Joined: 10-21-2000 Posts: 55,453 |
Speyside2 wrote:https://www.nature.com/articles/d41586-021-02483-w
This is a pretty good history of MRNA. Anyone who thinks Malone is the one to believe might want to read this article in it's entirety. I'll leave it at that. Whew, they sure mentioned him a whole lot in that article. In late 1987, Robert Malone performed a landmark experiment. He mixed strands of messenger RNA with droplets of fat, to create a kind of molecular stew. Human cells bathed in this genetic gumbo absorbed the mRNA, and began producing proteins from itRealizing that this discovery might have far-reaching potential in medicine, Malone, a graduate student at the Salk Institute for Biological Studies in La Jolla, California, later jotted down some notes, which he signed and dated. If cells could create proteins from mRNA delivered into them, he wrote on 11 January 1988, it might be possible to “treat RNA as a drug”. Another member of the Salk lab signed the notes, too, for posterity. Later that year, Malone’s experiments showed that frog embryos absorbed such mRNA. It was the first time anyone had used fatty droplets to ease mRNA’s passage into a living organism.But the path to success was not direct. For many years after Malone’s experiments, which themselves had drawn on the work of other researchers, mRNA was seen as too unstable and expensive to be used as a drug or a vaccine. Dozens of academic labs and companies worked on the idea, struggling with finding the right formula of fats and nucleic acids — the building blocks of mRNA vaccines.Today’s mRNA jabs have innovations that were invented years after Malone’s time in the lab, including chemically modified RNA and different types of fat bubble to ferry them into cells (see ‘Inside an mRNA COVID vaccine’). Still, Malone, who calls himself the “inventor of mRNA vaccines”, thinks his work hasn’t been given enough credit. “I’ve been written out of history,” he told Nature.Malone’s experiments didn’t come out of the blue. As far back as 1978, scientists had used fatty membrane structures called liposomes to transport mRNA into mouse3 and human4 cells to induce protein expression. The liposomes packaged and protected the mRNA and then fused with cell membranes to deliver the genetic material into cells. These experiments themselves built on years of work with liposomes and with mRNA; both were discovered in the 1960s (see ‘The history of mRNA vaccines’).Years later, Malone followed the Harvard team’s tactics to synthesize mRNA for his experiments. But he added a new kind of liposome, one that carried a positive charge, which enhanced the material’s ability to engage with the negatively charged backbone of mRNA. These liposomes were developed by Philip Felgner, a biochemist who now leads the Vaccine Research and Development Center at the University of California, Irvine.Despite his success using the liposomes to deliver mRNA into human cells and frog embryos, Malone never earned a PhD. He fell out with his supervisor, Salk gene-therapy researcher Inder Verma and, in 1989, left graduate studies early to work for Felgner at Vical, a recently formed start-up in San Diego, California. There, they and collaborators at the University of Wisconsin–Madison showed that the lipid–mRNA complexes could spur protein production in mice7. (Malone and his Vical coworkers also explored using mRNA for vaccines: their early patent filings describe injecting mRNA coding for HIV proteins into mice, and observing some protection against infection, although not the production of specific immune cells or molecules; this work was never published in a peer-reviewed journal).Malone contends that Verma and Vical struck a back-room deal so that the relevant intellectual property went to Vical. Malone was listed as one inventor among several, but he no longer stood to profit personally from subsequent licensing deals, as he would have from any Salk-issued patents. Malone’s conclusion: “They got rich on the products of my mind.”Verma and Felgner categorically deny Malone’s charges. “It’s complete nonsense,” Verma told Nature. The decision to drop the patent application rested with the Salk’s technology-transfer office, he says. (Verma resigned from the Salk in 2018, following allegations of sexual harassment, which he continues to deny.)Malone left Vical in August 1989, citing disagreements with Felgner over “scientific judgment” and “credit for my intellectual contributions”. He completed medical school and did a year of clinical training before working in academia, where he tried to continue research on mRNA vaccines but struggled to secure funding. (In 1996, for example, he unsuccessfully applied to a California state research agency for money to develop a mRNA vaccine to combat seasonal coronavirus infections.) Malone focused on DNA vaccines and delivery technologies instead.In 2001, he moved into commercial work and consulting. And in the past few months, he has started publicly attacking the safety of the mRNA vaccines that his research helped to enable. Malone says, for instance, that proteins produced by vaccines can damage the body’s cells and that the risks of vaccination outweigh the benefits for children and young adults — claims that other scientists and health officials have repeatedly refuted.Karikó had toiled in the lab throughout the 1990s with the goal of transforming mRNA into a drug platform, although grant agencies kept turning down her funding applications. In 1995, after repeated rejections, she was given the choice of leaving UPenn or accepting a demotion and pay cut. She opted to stay and continue her dogged pursuit, making improvements to Malone’s protocols, and managing to induce cells to produce a large and complex protein of therapeutic relevance.Although some involved in mRNA’s development, including Malone, think they deserve more recognition, others are more willing to share the limelight. “You really can’t claim credit,” says Cullis. When it comes to his lipid delivery system, for instance, “we’re talking hundreds, probably thousands of people who have been working together to make these LNP systems so that they’re actually ready for prime time.”This article plus the other research I've done on Malone doesn't detract from what he has been saying all along. Does anyone even know the name of the man that made space travel possible? Can it be surmised down to one man, or like this mRNA does it take many solid contributors to see the dream to completion? Discounting one of them is a disservice and especially when one helped create a key component and didn't get the "fruits" of his labor, well even I can see that would make someone jaded. I'm more interested in what he did and what he knows than to dispose of his work like a used Kleenex. I wonder how many here have taken the time to actually listen to his discussion with Joe Rogan? Not gonna hear that on CNN.
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