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Vaccines can be grown in and extracted from the leaves of plants.
- Vaccines are absolutely crucial to keeping the entire planet healthy. None of us is safe until all of us are safe.
- But low- and middle-income countries have a difficult time acquiring and distributing them.
- Plant-derived vaccines can be stored by harvesting and freeze-drying the leaves. They may help solve the problem of global vaccine distribution.
Vaccines are the mainstay of the efforts to quell the COVID-19 pandemic. The pace of their development and refinement has been astonishing, but the characteristics of many of the available vaccines will make getting them to poor countries challenging. We will need more heat-stable vaccines that can be easily transported and stored. One ongoing, promising approach to this is to produce them in plants.
Populations in many richer countries could return to a reasonable approximation of normal by the fourth quarter of this year if — a big if — they can vaccinate 80 percent or more of their populations against SARS-CoV-2. They will also need to perform constant surveillance for "variants of concern" that are more transmissible, cause more severe disease, or, especially, are better able to escape the immunity conferred by COVID-19 vaccines. An example is the coronavirus variant called "delta," first detected in India, which has become the dominant strain in the United Kingdom, despite that country's highly successful vaccination campaign. That variant now accounts for about 6 percent of infections in the United States, double its penetrance a month ago.
Vaccinating poorer countries is an enormous challenge
Prospects for poorer countries are very different, however, for every aspect of the pandemic — cases, hospitalization, deaths, and ability to suppress the pandemic with vaccines — which are, for many reasons, more elusive than for wealthier countries.
Some middle-income nations such as India and Brazil recently have experienced a devastating surge in cases after premature loosening of restrictions in their countries. Africa's toll of cases and deaths is surprisingly low, although the paucity of data makes the government-reported numbers suspect.
The task of rapidly manufacturing vast quantities of COVID-19 vaccines that are safe, efficacious, inexpensive, and transportable without stringent cold chain requirements is daunting.
Especially in lower- and middle-income countries, vaccines will be a lifeline, but providing sufficient COVID-19 vaccines for their populations will take years at current trajectories. At India's current vaccination rate of 1.8 million doses a day, for example, it would take more than three years to vaccinate 80 percent of its 1.4 billion people. Likewise, over 24 million people — less than two percent of the population — have been fully vaccinated in Africa (according to the Africa C.D.C.). Currently, a meager 0.3 percent of the vaccine doses that have been administered around the world have been provided to the 29 poorest countries. By contrast, in the United States, over 60 percent of adults have by now received at least one shot of vaccine.
Although the U.S. has purchased more than enough vaccines for its entire population, it may choose to hold onto some of its excess in case booster shots of existing vaccines are required this fall or early next year. It is also possible that the U.S. will be poised to divert domestic production to making new vaccines that will overcome "immune evasiveness" in subjects vaccinated with current vaccines.
This development could compromise the capacity to scale up manufacturing to provide global access to vaccines, further widening the gap between vaccine haves and have-nots, particularly in low resource settings where scaling access, distribution, refrigeration, and affordability are problematic. The Pfizer-BioNTech and Moderna mRNA vaccines, for example, which have cold chain limitations (an uninterrupted series of refrigerated production, storage, and distribution requirements), would be difficult to distribute in resource-poor settings such as rural India or Africa.
Advances have been made in the formulations of some vaccines so that the need for refrigeration can be avoided. Past successes include a freeze-dried version of the smallpox vaccine, which was critical for eradication of that deadly disease. Making a freeze-dried version of mRNA vaccines such as Pfizer and Moderna may be feasible but could be cost-prohibitive for a global market. The estimated costs of the global vaccination effort could reach $74 billion, according to a study published in The Lancet.
These challenges together could stymie our efforts to control the pandemic for years to come, bringing to mind the often-heard mantra: "None of us is safe until all of us are safe." Our inability to manufacture large quantities of vaccines rapidly would extend the pandemic, resulting in stress on healthcare and national economies, and increased mortality, all the while enabling more SARS-CoV-2 variants to emerge and gain a foothold.
The task of rapidly manufacturing vast quantities of COVID-19 vaccines that are safe, efficacious, inexpensive, and transportable without stringent cold chain requirements is daunting. These challenges may be insuperable unless we try to replicate with plant-based COVID-19 vaccines the recent clinical successes with mRNA vaccines.
Plant-based vaccines are a potential solution
Plant-based vaccines are likely the promise of the future for mass vaccination in lower- and middle-income countries. For millennia, plants have not only been sources of food, fiber, and fuel, but also, more recently, an important component of our medicine cabinet as well. The identification and application of bioactive molecules from medicinal plants is nothing new; examples include the active ingredient of aspirin, salicylic acid, derived from willow and used as a painkiller; taxol from yew trees to treat cancer; digitalis from the foxglove plant; and the malaria drug artemisinin from sweet wormwood; among others.
But those examples are yesterday's successes. Our newly-acquired ability to genetically engineer plants that express novel biologics, such as vaccines to combat pandemic flu or antibodies to block Ebola virus infection, shows how far we have come. These new pharmaceuticals are easily scalable, inexpensive to produce, and have no cold chain requirements. Plant-based vaccines to prevent COVID-19 are certainly within our grasp.
While much of the initial research concerning plant made vaccines has been conducted by stably expressing the protein of interest in genetically engineered plant tissue, plant viruses can also be harnessed to generate biopharmaceutical proteins rapidly (within a matter of days) and at low cost. Plant viruses can also act as scaffolds, displaying vaccine epitopes on the surface of self-assembled virus-like particles (VLPs). These VLPs lack nucleic acid and are, therefore, non-infectious and harmless to animals or plants.
Plant-derived vaccines can be stored by harvesting and freeze-drying the leaves, or merely by isolating the plant virus, if one was used as the antigen carrier. Moreover, a number of plant viruses have been shown to behave as adjuvants and help to stimulate a stronger immune response overall. This technology is currently being employed by several plant "molecular pharming" companies to produce vaccines for COVID-19 that would be suitable for India, Africa, and other places in need.
Plant-based COVID vaccines
Quebec plant molecular pharming company Medicago announced in a press release last month the successful completion of a phase 2 clinical trial of their plant-derived COVID-19 vaccine candidate, which contains an adjuvant obtained from GlaxoSmithKline (GSK). The titer of neutralizing antibody and the degree of cell mediated immunity the vaccine elicited were robust, and no severe adverse effects were reported.
