These new RNA vaccines are a triumph for science and medicine

This week the FDA approved a second vaccine against SARS-CoV-2, the virus that causes Covid-19. We now have two highly effective vaccines, one from BioNTech and Pfizer, and the other from Moderna. A third vaccine, from Oxford University and AstraZeneca, is very close to approval.

The two new vaccines, both based on RNA, are both remarkably effective. Below I’ll summarize some of the numbers, which have been published for the world to see.

This is a scientific triumph. Less than a year ago, no one outside China even knew this virus existed. The genome of the virus was first released in January, and within a few months scientists had designed the first vaccines. Clinical trials were launched immediately, and larger trials followed, leading us to where we are today: two new vaccines, tested and validated in tens of thousands of people, now being manufactured and shipped to billions.

For anyone who might be skeptical, or who just might want to know more, the test results are being published openly. The New England Journal of Medicine has a dedicated website with dozens of papers and audio summaries, including results from the large-scale (Phase 3) trials of the Pfizer vaccine.

Before getting into the numbers, let’s summarize what these two new vaccines are. (I wrote about this in July, if you want to read my previous explanation.) Both of them are RNA vaccines, which is itself a dramatic breakthrough. RNA vaccines have been discussed for years, but the technology was never employed for human vaccines until now.

Here’s how they work: our immune system (which is super-complicated, as Ed Yong explained in The Atlantic) recognizes microscopic invaders and destroys them. Once you’ve been infected with Covid-19, the immune system swarms over the viral particles and basically learns what they look like. SARS-CoV-2 has a protein all over its surface called “Spike,” so that’s what the immune system recognizes.

Once you’ve fought off the infection, the immune system remembers what Spike looks like. If you’re infected again, it can respond far more quickly, so you won’t get sick. This is what we call acquired immunity.

So for vaccines, the trick is to teach your immune system to recognize Spike. One way to do that is to manufacture lots and lots of the Spike protein, and put that in the vaccine (sort of–I’m greatly oversimplifying here).

But with modern genomics technology, we can use a different approach. Every cell in your body has machinery inside it to translate RNA into proteins. As soon as we had the SARS-CoV-2 genome, back in January, we knew the genetic code for Spike. So rather than make the protein, what if you just made the RNA, which is far easier and faster to manufacture, and injected that into people? Do our own cells then translate the RNA and make the Spike protein?

Well yes, they do. And not only that, but–as the Modern and Pfizer clinical trials have now proven–our immune system recognizes that the Spike protein is foreign (it’s complicated) and launches an attack.

So to make an effective RNA vaccine, you simply have to inject enough RNA so that the immune system responds. That’s what both the Modern and BioNTech/Pfizer vaccines have done.

Now let’s look at the numbers. As reported in NEJM just two weeks ago, the Phase 3 trail for the Pfizer vaccine tested 43,448 volunteers, of whom 21,720 got the vaccine and 21,728 got a placebo. At the time of the report, 162 people who received the placebo had become sick with Covid-19, but only 8 people in the vaccine group got sick. That’s a 95% reduction in illness, a remarkably good result. They also reported that 10 people had “severe” illness, and 9 of those ten were in the placebo group.

How about the Moderna vaccine? This vaccine has almost identical efficacy, published in a preliminary report a few weeks ago as 94.5%. Just a few days ago, an FDA review panel approved the vaccine and confirmed that its efficacy was above 94%. And the Modern vaccine doesn’t need the super-cold freezers that the Pfizer vaccine needs, which makes it easier to distribute.

Both vaccines have minimal side effects in most people, mostly soreness at the injection site, and sometimes headaches or chills, which subside within a day. RNA is quickly degraded in the body, so there’s no reason to expect any lingering side effects from these vaccines.

There’s also growing evidence that immunity lasts for many months, if not years. Another report in NEJM, on the Moderna vaccine, contains some of the latest data, which shows that immunity is still strong after 4 months. Of course, with a brand-new vaccine, we simply have to wait to see if the immunity lasts for years, but all signs are positive right now.

So yes, these are really good vaccines. I will get mine as soon as I can, although I expect I’ll have to wait several months because of short supply.

(The Oxford/AstraZeneca vaccine, a more traditional protein-based vaccine, has also shown positive results, either 62% or 90%, depending on the dosage regimen, but the 90% results are based on fewer cases. Even so, it is clearly effective and it should be approved soon, at least in the UK. So we might soon have 3 vaccines.)

A note to anti-vaxxers: no, you cannot catch Covid-19 from these vaccines. They don’t contain the virus! They only have a fragment of RNA from one protein, and the virus has RNA that encodes 28 other proteins. It’s simply impossible for the virus to self-assemble without the rest of its genome.

