Human Brain in a Mouse?

Would it be ethical to construct a mouse with a human brain? It sounds too impossible to worry about.

Yet various kinds of “humanized mice” are not just possible, but routinely for sale at breeding centers such as Jackson Laboratories. For example, a mouse’s population of bone marrow stem cells can be replaced with human stem cells, generating a mouse with a “human immune system.” I put this in quotes because how human can the system be, with all its connections to other parts of the mouse body?

Nonetheless, these “humanized” models lead to medical advances in cancer and other medical research. And bacterial humanized mice—mice harboring human gut microbiomes—are the kind of research even Kenyon undergradates may contemplate.

The trouble is, humanity is seductive—addictive, if you will. No matter how much you humanize, a bit more human is always better. That was the background of A Daughter of Elysium; human hybrids led to slaves, and experimental developmental models, all to help humans live past a thousand years. But the more human, the better model… so suppose the model gets to be 50% human? 90%? 99%?

Would a mouse with a human brain be a human in a mouse body?
In 2000, a researcher first proposed to develop a mouse with human brain cells, using a mouse strain whose own brain cells are genetically programmed to die early in development. Bioethicists formed a committee to address whether this research was ethical. How seriously, I’m not sure. They deliberated for five years before concluding that “the question does need further work.”

Today, researchers study mice with human brain cells.

Jonathan Hasselmann and a large team at UC-Irvine, UC-San Diego, and McGill University, developed mice with human microglia—not neurons, but the neurons’ intimate defense partners. To do this, the researchers converted adult human tissues into pluripotent stem cells (the kind that could almost make a baby). The stem cells, capable of many developmental paths, also were engineered with a fluorescent protein (GFP) to tag them. Researchers injected these tagged, development-capable stem cells into the fetal mouse forebrain. Eventually, a region of the brain showed 80% human microglia.

The human-origin cells could be detected as dots of green fluorescence. Ironically, the green-fluorescent GFP itself originates from jellyfish, a third participant in this Franken-human construct.

The aim of this research? Finding therapies for Alzheimer’s disease, Parkinson’s, and other dread human conditions. There is no denying the need to treat and prevent these devastating conditions. And we inexorably approach every nearer the daughters of Elysium.