COVID-19 vaccines for humans number 30, while only three vaccines are available for animals, even though many species have been infected.
“Several animal species have been predicted and found to be susceptible to SARS-CoV-2,” says Suresh V. Kuchipudi, interim director of the Animal Diagnostic Laboratory at the Huck Institutes of Life Sciences. But the risk remains unknown for many animals in several parts of the world, he says. “Therefore, there is an urgent need to monitor the SARS-CoV-2 exposure of high-risk animals in different parts of the world.”
In June, India introduced Ancovax, its first COVID-19 vaccine for animals. The development came a year after the nation reported that the virus had infected eight Asiatic lions, with two of them dying. While 30 COVID-19 vaccines for humans have been approved for general or emergency use across the world, Ancovax is only the third such vaccine for animals. The first, named Carnivac-Cov, was registered by Russia in March last year, followed by another vaccine four months later, developed by Zoetis, a U.S. pharmaceutical company.
Christina Lood, a Zoetis spokesperson, says the company has donated over 26,000 doses of its animal vaccine to over 200 zoos – in addition to 20 conservatories, sanctuaries and other animal organizations located in over a dozen countries, including Canada, Chile and the U.S. The vaccine, she adds, has been administered to more than 300 mammalian species so far.
“At least 75 percent of emerging infectious diseases have an animal origin, including COVID-19,” says Lood. “Now more than ever before, we can all see the important connection between animal health and human health."
The Dangers of COVID-19 Infections among Animals
Cases of the virus in animals have been reported in several countries across the world. As of March this year, 29 kinds of animals have been infected. These include pet animals like dogs, cats, ferrets and hamsters; farmed animals like minks; wild animals like the white-tailed deer, mule deer and black-tailed marmoset; and animals in zoos and sanctuaries, including hyenas, hippopotamuses and manatees. Despite the widespread infection, the U.S. Centres for Diseases Control and Prevention (CDC) has noted that “we don’t yet know all of the animals that can get infected,” adding that more studies and surveillance are needed to understand how the virus is spread between humans and animals.
Leyi Wang, a veterinary virologist at the Veterinary Diagnostic Laboratory, University of Illinois, says that captive and pet animals most often get infected by humans. It goes both ways, he says, citing a recent study in Hong Kong that found the virus spread from pet hamsters to people.
Wang’s bigger concern is the possibility that humans or domestic animals could transmit the virus back to wildlife, creating an uncontrollable reservoir of the disease, especially given the difficulty of vaccinating non-captive wild animals. Such spillbacks have happened previously with diseases such as plague, yellow-fever, and rabies.
It’s challenging and expensive to develop and implement animal vaccines, and demand has been lacking as the broader health risk for animals isn’t well known among the public. People tend to think only about their house pets.
In the past, other human respiratory viruses have proven fatal for endangered great apes like chimpanzees and gorillas. Fearing that COVID-19 could have the same effect, primatologists have been working to protect primates throughout the pandemic. Meanwhile, virus reservoirs have already been created among other animals, Wang says. “Deer of over 20 U.S. states were tested SARS-CoV-2 positive,” says Wang, pointing to a study that confirmed human-to-deer transmission as well as deer-to-deer transmission. It remains unclear how many wildlife species may be susceptible to the disease due to interaction with infected deer, says Wang.
In April, the CDC expressed concerns over new coronavirus variants mutating in wildlife, urging health authorities to monitor the spread of the contagion in animals as threats to humans. The WHO has made similar recommendations.
Challenges to Vaccine Development
Zoetis initiated development activities for its COVID-19 vaccine in February 2020 when the first known infection of a dog occurred in Hong Kong. The pharmaceutical giant completed the initial development work and studies on dogs and cats, and shared their findings at the World One Health Congress in the fall of 2020. A few months later, after a troop of eight gorillas contracted the virus at the San Diego Zoo Safari Park, Zoetis donated its experimental vaccine for emergency use in the great ape population.
Zoetis has uniquely formulated its COVID-19 vaccine for animals. It uses the same antigen as human vaccines, but it includes a different type of carrier protein for inducing a strong immune response. “The unique combination of antigen and carrier ensures safety and efficacy for the species in which a vaccine is used,” says Lood.
But it’s challenging and expensive to develop and implement animal vaccines, and demand has been lacking as the broader health risk for animals isn’t well known among the public. People tend to think only about their house pets. “As it became apparent that risk of severe disease for household pets such as cats and dogs was low, demand for those vaccines decreased before they became commercially available,” says William Karesh, executive vice-president for health and policy at EcoHealth Alliance. He adds that in affected commercial mink farms, the utility of a vaccine could justify the cost in some cases.
