September 17, 2002
Future Techniques For Progeny Genetic Engineering

Humans have been engaged in a crude form of genetic engineering for as long as they have been a species. Every time a man chooses a woman and a woman chooses a man for the purpose of reproduction they are (consciously in some cases; not consciously in others) choosing characteristics in the other that are attractive for them to have in their offspring. Humans are attracted to qualities (eg symmetry of shape, strength, healthy looking skin, etc) in potential mates that bode well for having healthy successful offspring.

Drawbacks in the ancient methods of choosing mates and reproducing

What are the major types of drawbacks in our current ways of passing along our genes to our progeny?

• We don't know what problems exist in our own personal genomes.
• We don't know what particularly beneficial variations we each might have.
• We don't know what of our own genetic endowment we are going to pass along.
• We don't know what our mates or potential mates have in their genomes or what they will pass along.

The result is uncertainty and sometimes tragic surprises. Two seemingly healthy people can give birth to a child that gets a recessive bad gene from both parents and therefore has a genetically caused disorder.

Abilities and knowledge that we need:

• To know the exact sequences we each individually have in our own genomes.
• To know what each variation means and therefore to be able interpret our own genomes.
• To be able control which of our chromosomes we pass along.
• To be able to change the genetic sequences what we pass along to give our progeny variations we don't have.

Humans have been using (consciously or not) methods of identifying potential mates with good genetic endowments for as long as the human race has existed. Many attributes of physical appearance, ability to tell jokes, prowess in sports and fighting, demonstrated personality characteristics such as patience or assertiveness, and still other characteristics have been used by males and females to judge each other since our species came into existence. Ancient religious texts even provide guidelines for choosing mates.

These methods are far from perfect. There are lots of reasons for this. Some qualities of a person may not manifest for many years (eg a genetic defect may give them a neurological disorder in their 30s or a heart attack in their 40s). It gets even more complicated. Some qualities will not ever manifest in the parents but will show up in some or all offspring. Two perfectly healthy looking people can both harbor a recessive harmful genetic mutation and can have offspring which suffer from any of a number of illnesses caused by such mutations (eg Tay Sachs). Or two who chose to become mates could have immune system weaknesses that never killed them since they never encountered a pathogen for which they are genetically poorly equipped to fight and then their offspring could encounter the pathogen and some or all of the offspring may die from it. The same can hold for other challenges that the environment throws up which do not happen for every generation.

But the problems with mating are even greater than that. Look at how much different children of the same parents can differ. Take some of the qualities that many women are attracted to in men: success in fields that require mental and or physical skills such as pro athletics, popular music writing and performance, science, or high status roles in government and industry. Just because a woman mates with a man who is enormously successful in some occupation does not mean that the resulting offspring will be equally capable of being successful in that or other high status and high income occupations.

Future advances in biotechnology will increase our ability to predict the outcomes of potential matings and even eventually to control exactly which part of our genomes we pass along to our offspring. Much of the uncertainty about what sort of offspring we will have will be removed. Not only will the uncertainty be removed but we will gain considerable control over what characteristics we pass along. Eventually biotech will allow us to go even farther and to give our offspring genetic variations that we do not ourselves possess.

The logical steps in advances in genetic engineering techniques

I'd like to go thru the logical steps of how genetic engineering techniques of offspring is likely to progress. Keep in mind that the logical steps are in order of increasing power of the techniques. These are techniques for changing the genetic endowments of future generations. While I'll cite some examples of how this will change the resulting offspring it is beyond the scope of this essay to enumerate all the ways that people will become different than they otherwise would have been.

While I'm going to describe successively more powerful techniques it is possible that some of the more powerful techniques may become available before some of the less powerful techniques. The ordering of the techniques is in order of much much the techniques can change us and not the order in which the techniques will become available. So while I view control of chromosome donation to be a less powerful technique that gene therapy on fertilized eggs it may well turn out to be the case that gene therapy on fertilized eggs will become possible before chromosome donation can be controlled.

Also, just because a technique becomes available does not mean that people will use it. There will inevitably be people who will find moral or other reasons to reject the use of some or all of these techniques. So the order here is not necessarily the order in which the techniques will become either possible or acceptable.

