By Arthur Allen, editor for California Healthline, joined Kaiser Health News in April 2020 after six years at Politico, where he created, edited and wrote for the first health IT-focused news team. Previously, he was a freelance writer for publications such as The New York Times, The Washington Post, Smithsonian, Lingua Franca magazine, The New Republic, Slate and Salon. Earlier in his career, he worked for The Associated Press for 13 years, including stints as a correspondent based in El Salvador, Mexico and Germany. He is the author of the books “V Kaiser Health News.accine: The Controversial Story of Medicine’s Greatest Lifesaver” (W.W. Norton, 2007); “Ripe: The Search for the Perfect Tomato” (Counterpoint Press, 2010) and “The Fantastic Laboratory of Dr. Weigl” (W.W. Norton, 2014). Originally published at Kaiser Health NewsKaiser Health News.
When he started researching a troublesome childhood infection nearly four decades ago, virologist Dr. Barney Graham, then at Vanderbilt University, had no inkling his federally funded work might be key to deliverance from a global pandemic.
Yet nearly all the vaccines advancing toward possible FDA approval this fall or winter are based on a design developed by Graham and his colleagues, a concept that emerged from a scientific quest to understand a disastrous 1966 vaccine trial.
Basic research conducted by Graham and others at the National Institutes of Health, Defense Department and federally funded academic laboratories has been the essential ingredient in the rapid development of vaccines in response to COVID-19. The government has poured an additional $10.5 billion into vaccine companies since the pandemic began to accelerate the delivery of their products.
The Moderna vaccine, whose remarkable effectiveness in a late-stage trial was announced Monday morning, emerged directly out of a partnership between Moderna and Graham’s NIH laboratory.
Coronavirus vaccines are likely to be worth billions to the drug industry if they prove safe and effective. As many as 14 billion vaccines would be required to immunize everyone in the world against COVID-19. If, as many scientists anticipate, vaccine-produced immunity wanes, billions more doses could be sold as booster shots in years to come. And the technology and production laboratories seeded with the help of all this federal largesse could give rise to other profitable vaccines and drugs.
The vaccines made by Pfizer and Moderna, which are likely to be the first to win FDA approval, in particular rely heavily on two fundamental discoveries that emerged from federally funded research: the viral protein designed by Graham and his colleagues, and the concept of RNA modification, first developed by Drew Weissman and Katalin Karikó at the University of Pennsylvania. In fact, Moderna’s founders in 2010 named the company after this concept: “Modified” + “RNA” = Moderna, according to co-founder Robert Langer.
“This is the people’s vaccine,” said corporate critic Peter Maybarduk, director of Public Citizen’s Access to Medicines program. “Federal scientists helped invent it and taxpayers are funding its development. … It should belong to humanity.”
Moderna, through spokesperson Ray Jordan, acknowledged its partnership with NIH throughout the COVID-19 development process and earlier. Pfizer spokesperson Jerica Pitts noted the company had not received development and manufacturing support from the U.S. government, unlike Moderna and other companies.
The idea of creating a vaccine with messenger RNA, or mRNA — the substance that converts DNA into proteins — goes back decades. Early efforts to create mRNA vaccines failed, however, because the raw RNA was destroyed before it could generate the desired response. Our innate immune systems evolved to kill RNA strands because that’s what many viruses are.
Karikó came up with the idea of modifying the elements of RNA to enable it to slip past the immune system undetected. The modifications she and Weissman developed allowed RNA to become a promising delivery system for both vaccines and drugs. To be sure, their work was enhanced by scientists at Moderna, BioNTech and other laboratories over the past decade.
Another key element in the mRNA vaccine is the lipid nanoparticle — a tiny, ingeniously designed bit of fat that encloses the RNA in a sort of invisibility cloak, ferrying it safely through the blood and into cells and then dissolving, thereby allowing the RNA to do its work of coding a protein that will serve as the vaccine’s main active ingredient. The idea of enclosing drugs or vaccines in lipid nanoparticles arose first in the 1960s and was developed by Langer and others at the Massachusetts Institute of Technology and various academic and industry laboratories.
