R M Cullen
MD MSc MFM BA DipStats DipProfEthics
|elite athlete development||diabetes||economics||evolution|
|Pro-Pare™||diabetes reversal||midinomics||chance or design?|
|tamaki sports academy||diabetes blog||genome topology|
|some thoughts||some opinions|
These are both reasonable questions, and the first aim of this lecture is to provide some applications of GT.
The previous lecture introduced some theoretical applications of GT in the fields of evo-devo, cell differentiation, and channeling/constraint of evolutionary possibilities
Geome topology is, in essence, the idea that the nucleosome is folded by chemical products of acquired characteristics called epenes (or epigenetic factors)
One effect of this folding is to bury some genes, so that they are not available for expression even if the appropriate triggers for expression are present in the nucleus. At the same time burying some genes normally means bringing others to the surface.
sports performance enhancement
One aspect of elite sporting performance is to have the right genes expressed at the right time for the right period of time.
For a number of years now I have been involved with a sports academy whose members are predominantly Polynesian teenagers. These youngsters have a huge physical advantage in contact sports over their European and Asian counterparts as they begin to develop adult muscle mass at an earlier age and they put on muscle mass easily (sleeping seems to do it!). Lean 100kg 15 year old athletes are normal.
European teenage boys have the genes, but they are often aged nineteen or even in their early twenties, and assisted by intensive weight training and dietary supplement regimes, before they catch up to their Polynesian rivals. By this time, the professional sports pathways are closed.
As a problem in genome topology this is an issue of the right genes being available for expression earlier and then being available for expression for longer. It is an issue of lifting genes to the genome surface (rather than burying them).
As an aside, these 'early developer' Polynesian boys are often crippled by gout and diabetes in their early thirties. Perhaps this suggests that their “early rising” muscle development genes are folded away by their late twenties.
What an individual cell does or produces depends on the chemicals found on a day to day basis in its nucleus. Some of these unroll the nucleosome in places, others roll it more tightly in other places. Control of those processes, day to day cellular activities, is a matter of regulating the chemicals found in cell nuclei so that the right gene is expressed at the right time for the right time (or buried for all time in the case of genes linked to cancer!). This is a field of medicine so new it doesn’t have an agreed name yet. I am going to refer to it as topology medicine. Topology is the (mathematical) study of surfaces.
Topology medicine introduces a whole new range of (drug) interventions.
Many diseases, including Huntingdon’s chorea, cystic fibrosis, and some cancers, are directly associated with the expression of a single deleterious gene. One therapeutic approach (that of topology medicine) to these diseases is to fold the nucleosome in such a way that the deleterious gene is not expressed.
One explanation for the origin of type two diabetes in obese people is that certain fat cells produce chemicals which are poisonous to the pancreatic cells which produce insulin. The development of type two diabetes in these people might be delayed or even prevented if that part of the genome which is responsible for the production of the pancreatic poison were buried or folded into inaccessibility.
biological weapons of mass destruction
Epenes provide a new way for humans to kill other humans. Epenes exist which are quickly fatal to cells (by folding away all copies of critical metabolic genes).
Delivery could be by conventional means (chaff bombs exploded above cities), or less conventional means such as 3D printers.
The ultimate delivery mechanism would be via a viral vector (see lecture covering gene therapy), especially one that targetted race specific genes and instructed cells to produce more epenes.
production of HOPS (human - other primate hybrids or infra-humans)
The chimpanzee gestation period is 237 days, compared to 266 days in humans.
There are three approaches, which may be run in sequence, to developing a human chimpanzee hybrid
The first is to use the techniques of gene therapy to introduce, say, chimp genes into a human.
The second is to attempt to create a 'natural' human chimp hybrid through either 'test tube baby' techniques or egg nucleation/renucleation where, for example the nucleus of a chimp oocyte is removed and replaced with a human oocyte nucleus and the hybrid ocyte is then fertilized using 'test tube baby' techniques.
The third approach is to use epenes to increase the time the hybrid embryo spends in certain critical stages
Why would one want to do this? The reasons are military and economic.
HOPS may well make good combat soldiers. Better than one of my kids.
HOPS may well make good workers, and in surprisingly skilled jobs.
engineering human evolution
This is the topic of a full lecture later.
What is evolution? What is it that is evolving?
Ontogenies, or the sequence of genome rolls, evolve by adding a new twist to the end of the current ontogeny. The epenes may have other effects (such as shortening or lengthening the time spent in prior ontological conformations)
What has natural selection got to do with evolution?
Natural selection alters the frequency with which alleles occur in a population. There is a different source of new or altered inherited characteristics. Genome rolls are a source of speciation.
why don't plants walk? why don't pigs have wings?
One of the central claims of GT is that genomes "roll" in the sense that development of the individual is a carefully choreographed sequence of topologies, or appearances on the surface of the genome of gene combinations. From any one topology only certain future "rolls" or topologies are possible. GT hypothesizes that plants can not reach a "legs" topology and pigs can not reach a "wings" topology.
why do whales have legs?
Whales, in their embryological development, now pass through the "roll" of the genome where legs are produced more quickly than when they were land based with the result that the process is begun but not finished.
why do we have multiple copies of some genes/
So there is always one copy on the surface of the nucleosome when one is needed.
Why don't common ancestors reappear?
In general, genome rolls are not reversible
why are there living fossils, such as coelacanths, lungfish, and tuatara?
Sometimes genomes rolls reach a dead end, in that with the available epenes no further rolls are possible
if it is incredibly rare for the first proto-eye or wing to appear, why does that juvenile survive to breed when most juveniles die before breeding?
It is not incredibly rare for the first proto-eye or proto-wing to appear. Given the genome topology the appearance of eyes or wings occurs many times
the origin of life
GT is a theory about the instability of genomes. It says nothing about history before there were any genomes.
Periods of stasis correspond to the time between genome rolls. A new topology provides many opportunities for new inherited cahracteristics to develop
Many conformations can reach a given conformation type (e.g 'eyes')
There are a finite number of conformations, and these fall into groups, corresponding to body forms
A single 'genome roll' corresponds to many, many mutations
the step to human
The ape conformation is unstable