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.
Brain inflammation from Alzheimer's disease.
Alzheimer's is a terrible disease that robs a person of their personality and memory before eventually leading to death. It's the sixth-largest killer in the U.S. and, currently, there are 5.8 million Americans living with the disease.
Wang's vaccine is a significant improvement over previous attempts because it can attack the Alzheimer's protein without creating any adverse side effects.
It devastates people and families and it's estimated that Alzheimer's and other forms of dementia will cost the U.S. $290 billion dollars this year alone. It's estimated that it will become a trillion-dollar-a-year disease by 2050.
There have been over 200 unsuccessful attempts to find a cure for the disease and the clinical trial termination rate is 98 percent.
Alzheimer's is caused by plaque deposits that develop in brain tissue that become toxic to brain cells. One of the major hurdles to finding a cure for the disease is that it's impossible to clear out the deposits from the tissue. So scientists have turned their attention to early detection and prevention.
One very encouraging development has come out of the work done by Dr. Chang Yi Wang, PhD. Wang is a prolific bio-inventor; one of her biggest successes is developing a foot-and-mouth vaccine for pigs that has been administered more than three billion times.
Mei Mei Hu
Brainstorm Health / Flickr.
In January, United Neuroscience, a biotech company founded by Yi, her daughter Mei Mei Hu, and son-in-law, Louis Reese, announced the first results from a phase IIa clinical trial on UB-311, an Alzheimer's vaccine.
The vaccine has synthetic versions of amino acid chains that trigger antibodies to attack Alzheimer's protein the blood. Wang's vaccine is a significant improvement over previous attempts because it can attack the Alzheimer's protein without creating any adverse side effects.
"We were able to generate some antibodies in all patients, which is unusual for vaccines," Yi told Wired. "We're talking about almost a 100 percent response rate. So far, we have seen an improvement in three out of three measurements of cognitive performance for patients with mild Alzheimer's disease."
The researchers also claim it can delay the onset of the disease by five years. While this would be a godsend for people with the disease and their families, according to Elle, it could also save Medicare and Medicaid more than $220 billion.
"You'd want to see larger numbers, but this looks like a beneficial treatment," James Brown, director of the Aston University Research Centre for Healthy Ageing, told Wired. "This looks like a silver bullet that can arrest or improve symptoms and, if it passes the next phase, it could be the best chance we've got."
"A word of caution is that it's a small study," says Drew Holzapfel, acting president of the nonprofit UsAgainstAlzheimer's, said according to Elle. "But the initial data is compelling."
The company is now working on its next clinical trial of the vaccine and while hopes are high, so is the pressure. The company has already invested $100 million developing its vaccine platform. According to Reese, the company's ultimate goal is to create a host of vaccines that will be administered to protect people from chronic illness.
"We have a 50-year vision -- to immuno-sculpt people against chronic illness and chronic aging with vaccines as prolific as vaccines for infectious diseases," he told Elle.
[Editor's Note: This article was originally published by Upworthy here and has been republished with permission.]