Karikó began investigating RNA in 1978 in her native Hungary and wrote her first NIH grant proposal to use mRNA as a therapeutic in 1989. She and Weissman achieved successes starting in 2004, but the path to recognition was often discouraging.
“I keep writing and doing experiments, things are getting better and better, but I never get any money for the work,” she recalled in an interview. “The critics said it will never be a drug. When I did these discoveries, my salary was lower than the technicians working next to me.”
Eventually, the University of Pennsylvania sublicensed the patent to Cellscript, a biotech company in Wisconsin, much to the dismay of Weissman and Karikó, who had started their own company to try to commercialize the discovery. Moderna and BioNTech later would each pay $75 million to Cellscript for the RNA modification patent, Karikó said. Though unhappy with her treatment at Penn, she remained there until 2013 — partly because her daughter, Susan Francia, was making a name for herself on the school’s rowing team. Francia would go on to win two Olympic gold medals in the sport. Karikó is now a senior officer at BioNTech.
In addition to RNA modification and the lipid nanoparticle, the third key contribution to the mRNA vaccines — as well as those made by Novavax, Sanofi and Johnson & Johnson —- is the bioengineered protein developed by Graham and his collaborators. It has proved in tests so far to elicit an immune response that could prevent the virus from causing infections and disease.
The protein design was based on the observation that so-called fusion proteins — the pieces of the virus that enable it to invade a cell — are shape-shifters, presenting different surfaces to the immune system after the virus fuses with and infects cells. Graham and his colleagues learned that antibodies against the post-fusion protein are far less effective at stopping an infection.
The discovery arose in part through Graham’s studies of a 54-year-old tragedy — the failed 1966 trial of an NIH vaccine against respiratory syncytial virus, or RSV. In a clinical trial, not only did that vaccine fail to protect against the common childhood disease, but most of the 21 children who received it were hospitalized with acute allergic reactions, and two died.
About a decade ago, Graham, now deputy director of NIH’s Vaccine Research Center, took a new stab at the RSV problem with a postdoctoral fellow, Jason McLellan. After isolating and obtaining three-dimensional models of the RSV’s fusion protein, they worked with Chinese scientists to identify an appropriate neutralizing antibody against it.
“We were sitting in Xiamen, China, when Jason got the first image up on his laptop, and I was like, oh my God, it’s coming together,” Graham recalled. The prefusion antibodies they discovered were 16 times more potent than the post-fusion form contained in the faulty 1960s vaccine.
Two 2013 papers the team published in Science earned them a runner-up prize in the prestigious journal’s Breakthrough of the Year award. Their papers, which showed it was possible to plan and create a vaccine at the microscopic structural level, set the NIH’s Vaccine Research Center on a path toward creating a generalizable, rapid way to design vaccines against emerging pandemic viruses, Graham said.
In 2016, Graham, McLellan and other scientists, including Andrew Ward at the Scripps Research Institute, advanced their concept further by publishing the prefusion structure of a coronavirus that causes the common cold and a patent was filed for its design by NIH, Scripps and Dartmouth — where McLellan had set up his own lab. NIH and the University of Texas — where McLellan now works — filed an additional patent this year for a similar design change in the virus that causes COVID-19.
Graham’s NIH lab, meanwhile, had started working with Moderna in 2017 to design a rapid manufacturing system for vaccines. In January, they were preparing a demonstration project, a clinical trial to test whether Graham’s protein design and Moderna’s mRNA platform could be used to create a vaccine against Nipah, a deadly virus spread by bats in Asia.
Their plans changed rapidly when they learned on Jan. 7 that the epidemic of respiratory disease in China was being caused by a coronavirus.
“We agreed immediately that the demonstration project would focus on this virus” instead of Nipah, Graham said. Moderna produced a vaccine within six weeks. The first patient was vaccinated in an NIH-led clinical study on March 16; early results from Moderna’s 30,000-volunteer late-stage trial showed it was nearly 95% effective at preventing COVID-19.
Although other scientists have advanced proposals for what may be even more potent vaccine antigens, Graham is confident that carefully designed vaccines using nucleic acids like RNA reflect the future of new vaccines. Already, two major drug companies are doing advanced clinical trials for RSV vaccines based on the designs his lab discovered, he said.