The vaccine is based on the virus-like particle technology mentioned above. These VLPs assemble in plants with the spike protein displayed on their surface, so that the end product looks just like the real thing but is non-infectious. Medicago is currently moving their vaccine through a stage 3 clinical trial and has "fast track" designation from the FDA. The company estimates that they will be able to produce up to 80 million annual doses beginning this year, and by 2023, over a billion doses of COVID-19 vaccine doses per year. That could be just what low- and middle-income countries will need to suppress the COVID-19 pandemic.
Other plant molecular pharming companies are not far behind. Kentucky BioProcessing (KBP), a member of British American Tobacco group, uses a technology similar to Medicago's to produce COVID-19 vaccines in plants. KBP's previous claim to fame was producing antibodies in plants to block Ebola infection, and KBP's plant-based COVID-19 vaccine has successfully elicited an immune response to the virus in animals and is currently moving into clinical trials. The company also uses a virus-based technology. Attaching the vaccine antigen to the plant virus provides the vaccine with greater stability at room temperature. This plant virus is also non-infectious to humans but can be taken up by immune cells to elicit a strong response.
A third company that is making headway is Texas-based iBio, which is working on several vaccine candidates. These include a virus-like particle, a subunit vaccine, and a second-generation vaccine that targets the SARS-CoV-2 virus's N protein, which is more conserved than the spike protein. The N protein is, therefore, less likely to mutate, even when virus variants emerge and circulate, thus making the vaccine more likely to be successful against variants. These vaccines have performed well in pre-clinical and toxicology studies.
As microbes mutate, we must innovate
The current pandemic is far from over, and scaled up vaccination programs are needed immediately to reduce the spread of COVID and decrease the emergence of new variants of concern. While vaccine distribution certainly remains a significant obstacle for many countries, simply ramping up vaccine manufacturing is currently our greatest challenge. At least some of this burden could be alleviated by adding plant-made vaccines to our global arsenal. They are safe, inexpensive, efficacious, easy to produce in large amounts, and are less susceptible to cold chain requirements for distribution and administration. The rapid scale-up of COVID-19 plant-made vaccines could be a significant step toward suppressing or even ending the pandemic, as well as offering an important new technology for the future.
Kathleen Hefferon, Ph.D., teaches microbiology at Cornell University. Find Kathleen on Twitter @KHefferon. Henry Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. He was a Research Associate at the NIH and the founding director of the U.S. FDA's Office of Biotechnology. Find Henry on Twitter @henryimiller.
- Robert Koch proved that microbes cause infectious diseases and famously identified the etiological agents of anthrax, tuberculosis, and cholera.
- Louis Pasteur proved that life does not spontaneously generate from non-living material, made a significant advance in chemistry, invented pasteurization, and revolutionized vaccines.
- Koch and Pasteur had a bitter rivalry over the invention of the anthrax vaccine.
This following is an excerpt from Viruses, Pandemics, and Immunity by Arup K. Chakraborty and Andrey S. Shaw. Reprinted with Permission from The MIT PRESS. Copyright 2021.
Koch's Postulates, Anthrax, Tuberculosis, and Cholera
Robert Koch was born in Germany in 1843. His father was a mining engineer. He taught himself to read by the time he was five years old, and was a brilliant student from a young age. After a brief time studying natural sciences in college, he decided to pursue a career in medicine. Koch held positions as a physician in various capacities in Poland, Berlin, and other places, including service as a doctor during the Franco-Prussian War. Koch also developed a deep interest in basic scientific research. Today, we would consider him a clinician-scientist, someone who tries to understand clinical aspects of diseases using basic scientific principles. Anthrax is a disease that affects both animals and humans, and was a problem in Koch's time. Koch showed that, for a wide variety of animals, he could transfer disease from one animal to another by transferring blood from the infected animal to the healthy animal. All animals thus infected exhibited the same disease symptoms, and had the same rod-shaped bacteria in their blood. This convinced Koch that this specific bacterium caused anthrax. Koch's work on anthrax was the first to associate a specific microbe with a particular disease.
Credit: Wikipedia / Public domain
It was known that healthy cattle got sick if they grazed on fields long after anthrax-infected cattle had grazed there. This was a puzzle because Koch had determined that anthrax bacteria in the blood of infected animals lost their infectivity after a few days. He decided that he would need to watch the bacteria over time and would need to develop methods to grow the bacteria in the lab. Koch developed methods to keep bacteria growing for days. This process is called "growing bacteria in culture" — "culture" refers to the medium in which the bacteria are grown. This method is now used millions of times every day around the world. When a doctor suspects that you have a bacterial infection, a small sample is collected from the suspected site of infection (e.g., a wound) and is sent to the pathology department. If the sample contains bacteria, they grow out in culture and can be identified. The doctor can use such a positive test result to prescribe the right treatment to kill the identified bacteria.
With the technique to culture bacteria in hand, using his careful observational skills, Koch noted that on occasion anthrax bacteria would convert into opaque spheres. He showed that these spheres could be dried and then reconstituted weeks later by immersing them into fluid. He suspected that the bacteria, if converted into the dry spheres, or spores, could remain dormant for years. Indeed, this is the case, and they can cause bacterial infection when ingested by uninfected cattle. Some readers will remember the anthrax scares in the United States right after the September 11, 2001, terrorist attacks when an individual placed anthrax spores into envelopes that were sent to members of the US Congress.
As Koch become more skilled in the identification of disease causing bacteria, his methods became codified into rules known as "Koch's postulates":
- The microorganism must be present in every instance of the disease.
- The microorganism must be isolated from a human with the disease and grown in culture.
- The microorganism grown in culture must cause the same disease upon injection in an animal.
- Samples from the animal in which disease thus occurs must contain the same organism that was present in the original diseased human.
These principles were applied successfully to determine the causative agents of many of the infectious diseases known today. Knowing the identity of specific bacteria that cause a particular disease, scientists and drug companies can develop antibiotics that can kill the bacteria and cure disease. Before the discovery of antibiotics, a small skin cut could get infected and result in death. We live in a world that would be unrecognizable to a nineteenth-century inhabitant because many previously lethal infections and diseases are easily treatable today.
