Ennetech by Erasmus and Kinkajou Authors

 

 

Erasmus and Kinkajou share their vision of technologies that will help us on our way.

Genetics & Disease --- --- ? Paill

 

 

 

 

Many human illnesses have still no known genetic cause.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Everyone talks about how we are learning so much about genetics and rewriting our understanding of the physical world,” pontificates Kinkajou. “There are lots of claims that an understanding of genetics will cure lots of human diseases and completely change how we treat these conditions.” “Bullshit’” says Erasmus. “Yeah, I agree” says Kinkajou.”

KinkajouKinkajou : I get the impression that lots of people are talking big and totally ignoring the reality of what we know already”. Genetics and genes are not going to find reasons for a lot of diseases. You can tell because there is lots of evidence already that it’s just not going to happen that way. Genes are just a jump on the bandwagon response for lots of people who don’t know much and have decided they could not be bothered finding out anything about the issue.


“Give us same examples”, says Kinkajou.
Erasmus considers


ErasmusErasmus :For a start no one has isolated any genes that cause schizophrenia.  I only ever saw one article that thought it may have found a gene that could be responsible at least for some cases of schizophrenia. The gene produced an unstable receptor and from the properties of this gene it looked like a real possibility. Unfortunately, the article concluded that the other gene was more likely to be statistically NOT associated with schizophrenia.

Depression is another condition. In fact, recent editions of the DSM: Diagnostic and Statistical Manual of the American Association of Psychiatrists have even begun to shy away from saying that there appears to be any underlying component of genetics. 

In fact, if you look at most big or common human diseases and pretty well all the psychiatric disorders, the silence is deafening. There is no genetic component to these illnesses. In short, these diseases are due to environmental factors. In fact, even the familial preponderance, the tendency of the same disease to appear in family groups, is now often being blamed for common environmental conditions, not common genes.


KinkajouKinkajou : Aren’t conditions like stress responsible for depression.
ErasmusErasmus :  People like to think that.  The incontrovertible fact is that lots of people suffer from problems in their lives. Mum dies. Dad dies. Their children have marriages that bust up and relatives develop cancer. Yet these people stay well. Of course, when they develop depression, it was the stress caused by the dog dying a few months ago, that must have triggered off the depression.

I think humans have an infinite capacity to apportion blame and no capacity to admit that they might be wrong. You can’t argue with someone who says the dog dying must have triggered off their depression in the last few months. There is no need to address the issue of the apocalypse of hurt that struck the family for the last decade. To the mind of the afflicted they must be right and no discussion will be entertained.


KinkajouKinkajou Exclaims:  Hey, what about that doctor who says that most human diseases are due to an environmental pathogen, a bacterium.

ErasmusErasmus :replies: “The Paill Spectrum man.” 

ErasmusErasmus : Look, at least what he says fits the facts. There has been no gene or genes found to cause all these illnesses. Ditto, an environmental factor must cause all these illnesses. He even claims that there are medical tests that correlate with disease presence, treatment response and relapse. Most doctors as a species are bull headed enough not to look at any new answers. 

Erasmus makes a snide aside:  ‘You could say they’ve never learnt anything that they haven’t been taught”.  But then the education process does not reward personal thought and initiative. I went to University with a bloke who had the student medical mindset. I asked old Geoff what he was doing one day. He replied that he was learning the ten causes of xxx. I said, if you look at that list this way there are five causes and if you look at that list another way there are 12 causes. 

Geoff: “No, Erasmus,” he replies.

ErasmusErasmus : Of course come exam day, when the exam asks what the causes of xxx are, he replies there are ten causes of xxx. Guess who gets the best grade for the subject, does better at University subject exams and goes on to a more specialised career, where his learned point of view can be inflicted upon others.  Unfortunately, they say tuned to that model their whole lives. “There are ten causes of xxx. Like I said, they never learn anything that they haven’t been taught.
“So “says Kinkajou, “we digress”.”


Erasmus, let’s get back to our discussion on genetics.”

