04 February 2024

Potential Approaches To Genetic Engineering

We are fast approaching the point where the transhumanist goal of intentionally modifying humans to further our own objectives with tools that include genetic engineering is possible.

There are several approaches that could be taken to doing this that are easier and less sophisticated than simply synthesizing whole genomes, or large parts of them from scratch. And, these are the approaches the would probably dominate the early days of transhumanist genetic engineering that seeks to improve the human genome. 

Of course, each approach also comes with its own particular risks. The risks mostly flow from the fact that biological systems are highly interrelated and tweaking any one part of them can have unintended consequences if we don't perfectly understand those interrelationships (which will probably won't for the foreseeable future).

Fixing Existing Simple Genetic Disorders

The first wave of genetic engineering, which is just starting to be utilized medically, is to change single genes that cause Medellin genetic disorders like sickle cell anemia or achromatopsia, to cure these disorders.

This is among the lowest risk forms of genetic engineering. A known harm is alleviated. But it isn't completely without side effects. The sickle cell anemia gene also creates resistance to malaria when only one rather than two copies of it are present. But removing this benefit from someone's descendants is a small price to pay in someone who had sickle cell anemia and doesn't live in a place where malaria is a problem (or when someone who can be protected from malaria by other means such as a malaria vaccine).

Purging Recessive Genetic Disorder Genes

Everyone has some recessive genes for genetic disorders. And, as long as you don't have children with someone else who has the same recessive genes, this is basically harmless.

The main reason that inbreeding is fitness reducing is that it increases that likelihood that a couple's children will end up with both copies of recessive genes for genetic disorders.

But, in addition to genetic engineering to remove genes that cause genetic disorders from people who already have genetic disorders, essentially the same approach could be used to remove recessive genes that cause genetic disorders from people who are merely carriers for those genetic disorders.

This might be particularly attractive for participants in a space colonization mission that would have a low effective population size and, necessarily, a higher inbreeding coefficient.

This kind of genetic engineering is particularly low risk, because we would be replacing the recessive gene known to present a risk of a genetic disorder, with genes found in the vast majority of the population that are known to be harmless.

Genetic Engineering With Existing Human Coding Genes

It is elementary that there is genetic diversity among humans. Some people have genes that make you tall or smart. Other people have genes that make you short or stupid. People have different blood types, different skin and eye and hair colors, different skin and hair textures, different ability to tolerate high altitudes, etc.

One fairly straightforward, if not necessarily technically easy, form of genetic engineering is to take genes from people who have a desirable genetic trait and place them in people who do not have that trait (often replacing a gene that codes an alternative to that trait).

In other words, basically doing that same thing that could be accomplished with selective breeding, but much more rapidly, directly, and precisely.

This is higher risk than simply removing recessive genes that cause genetic mutations (and even the example of sickle cell anemia which also confers malaria resistance illustrates the trade offs of that), because it could be that a known desirable gene interacts with other genes in an important unknown way that is disrupted when the known desirable gene is transplanted. But it is still lower risk than giving someone a gene that isn't found in humans at all.

Tweaking Top Level Designs That Utilize Existing Coding Genes

Our DNA devotes lots of its coding genes to the blueprints for a mix of proteins, and how to combine those proteins into particular kinds of tissues, and how to combine those tissues into particular organs and structures in the human body. By comparison, our DNA devotes a far smaller share of our genome to specifying which organs and structures go where, and how many of those structures we have.

A genetic modification that hacks this small portion of our DNA governing which organs and structures go where and how many of them we have could create noticeable macroscopically observable changes with comparatively minor tweaks to our DNA and with less risk of adverse side effects on the complex, multifaceted biochemical interrelationships of other parts of our bodies.

For example, a tweak to our DNA that gave us four figures or six, instead of five, would be much easier to accomplish than a tweak to our DNA that gave humans the organ that electric eels use to create electromagnetic shocks which we don't have the blueprints for in our genome.

Similarly, tweaks to our DNA to give us an extra pair of eyes in the sides of our heads, or an extra pair of kidneys, or to rearrange the location of the internal organs in our torsos, ought to be possible with a fairly modest amount of DNA modification.

Genetic Engineering With Pseudo-Genes

Pseudo-genes are genes in our DNA that are no longer part of our coding DNA and have been deactivated by mutations.

