Synthetic embryos, curing genetic diseases, super rice, and AI protein revolution…

There have been some really big steps forward in biology and medicine this week, so many that I had an embarrassment of riches to choose from. First off, in my own field of developmental biology, an astonishing first: researchers have managed to make “synthetic embryos” from mouse stem cells – without sperm, eggs, fertilisation, or, indeed a uterus for the embryo to grow in. We’ve been able to “re-programme” cells that have differentiated (specialised) into e.g. skin or gut cells back to a state in which they can generate other types of cells for a while – those are stem cells. We’ve even been able, more recently, to make organoids, which are slightly more complex 3D structures resembling very simplified mini-organs (and I do mean mini, only up to a couple millimetres or so). We can also use “natural” stem cells from the embryo and add chemicals to them to make them differentiate into different cell types. But we’ve never been able to make those embryonic stem cells (ESCs) re-construct a mammalian embryo when taken out of one before. Researchers managed to instruct the cells to form an embryo and successfully grow it past the gastrulation stage (the tricky bit when it goes from a ball of cells to a layered structure with a gut) and into the organ-forming stage, complete with beating hearts. Original research published in Cell here. Naturally, this raises a number of ethical questions if the same process could be applied to human embryos, but it should really help advance of knowledge of early mammalian embryo development.

Our next breakthrough is in the field of gene editing. You’ve probably heard of “CRISPR” gene editing – which made introducing specific changes in the DNA of living organisms extremely easy, instead of the complicated and often inaccurate ways of editing genes before (which also had a rather low success rate). From the start, the potential of this technology to correct disease-causing mutations was evident and one of the key aims of using it. There’s just one snag though – in order to work, CRISPR has to break both strands of your double-stranded DNA molecule, which are then later rejoined by the cell’s own DNA repair machinery. This can lead to a risk of errors. Nevertheless, there are some careful CRISPR-clinical trials underway for some diseases, including beta-thalassaemia, an inherited blood disease which I’ve written about before. Researchers have been busy modifying gene editing techniques to make them even better, however, and now the first major clinical trials are due to be launched that use “base editing”, a modified form of CRISPR that only breaks one DNA strand at a time, and couples it an enzyme that changes a single base, or “letter” of the DNA to correct a mutation. The first trials will focus on correcting genes causing sickle cell anaemia and a hereditary form of high cholesterol that causes heart disease. The progress made in this field is really promising and genuinely astonishing – twenty or so years ago, when the human genome was first sequenced, the idea that you might be able to repair genetic diseases in living humans was science fiction.

Another story that makes me feel ancient: DeepMind’s AlphaFold programme has predicted the structures for every known protein, which is well over 200 million. When I was a student, I remember being told in lectures that it was currently not possible for computers to predict the complicated 3D structures of proteins and probably wouldn’t be for decades, if ever…Well, two decades later, here we are, with an AI that has churned out a protein structure in less than a minute – when it could take over a year get a crystal structure of a protein the old-fashioned way. Of course, we don’t know if all these predictions are correct, and AlphaFold itself predicts the accuracy of these as being good in only about half of them, but early signs are good for many. At any rate, it’s a treasure trove for researchers to take further in our understanding of molecular biology, disease and drug design. There’s a good thoughtful analysis in Prospect magazine.

Some great plant news here too: genetically engineered “super rice” yields up to 40% more grain. Now, if the term “genetically engineered” made you recoil, then here’s something that you will hopefully make you reconsider. The genetic change, in this case, has not been to introduce a gene from another species, or something that produces a pesticide, but simply making the rice overexpress a gene it already has by putting in a second copy of the gene. In other words, it’s just doubled up so it makes more of a particular protein that was already there. As this protein is a transcription factor, a protein that can turn on and off a whole battery of other genes, it doing this has a number of enhanced effects. Namely, a significantly increased yield of grain, a shorter growing time, and a more efficient use of nitrogen – which will reduce the need for chemical fertiliser. The gene had similar, if more modest effects, when over-expressed in wheat as well, suggesting that it may play a conserved role across different crop species and that they could similarly be improved. And hey, we need to feed a growing world in the face of climate change, so this could really help. Original research published in Science here.

Phew! What an embarrassment of riches. Just time to squeeze in our featured animal, the sponge crab. There’s a whole family of these cute fluffy crustaceans, the Dromiidae, and they like to wear sponges as a portable shelter, trimming them nicely to fit and holding them in place with a pair of specialised limbs. A new species, Lamarckdromia beagle, has just been discovered, reported here in the Express, of all places, and, more formally, in Zootaxa here.

