Futurists on the Future


Michio Kaku: Can We Download Our Brains?

One day we might be able to download our consciousness into a computer chip, preserving our personalities forever—but first we will have to better understand brain architecture.

Ray Kurzweil: Your Robot Assistant Will Be Able to Do What No Human Can Do

Your computer will be an assistant that helps you through the day, will answer your questions before you ask them or even before you realize you have a question

Richard Branson Imagines the Future

The British entrepreneur's plan to populate outer space.

Elon Musk: Why I'm Betting on Solar

Elon Musk tends to be interested in industries that "a lot of people think are impossible or think you can’t succeed at - that’s usually where there’s opportunity."

Peter Thiel: Today, Silicon Valley; Tomorrow, the Atlantic

California is still the best place for tech companies to do business. But colonies on offshore platforms might one day become our centers of innovation.

More playlists
  • A new review of a famous study on declining sperm counts finds several flaws.
  • The old report makes unfounded assumptions, has faulty data, and tends toward panic.
  • The new report does not rule out that sperm counts are going down, only that this could be quite normal.

Several years ago, a meta-analysis of studies on human fertility came out warning us about the declining sperm counts of Western men. It was widely shared, and its findings were featured on the covers of popular magazines. Indeed, its findings were alarming: a nearly 60 percent decline in sperm per milliliter since 1973 with no end in sight. It was only a matter of time, the authors argued, until men were firing blanks, literally.

Well… never mind.

It turns out that the impending demise of humanity was greatly exaggerated. As the predicted infertility wave crashed upon us, there was neither a great rush of men to fertility clinics nor a sudden dearth of new babies. The only discussions about population decline focus on urbanization and the fact that people choose not to have kids rather than not being able to have them.

Now, a new analysis of the 2017 study says that lower sperm counts is nothing to be surprised by. Published in Human Fertility, its authors point to flaws in the original paper's data and interpretation. They suggest a better and smarter reanalysis.

Counting tiny things is difficult

The original 2017 report analyzed 185 studies on 43,000 men and their reproductive health. Its findings were clear: "a significant decline in sperm counts… between 1973 and 2011, driven by a 50-60 percent decline among men unselected by fertility from North America, Europe, Australia and New Zealand."

However, the new analysis points out flaws in the data. As many as a third of the men in the studies were of unknown age, an important factor in reproductive health. In 45 percent of cases, the year of the sample collection was unknown- a big detail to miss in a study measuring change over time. The quality controls and conditions for sample collection and analysis vary widely from study to study, which likely influenced the measured sperm counts in the samples.

Another study from 2013 also points out that the methods for determining sperm count were only standardized in the 1980s, which occurred after some of the data points were collected for the original study. It is entirely possible that the early studies gave inaccurately high sperm counts.

This is not to say that the 2017 paper is entirely useless; it had a much more rigorous methodology than previous studies on the subject, which also claimed to identify a decline in sperm counts. However, the original study had more problems.

Garbage in, garbage out

Predictable as always, the media went crazy. Discussions of the decline of masculinity took off, both in mainstream and less-than-reputable forums; concerns about the imagined feminizing traits of soy products continued to increase; and the authors of the original study were called upon to discuss the findings themselves in a number of articles.

However, as this new review points out, some of the findings of that meta-analysis are debatable at best. For example, the 2017 report suggests that "declining mean [sperm count] implies that an increasing proportion of men have sperm counts below any given threshold for sub-fertility or infertility," despite little empirical evidence that this is the case.

The WHO offers a large range for what it considers to be a healthy sperm count, from 15 to 250 million sperm per milliliter. The benefits to fertility above a count of 40 million are seen as minimal, and the original study found a mean sperm concentration of 47 million sperm per milliliter.

Healthy sperm, healthy man?

The claim that sperm count is evidence of larger health problems is also scrutinized in this new article. While it is true that many major health problems can impact reproductive health, there is little evidence that it is the "canary in the coal mine" for overall well-being. A number of studies suggest that any relation between lifestyle choices and this part of reproductive health is limited at best.

