Scientists Attempt to Make Human Cells Resistant to Coronaviruses and Ebola
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.
Under the electronic microscope, the Ebola particles looked like tiny round bubbles floating inside human cells. Except these Ebola particles couldn't get free from their confinement.
They were trapped inside their bubbles, unable to release their RNA into the human cells to start replicating. These cells stopped the Ebola infection. And they did it on their own, without any medications, albeit in a petri dish of immunologist Adam Lacy-Hulbert. He studies how cells fight infections at the Benaroya Research Institute in Seattle, Washington.
These weren't just any ordinary human cells. They had a specific gene turned on—namely CD74, which typically wouldn't be on. Lacy-Hulbert's team was experimenting with turning various genes on and off to see what made cells fight viral infections better. One particular form of the CD74 gene did the trick. Normally, the Ebola particles would use the cells' own proteases—enzymes that are often called "molecular scissors" because they slice proteins—to cut the bubbles open. But CD74 produced a protein that blocked the scissors from cutting the bubbles, leaving Ebola trapped.
"When that gene turns on, it makes the protein that interferes with Ebola replication," Lacy-Hulbert says. "The protein binds to those molecular scissors and stops them from working." Even better, the protein interfered with coronaviruses too, including SARS-CoV-2, as the team published in the journal Science.
This begs the question: If one can turn on cells' viral resistance in a lab, can this be done in a human body so we that we can better fight Ebola, coronaviruses and other viral scourges?
Recent research indeed shows that our ability to fight viral infections is written in our genes. Genetic variability is at least one reason why some coronavirus-infected people don't develop symptoms while others stay on ventilators for weeks—often due to the aberrant response of their immune system, which went on overdrive to kill the pathogen. But if cells activate certain genes early in the infection, they might successfully stop viruses from replicating before the immune system spirals out of control.
"If my father who is 70 years old tests positive, I would recommend he takes interferon as early as possible."
When we talk about fighting infections, we tend to think in terms of highly specialized immune system cells—B-cells that release antibodies and T-cells that stimulate inflammatory responses, says Lacy-Hulbert. But all other cells in the body have the ability to fight infections too via different means. When cells detect the presence of a pathogen, they release interferons—small protein molecules named so because they set off a genetic chain reaction that interferes with viral replication. These molecules work as alarm signals to other cells around them. The neighboring cells transduce these signals inside themselves and turn on genes responsible for cellular defenses.
"There are at least 300 to 400 genes that are stimulated by type I interferons," says professor Jean-Laurent Casanova at Rockefeller University.
Scientists don't yet know exactly what all of these genes do, but they change the molecular behavior of the cells. "The cells go into a dramatic change and start producing hundreds of proteins that interfere with viral replication on the inside," explains Qian Zhang, a researcher at Casanova's lab. "Some block the proteins the virus needs and some physically tether the virus."
Some cells produce only small amount of interferon, enough to alert their neighbors. Others, such microphages and monocytes, whose jobs are to detect foreign invaders, produce a lot, injecting interferons into the blood to sound the alarm throughout the body. "They are professional cells so their jobs [are] to detect a viral or bacterial infection," Zhang explains.
People with impaired interferon responses are more vulnerable to infections, including influenza and coronaviruses. In two recent studies published in the journal Science, Casanova, Zhang and their colleagues found that patients who lacked a certain type of interferon had more severe Covid-19 symptoms and some died from it. The team ran a genetic comparison of blood samples from patients hospitalized with severe coronavirus cases against those with the asymptomatic infections.
They found that people with severe disease had rare variants in the 13 genes responsible for interferon production. More than three percent of them had a genetic mutation resulting in non-functioning genes. And over ten percent had an autoimmune condition, in which misguided antibodies neutralized their interferons, dampening their bodies' defenses—and these patients were predominantly men. These discoveries help explain why some young and seemingly healthy individuals require life support, while others have mild symptoms or none. The findings also offer ways of stimulating cellular resistance.
A New Frontier in the Making
The idea of making human cells genetically resistant to infections—and possibly other stressors like cancer or aging—has been considered before. It is the concept behind the Genome Project-write or GP-write project, which aims to create "ultra-safe" versions of human cells that resist a variety of pathogens by way of "recoding" or rewriting the cells' genes.
To build proteins, cells use combinations of three DNA bases called codons to represent amino acids—the proteins' building blocks. But biologists find that many of the codons are redundant so if they were removed from all genes, the human cells would still make all their proteins. However, the viruses, whose genes would still include these eliminated redundant codons, would no longer successfully be able to replicate inside human cells.
In 2016, the GP-Write team successfully reduced the number of Escherichia coli's codons from 64 to 57. Recoding genes in all human cells would be harder, but some recoded cells may be transplanted into the body, says Harvard Medical School geneticist George Church, the GP-Write core founding member.
"You can recode a subset of the body, such as all of your blood," he says. "You can also grow an organ inside a recoded pig and transplant it."
Church adds that these methods are still in stages that are too early to help us with this pandemic.
LeapsMag exclusively interviewed Church in 2019 about his latest progress with DNA recoding:
The Push for Clinical Trials
In the meantime, interferons may prove an easier medicine. Lacy-Hulbert thinks that interferon gamma might play a role in activating the CD74 gene, which gums up the molecular scissors. There also may be other ways to activate that gene. "So we are now thinking, can we develop a drug that mimics that actual activity?" he says.
Some interferons are already manufactured and used for treating certain diseases, including multiple sclerosis. Theoretically, nothing prevents doctors from prescribing interferons to Covid patients, but it must be done in the early stages of infection—to stimulate genes that trigger cellular defenses before the virus invades too many cells and before the immune systems mobilizes its big guns.
