Sunday, January 1, 2017

What Genetic Modifications are Magic?

‘Magic’ is used here as a code word to mean something that, for one reason or another, cannot happen. Magic items can be impossible because of scientific reasons or economic ones. In this example, that would mean that there is some technical barrier that would prevent some type of genetic modifications from becoming universal, or that the cost of doing so would be prohibitive, even in an advanced alien civilization. One extreme case would be that any genetic modification would be feasible and affordable, and then the conclusion would be that no genetic modifications were magic. Another extreme case would be that the cost of a certain level of genetic modifications was comparable to the cost of raising a young alien from the first steps until they reached adult status, effectively doubling the cost to add a new alien to the adult population.

Since genetic modifications would create a tremendous difference in the nature of an advanced alien civilization, it is worthwhile examining this question. Previous discussions have assumed that the feasibility is there and the costs are low, but is this true?

There are two aspects to genetic modification. One is the technical side, meaning the procedures and equipment needed to either create a new string of genes, or to modify an existing one. It would also include the ability to map an existing string of genes, prior to any modifications. This is close to where Earth science is now. We on Earth have invented machines able to decipher and record strings of genes on almost any set of chromosomes, for any organism. The cost of such deciphering has dropped astronomically over the last few years. The modification part is also currently a topic of research, and appears likely to be solved within a few more years here on Earth. By solved, we mean the ability to remove any gene from a series, insert a new one wherever desired, or both, meaning replacing an existing gene with a different one. The methods used today do not do modifications of genes in place, but that step will likely occur over the next few decades. This last step will make modifications somewhat less chancy and more robust. But whether or not this step is completed here in a few years or much later than that, it does not seem to pose any feasibility problems.

The other aspect of genetic modification is further off for us, and therefore may be an obstacle not clearly envisioned. That aspect is the determination of what each gene does, in the context of the complete organism. The two ways of assessing the functions of each gene are the same two that appear in any investigation of a complex problem. One is statistical, and the other is normative.

With a large number of organisms of the same kind, with some genetic variation between them, a collection of attributes, perhaps quantitative, can be matched against the genetic code for each individual organism. For those genes where there are variations, it might be possible to determine a correlation between attributes and gene variations. This is easier to do with gene variations that lead to single changes, such as some non-fatal problem. When there are interacting genes, the problem of translating gene variations to attribute changes becomes much harder. First, there is no list of all attributes that might be affected, and creating a list requires more than just taxonomy. Second, there is no reason to assume that a single gene only creates a single change. Third, there is no reason to assume that genes do not cooperate to produce some attribute. These three reasons, and certainly more, mean that the statistical approach will be a slow one, and perhaps not successful.

Another problem with the statistical approach is that there may be no variations present in some genes. Without these variations, nothing about the function of the genes can be determined. Even if there are some variations, the numbers present may be small. If a gene variation is only present in one in a million individuals, there will be no good statistics without a very large population. This means genetic deciphering of a huge number of individuals, at a large cost. For bacteria this might be a feasible approach, but for larger organisms, not so much.

These and other problems with the statistical approach to interpreting the functions of individual genes means the other approach, the normative one, needs to be considered as well. This approach means that an understanding of the entire ontogeny of the organism. The problem with this is that the original zygote or equivalent is composed of identical cells, but they soon differentiate. This differentiation is one part of the genetic control of the cells, and this differentiation would not be solely controlled by the genetic code, but also by chemical signals from other cells. In other words, each successive modification of a pluripotent stem cell would have to be understood, as well as the determination of the signals which lead to each of these modifications. Some genes in the genetic code may be tail-end genes, which only come into operation after a cell has differentiated to the final stage, such as Kupffer cells, which are macrophagic cells only found in a liver, or photoreceptive ganglions in a retina or a thousand others. Others could be front-end genes that operate even in the stem cell. Others could be coding for the chemical receptors which govern differentiation.

To understand genes from a normative viewpoint, a complete ontogenic map would have to be drawn, showing what different differentiations occur, in all the different organs of the organism, and what genes control the differentiation and then which genes control the quantitative aspects of each differentiated cell. Genes do not differ between differently differentiated cells, but the epigenetic methylation on each gene can control how the gene operates, or if it operates at all. The question, is the situation simply too complex to be completely figured out? If so, the genetic transformation will not be able to reach the limits that can be so easily imagined.

It is possible to do, not a genetic transcription, but an epigenetic transcription. These would have to be done for each type of differentiated cell in the organism in order to figure out the functions of genes in different cell types. Knowing the difference in epigenetic controls in each type of cell would help to determine the function of the genes, but would certainly not provide the full story. There would have to be a coupling of the genetic variation information with the differentiation information, as well as the mechanisms by which differentiation happens. The very large amount of research needed for all this might never be supported on an alien planet, as the large majority of it does not lead to any clear benefits. Perhaps the best tentative conclusion would be that only in alien civilizations which have a surfeit of productivity at the time of the genetic grand transformation would be able to accomplish the transformation. Both the success stories and the failures need to be considered in assessing the presence, longevity, and traveling of alien species.

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