Mendel’s peas, dog origins, covid “decoy” treatment and the diet of a giant prehistoric shark…

July marks the bicentenary of Gregor Mendel’s birth, the famous monk whose experiments in peas determined the means of inheritance of genetic traits long before we knew what genes or DNA were, leading to him being hailed as “the father of genetics”. This is the power of scientific methodology: that a careful and logical observation of natural processes (and selectively altering some of their conditions) can reveal fundamental truths about the natural laws underlying those processes, even when the mechanistic details are unknown. There’s a special issue in the Nature Reviews Genetics, the highlight of which is the accessible perspective piece here. There is a wonderful quote therein from Francois Jacob (a pioneer of molecular biology): “The process of experimental science does not consist in explaining the unknown by the known, as in certain mathematical proofs, it aims to give an account of what is observed by the properties of what is imagined”.

The evolution of dogs from grey wolves has fascinated researchers (and many others!) for a long time. Dogs were the earliest example of domestication of a wild species by humans, and uniquely occurred about 15,000 years ago, during the last Ice Age. It has always been a challenge proving where the first dogs were domesticated though, and whether there was one origin, or if it occurred in multiple times and places. Comparing the DNA of modern wolves and dogs, or looking at the archaelogical record, didn’t solve the mystery. So a big team of researchers has instead looked at DNA from over 70 ancient wolf remains from across Europe, Siberia and North America, spanning a time range of 100,000 years – and whole genomes too, not just snippets of DNA. Both early and modern dogs were most similar to ancient wolves from eastern Eurasia, but it’s not quite that simple.

As the figure below shows, dogs in the Near East and Africa also appear to have ancestry from a distinct population related to modern southwest Eurasian wolves. Either there were two separate domestication events, or one domestication event with early dog populations then interbreeding with a different population of grey wolves a second time. None of the analysed genomes was a direct match, meaning the exact local population is still to be determined. A good research summary from which the below figure is taken can be found here. Original research published in Nature here.

Figure 1 from “Ice Age wolf genomes home in on dog origins”| Two sources of ancestry for dogs. A map representing the ancestry of early dogs relative to ancient-wolf genomes. Pie charts show the proportion of each dog’s ancestry that derives from an eastern dog progenitor (blue) and a western one (yellow). Dogs from northeastern Europe, Siberia and the Americas (not shown) have a shared origin from an eastern source, whereas those from western Eurasia and Africa also have ancestry from a second, western, source. Black crosses indicate locations of ancient wolves (25,000 to 10,000 years old) that our analyses show are not progenitors of dogs. kyr, thousand years.Credit: Bergström, A. et al./Nature (CC BY 4.0) https://doi.org/10.1038/d41586-022-01551-z

Following on from my last post, here is a good update on the child hepatitis outbreak. US cases seem to have stabilised (for now) but UK ones have not. A role for coronavirus infection still seems to be the most plausible explanation, particularly as the UK has been very slow to vaccinate children under 11 compared to other countries.

A novel approach to tackling Sars-CoV2 has been trialled in mice. Sars-CoV-2 virus binds to the ACE2 receptor on our cell surfaces to gain access. So the researchers engineered ACE2 protein “decoys” to bind up the virus instead, harmlessly neutralising it. The decoys showed good results against different covid variants, including Omicron, whereas 2 out of the 3 antibody treatments they compared the decoys to did not. This is potentially a good weapon that could be added to the anti-Sars arsenal. Published in Science Translational Medicine here.

Today’s fantastic animal is the sadly extinct megalodon, the largest shark that ever lived, at around 20 metres long (compare to the great white shark, which is around 6 metres). Researchers have used an analysis of nitrogen levels in fossilised shark teeth to determine what these apex predators ate. The answer agrees (more or less) with those glorious monster movies: it ate everything, including other top predators. Original research published in Science Advances here (for the technically minded). There’s a fun informative video about why megalodon went extinct on Youtube here. Or you could watch all the crazy videos of people who think it’s still around today!

Featured Image

Reconstrucción de un Megalodon a escala real (16 metros de largo) y una dentadura en el Museo de la Evolución de Puebla, photo by Luis Alvaz, Wikimedia Commons.

Figure 1 from “Ice Age wolf genomes home in on dog origins”. https://doi.org/10.1038/d41586-022-01551-z

Plague, long covid theories, covid hepatitis in kids, and plastic-chomping worms

(Guess which story in the headline will be the light relief one!)

As the Covid pandemic roars apace (no, it is not “endemic” now, and, plainly no, there is no lasting “herd immunity”!) increasing numbers of people are suffering from long-term symptoms collectively dubbed Long Covid. What exactly causes these symptoms is an urgent question for science, as effective treatments cannot be fully developed until we know what underlying pathology. A nice piece in Science magazine neatly summarises the three key hypotheses for this (which are not necessarily mutually exclusive): persistent viral infection, a dysregulated immune response, and damage and poor oxygenation caused by micro blood clots.

