#2: Big studies and very big findings

This week: Vaccines against heart attacks, giant bacteria, plus some great new books and podcasts.

This is my second post of Scientific Discovery, a weekly newsletter where I’ll share great new scientific research that you may have missed. Check out the About page if you’re interested in why I’m writing this.

Highlights

#1: Flu vaccines reduce your risk of getting a heart attack or stroke

Paper: Association of Influenza Vaccination With Cardiovascular Risk: A Meta-analysis. (Behrouzi et al., 2022)

Every year, around 10–20% of people are infected by influenza. Roughly half have no symptoms. But in the other half, symptoms can vary widely. In young infants and the elderly, flu tends to be more severe.

In severe cases, flu can cause a lot of complications, and occasionally it causes heart attacks and strokes. I used the c-word (‘cause’) there because there’s pretty solid evidence that this is the case, from many angles.

For a long time, it’s been recognised that heart attacks and strokes are more likely in the winter – during flu seasons, and worse in worse flu seasons. They’re more likely to occur in the week (or few weeks) after people have the flu.

Flu infections cause inflammation, trigger blood clotting, and affect your heart rhythm and blood volume – and all of these changes are linked to increased risks of heart attacks and strokes.

But there’s more.

It’s a good idea, if you want to test a theory, to think about what else you would to expect to see if the theory was true. One thing I’d expect is that if flu caused heart attacks and strokes, flu vaccines would reduce them.¹

And that’s exactly what we see. This recent study, which pools together data from randomised controlled trials, estimates that getting a flu shot reduces the risk of heart attacks, strokes and other major cardiovascular events by around 34% in the elderly.²

Because of this, the biggest trial included also estimates that it reduces the risk of death from all causes by 25% in the elderly.

A ‘forest plot’ showing that people who received influenza vaccines in randomized controlled trials had a reduced risk of cardiovascular outcomes (such as heart attacks and strokes). The box and whisker plots show estimates from each smaller trial, while the diamonds show the overall estimates from across them. Behrouzi et al. (2022)

This isn’t actually a new finding – you could also see it by comparing these risks in people who received influenza vaccines with similar people who didn’t. But until the last two decades, there wasn’t this much evidence from randomised controlled trials to bolster it.

The problem is, most flu vaccine trials aren’t trying to find out how well they protect against heart attacks, strokes, or death. They’re trying to see whether these vaccines prevent the flu. And it’s not that common for people in a trial to have a stroke or die, even if they’re in the placebo group.

So, if you want to precisely estimate how well they protect people against these rarer risks, you either get a bigger sample or recruit people who are at higher risk to begin with.

This meta-analysis combines both: their estimate is much more precise with a big pooled sample of elderly people. There are other recent meta-analyses too, and they make similar estimates.

So, here’s the bottom line: get your flu shot this year. Tell your parents, grandparents, aunts, uncles, and people you know at high risk of cardiovascular disease, to get it too.

Based on the rates³, it’s expected that flu vaccines prevent 1 heart attack, stroke or other major cardiovascular event, for every 56 elderly people who get vaccinated.

Saving lives is easier than you might think.

#2: The biggest bacteria we know of

Paper: A centimeter-long bacterium with DNA contained in metabolically active, membrane-bound organelles (Volland et al., 2022)

Last week, a new study was published on the biggest bacterium discovered so far.

It was named Thiomargarita magnifica by the authors. And it’s around a centimetre long, which makes it 50 times larger than the previous ‘biggest bacteria we knew of’.

The BBC had this great quote from the lead author, which made me laugh: “These bacteria are about 5,000 times larger than most bacteria. And to put things into perspective, it is the equivalent for us humans to encounter another human who would be as tall as Mount Everest.”

A diagram showing the size of the newly discovered bacteria, Thiomargarita magnifica, relative to other organisms. Volland et al. (2022)

Sadly, it’s been a while since I’ve had lectures on bacterial cell biology. But this was intriguing – and I had a newsletter to write! – so I thought about which points I needed to look for to judge this study and understand it, from a field outside of my own.