Koch's other significant discoveries were the bacteria that cause tuberculosis and cholera. Tuberculosis (TB) is a disease that has longed plagued the world. It was often called consumption, because it made the person look pale and thin as the disease progressed. In opera, it is the disease from which both Mimi in La Bohème and Violetta in La Traviata suffer, reflecting a nineteenth century association of romantic tragedy with this disease. TB caused enormous numbers of deaths in the nineteenth century. Since it is a contagious disease, it flourished partly because of the increased population density in growing cities during the industrial revolution. Throughout the nineteenth century, about one out of a 100 people living in New York City died of tuberculosis, roughly the same percentage as the number of reported COVID-19 deaths in the city and ten times more than die of influenza in an average year.
Until Koch showed that it was an infectious disease caused by bacteria, many thought that TB was an inherited disease. In 1882, using his postulates, Koch identified the causative organism and called it Mycobacterium tuberculosis. This discovery led to a better understanding of the disease and the development of TB-specific antibiotics, which along with better sanitation resulted in a significant decline in infections and deaths. However, TB is still widespread and remains a scourge in many parts of the world. In 2018 TB killed 1.5 million people globally. An especially worrisome development has been the recent emergence of antibiotic-resistant forms of M. tuberculosis. A vaccine that is used around the world to protect against TB infection has only limited efficacy.
Cholera is a waterborne disease that causes severe diarrhea and vomiting. Cholera outbreaks still cause havoc in the developing world today. The most recent outbreak of cholera was in Sudan in 2019. Another recent cholera epidemic was in Haiti in 2010 following a devastating earthquake. There are indications that, sadly, peacekeepers from the United Nations who came to provide aid may have inadvertently brought the disease to Haiti.
Koch received worldwide fame for his identification of the organism that causes cholera. However, the causative bacterium was, in fact, first described by an Italian physician, Filippo Pacini (1812–1883), many years earlier. During the period from the late 1810s to the early 1860s, there were worldwide cholera pandemics that started in India in the state of Bengal. Pacini was a doctor in Florence, Italy, when the pandemic spread into that city. Using a microscope to examine tissues collected during autopsies of those who had succumbed to cholera, Pacini discovered the bacterium, Vibrio cholerae, that causes the disease. Remarkably, few, including Koch, knew of his discovery, perhaps partly because the germ theory of disease was not widely accepted when Pacini described his observations. Better sanitation has made cholera a disease that is nonexistent in the developed world.
Koch, who passed away in 1910, received many significant recognitions for his work, including the 1905 Nobel Prize for Physiology and Medicine. We now turn to the work of his bitter rival, Louis Pasteur.
Pasteur, Rabies, and a New Paradigm for Vaccination
Pasteur was born in 1822 in France. His father was a tanner. Pasteur did not distinguish himself academically as a youngster. After earning a bachelor's degree in philosophy in 1840, he was drawn to the study of science and mathematics. As is true today, in Pasteur's time only the very best students in France were admitted to the École Normale Supérieure. Pasteur was ranked very poorly the first time he took the admission test, but he was ultimately admitted in 1843. This hiccup at an early stage of his scientific career did not prevent Pasteur from going on to make transformative discoveries.
When he was a professor at the University of Strasbourg, in France, Pasteur made a very important fundamental discovery which involved the mathematical concept of chirality. Two similar objects that have non-superimposable mirror images are chiral. The simplest example is our right and left hands — look at images of your hands in a mirror and you will see what we mean. While studying crystals of salts of certain acids, Pasteur demonstrated that molecules can also be chiral, either "right-handed" or "left-handed." He developed a way to detect the handedness of such so-called optical isomers. A good example of handedness is sugar. Sugar is a chiral molecule that is right-handed, and sugar substitutes can be composed of its left-handed optical isomer. The molecule in our body that metabolizes sugar does not act on its left-handed isomer, and thus we do not metabolize it. But our taste buds cannot tell the difference between the right- and left-handed molecules, and so such sugar-substitutes would taste the same to us — a free lunch, so to speak.
Pasteur's next big achievement was inventing a process which was later named pasteurization. One of Pasteur's students was the son of a wine merchant, and he interested Pasteur into thinking about how to prevent wine from spoiling. It was commonly believed at the time that wine spoiled because it spontaneously decomposed into constituents that tasted like vinegar. Pasteur showed that this was not true and that a microbe called yeast was required to carry out these chemical transformations. Pasteur also showed that contamination of wine with various other microbes causes it to spoil. He invented a process to prevent this, which exploited the fact that microbes die at high temperatures. The wine was heated to about 120–140°F, and then sealed and cooled. Although this pasteurization process was invented to prevent wine from spoiling, it is rarely used for this purpose today. Rather, pasteurization is used all over the world to prevent milk from spoiling.
Pasteur also played a significant role in laying to rest the popular idea that many living organisms were spontaneously generated from nonliving matter. As old bread begins to grow mold and maggots suddenly appear in old meat, it wasn't illogical to believe that these changes occurred spontaneously. Evidence against this so-called spontaneous generation theory had already been presented many times by other scientists, but Koch's postulates and an elegant and definitive experiment that Pasteur did in 1859 finally proved to be its death knell. Pasteur stored boiled (pasteurized) water in two curved, swan-necked flasks. Boiling the water ensured that there were no microbes in it when the experiment was started. The construction of the swan-neck flask was such that microbes in the air would get stuck to the walls of the tube and not reach the water if the flask was vertically positioned. Pasteur positioned one flask vertically, and the other was tilted. As time passed, the water in the vertical flask did not show any signs of a developing biofilm (you must have seen such disgusting biofilms when you leave food in the refrigerator too long and microbes grow on it). A biofilm developed in the water in the tilted flask because microbes in the air could reach the water. This demonstration was the end of the spontaneous generation theory.
Most scientists can only dream of making contributions as important as Pasteur's discovery of optical isomers, his invention of pasteurization, and his experiment ending the debate on the spontaneous generation of microbes. But his contributions to vaccination had such a major impact on humankind that the achievements described above have been completely overshadowed.
Pasteur's paradigm-shifting advance in vaccine development was the result of a serendipitous observation he made while studying chicken cholera. On one occasion, after chickens were injected with the bacteria that causes this disease, they did not fall ill. On further investigation, Pasteur discovered that the batch of chicken cholera he had injected had spoiled. Rather than buy new chickens, he reinjected the first set of chickens with the properly cultured bacteria. To his surprise, the chickens did not fall ill. Pasteur is often credited with the famous remark, "In the field of observation, chance favors the prepared mind." Pasteur's mind was apparently prepared, as he immediately understood that he had stumbled on to an important finding. He realized that you could protect animals from infection with a live disease-causing microbe by vaccinating them with a weakened form of the same microbe.