In a larger sense, the pandemic could be the event that paves the way for better, perhaps cheaper and more plentiful vaccines.
“It’s a silver lining, but I think we are definitely pushing forward the way everyone is thinking about vaccines,” said Michael Farzan, chair of the department of immunology and microbiology at Scripps Research’s Florida campus. “Certain techniques that have been waiting in the wings, under development but never achieving the kind of funding they needed for major tests, will finally get their chance to shine.”
Under a 1980 law, the NIH will obtain no money from the coronavirus vaccine patent. How much money will eventually go to the discoverers or their institutions isn’t clear. Any existing licensing agreements haven’t been publicized; patent disputes among some of the companies will likely last years. HHS’ big contracts with the vaccine companies are not transparent, and Freedom of Information Act requests have been slow-walked and heavily redacted, said Duke University law professor Arti Rai.
Some basic scientists involved in the enterprise seem to accept the potentially lopsided financial rewards.
“Having public-private partnerships is how things get done,” Graham said. “During this crisis, everything is focused on how can we do the best we can as fast as we can for the public health. All this other stuff is going to have to be figured out later.”
“It’s not a good look to become extremely wealthy off a pandemic,” McLellan said, noting the big stock sales by some vaccine company executives after they received hundreds of millions of dollars in government assistance. Still, “the companies should be able to make some money.”
For Graham, the lesson of the coronavirus vaccine response is that a few billion dollars a year spent on additional basic research could prevent a thousand times as much loss in death, illness and economic destruction.
“Basic research informs what we do, and planning and preparedness can make such a difference in how we get ahead of these epidemics,” he said.
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I appreciate the recent re-look at the nexus of public investment funding private profit in the pharma space. I’m not old enough to recall how things were done prior to the 1980s with regards to promising academic discoveries getting commercialized in the United States. There is also a glaring omission here in that there are mechanisms for the Federal Government to take control of patents and price fix in an emergency, but it’s clear that was never going to happen and was never whispered in the lead up to operation Warp Speed. Pfizer keeps pointing out they never took government money, which is a set up for them to set the price at whatever they want while executives line their pockets.
The second point, that is not a focus of the article, is that these technologies are still completely unproven. I am optimistic about the early results, though would feel better if they were published in quality journals and not press releases. We simply don’t know anything about long term affects of dosing with this technology. These articles make it sound like we’re out of the woods and these vaccines are here to stay, but what if there are high percentages of people that get major side effects? We still have no idea.
But Joe Biden is now president. So of course the vaccines will work.
I was just thinking about that this morning. I thought about the little boy who cried wolf. If Don had not tarnished his (??where-with-all??) by not leading. He still be the Prez.
So, Larry, what would it take to convince you? A million volunteers? A billion? 2 years? 5 years?
So, Wobbly, can I safely assume that you and your family have already volunteered for one of the trials?
As I have stated here, yes.
I applaud you for standing with power of your convictions. Not many have the integrity to do so. This is meant sincerely.
On the other hand I think Larry has a point. Hopefully his and my concerns will prove to be unfounded. I believe it is too soon to tell. Your question about the quantification of risk is a fair question and is difficult for the layman judge.
I share the concerns that have been and are voiced here. Still, there is a class aspect to it all. It seems as if this war is like every other war; the poors are sent in first. There are many, perhaps the majority of volunteers, that need the couple of hundred bucks the pharmas are offering the participants. They are the same people that line up to sell their blood plasma every week. Big business, that. So, I woke up, looked in the mirror, and told the old man there to “Suck it up, Buttercup.”
And Lambert and others are right when they say our leaders should be first in line to roll up their sleeves. Just don’t forget the many that have already done so.
