Scientists turn skin cells into sperm cells, but raise provocative new questions

[Reefa]

Scientists can now reprogram cells from the skin of an adult to turn into cells that would be at home in any organ of the body. An exception to this has been that making germ cells — the egg and sperm — still requires a fully developed human. New research, just published in the journal Cell Reports, suggests that even these special cells can be created in the lab. What this really means is that the limitations to further progress are no longer scientific or technological in nature. Instead, the limits have become the problem of a new kind of engineering — ethical engineering.

In our age, getting pregnant can often be harder (and more expensive) than avoiding pregnancy. While men shoot blanks for a variety of reasons, inherited genetic defects and chemotherapy are common ones. The ability to convert the skin cells of these men into sperm — thus reopening the doors to biologic fatherhood — would be nothing short of miraculous. But to make mature sperm cells, you need to do more than just arrange things properly inside the cell or its nucleus. In addition, you need to coddle the cells in the proper environment, which prods them continuously with formative external influences.

Among the developmental tricks nature uses to rough out many organs and tissues, a particular favorite is for localities of cells to coalesce and essentially hack for themselves an interior fluid space known as a lumen. The cells that line these hollow lumens, whether they are to become the ventricles of the brain, or perhaps future sensory organs or air passages, typically sport hair-like cilia that wave like sea creatures permanently affixed to the sea floor. With just a few changes to this basic plan, you get sperm cells lining the insides the seminiferous tubules in the testes, with their tails projecting into the inner space.

To sidestep the procedural risk and ethical unknowns of injecting rebuilt sperm precursors into the testes of men, the researchers did something a little different. After harvesting the men’s skin cells and transforming them into all-powerful stem cells, they injected them into the testes of mice. There was evidence this plan might work because mice have previously been bred from other mice using skin cells that have been transformed into both eggs and sperm. Using the human cells, the researchers were able to grow cells that went on to become sperm cell protégés inside the mice. They’re not quite fully developed sperm with tails, but rather, are immature apprentices to sperm with all the molecular hallmarks of potential.

These hallmarks are basically protein or nucleic acid markers that the cell produces when dedicated to any particular fate. They are often visualized using what molecular biologists refer to as a “heat map.” These maps are basically colorized matrices that indicate relative abundance of different things in the cell. Mentioning a heat map to your genetics counselor will let them know you are not one to be trifled with. It’s kind of like asking a potential mechanic if they can read U281 OBD2 codes for CAN VW Audi.

It doesn’t require too much imagination to see potential concerns with this new capability. Bioethicists have pointed out that little would stand in the way of someone lifting a hair from say, George Clooney, and running off to the lab to make Clooney clones. It would also be conceivable that samples from those long dead and gone could even be used, perhaps a husband killed at war can still be father. Talk of establishing new human rights, rights of consent, or of criminalizing such activities may be premature without any ethical infrastructure to support them. Fore example, “ownership” of DNA — particularly for something like the DNA in our mitochondria — would be tough to definitively establish. We inherit these sequences from our mothers with little change, and she in turn inherited it from her mother. Many people, especially those related, share very similar sequences.

The idea that mere rules can govern all the ethical situations that arise seems futile. Like any engineering discipline, physical instruments, structures, and protocols will need to be designed, implemented, and operated with an as yet unimagined cohesion. Properly constructed inter-dependencies among new civil, biomedical, and social tools may both limit and enable according to precedent and consensus that is newly laid seemingly as fast as it can be advertised. Included in a new ethical science then, may be rules that do not deal directly with times and places, people or events. Instead, it will deal with what we might recognize as the core problem in ethics: that of predicting and dealing with contradictions in general. A science of contradictions, in which they are not just expected, but sought, may be more efficient and practical than trying to microlegislate specific instances of them as they arise.

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