This was a paradigm shift compared to previous methods. Variolation involved administering the real pathogen. Jenner's use of cowpox involved finding a pathogen that was harmless to humans but related to the one that caused human disease. Pasteur's new method did not involve hunting for a related harmless pathogen or risking the life of the patient by administering the real pathogen. Rather, a weakened or attenuated form of the pathogen could be used. It is worth remarking here that variolation involved powdering material from smallpox scabs and waiting a few days before administering it. These procedures were probably inadvertent ways to attenuate the virulence of the pathogen. But it was Pasteur who in the period between 1879 and 1880 formalized the procedure of using an attenuated pathogen to protect people from infectious diseases, and established a method that continues to be used today. Pasteur labeled his new method of protecting against various infectious diseases "vaccination," in honor of Jenner's use of vaccinia (cowpox) to protect against smallpox. Pasteur used his method to vaccinate birds to prevent cholera and vaccinate sheep to prevent anthrax.
Pasteur then developed a vaccine to protect against rabies. Rabies is an infection of the brain caused by the bite of an infected dog or, more often today, a bat. People infected with rabies exhibit symptoms like paralysis and fear of water. This fear of water is why the disease is sometimes called hydrophobia. Almost everyone afflicted with the disease died. Pasteur was a chemist and not a physician, but having successfully developed two animal vaccines, he was keen to use his skills to cure a human disease or protect people from it. We know today that rabies is caused by a virus, but the concept of a virus was not known at that time. Therefore, Pasteur could neither follow Koch's postulates to identify the causative agent of the disease, nor grow the microbe in culture using methods that worked for bacteria. It was known, however, that the infectious agent was present in saliva. Pasteur is claimed to have been fearless, having used his mouth to suck on a glass tube to draw saliva from a rabid dog.
Using a method developed by his close collaborator, Emile Roux, Pasteur then attenuated the infectious agent. Pasteur and Roux administered the attenuated infectious agent and showed that multiple doses of this vaccine could protect dogs from rabies infection. Pasteur was anxious to try his vaccine in humans. He knew that the onset of symptoms usually lagged the dog bite by about a month. His idea was to vaccinate people soon after the dog bite, and hope that the protective mechanism (about which they knew nothing) would kick in quickly enough to cure them. The first two patients on whom this procedure was tried were in the late stages of the disease, however, and both died before they could receive the second dose of the vaccine. But Pasteur persevered.
In 1885, Joseph Meister, a 9-year-old boy living in Alsace, was bitten multiple times by a rabid dog that was subsequently shot by the police. His doctor learned that Pasteur had developed a vaccine to treat rabies. In an attempt to evade what was a certain death sentence, he brought Joseph and his family to Paris the next day to seek Pasteur's help. Emile Roux refused to use the vaccine on Joseph as he worried that it was not ready for humans and was too dangerous to try on a child who did not yet have any symptoms of the disease. Pasteur found another physician to administer the treatment and it worked — the boy was cured. Subsequently, others would undergo the same procedure with similar success, and Pasteur became a hero. Years later, Meister, who was devoted to Pasteur, would serve as a caretaker at the Pasteur Institute.
Throughout this period, Pasteur worked on an anthrax vaccine even though Koch, who discovered the bacterium that causes anthrax, was also working on a vaccine. This led to terrible arguments between the two acclaimed scientists. Koch and his students wrote that Pasteur did not even know how to make pure cultures of bacteria. Pasteur fought back. These arguments took on an even more vicious tone during the Franco-Prussian War. In 1868, Pasteur had been awarded an honorary degree by the faculty of Bonn in Germany. He returned it during the war with an angry accompanying note. Thus began a division between German and French immunologists that would continue for decades, to the detriment of scientific advances. Pasteur ultimately achieved success in a public experiment in 1881 when he successfully vaccinated several sheep and cows, and a goat, to protect them from anthrax. He then declared it to be a great French victory. Ironically, an anthrax vaccine had earlier been developed by Jean Joseph Henri Toussaint (1847–1890) in France. Pasteur used the same method as Toussaint, but claimed that his approach was different.
When Pasteur died, he left his laboratory notebooks to his oldest male child, and his will stipulated that these notebooks should never leave the family and were to be passed on from generation to generation by male inheritors. In 1964, Pasteur's last surviving direct male descendant donated his laboratory notebooks to the Bibliotheque Nationale in Paris. Scholars studying these notebooks found that Pasteur often cut corners in his work, sometimes did not describe exactly how experiments were done, and did not always publicly report results transparently. This straddling of ethical boundaries or, worse, fraud is severely punished by the modern scientific community. Indeed, as it should be, because the scientific edifice is built on the trust that scientists have described their studies honestly. Mistakes can happen, of course, but deceit is not allowed.
Pasteur's straddling of ethical boundaries notwithstanding, he made groundbreaking advances that had a transformative effect. Vaccines designed using Pasteur's methods have saved more lives than any other medical procedure. Vaccines that protect children from diseases are a major contributor to the dramatic reduction in childhood mortality. Today, we crave a vaccine against the ongoing COVID-19 pandemic, and hopefully, we will have one soon. Pasteur's work is the foundation for this hope.
For his achievements, Pasteur received many honors and awards. Many streets around the world are named after him, and the Pasteur Institute in Paris is a famed medical research laboratory that Pasteur himself founded. He died in 1895, when he was 72, and his body is interred in the first floor of the original building of the Pasteur Institute. Visitors are welcome to see his tomb and the apartment where Pasteur lived at the end of his life. Pasteur did not receive a Nobel Prize because the first of these was awarded in 1901.
According to this research, eight percent of Americans always refuse vaccines. Why?
- New research found that 22 percent of Americans identify as somewhat or fully resistant to vaccination.
- Researchers used two social psychology theories to explore the causes of vaccine resistance.
- The more one identifies with an anti-vaccine group, the harder it is to dissuade them from their ideas.
Vaccine hesitancy is top of mind for global public health officials, and the reasons for this resistance are manifold. A group of American researchers recently focused on social identity as a motivating factor. Their study, published in the journal Politics, Groups, and Identities, found that group identification was an important factor for just over one-fifth of citizens.