It was a revelation to me that RNA vaccines had been in the works since the 60s. That makes me a little more in-favor of them. It is still frightening that this vaccine will be mandated for all medical personnel before the rest of the population. Also interesting that RNA gets greased up to slip past the enzymes(?) that destroy errant RNA… I’m still trying to think how that might not be such a good thing. But you are right – it looks like it works. Extremely well in fact. But a timeline to prove it is safe? I’d say one or two generations. If this mRNA slips past the mechanisms to protect the cell from foreign RNA then it could hang around long enough to communicate itself back to the genetic DNA – it’s just that they don’t quite know how that process works yet. And that’s scary as hell. (Lamarck’s Signature). I’d say maybe we should not give this vaccine to anyone under the age of 35 until we know more about possible negatives involving inheritance. Instead we should produce good medicines to treat these infections.
Don’t we have laws for price gouging in a crisis? As for untested. Check the thread for data started compiling 1966.
Yes, we need volunteers. And they need to be fully informed. I hope you noticed this remark in yesterday’s Water Cooler. Of course, we don’t know that the commentor’s claimed bona fides are factual, but if so, his/her take seems appropriate to me.
I did, and I take them at their word as to background. Valid concerns, well expressed.
The publications and a full accounting of side effects are important for a new technology like this. Traditional vaccinations are in the billions of doses at this point and quite safe. For this new technology, it’s quite hard to say. The publications might bowl me over and convince me, but press releases do not.
The Moderna study (n=45) was published in NEJM. Haven’t read beyond the abstract or looked for the Pfizer study yet.
href=”https://www.nejm.org/doi/full/10.1056/nejmoa2022483″>
It should be noted that, so far, we have proof of effectiveness in the form of press releases that are intended to goose stock prices.
Long story, but the neoliberalization of basic biomedical science is complete. This was foreseeable upon passage of the Bayh-Dole Act of 1980. I remember how such science was done way back then. Scientists did science. Those without the patience and essentially self-abnegation required for that, went to work at Ciba-Geigy or Burroughs-Welcome or Merck. The system worked, more or less. At the time I was a very junior lab member, and I told my labmates that Bayh-Dole meant only that we would pay for most science (at least) twice, the first time when NIH/NSF/ACS/AHA/March of Dimes funded it and the second time when Big Pharma “bought” it and charged what a false, not free, market in research and health care would bear. They just stared at me, with stars in their eyes.
Dolly Parton invested $1 million in the Moderna vaccine. I can’t wait till Tennessee takes down all these Nathan Bedford Forrest statues and replaces them with Dolly Parton.
Dolly Parton is a great songwriter and performer but is also a shrewd businesswoman who is hyper-focused on helping “her people” in the region where she grew up dirt poor. “Coat of Many Colors” is one of the truly great autobiographical songs. https://en.wikipedia.org/wiki/Coat_of_Many_Colors_(song)
Appreciation for Dolly shows up in many interesting corners in the region. Several years ago, a newly discovered lichen in southern Appalachia was named in her honor. I never heard a comment from her on this, but she probably thought it was great. https://www.nybg.org/blogs/science-talk/2015/05/honoring-a-musical-legend-of-the-southern-appalachians/
Replacing a Nathan Bedford Forest statue with her would be a great move.
1.So if there were to be no vaccine and the virus had it’s way with us, killing 1% of us, that’s what,— 3 million souls?
2. Alternatively, if there is a vaccine and everyone is vaccinated and that brings an end to the pandemic, with deaths much curtailed, but 25,000 get Guillian Barre’, that’s still a win right?
(Though not if you are one of the 25,000.)
3. Lastly, given their penchant for maximizing clicks and eyeballs,
how do you think the media would handle situations 1 or 2?
Trust in Public Health is easier to knock down than to build back up, especially vaccines.
As Greg Brown says, “It’s a long way up but it’s a short way down.”
South Dakota will be very informative on this front. It appears to be trying to drag-race herd immunity through infection before a vaccine shows up. It will probably be the control group for the statistical study of the relative efficacy on lives saved by a vaccine vs. letting the disease take its natural course. Beer appears to be the placebo vaccine of choice in South Dakota.
My reading of this is that even if Pfizer didn’t take government money as part of the Warp Speed initiative, as a mRNA vaccine it still likely builds on the earlier work. I have no problem with pharma companies making a profit of their later work – they did do the last critical developments – but nothing for the earlier work isn’t right.
