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Plant-based vaccines can change the vaccine landscape
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
Credit: THOMAS LOHNES via Getty Images
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.
Credit: Albert Edelfelt via Wikipedia / Public domain
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.
How a rubber hand could treat OCD
A well-known psychology trick called the "rubber hand illusion" could be useful for treating patients with obsessive-compulsive disorder.
- It is easy to trick your brain into believing that a rubber hand belongs to your body.
- OCD is a crippling condition afflicting 1 in 50 people.
- The "rubber hand illusion" could offer a novel strategy to treat this condition.
I feel anchored "here and now" in my body. But this sense of embodiment which we take for granted is an illusion created by the brain. In fact, in just five minutes, I can make you feel like a rubber hand is yours!
I simply ask you to place both your hands flat on a table in between a piece of cardboard serving as a "little wall." You can't see your real right hand. And left to the "cardboard screen" you see a rubber hand, which looks like your own. Now, when you look down on the table you see two hands in front of you. But only one is yours — that is, the left one. Sitting across from you, I stroke the fake hand and the hidden right hand in perfect synchrony with a paintbrush. Astonishingly, after just a few minutes you'll most likely feel touch sensations arising from the rubber hand as if it were yours!
This compelling illusion illustrates the fragility of the sense of self and how your brain creates this feeling based on statistical correlations. It's extremely unlikely for such stroking seen on the rubber hand and felt on the hidden real right hand to occur by random chance. So, your brain concludes, however illogical, that the rubber hand is yours. This famous psychology trick — the "rubber hand illusion" — has been known for decades, but no one had examined how it could be used to treat obsessive-compulsive disorder (OCD) until my colleagues and I hit upon a novel technique: "multisensory stimulation therapy."
Treating OCD with a rubber hand
OCD is a crippling condition afflicting 1 in 50 people. A common type of OCD involves repetitive handwashing sometimes for hours until they bleed. These patients are petrified of trivial things like touching a garbage bin. Unsurprisingly, OCD patients suffer immensely. Yet there are few treatment options for them.
The most widely used "talking therapy" — dubbed "exposure and response prevention" — entails instructing patients to touch things they consider "disgusting" like a toilet seat and not washing their hands afterward. The aim is to make them feel anxious initially but then showing that nothing horrible occurs when they refrain from handwashing. However, a substantial limitation of this therapy is that patients fear touching things they consider contaminated. As many as 25 percent of patients outright refuse this treatment and 20 percent drop out before completion. But what if a rubber hand were to touch the disgusting objects instead — I thought to myself — one that feels like the patient's hand? Then one could create a less fear-provoking yet realistic therapy for OCD.
To show if this could work, V.S. Ramachandran, D. Krishnakumar, and I explored if healthy volunteers (without OCD) would experience disgust if we were to contaminate the fake hand during the aforementioned rubber hand illusion. So, we first induced the illusion, and after a few minutes, we put disgusting things like fake feces on the rubber hand. Curiously, participants experienced disgust, as if the sensation was emanating from the fake hand. In other words, when they felt like the fake hand was theirs, they were grossed out by what it was touching. These findings were later replicated in a large study from Japan, suggesting that these results are reliable even across cultures.
Therefore, my colleagues at Harvard and I (in collaboration with McLean Hospital and V.S. Ramachandran) later tested this trick in OCD patients and found the same result: that is, after stroking the rubber hand for 10 minutes, OCD patients displayed disgust reactions, just as if their real hand had been contaminated.
These results are striking because they show that OCD patients can experience contamination feelings, even from a rubber hand. Such contamination feelings are, as noted above, the basis for treating OCD. Over time, by repeating this rubber hand trick, patients should build up disgust tolerance — just like standard OCD therapy — and this could therefore represent a new way of treating the disorder that keeps so many souls hostage.
OCD is a strange disorder that blurs the boundary between mind and body, reality and illusion. It may just be that one has to trick the brain to tackle OCD, combating one illusion with another.