Lastly, ideas that environmental factors could be at play have been debunked since 2017. While the original paper considered the idea that pollutants, especially from plastics, could be at fault, it is now known that this kind of pollution is worse in the parts of the world that the original paper observed higher sperm counts in (i.e., non-Western nations).

There never was a male fertility crisis

The authors of the new review do not deny that some measurements are showing lower sperm counts, but they do question the claim that this is catastrophic or part of a larger pathological issue. They propose a new interpretation of the data. Dubbed the "Sperm Count Biovariability hypothesis," it is summarized as:

"Sperm count varies within a wide range, much of which can be considered non-pathological and species-typical. Above a critical threshold, more is not necessarily an indicator of better health or higher probability of fertility relative to less. Sperm count varies across bodies, ecologies, and time periods. Knowledge about the relationship between individual and population sperm count and life-historical and ecological factors is critical to interpreting trends in average sperm counts and their relationships to human health and fertility."

Still, the authors note that lower sperm counts "could decline due to negative environmental exposures, or that this may carry implications for men's health and fertility."

However, they disagree that the decline in absolute sperm count is necessarily a bad sign for men's health and fertility. We aren't at civilization ending catastrophe just yet.

  • Junior members of the workforce, including Generation Z, are facing digital burnout.
  • 41 percent of workers globally are thinking about handing in their notice, according to a new Microsoft survey.
  • A hybrid blend of in-person and remote work could help maintain a sense of balance – but bosses need to do more.

More than half of 18 to 25 year-olds in the workforce are considering quitting their job. And they're not the only ones.

In a report called The Next Great Disruption Is Hybrid Work – Are We Ready?, Microsoft found that as well as 54% of Generation Z workers, 41% of the entire global workforce could be considering handing in their resignation.

Similarly, a UK and Ireland survey found that 38% of employees were planning to leave their jobs in the next six months to a year, while a US survey reported that 42% of employees would quit if their company didn't offer remote working options long term.

New work trends

Based on surveys with over 30,000 workers in 31 countries, the Microsoft report – which is the latest in the company's annual Work Trend Index series – pulled in data from applications including Teams, Outlook and Office 365, to gauge productivity and activity levels. It highlighted seven major trends, which show the world of work has been profoundly reshaped by the pandemic:

  • Flexible work is here to stay
  • Leaders are out of touch with employees and need a wake-up call
  • High productivity is masking an exhausted workforce
  • Gen Z is at risk and will need to be re-energized
  • Shrinking networks are endangering innovation
  • Authenticity will spur productivity and wellbeing
  • Talent is everywhere in a hybrid world

"Over the past year, no area has undergone more rapid transformation than the way we work," Microsoft CEO Satya Nadella says in the report. "Employee expectations are changing, and we will need to define productivity much more broadly – inclusive of collaboration, learning and wellbeing to drive career advancement for every worker, including frontline and knowledge workers, as well as for new graduates and those who are in the workforce today. All this needs to be done with flexibility in, when, where and how people work."

Organizations have become more siloed

While the report highlights the opportunities created by increased flexible and remote working patterns, it warns that some people are experiencing digital exhaustion and that remote working could foster siloed thinking. With the shift to remote working, much of the spontaneous sharing of ideas that can take place within a workplace was lost. In its place are scheduled calls, regular catch-ups and virtual hangouts. The loss of in-person interaction means individual team members are more likely to only interact with their closest coworkers.

"At the onset of the pandemic, our analysis shows interactions with our close networks at work increased while interactions with our distant network diminished," the report says. "This suggests that as we shifted into lockdown, we clung to our immediate teams for support and let our broader network fall to the wayside. Simply put, companies became more siloed than they were pre-pandemic."

Burnout or drop out

One of the other consequences of the shift to remote and the reliance on tech-based communications has been the phenomenon of digital burnout. And for those who have most recently joined the workforce, this has been a significant challenge.