We pay for it but they profit from it. Why? Why is there for profit pharma and corporate medicine to begin with? Why is there competition instead of cooperation in the production of life saving/extending and other commonly needed goods and services? The provision of pharmaceuticals and medicine are a free market failure. We are not adequately provided with what we all must have at prices we all can afford. They’ve failed not because of the scientists and medical practitioners who do the real work. They’ve failed because of the capitalist parasites that own the corporations that employ the professionals who create the products and provide the services on the ground.
One thought unsupported by any relevant technical expertise: the delivery mechanism sounds well suited for bio weaponry given it bypasses your immune reaction to RNA.
The protein design was based on the observation that so-called fusion proteins — the pieces of the virus that enable it to invade a cell — are shape-shifters, presenting different surfaces to the immune system after the virus fuses with and infects cells. Graham and his colleagues learned that antibodies against the post-fusion protein are far less effective at stopping an infection.
Reminds me of this other mysterious shape-shifter: From Wikipedia:
Prions are misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It is not known what causes the normal protein to misfold, but the abnormal three-dimensional structure is suspected of conferring infectious properties, collapsing nearby protein molecules into the same shape. The word prion derives from “proteinaceous infectious particle”.
Long-term follow-up of individuals who have received this vaccine versus their placebo compatriots is essential!
Not likely to be similar. The “shape shifting” of the viral fusion protein means that different epitopes (i.e., different constellations of 3-D structure that elicit immune/antibody responses) of the fusion protein, which is embedded in the viral membrane envelope, are presented pre- and post-fusion. Antibodies against “post-fusion” fusion protein are unlikely to work because fusion with the host cell is the key phase of infection. But, and this is a big consideration, rushing into this is foolish, despite the rise in Big Pharma stock prices.
COVID vaccine revelation sinks like a stone; disappears
In major media, certain stories gain traction. The trumpets keep blaring for a time before they fade.
Other stories are one-offs. A few of them strike hard. Their implications—if anyone stops to think about them—are powerful. Then…nothing.
“Wait, aren’t you going to follow up on that? Don’t you see what that MEANS?”
Apparently not, because…dead silence. “In other news, the governor lost his pet parakeet for an hour. His chief of staff found it taking a nap in a desk drawer…”
One-offs function like teasers. You definitely want to know more, but you never get more.
Over the years, I’ve tried to follow up on a few. The reporter or the editor has a set of standard replies: “We didn’t get much feedback.” “We covered it.” “It’s now old news.” “There wasn’t anything else to find out.”
Oh, but there WAS.
A few weeks ago, I ran a one-off. The analysis and commentary were mine, but the story was an opinion piece in the New York Times. The Times called it an opinion piece to soften its blow. I suspected it would disappear, and it did.
Its meaning and implication were too strong. It would be a vast embarrassment for the White House, the Warp Speed COVID vaccine program, the vaccine manufacturers, the coronavirus task force, and vaccine researchers.
And embarrassment would be just the beginning of their problem.
So…here it is again. The vanished one-off, back in business:
COVID vaccine clinical trials doomed to fail; fatal design flaw; NY Times opinion piece exposes all three major clinical trials.
Peter Doshi, associate editor of the medical journal BMJ, and Eric Topol, Scripps Research professor of molecular medicine, have written a devastating NY Times opinion piece about the ongoing COVID vaccine clinical trials.
They expose the fatal flaw in the large Pfizer, AstraZeneca, and Moderna trials.
September 22, the Times: “These Coronavirus Trials Don’t Answer the One Question We Need to Know”
“If you were to approve a coronavirus vaccine, would you approve one that you only knew protected people only from the most mild form of Covid-19, or one that would prevent its serious complications?”
“The answer is obvious. You would want to protect against the worst cases.”
“But that’s not how the companies testing three of the leading coronavirus vaccine candidates, Moderna, Pfizer and AstraZeneca, whose U.S. trial is on hold, are approaching the problem.”
“According to the protocols for their studies, which they released late last week, a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild Covid-19, but was never shown to reduce moderate or severe forms of the disease, or the risk of hospitalization, admissions to the intensive care unit or death.”