Dr. Baland S. Jalal is a researcher at Harvard University, Department of Psychology and visiting researcher at Cambridge University, Department of Psychiatry. He obtained his PhD at Cambridge University in the School of Clinical Medicine (Trinity College Cambridge) and was a Fellow at Harvard University (2016, 2018). He is a close collaborator and co-author on ten papers with the renowned neuroscientist V.S. Ramachandran (2011 TIME magazine 100 most influential people in the world).
Hidden philosophy of the Pythagorean theorem
Pythagoras may have believed that the entire cosmos was constructed out of right triangles.
- Ancient Greeks believed that fire, air, water, and earth were the four elements of the universe.
- Plato associated these four elements with 3D geometrical solids.
- Pythagoras may have believed that the right triangle formed the basis of all reality.
In Plato's dialogue, the Timaeus, we are presented with the theory that the cosmos is constructed out of right triangles.
This proposal Timaeus makes after reminding his audience [49Bff] that earlier theories that posited "water" (proposed by Thales), or "air" (proposed by Anaximenes), or "fire" (proposed by Heraclitus) as the original stuff from which the whole cosmos was created ran into an objection: if our world is full of these divergent appearances, how could we identify any one of these candidates as the basic stuff? For if there is fire at the stove, liquid in my cup, breathable invisible air, and temples made of hard stone — and they are all basically only one fundamental stuff — how are we to decide among them which is most basic?
A cosmos of geometry
However, if the basic underlying unity out of which the cosmos is made turns out to be right triangles, then proposing this underlying structure — i.e., the structure of fire, earth, air, and water — might overcome that objection. Here is what Timaeus proposes:
"In the first place, then, it is of course obvious to anyone, that fire, earth, water, and air are bodies; and all bodies have volume. Volume, moreover, must be bounded by surface, and every surface that is rectilinear is composed of triangles. Now all triangles are derived from two [i.e., scalene and isosceles], each having one right angle and the other angles acute… This we assume as the first beginning of fire and the other bodies, following the account that combines likelihood with necessity…" [Plato. Timaeus 53Cff]
A little later in that dialogue, Timaeus proposes further that from the right triangles, scalene and isosceles, the elements are built — we might call them molecules. If we place on a flat surface equilateral triangles, equilateral rectangles (i.e., squares), equilateral pentagons, and so on, and then determine which combinations "fold-up," Plato shows us the discovery of the five regular solids — sometimes called the Platonic solids.
Three, four, and five equilateral triangles will fold up, and so will three squares and three pentagons.
If the combination of figures around a point sum to four right angles or more, they will not fold up. For the time being, I will leave off the dodecahedron (or combination of three pentagons that makes the "whole" into which the elements fit) to focus on the four elements: tetrahedron (fire), octahedron (air), icosahedron (water), and hexahedron (earth).
Everything is a right triangle
Now, to elaborate on the argument [53C], I propose to show using diagrams how the right triangle is the fundamental geometrical figure.
All figures can be dissected into triangles. (This is known to contemporary mathematicians as tessellation, or tiling, with triangles.)
Inside every species of triangle — equilateral, isosceles, scalene — there are two right triangles. We can see this by dropping a perpendicular from the vertex to the opposite side.
Inside every right triangle — if you divide from the right angle — we discover two similar right triangles, ad infinitum. Triangles are similar when they are the same shape but different size.
And thus, we arrive at Timaeus' proposal that the right triangle is the fundamental geometrical figure, in its two species, scalene and isosceles, that contain within themselves an endless dissection into similar right triangles.
Now, no one can propose that the cosmos is made out of right triangles without a proof — a compelling line of reasoning — to show that the right triangle is the fundamental geometrical figure. Timaeus comes from Locri, southern Italy, a region where Pythagoras emigrated and Empedocles and Alcmaon lived. The Pythagoreans are a likely source of inspiration in this passage but not the other two. What proof known at this time showed that it was the right triangle? Could it have been the Pythagorean theorem?
