The Women of RNA: Two Award-Winners Share Why They Spent Their Careers Studying DNA's Lesser-Known Cousin
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Joan Steitz (left) and Lynne Maquat (right) were honored with the Wolf Prize in Medicine and the Warren Alpert Foundation Prizer this year for their fundamental work on RNA.
When Lynne Maquat, who leads the Center for RNA Biology at the University of Rochester, became interested in the ribonucleic acid molecule in the 1970s, she was definitely in the minority. The same was true for Joan Steitz, now professor of molecular biophysics and biochemistry at Yale University, who began to study RNA a decade earlier in the 1960s.
"My first RNA experiment was a failure, because we didn't understand how things worked," Steitz recalls. In her first undergraduate experiment, she unwittingly used a lab preparation that destroyed the RNA. "Unknowingly, our preparation contained enzymes that degraded our RNA."
At the time, scientists pursuing genetic research tended to focus on DNA, or deoxyribonucleic acid — and for good reason. It was clear that the enigmatic double-helix ribbon held the answers to organisms' heredity, genetic traits, development, growth and aging. If scientists could decipher the secrets of DNA and understand how its genetic instructions translate into the body's functions in health and disease, they could develop treatments for all kinds of diseases. On the contrary, the prevailing dogma of the time viewed RNA as merely a helper that passively carried out DNA's genetic instructions for protein-making — so it received much less attention.
But Maquat and Steitz weren't interested in heredity. They studied biochemistry and biophysics, so they wanted to understand how RNA functioned on the molecular level — how it carried instructions, catalyzed reactions, and helped build protein bonds, among other things.
"I'm a mechanistic biochemist, so I like to know how things happen," Maquat says. "Once you understand the mechanism, you can think of how to solve problems." And so the quest to understand how RNA does its job became the focus of both women's careers.
"People can now appreciate why some of us studied RNA for such a long time."
Half a century later, in 2021, their RNA work has earned two prestigious recognitions only months from each other. In February, they received the Wolf Prize in Medicine, followed by the Warren Alpert Foundation Prize in May, awarded to scientists whose achievements led to prevention, cure or treatments of human diseases.
It was the development of the COVID-19 vaccines that made RNA a household name. Made by Moderna and Pfizer, the vaccines use the RNA molecule to deliver genetic instructions for making SARS-CoV-2's characteristic spike protein in our cells. The presence of this foreign-looking protein triggers the immune system to attack and remember the pathogen. As the vaccines reached the finish line, RNA took center stage, and it was Maquat's and Steitz's research that helped reveal how these molecular cogwheels drive many biological functions within cells.
If you think of a cell as a kingdom, the DNA plays the role of a queen. Like a monarch in a palace, DNA nestles inside the cell's nucleus issuing instructions needed for the cell to function. But no queen can successfully govern without her court, her messengers, and her soldiers, as well as other players that make her kingdom work. That's what RNAs do — they act as the DNA's vassals. They carry instructions for protein assembly, catalyze reactions and supervise many other processes to make sure the cellular kingdom performs as it should.
There are a myriad of these RNA vassals in our cells, and each type has its own specific task. There are messenger RNAs that deliver genetic instructions for protein synthesis from DNA to ribosomes, the cells' protein-making factories. There are ribosomal RNAs that help stitch together amino acids to make proteins. There are transfer RNAs that can bring amino acids to this protein synthesis machine, keeping it going. Then there are circular RNAs that act as sponges, absorbing proteins to help regulate the activity of genes. And that's only the tip of the iceberg when it comes to RNA diversity, researchers say.
"We know what the most abundant and important RNAs are doing," says Steitz. "But there are thousands of different ones, and we still don't have a full knowledge of them."
Critical to RNA's proper functioning is a process called splicing, in which a precursor mRNA is transformed into mature, fully-functional mRNA — a phenomenon that Steitz's work helped elucidate. The splicing process, which takes place in cellular assembly lines, involves removing extra RNA sequences and stringing the remaining RNA pieces together. Steitz found that tiny RNA particles called snRNPs are crucial to this process. They act as handy helpers, finding and removing errant genetic material from the mRNA molecules.
A dysfunctional RNA assembly line leads to diseases, including many cancers. For instance, Steitz found that people with Lupus — an autoimmune disorder — have antibodies that mistakenly attack the little snRNP helpers. She also discovered that when snRNPs don't do their job properly, they can cause what scientists call mis-splicing, producing defective mRNAs.
Fortunately, cells have a built-in quality-control process that can spot and correct these mistakes, which is what Maquat studied in her work. In 1981, she discovered a molecular quality-control system that spots and destroys such incorrectly assembled mRNA. With the cryptic name "nonsense-mediated mRNA decay" or NMD, this process is vital to the health and wellbeing of a cellular kingdom in humans — because splicing mistakes happen far more often than one would imagine.
"We estimate that about a third of our mRNA are mistakes," Maquat says. "And nonsense-mediated mRNA decay cleans up these mistakes." When this quality-control system malfunctions, defective mRNA forge faulty proteins, which mess up the cellular machinery and cause disease, including various forms of cancer.
