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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
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.
Ever since we've had the technology, we've looked to the stars in search of alien life. It's assumed that we're looking because we want to find other life in the universe, but what if we're looking to make sure there isn't any?
Here's an equation, and a rather distressing one at that: N = R* × fP × ne × f1 × fi × fc × L. It's the Drake equation, and it describes the number of alien civilizations in our galaxy with whom we might be able to communicate. Its terms correspond to values such as the fraction of stars with planets, the fraction of planets on which life could emerge, the fraction of planets that can support intelligent life, and so on. Using conservative estimates, the minimum result of this equation is 20. There ought to be 20 intelligent alien civilizations in the Milky Way that we can contact and who can contact us. But there aren't any.
The Drake equation is an example of a broader issue in the scientific community—considering the sheer size of the universe and our knowledge that intelligence life has evolved at least once, there should be evidence for alien life. This is generally referred to as the Fermi paradox, after the physicist Enrico Fermi who first examined the contradiction between high probability of alien civilizations and their apparent absence. Fermi summed this up rather succinctly when he asked, “Where is everybody"?
But maybe this was the wrong question. A better question, albeit a more troubling one, might be “What happened to everybody?" Unlike asking where life exists in the universe, there's a clearer potential answer to this question: the Great Filter.
Why the universe is empty
Alien life is likely, but there is none that we can see. Therefore, it could be the case that somewhere along the trajectory of life's development, there is a massive and common challenge that ends alien life before it becomes intelligent enough and widespread enough for us to see—a great filter.
This filter could take many forms. It could be that having a planet in the Goldilocks' zone—the narrow band around a star where it is neither too hot nor too cold for life to exist—and having that planet contain organic molecules capable of accumulating into life is extremely unlikely. We've observed plenty of planets in the Goldilock's zone of different stars (there's estimated to be 40 billion in the Milky Way), but maybe the conditions still aren't right there for life to exist.
The Great Filter could occur at the very earliest stages of life. When you were in high school bio, you might have the refrain drilled into your head “mitochondria are the powerhouse of the cell." I certainly did. However, mitochondria were at one point a separate bacteria living its own existence. At some point on Earth, a single-celled organism tried to eat one of these bacteria, except instead of being digested, the bacterium teamed up with the cell, producing extra energy that enabled the cell to develop in ways leading to higher forms of life. An event like this might be so unlikely that it's only happened once in the Milky Way.
Or, the filter could be the development of large brains, as we have. After all, we live on a planet full of many creatures, and the kind of intelligence humans have has only occurred once. It may be overwhelmingly likely that living creatures on other planets simply don't need to evolve the energy-demanding neural structures necessary for intelligence.
What if the filter is ahead of us?
These possibilities assume that the Great Filter is behind us—that humanity is a lucky species that overcame a hurdle almost all other life fails to pass. This might not be the case, however; life might evolve to our level all the time but get wiped out by some unknowable catastrophe. Discovering nuclear power is a likely event for any advanced society, but it also has the potential to destroy such a society. Utilizing a planet's resources to build an advanced civilization also destroys the planet: the current process of climate change serves as an example. Or, it could be something entirely unknown, a major threat that we can't see and won't see until it's too late.
The bleak, counterintuitive suggestion of the Great Filter is that it would be a bad sign for humanity to find alien life, especially alien life with a degree of technological advancement similar to our own. If our galaxy is truly empty and dead, it becomes more likely that we've already passed through the Great Filter. The galaxy could be empty because all other life failed some challenge that humanity passed.
If we find another alien civilization, but not a cosmos teeming with a variety of alien civilizations, the implication is that the Great Filter lies ahead of us. The galaxy should be full of life, but it is not; one other instance of life would suggest that the many other civilizations that should be there were wiped out by some catastrophe that we and our alien counterparts have yet to face.
Fortunately, we haven't found any life. Although it might be lonely, it means humanity's chances at long-term survival are a bit higher than otherwise.
Cross-disciplinary cooperation is needed to save civilization.