Also, each technique will first become available in less powerful partial implementations and later in more powerful implementations that allow the full theoretical benefits of the general technique. For example, the first logical step of genetic profiling will start out with a small number of testable genetic locations for particular genetic diseases (this is already the case with Tay Sachs and other genetic disorders). Only gradually with time will it become sufficiently fast and cheap to allow each person to get all of the genetic variations of their genome mapped in complete detail. So the initial use of genetic profiling will give one an only partial picture of oneself and one's potential mate(s). Also, the initial high cost for each step will initially restrict the number of people who use each technique and as costs fall each technique will spread into more widespread usage.

First a listing of the steps in advances in genetic engineering techniques:

• Step 1: Screen potential mates or potential DNA donors (eg egg donors or sperm donors) by genetic profile.
• Step 2: Select which of each pair of our chromosomes we pass on to our progeny.
• Step 3: Assemble chromosome sets from more than 2 people.
• Step 4: Gene therapy on eggs, sperm or fertilized eggs.
• Step 5: Build chromosomes by combining genetic variations from chromosomes of many people.
• Step 6: Introduce genetic variations new to the human race.
• Step 7: Introduce genes from other species
• Step 8: Create entirely new genes

As you can see the first logical step will simply refine our methods of mate selection. We will simply know more about potential mates from a genetic perspective. But then we will gain successively more control over what our progeny will receive as the genetic structure in all of their bodies. As an aside we will discuss gene therapy that takes place on the egg or sperm or fertilized egg with the goal of permanently affecting the entire resulting person. While we will also gain the ability to use gene therapy to change the genetic structure of subsets of our cells that topic is outside the scope of this essay.

So this brings us to our first step forward into a Brave New World:

Step 1: Screen Potential Mates By Genetic Profile

Once genetic sequencing becomes very cheap and widely available everyone will be able to know their exact genetic sequence. Any and all genetic variations that contribute to appearance, health risks, and ability for various types of sports, music composition, mathematics, and assorted other pursuits will be identified. How will this change the mating game? Initially I foresee dating/mating services where people register and provide their genetic profile (this could be done with some anonymity so that the service doesn't know which real life individual has which profile btw). Along with a genetic profile someone could submit a "what I want in a mate" genetic profile that would consist to absolute requirements for variations in some genes and preferences for variations in other genes.

The ability to search rapidly thru large numbers of other people to look for preferred characteristics will lead people to take a much more critical look at potential mates. Imagine a woman named Sue has a choice between two males named Bob and Joe that outwardly are very similar. They have similar levels of intelligence, looks, risks for diseases, and other qualitiies. But while Bob and Joe both have straight shiny teeth at the genetic level they are not the same. Suppose the gene for this characteristic (I'm making this up as example though surely there are genes that code for teeth shape) acts as a classical Mendelian dominant. Whether you have one or two copies as long as you have at least one copy of it you get the outward characteristic. Lets assume Bob has 2 copies of the straight shiny tooth gene while Joe has just one copy of the straight shiny gene along with a recessive not-nice-looking tooth gene variation). Joe has teeth that look as good as Bob's. But there is an important difference when it comes to offspring. Sue has just one copy of the good tooth gene. So if Sue mates with Joe each kid will have a 1 in 4 chance of having bad teeth (a child would have get a bad tooth gene from both parents and that will happen on average once every 4 kids they have). But if Sue mates with Bob no matter what tooth gene Sue donates to her children Sue can be secure in the knowledge that Bob will donate a good tooth gene (since Bob has only good tooth genes to donate). Both of Bob's copies are what Sue wants and so Sue has a better chance of having kids with great teeth if Sue goes for Bob.

This stage of advance in mating will be most advantageous for women who aren't looking for a husband. Women who are just looking for sperm donors won't need to be attractive to the men who might donate. The men don't need to sign up to raise kids with the women who are looking for sperm donors. So a single woman who wants to raise a kid on her own will be able to search all the sperm donor banks and choose a donor with a much clearer idea of what she will be getting.

