Sustainable Urban Farming Has a Rising Hot Star: Bugs
In Sydney, Australia, in the basement of an inner-city high-rise, lives a mass of unexpected inhabitants: millions of maggots. The insects are far from unwelcome. They are there to feast on the food waste generated by the building's human residents.
Goterra, the start-up that installed the maggots in the building in December, belongs to the rapidly expanding insect agriculture industry, which is experiencing a surge of investment worldwide.
The maggots – the larvae of the black soldier fly – are voracious, unfussy eaters. As adult flies, they don't eat, so the young fatten up swiftly on whatever they can get. Goterra's basement colony can munch through 5 metric tons of waste in a day.
"Maggots are nature's cleaners," says Bob Gordon, Head of Growth at Goterra. "They're a great tool to manage waste streams."
Their capacity to consume presents a neat response to the problem of food waste, which contributes up to 8% of global greenhouse gas emissions each year as it rots in landfill.
"The maggots eat the food fairly fresh," Gordon says. "So, there's minimal degradation and you don't get those methane emissions."
Alongside their ability to devour waste, the soldier fly larvae hold further agricultural promise: they yield an incredibly efficient protein. After the maggots have binged for about 12 days, Goterra harvests and processes them into a protein-rich livestock feed. Their excrement, known as frass, is also collected and turned into soil conditioner.
"We are producing protein in a basement," says Gordon. "It's urban farming – really sustainable, urban farming."
Goterra's module in the basement at Barangaroo, Sydney.
Supplied by Goterra
Goterra's founder Olympia Yarger started producing the insects in "buckets in her backyard" in 2016. Today, Goterra has a large-scale processing plant and has developed proprietary modules – in shipping containers – that use robotics to manage the larvae.
The modules have been installed on site at municipal buildings, hospitals, supermarkets, several McDonald's restaurants, and a range of smaller enterprises in Australia. Users pay a subscription fee and simply pour in the waste; Goterra visits once a fortnight to harvest the bugs.
Insect agriculture is well established outside of the West, and the practice is gaining traction around the world. China has mega-facilities that can process hundreds of tons of waste in a day. In Kenya, a program recently trained 2000 farmers in soldier fly farming to boost their economic security. French biotech company InnovaFeed, in partnership with US agricultural heavyweight ADM, plans to build "the world's largest insect protein facility" in Illinois this year.
"The [maggots] are science fiction on earth. Watching them work is awe-inspiring."
But the concept is still not to everyone's taste.
"This is still a topic that I say is a bit like black liquorice – people tend to either really like it or really don't," says Wendy Lu McGill, Communications Director at the North American Coalition of Insect Agriculture (NACIA).
Formed in 2016, NACIA now has over 100 members – including researchers and commercial producers of black soldier flies, meal worms and crickets.
McGill says there have been a few iterations of insect agriculture in the US – beginning with worms produced for bait after World War II then shifting to food for exotic pets. The current focus – "insects as food and feed" – took root about a decade ago, with the establishment of the first commercial farms for this purpose.
"We're starting to see more expansion in the U.S. and a lot of the larger investments have been for black soldier fly producers," McGill says. "They tend to have larger facilities and the animal feed market they're looking at is potentially quite large."
InnovaFeed's Illinois facility is set to produce 60,000 metric tons of animal feed protein per year.
"They'll be trying to employ many different circular principles," McGill says of the project. "For example, the heat from the feed factory – the excess heat that would normally just be vented – will be used to heat the other side that's raising the black soldier fly."
Although commercial applications have started to flourish recently, scientific knowledge of the black soldier fly's potential has existed for decades.
Dr. Jeffery Tomberlin, an entomologist at Texas A&M University, has been studying the insect for over 20 years, contributing to key technologies used in the industry. He also founded Evo, a black soldier fly company in Texas, which feeds its larvae the waste from a local bakery and distillery.
"They are science fiction on earth," he says of the maggots. "Watching them work is awe-inspiring."
Tomberlin says fly farms can work effectively at different scales, and present possibilities for non-Western countries to shift towards "commodity independence."
"You don't have to have millions of dollars invested to be successful in producing this insect," he says. "[A farm] can be as simple as an open barn along the equator to a 30,000 square-foot indoor facility in the Netherlands."
As the world's population balloons, food insecurity is an increasing concern. By 2050, the UN predicts that to feed our projected population we will need to ramp up food production by at least 60%. Insect agriculture, which uses very little land and water compared to traditional livestock farming, could play a key role.