Pythagorean theorem goes beyond squares
We now know that there are more than 400 different proofs of the famous theorem. Does one of them show that the right triangle is the basic geometrical figure? Be sure, it could not be a² + b² = c² because this is algebra, and the Greeks did not have algebra! A more promising source — the proof by similar right triangles — is the proof preserved at VI.31.
Notice that there are no figures at all on the sides of the right triangle. (In the above figure, the right angle is at "A.") What the diagram shows is that inside every right triangle are two similar right triangles, forever divided.
Today, the Pythagorean theorem is taught using squares.
But, the Pythagorean theorem has nothing to do with squares! Squares are only a special case. The theorem holds for all figures similar in shape and proportionately drawn.
So, why the emphasis on squares? Because in the ancient Greek world proportional-scaling was hard to produce exactly and hard to confirm, and the confirmation had to come empirically. But squares eliminate the question of proportional scaling.
Pythagoras and the philosophy of cosmology
We have an ancient report that upon his proof, Pythagoras made a great ritual sacrifice, perhaps one hundred oxen. What precisely was his discovery that merited such an enormous gesture?
Could this review help us to begin to understand the metaphysical meaning of the hypotenuse theorem — namely, that what was being celebrated was not merely the proof that the area of the square on the hypotenuse of a right triangle was equal to the sum of the areas of the squares on the other two sides, but moreover, was the proof that the fundamental figure out of which the whole cosmos was constructed was the right triangle?
Prof. Robert Hahn has broad interests in the history of ancient and modern astronomy and physics, ancient technologies, the contributions of ancient Egypt and monumental architecture to early Greek philosophy and cosmology, and ancient mathematics and geometry of Egypt and Greece. Every year, he gives "Ancient Legacies" traveling seminars to Greece, Turkey, and Egypt. His latest book is The Metaphysics of the Pythagorean Theorem.
Tiny genetic differences add up to big behavioral effects
Many thousands of different genetic variants are responsible for complex behavior.
- Genome-wide association studies (GWAS) allow us to correlate genetic differences with behavioral traits.
- There is no single gene that explains behavior; rather, behavior arises from the complex interaction of many different genes, each of which only plays a small role.
- Society must be cautious as we learn more about behavioral genetics.
Life flourishes with diversity, as diversity gives nature something to choose from, providing flexibility to adapt to change. Variation between humans seems endless, both in appearance and in behavior. Variation between humans is largely due to our flexible nature that allows us to adapt to a wide variety of potential life trajectories, and partly due to set dimensions of variation in our biological make-up carefully molded by the hands of time.
Genome-wide association studies
Four billion years of natural selection crafted the refined machinery we all share — encoded in most of our DNA — as well as carefully selected room for variation — encoded in a minority of DNA differences. If the 3.2 billion nucleotides in our DNA would fit into a 300-page book, the differences between two random people would barely add up to two pages. Many decades of research in twins and family members suggest that considerable portions of differences in human behavior are associated with some of the tiny differences within those two pages.
If the 3.2 billion nucleotides in our DNA would fit into a 300-page book, the differences between two random people would barely add up to two pages.
It is hard to uncover the evolutionary stories behind these differences, but it would probably help to first find out how these genetic differences exactly give rise to the diversity in our behavioral repertoire. Recent advances in genetics research allow us to link specific DNA nucleotides on those two pages to complex behavioral outcomes. Studies that link genetic variation on a molecular level with complex traits are called genome-wide association studies (GWAS). In a GWAS, millions of single DNA nucleotides are tested one by one in order to quantify their relationship with the most complex of human traits, including behavior.
Professor Karin Verweij and I recently published an article in Nature Human Behavior, in which we review what we have learned so far from GWAS on human behavior and what steps we need to take to learn more. Here, I will summarize some highlights from our article and reflect on their societal relevance.