See this previous FuturePundit post for greater detail about the ramifications of this step.

Step 2: Control Which Member Of Each Chromosome Pair Gets Passed On

Okay, suppose you are a woman who has just chosen the best mate your genetic profile could attract from the genetic profile dating service. Or maybe you fell in love the old fashioned way. But still, you know your own genetic profile and that of your mate. Your mate has a variation of some gene you desire to pass on to your offspring (lets say red hair). But the lug only has that gene on one chromsome of his pair of chromosomes that carry the hair color gene (and, again, this is a simplication for the sake of illustration; there might be multiple genes controlling hair color). You have only a 50:50 chance that he'll pass the desired gene on to your offspring (and you so want the kid to have red hair just like you and your mother before you). For most of human history you just had to roll the dice, get pregnant, and hope for the best. But eventually biotech advances will let you fix the dice and control which of each pair of chromosomes each of you donate to your offspring.

The ability to exercise this control will actually relax mate choices. Someone with undesireable genetic variants on one chromosome and desireable genetic variants on another chromosome of the same chromosome pair will no longer be shunned by the choosiest mate hunters. Only the most desireable chromosome of each chromosome pair of each potential mate will matter. The worse member of each chromosome pair will be avoidable in offspring.

Aside for those who know that DNA crossover during meiosis complicates this picture: I'm assuming that a drug will be developed that can suppress that from happening.

Step 3: Assemble Chromosome Sets From More Than 2 People.

Okay, you can't find your perfect mate. Plus, you have some genes on both members of a chromosome pair that you don't want to pass on to your offspring. But you think one of your chromosomes is so great you want your kid to get both copies of it. What you need is total control over which chromosomes of yours and of one or more other people you want to use to construct your offspring.

Basically, some manipulation technique will lift the requirement that each parent donate exactly one of each chromosome pair to offspring. For one particular pair you might not donate anything. For another pair you might donate both. Once that basic capability of pulling out particular chromosomes and assembling your choices together is possible then it will be no harder to do with with chromosomes selected from 5 people than with chromosomes selected from 2 people.

This will be a big step forward in the ability to optimize the genetic endowment of offspring. Combinations of chromomes that can not be assembled from any two pair of existing people will be able to be put together. Outcomes that previously would haven taken multiple generations will now be achieveable in a single generaiton.

Step 4: Gene Therapy On Eggs, Sperm Or Fertilized Eggs.

Staying within the range of variations that humans naturally have go into a fertilized egg (or the egg or sperm before fertilization) and modify the DNA to change a gene. In some cases this will be done to prevent children from receiving a defect that their parents have. However, it could also be done to give one's children features that the parents don't possess that other people possesss. This could be done for reasons that range anywhere from cosmetic (red hair or green eyes or greater height) to rather substantial things such as a personality type or greater coordination or muscles that could be developed to make someone a natural sprinter.

For people carrying genetic defects the prospect of gene therapy will be seen by many as extremely beneficial. Suppose, for instance, a couple both carry genes for hemophilia (where the blood doesn't clot properly). They may want to have children that do not carry the genetic defect that they carry. So gene therapy done at a very early stage of fetal development could change the DNA of the fetus so that the child will grow up free of the defect of the parents and will even be able to have children that do not have the defect.

Step 5: Build Chromosomes By Combining Genetic Variations From Chromosomes Of Many People.

The limitation of gene therapy (step 4) on the early stage of development is that its hard to use it to introduce a large number of genetic changes. At the same time, the ability to assemble sets of chromosomes by taking chromosomes from more than 2 people (Step 3) is still limited by what combinations of genetic variations can be found on individual existing chromsomes of all the people in the human race.

You may choose a set of features that you want your child to have that all are controlled by genes on a particular chromosome. But there may be no existing copy of that chromosome that has the particular combination of those features that you desire.

There's another reason why it will desireable to do larger scale changes to chromosomes. Some genetic theorists believe that we each carry dozens or even hundreds of deleterious mutations (we don't all carry the same deleteriousl mutations and some of the harm from these mutations manifests in rather mild ways). Every person on every chromosome may have mutations that are harmful to them. Well, we really need to be able to get into each chromosome and basically scrub it clean of deleterious mutations.