"If my father who is 70 years old tests positive, I would recommend he takes interferon as early as possible," says Zhang. But to make it a mainstream practice, doctors need clear prescription guidelines. "What would really help doctors make these decisions is clinical trials," says Casanova, so that such guidelines can be established. "We are now starting to push for clinical trials," he adds.
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.
If you were one of the millions who masked up, washed your hands thoroughly and socially distanced, pat yourself on the back—you may have helped change the course of human history.
Scientists say that thanks to these safety precautions, which were introduced in early 2020 as a way to stop transmission of the novel COVID-19 virus, a strain of influenza has been completely eliminated. This marks the first time in human history that a virus has been wiped out through non-pharmaceutical interventions, such as vaccines.
The flu shot, explained
Influenza viruses type A and B are responsible for the majority of human illnesses and the flu season.
Centers for Disease Control
For more than a decade, flu shots have protected against two types of the influenza virus–type A and type B. While there are four different strains of influenza in existence (A, B, C, and D), only strains A, B, and C are capable of infecting humans, and only A and B cause pandemics. In other words, if you catch the flu during flu season, you’re most likely sick with flu type A or B.
Flu vaccines contain inactivated—or dead—influenza virus. These inactivated viruses can’t cause sickness in humans, but when administered as part of a vaccine, they teach a person’s immune system to recognize and kill those viruses when they’re encountered in the wild.
Each spring, a panel of experts gives a recommendation to the US Food and Drug Administration on which strains of each flu type to include in that year’s flu vaccine, depending on what surveillance data says is circulating and what they believe is likely to cause the most illness during the upcoming flu season. For the past decade, Americans have had access to vaccines that provide protection against two strains of influenza A and two lineages of influenza B, known as the Victoria lineage and the Yamagata lineage. But this year, the seasonal flu shot won’t include the Yamagata strain, because the Yamagata strain is no longer circulating among humans.
How Yamagata Disappeared
Flu surveillance data from the Global Initiative on Sharing All Influenza Data (GISAID) shows that the Yamagata lineage of flu type B has not been sequenced since April 2020.
Nature
Experts believe that the Yamagata lineage had already been in decline before the pandemic hit, likely because the strain was naturally less capable of infecting large numbers of people compared to the other strains. When the COVID-19 pandemic hit, the resulting safety precautions such as social distancing, isolating, hand-washing, and masking were enough to drive the virus into extinction completely.
Because the strain hasn’t been circulating since 2020, the FDA elected to remove the Yamagata strain from the seasonal flu vaccine. This will mark the first time since 2012 that the annual flu shot will be trivalent (three-component) rather than quadrivalent (four-component).
Should I still get the flu shot?
The flu shot will protect against fewer strains this year—but that doesn’t mean we should skip it. Influenza places a substantial health burden on the United States every year, responsible for hundreds of thousands of hospitalizations and tens of thousands of deaths. The flu shot has been shown to prevent millions of illnesses each year (more than six million during the 2022-2023 season). And while it’s still possible to catch the flu after getting the flu shot, studies show that people are far less likely to be hospitalized or die when they’re vaccinated.
Another unexpected benefit of dropping the Yamagata strain from the seasonal vaccine? This will possibly make production of the flu vaccine faster, and enable manufacturers to make more vaccines, helping countries who have a flu vaccine shortage and potentially saving millions more lives.
After his grandmother’s dementia diagnosis, one man invented a snack to keep her healthy and hydrated.
On a visit to his grandmother’s nursing home in 2016, college student Lewis Hornby made a shocking discovery: Dehydration is a common (and dangerous) problem among seniors—especially those that are diagnosed with dementia.
Hornby’s grandmother, Pat, had always had difficulty keeping up her water intake as she got older, a common issue with seniors. As we age, our body composition changes, and we naturally hold less water than younger adults or children, so it’s easier to become dehydrated quickly if those fluids aren’t replenished. What’s more, our thirst signals diminish naturally as we age as well—meaning our body is not as good as it once was in letting us know that we need to rehydrate. This often creates a perfect storm that commonly leads to dehydration. In Pat’s case, her dehydration was so severe she nearly died.
When Lewis Hornby visited his grandmother at her nursing home afterward, he learned that dehydration especially affects people with dementia, as they often don’t feel thirst cues at all, or may not recognize how to use cups correctly. But while dementia patients often don’t remember to drink water, it seemed to Hornby that they had less problem remembering to eat, particularly candy.
Where people with dementia often forget to drink water, they're more likely to pick up a colorful snack, Hornby found. alzheimers.org.uk
Hornby wanted to create a solution for elderly people who struggled keeping their fluid intake up. He spent the next eighteen months researching and designing a solution and securing funding for his project. In 2019, Hornby won a sizable grant from the Alzheimer’s Society, a UK-based care and research charity for people with dementia and their caregivers. Together, through the charity’s Accelerator Program, they created a bite-sized, sugar-free, edible jelly drop that looked and tasted like candy. The candy, called Jelly Drops, contained 95% water and electrolytes—important minerals that are often lost during dehydration. The final product launched in 2020—and was an immediate success. The drops were able to provide extra hydration to the elderly, as well as help keep dementia patients safe, since dehydration commonly leads to confusion, hospitalization, and sometimes even death.
Not only did Jelly Drops quickly become a favorite snack among dementia patients in the UK, but they were able to provide an additional boost of hydration to hospital workers during the pandemic. In NHS coronavirus hospital wards, patients infected with the virus were regularly given Jelly Drops to keep their fluid levels normal—and staff members snacked on them as well, since long shifts and personal protective equipment (PPE) they were required to wear often left them feeling parched.
In April 2022, Jelly Drops launched in the United States. The company continues to donate 1% of its profits to help fund Alzheimer’s research.