The excitement of joining a new employer, maybe even securing a job for the first time, usually comes with meeting lots of new people, becoming familiar with a new environment and adapting to new situations. But for many, the pandemic turned that into a daily routine of working from home while isolated from co-workers.

"Our findings have shown that for Gen Z and people just starting in their careers, this has been a very disruptive time," says LinkedIn Senior Editor-at-Large, George Anders, quoted in the report. "It's very hard to find their footing since they're not experiencing the in-person onboarding, networking and training that they would have expected in a normal year."

But it is perhaps the data around quitting that is one of the starkest indications that change is now the new normal. Being able to work remotely has opened up new possibilities for many workers, the report found. If you no longer need to be physically present in an office, your employer could, theoretically, be located anywhere. Perhaps that's why the research found that "41% of employees are considering leaving their current employer this year".

In addition to that, 46% of the people surveyed for the Microsoft report said they might relocate their home because of the flexibility of remote working.

A hybrid future

In looking for ways to navigate their way through all this change, employers should hold fast to one word, the report says – hybrid. An inflexible, location-centred approach to work is likely to encourage those 41% of people to leave and find somewhere more to their tastes. Those who are thinking of going to live somewhere else, while maintaining their current job, might also find themselves thinking of quitting if their plans are scuppered.


But remote working is not a panacea for all workforce ills. "We can no longer rely solely on offices to collaborate, connect, and build social capital. But physical space will still be important," the report says. "We're social animals and we want to get together, bounce ideas off one another, and experience the energy of in-person events. Moving forward, office space needs to bridge the physical and digital worlds to meet the unique needs of every team – and even specific roles."

Bosses must meet challenges head on

Although the majority of business leaders have indicated they will incorporate elements of the hybrid working model, the report also found many are out of touch with workforce concerns more widely.

For, while many workers say they are struggling (Gen Z – 60%; new starters – 64%), and 54% of the general workforce feels overworked, business leaders are having a much better experience. Some 61% said they were 'thriving', which is in stark contrast to employees who are further down the chain of command.


Jared Spataro, corporate vice president at Microsoft 365, writes in the report: "Those impromptu encounters at the office help keep leaders honest. With remote work, there are fewer chances to ask employees, 'Hey, how are you?' and then pick up on important cues as they respond. But the data is clear: our people are struggling. And we need to find new ways to help them."

Reprinted with permission of the World Economic Forum. Read the original article.

  • Modular construction involves building the components of a habitable structure in a factory, and then assembling those components on-site.
  • The history of modular construction stretches back centuries, and it became briefly popular in the U.S. after World War II, but it's never quite caught on.
  • Construction firms like iMod Structures, which constructs buildings that can be modified and relocated, may soon change that.

Modular construction is on the rise. Once a marginal sector focused on building affordable homes, modular construction is now building an increasing share of structures used for commerce, healthcare, and education. By 2028, the modular construction market is projected to be worth $114 billion.

What is modular construction? It's like building with Legos but on an industrial scale: standardized block-shaped modules are constructed in a factory, transported to a building site, and assembled together to form a habitable structure.

What's most striking about modular buildings isn't appearance but the speed of construction. In 2015, for example, a Chinese construction company built a 57-story glass-and-concrete skyscraper made of 2,736 rectangular modules in a record-breaking 19 days. That's three stories per day.

In addition to speed, modular construction promises to be more modifiable, more transportable, and less wasteful than traditional construction methods. The method could transform construction, which, despite being one of the world's biggest sectors, is one of the slowest growing in terms of labor productivity and digitization.

One modular construction firm aiming to bring the sector into the 21st century is iMod Structures, which builds shipping container-sized modules that can be assembled into buildings. The modules can then be disassembled to modify the existing structure or transported to a different site to build a new one.

Freethink recently visited iMod Structures to get an up-close look at its unique spin on modular construction.