ErasmusErasmus : I think we are at a very early stage of understanding genetics. I read stuff on- line that talks about junk DNA. These are DNA sequences that are incorporated into organisms but don’t have a definable gene product.  Strangely, mutations in these regions are often lethal for the organism concerned and the DNA sequences in these segments are more strongly conserved than are the genes for specific protein gene products. It is obvious that these DNA sequences are not “junk “DNA at all. They are highly sophisticated and highly important sequences. I would guess they relate to control segments for gene expression and gene function. It’s amazing that anyone could think these intron segments are “junk “at all.

Humans have a lot less genes than many other organisms on the planet. Yet we regard humans as the apex of complexity. It becomes obvious in looking at the facts the complexity is in the organisation of the function of the genes, not in the genes themselves, or in the number of genes present. Chimpanzees share almost all of our genes. Yet there are still important differences between the two organisms. The devil is in the detail: not the genes coding for proteins but in the gene segments controlling the expression of the genes involved.  .

So I think we have a long way to go before we are at the stage of understanding gene programming and gene control.  Currently, our understanding focuses on genes that make thing and not genes that control things (to the outside world looking like they do nothing). This does not reflect the real world.

HIV Complex Operons HIV Complex Operons

ErasmusErasmus :We (humans) pride ourselves on introducing genes into various plants or organisms, when the manner in which this was done is primitive and hopelessly hit and miss in the extreme. We are certainly nowhere near the stage of linking DNA segments or of building genomes to create functional organisms. At best we could steal genes from existing animals, but we have no idea how to control or regulate them.

In the long run I think we need to build the tools that we need to start to become involved in genetics. The appearance of on line genetics libraries is the first step to discovering what genes do. While we can build short DNA sequences, we are still nowhere near the stage of modifying existing animals .If nature does it though, we can selector test for it. Nature is till the master.

For example, all modern horses are descended from a specific few horses in early times. It appears that modern horses have fewer chromosomes than ancient horses. This derives from a balanced gene translocation in the earlier horses, which humans have selectively bred for. In terms of deciding to design a better horse, better cow, better sheep, and better blade of wheat or better anything, we are a long way from even being able to decide what genetic elements we would need to get there.
Kinkajou: If you believe some of the Human birth of civilisation gossip, there looks to be some incredible feats of bio engineering in humanity’s past. 

ErasmusErasmus : Yes. I’m well aware of the evolutionary significance of our agrarian or herding past.

Wheat Structure Rachis Wheat Structure Rachis

Somewhere a few thousand years ago barley underwent an incredible genetic transformation. It developed a six row seed head, instead of the traditional 2 row seed head: effectively increasing the plant’s yield. The Barley also developed a tough rachis stalk. The main difference between wild barley and cultivated barley is the rachis, which is more brittle in the wild barley and promotes the natural dispersal of seed. In wild barley at the end of the growing season, the rachis bends, allowing the seed heads to droop. Dropping the seed to the ground and allowing the barley brass to seed. 

Thousands of years ago, there also developed a “rachisless” stalk. These seeds heads would not droop losing their seeds as harvest approached. This meant that the barley plants became much more dependent on human beings for cultivation. Also, the upright seeds heads could be harvested. So barley grass became worthwhile cultivating as a crop for Sumerian and Egyptian farmers.

For wheat, the term used was a brittle rachis which ruptured easily releasing their seeds with even small amounts of wind.

There are some incredible genetic advances several thousand years ago. Simple as they may be, these probably made civilisation possible.

Wheat Spikes Close Up
Wheat Spikes Close Up



Cows, Sheep are incredible bits of biological; nano-engineering capable of converting inedible grass or vegetation into food: meat milk. They are functionally adapted to nomadic type animal husbandry due to their tendencies to herd. Perhaps the Australian aborigine never had a chance to introduce civilisation into their continent because it’s almost impossible to herd kangaroos.

ErasmusErasmus : Wheat barley: changes in the rachis and the seed head affected yield and introduced farming as a viable lifestyle.

ErasmusErasmus : We don’t think much of these things, but these bits of biotech may well be what started our ancestors on the road to civilisation. We would not be here without these incredible innovations. At this stage of our understanding of bioengineering, we do not have the capacity to change wheat or barley or rice or bananas or cows or sheep. We are quite capable of breeding for desired traits that nature drops into our laps, but we have no capacity to plan, the capacity to plan involves knowing:

  • Which gene products we want
  • How do we regulate gene expression?
  • Where do we integrate these genes into the existing genome with favourable effects?