Anti-vaxx social identification (AVSID) includes 22 percent of Americans — 14 percent of whom identify as "sometimes" resistant, while eight percent claim to "always" refuse vaccines. While on its face this appears to be a medical decision, the research team, led by Oklahoma State University political scientist Matt Motta, sought to discover the relevance of group acceptance.
Social psychology really matters
Previous research has found that anti-vaxxers conform to in-group norms by expressing skepticism against anyone that questions their autonomy and rejecting broader public health recommendations by out-group experts. Such resistance, they write, may result from identity protective cognition, that is, the avoidance of anything that challenges deeply held beliefs.
For this study, the team relied on the following two psychological theories:
- Social identity theory (SIT). Coined by social psychologists Henri Tajfel and John Turner, this theory predicts in-group behavior is due to perceived status differences as well as the legitimacy and stability of such differences. SIT predominantly focuses on the psychological motivations for group membership and attachment.
- Self-categorization theory (SCT). This social psychology theory is focused on the cognitive motivations for defining group membership. Also developed by John Turner, SCT investigates the consequences of perceiving people in group terms.
SIT argues that categorization can lead to identification depending on how personally each individual takes the content matter. In this case, when vaccine resistance provides self-esteem and personal meaning, then heightened group identification will merge with their identity. SCT steps in to cement the individual relationship to the content (vaccine resistance) and provides context for the group to flourish.
"Upon socially identifying with a group, people come to understand group membership in comparison to those not in the group, or to those in opposing groups. People then tend to favor members of the in-group and imbue positive characteristics onto them, whereas members of the out-group are viewed with suspicion and oftentimes are seen negatively."Rally goers protest vaccines and the current administration during the "World Wide Rally for Freedom", an anti-mask and anti-vaccine rally, at the State House in Concord, New Hampshire, May 15, 2021.
Rally goers protest vaccines and the current administration during the "World Wide Rally for Freedom", an anti-mask and anti-vaccine rally, at the State House in Concord, New Hampshire, May 15, 2021. Photo by Joseph Prezioso / AFP via Getty Images
Following the herd, but not the immune kind
This mindset has profound social implications. While the U.S. has a goal to vaccinate 70 percent of American adults by July 4, public health officials are still concerned that another wave of COVID-19 will hit this summer due to millions of Americans refusing the jab.
While social psychology theories cannot explain all 22 percent of vaccine-hesitant individuals, the researchers are confident that they provide meaning for at least part of that population. People in this group often refuse to have their children vaccinated and also are more likely to express interest in "intuitive" thinking around health and medicine rather than accept empirical data offered by professionals.
Surveying over 5,000 Americans, the team discovered that full-blown anti-vaxxers (8 percent) were more likely to identify as a group than vaccine-hesitant respondents (14 percent). They also found that such respondents were more likely to engage in conspiratorial thinking. They write:
"People who embrace folk theories about medicine — i.e., inter-generationally transmitted beliefs about medicine that are widely held, but factually inaccurate — have been shown to be more likely to think about the world in conspiratorial ways, and less knowledgeable about basic scientific facts."
The power of tribalism
The team notes that this is more than a barrier to herd immunity. Individuals that score high on the AVSID scale are more likely to share misinformation about vaccines and disrupt important public health communications. The challenge of combating such trends, they note, is especially difficult when anti-vaxx identity is bound to the group.
Reaching the 14 percent of vaccine-hesitant individuals will prove easier than trying to convince the 8 percent of anti-vaxxers. As long as their identity is tied with the group, changing their minds will be nearly impossible.
Stay in touch with Derek on Twitter. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Many workers moved home on the promise or hope that they'd be able to keep working remotely at least some of the time after the pandemic ended.
A good example of this is a recent op-ed written by the CEO of a Washington, D.C., magazine that suggested workers could lose benefits like health care if they insist on continuing to work remotely as the COVID-19 pandemic recedes. The staff reacted by refusing to publish for a day.
While the CEO later apologized, she isn't alone in appearing to bungle the transition back to the office after over a year in which tens of millions of employees were forced to work from home. A recent survey of full-time corporate or government employees found that two-thirds say their employers either have not communicated a post-pandemic office strategy or have only vaguely done so.
As workforce scholars, we are interested in teasing out how workers are dealing with this situation. Our recent research found that this failure to communicate clearly is hurting morale, culture and retention.
We first began investigating workers' pandemic experiences in July 2020 as shelter-in-place orders shuttered offices and remote work was widespread. At the time, we wanted to know how workers were using their newfound freedom to potentially work virtually from anywhere.
We analyzed a dataset that a business and technology newsletter attained from surveying its 585,000 active readers. It asked them whether they planned to relocate during the next six months and to share their story about why and where from and to.
After a review, we had just under 3,000 responses, including 1,361 people who were planning to relocate or had recently done so. We systematically coded these responses to understand their motives and, based on distances moved, the degree of ongoing remote-work policy they would likely need.
We found that a segment of these employees would require a full remote-work arrangement based on the distance moved from their office, and another portion would face a longer commute. Woven throughout this was the explicit or implicit expectation of some degree of ongoing remote work among many of the workers who moved during the pandemic.
In other words, many of these workers were moving on the assumption – or promise – that they'd be able to keep working remotely at least some of the time after the pandemic ended. Or they seemed willing to quit if their employer didn't oblige.
One of authors explains the research.
We wanted to see how these expectations were being met as the pandemic started to wind down in March 2021. So we searched online communities in Reddit to see what workers were saying. One forum proved particularly useful. A member asked, “Has your employer made remote work permanent yet or is it still in the air?" and went on to share his own experience. This post generated 101 responses with a good amount of detail on what their respective individual companies were doing.
While this qualitative data is only a small sample that is not necessarily representative of the U.S. population at large, these posts allowed us to delve into a richer understanding of how workers feel, which a simple stat can't provide.
We found a disconnect between workers and management that starts with but goes beyond the issue of the remote-work policy itself. Broadly speaking, we found three recurring themes in these anonymous posts.
1. Broken remote-work promises
Others have also found that people are taking advantage of pandemic-related remote work to relocate to a city at a distance large enough that it would require partial or full-time remote work after people return to the office.