At this point, their main practical use is that they allow us to trace historically what genes organisms have lost due to mutations, approximately when that happened, and what those genes looked like immediately prior to being deactivated.

For example, one deactivated gene allowed predecessors to primates to produce their own Vitamin C, which was no longer critical since fruit supplied it. Another allowed us to better break down uric acid in our blood, which has bad aspects since this can cause gout, but also helps us turn fructose into fat which helps us weather fruit scarcity in the winter. We've also lost taste receptors for bitter tastes, in part, because we've learned to distinguish safe and unsafe plants culturally so we don't need the receptors as much.

The thing about pseudo-genes, though, is that often a single slight mutation can undo the mutation that deactivated them in the first place, can reactivate the ability of the pseudo-gene to make the very complex molecule that was genetic fitness enhancing at some point in our evolutionary history.

Mutations that reactive pseudo-genes are extremely rare as a matter of random chance. But if one is engaged in intentional genetic engineering in order to do a transhuman biohack because you believe that the pseudo-gene might be fitness enhancing at our current level of technology and in current environmental conditions, it would often be easier to reactivate a pseudo-gene than it would be to insert all of the genetic code necessary to code a molecule into someone's DNA with a much more complex custom designed retrovirus.

A catalog of pseudo-genes in humans is basically a menu of biological functions that could easily be added to people with a simple biohack.

The risk here is that pseudo-genes were usually purged from the genome to the point of fixation for a fitness enhancing reason. Sometimes the circumstance that enhanced fitness at the time is no longer present, but sometimes it is and we just don't understand it well enough.

Another possibility to consider is that if much of the 90% of the human genome that is non-coding really is literally "junk DNA" that doesn't serve any fitness enhancing function, there might be some form of benefit to simply purging it from our genomes.

The risk of purging junk DNA, of course, is that some of it might have purposes that we just don't understand yet that are still important. So far as we know, simply having junk that does nothing in our DNA isn't a big problem.

Genetic Engineering With Exogenes

Another categories of genes that code molecules which are out there are genes that aren't present in either the coding or non-coding DNA of humans, but are present as coding DNA in other organisms. I don't actually know what the proper scientific name for them is, but I'll call them for convenience in this post, "exogenes."

Suppose, for example, that a honey bee produces a pheromone not found in human genes or pseudo-genes that it would be nice for humans to have. You could cut that gene out of the honey bee genome, splice it onto a retrovirus, infect a human with that retrovirus, and then that human and that human's descendants could produce that pheromone too.

Of course, inserting exogenes into a human could potentially be harmful in all sorts of hard to see ways, because we have no good way of knowing if the exogenes are incompatible with our existing genome until we try it.

Genetic Engineering With Derived Genes

There are some genes in humans that share a common ancestor with different genes in another species, even though the human genes now code for a different molecule with a different purpose than the non-human gene with which it shares a common ancestor.

For example, some of the biochemicals in human saliva are derived from the same ancestral biochemicals that evolved in some snakes into a kink of snake venom.

If you wanted to make it possible for humans to produce that venom, it might be easier to genetically modify human DNA that makes those biochemicals in saliva into DNA that produces snake venom, than it would be to insert the entire snake venom exogene into a human through a much larger retrovirus than one that would merely tweak our existing salvia biochemical gene.

This is less risky that a straight out exogene, because humans already have something similar, but it is still far from risk free.

For example, maybe snakes have genes that give them immunity from their own venom, in addition to the genes that create the venom, that a human with a tweaked salvia gene that creates the same venom would not have.

Small Tweaks To Create Chemically Similar Molecules

Similar to genetic engineering of genes with a common origin is genetic engineering of genes that produce a molecule that is chemically similar to another molecule, even if the genes that produce the two different biochemicals do not share a recent common origin.

For example, the caffein molecule and the chocolate molecule differ by only a single atom. So, it probably wouldn't be too hard to engineer a cocoa bean that was caffeinated instead of chocolaty, or a coffee bean that was chocolaty instead of caffeinated.

The general concern about unintended consequences that is present throughout genetic engineering is present here, but to the extent that tweak is small, and we understand what the purpose of the molecule being tweaked is in the original organism, the risk can be fairly modest.

1 comment:

Dave Barnes said...

read The Seedling Stars by James Blish