On the (admittedly depressing subject) of covid, an Israeli study is also pointing the finger at covid for the recent rises in cases of paediatric hepatitis and liver failure. Several countries have seen a rise in serious hepatitis (liver inflammation) in children, with unfortunately some children requiring transplants and even some deaths. One of the largest increases has been seen in the UK, with 240 cases as of 7th June (source: UKHSA here). Most are in children under 5 years old (so unvaccinated against covid, before the anti-vaxxers start frothing at the mouth). Should you go to the UKHSA website, you will note that they still list adenovirus as the leading suspect for the rise, but this has been hotly disputed – largely because this particular strain of virus has not been previously associated with hepatitis, and, whilst it’s sometimes being found in these children, it’s not really being found in the liver. In fact, several experts pointed out that it was a bizarre hypothesis with no real evidence to support it. I personally couldn’t understand this focus. Others suggested lockdowns leading to an “immunity debt” – which was frankly absurd, given that many countries with affected children didn’t even have lockdowns!

Several experts have pointed the finger at Sars-CoV2 – and notably, the UK was very late in approving the vaccine for 5-11 year olds, compared to other countries. Hepatitis has already been noted as a complication of serious covid. Now, an Israeli study has confirmed what everyone without their head in the sand knew: it’s a sequel of covid infection, caused by an autoimmune reaction. Importantly, this means it needs treating with steroids not anti-virals alone. Findings of adenovirus were likely coincidental, or an opportunistic infection after the children were already ill. “The scientists concluded that the most likely causes of the acute hepatitis were either a post-infection immune reaction like MIS-C or an abnormal immune response to the novel coronavirus which primed the body for other infectious agents like adenovirus.” The study is paywalled, but there is a good write-up in The Jerusalem Post here.

The persistent denial of reputable organisations like the UKHSA of this being covid-related is hugely concerning to see. There seems to be a vested interest in denying covid as the cause – possibly because that would mean admitting that we are letting an unknown virus rip through our largely unvaccinated children uncontrolled after saying it was “mild”.

So, sorry to bang on the same drum repeatedly, but I’m cross about this – especially as my own child just recently contracted covid in April, right after I was finally able to book a vaccine for him (which I then had to postpone). Covid is much more dangerous than flu, including to children, and multiple infections can only spell bad news – if not hepatitis, and the increased risk of other complications – then a big risk of developing long covid. What’s worse, it seems that vaccination may not significantly lower your risk of getting long covid. They are working on better vaccines – a key step up would be intranasal vaccines to stop transmission, but you can’t wait for that. So, vaccinate yourself and your children, wear a good quality (FFP2/N95) mask in indoor settings in public, and petition your schools and governments to install proper air filtration. There is a way out of this – and it’s not denial and pretending everything is fine now.

Had enough of viruses? How about a deadly bacterium? One of the worst ever, in fact: Yersinia pestis, the causative microbe of plague. The origins of the infamous Black Death of 1346-53, which has the distinction of being the worst pandemic in human history, wiping out some 60% of the population of Europe, have always been something of a mystery. It was known it came from somewhere in East Asia, before spreading throughout Europe, but never exactly where. Now, researchers have done a remarkable piece of detective work and traced its origins back to modern-day Kyrgyzstan. They examined skeletons from cemeteries near Lake Issyk-Kul, which had a sudden surge in the number of deaths in the 1300s. The graves described their owners as having died of the “pestilence”, and, sure enough, they found DNA from the bacterium in teeth from people that died in 1338-39. Not only that, but genomic analysis revealed it as the direct ancestor of the strain that caused the Black Death some 8 years later (and of modern day strains). The most probable means of its spread was therefore via trade routes that passed through the region. Full study in Nature here.

And finally, two piece of lighter news. Bones of the largest carnivorous dinosaur in Europe have been unearthed in the Isle of Wight in the UK, a treasure trove of dinosaur fossils. It seems to belong to a species of spinosaurus, and was up to 10 metres long – bigger than a T.rex.

This week’s Featured Image is Zophobas morio, the superworm, which is actually a beetle larva. Anyway, this cool little beastie will happily eat polystyrene for dinner – and even thrive on it. The larvae munches the plastic – a common staple of takeaway containers and packaging – into tiny bits, but the real work is done by bacteria in its gut, which have key enzymes able to break down the polystyrene. It’s hoped that these enyzmes can be engineered for use in plastics recycling. Full study in Microbial Genomics here (favourite quote: “the faeces changed from light brown to white”!)

Featured Image

The superworm, photo from University of Queensland.

Smart tech for diabetes, new improved human genome, and return of the beaver.