 

  • Which genes may affect disease resistance in plants or animals and how to regulate these genes?

  • The capacity to breed out undesirable and inadvertent qualities of our food crops. E.g. Wheat causes gluten allergy or intolerance in a lot of people. The same protein that causes this also gives the wheat the ability to rise and to be baked into light fluffy tasty foodstuffs.

    Humanity, especially those learned doctors can’t even agree on the extent of wheat allergy in the population, are blind to the symptomatic and immune effects of wheat allergy, and are blind to the nutritional aspects of even low grade food sensitivity.

How can you develop a genetic master plan for wheat genetics if you have no idea what you are doing? How can you develop a master plan for wheat genetics if you don’t; understand that there are consequences of choices.

Will vested interests , these  interested in selling a lot of wheat be willing to allow these heretical views (about the health dangers posed by wheat to a large proportion of the population) allow these ideas to take root in the general population without a tooth and nail struggle to hide the truth, because there is money involved.

KinkajouKinkajou : The first step in planning is an honest appraisal of potentials. We can’t do it for plants. We are blind to the likelihood (or improbability) of it in ourselves.

ErasmusErasmus :Another key example of our skill in genetic manipulation is the insulin story. The world has shifted to using human insulin in the last decade, replacing animal insulin such as beef insulin and pork insulin. This differs slightly in their protein sequences from human insulin.

Synthesising the amino acid chains was achieved quite rapidly. Then for a few years the entire project ground to a halt as researchers tussled with the problems causes by protein folding. Yes, you could make the amino acids in a particular sequence. Yes, you could generate the sub-fragments. Then you had to achieve the correct folding of the amino acids to form the correct proteins, Assembly of the sub-proteins, also proved difficult.

ErasmusErasmus :In short, what we are doing here are baby steps into the understanding of genes, proteins, and the very complex science of protein folding, (currently the latest realm of super computers and multiple parallel computers). We are nowhere near the stage of designing our own unique molecules to do particular jobs, and folding and assembling these constituents.

Biology has a complexity that can put physics to shame. It is a frontier that will require a lot of investment in terms of both time and money.DNA Chemical Structure DNA Chemical Structure


KinkajouKinkajou :“So it’s going to be a hard road, and we’re just children on this road. But what should we be doing?”

ErasmusErasmus :  I think there are some achievements that would really be important to the human race and would make a big difference in assuring our future.
Conversion of cellulose to glucose: This is a critically important step to ensure food supplies for the human race. Currently, there are many crises that can befall us. The trouble with food supplies, Is that the only way we can “make” more food is to grow it. This means we need to put in in the ground and then wait.

One of the major advances of the 20th century is the industrialisation of food supplies. People in most western countries can enjoy apples and oranges all year round. Much of this provision of food is due to improved methods of food storage such as refrigeration and controlled ripening.

Now many fruits can be stored for months and ripened with e.g. ethylene oxide. Many greenies complain about our use of this tech. Still it means less wastage, cheaper food and the availability of these types of foods to more people for much longer. In the western world we are probably one of the first generations not to have faced hunger regularly.

Conversion of sunlight to glucose or fats: This is a similar problem except that we don’t take indigestible cellulose as the feedstock for the industrial process to turn it into food. We use for example algae as little sunlight harvesting and storage factories. We select and modify a plant form that can maximise storage and minimise the diversion of photosynthesised chemicals into growth.

Controlling growth is the key. To be useful we want minimal growth biomass and maximal foodstuff biomass. It would be interesting to see if we can   harvest: complex sugars like glycogen, fat or oils or proteins.

Conversion of glucose or other feedstock into alcohol. One method proposed has been the selection of bacteria that can take an input chemical such as glucose and metabolise it to alcohol.

Currently, we use yeast as the main alcohol production organism. The trouble with yeast is that alcohol is really a by-product of the growth cycle. So it is impossible to separate alcohol production from growth.  This means that we routinely divert proportion of our energy from alcohol production to growth. This reduces yields and efficiencies.