- There is a great disconnect between the sciences and the humanities.
- Solutions to most of our real-world problems need both ways of knowing.
- Moving beyond the two-culture divide is an essential step to ensure our project of civilization.
For the past five years, I ran the Institute for Cross-Disciplinary Engagement at Dartmouth, an initiative sponsored by the John Templeton Foundation. Our mission has been to find ways to bring scientists and humanists together, often in public venues or — after Covid-19 — online, to discuss questions that transcend the narrow confines of a single discipline.
It turns out that these questions are at the very center of the much needed and urgent conversation about our collective future. While the complexity of the problems we face asks for a multi-cultural integration of different ways of knowing, the tools at hand are scarce and mostly ineffective. We need to rethink and learn how to collaborate productively across disciplinary cultures.
The danger of hyper-specialization
The explosive expansion of knowledge that started in the mid 1800s led to hyper-specialization inside and outside academia. Even within a single discipline, say philosophy or physics, professionals often don't understand one another. As I wrote here before, "This fragmentation of knowledge inside and outside of academia is the hallmark of our times, an amplification of the clash of the Two Cultures that physicist and novelist C.P. Snow admonished his Cambridge colleagues in 1959." The loss is palpable, intellectually and socially. Knowledge is not adept to reductionism. Sure, a specialist will make progress in her chosen field, but the tunnel vision of hyper-specialization creates a loss of context: you do the work not knowing how it fits into the bigger picture or, more alarmingly, how it may impact society.
Many of the existential risks we face today — AI and its impact on the workforce, the dangerous loss of privacy due to data mining and sharing, the threat of cyberwarfare, the threat of biowarfare, the threat of global warming, the threat of nuclear terrorism, the threat to our humanity by the development of genetic engineering — are consequences of the growing ease of access to cutting-edge technologies and the irreversible dependence we all have on our gadgets. Technological innovation is seductive: we want to have the latest "smart" phone, 5k TV, and VR goggles because they are objects of desire and social placement.
Are we ready for the genetic revolution?
When the time comes, and experts believe it is coming sooner than we expect or are prepared for, genetic meddling with the human genome may drive social inequality to an unprecedented level with not just differences in wealth distribution but in what kind of being you become and who retains power. This is the kind of nightmare that Nobel Prize-winning geneticist Jennifer Doudna talked about in a recent Big Think video.
CRISPR 101: Curing Sickle Cell, Growing Organs, Mosquito Makeovers | Jennifer Doudna | Big Think www.youtube.com
At the heart of these advances is the dual-use nature of science, its light and shadow selves. Most technological developments are perceived and sold as spectacular advances that will either alleviate human suffering or bring increasing levels of comfort and accessibility to a growing number of people. Curing diseases is what motivated Doudna and other scientists involved with CRISPR research. But with that also came the potential for altering the genetic makeup of humanity in ways that, again, can be used for good or evil purposes.
This is not a sci-fi movie plot. The main difference between biohacking and nuclear hacking is one of scale. Nuclear technologies require industrial-level infrastructure, which is very costly and demanding. This is why nuclear research and its technological implementation have been mostly relegated to governments. Biohacking can be done in someone's backyard garage with equipment that is not very costly. The Netflix documentary series Unnatural Selection brings this point home in terrifying ways. The essential problem is this: once the genie is out of the bottle, it is virtually impossible to enforce any kind of control. The genie will not be pushed back in.
Cross-disciplinary cooperation is needed to save civilization
What, then, can be done? Such technological challenges go beyond the reach of a single discipline. CRISPR, for example, may be an invention within genetics, but its impact is vast, asking for oversight and ethical safeguards that are far from our current reality. The same with global warming, rampant environmental destruction, and growing levels of air pollution/greenhouse gas emissions that are fast emerging as we crawl into a post-pandemic era. Instead of learning the lessons from our 18 months of seclusion — that we are fragile to nature's powers, that we are co-dependent and globally linked in irreversible ways, that our individual choices affect many more than ourselves — we seem to be bent on decompressing our accumulated urges with impunity.