Many genes with tiny effects
Credit: Mario Tama via Getty Images
In the last decade or so, we have been able to link thousands of genetic variants to human behavioral traits, including personality, education, cognition, sexuality, and mental health. The effects of these genetic variants on behavior are, individually, very weak. Twin and family studies have estimated that, on average, about half of the individual differences in behavioral outcomes are due to genetic differences, which would mean that tens of thousands of genetic variants would be needed to account for these heritability estimates.
The tiny effects of individual genetic variants are hard to estimate, unless unusually large groups are studied. In a typical GWAS, we study millions of DNA variants from hundreds of thousands of individuals. The sum of these small effects can be used to predict people's genetic risk for all kinds of outcomes. The predictive power of DNA is increasing as our studies grow, but we still understand very little about the nature of these predictions.
There are probably no genes that directly influence complex behavioral outcomes. Instead, the many small genetic effects travel through many cascades of mostly unknown biological processes that react to and influence the physical and social environments that people live in.
Before we let DNA prediction reach the clinic or other uses with unpredictable ramifications, such as embryo selection or mate selection, it is important that we first invest in better understanding the nature of the relationship between genetic differences and behavioral outcomes.
Everything is connected
The physical machinery that carries our emergent minds and behaviors consists of many intricate and interconnected systems. Modifying one part will affect multiple other outcomes. This is visible at the level of genes: genetic effects are often shared between different behavioral outcomes in a systematic way. Genes that increase the chances of getting addicted to alcohol tend to increase the risk of feeling lonely. Genes that increase the risk for autism increase the chances of a higher IQ. Genes that increase the risk for anorexia increase the chances of getting a higher education.
These shared genetic effects are widespread among behavioral outcomes. The genetic effects we estimate reflect a patchwork of multiple underlying behavioral outcomes. While many are eager to use these genetic effects to dive into the biology of behavior, we argue that we first need to put more effort into dissecting these genetic effects into their subcomponents.
For educational attainment, for example, we recently split up the part of the genetic effects associated with IQ, which makes up 43 percent of genetic effects on educational attainment, and a "non-IQ" part, making up the remaining 57 percent. We are not sure yet what that remaining 57 percent exactly entails, but we do see that those genes increase the risk for schizophrenia and bipolar disorder. This could be because people with a higher genetic risk for schizophrenia or bipolar disorder tend to be more creative and more open to new experiences.
These shared genetic effects teach us a lot about the genetic architecture of human behavior and also make us realize that it is difficult to select for one trait without also influencing many others. This is a strong argument against using DNA prediction to influence your offspring's DNA through embryo selection, a service that, unfortunately, some companies have already started to offer.
Behavioral genetics is controversial
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The highest portion of shared genetic effects was observed between educational attainment and income. These associations have been reported in separate publications, and the genetic effect on each is roughly the same. Both publications received much attention in the media and on social media. While for educational attainment, the reactions were mostly positive, the publication on genetic effects on income was met mostly with criticism.
These opposite reactions to the same genetic signal might have to do with income being more closely associated in people's minds with social inequalities. Trying to explain social inequalities in terms of something that people are born with may instill the fear that science is being misused to justify the position of marginalized groups. Instead, these molecular genetic effects are helping to elucidate an inherent unfairness in the way we organize our societies.
A closer look at these genetic effects shows that they contain substantial amounts of environmental influences. Our initial studies had trouble separating the two because they are highly correlated. When your genes predispose you to a higher education, that means that your parents also carry those genes and are thus more likely to also have a higher education, giving them better resources (money) to nurture you with a better environment. If you are born with genes that make it easier for you to learn, it will also increase the chances that you will move to a richer neighborhood with healthier living circumstances. These "double advantages" and "double disadvantages" make us mistake the impact of systematic social disadvantages for genetic effects, inflating heritability estimates.
