology is most likely to be used for the new products and formulations that are just being created. New and improved vaccines will be the first to benefit. Good candidates include the plethora of mRNA vaccines, as well as biologic pharmaceuticals for neglected diseases that affect parts of the world where reliable cold chain is difficult to maintain, Boothby says. Some examples include new, more effective vaccines for malaria and for pathogenic Escherichia coli, which causes diarrhea.
Tallying up the benefits
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits. For instance, MenAfriVac, a meningitis vaccine (without tardigrade proteins) developed for sub-Saharan Africa, can be stored at up to 40 degrees Celsius for four days before administration. “If you have a few days where you don’t need to maintain the cold chain, it’s easier to transport vaccines to remote areas,” Fox says, where refrigeration does not exist or is not reliable.
Better health is an obvious benefit. MenAfriVac reduced suspected meningitis cases by 57 percent in the overall population and more than 99 percent among vaccinated individuals.
Lower healthcare costs are another benefit. One study done in Togo found that the cold chain-related costs increased the per dose vaccine price up to 11-fold. The ability to ship the vaccines using the usual cold chain, but transporting them at ambient temperatures for the final few days cut the cost in half.
There are environmental benefits, too, such as reducing fuel consumption and greenhouse gas emissions. Cold chain transports consume 20 percent more fuel than non-cold chain shipping, due to refrigeration equipment, according to the International Trade Administration.
A study by researchers at Johns Hopkins University compared the greenhouse gas emissions of the new, oral Vaxart COVID-19 vaccine (which doesn’t require refrigeration) with four intramuscular vaccines (which require refrigeration or freezing). While the Vaxart vaccine is still in clinical trials, the study found that “up to 82.25 million kilograms of CO2 could be averted by using oral vaccines in the U.S. alone.” That is akin to taking 17,700 vehicles out of service for one year.
Although tardigrades’ protective proteins won’t be a component of biologic pharmaceutics for several years, scientists are proving that this approach is viable. They are hopeful that a day will come when vaccines and biologics can be delivered anywhere in the world without needing refrigerators or freezers en route.