Genetics or molecular biology advice for fiction writing - post any questions here

[Ray McCarthy]

Just as Ethanol is okay and other alcohols are not.

Perhaps a very little of it, with water, oak scented, sourced from fermented barley. If a philistine, maybe some Stone's ginger wine or C &C ginger
I doubt much more than a very little is wise

Overheating an oil is bad, for sure. I think Olive Oil can't be used as hot as Corn Oil.

Again it's the question of did the giant virus start small and accumulate bits over time, or did it start with a bigger complement of genes and lose them over time?

I remember a good Horizon (back when BBC did actual science programs rather than pop junk science) called "Invasion of the Virions" that suggested that all viruses unlike bacteria, were broken off bits of plants and animals (they are far more species specific than bacteria?) hence hijacking host cells to replicate unlike everything else?

The majority of bacteria do us no harm at all and some are beneficial. Hence a too clean surface in a hospital can be a breeding ground for something nasty from a patient, or be populated with stuff blown in the open window making it hard for the nasty bacteria to colonise?

Bactericides maybe be a bad idea, not just in building resistant strains, but "clearing the decks" of the benign or harmless ones?

 

[Piousflea84]

Welcome to Chrons, Ed.

Your arrival is timely and your offer very generous. Thank you.

I'm at the point where I need to know a little more about genetics. (I might need to know about molecular biology too, if, I knew what that is!) I have a character who's developing a human/animal hybrid. His intention is to produce a large, strong and ferocious humanoid, in order to wipe out the human race.

My main question would be, "why would a character who's powerful enough to create a human/animal hybrid feel like that's the best way to wipe out the human race?"

It seems to me that any being with the scientific knowledge (or magical prowess) to create a mankind-eradicating beast would save himself a lot of trouble by making a super-virus or other parasite. They'd be much cheaper to manufacture and replicate a lot faster than a human-sized beast.

 

[Ed Ryder]

One more thing: Some vitamin deficiencies in humans are really a deficiency in our metabolism. The most glaring example is vitamin C, which is only a vitamin for humans at all (also for a few other species such as the "great apes", guinea pigs and a couple of obscure tropical birds) because of a point mutation which deactivates one enzyme in the vitamin C biosynthesis pathway. It's thought that said mutation persisted because a human ancestor didn't need to make the stuff - because of very high fruit intake.

Given that, one might think that if one is going to muck around with the human genome repairing that defect would be one of the first things to do.

Incidentally, if incorporating genes from other species (cats perhaps) it would be a good idea to avoid introducing more errors and vulnerabilities. Two examples are the fact that cats need taurine from external sources, and that dogs are highly sensitive to caffeine and theobromine. Which is why one needs to buy highly expensive special chocolate to give to one's dog.

One thing that can't currently be done of course is to cut and paste large chunks of genome to get traits from one unrelated species to another in a dinosaur -> frog Jurassic Park style, for example making a human armoured by putting in genes from an armadillo. Genes work in huge and complex networks most of which we know little about, and are highly regulated by a number of mechanisms, one of which (RNAi) was only fairly recently described. Even small changes can have large consequences when things are not in the correct context; when we knock out genes by replacing part of them with an antibiotic selection marker for example the promoter for the marker can have effect the expression of the surrounding genes and cause phenotypes, or even those far away depending how the DNA is packaged. There's also the question of how such a change would be incorporated into the developing embryo where timing of expression, existing protein gradients in the differentiating cells etc are critical.
You can do it with conserved genes in a direct swap in some cases; eg the 'humanised' mouse (or Drosophila) models available which express a human gene used in the immune response or express a disease gene instead of the normal wild type copy), but any major changes are beyond our current understanding.

Still, it makes for some great stories or computer games (if anyone's played Bioshock), if anyone wants to presume that in the future that kind of thing will have been solved!

By the way thanks everyone for contributing to the thread - I kind of thought I'd be rattling around talking to myself most of the time!

 

[Piousflea84]

One more thing: Some vitamin deficiencies in humans are really a deficiency in our metabolism. The most glaring example is vitamin C, which is only a vitamin for humans at all (also for a few other species such as the "great apes", guinea pigs and a couple of obscure tropical birds) because of a point mutation which deactivates one enzyme in the vitamin C biosynthesis pathway. It's thought that said mutation persisted because a human ancestor didn't need to make the stuff - because of very high fruit intake.

Given that, one might think that if one is going to muck around with the human genome repairing that defect would be one of the first things to do.

Well if you're going by those standards, you'd have to classify almost all non-elemental nutrients as a "metabolic defect". Humans require nine essential amino acids and two essential fatty acids because we cannot biosynthesize them; some species can synthesize more and other species can synthesize fewer. Biosynthesis is not a cost-free process; if you grow leucine synthesis-deficient yeast on a leucine-rich medium, they will out-compete the same yeast that is leucine synthesis wild type. In mixed communities of microorganisms, each individual species will evolve toward synthesizing some nutrients while obtaining other nutrients from their neighbors.