These gene-environment correlations were recently detected studying DNA from people that were exclusively of white European origin. Systematic differences in environmental influences are likely much worse between different ethnic groups, casting more doubts on white supremacists' claims who love to use these inflated heritability estimates to support their genetic explanations for socio-economic group differences.
Conclusions
After two decades of reading out human genomes, we are still only scratching their surface. We are just starting to dissect only a fraction of the total heritability that we are currently able to capture with molecular genetic data. Large parts of humanity are still underrepresented in our measurements, which makes it difficult to make more general claims. We outline in more detail in our Nature Human Behavior paper which steps we need to take in our methods and data collection strategies to better understand the differences in our DNA.
Reference
Abdel Abdellaoui & Karin J.H. Verweij (2021). Dissecting polygenic signals from genome-wide association studies on human behavior. Nature Human Behavior. https://doi.org/10.1038/s41562-021-01110-y
Sleep paralysis: a terrifying encounter with our own mind
Neuroscience explains terrifying ordeals, from out-of-body experiences to alien abductions.
- Sleep paralysis, which 20 percent of people experience at least once, can be terrifying.
- Though it is a neurological phenomenon, our culture and beliefs can make the experience worse.
- One potential treatment is to learn to control the content of our dreams.
Imagine waking up in the middle of pitch darkness, only to realize you are completely paralyzed. You suddenly notice out of nowhere, an aggressive and horrendous human-like cat is on your bed. Next, the worst-case scenario unfolds: The creature viciously attacks you, and you vividly feel its razor-sharp teeth penetrating your flesh. Next morning, you wake up with a bruise on your body.
It sounds like something out of a Stephen King horror novel, but the events describe a real-life case of sleep paralysis, as my colleagues and I recently reported in a study conducted in Italy.
Sleep paralysis is a condition in which a person awakens from sleep but is temporarily paralyzed, unable to move or speak. The phenomenon, in fact, is not uncommon. Around 20 percent of people experience sleep paralysis at least once in their life.
Though the episodes of sleep paralysis are brief, lasting a few seconds to minutes, they are rich with mystery and potential insight into the nature of the human brain. How does sleep paralysis happen, and why does it accompany the strangest hallucinations?
Neurological origins of sleep paralysis
Credit: Albert Anker via Wikipedia / Public domain
Sleep paralysis often occurs when we take a nap during the day, when jet lagged, or in any way, when sleep deprived. It happens when we wake up while still in a stage of sleep, called rapid eye movement sleep (REM), during which most vivid dreams occur. During REM, a part of the front brain called the dorsolateral prefrontal cortex, central to our ability to plan and think logically, turns off. This explains why our dreams during REM seem so real, and why the fabric of reality is so out of control when we dream — with warped landscapes and abruptly changing times, places, and people. (The Hollywood blockbuster Inception brilliantly captures the surreal flavor of dreams.)
I was once able to slide into a lucid dream during my own sleep paralysis. Lucky for me, no terrifying intruders were present.
To prevent us from acting out such intensely "real" dreams during REM and potentially hurting ourselves, our brain has a brilliant solution: it makes our bodies temporarily paralyzed.
REM is also the stage that most resembles wakefulness. Our blood pressure and heartbeat increase, and our breathing quickens. Even brain waves speed up, becoming virtually indistinguishable from wakefulness.
Sometimes, however, we actually do wake up while still in REM sleep. In a sense, we have a "switch" in the brain that tilts us between REM and wakefulness. And all it takes is a few neurochemicals to leave us stuck in this borderline state between parallel "realities" — sleep and wakefulness.
As if being paralyzed and unable to speak when waking up isn't chilling enough, occasionally, the vivid and sometimes threatening dreaming of REM can "spill over" into conscious awakening. This state — in medical jargon referred to as "sleep paralysis accompanied by hypnopompic hallucinations" — can best be described as a dream, or worse yet, a nightmare coming alive before our eyes.