A solution to this problem is to use bacteria in steady state “starvation” mode. In this mode bacteria do not grow as they retain too little energy for growth. They do however continue to metabolise in steady state. This chemical process could generate clean green recyclable fuel production. But in the long term unless we can improve efficiency, the process produces a costly fuel. (With yeast as the conversion factory).

Also, the less efficient the chemical process is, in the long term the more land is to be diverted away from food production and into feedstock for fuel production. This again pinches our food supply. As we have already commented, food production is one of our slowest production processes.

Conversion of petroleum to “manna”. The need addressed here is to have an industrial process which is independent of biological processes able to produce food. This reduces our dependence on critical processes such as growing food stocks. This process has been sort of mentioned in the bible. The manna that was deposited on the ground would decay into a black sticky substance if not harvested.

KinkajouKinkajou : Well it does remind you of oil, even if they used some other feedstock for this chemical reaction

Ability to program DNA to produce designer proteins which then fold and assemble themselves correctly. This is the cutting edge of altering diseases activity in a number of conditions. Protein folding is a complex task, but the genetic programming of DNA segments to produce, regulate and assemble proteins is an even bigger goal for modern science.

DNA Structure DNA Structure

KinkajouKinkajou : I think it will be at least a century before start to build a substantial level of skill in this area. To achieve this, would need massive investment and a massive investment in human resources.


Erasmus: Since the world’s emphasis at the moment is on the cheapest possible pharmaceutical drugs to be produced by anyone (i.e. companies who have lean mean operations and no R&D), , I don’t think we’ll see the R&D dollars flow into  this area unless a pretty persuasive business model  builds itself. I think about the only thing that will start work in this area, is people being confronted by their own mortality. Sort of like the HIV scenario. That would work.

ErasmusErasmus : the issue of course is what protein or genetic products are valuable and would give a return on investment. Currently, I can only think of enzymes to catalyse a number of manufacturing processes may warrant this amount of R&D. 

KinkajouKinkajou : Interesting. What we can achieve may be more in tune with how good our R&D model is, than with our capabilities. Once again past expedience and short sightedness decides our future.
Erasmus: The Ability to manipulate Mangrove genetics and mangrove cell growth will one day be a critical skill for the human race.
KinkajouKinkajou : Erasmus, old man I think you’ve finally lost it. How could knowing lots about growing mangroves be important for the human race?

ErasmusErasmus :See my article on the colonisation of the Oceans.

KinkajouKinkajou : Any comments on what you’ve learnt Goo?

Our Little Numbat FriendGoo : Genetics is complex.

While many things are possible, one of the main blocks to development in this area is again social. What is the business model that makes this type of research worthwhile? 

Can the investment justify the return: especially over the short life of a patent? How can long term development be supported in an era of short sighted governments? Perhaps a few really good and lethal diseases with interesting genetics may be the thing that triggers long term research.

There needs to be the development of long term fundamental supporting or enabling technology before the commercial entities may find it profitable to enter the market.
You always need to hope that it doesn’t get too easy.

Everyone could design a computer virus with simple toolkits. Let’s hope the idiots don’t start doing similar things for humans or animals in the real world. I can see  that if a country is dependent on rice as a staple food and a new rice “bug” is created it will tend to affect the target country much more than the perhaps the originator country. Let’s hope we never face the militarisation of genetic research.

PCR Amplification MachinePCR Amplification Machine

 


ErasmusErasmus : Yes the world of the novel Wind-Up Girl tells of a future blighted by predatory companies creating diseases to destroy the crops of others, forcing people to buy propriety and resistant food crop seeds from the Seed Companies. The rust blight and other diseases lurk as a constant threat to human survival. This type of future can never be allowed.

Our Little Numbat FriendGoo :The mangrove genetics idea may well have some future, at least as an interesting concept. Growing your ships rather than building them would reduce the cost of ship home building to the point where perhaps the world’s oceans could indeed be colonised.

The use of biological mechanisms such as bacteria to produce chemical feedstocks for industry or to produce food (glucose) begins to look somewhat like a necessity to me in the face of the burgeoning human population on planet earth.

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