Insects may become more common human food, but the current commercial focus is animal feed. Aquaculture is a key market, with insects presenting an alternative to fish meal derived from over-exploited stocks. Insect meal is also increasingly popular in pet food, particularly in Europe.
While recent investment has been strong – NACIA says 2020 was the best year yet – reaching a scale that can match existing agricultural industries and providing a competitive price point are still hurdles for insect agriculture.
But COVID-19 has strengthened the argument for new agricultural approaches, such as the decentralized, indoor systems and circular principles employed by insect farms.
"This has given the world a preview – which no one wanted – of [future] supply chain disruptions," says McGill.
As the industry works to meet demand, Tomberlin predicts diversification and product innovation: "I think food science is going to play a big part in that. They can take an insect and create ice cream." (Dried soldier fly larvae "taste kind of like popcorn," if you were wondering.)
Tomberlin says the insects could even become an interplanetary protein source: "I do believe in that. I mean, if we're going to colonize other planets, we need to be sustainable."
But he issues a word of caution about the industry growing too big, too fast: "I think we as an industry need to be very careful of how we harness and apply [our knowledge]. The black soldier fly is considered the crown jewel today, but if it's mismanaged, it can be relegated back to a past."
Goterra's Gordon also warns against rushing into mass production: "If you're just replacing big intensive animal agriculture with big intensive animal agriculture with more efficient animals, then what's the change you're really effecting?"
But he expects the industry will continue its rise though the next decade, and Goterra – fuelled by recent $8 million Series A funding – plans to expand internationally this year.
"Within 10 years' time, I would like to see the vast majority of our unavoidable food waste being used to produce maggots to go into a protein application," Gordon says.
"There's no lack of demand. And there's no lack of food waste."
Three Big Biotech Ideas to Watch in 2020—And Beyond
1. Happening Now: Body-on-a-Chip Technology Is Enabling Safer Drug Trials and Better Cancer Research
Researchers have increasingly used the technology known as "lab-on-a-chip" or "organ-on-a-chip" to test the effects of pharmaceuticals, toxins, and chemicals on humans. Rather than testing on animals, which raises ethical concerns and can sometimes be inaccurate, and human-based clinical trials, which can be expensive and difficult to iterate, scientists turn to tiny, micro-engineered chips—about the size of a thumb drive.
It's possible that doctors could one day take individual cell samples and create personalized treatments, testing out any medications on the chip.
The chips are lined with living samples of human cells, which mimic the physiology and mechanical forces experienced by cells inside the human body, down to blood flow and breathing motions; the functions of organs ranging from kidneys and lungs to skin, eyes, and the blood-brain barrier.
A more recent—and potentially even more useful—development takes organ-on-a-chip technology to the next level by integrating several chips into a "body-on-a-chip." Since human organs don't work in isolation, seeing how they all react—and interact—once a foreign element has been introduced can be crucial to understanding how a certain treatment will or won't perform. Dr. Shyni Varghese, a MEDx investigator at the Duke University School of Medicine, is one of the researchers working with these systems in order to gain a more nuanced understanding of how multiple different organs react to the same stimuli.
Her lab is working on "tumor-on-a-chip" models, which can not only show the progression and treatment of cancer, but also model how other organs would react to immunotherapy and other drugs. "The effect of drugs on different organs can be tested to identify potential side effects," Varghese says. In addition, these models can help the researchers figure out how cancers grow and spread, as well as how to effectively encourage immune cells to move in and attack a tumor.
One body-on-a-chip used by Dr. Varghese's lab tracks the interactions of five organs—brain, heart, liver, muscle, and bone.
As their research progresses, Varghese and her team are looking for ways to maintain the long-term function of the engineered organs. In addition, she notes that this kind of research is not just useful for generalized testing; "organ-on-chip technologies allow patient-specific analyses, which can be used towards a fundamental understanding of disease progression," Varghese says. It's possible that doctors could one day take individual cell samples and create personalized treatments, testing out any medications on the chip for safety, efficacy, and potential side effects before writing a prescription.
2. Happening Soon: Prime Editing Will Have the Power to "Find and Replace" Disease-Causing Genes
Biochemist David Liu made industry-wide news last fall when he and his lab at MIT's Broad Institute, led by Andrew Anzalone, published a paper on prime editing: a new, more focused technology for editing genes. Prime editing is a descendant of the CRISPR-Cas9 system that researchers have been working with for years, and a cousin to Liu's previous innovation—base editing, which can make a limited number of changes to a single DNA letter at a time.