The experience from our experiment with the Institute for Cross-Disciplinary Engagement has taught us a few lessons that we hope can be extrapolated to the rest of society: (1) that there is huge public interest in this kind of cross-disciplinary conversation between the sciences and the humanities; (2) that there is growing consensus in academia that this conversation is needed and urgent, as similar institutes emerge in other schools; (3) that in order for an open cross-disciplinary exchange to be successful, a common language needs to be established with people talking to each other and not past each other; (4) that university and high school curricula should strive to create more courses where this sort of cross-disciplinary exchange is the norm and not the exception; (5) that this conversation needs to be taken to all sectors of society and not kept within isolated silos of intellectualism.
Moving beyond the two-culture divide is not simply an interesting intellectual exercise; it is, as humanity wrestles with its own indecisions and uncertainties, an essential step to ensure our project of civilization.
New study analyzes gravitational waves to confirm the late Stephen Hawking's black hole area theorem.
- A new paper confirms Stephen Hawking's black hole area theorem.
- The researchers used gravitational wave data to prove the theorem.
- The data came from Caltech and MIT's Advanced Laser Interferometer Gravitational-Wave Observatory.
The late Stephen Hawking's black hole area theorem is correct, a new study shows. Scientists used gravitational waves to prove the famous British physicist's idea, which may lead to uncovering more underlying laws of the universe.
The theorem, elaborated by Hawking in 1971, uses Einstein's theory of general relativity as a springboard to conclude that it is not possible for the surface area of a black hole to become smaller over time. The theorem parallels the second law of thermodynamics that says the entropy (disorder) of a closed system can't decrease over time. Since the entropy of a black hole is proportional to its surface area, both must continue to increase.
As a black hole gobbles up more matter, its mass and surface area grow. But as it grows, it also spins faster, which decreases its surface area. Hawking's theorem maintains that the increase in surface area that comes from the added mass would always be larger than the decrease in surface area because of the added spin.
Will Farr, one of the co-authors of the study that was published in Physical Review Letters, said their finding demonstrates that "black hole areas are something fundamental and important." His colleague Maximiliano Isi agreed in an interview with Live Science: "Black holes have an entropy, and it's proportional to their area. It's not just a funny coincidence, it's a deep fact about the world that they reveal."
What are gravitational waves?
Gravitational waves are "ripples" in spacetime, predicted by Albert Einstein in 1916, that are created by very violent processes happening in space. Einstein showed that very massive, accelerating space objects like neutron stars or black holes that orbit each other could cause disturbances in spacetime. Like the ripples produced by tossing a rock into a lake, they would bring about "waves" of spacetime that would spread in all directions.
As LIGO shared, "These cosmic ripples would travel at the speed of light, carrying with them information about their origins, as well as clues to the nature of gravity itself."
The gravitational waves discovered by LIGO's 3,000-kilometer-long laser beam, which can detect the smallest distortions in spacetime, were generated 1.3 billion years ago by two giant black holes that were quickly spiraling toward each other.
What Stephen Hawking would have discovered if he lived longer | NASA's Michelle Thaller | Big Think www.youtube.com
Confirming Hawking's black hole area theorem
The researchers separated the signal into two parts, depending on whether it was from before or after the black holes merged. This allowed them to figure out the mass and spin of the original black holes as well as the mass and spin of the merged black hole. With this information, they calculated the surface areas of the black holes before and after the merger.
"As they spin around each other faster and faster, the gravitational waves increase in amplitude more and more until they eventually plunge into each other — making this big burst of waves," Isi elaborated. "What you're left with is a new black hole that's in this excited state, which you can then study by analyzing how it's vibrating. It's like if you ping a bell, the specific pitches and durations it rings with will tell you the structure of that bell, and also what it's made out of."
The surface area of the resulting black holes was larger than the combined area of the original black holes. This conformed to Hawking's area law.