A recent survey by consulting firm PwC found that almost a quarter of workers were considering or planning to move more than 50 miles from one of their employer's main offices. The survey also found 12% have already made such a move during the pandemic without getting a new job.
Our early findings suggested some workers would quit their current job rather than give up their new location if required by their employer, and we saw this actually start to occur in March.
One worker planned a move from Phoenix to Tulsa with her fiancé to get a bigger place with cheaper rent after her company went remote. She later had to leave her job for the move, even though “they told me they would allow me to work from home, then said never mind about it."
Another worker indicated the promise to work remotely was only implicit, but he still had his hopes up when leaders “gassed us up for months saying we'd likely be able to keep working from home and come in occasionally" and then changed their minds and demanded employees return to the office once vaccinated.
2. Confused remote-work policies
Another constant refrain we read in the worker comments was disappointment in their company's remote-work policy – or lack thereof.
Whether workers said they were staying remote for now, returning to the office or still unsure, we found that nearly a quarter of the people in our sample said their leaders were not giving them meaningful explanations of what was driving the policy. Even worse, the explanations sometimes felt confusing or insulting.
One worker complained that the manager “wanted butts in seats because we couldn't be trusted to [work from home] even though we'd been doing it since last March," adding: “I'm giving my notice on Monday."
Another, whose company issued a two-week timeline for all to return to the office, griped: “Our leadership felt people weren't as productive at home. While as a company we've hit most of our goals for the year. … Makes no sense."
After a long period of office shutterings, it stands to reason workers would need time to readjust to office life, a point expressed in recent survey results. Employers that quickly flip the switch in calling workers back and do so with poor clarifying rationale risk appearing tone-deaf.
It suggests a lack of trust in productivity at a time when many workers report putting in more effort than ever and being strained by the increased digital intensity of their job – that is, the growing number of online meetings and chats.
And even when companies said they wouldn't require a return to the office, workers still faulted them for their motives, which many employees described as financially motivated.
“We are going hybrid," one worker wrote. “I personally don't think the company is doing it for us. … I think they realized how efficient and how much money they are saving."
Only a small minority of workers in our sample said their company asked for input on what employees actually want from a future remote work policy. Given that leaders are rightly concerned about company culture, we believe they are missing a key opportunity to engage with workers on the issue and show their policy rationales aren't only about dollars and cents.
3. Corporate culture 'BS'
A company's culture is essentially its values and beliefs shared among its members. That's harder to foster when everyone is working remotely.
That's likely why corporate human resource executives rank maintaining organizational culture as their top workforce priority for 2021.
But many of the forum posts we reviewed suggested that employer efforts to do that during the pandemic by orchestrating team outings and other get-togethers were actually pushing workers away, and that this type of “culture building" was not welcome.
One worker's company “had everyone come into the office for an outdoor luncheon a week ago," according to a post, adding: “Idiots."
Surveys have found that what workers want most from management, on the issue of corporate culture, are more remote-work resources, updated policies on flexibility and more communication from leadership.
As another worker put it, “I can tell you, most people really don't give 2 flips about 'company culture' and think it's BS."
Kimberly Merriman, Professor of Management, Manning School of Business, University of Massachusetts Lowell; David Greenway, Doctoral Candidate in Leadership/Organization Studies, University of Massachusetts Lowell, and Tamara Montag-Smit, Assistant Professor of Business, University of Massachusetts Lowell
Virtual tourism has thus far been a futuristic dream, but a world shaped by Covid-19 may be ready to accept it.
- The COVID-19 pandemic has upended the travel and tourism industries;
- Businesses in this sector must build infrastructure and practices that allow people to travel safely in a post-pandemic world and support local communities that benefit from tourism;
- Augmented, virtual and mixed reality technologies can offer alternative ways to travel the world and an exciting new model for the industry.
The tourism industry has hit a nadir owing to the COVID-19 pandemic. It will continue to feel the effects for at least the first three quarters of 2021 – according to a recent UN report, tourist arrivals globally in January 2021 were down 87% when compared to January 2020.
Travel will prevail over post-pandemic anxiety, making it incumbent on the aviation and tourism industry to build safer infrastructure and practices that take care of travellers' well being.
After a year thwarted by the pandemic and with the future not looking too upbeat for the industry at this juncture, tourism business owners should look at alternative modes of interaction for holidaymakers that can also aid the people and economies who depend on tourism.
The COVID-19 pandemic has noticeably hastened the testing and rollout of forward-looking technologies. Technology has not only enabled citizens globally to interact with loved ones, but also helped industries such as healthcare, information technology, education and many more to work remotely.
In the last few decades, technology has helped travel and tourism industries increase their reach through travel booking websites, videos, blogs and travel photography. Digital tools and content are a vital source of information for vacationists organizing their next holiday or creating a destination wish list. Whilst remote or virtual tourism has been a futuristic theme within industry forums for some time, the world today, shaped by the COVID-19 pandemic, might now be ready to accept it.
A human-centric design that draws insights from cognitive behaviour, social psychology, neuroscience and behavioural economics applied with cutting edge technologies such as augmented, virtual or mixed reality (AR, VR, MR) could be a game-changer. AR, VR and MR can enable a seamless, uninterrupted interactive experience for viewers from their own private space. The design principles will create a frictionless digital user experience and construct a positive perception of a tourist destination.
There have been previous attempts to achieve this feat: if you are an aqua sightseer, you might be aware of a documentary exploring the Great Barrier Reef. Through an interactive website, one can view the clear, tranquil currents of the Pacific Ocean and the biodiversity of the reef, and experience the sounds of a healthy coral reef. Another much-discussed VR experience is Mission 828 which allows you to take a virtual parachute jump from the world's tallest building, Burj Khalifa in Dubai. The Official Tourist Board of the Faroe Islands has also crafted a virtual experience to entice post-pandemic visitors from across the world.
Imagine a human-centric designed, interactive space online that makes a destination accessible and so real for a sightseer with sound captured by electro-acoustics researchers. You could view holiday sites in a video or through self-navigation using voice or joystick controls, interact with people using video-calling platforms, travel through the streets of said location, eavesdrop on local music and much more. This could be stitched together in a single platform individually or in silos on the internet and further enhanced by setting up physical experience tourism centres locally. Such a setup would allow tourist guides, artisans, craftspeople, hoteliers and transport business to create their own digital and virtual offerings and interact with possible customers.