By contrast, prime editing has the potential to make much larger insertions and deletions; it also doesn't require the tweaked cells to divide in order to write the changes into the DNA, which could make it especially suitable for central nervous system diseases, like Parkinson's.
Crucially, the prime editing technique has a much higher efficiency rate than the older CRISPR system, and a much lower incidence of accidental insertions or deletions, which can make dangerous changes for a patient.
It also has a very broad potential range: according to Liu, 89% of the pathogenic mutations that have been collected in ClinVar (a public archive of human variations) could, in principle, be treated with prime editing—although he is careful to note that correcting a single genetic mutation may not be sufficient to fully treat a genetic disease.
Figuring out just how prime editing can be used most effectively and safely will be a long process, but it's already underway. The same day that Liu and his team posted their paper, they also made the basic prime editing constructs available for researchers around the world through Addgene, a plasmid repository, so that others in the scientific community can test out the technique for themselves. It might be years before human patients will see the results, and in the meantime, significant bioethical questions remain about the limits and sociological effects of such a powerful gene-editing tool. But in the long fight against genetic diseases, it's a huge step forward.
3. Happening When We Fund It: Focusing on Microbiome Health Could Help Us Tackle Social Inequality—And Vice Versa
The past decade has seen a growing awareness of the major role that the microbiome, the microbes present in our digestive tract, play in human health. Having a less-healthy microbiome is correlated with health risks like diabetes and depression, and interventions that target gut health, ranging from kombucha to fecal transplants, have cropped up with increasing frequency.
New research from the University of Maine's Dr. Suzanne Ishaq takes an even broader view, arguing that low-income and disadvantaged populations are less likely to have healthy, diverse gut bacteria, and that increasing access to beneficial microorganisms is an important juncture of social justice and public health.
"Basically, allowing people to lead healthy lives allows them to access and recruit microbes."
"Typically, having a more diverse bacterial community is associated with health, and having fewer different species is associated with illness and may leave you open to infection from bacteria that are good at exploiting opportunities," Ishaq says.
Having a healthy biome doesn't mean meeting one fixed ratio of gut bacteria, since different combinations of microbes can generate roughly similar results when they work in concert. Generally, "good" microbes are the ones that break down fiber and create the byproducts that we use for energy, or ones like lactic acid bacteria that work to make microbials and keep other bacteria in check. The microbial universe in your gut is chaotic, Ishaq says. "Microbes in your gut interact with each other, with you, with your food, or maybe they don't interact at all and pass right through you." Overall, it's tricky to name specific microbial communities that will make or break someone's health.
There are important corollaries between environment and biome health, though, which Ishaq points out: Living in urban environments reduces microbial exposure, and losing the microorganisms that humans typically source from soil and plants can reduce our adaptive immunity and ability to fight off conditions like allergies and asthma. Access to green space within cities can counteract those effects, but in the U.S. that access varies along income, education, and racial lines. Likewise, lower-income communities are more likely to live in food deserts or areas where the cheapest, most convenient food options are monotonous and low in fiber, further reducing microbial diversity.
Ishaq also suggests other areas that would benefit from further study, like the correlation between paid family leave, breastfeeding, and gut microbiota. There are technical and ethical challenges to direct experimentation with human populations—but that's not what Ishaq sees as the main impediment to future research.
"The biggest roadblock is money, and the solution is also money," she says. "Basically, allowing people to lead healthy lives allows them to access and recruit microbes."
That means investment in things we already understand to improve public health, like better education and healthcare, green space, and nutritious food. It also means funding ambitious, interdisciplinary research that will investigate the connections between urban infrastructure, housing policy, social equity, and the millions of microbes keeping us company day in and day out.
Scientists Just Started Testing a New Class of Drugs to Slow--and Even Reverse--Aging
Imagine reversing the processes of aging. It's an age-old quest, and now a study from the Mayo Clinic may be the first ray of light in the dawn of that new era.
The immune system can handle a certain amount of senescence, but that capacity declines with age.
The small preliminary report, just nine patients, primarily looked at the safety and tolerability of the compounds used. But it also showed that a new class of small molecules called senolytics, which has proven to reverse markers of aging in animal studies, can work in humans.
Aging is a relentless assault of chronic diseases including Alzheimer's, cardiovascular disease, diabetes, and frailty. Developing one chronic condition strongly predicts the rapid onset of another. They pile on top of each other and impede the body's ability to respond to the next challenge.
