Tuesday, February 12, 2008

Third Party Genes and Ethics

Recently a team of British scientists from Newcastle University created a human embryo with genetic contributions from three donors. They used defective embryos left over from fertility treatments. Removing the nuclear genes from such defective embryos they transferred these nuclear genes into another donor egg which had been previously emptied of it nucleus. The recipient egg though had its mitochondria intact. Mitochondria contain their own DNA, separate from the nuclear DNA. So, the resulting fertilized egg now contained genes from three parents. All this as part of research to figure out if a class of diseases brought on by defective mitochondria can be eliminated by such a mitochondria transfer from a third party.

The Times of India carried a debate of this with a for and against forum. Uma Sethi who wrote against carrying out any such modifications to the reproductive process makes a strange case:

"One of the reasons for their jubilation is their claim that by genetically modifying life at the embryonic stage, we can effectively protect the to-be-born from risk of contracting some 50-odd diseases. However, the truth is that many diseases could be inherent in your genes, but you could live your entire life without any of those diseases affecting you; you might just carry those tendencies to your grave."

Carrying a faulty gene may enhance your chances of contracting a disease, the relation is probabilistic. Since there is no certainty that carrying a particular faulty gene will cause the disease we should take a chance and let nature take its course. Playing Russian roulette with a person's life does not strike me as a particularly ethical position to take. And what about the next generation? The person may well be unharmed during her lifetime but mitochondria are inherited along the female line. The child inheriting faulty mitochondria from a parent is still in danger of contracting a disease. Should we keep taking chances across generations? If the technology is available the solution would be to make a permanent change to the germ line.

This is what causes a revulsion in many people. Organ transplants from strangers are fine since we are not modifying genes and organs are not inherited by the next generation. But interfering with the process of sexual reproduction with a two parent system is anathema. If nature has dictated a two donor system for our genes then tampering with it means "tampering with the blueprint of life that is sacred" according to Uma Sethi. But how sacred has been this blueprint of life throughout eukaryote evolution?

Turns out that the eukaryote cell, the cell type that all multicellular complex life is composed off was itself created from a merger of different prokaryote cell types. Ironically the most important merger involved the would be mitochondria. Prokaryote cells specializing in extracting energy in the presence of oxygen (aerobic bacteria) were engulfed by larger prokaryotes which didn't have that specialization (anaerobic bacteria). The result was a symbiosis. Over time the smaller prokaryote evolved into the mitochondria and in the process transferred most of its genes into the nucleus of the host cell, retaining just those required for the functioning of the mitochondria. Mitochondria is just one example but it seems that the evolving eukaryote genome has been built through such donations from many parties since its earliest days.

Third party genes may also have played an important role in the evolution of placental mammals. Why doesn't the immune system of the mother reject a fetus as a foreign body. Turns out that :

A significant chunk of our DNA had its origins as retroviral DNA. Most of these are now inactive, but a tiny portion actually appear to still code proteins. It's been found in mice, sheep and humans (and presumably generalizes to all placental mammals) that a particular kind of endogenous retrovirus is highly expressed in the outermost layer of the blastocyst (see e.g. Venables et al. 1995 for the human example). Furthermore, when you inhibit the expression of these genes the result is uniform spontaneous abortion immediately following implantation (Dunlap et al. 2006).

Most retroviruses are immunosuppressive, the most infamous example being HIV. Connecting the dots, it's quite plausible that these particular ancient retroviruses have been recruited into the mammalian genome and serve as local immunosuppressors in the uterus during development. In fact, we already know that syncytin, a protein crucial in placenta formation, is the product of a retroviral gene (Knerr et al. 2004), so there's nothing at all far-fetched about this.

In this case, viral genes were first transferred into our ancestral genomes. Evolution modified them to serve as immunosuppressors. Those genes can no longer be looked upon as foreign third party pieces of virus. They are now functioning bits of our own genome. The eukaryote genome has always seen lateral gene transfer from third parties especially from retroviruses. For any one generation our present natural system allows genes to be transferred through only two donors. But over generations sexual reproduction means that genes are being shuffled and mixed with genes from various donors. That means say my parent's genomes are made up of genes which may have been contributed by people from all over the globe at various times during my paternal and maternal family ancestries. This mixing of genes is what make us one species. If that is the case why argue about transferring mitochondria within our species?

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