Scientists' newfound appreciation of RNA opens door to many novel treatments.
Now that the first RNA-based shots were approved, the same principle can be used for create vaccines for other diseases, the two RNA researchers say. Moreover, the molecule has an even greater potential — it can serve as a therapeutic target for other disorders. For example, Spinraza, a groundbreaking drug approved in 2016 for spinal muscular atrophy, uses small snippets of synthetic genetic material that bind to the RNA, helping fix splicing errors. "People can now appreciate why some of us studied RNA for such a long time," says Maquat.
Steitz is thrilled that the entire field of RNA research is enjoying the limelight. "I'm delighted because the prize is more of a recognition of the field than just our work," she says. "This is a more general acknowledgment of how basic research can have a remarkable impact on human health."
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Chicken that is grown entirely in a laboratory, without harming a single bird, could be sold in supermarkets in the coming months. But critics say the doubts about lab-grown meat have not been appropriately explored.
Last November, when the U.S. Food and Drug Administration disclosed that chicken from a California firm called UPSIDE Foods did not raise safety concerns, it drily upended how humans have obtained animal protein for thousands of generations.
“The FDA is ready to work with additional firms developing cultured animal cell food and production processes to ensure their food is safe and lawful,” the agency said in a statement at the time.
Assuming UPSIDE obtains clearances from the U.S. Department of Agriculture, its chicken – grown entirely in a laboratory without harming a single bird – could be sold in supermarkets in the coming months.
“Ultimately, we want our products to be available everywhere meat is sold, including retail and food service channels,” a company spokesperson said. The upscale French restaurant Atelier Crenn in San Francisco will have UPSIDE chicken on its menu once it is approved, she added.
Known as lab-grown or cultured meat, a product such as UPSIDE’s is created using stem cells and other tissue obtained from a chicken, cow or other livestock. Those cells are then multiplied in a nutrient-dense environment, usually in conjunction with a “scaffold” of plant-based materials or gelatin to give them a familiar form, such as a chicken breast or a ribeye steak. A Dutch company called Mosa Meat claims it can produce 80,000 hamburgers derived from a cluster of tissue the size of a sesame seed.
Critics say the doubts about lab-grown meat and the possibility it could merge “Brave New World” with “The Jungle” and “Soylent Green” have not been appropriately explored.
That’s a far cry from when it took months of work to create the first lab-grown hamburger a decade ago. That minuscule patty – which did not contain any fat and was literally plucked from a Petri dish to go into a frying pan – cost about $325,000 to produce.
Just a decade later, an Israeli company called Future Meat said it can produce lab-grown meat for about $1.70 per pound. It plans to open a production facility in the U.S. sometime in 2023 and distribute its products under the brand name “Believer.”
Costs for production have sunk so low that researchers at Carnegie Mellon University in Pittsburgh expect sometime in early 2024 to produce lab-grown Wagyu steak to showcase the viability of growing high-end cuts of beef cheaply. The Carnegie Mellon team is producing its Wagyu using a consumer 3-D printer bought secondhand on eBay and modified to print the highly marbled flesh using a method developed by the university. The device costs $200 – about the same as a pound of Wagyu in the U.S. The initiative’s modest five-figure budget was successfully crowdfunded last year.
“The big cost is going to be the cells (which are being extracted by a cow somewhere in Pennsylvania), but otherwise printing doesn’t add much to the process,” said Rosalyn Abbott, a Carnegie Mellon assistant professor of bioengineering who is co-leader on the project. “But it adds value, unlike doing this with ground meat.”
Lab-Grown Meat’s Promise
Proponents of lab-grown meat say it will cut down on traditional agriculture, which has been a leading contributor to deforestation, water shortages and contaminated waterways from animal waste, as well as climate change.
An Oxford University study from 2011 concludes lab-grown meat could have greenhouse emissions 96 percent lower compared to traditionally raised livestock. Moreover, proponents of lab-grown meat claim that the suffering of animals would decline dramatically, as they would no longer need to be warehoused and slaughtered. A recently opened 26-story high-rise in China dedicated to the raising and slaughtering of pigs illustrates the current plight of livestock in stark terms.
Scientists may even learn how to tweak lab-grown meat to make it more nutritious. Natural red meat is high in saturated fat and, if it’s eaten too often, can lead to chronic diseases. In lab versions, the saturated fat could be swapped for healthier, omega-3 fatty acids.
But critics say the doubts about lab-grown meat and the possibility it could merge “Brave New World” with “The Jungle” and “Soylent Green” have not been appropriately explored.
A Slippery Slope?
Some academics who have studied the moral and ethical issues surrounding lab-grown meat believe it will have a tough path ahead gaining acceptance by consumers. Should it actually succeed in gaining acceptance, many ethical questions must be answered.