"Potentially, by targeting fundamental aging processes, it may be possible to delay or prevent or alleviate multiple age-related conditions and many diseases as a group, instead of one at a time," says James Kirkland, the Mayo Clinic physician who led the study and is a top researcher in the growing field of geroscience, the biology of aging.
Getting Rid of "Zombie" Cells
One element common to many of the diseases is senescence, a kind of limbo or zombie-like state where cells no longer divide or perform many regular functions, but they don't die. Senescence is thought to be beneficial in that it inhibits the cancerous proliferation of cells. But in aging, the senescent cells still produce molecules that create inflammation both locally and throughout the body. It is a cycle that feeds upon itself, slowly ratcheting down normal body function and health.
Disease and harmful stimuli like radiation to treat cancer can also generate senescence, which is why young cancer patients seem to experience earlier and more rapid aging. The immune system can handle a certain amount of senescence, but that capacity declines with age. There also appears to be a threshold effect, a tipping point where senescence becomes a dominant factor in aging.
Kirkland's team used an artificial intelligence approach called machine learning to look for cell signaling networks that keep senescent cells from dying. To date, researchers have identified at least eight such signaling networks, some of which seem to be unique to a particular type of cell or tissue, but others are shared or overlap.
Then a computer search identified molecules known to disrupt these signaling pathways "and allow cells that are fully senescent to kill themselves," he explains. The process is a bit like looking for the right weapons in a video game to wipe out lingering zombie cells. But instead of swords, guns, and grenades, the list of biological tools so far includes experimental molecules, approved drugs, and natural supplements.
Treatment
"We found early on that targeting single components of those networks will only kill a very small minority of senescent cells or senescent cell types," says Kirkland. "So instead of going after one drug-one target-one disease, we're going after networks with combinations of drugs or drugs that have multiple targets. And we're going after every age-related disease."
The FDA is grappling with guidance for researchers wanting to conduct clinical trials on something as broad as aging rather than a single disease.
The large number of potential senolytic (i.e. zombie-neutralizing) compounds they identified allowed Kirkland to be choosy, "purposefully selecting drugs where the side effects profile was good...and with short elimination half-lives." The hit and run approach meant they didn't have to worry about maintaining a steady state of drugs in the body for an extended period of time. Some of the compounds they selected need only a half hour exposure to trigger the dying process in senescent cells, which can then take several days.
Work in mice has already shown impressive results in reversing diabetes, weight gain, Alzheimer's, cardiovascular disease and other conditions using senolytic agents.
That led to Kirkland's pilot study in humans with diabetes-related kidney disease using a three-day regimen of dasatinib, a kinase inhibitor first approved in 2006 to treat some forms of blood cancer, and quercetin, a flavonoid found in many plants and sold as a food supplement.
The combination was safe and well tolerated; it reduced the number of senescent cells in the belly fat of patients and restored their normal function, according to results published in September in the journal EBioMedicine. This preliminary paper was based on 9 patients in an ongoing study of 30 patients.
Kirkland cautions that these are initial and incomplete findings looking primarily at safety issues, not effectiveness. There is still much to be learned about the use of senolytics, starting with proof that they actually provide clinical benefit, and against what chronic conditions. The drug combinations, doses, duration, and frequency, not to mention potential risks all must be worked out. Additional studies of other diseases are being developed.
What's Next
Ron Kohanski, a senior administrator at the NIH National Institute on Aging (NIA), says the field of senolytics is so new that there isn't even a consensus on how to identify a senescent cell, and the FDA is grappling with guidance for researchers wanting to conduct clinical trials on something as broad as aging rather than a single disease.
Intellectual property concerns may temper the pharmaceutical industry's interest in developing senolytics to treat chronic diseases of aging. It looks like many mix-and-match combinations are possible, and many of the potential molecules identified so far are found in nature or are drugs whose patents have or will soon expire. So the ability to set high prices for such future drugs, and hence the willingness to spend money on expensive clinical trials, may be limited.
Still, Kohanski believes the field can move forward quickly because it often will include products that are already widely used and have a known safety profile. And approaches like Kirkland's hit and run strategy will minimize potential exposure and risk.
He says the NIA is going to support a number of clinical trials using these new approaches. Pharmaceutical companies may feel that they can develop a unique part of a senolytic combination regimen that will justify their investment. And if they don't, countries with socialized medicine may take the lead in supporting such research with the goal of reducing the costs of treating aging patients.