Although scientists have made tremendous advances in making vaccines for animals, Kuchipudi thinks that the need for COVID-19 vaccines for animals “must be evaluated based on many factors, including the susceptibility of the particular animal species, health implications, and cost.”.
Not every scientist feels the need for animal vaccines. Joel Baines, a professor of virology at Cornell University’s Baker Institute for Animal Health, says that while domestic cats are the most susceptible to COVID-19, they usually suffer mild infections. Big cats in zoos are vulnerable, but they can be isolated or distanced from humans. He says that mink farms are a relatively small industry and, by ensuring that human handlers are COVID negative, such outbreaks can be curtailed.
Baines also suggests that human vaccines could probably work in animals, as they were tested in animals during early clinical trials and induced immune responses. “However, these vaccines should be used in humans as a priority and it would be unethical to use a vaccine meant for humans to vaccinate an animal if vaccine doses are at all limiting,” he says.
William Karesh, president of the World Animal Health Organization Working Group on Wildlife Diseases, says the best way to protect animals is to reduce their exposure to infected people.
William Karesh
In the absence of enough vaccines, Karesh says that the best way to protect animals is the same as protecting unvaccinated humans - reduce their exposure to infected people by isolating them when necessary. “People working with or spending time with wild animals should follow available guidelines, which includes testing themselves and wearing PPE to avoid accidentally infecting wildlife,” he says.
The Link between Animal and Human Health
Although there is a need for animal vaccines in response to virus outbreaks, the best approach is to try to prevent the outbreaks in the first place, explains K. Srinath Reddy, president of the Public Health Foundation of India. He says that the incidence of zoonotic diseases has increased in the past six decades because human actions like increased deforestation, wildlife trade and animal meat consumption have opened an ecological window for disease transmission between humans and animals. Such actions chip away at the natural barriers between humans and forest-dwelling viruses, while building conveyor belts for the transmission of zoonotic diseases like COVID-19.
Many studies suggest that the source of COVID-19 was infected live animals sold at a wet market in China’s Wuhan. The market sold live dogs, rats, porcupines, badgers, hares, foxes, hedgehogs, marmots and Chinese muntjac (small deer) and, according to a study published in July, the virus was found on the market’s stalls, animal cages, carts and water drains.
This research strongly suggests that COVID-19 is a zoonotic disease, one that jumps from animals to humans due to our close relationship with them in agriculture, as companions and in the natural environment. Half of the infectious diseases that affect people come from animals, but the study of zoonotic diseases has been historically underfunded, even as they can reduce the likelihood and cost of future pandemics.
“We need to invest in vaccines,” says Reddy, “but that cannot be a substitute for an ecologically sensible approach to curtailing zoonotic diseases.”
Artificial Intelligence is already helping to grow some of the food we eat.
The chef-farmers choose from among 45 types of herb and leafy-greens seeds, plop them into grow trays, and a few weeks later they pick and serve. While success is predicated on at least a small amount of these humans’ care, the systems are autonomously surveilled round-the-clock from Babylon’s base of operations. And artificial intelligence is helping to run the show.
Babylon piloted the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off.
Imagine consistently perfect greens and tomatoes and strawberries, grown hyper-locally, using less water, without chemicals or environmental contaminants. This is the hefty promise of controlled environment agriculture (CEA) — basically, indoor farms that can be hydroponic, aeroponic (plant roots are suspended and fed through misting), or aquaponic (where fish play a role in fertilizing vegetables). But whether they grow 4,160 leafy-green servings per year, like one Babylon farm, or millions of servings, like some of the large, centralized facilities starting to supply supermarkets across the U.S., they seek to minimize failure as much as possible.
Babylon’s soilless hydroponic growing system
Courtesy Babylon Micro-Farms
Here, AI is starting to play a pivotal role. CEA growers use it to help “make sense of what’s happening” to the plants in their care, says Scott Lowman, vice president of applied research at the Institute for Advanced Learning and Research (IALR) in Virginia, a state that’s investing heavily in CEA companies. And although these companies say they’re not aiming for a future with zero human employees, AI is certainly poised to take a lot of human farming intervention out of the equation — for better and worse.
Most of these companies are compiling their own data sets to identify anything that might block the success of their systems. Babylon had already integrated sensor data into its farms to measure heat and humidity, the nutrient content of water, and the amount of light plants receive. Last year, they got a National Science Foundation grant that allowed them to pilot the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off. “Will this plant be healthy tomorrow? Are there things…that the human eye can't see that the plant starts expressing?” says Amandeep Ratte, the company’s head of data science. “If our system can say, Hey, this plant is unhealthy, we can reach out to [users] preemptively about what they’re doing wrong, or is there a disease at the farm?” Ratte says. The earlier the better, to avoid crop failures.