Firstly, smart tech starting to make a big impact in health. A new hybrid artificial pancreas system for type 1 diabetes makes it much easier to manage insulin doses and blood glucose, particularly for young children. Type 1 diabetes results from autoimmune destruction of the beta cells of the pancreas, which normally make insulin, a hormone that promotes glucose uptake from the blood. Long term, it is fatal if untreated. Insulin injections have been the standard therapy for years, but it’s difficult to manage well with the daily fluctuations in blood glucose that occur with food intake and activity levels, particularly overnight. The new system combines a glucose monitor, insulin pump and an app into a “closed loop hybrid system.” This means that insulin doses need to be administered manually at mealtimes, but all the rest of the time the system works by itself. This is particularly useful in young children, for whom it is difficult to manage peaks and troughs in blood glucose, especially given their highly variable activity levels, food intake and growth spurts. It showed much better results than a control group. Study published in the New England Journal of Medicine here.

Related to that, the NHS in England is rolling out a skin sensor to monitor glucose levels, as a trial showed that, paired with an app, it reduced the need for fingerprick blood tests by up to 50%. This is a big difference, and will significantly improve diabetics quality of life (and hopefully also their health, as good blood glucose management is key to preventing complications).

Regrettably, we can anticipate a substantial increase in type 1 diabetes in children, as covid-19 infection raises the risk of developing the disease by up to 166%. This is a risk that could have anticipated, given that it’s known that type 1 diabetes often develops subsequent to viral infections such as rubella, and is another damning indictment of the current policy of mass infection.

On the lines of “new and improved”, we now have a beautifully sequenced new and improved version of the human genome. I’m old enough to remember when the first draft of the human genome came out, to great excitement, 21 years ago, when I was a student. Everyone in science had been watching the race between the publicly funded Human Genome Project and private Celera Corporation. When the project started, the computing power available wasn’t even sufficient to complete the job in anything like a reasonable time – the researchers relied on Moore’s law giving a doubling of processing power every year, meaning that it would later be sufficient – which it was. That original, although a hugely significant scientific achievement, didn’t in fact manage to sequence every last bit of the genome: there’s a lot of repetitive DNA outside of genes that’s quite difficult to sequence, and, of course, there is variability amongst human genomes. Specifically, they sequenced the “euchromatic” DNA, which is less densely packed and gene-rich, and left out the “heterochromatic” DNA. The latter is largely in the centromeres that hold the two sister chromatids of the chromosome together, and the telomeres, which form protective buffers at the end of chromosomes (and are selectively lost as we age). The “Telomere to Telomere” consortium has filled in the last remaining unsequenced 8%, giving us a much better understanding of the genomic architecture of the chromosomes. Additionally, they discovered more than 2 million additional variants in the human genome. The research is published in Science magazine, in 6 related papers, the first of which may be found here.

Today’s wonderful animal is the Eurasian beaver, which has been reintroduced to London 400 years after they became locally extinct. Beavers are ecosystem engineers, and it’s hoped they will restore biodiversity and limit flooding. A pair were released on the Thames in Enfield. Here’s hoping they flourish (and that our water companies stop dumping sewage in rivers).

Featured image

Eurasian Beaver (nature reserve in Ukraine), Ryzhkov Sergey, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

Intermittently fasting flies, spiders, covid news (good and bad) and dancing PhD students.

In my last post, I focused on how what you eat, rather than how much of it, is an important predictor of obesity. There is increasing evidence that when you eat is also important too. There has been a rise in popularity of intermittent fasting diets – either eating only at certain times, or alternating days when you and eat. It seems like, in fruit flies at least, time-restricted eating increases their lifespan and improves their health. This involved an extended period of overnight fasting, which seems a lot more achievable (and probably safer) than alternate day fasting, for example. The study links this to the circadian rhythm, which may also explain why shift workers on irregular or night shifts are more prone to ill health. Full study here.

Good news, bad news with Covid-19. Good first: a large-scale trial has shown that a commonly used drug to treat rheumatoid arthritis, baracitinib, reduces the risk of hospitalised patient’s dying by 13%, which is not insignificant. It works by dampening down the immune response: the steroid dexamethasone, also used to treat covid, does the same thing by a different means, highlighting that an over-active immune response could be causing severe disease in some people. Bad news now: even if you only had a mild case of covid (like I did, pre-vaccines, gulp), it significantly elevates your risk of having a heart attack for up to a year after infection, not to mention other cardiovascular problems, such as pulmonary, embolisms, stroke, etc. This is a massive study, so a robust finding, and the risk applied even if you were young and relatively healthy. Yet another reason why we should be taking the long-term effects of covid seriously, rather than let infections rip around the globe. Full study published here.