The Transition From Using Best Existing Variations To Variations And Genes New To Humans

The average human being's health and general abilities can rise very dramatically just by sorting thru the genetic variations that already exist among humans. There are literally millions of locations in the DNA that vary from one person to the next. Many of those variations have no effect on us. Some variations are in silent areas of the genome. Still other variations are in used areas but don't cause any functional changes. Still, estimates for the number of significant differences in human DNA start at around 100,000 and range upward from there.

Scientists are already trying to sort thru the genetic differences between people to find out what effects they have. As the meanings of these differences become elucidated we will be able to make more intelligent choices about which existing variations we want to pass long to our offspring. This alone will cause a large change in the average of the human race as poeple make different choices about the height, appearance, personality types, intellectual abilities, and risk of diseases that their children will have.

But at some point scientists will begin to discover ways to improve upon the sum total of all the existing human variations. These ways to improve upon existing human designs may well occur years before all the existing variations are fully understood. But I'm placing them here as later steps just to make clear that they represent a further logical step in the progression of types of genetic engineering that will be done to humanity.

Step 6: Introduce Genetic Variations New To The Human Race

Steps 4 and 5 can be done with genetic variants that exist in the human population. However, more advanced genetic engineering will involve the introduction of new genetic variations that do not now exist in humans. Some of those variations and genes will come from other species. Still others will be designed by trying out or simulating variations of existing structures to see if the variations yield desired improvements in functionality.

Some of what will be done here is to take human existing genes and the proteins that get made from them and to run computer simulations that show how the genes and proteins would function if each position in the gene was changed to other letters in the genetic code. By trying variations that have not yet occurred naturally it will be possible to find for improvements over the variations that already exist.

This step does not involve introducing new genes. It just involves changing the genetic letters in positions of the genetic code of existing genes. However, as we can clearly see by looking at the enormous range of variations in existing humans even this approach can produce dramatic differences between humans.

Since other species contain many of the same genes as humans do and with very similar sequences one place to go looking for promising variations is in other species. However, other species also contain genes that humans do not have. This brings us to our next step.

Step 7: Introduce Genes From Other Species

A more radical way to get improvements is to look for genes to use in humans that come from other species of plants, animals and even from single cell organisms such as bacteria. The advantage of looking at other organisms for improvements is that so many organisms have had to survive in so many kinds of environments and they have adaptations that probably just never had a chance to arise in humans. So there are lots of well tested genes in other species that are worth examining to look for useful parts.

There are scientists looking at bacterial DNA repair enzymes with an eye toward putting them in humans to slow DNA damage accumulation that accompanies aging. There are also scientists looking at bacterial enzymes that break up waste products that accumulate in cells. One goal would be to insert the genes for these enzymes into human cells so that the lipofuscin and other compounds that accumulate with age could be broken down.

Step 8: Create Entirely New Genes

Still another way to try to improve the human species is to try to come up with entirely new and novel genes which code for proteins that do things not found in humans or other organisms. This is harder than trying to improve on existing designs and is also harder than looking for better designs in other species. But eventually bioengineering will advance to the point where this becomes possible as well.

Our Genetic Future

The 21st century will see an acceleration of the rate of change in the human genome to a speed many orders of magnitude faster than what has been its historical rate of change. Some of the early stages of the change will not seem superficially so dramatic because people will initially just select among existing variations. Future generations will be chosen to be more attractive, healthier, and with the most desired intellectual and personality characteristics. However, as bioengineering advances new types of genetic variations and genes from other species will lead to still greater changes in humanity.

People will have many motives for genetically engineering their children and many types of changes that they will desire to introduce into their children's genomes. In future posts I will explore in greater detail all the different categories of modifications that people will decide that they want to make in their progeny. Another incredibly important topic to be explored in future posts is the question of whether genetic engineering could lead to offspring who have characteristics that literally threaten the fabric of civilization.

Share |      Randall Parker, 2002 September 17 02:05 PM  Biotech Reproduction

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