R M Cullen MD MSc MFM BA DipStats DipProfEthics

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ethics, lecture two: engineering human 2.0

Let's make the ethical issues stand out by producing an 'executive summary' of how a 100 year programme to produce a 'more evolved' human subspecies might be executed.

Those of you with an eye on the assessment essays might notice that this part of the lecture is, in fact, an answer to option E. Please note - I will be aware if you copy and paste! It would be fair to conclude that this is not how I would actually proceed to engineer human 2.0. There are multiple other approaches.

The basis of this approach is the idea that the further evolution of humans can be triggered by producing 'humans' with a greater genetic diversity and in such a way that if the genome topology is unstable it is encouraged to roll.

Once the more diverse product, possibly with a further roll added to the ontological sequence, is available then a combination of deliberate breeding and manipulation of the time the embryo spends in various states will produce human 2.0 with the desired attributes.

For the sake of argument, we will aim to produce human 2.0 as a more robust (stronger, faster, less prone to breakage) more intelligent version of existing humans.

step one: produce a troop of human-chimp hybrids

A human-chimp hybrid would have a full complement of both human genes (from one parent) and chimp genes (from the other parent). Although humans have 23 pairs of chromosomes and chimpanzees have 24, this difference is not an absolute bar to successful mating with the issue of fertile offspring.

It would seem that a human-chimp hybrid would be regarded as a non-human primate, although that is perhaps a question of law and external appearance rather than of science. "Oliver", a famous candidate humanzee looked like a chimp and was treated like a chimp - being used for drug testing.

There is a definite possibility that a hybrid would be able to breed (and produce fertile offspring) with both chimps and humans. Would this make the hybrid both chimp and human, or would it be neither (a defining characteristic of humans being, possibly, that a human can not reproduce naturally with a chimpanzee)?

An initial approach would be to create a 'test tube' hybrid, replacing the nucleus of a human oocyte with a chimp oocyte nucleus and fertilizing the result with human sperm. If an embryo forms this would be implanted in a human female uterus (that of the egg donor) using standard IVF (in-vitro fertilization) techniques. It is my understanding that the first part of this experiment has been performed and the resulting embryos remain frozen (i.e not yet implanted)

The advantage of using a human oocyte and womb is that IVF and pregnancy are much better understood in humans than in chimps. Also, the offspring would likely be a smaller than (human) average baby and easily delivered. If a chimp oocyte and uterus were used there might be problems with delivering a larger than average size (for a chimp mother) infant

However, a chimp mum should be tried as there may be differences in gene expression and offspring fertility depending on whether it is the mother or father which is human.

This nuclear transfer +IVF technique is expensive. Less expansive options (and preferable because they would produce a larger troop more quickly) are

• IVF. Where human sperm is used to fertilize a chimp occyte, or chimp sperm is used to fertilize a human oocyte. The problem here is getting the sperm head inside the oocyte. One possibility is to immerse the chimp sperm in human seminal fluid and the human sperm in chimp seminal fluid. Another is the established technique of intra-cytoplasmic sperm injection (ICSI)
• Artificial Insemination. Where semen/sperm is collected and deposited by a technician in the uterus of an ovulating female. This was reportedly attempted in the Soviet Union in the 1920s but the actual data records have never been produced. For example, if the attempt was made it is unknown how ovulation in the female was determined (or even if this was known to be important)
• Wild breeding. Cheapest. May have better prospects of success if both chimp and human subjects are chosen so as to minimize the genetic distance between them, at least with respect to key markers (whatever they might be)

There are two reasons for producing these hybrids

1. They will be a lot more genetically diverse than humans. That is, there is a wider range of inherited material, and many more potential combinations of factors, on which evolutionary forces can act.

2. The 'shock' of combining two different genome conformations may induce a roll in the genome

breed, breed, breed, and artificially select

All being well, after 15-20 years there may be twenty fertile sexually mature hybrids

These should be encouraged to breed. The female hybrids reproductive breeding should be limited to breeding with the male hybrids

The males can reasonably be expected to father 100 offspring each, with chimp and human as well as hybrid partners. Tastes and inclination may well mean that a combination of wild breeding and IVF is required.

It is probable that the hybrids will be able to breed 'in the wild' with humans. If fertile offspring are the result does that mean the hybrids are human, regardless of what decision was made when they were juveniles?

After forty years, there may be a breeding population of 1,000 hybrids, with a bimodal distribution of genetic makeup, roughly speaking from a few that are 'almost human 1.0' through a local peak of '75% human 1.0' through a trough at 50:50 to another local peak of '75% chimp 1.0' to a few that are 'almost chimp 1.0'

Artificial selection is a powerful tool. Ask any dog or plant breeder. At this stage careful consideration needs to be given as to what inherited characteristics are being bred for and which members of the troop should be bred with which other members.

Careful consideration too needs to be given to the extremes. Should 'almost chimp 1.0' be culled, or should these transgenic animals be dealt with in some other way. Are 'almost human 1.0' humans? If so, are they to be released into the wider community and allowed to breed at will? Can they compete in human sporting events?

use epenes to manipulate embryonic development

This is where the big payoffs are.

If the aim is to produce more intelligent, more robust humans then maybe this can be achieved by influencing the time spent in various stages of embryological devlopment.

This may be achieved by using epenes

genome topology

Genomes exist in three dimensional space, four if one allows that the topology changes over time. But that is the central question. If genomes really are just one dimensional structures and all genes are available for transcription at all times if they are switched on, then research into genome topology is a waste of money and that is really the end of the matter.

However, if there really are epenes - small molecules which control (by folding the nucleosome) which areas of the genome are available for expression, when, and for how long, then matters are quite different.

For, if that is the case, then genome topology offers the prospect of what are essentially drug therapies with huge profit potential, huge capacity for good, and huge capacity for harm.

To a certain extent the cat is already out of the bag. Sports supplements, homeopathic remedies with biological effects

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