“People might be interested” in lab-grown meat, perhaps as a curiosity, said Carlos Alvaro, an associate professor of philosophy at the New York City College of Technology, part of the City University of New York. But the allure of traditionally sourced meat has been baked – or perhaps grilled – into people’s minds for so long that they may not want to make the switch. Plant-based meat provides a recent example of the uphill battle involved in changing old food habits, with Beyond Meat’s stock prices dipping nearly 80 percent in 2022.
"There are many studies showing that people don’t really care about the environment (to that extent)," Alvaro said. "So I don’t know how you would convince people to do this because of the environment.”
“From my research, I understand that the taste (of lab-grown meat) is not quite there,” Alvaro said, noting that the amino acids, sugars and other nutrients required to grow cultivated meat do not mimic what livestock are fed. He also observed that the multiplication of cells as part of the process “really mimic cancer cells” in the way they grow, another off-putting thought for would-be consumers of the product.
Alvaro is also convinced the public will not buy into any argument that lab-grown meat is more environmentally friendly.
“If people care about the environment, they either try and consume considerably less meat and other animal products, or they go vegan or vegetarian,” he said. “But there are many studies showing that people don’t really care about the environment (to that extent). So I don’t know how you would convince people to do this because of the environment.”
Ben Bramble, a professor at Australian National University who previously held posts at Princeton and Trinity College in Ireland, takes a slightly different tack. He noted that “if lab-grown meat becomes cheaper, healthier, or tastier than regular meat, there will be a large market for it. If it becomes all of these things, it will dominate the market.”
However, Bramble has misgivings about that occurring. He believes a smooth transition from traditionally sourced meat to a lab-grown version would allow humans to elide over the decades of animal cruelty perpetrated by large-scale agriculture, without fully reckoning with and learning from this injustice.
“My fear is that if we all switch over to lab-grown meat because it has become cheaper, healthier, or tastier than regular meat, we might never come to realize what we have done, and the terrible things we are capable of,” he said. “This would be a catastrophe.”
Bramble’s writings about cultured meat also raise some serious moral conundrums. If, for example, animal meat may be cultivated without killing animals, why not create products from human protein?
Actually, that’s already happened.
It occurred in 2019, when Orkan Telhan, a professor of fine arts at the University of Pennsylvania, collaborated with two scientists to create an art exhibit at the Philadelphia Museum of Art on the future of foodstuffs.
Although the exhibit included bioengineered bread and genetically modified salmon, it was an installation called “Ouroboros Steak” that drew the most attention. That was comprised of pieces of human flesh grown in a lab from cultivated cells and expired blood products obtained from online sources.
The exhibit was presented as four tiny morsels of red meat – shaped in patterns suggesting an ouroboros, a dragon eating its own tail. They were placed in tiny individual saucers atop a larger plate and placemat with a calico pattern, suggesting an item to order in a diner. The artwork drew international headlines – as well as condemnation for Telhan’s vision.
Telhan’s artwork is intended to critique the overarching assumption that lab-grown meat will eventually replace more traditional production methods, as well as the lack of transparency surrounding many processed foodstuffs. “They think that this problem (from industrial-scale agriculture) is going be solved by this new technology,” Telhan said. “I am critical (of) that perspective.”
Unlike Bramble, Telhan is not against lab-grown meat, so long as its producers are transparent about the sourcing of materials and its cultivation. But he believes that large-scale agricultural meat production – which dates back centuries – is not going to be replaced so quickly.
“We see this again and again with different industries, like algae-based fuels. A lot of companies were excited about this, and promoted it,” Telhan said. “And years later, we know these fuels work. But to be able to displace the oil industry means building the infrastructure to scale takes billions of dollars, and nobody has the patience or money to do it.”
Alvaro concurred on this point, which he believes is already weakened because a large swath of consumers aren’t concerned about environmental degradation.
“They’re going to have to sell this big, but in order to convince people to do so, they have to convince them to eat this product instead of regular meat,” Alvaro said.
Hidden Tweaks?
Moreover, if lab-based meat does obtain a significant market share, Telhan suggested companies may do things to the product – such as to genetically modify it to become more profitable – and never notify consumers. That is a particular concern in the U.S., where regulations regarding such modifications are vastly more relaxed than in the European Union.
“I think that they have really good objectives, and they aspire to good objectives,” Telhan said. “But the system itself doesn't really allow for that much transparency.”
No matter what the future holds, sometime next year Carnegie Mellon is expected to hold a press conference announcing it has produced a cut of the world’s most expensive beef with the help of a modified piece of consumer electronics. It will likely take place at around the same time UPSIDE chicken will be available for purchase in supermarkets and restaurants, pending the USDA’s approvals.
Abbott, the Carnegie Mellon professor, suggested the future event will be both informative and celebratory.
“I think Carnegie Mellon would have someone potentially cook it for us,” she said. “Like have a really good chef in New York City do it.”
In this week's Friday Five, breathing this way may cut down on anxiety, a fasting regimen that could make you sick, this type of job makes men more virile, 3D printed hearts could save your life, and the role of metformin in preventing dementia.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.