Here’s what I decided to look for. There should be clear evidence that these are single cell bacteria (not several cells clumped together) from reliable imaging techniques. There should be good evidence that this is a bacterium (not some other type of organism of that size) with evidence from its genome, cell structure, properties, and so on. And ideally there would be some convincing details to explain why it’s able to be so big – although there’s a limit to how much we’d be able to explain already if this was a massively groundbreaking finding.

So I was very satisfied to see all of these addressed in the paper, and I learnt a lot from it!

The authors used several standard imaging methods to make sure these really were single, very long bacteria, without divides. They sequenced their DNA, and found they were genetically similar to other (smaller) giant bacteria that had been identified in the past.

Image of a giant bacterial cell, Thiomargarita magnifica, using transmission electron microscopy. Each panel is magnified from the previous. You can see that the centre has a large space – the vacuole – while the rest of the cell’s contents are around the edges. Volland et al. (2022)

How can bacteria be so big, though?

When cells are larger, they need more energy to diffuse nutrients and proteins to where they’re needed.

The other giant bacteria scientists know about have many copies of their DNA so they can produce proteins in many places around the cell. Some have big vacuoles – spaces just containing solution and small molecules, which reduce how much diffusion needs to occur across the rest of the cell.

These bacteria had those properties too.

They had lots of ribosomes and ATP-synthesising enzymes, which release energy. They had enormous numbers of copies of their DNA – this study estimates over 700,000 copies per cell, way more than has ever been seen before! (We have two copies of our DNA per cell, for comparison...) And they had a massive vacuole that made up around 73% of their total volume.

They were found in a mangrove swamp with high sulfide concentrations, in Guadeloupe. To survive and grow in such an environment, bacteria need sulfur-oxidising enzymes to release energy, and these bacteria had those enzymes too. They had more genes that coded for these enzymes, many sulfur granules in their cells, and DNA highly similar to other giant bacteria with these sulfur-oxidising properties.

The paper has many more fascinating details, and at the end, the authors say their discovery “suggests that large and more complex bacteria may be hiding in plain sight.” As a fan of absolute units, I hope they are right.

More links

I was planning to add a few more studies here too, but I still need some time to read and process them, so they’ll be in the next post.

In the meantime, Stripe Press has new publications!

• Pieces of the Action – Vannevar Bush. Vannevar Bush isn’t a household name today, but he had an enormous influence on scientific research during and after WWII. He coordinated huge projects and oversaw funding for them, like the development of radar, anti-malarial drugs, and the Manhattan Project. This is a sincere and inspiring memoir, which I loved reading. It was originally published in 1970 and was republished by Stripe Press this week; you can order it here.

• Growing Pains and Bullet Trains – Beneath the Surface. A podcast episode all about trains in Japan! How are they so fast, extensive and efficient? My wonderful colleague Tamara Winter hosts this great deep-dive with train experts who tell you everything you want to know. She also has a very soothing ASMR voice.

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That’s all for this week. As before, please let me know if you spot any mistakes or think I’ve missed anything important.⁴

I hope you enjoyed my walkthrough of great new research, and I hope you’ll subscribe if you haven’t already! See you next time.

– Saloni

If you don’t know me from Twitter, here’s a short bio of myself. I’m a founding editor at the online magazine Works in Progress, a researcher on health for Our World in Data, a commissioning editor at Stripe Press, and a final year PhD student at the University of Hong Kong and King’s College London.

1. This effect would be larger in years when a larger share of all heart attacks and strokes are triggered by flu infections.

2. It’s likely that this varies year by year, depending on how well the flu vaccines are matched with the dominant flu strains that season. The estimates in this meta-analysis are of the average across many flu seasons.

3. These estimates were made from participants in the trial. 5.4% of the elderly who received the placebo had a heart attack or stroke within the following year, versus 3.6% who received the flu vaccine. People who participate in clinical trials tend to be healthier than the average person, meaning that the number (56 elderly people) needed to vaccinate to prevent a major cardiovascular event is likely an overestimate, for the wider population of elderly people.

4. I have open DMs on Twitter here, but you can also get in touch with me by commenting on this Substack post.