This came out a little while, but I’m highlighting it here because it’s so shocking. What do you think the leading cause of death in pregnant women in the US is? Pre-eclampsia? Haemorrhage? Infection? No, it’s homicide. That’s right: if you’re a pregnant woman in the United States, you’re more likely to be murdered than die of any pregnancy related complication. Oh, and if you’re a Black woman in the US, that risk is triple that of a white woman. Younger women (and underage, pregnant girls), are also at greatly heightened risk. As the study found: “Homicide during pregnancy or within 42 days of the end of pregnancy exceeded all the leading causes of maternal mortality by more than twofold.” No prizes for guessing which sex is doing the murdering. People working with victims of domestic violence have known for a long time that the risk of violence often begins or escalates during pregnancy. I’m actually lost for words, but at least with the data now being collected, it can hopefully attract both funding and action to tackle it. Original study published in Obstetrics and Gynecology here (paywalled).

Definitely time for something more light-hearted: how about watching the winners of this year’s “Dance your PhD” competition?

And finally, this post’s weird and wonderful animal (featured image) is the false widow spider. Actually, this is just disturbing and creepy. This species has been invading the UK (not its natural home) for over a century now, and is notorious for its painful bites. Well, now, for the first time, it has been recorded capturing a bat in its web, and feeding on it. Yes, that’s right, an actual bat – a pipistrelle bat, to be precise: the smallest in the UK but nonetheless prey of considerable size compared to the spider. You’re welcome, arachnophobes. Study here (and the researchers encourage you to email them if you see one).

Featured image

Steatodis nobilis, the noble false widow spider. By Alexis Lours – Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=114760823

Children burn energy “like a different species”, obesity, and resurrecting a woolly mammoth’s Arctic wanderings…and maybe the species

Children burn so much energy they’re “like a different species”, a new study has found. This was a comprehensive analysis of the metabolic rates of humans across a range of ages, with many interesting findings. Initially, newborns don’t have a particularly fast metabolic rate, but this quickly ramps up in small children, likely due to the phenomenal brain growth they undergo, before gradually slowing until adulthood and thereafter remaining fairly constant. Interestingly, there is a marked decline after about the age of 60, which also coincides with when most age-linked diseases such as neurodegeneration and cancer start taking a significant toll, so it is possible there is a connection there. Full study published in Science here.

Whilst we’re on the subject of energy balance, let’s talk about obesity (again). Calories in = calories out, right? So if you’re overweight or obese, you just need to cut down the calories. This is known as the “energy balance” model, and it considers all calories the same, regardless of whether they came from fat, protein, carbohydrate, etc. Well, it might not be that simple (as pretty much anyone who’s been on a diet could tell you). This is an argument that has gone back and forth for decades, based on how much influence genes have over your metabolism (definitely some), and also on whether what you eat is important. It’s the “what you eat” that’s the focus of a new (or perhaps more accurately, newly revised) hypothesis of obesity being due to a “carbohydrate-insulin” model: simply put, excess high “glycaemic load” foods (which basically means simple/refined sugars that are very quickly digested and absorbed, as opposed to starchy carbs with lots of fibre) are the culprits. This leads to excess insulin secretion, excess fat deposition, and then a rather complicated cycle of negative metabolic effects leading to obesity. I lecture a lot on this for our second year Biomedical Science students, with respect to type 2 diabetes (strongly linked to obesity), and I have some time for the idea. Sure, if you consume 3000 calories a day of super healthy food versus the recommended 2000 calories a day of super healthy food, you’re going to put on more weight. However, if you’re having, say, 2500 calories a day in a balanced diet, versus 2500 calories a day of a really sugary food, I’d be willing to bet you could probably stay a healthy weight on the former but not the latter diet. It correlates with the observation that the increased mass availability of highly processed, high glycaemic index foods in Western populations has been paralleled by the increase in obesity. I think it also helps explain the observation why, in the Western world at least, obesity is a disease of the poor. Poverty here means not being able to buy a variety of healthy foods, lacking cooking skills or equipment, and lacking time to make balanced meals. It means, ironically, focussing on calories: poor people who can just about afford to feed themselves, have to go for the “bang for your buck” approach – energy and calorie dense food, which costs less, calorie for calorie. This doesn’t mean “carbohydates” are “bad”, by the way – we have an absolute need for carbohyrates, but, ideally, more in vegetable than biscuit form. Eating a low-glycaemic diet may be a more effective way of losing weight than simply counting calories – but there need to be more studies done on this, as it’s very difficult to disentangle all the interacting factors. Oh, and exercise – even if doesn’t make the pounds drop off quickly, it improves the insulin sensitivity of your muscles and will help with long term health and weight maintenance. Original paper here.

Today’s amazing (but alas extinct) animal is the woolly mammoth. By analysing his tusks, researchers have calculated that a woolly mammoth named Kik, who lived some 17,000 years ago, walked far enough in his lifetime to circle the Earth twice, or 70,000km. He lived to be 28 years old, so that averages around 7km a day, varying between life stages, traipsing largely around Alaska. They worked this out by analysing isotypes of strontium in each of the layers of his tusks, which were added to each day. These vary dramatically depending on where the food is from, due to variations in these isotopes in the underlying rocks. It’s a fascinating insight into the life of a prehistoric animal, revealing, for example, a dramatic increase in activity at 16 years old, when he might have been booted out of the matriarchal herd he grew up in, as modern day elephants are. Their analysis also lends support to the idea that climate change helped drive the mammoth to extinction, as it would have been difficult to maintain this level of mobility as the ice age ended. Full study published in Science here (paywalled, unfortunately).