Becoming a ghost
Sleep paralysis can sometimes cause eerie sensations of floating outside one's body or looking down upon oneself from the bedroom ceiling. In certain cultures, such out-of-body experiences are attributed to the "soul" — a type of "astral travel" — where the spiritual self projects itself into an alternative realm of existence.
But out-of-body experiences originate in the brain. In fact, they can reliably be produced in the laboratory. We simply have to disrupt the activity of a brain region called the temporoparietal junction. This region helps us build a "body image" in the parietal lobes (the top-middle part of the brain) or a type of neural representation of the self, based on the inputs it receives from the senses. The temporoparietal junction, which is also critical for our ability to distinguish between "self" and "other," is normally turned off during REM sleep. This is why there is a loosening of the sense of self when we dream: we sometimes see ourselves from a third-person perspective, and other times the self occupies another person's body.
It is thought that similar disturbances in the temporoparietal junction can occur during sleep paralysis. When we realize we are paralyzed, the motor cortex in the brain immediately sends signals to the rest of the body to move and to overcome the paralysis. It also sends additional signals (sort of like "cc'ing" when emailing) to the parietal lobes. Normally, there is feedback from the limbs telling the brain how to build our body image but not during sleep paralysis.
The confusing signals received by the brain can influence how the brain builds our sense of "self," and the result is all kinds of bizarre bodily hallucinations, such as out-of-body experiences or seeing one's limbs or entire body rotate in the air like a tornado or sink deep into the bed as if drowning in quicksand.
Seeing a ghost
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Perhaps more distressing than becoming a ghost is seeing one. Sleep paralysis is arguably most infamous for the sinister shadowy "bedroom-intruder" that sometimes attacks the sleeper. The "creature" is usually lurking in the distant dark, slowly approaching in on its victim.
From here, all kinds of ominous things can happen, as far as the imagination can stretch. Commonly, the intruder chokes and suffocates the person by crushing his chest or pressing on his neck. And occasionally, the creature brutally rapes the paralyzed sleeper. The figure often appears simply as a dark shadow, similar to the human size and shape. But, it can also include detailed features, say, a scary demonic face with animal characteristics, like sharp teeth and cat eyes.
This figure goes by different names around the world. My colleague Devon Hinton of Harvard Medical School and I found that in Egypt, the creature is thought to be a Jinn (an "evil genie") — a spirit-like entity that may hunt down, terrorize, and even kill its victims. In another study, we've discovered that among some Italians, it is believed to be a malevolent witch or a terrifying human-like cat, known locally as the Pandafeche. Some space alien abduction cases also fit the sleep paralysis scenario: the person is laying in his bed paralyzed; suddenly the alien appears and begins to experiment on the sleeper's sexual organs, collecting eggs and semen.
A disturbance in the brain's body map
Credit: John A Beal via Wikipedia and licensed under CC BY 2.5
UC-San Diego neuroscientist VS Ramachandran and I recently proposed a neurological explanation for why we see this shadowy creature during sleep paralysis.
The idea was sparked by research showing that people who are born with a missing arm may experience phantom limbs, meaning that they feel the presence of missing limbs. This led to the idea that there might be a "hardwired" template, or map, of a person's body surface in the right parietal lobe of the brain. So when a person born with no arm is experiencing a phantom arm, he is really feeling the presence of the "arm" that is part of his internal body map. This map would be connected to emotional and visual centers in the brain, causing us to be attracted to body shapes similar to our own. In other words, causing us as humans to be innately attracted to other humans, and not to, say, pigs (at least for most of us!).
More clues about such a hardwired body map come from a rare disorder called apotemnophilia, in which a person has a desire to have a limb amputated and is attracted to people with missing limbs.
Ramachandran and I suggested that a disturbance in the processing of "self" and "other" — at the temporoparietal junction — results in a hallucinated projection of one's own body map; the mind literally casts a shadow, just like the body does. As the barrier between self and other dissolves, the person mistakes his own "shadow" (or body template) for a separate entity.