Do buildings have to be permanent? | Hard Reset by Freethink www.youtube.com

Techniques like this could help bring construction into the 21st century. But despite its futuristic and transformative appeal, modular construction is far from a new idea. In fact, the history of prefabrication — the broader category of construction to which modular belongs — goes back centuries.

Prefabrication: From 17th-century cottages to diners to skyscrapers

One of the earliest examples of prefabrication came in 1624, when a colonial American fisherman commissioned an English construction company to fabricate components of a building and ship them overseas to the fishing village of Cap Anne.

In the 17th and 18th centuries, English firms also shipped prefabricated structures — storehouses, cottages, and hospitals — to Australia, South Africa, and New Zealand. In the U.S., prefabricated homes became popular during the Gold Rush when California towns had too many people but too few houses.

In the early 20th century, mass-production made modular construction more practical and, sometimes, more popular. From 1908 to 1940, Sears sold about 70,000 kit homes across the country; some of the cheapest models started around $160. (Kit homes were like IKEA products: the manufacturer builds and precuts the parts, and the buyer assembles them.)

Still, prefabricated homes weren't particularly popular in the first half of the 20th century; homebuyers generally viewed the structures — especially the metal and experimental ones — as strange and undesirable.

Modular construction Pre fabricated house shipped via boxcarThe Aladdin Company via Wikipedia

But appearance wasn't a major concern during World War II. Facing huge demand for cheap and simple housing for soldiers in the early 1940s, the U.S. produced hundreds of thousands of Quonset huts — prefabricated, semi-cylindrical structures made of corrugated galvanized steel — which about six unskilled laborers could construct in a day.

Modular construction A Quonset hut being put in place at the 598th Engineer Base Depot in Japan, post-World War IIUS Army Corps of Engineers via Wikipedia

After the war, millions of U.S. soldiers returned home, and the nation faced a housing shortage crisis. Hundreds of companies entered the prefabricated housing market, with several receiving support from the federal government. One of the most iconic models was the enameled-steel Lustron house, which cost $7,000 to $10,000, took two weeks to assemble, and promised to "defy weather, wear, and time."

Modular construction Lustron HouseAdirondack Architectural Heritage

By 1958, roughly 10 percent of all homes in the U.S. were prefabricated. In addition to homes, the prefabrication industry also built thousands of diners throughout the 20th century, especially after World War II when owning a prefabricated diner was a decent small-business opportunity. Popular in New Jersey, the narrow diners could easily be shipped to buyers by rail.

Interior of a 1938 Sterling manufactured diner, with curved ceiling, in Wellsboro, PennsylvaniaI, Ruhrfisch via Wikipedia

Despite the post-war boom, modular construction never really caught on in most parts of the world, though many architects and builders have long been attracted to the method. Some of the reasons include consumer perception that modular homes are unattractive, technological constraints, and the high costs of researching and developing new building techniques.

These challenges can be prohibitive, especially for large-scale projects.

"Building anything over 10 stories in modular is something no one has wanted to do because you have to invest in research and development," Susi Yu, executive vice president of residential development for the Forest City Ratner Corporation, told Fast Company. "There's science behind it that you need to figure out."

But attitudes on modular buildings may be shifting.

"Today, modular construction is experiencing a new wave of attention and investment, and several factors suggest it may have renewed staying power," noted a 2019 report from the consulting firm McKinsey & Company. "The maturing of digital tools has radically changed the modular-construction proposition — for instance, by facilitating the design of modules and optimizing delivery logistics. Consumer perceptions of prefab housing are beginning to change, particularly as new, more varied material choices improve the visual appeal of prefab buildings."

The report goes on: "Perhaps most important, we see a change in mind-set among construction-sector CEOs, as many leaders see technology-based disruptors entering the scene — and realizing it may be time to reposition themselves."

In recent decades, construction firms around the world have built all kinds of modular buildings, including modular skyscrapers in the U.K., U.S., and China; containerized homes in Mexico; and classrooms in rural South Africa.