Here's how it might look: a vacationer starts their experience from the time their flight commences. The plane descends to the destination runway and pictures of the vicinity from the aircraft window pane are captured. The airport signage welcomes passengers and directs them to a pre-booked taxi. The vacationer gets to choose their first destination and travels through the streets in a chauffeur-driven car whose interactions en route become part of their cherished memories. On arrival, a tourist guide walks you through the destination all controlled with just a tap on your gadget. During the sightseeing, you hear random people speaking, posing for photographs and more. You take a photo to post on social media, go shopping and negotiate with a local vendor to purchase an artwork and get it delivered to your door. You learn how a local dish is prepared and get familiar with local customs.
A virtual platform could even provide an opportunity for people to explore areas that are affected by or fighting terrorism. For example, imagine seeing the diverse wildlife and snow leopard of the Gurez Valley, in the union territory of Jammu and Kashmir, India. It doesn't stop there: if thought through, one could experience travelling to the South Pole, space and beyond. It could also serve as a learning portal for students to understand geographies, culture, art and history.
With technology improving lives globally, virtual tourism could reignite the tourism industry and its people and help build a more sustainable economic model. As a human-centric platform, it can establish local tourist guides, artisans and others as global citizens in the tourism industry.
Contact-tracing apps can be a useful tool for public health, but they have considerable false positive and false negative rates.
- The COVID-19 pandemic witnessed the widespread adoption of contact-tracing apps.
- Research shows that these apps aren't as accurate as we might think.
- There are several physical and biological factors than can interfere with the accuracy of contact-tracing apps.
The following is an excerpt adapted from People Count: Contact-Tracing Apps and Public Health.
To stop an epidemic, public health authorities focus on lowering R0. Even for a given illness, this number varies tremendously according to the protective measures a society takes (wearing masks, practicing social distancing, and other measures). In early March 2020, COVID-19's R0 was just below 4 in New York State. Once the state instituted a shelter-in-place order and virtually no one was on the streets, R0 dropped below 1. It continued to hover quite close to 1 for the summer and into the fall, even after the state came back to life and began to open bars and restaurants.
By helping to keep spread in check, could contact-tracing apps have lowered R0 enough to allow people to safely work, participate in social life, and be with their families? Lacking a real-life human experiment to answer this question, epidemiologists turn to models; these are in turn based on existing data. In the case of COVID-19, some of the best data comes from a citizen-science app developed by the BBC to accompany its 2018 documentary on the Spanish flu, Contagion! The BBC4 Pandemic. Participants agreed to provide a twenty-four-hour snapshot of their locations and self-reported contacts, which epidemiologists then used to model how a similar epidemic would spread in twenty-first-century Britain.
The BBC database ultimately included the locations and contacts of 36,000 people. It showed their movements over the course of a day, including how many people they saw at work, at school, and elsewhere. The data allowed researchers to develop a model that could simulate various interventions at the population level, from isolation, testing, contact tracing, and social distancing to app usage.
The resulting model showed that if 90 percent of ill people self-isolated and their household quarantined upon learning of their infection, 35 percent of cases would have already spread the disease to another person. If 90 percent of the contacts of those infected also isolated upon learning of the previous person's infection, only 26 percent of cases would have infected someone else. The contact tracers, in other words, bought time. By having potentially infected people isolate, contact tracing prevented new rounds of infections. In another iteration, the researchers added apps to the mix and assumed that 53 percent of the population would use them. By notifying people of potential infections faster than a contact tracer could, the apps lowered the infection rate further, so that only 23 percent of cases infected another person. At that high adoption rate, the disease doesn't disappear, but it also doesn't cause a pandemic.
Models, of course, are only as good as the assumptions on which they're based. The idea that 53 percent of any given population would voluntarily use a contact-tracing app and that anyone receiving an exposure notification would isolate is doubtful, at best. Still, because the apps appear to help lower R0, governments and public health officials have jumped to add them to the mix of public health tools available to combat COVID-19's spread.
Signal strength varied depending on whether a person carried their phone in their back pocket, their front pocket, or in a backpack or handbag. The signal strength varied by device model, by the shape of the room, even by the construction materials.
Given the high stakes involved, we need to look at how apps are deployed in real life. How well do apps actually work? Are they more effective than more traditional, and less invasive, public health tools? Can they usefully supplement manual contact-tracing efforts? COVID-19 has hit low-income and Black, Latinx, and indigenous communities particularly hard. The possibility of public health organizations embracing contact-tracing apps as a line of defense against epidemics raises new questions about equity and the balance of individual privacy and public safety. Will contact-tracing apps exacerbate inequities already present in society?
A robust public debate about the implications of deploying what is effectively a public surveillance system didn't occur; instead, many officials deployed these apps essentially overnight. We need that debate, but first we must look at efficacy. If the apps aren't efficacious, then there is no reason to consider them further.
The many problems with contact-tracing apps
Following advice from the WHO, most public health agencies have promoted the idea that "social distancing" is the safest way to guard against exposure to the coronavirus. For the CDC, the magic number is six feet (in metric-based nations, it's usually two meters). Stay at least that far away from other people, so the theory goes, and you're safe. Since the BLE [Bluetooth Low Energy] technology on which contact-tracing apps run depends on proximity, engineers hoped that phone-to-phone contacts could serve as a reasonable proxy for risky exposures. In practice, this has turned out to be not entirely straightforward.
In theory, the strength of the BLE signal that a phone receives from another indicates the distance of the device emitting it. To test the accuracy of this assumption, researchers at Germany's Fraunhofer-Gesellschaft simulated the experiences of people sitting on a train, waiting on line, being served by a waiter in a restaurant, and attending a cocktail party. Over 139 tests, the phones correctly determined time and distance exposure 70 percent of the time. This information seems encouraging, but the simulation took place in a test facility that lacked walls. The "train car" had no metal sides, the people waiting on line encountered no checkout counters or supermarket shelves, and neither the restaurant nor the cocktail party included walls or serving stations. This matters because radio waves often reflect off surfaces.
When researchers from the University of Dublin tried these tests in actual train cars, they obtained different results. Seven volunteers with phones running GAEN [(Google/Apple) Exposure Notification]-based apps distributed themselves around a train car and measured the signals their phones received over a fifteen-minute period. Radio waves are supposed to vary inversely according to the square of distance, so the researchers were surprised to find that the signals stayed constant at a distance of 1.5–2.5 meters and began to increase after that. Apparently, a flexible metal joint between train carriages concentrated the signal.