Compare this to an out-of-body experience: here your sense of self is shifted and you identify with your "ghostly self," not your "bodily self." When you see a "ghost," on the other hand, your vantage point doesn't get shifted, and you identify with your "bodily self," instead of your "ghostly self." And with the "threat detection system" of the brain on high alert (also known as threat hypervigilance), we are even more likely to interpret the human-like shadow as an evil, other entity.
Moreover, our brain regards it as highly improbable that chest pressure, sensations of suffocation, rapid breathing (which are caused by REM physiology), and — on top of everything — seeing a human-like shadow, occur by random chance. When REM dreaming becomes activated as well, the shadowy figure can take on all kinds of sophisticated shapes and dimensions, and the entire plot thickens. At this point, memory and the narrative abilities of other brain regions play a role in the evolving hallucination.
While our neurological explanation for the shadowy figure has yet to be proven, it fits well with previous observations. It has been shown that occasionally when the temporoparietal junction is disrupted using an electric current, instead of having an out-of-body experience, the person senses the presence of a shadowy figure. This figure is perceived to stand behind the person and to mimic his posture; even though the person is aware that the postural features of the shadowy figure are similar to his, he still regards it as a separate person. Based on this, the scientists who conducted the study concluded that they had created a "ghost-like" double.
Fear feeds terrifying sleep paralysis
Credit: Henry Fuseli via Wikipedia / Public domain
In the 1986 Stephen King horror Novel It, the clown-like killer exploits the fears of its victims to hunt down its prey — young children who fear monsters. Although fictional, literature is sometimes closer to science than one would think. Our own research suggests that one's beliefs about sleep paralysis can profoundly shape the experience.
In one study, Devon Hinton and I found that in Denmark, people regard their sleep paralysis as something trivial caused by the brain. In sharp contrast, we found Egyptians often hold very specific cultural and supernatural beliefs about theirs. In another study, we discovered that Egyptians experiencing sleep paralysis not only fear it much more than Danes do — to the extent that many fear dying from it — but they also have longer episodes and on average experience sleep paralysis three times more often.
These findings strongly indicate that for Egyptians, beliefs have radically transformed the experience — a form of mind-body interaction — causing not only psychological fear but also conditioned physiological fear of sleep paralysis. When they go to bed, they fear the "cultural creature" might attack them. Ironically, this will activate fear centers in the brain (such as the amygdala), making them more likely to wake up during REM and have sleep paralysis. And once they have sleep paralysis, they interpret it in light of their cultural beliefs, thinking, "I am being attacked by an evil spirit," making them even more terrified. Escalating fear and arousal would worsen sleep paralysis by prolonging the episode and resulting in more intense bodily hallucinations, as they are more likely to try to move during the paralysis, causing body image disturbances.
It doesn't end there. Now, they notice that they are experiencing sleep paralysis more often and that episodes are longer and more horrifying. They become convinced that they are targeted, perhaps even possessed, by a supernatural creature. This, in turn, makes them even more afraid, and the vicious cycle continues to feed on itself.
It is still unclear whether the fear generated by sleep paralysis can be pathological. But in our recent study, we found that experiencers of sleep paralysis in Egypt have greater symptoms of trauma and anxiety compared to those who have never experienced it. Intriguingly, we also found that those who experience hallucinations during their sleep paralysis have more trauma and anxiety symptoms. These findings point to the possibility that sleep paralysis, if accompanied by certain beliefs, might be a traumatizing experience. This is also consistent with the findings of Richard McNally, also at Harvard, that sleep paralysis interpreted as alien abduction can elicit physiological fear comparable to patients with post-traumatic stress disorder.
Control your dreams: a cure for sleep paralysis?
In the 1984 horror movie A Nightmare on Elm Street, the ghost Freddy Krueger ferociously terrorizes and kills young teenagers during their nightmares. But the protagonist Nancy is finally able to make Krueger vanish from her nightmares; she follows the advice of her friend Glen (played by a young Johnny Depp), who insists that if you turn your back on the monster, you "take away its energy and it disappears."