"In many countries, modular construction is still very much an outlier," McKinsey noted. "But there are strong signs of what could be a genuine broad-scale disruption in the making. It is already drawing in new competitors — and it will most likely create new winners and losers across the entire construction ecosystem."

The benefits of modular construction

Modular construction has the potential to deliver $22 billion in annual savings to U.S. and European markets, mainly because of the inherent benefits of building components in a controlled factory setting. The Modular Building Institute lists a few examples:

  • Shorter construction schedule. Because construction of modular buildings can occur simultaneously with the site and foundation work, projects can be completed 30 percent to 50 percent sooner than traditional construction.
  • Elimination of weather delays. 60 to 90 percent of the construction is completed inside a factory, which mitigates the risk of weather delays. Buildings are occupied sooner, creating a faster return on investment.
  • Improved air quality. Because the modular structure is substantially completed in a factory controlled setting using dry materials, there's virtually no potential for high levels of moisture (which can cause mold growth) to get trapped in the new construction.
  • Less material waste. When building in a factory, waste is eliminated by recycling materials, controlling inventory, and protecting building materials.
  • Safer construction. The indoor construction environment reduces the risks of accidents and related liabilities for workers.

But perhaps the biggest benefit of modular construction is relocatability and modifiability.

Future-proofing buildings and cities

Buildings are hard to modify and practically impossible to move. That's a problem for many organizations, including the Los Angeles Unified School District. The district currently maintains thousands of decades-old trailers it built to accommodate a fast-growing student population.

Seeking to replace those trailers with structures, the district partnered with iMod Structures to build "future proof" modular classrooms that can be reconfigured and relocated, depending on fluctuating enrollment levels.

"If you have one of our classrooms in a particular location and 5, 10, or 20 years later, you need them across town at another campus within the school district, you simply disassemble, relocate, and reassemble them where they are needed," Craig Severance, Principal with iMod Structures, said in a statement. "And it can be done within a few days, minimizing school [downtime] and disruption of our children's education."

Modular construction iMod Structures classroomiMod Structures

Founded in 2009 by former real estate investors John Diserens and Craig Severance, iMod Structures takes a hyper-efficient approach to modular construction. Instead of making many types of prefabricated components, the firm makes only one standardized block-shaped frame, each roughly the size of a shipping container. The firm builds the frames in factories and then outfits them with walls, windows, and other custom features the client wants.

Because the frames have the dimensions of a standard shipping container, they can be easily transported to the building site by truck or rail. On site, the frames are connected together or stacked on top of each other. Once the structure is intact, workers finish the job by adding plumbing, electricity, and other final touches.

The process saves a lot of time.

"Typically, it would take nine to 15 months to manufacture a classroom out in the field," said Mike McKibbin, the head of operations for iMod. "We're doing that in twelve days."

Movable neighborhoods

Today, iMod Structures is focusing on future-proofing classrooms in California. But it's not hard to imagine how this kind of modular construction could transform not only the ways we build buildings but also organize cities. For example, if a company wants to set up offices in a new part of town, it could build an office park out of iMod Structures frames.

But what if the company needs to expand? It could attach more modules to its existing structure. If it needs to shut down? Instead of demolishing the office park, the structure could be modified and converted into, say, a hospital or apartment building. Alternatively, the modules could be removed from the site, and reused elsewhere, so the city could construct a park.

Under this kind of framework, cities could become far more flexible and dynamic, able to quickly adapt to changing needs. And with no need to demolish buildings, modular construction could prove far more sustainable than any method the industry uses today.

"We don't want our buildings to ever end up in a landfill. Ever," said Reed Walker, head of production and design at iMod Structures. "We want to take that system and use it again and again and again."

    For the past few years, Annabelle Singer and her collaborators have been using flickering lights and sound to treat mouse models of Alzheimer's disease, and they've seen some dramatic results.


    Now they have results from the first human feasibility study of the flicker treatment, and they're promising.