Natural light accounts for 70 percent of Greenswell Growers’ energy use on a sunny day.
Courtesy Greenswell Growers
IALR’s Lowman says that other CEA companies are developing their AI systems to account for the different crops they grow — lettuces come in all shapes and sizes, after all, and each has different growing needs than, for example, tomatoes. The ways they run their operations differs also. Babylon is unusual in its decentralized structure. But centralized growing systems with one main location have variabilities, too. AeroFarms, which recently declared bankruptcy but will continue to run its 140,000-square foot vertical operation in Danville, Virginia, is entirely enclosed and reliant on the intense violet glow of grow lights to produce microgreens.
Different companies have different data needs. What data is essential to AeroFarms isn’t quite the same as for Greenswell Growers located in Goochland County, Virginia. Raising four kinds of lettuce in a 77,000-square-foot automated hydroponic greenhouse, the vagaries of naturally available light, which accounts for 70 percent of Greenswell’s energy use on a sunny day, affect operations. Their tech needs to account for “outside weather impacts,” says president Carl Gupton. “What adjustments do we have to make inside of the greenhouse to offset what's going on outside environmentally, to give that plant optimal conditions? When it's 85 percent humidity outside, the system needs to do X, Y and Z to get the conditions that we want inside.”
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen.
Nevertheless, every CEA system has the same core needs — consistent yield of high quality crops to keep up year-round supply to customers. Additionally, “Everybody’s got the same set of problems,” Gupton says. Pests may come into a facility with seeds. A disease called pythium, one of the most common in CEA, can damage plant roots. “Then you have root disease pressures that can also come internally — a change in [growing] substrate can change the way the plant performs,” Gupton says.
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen. So, while companies amass their own hyper-specific data sets, Lowman foresees a time within the next decade “when there will be some type of [open-source] database that has the most common types of plant stress identified” that growers will be able to tap into. Such databases will “create a community and move the science forward,” says Lowman.
In fact, IALR is working on assembling images for just such a database now. On so-called “smart tables” inside an Institute lab, a team is growing greens and subjects them to various stressors. Then, they’re administering treatments while taking images of every plant every 15 minutes, says Lowman. Some experiments generate 80,000 images; the challenge lies in analyzing and annotating the vast trove of them, marking each one to reflect outcome—for example increasing the phosphate delivery and the plant’s response to it. Eventually, they’ll be fed into AI systems to help them learn.
For all the enthusiasm surrounding this technology, it’s not without downsides. Training just one AI system can emit over 250,000 pounds of carbon dioxide, according to MIT Technology Review. AI could also be used “to enhance environmental benefit for CEA and optimize [its] energy consumption,” says Rozita Dara, a computer science professor at the University of Guelph in Canada, specializing in AI and data governance, “but we first need to collect data to measure [it].”
The chef-farmers can choose from 45 types of herb and leafy-greens seeds.
Courtesy Babylon Micro-Farms
Any system connected to the Internet of Things is also vulnerable to hacking; if CEA grows to the point where “there are many of these similar farms, and you're depending on feeding a population based on those, it would be quite scary,” Dara says. And there are privacy concerns, too, in systems where imaging is happening constantly. It’s partly for this reason, says Babylon’s Ratte, that the company’s in-farm cameras all “face down into the trays, so the only thing [visible] is pictures of plants.”
Tweaks to improve AI for CEA are happening all the time. Greenswell made its first harvest in 2022 and now has annual data points they can use to start making more intelligent choices about how to feed, water, and supply light to plants, says Gupton. Ratte says he’s confident Babylon’s system can already “get our customers reliable harvests. But in terms of how far we have to go, it's a different problem,” he says. For example, if AI could detect whether the farm is mostly empty—meaning the farm’s user hasn’t planted a new crop of greens—it can alert Babylon to check “what's going on with engagement with this user?” Ratte says. “Do they need more training? Did the main person responsible for the farm quit?”
Lowman says more automation is coming, offering greater ability for systems to identify problems and mitigate them on the spot. “We still have to develop datasets that are specific, so you can have a very clear control plan, [because] artificial intelligence is only as smart as what we tell it, and in plant science, there's so much variation,” he says. He believes AI’s next level will be “looking at those first early days of plant growth: when the seed germinates, how fast it germinates, what it looks like when it germinates.” Imaging all that and pairing it with AI, “can be a really powerful tool, for sure.”
Researchers from the University of Cambridge have laid the foundations for growing synthetic embryos that could develop a beating heart, gut and brain.
The organoid revolution
In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.
Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.
For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.
For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells.
By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.
Synthetic embryos
Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.
Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.
As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.
“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”
If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