Indeed, dispelling the fear surrounding sleep paralysis is an important means to help people cope with their experience and, crucially, to prevent escalating fear cycles that can lead to worse and more frequent episodes. One way to do this is to disseminate scientific knowledge about the experience. This often works. People are genuinely relieved to hear that they aren't "crazy," that they aren't the only ones experiencing it, and that the phenomena seem to originate in the brain.
A more radical approach to overcome the fear of sleep paralysis is by "literally" turning your back on the terrifying monster, by sliding into a lucid dream — that is, a dream in which you are aware that you are dreaming. It is not surprising that sleep paralysis can be a gateway to lucid dreaming. Both sleep paralysis and lucid dreaming are consciousness states that lie between REM and wakening; the former is dreaming while awake; the latter, being awake while dreaming.
Neural circuitry associated with wakefulness is more likely to become activated during sleep paralysis, such as the dorsolateral prefrontal cortex that helps us organize our logical thoughts when awake (and which is normally turned off during REM). When the dorsolateral prefrontal cortex becomes active during sleep, we enter a type of hybrid consciousness that combines the surrealness of dreams and the rationality of wakefulness. And so, we become aware that we are dreaming — and like a great Michelangelo we can create our own fantasy worlds composed of colorful landscapes and creatures of all kinds conjured by our minds. Being able to manipulate the content of one's sleep paralysis hallucinations and REM-dream imagery could give the experiencer a sense of control over the situation and might therefore be therapeutic.
I was once able to slide into a lucid dream during my own sleep paralysis. Lucky for me, no terrifying intruders were present. When I became aware that my dreaming "self" was walking around in my bedroom, it occurred to me to do an "experiment." I found a piece of scrap paper on the floor and put it in my pocket. I thought to myself, if it's still there upon awakening, I would have to reconsider some of my own scientific theories about the role of the brain in favor of more uncanny explanations. My pocket was empty when I woke up.
On a different occasion, I wanted to test whether by deliberately trying to move during the paralysis (causing disturbances to my body image) and imagining that a sinister creature was present in my bedroom (activating dream imagery), I could create my own hallucinated "Frankenstein monster." I wasn't able to complete the "experiment" out of sheer horror, but I still joke with my colleagues telling them that we're among a select group of people who can say we're working while sleeping.
Based on my scientific work on sleep paralysis around the world and our proposed neurological explanation for why people hallucinate ghosts during the episode, I thought to myself, "How do I create a simple, yet effective therapy for sufferers?" Meditation-relaxation (MR) therapy was recently designed as a direct treatment for sleep paralysis. The treatment, which includes techniques of cognitive reappraisals and emotional distancing, meditation, and muscle relaxation, aims to minimize current attacks and decrease the frequency, severity, and duration of future ones. In a recent pilot study, we found that MR therapy reduced sleep paralysis episodes by 50+ percent when applied for eight weeks in patient with narcolepsy.
As we are just beginning to probe this fascinating condition and unlock its neural basis, the mystery remains. Here is a single phenomenon that can make us see and become ghosts, have encounters with space aliens from distant galaxies, and plunge us into far and exotic lands of lucid dreaming, where we are the sculptors of our own realities, all the while laying silently in our beds. It shows us firsthand how the feeling of a sense of self as a unified entity separate from others arises in the brain and how vulnerable this feeling is to disruption.
Dr. Baland S. Jalal is a researcher at Harvard University, Department of Psychology and visiting researcher at Cambridge University, Department of Psychiatry. He obtained his PhD at Cambridge University in the School of Clinical Medicine (Trinity College Cambridge) and was a Fellow at Harvard University (2016, 2018). He is a close collaborator and co-author on 10 papers with the renowned neuroscientist VS Ramachandran (2011 TIME magazine 100 most influential people in the world).
