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.