The woolly mammoth has also been in the news recently for another reason: a “de-extinction” project is aiming to (partially) “resurrect” this ancient species. There’s been talk of cloning the woolly mammoth from preserved DNA for some time – this is actually something different. Instead, the project aims to genetically engineer an Asian elephant embryo with traits adapted for the Arctic tundra, which they describe as a “elephant-mammoth hybrid”, and, later, other extinct mammals, partly to restore ecosystems damaged by climate change. There’s a more nuanced overview of some of the questions and answers at the Natural History Museum website here. I have so many problems with this. Firstly, it’s not a “hybrid”, really – that would imply a successful fertilisation between an elephant and a mammoth. It’s a mutant. An elephant mutant genetically engineered to be hairy and with some extra fat, and likely a lot of problems successfully gestating it and bringing it to term. It’s not even clear which mutations will be required – we don’t have that detailed a view of the different genomes. The fact that the two species have 99.6% genetic similarity doesn’t mean it would be easy – or right. This is like trying to engineer a chimpanzee embryo to be more like a human, which I hope illustrates the difficulty – and let’s not go there, please. As for re-creating ecosystems: we’re not talking about recent ecosystems, and an animal that has been driven to extinction by recent climate change, we’re talking about something that went extinct as the last Ice Age ended. We’re not in an Ice Age now, clearly. What you would be doing is introducing a new species into a different environment from either the Asian elephant or the woolly mammoth and expecting it to – what? Not to mention that cloning 1 animal does not a viable breeding population make. Anyway, this is all my scientifically polite way of saying that I think it’s a stupid, unethical idea, and I don’t care who knows it. If you want to restore something to help with modern climate change and ecosystem, stop chopping down the Amazon and restore peat bogs, for a start.

Image

Woolly mammoth skull and tusks in front of a reconstructed image, Natural History Museum, London, UK. Photograph by Emőke Dénes, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

Carb-loading, obesity and the greater of two weevils.

One of the things that has always slightly irritated me in discussion of diets is the common assumption (notably in the so-called “paleo” diet) that ancient humans didn’t consume much starchy food, or carbohydrates in general. Apart from the scarcity of meat, a lot of plant material would contain a fair amount of carbohydrate anyway, and the brain has an absolute dependence on glucose. Carbohydrates, if they could get them, would be a valuable source of calories. Besides, I love carbs, and nobody’s going to take them away from me! So it’s gratifying to see emerging research that our ancestors – including ancient hominins like Neanderthals – were carb-loading long before agriculture was invented. In fact, they probably ate a fairly balanced diet (as we should) – oh, and many societies also drank beer very early on, which I can also get behind. There’s an audio version of the story here. What’s more, studies of residues from Neanderthal teeth indicate that it was likely carbohydrates – not meat – that drove the evolution of big brains in hominid species.

Whilst I’m on the subject of diets, are you one of those annoying people who can eat whatever they want and never put on any weight? (At the risk of losing all reader sympathy, I am, although my metabolism is clearly slowing as I hit middle age so it may not last). Or does a single square of chocolate go straight to your hips? Well, it seems you can thank/blame your DNA a bit either way. A huge DNA study, involving sequencing the genomes of over 600,000 people worldwide, has identified genetic variants that protect against obesity. I’m always slightly leery of these huge screens because you can pull up a lot of red herrings in your genetic fishing net, but this one is very comprehensive. Fascinatingly, a comparatively large number of these variants were in a family of signalling molecules called GPCRs (G-protein coupled receptors), which bind hormones and neurotransmitters and regulate virtually every process in your body. People who carried an inactivated version of one receptor were on average 5.3kg lighter than those with the full version, and a mouse study mutating the same gene backed up this effect. Over 5kg is a big difference, and could lead to potential treatments and a greater understanding of how our metabolism is regulated. Original study published in Science here (paywalled).

Are you confused/completely fed up with people discussing “herd immunity”? Well I am, especially as so many non-experts get it hopelessly wrong. There’s a nice, clear explanation of herd immunity and what it means for Covid here.

And finally, our amazing organism for this post is the humble weevil. Or not so humble weevil in this case. A new fossilised species of weevil (a type of beetle) with an enormously long trunk/beak has been discovered. It’s so novel it’s not only a new species but a new tribe and genus too. (There are over 100,000 types of weevil: if I know anything about biologists, it’s that the specific relationship of this type of weevil will result in impassioned scientific discussion for some time). Males of Rhamphophorus legalovii probably used their long trunks to battle with other males. Original article here (paywalled).

