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Down Syndrome Discovery Has Implications for Human Genetic Engineering

*subhead*Small changes, big effects*subhead*
The 21st human chromosome is the smallest of all our chromosomes. It contains a few hundred genes and is only 1% of our total DNA. As most people know, an extra chromosome 21 causes Down Syndrome. What most people did not know, until research published this week, is that tiny chromosome has an effect across the whole human genome.

Instead of simply being an extra copy of each of the genes on chromosome 21, trisomy 21 has an effect on the expression of genes on other chromosomes. The Scientist has the story of the fascinating research that lead to this discovery:
The deleterious effects of trisomy 21—the extra chromosome behind Down’s syndrome—can be seen across the entire genome, according to a study published today (April 16) in Nature. While studying a pair of monozygotic twins in which only one person had Down’s syndrome, a team led by Stylianos Antonarakis of the University of Geneva Medical School in Switzerland discovered that trisomy 21 can affect other chromosomes.

This rare twin pair allowed the researchers to compare the effects of Down’s syndrome on gene expression in two otherwise genetically identical individuals. The researchers found that in the twin with Down’s syndrome, genes in territories along the chromosomes that are highly expressed in people without the disorder showed reduced expression, while genes in territories that are normally suppressed were more highly expressed.

“The fact that they’ve got these really nice domain structures genome-wide further implicates the rising perception of the Down’s syndrome response as being more of a systems-level response, rather than . . . just the simplified perspective that we’ve had for a long time”—that the extra chromosome 21 is alone responsible for the symptoms of Down’s syndrome, said Robin Dowell of the University of Colorado at Boulder, who was not involved in the work.
Understanding how the extra genetic material in those with Down Syndrome affects the rest of the DNA in the cell is a critical step toward effective gene therapy, so this is a major breakthrough.

This discovery also reinforces what we are beginning to understand: genetics and gene expression are a lot more complex than just a sequence of DNA. There is a symphony of influences that affect how genes are expressed and even a tiny piece of DNA can alter the music. This quote really stood out to me:
“The mere addition of a small piece of DNA—about 30 megabases, or 1 percent of the genome—can disturb the entire transcriptome, all the genes of the genome. And not only disturb them, but disturb them in a specific and programmed way,” said Antonarakis
In other words, when it comes to genetics, small changes can have big effects.

Which makes me wonder about the wisdom of creating children with three-genetic parents. The mitochondrial DNA outside the nucleus that is "switched out" for donor DNA in this process may seem so small as to be insignificant, but is it? Will that tiny piece of DNA have much larger effects than expected? This new understanding about the effect of our tiniest chromosome suggests that to proceed with the genetic engineering of children to have three genetic parents is really a reckless shot in the dark.

Also, there are the transhumanist dreams of radical genetic modification of humans. How does this discovery speak to the idea of genetically engineering otherwise healthy human beings with artificial chromosomes for enhancement purposes? Transhumanist George Dvorsky thinks an extra artificial human chromosome (AHC) is not a bad idea:
But adding extra chromosomes artificially won’t necessarily be a bad thing. And in fact, they could be quite advantageous. When inserted during the in vitro fertilization (IVF) stage, they could serve as remarkable and flexible platform for the insertion of genetics.

“The main attraction of creating an artificial human chromosome is that they can be passed down from generation to generation,” says Stock. “There’s all sorts of mechanisms and structures in place that would allow for the division and faithful reproduction of those chromosomes.”

...AHCs could also give humans new capacities altogether. Stock speculates about a range of futuristic enhancements, including the ability to see ultraviolet light, or navigation in the dark by a system of sonar similar to that employed by bats.
This new research suggests that AHCs may have serious unintended consequences, and, if done as Dvorsky explains above, these would plague generation after generation.

This is why the Church teaches that any genetic intervention must be for therapeutic reasons where the intent is restoring natural development and the risk is balanced with the opportunity for healing. As this passage from the Charter for Health Care Workers states:
"In moral evaluation a distinction must be made between strictly <therapeutic> manipulation, which aims to cure illnesses caused by genetic or chromosome anomalies (genetic therapy), from manipulation <altering> the human genetic patrimony. A curative intervention, which is also called "genetic surgery," "will be considered desirable in principle. provided its purpose is the real promotion of the personal well-being of the individual, without damaging his integrity or worsening his condition of life.

On the other hand, interventions which are not directly curative, the purpose of which is 'the production of human beings selected according to sex or other predetermined qualities,' which change the genotype of the individual and of the human species, 'are contrary to the personal dignity of the human being, to his integrity and to his identity. Therefore they can be in no way justified on the pretext that they will produce some beneficial results for humanity in the future,' 'no social or scientific usefulness and no ideological purpose could ever justify an intervention on the human genome unless it be therapeutic, that is its finality must be the natural development of the human being."
Rebecca Taylor blogs at Mary Meets Dolly

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