But hey, if you don’t want the vaccine, go to the back of the line. Most of the world is desperate for it.

The success of RNA vaccines is a huge win for science, but even more, it’s a huge win for the human population. We’re still many months away from vaccinating the whole world, but with two highly effective vaccines, we can finally have hope to end this pandemic.

New Nature open access policy is little more than a money grab

We scientists love to publish papers, and we get especially excited when our papers appear in “top” journals. The journals know this, and sometimes it seems they just want to see how much they can get scientists to grovel.

That’s what I was thinking a couple of weeks ago, when the publishers of Nature announced that they will charge authors €9,500 ($11,500) to publish a paper as open access, meaning readers can get the paper without a subscription. They called this, without a trace of irony, their “gold open access option.”

$11,500??? Sadly, the Nature publishers were not kidding.

This is outrageous. $11,500 is more than scientists earn in a year in some countries, as Forbes blogger Madhukar Pai pointed out. What’s truly outrageous is that they’re asking for this payment from a community that does all the work for them for free. If Nature is going to treat scientists like suckers, it’s time we stopped playing along.

Let’s back up a minute and look at how the academic publishing system works. (When I explain this to non-scientists, they are often flabbergasted.) Consider: a typical science paper describes experiments that cost tens or hundreds of thousands of dollars, most of which comes from government grants (the most common source of funding) or from private foundations. Scientists write the paper and then submit it to a journal. The journal, in turn, asks other scientists to review the paper, which they do, using their own time and expertise.

All of this–the scientific experiments, the writing, and the reviewing–is done for free, from the journal’s perspective.

Journals then claim copyright on the papers and charge fees to anyone who wants to read them. Not a bad deal for them: virtually all the labor is free. Scientific journals, most of which are owned by a small number of large, for-profit publishers, are very, very profitable.

The whole system, as Berkeley professor Mike Eisen explained in a recent interview in Science, “was built for the printing press.” When journals had to print everything on paper and ship the journals to libraries around the world, it kind of made sense. They were providing a valuable service for science, and it does cost money to print and deliver all those journals.

For over two decades, though, we have been distributing papers electronically, and there’s almost no need for paper copies. One might expect that journals would change their model, but they haven’t. In fact, they’re even more profitable now than they were before the Internet.

Not content with their enormous profits, it now seems that Springer Nature wants to suck even more money out of academic science. It’s true that Nature publishes some highly prestigious scientific journals, but their announcement of this new “gold” open access policy just drips with self-congratulation. “Research published in Nature and the Nature research journals is downloaded ... over 30 times more than papers in a typical journal,” they write. (Who wants to publish in a “typical” journal after reading that?) They also claim to be an “innovator in open access,” which is, frankly, nonsense. Springer and the other for-profit journals have been fighting open access since the mid-2000s, and this latest announcement is yet one more salvo in their battle against it.

(Or maybe Springer thinks that charging $11,500 to make a paper open access is an innovative move? It does take chutzpah, I’ll grant them that.)

The open access movement, which I’ve long been a part of, wants to make all scientific research freely available to anyone, with no costs or delays. As every scientist knows, science only progresses by sharing its discoveries, and barriers such as subscription fees serve only to slow down that progress. Given that most research is paid for by the public, it makes no sense at all to allow for-profit journals to control access. The only reason they still do is because they’ve done so for decades, and it’s hard to change an entrenched system.

Nature’s outrageously high fee also excludes virtually every scientist from low and middle-income countries, as fellow Forbes blogger (and scientist) Madhukar Pai wrote last week.

Rather than a move to support open access, this new fee is little more than a money grab. It’s actually even worse: in addition to the new $11,500 open access fee, Nature also announced an option (they call it a “new OA pilot”) whereby you pay them $2,600 for a preliminary review, and they evaluate your paper for six of their journals. In this option, they might reject your paper outright, and you’re out $2,600 with nothing to show for it. If they think it’s worthy, you pay the remainder of the open access fee later. Gee, this seems like a great idea–paying $2,600 for something that currently is free. Thanks, Nature!

Of course, Nature journals will still allow scientists to publish papers the old-fashioned way, where they don’t pay the €9,500 fee and where the journal then owns the paper. Rather than doing that, or paying the outrageous fee, let’s hope this money grab makes scientists look elsewhere for a place to publish their findings. And while we’re at it, let’s tell the Nature editors we won’t be reviewing for them any longer, not while they’re charging this ridiculous $2,600 fee for a service that we scientists have been providing for free. I’ve already done that once, and I plan to continue until they drop this idea.