“To say a vaccine works should mean that most people no longer run the risk of getting seriously sick. That’s not what these trials will determine.”
This means these clinical trials are dead in the water.
The trials are designed to show effectiveness in preventing mild cases of COVID, which nobody should care about, because mild cases naturally run their course and cause no harm. THERE IS NO NEED FOR A VACCINE THAT PREVENTS MILD CASES.
There. That’s the NY Times one-off. My piece analyzing it went on much longer, but you get the main thrust:
The leading vaccine clinical trials are useless, irrelevant, misleading, and deceptive.
But now, it gets much worse. Because Pfizer has just announced their vaccine is almost ready. CNBC headline, November 9: “Pfizer, BioNTech say Covid vaccine is more than 90% effective—‘great day for science and humanity’”
And not a peep about the NY Times one-off. That’s gone, as if it never was.
Trump’s coronavirus task force knows the truth. Biden’s new task force, waiting in the wings, knows the truth. But they don’t care. They’re criminals. They’d sell a car with a gas tank ready to explode to a customer with cash.
But you care, because you can read and think.
You can raise hell.
Now, in case anyone is interested in knowing WHY the major clinical trials of the COVID vaccine are designed only to prevent mild cases of COVID, I’ll explain.
A vaccine maker assumes that, during the course of the clinical trial, a few of the 30,000 volunteers are going to “catch COVID-19.”
They assume this because “the virus is everywhere,” as far as they’re concerned. So it’ll drop down from the clouds and infect a few of the volunteers.
The magic number is 150. When that number of volunteers “catch COVID,” everything stops. The clinical trial stops.
At this point, the vaccine maker hopes that most of the volunteers who “got infected” are in the placebo group. They didn’t receive the real vaccine; they received the saltwater placebo shot.
Then the vaccine maker can proudly say, “See? The volunteers who caught COVID-19? Most of them didn’t receive the vaccine. They weren’t protected. The volunteers who received the real vaccine didn’t catch COVID. The vaccine protected them.”
Actually, the number split the vaccine makers are looking for is 50 and 100. If 50 people in the vaccine group catch COVID, and 100 in the placebo group catch COVID, the vaccine is said to be 50% effective. And that’s all the vaccine maker needs to win FDA approval for the vaccine.
But wait. Let’s look closer at this idea of “catching COVID.” What are they really talking about? How do they define that? Claiming a volunteer in the clinical trial caught COVID adds up to what?
Does it add up to a minimal definition of COVID-19—a cough, or chills and fever? Or does it mean a serious case—severe pneumonia?
Now we come to the hidden factor, the secret, the source of the whole con game.
You see, the vaccine maker starts out with 30,000 HEALTHY volunteers. So, if they waited for 150 of them to come down with severe pneumonia, a serious case of COVID, how long do you think that would take? Five years? Ten years?
The vaccine maker can’t possibly wait that long.
These 150 COVID cases the vaccine maker is looking for would be mild. Just a cough. Or chills and fever. That scenario would only take a few months to develop. And face it, chills, cough, and fever aren’t unique to COVID. Anyone can come down with those symptoms.
THEREFORE, THE WHOLE CLINICAL TRIAL IS DESIGNED, UP FRONT, TO FIND 150 CASES OF MILD AND MEANINGLESS AND SELF-CURING “COVID.”
About which, no one cares. No one should care.
But, as we see, Pfizer is trumpeting their clinical trial of the vaccine as a landmark in human history.
And THAT’S the story of the one-off the NY Times didn’t think was worth a second glance.
Because they’re so stupid? No. They’re not that stupid.
They’re criminals.
And the government wants you to take the experimental COVID vaccine, whose “effectiveness” was designed to prevent nothing worth losing a night’s sleep over.
The only worry are the adverse effects of the vaccine, about which I’ve written extensively. These effects include, depending on what’s in the vial, a permanent alteration of your genetic makeup, or an auto-immune cascade, in which the body attacks itself.
by Jon Rappoport
November 11, 2020
Hoo boy.
In case anyone is wondering most of that is inaccurate but I don’t feel like debunking it cause no one will read it.