    "We looked at safety, tolerance, and adherence, and several different biological outcomes, and the results were excellent—better than we expected," says Singer, assistant professor in the biomedical engineering department at Georgia Institute of Technology and Emory University.

    Singer shared preliminary results of the feasibility study in October at the American Neurological Association annual meeting. Now she is a corresponding author with Emory neurology researcher James Lah of a paper outlining their findings in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.

    The flicker treatment stimulates gamma waves, manipulating neural activity, recruiting the brain's immune system, and clearing pathogens—in short, waging a successful fight against a progressive disease that still has no cure.

    Previous research already had shown that sensory areas in the human brain will entrain to flickering stimuli for seconds to hours. But this was the first time Singer and her team were able to test gamma sensory stimulation over an extended period of time.

    The study included 10 patients with Alzheimer's-associated mild cognitive impairment, which required them to wear an experimental visor and headphones that exposed one group to light and sound at 40 hertz for an hour a day over eight weeks, and another group for four weeks after a delayed start.

    "We were able to tune the devices to a level of light and sound that was not only tolerable, but it also successfully provoked an underlying brain response," Lah says.

    As they hoped and expected, Singer says, "there was widespread entrainment." That is, brain activity—in this case, gamma waves—synchronized to the external stimulation.

    Gamma waves are associated with high-level cognitive functions, like perception and memory. Disruptions to these waves have been found in various neurological disorders, not just Alzheimer's.

    The human feasibility study showed that the gamma flicker treatment was safe and tolerable. And perhaps most surprising, patients followed the full treatment schedule.

    "Adherence was one of our major concerns," Singer says. "When we sent the device home with the participants, would they use it? Would they use it for a couple of days, and that would be it? We were pleasantly surprised that this wasn't the case."

    Adherence rates hovered around 90%, with no severe adverse effects reported during the study or the 10-month open label extension (some patients even volunteered to continue being monitored and assessed after the study, though this data wasn't part of the published research).

    Some participants reported mild discomfort that could have been flicker related—dizziness, ringing in the ears, and headaches. But overall, Singer says, the device's safety profile was excellent. She also reported some positive biological outcomes.

    "We looked at default mode network connectivity, which is basically how different brain regions that are particularly active during wakeful rest and memory, interact with each other," Singer says.

    "There are deficits in this network in Alzheimer's, but after eight weeks [of treatment], we found strengthening in that connectivity." This may indicate stronger interactions and therefore better communication between these regions.

    In previous animal studies, the 40Hz of flicker stimulated mouse gamma waves, significantly reducing some Alzheimer's pathogenic hallmarks and recruited microglia to the cause—these are the primary immune cells in the brain. But in the human study, there were no clear changes in the presence of pathogens amyloid beta or p-Tau.

    However, as with the mouse studies, "we are getting immune engagement in humans," Singer says. The flicker treatment sparked the activity of cytokines, proteins used in cell signaling—a sign that flicker had engaged the brain's immune system.

    "That is something we want to see, because microglia do things like clear out pathogens. Some people think that part of what's going wrong in Alzheimer's is a failure of this clearance mechanism," Singer says.

    She and Lah have wondered if a longer human trial would make a difference—would there be reduced amyloid activity, for example.

    "So far, this is very preliminary, and we're nowhere close to drawing conclusions about the clinical benefit of this treatment," Lah says. "But we now have some very good arguments for a larger, longer study with more people."

    Funding for the study came from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the Packard Foundation, the Friends and Alumni of Georgia Tech, the Lane Family, the Wright Family, and Cognito Therapeutics. Any findings, conclusions, and recommendations are those of the researchers and not necessarily of the sponsors.

    Annabelle Singer owns shares in Cognito Therapeutics, which funded the human study at Emory Brain Health Center. Cognito aims to develop gamma stimulation-related products. These conflicts are managed by Georgia Tech's Office of Research Integrity Assurance.

    Source: Georgia Tech

    Original Study DOI: 10.1002/trc2.12178

    Reprinted with permission of Futurity. Read the original article.

    • 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.