I’ll just leave you with Captain Aubrey’s terrible joke now…

Featured image: Rhamphophorus legalovii by G. Poiner, Cretaceous Research https://doi.org/10.1016/j.cretres.2021.104948

Is a pan-coronavirus vaccine possible? Plus: sweaty humans and the barn owl of dinosaurs.

I’m aware that I’ve already broken my promise not to talk about coronavirus, so I guess it won’t hurt if I break it again, right? Anyway, you may be concerned about all this talk of variants in the news, particularly the India variant that is wreaking such havoc in Asia. There is justifiable concern that the vaccines we’ve developed may not be as effective against variants that will evolve. This, of course, is one good reason why we should aim to get as close to “zero covid” as possible: keeping the number of cases down limits the possibility of advantageous (to the virus) mutations to arise, potentially ones that we would have to develop new vaccines against, in a potentially endless cycle.

But what if we could make a global coronavirus vaccine that would not only be effective against all the different variants of covid-19, but also potentially against other deadly coronaviruses like MERS and SARS-CoV-1? This could preventially prevent the next pandemic. Researchers are already looking into this, as this interesting and thoughtful (and hopeful!) piece in Science explores. Many of these are targeting the common “spike” protein that these viruses use to infect cells, but focusing on generating antibodies against multiple different regions, particularly those that are common across different virus species and that do not vary as much. Others take the approach of trying to active T-cell responses, rather than B-cell producing antibodies, or even the old-school tried and tested means of using a combination of inactivated whole viruse to generate an immune response. It’s encouraging that scientists are already thinking ahead and trying to tackle this problem.

Why are humans so sweaty? Sorry: but yes, we are. Really sweaty. Compared to most other primates, we have 10x the density of sweat glands in our skin. This is our key way of regulating our body temperature and helping us to cool down. Unlike most other apes, we evolved on the hot, dry African savannah, and not the jungle. Not only that, but we relied heavily on the ability to run to hunt prey, particularly over long distances. All that makes for a hot hot human who needs to cool down: sweating works by evaporative cooling, in which the heat energy dissipates as the moisture on our skin vaporises.

But how did we evolve this ability? A lot of the traits that we think of as human are complex, evolving changes in multiple genes. Increasing the density of sweat glands, however, appears to have been relatively simple. This is controlled by the activity of the gene Engrailed (first discovered in fruit flies – another example of how important this model organism has been). By altering the activity of control “enhancer” elements of Engrailed in mice, researchers have demonstrated that multiple changes in the control regions of this gene have resulted in higher levels of Engrailed, and so more sweat glands. It’s a really neat piece of work that also demonstrates a key theme of evolutionary developmental biology: changes in regulatory DNA often have more profound effects than changes in the bits that actually code for proteins. There’s an accessible Science Daily article here:

Today’s amazing animal is, alas, extinct. It’s an extremely bizarre (and cute) dinosaur called the shuvuuia that had extremely good hearing and night vision, judging by analysis of fossils of its skull. Of course, birds are descended from dinosaurs (theropod dinosaurs, to be precise, which are the ones that tended to walk on two legs, like T. rex) but it’s interesting to see that some had specialised adaptations that we see in much later bird species, like barn owls. Shuvuuia is part of a group of dinosaurs called alvarezsaurids, which share a unique characteristic in common with modern birds: they can lift the upper part of their jaws in relation to their skulls. Indeed, the alvarezsaurids may be more “bird” than “dinosaur”. It may also help explain the shuvuuia’s bizarre appearance: this funny little creature not only had feathers, but long legs and tough little forearms with a single claw. Likely it hunted insects at night and used the claws to excavate prey from burrows. Original paper published in Science here, with a brief news piece here (both paywalled, alas).

Featured image

Shuvuuia deserti: artist’s impression by Victor Radermaker

Brains, ears, tongues (and a bit of Covid)

Good news for those suffering from tinnitus, in which a persistent ringing or buzzing is heard, not caused by external sounds. Although this doesn’t seem serious (if you don’t suffer from it…) it affects a whopping 15-20% of the worldwide population, and can range from annoying to downright dibilitating. Moreover, it looks like there’s been a rising incidence during the pandemic, possibly due in some cases to long-term effects of covid infection. So it’s great to see an effective new treatment do well in clinical trials (I missed this study when it came out last October). Oddly enough, it involves electrically stimulating the tongue at the same time as sending audio pulses to the ears, calibrated for each individual patient. This is a process of medical neuromodulation, in which a targeted stimulus is used to alter nerve activity. After a 12 week course of treatment, the majority of participants in the trial reported improved symptoms for up to 12 months afterwards. The study is published in Science Translational Medicine here (paywalled).

