In recent years, there has been a lot of excitement about the potential for studying human diseases in what are called "organoids." These small patches of tissue, formed using stem cells, appear to produce many of the same cell types and at least some of the structures normally formed in actual organs, and thus can provide a better model for diseases that rely on the sometimes complex interactions among multiple specialized cell types that are a feature of the human body.

But even the most sophisticated organoids lack a lot of the features of a real human body. This is especially true for brain organoids, which don't form any of the connections with specialized brain structures needed to behave "normally." On Wednesday, a research group at Stanford University described a possible way to study brain organoids in a somewhat more natural context: They genetically wiped out a large portion of the mouse brain and replaced it with human brain organoid cells.

The replacements

Organoids, because they adopt a three-dimensional tissue structure and consist of various specialized cells, provide a much better model for an intact tissue than simply having a bunch of disassociated cells lying flat on a culture dish. But they still have a lot of limitations—they're not hooked up to a circulatory system that allows the liver to process chemicals the organoid produces and don't have immune cells moving through them, to give just a couple of examples.

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The genetic code is what life everywhere uses to convert the information contained in DNA into specific protein sequences. With minor variations, the same genetic code is used by every living thing on Earth, suggesting it was already present in the last common ancestor of all of them. It's not an easy thing to change, because so many things in every cell depend on it.

Nevertheless, some preliminary steps have been taken. Researchers have managed to add some new amino acids to a bacterial cell and were able to make proteins that were one amino acid less than usual. But it's a slog; for some of this work, people have had to re-engineer every single gene in a bacterial genome.

Now, researchers have found a way to operate two separate genetic codes simultaneously, avoiding the need to do any work to compensate for altering the code that every protein in a cell relies on. They didn't test it in an actual cell, and it might cause some problems there. But it's a creative solution that should accelerate some synthetic biology work.

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When the history of our ancestry is written, the fact that we've interbred with some of our closest relatives, the Neanderthals and Denisovans, will have a central role. And it will be tempting to write it as a very tidy story: Once we got genomes from these other groups, it was possible to identify the sequences in our genomes that we shared with them.

But in reality, as scientists started poking large enough collections of data, there were regular hints of some strange ancestry in our genomes. It was hard to pin down, though, at least in part because the 2 percent on average of Neanderthal DNA found in many populations does not guarantee that any two individuals will have the same 2 percent. So having the genomes of those two groups made sense of some things researchers had already been seeing.

But knowing what we do about Neanderthal and Denisovan DNA is now allowing researchers to answer a somewhat different question: Is there anything else? Using recently developed analytical techniques, they find evidence of a third lineage that we apparently interbred with before any modern humans left Africa. Again, there were hints of this earlier, but so far, there has been no genome from a modern human relative to help us understand the details—the source of this DNA remains a "ghost lineage."

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