As they looked more closely at the results, the researchers found more surprises. Signal strength varied depending on whether a person carried their phone in their back pocket, their front pocket, or in a backpack or handbag. The signal strength varied by device model, by the shape of the room, even by the construction materials. Depending on the construction material, BLE signals can indicate that people are near each other when they are actually in neighboring apartments.
Epidemiologists understand that the six-foot measure is somewhat arbitrary; engineers know that BLE signals don't measure distances precisely. If the rest of us come to use these systems, we also need to understand their limitations.
Apps don't account for real-life circumstances
Credit: Jeff J Mitchell via Getty Images
Measurement imprecision isn't the only problem for contact-tracing and exposure-notification apps. The apps are not built to record the real-life circumstances that affect the likelihood of transmission in any given case. If Alyssa is six feet away from Ben in a small room for fifteen minutes, there's likely risk of exposure. But if Alyssa is four feet from Ben, outside, and wearing a mask, she's likely to be safe. Large gatherings of people indoors carry risks of spread, while similarly sized groups of masked people outdoors are less dangerous. Apps can't distinguish between these situations. Nor do apps know if the person standing eight feet away from you is belting out a song — dangerous if they're infected — or just standing quietly.
The apps are also ignorant of a room's ventilation, an important factor in how the virus spreads. When an infected person breathes — or speaks, sings, coughs, or sneezes — they emit viral particles packaged in a mixture of mucus, saliva, and water. The smallest of these, aerosols, evaporate as they travel, losing some of their potency. The bigger ones, droplets, typically fall to the ground within three feet. Sometimes, though, air flow, particularly air conditioning, can push these along, putting people at further distances at risk of infection. This is apparently what happened in a restaurant in Guangzhou, China, when two people sitting well beyond the six-foot measure — and on different sides of the ill person — were infected. One was at a table more than a dozen feet away.
Biology also confuses apps. A review of published reports indicates that as many as 30–40 percent of people never show symptoms. While these studies are not based on random samples, a single study based on a large random sample of Icelanders showed a similar result: a startling 43 percent of participants tested positive without showing symptoms. Even if one assumes that only 30 percent of cases are asymptomatic — a not unreasonable assumption — then epidemiologists believe that 7 percent of transmission will arise from asymptomatic cases. This matters for the apps' effectiveness. Asymptomatic people are less likely to get tested than those who are sick — and if there's no test, there's no trigger for exposure notifications.
Contact-tracing and exposure-notification apps nevertheless do have value. They pick up cases that people, including contact tracers, wouldn't. Aliyah might not remember a chance hallway encounter with Bobby, but her app will. And the app will be ready to notify Aliyah if Bobby's phone reports a positive COVID-19 test. Perhaps even more critically, Aliyah's app will register encounters with nearby strangers in the bar or theater lobby — as long as they are also using the app. If those strangers later test positive, Aliyah will learn she's been exposed. Without a phone app, she'd have little chance of discovering this.
False positives and false negatives
These technical and practical limitations of contact-tracing apps mean that they can produce both false positives and false negatives. (Note that these are false positives and false negatives of exposure, not false positive and false negatives of having COVID-19.) Virginia's website for the state's GAEN-based app, for example, warns that students in adjacent dorm rooms might receive exposure notifications of close contact while being in different rooms. When tested in August 2020, the UK exposure-notification app had a 45 percent false positive rate and 31 percent false negative rate.
These numbers sound bad, but the false positives aren't entirely "false" — most of them represented exposures at 2.5–4 meters away rather than 2 meters. Depending on the circumstances, a person might well have been exposed at 3 meters. In the case of false negatives, however, users received no notification whatsoever that they had been in the presence of someone infected with COVID-19.
The apps are not built to record the real-life circumstances that affect the likelihood of transmission in any given case.
Both types of inaccuracies present challenges for users and public health agencies — some more obvious than others. If Aliyah receives a false positive notification, she might quarantine unnecessarily, losing a paycheck. If she's following the rules, she should also urge her roommates and family members she's in close contact with to do so, causing more disruption. Alternatively, if this is the second time that the app warns Aliyah that she's been exposed without her developing any symptoms, she might just ignore the notification and disable the app.
False negatives place the public's health at risk. If Bobby was asymptomatic and never tested, Aliyah will not receive a notification even though she may have spent fifty minutes sitting six feet away from Bobby in a classroom. False negatives can also be produced by circumstance: from an air conditioner dispersing aerosols farther than expected or an infected singer who propels droplets farther than six feet.
Some communities are at higher risk for false positives than others. Many low-income people, for instance, hold jobs that bring them in constant contact with a stream of strangers (e.g., grocery store clerks, health care workers, workers in food service and production). For these workers, a small variation in the proximity measurement (say, nine feet instead of six) can multiply into a high risk of false positives from contact-tracing apps. What's more, many of these workers routinely wear protective gear or work behind barriers that reduce their risk from even four-foot interactions. Similarly, people who live in high-density housing situations, whether multifamily housing units or apartment complexes, are more likely to receive false positives than people who live in stand-alone suburban or rural houses.
Hourly workers living paycheck to paycheck can't afford to take time off unless it's absolutely necessary. A false positive keeps them from clocking in. Alyssa, in Singapore, or Amelie, in Switzerland, can each expect to receive financial support from the government if they isolate after an exposure notification. But in the United States, few low-income or gig workers receive paid time off, even for isolating during a pandemic. The privilege of staying at home is not evenly distributed. Workers who realize that the apps consistently generate false positives are less likely to use them voluntarily — or to heed them when they provide alerts.
False negatives, too, have a differential impact. White-collar workers who already work from home and who drive their own vehicles on necessary errands have fewer contacts than those who take public transportation to jobs that have been deemed "essential." The fewer contacts each of us has with other people, the less chance we have of spreading COVID-19. A false negative of exposure for someone who works outside the home and uses public transit carries greater risk of infecting others than the same false negative for someone who works at home and uses their own transportation.
Contact-tracing apps were supposed to resolve this problem, allowing people to emerge from lockdowns with the ability to interact with friends, family, and strangers. It's not clear that they will.
Adapted excerpt from People Count: Contact-Tracing Apps and Public Health by Susan Landau. Reprinted with Permission from The MIT PRESS. Copyright 2021.