One jab or two to protect against Covid-19? It’s a debate that’s been going back and forth; generally you will need a booster vaccine, but some of the vaccines coming through are designed to give protection with only one dose. However, if, like me, you’ve already had Covid-19, it looks like you only need one dose of the mRNA vaccines (Pfizer, Moderna) to get protection, with this triggering a robust immune response, and the second dose not making much difference (not that would hurt it you had it anyway) If you haven’t had Covid, you’d need both doses. Study published here in Science Immunology (and really one for the immunologists, as it’s quite technical).

Today’s weird and wonderful animal is the Indian Jumping Ant, which can selectively shrink and regrow its brain in response to its reproductive status (no jokes about baby brain please!). Worker ants, who do not reproduce, have larger brains, but, if the colony lacks a queen, they can shrink their brains and grow their ovaries to invest all their energy into laying eggs. The researchers found that they were fully capable of transitioning back to worker status if they artificially simulated that environment, shrinking their ovaries and regrowing their brains. Amazing! Full study published in Proceedings of the Royal Society B here.

Image Credit

“This image reveals a worker jumping ant Harpegnathos saltator murdering the queen. The queen had just torn off her own wings after a successful mating and was scouring the forest floor in search for a suitable nest site. Though this de-alated queen was ‘murdered’, a large number of her sisters successfully established nests, thus completing their life’s mission – passing on the colony’s genes.”

Kalyan Varma, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

Placentas as mutation landfill, and solar-powered, self-decapitating seaslugs that regrow their own bodies

Well, now I’ve got your attention with possibly the weirdest title I’ve ever given a blog post, I do have some weird and wonderful stories for you.

First up: placentas as mutation landfill. I was trying to think of a more “sciency” way to describe this, but it got too complicated. And anyway, it’s (sort of) true. We’re used to thinking of the placenta (if we think of it at all) as a lovely, nurturing organ that sits there stuck to the side of your womb when you’re pregnant, supplying all the good stuff to the developing baby and taking the waste away. Turns out that it’s not just waste in the sense of waste byproducts from metabolism. The placenta actually acts as a sort of dumping ground for genetic mutations in the early embryo. How?

Just a bit of embryology to start: the placenta isn’t part of the mother, it originates from the foetus. In the very early developing mammal embryo, at the blastocyst stage, it consists of a hollow ball of cells. In the middle of the ball is the inner cell mass, which will go onto form the actual foetus. The outer layer is the trophoblast, which implants into the lining of the uterus (womb) and forms the placenta. (Quick video of implantation here). Theoretically, they should be genetically the same. But it’s been known for a while that in 1-2% of placentas, some of the cells have a different number of chromosomes than they should. Having just one extra chromosome can cause significant problems and is frequently fatal; Down’s syndrome, in which three copies of chromosome 21 are present instead of the usual two, is one of the rare survivable conditions, for example. It’s also the case that aneuploidy – having too many or too few chromosomes – is a very common defect in human eggs, and is one the leading causes of early miscarriage. So, too, are problems with the placenta.

A new study has taken a detailed look at the genomic architecture of the placenta, and the organ is like no other human organ: it resembles something more like a patchwork of tumours, with distinct clonal populations having different mutations in them. Surprisingly, in many cases, the placenta seems to function fairly well. But why is it such a mutation-riddled mess? Interestingly, many of these mutations are associated with childhood cancers. But what’s fascinating is that in at least one case, a defect present in the fertilised egg seems to have been corrected: a “trisomic rescue”: the cells that went on to develop into the foetus had managed to revert to having just two copies of their chromsomes (correctly), but the placental cells did not. This fascinating finding seems to support the theory that the placenta is, in part, acting as a “dumping ground” for harmful mutations present in the fertilised egg: the embryo avoids them, but the placenta does not. Original study, published in Nature, can be found here. An accessible Science Daily summary can be found here.

Today’s weird and wonderful animal is the sacoglossan seaslug. Specifically, two species that are able to grow a whole new body once their head is severed, which they do deliberately to get rid of a parasite infection. It’s an extreme example of autotomy, the self-amputation of a body part (e.g. a lizard shedding its tail to avoid a predator). It’s the severed head of the seaslug that grows a new body: the cast off body dies. How does the head manage to grow a new body when the seaslug can’t digest any nutrients? Well, and this is just as cool/strange: the seaslug is able to incorporate chloroplasts, the photosynthetic machines of plants, into their own cells from the algae they eat, and use this to get energy and carbon compounds from sunlight. Incredible. Great video from the Guardian below. Original research article, with more video, published in Current Biology here.

Image credit

Elysia marginata, Rickard Zerpe, CC BY-SA 2.0 https://creativecommons.org/licenses/by-sa/2.0, via Wikimedia Commons