Katalin Karikó, pictured, and Drew Weissman won the Nobel Prize for advances in mRNA research that led to the first Covid vaccines.
When Drew Weissman received a call from Katalin Karikó in the early morning hours this past Monday, he assumed his longtime research partner was calling to share a nascent, nagging idea. Weissman, a professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, and Karikó, a professor at Szeged University and an adjunct professor at UPenn, both struggle with sleep disturbances. Thus, middle-of-the-night discourses between the two, often over email, has been a staple of their friendship. But this time, Karikó had something more pressing and exciting to share: They had won the 2023 Nobel Prize in Physiology or Medicine.
The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
The larvae of adult black soldier flies can turn food waste into sustainable protein with minimal methane gas emissions.
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."