With that in mind, restoring nutrient-synthesis pathways to humans may actually be harmful to our health. Our cholesterol-synthesis pathway (HMG-CoA reductase) is partially responsible for cardiovascular disease, therefore a majority of older humans in developed countries are taking some kind of statin. (HMG-CoA reductase inhibitor) There is no telling what metabolic disorders may occur if we restore the human body's ability to synthesize other nutrients. If nothing else, the increased workload may place more oxidative stress on our liver. The fact that the great apes share our unusual nutritional requirements suggests that there may have been some evolutionary advantage to obtaining Vitamin C through fruit consumption instead of endogenous synthesis. (Yes, this is wild speculation - but so is restoring human ascorbate biosynthesis)

The modern-day human suffers from relatively few nutritional deficiencies - it's been centuries since scurvy and rickets were a big deal. Why risk metabolic diseases by re-introducing biosynthesis pathways when we can just drink vitamin D milk, eat fortified wheat and citrus fruits, and swallow a daily multivitamin?

 

[Dave]

Bactericides maybe be a bad idea, not just in building resistant strains, but "clearing the decks" of the benign or harmless ones?

In the same way, people have stopped using wooden chopping boards in favour of colour-coded plastic boards. Wood is naturally antiseptic and once you make cut marks into a plastic chopping board it is difficult to ever get it completely sterile, whereas there is no problem with a wooden board.

 

[Ray McCarthy]

it's been centuries since scurvy and rickets were a big deal.

Except for people adopting processed "almond milk" instead of other products for small children. There was a death in England recently due to this.

Which gets back to the thought that the less varied or more faddish your diet might be, the more that accurate knowledge of you need to eat is needed.

With a decent diet you don't even need fortified products (though some may indeed be a good idea, folic acid in bread and vitamin D in vegetable spreads etc .) and not any supplements or multivitamins unless you are prescribed them due to some health issue.

 

[Ed Ryder]

You can do it with conserved genes in a direct swap in some cases; eg the 'humanised' mouse (or Drosophila) models available which express a human gene used in the immune response or express a disease gene instead of the normal wild type copy), but any major changes are beyond our current understanding.

That's in animals of course; plants on the other hand seem to have a much higher tolerance to that kind of thing, hence fertile hexaploid hybrids and suchlike.

 

[Mirannan]

There is a biosynthesis pathway for vitamin D in humans. The trouble is that an essential step in it is photolytic, and in some cases that's asking for trouble. I'm told that there is an increasing problem of rickets and osteomalacia in some ethnic communities in Britain; specifically, people of South Asian origin living in northern towns. Triple threat, because of 1) cloudy and/or polluted skies leading to low UV levels in sunlight; 2) dark skin; and 3) a cultural habit of covering most of the skin in fabric.

There's an interesting side point here. The current hysteria about skin cancer is leading to low blood levels of vitamin D in the population generally - and this may well be leading to increased illness and death in the population at large, because vitamin D is protective against various diseases - including some cancers!

So what might well happen is that you slap on the sunscreen to prevent melanoma - and leave yourself open to some other sort of cancer instead.

Regarding statins - one problem with them is that the same enzyme is also part of the synthesis pathway for coenzyme Q10 so statins lead to a deficiency in it.

 

[Ed Ryder]

I just eat Cornflakes for breakfast

 

[Ray McCarthy]

. The current hysteria about skin cancer is leading to low blood levels of vitamin D in the population generally

There is a new sunscreen cream supposed to be out shortly more selective on UV etc supposed to allow more vitamin D than comparitive SFP creams. Read about it this week.

 

[Ray McCarthy]

I just eat Cornflakes for breakfast

The milk though might be more nutritious than the cereal?

 

[Piousflea84]

There is a biosynthesis pathway for vitamin D in humans. The trouble is that an essential step in it is photolytic, and in some cases that's asking for trouble. I'm told that there is an increasing problem of rickets and osteomalacia in some ethnic communities in Britain; specifically, people of South Asian origin living in northern towns. Triple threat, because of 1) cloudy and/or polluted skies leading to low UV levels in sunlight; 2) dark skin; and 3) a cultural habit of covering most of the skin in fabric.

There's an interesting side point here. The current hysteria about skin cancer is leading to low blood levels of vitamin D in the population generally - and this may well be leading to increased illness and death in the population at large, because vitamin D is protective against various diseases - including some cancers!

So what might well happen is that you slap on the sunscreen to prevent melanoma - and leave yourself open to some other sort of cancer instead.

Regarding statins - one problem with them is that the same enzyme is also part of the synthesis pathway for coenzyme Q10 so statins lead to a deficiency in it.

Okay... this is such a common (and harmful) medical myth that I'm going to have to put on my M.D. hat.

* * *

The idea that mildly low levels of Vitamin D could cause cancers, autoimmune disorders, or other severe diseases is very controversial in the medical literature, and the idea that sunlight is somehow superior to oral Vitamin D supplementation is widely discredited nonsense.

It's a well known fact that low Vitamin D is associated with poor health. People who are already sick are much less likely to have good sunlight exposure, more likely to have poor intestinal absorption of dietary vitamin D, and their bodies are less likely to have good activation and storage of Vitamin D. It's likely that low vitamin D is a marker for poor health, not a cause of it.

The one major randomized clinical trial of Calcium + Vitamin D supplementation showed that it prevented bone fractures but had no effects on cancer incidence. (MMS: Error) While there are other studies in progress looking at higher doses of Vitamin D without all the calcium, at the moment there is no high-level medical evidence that Vitamin D benefits anything other than bone health.

There is absolutely zero rationale or evidence that photosynthesized Vitamin D is any better than oral supplementation of Vitamin D. The photosynthesis process creates only Vitamin D3, and most oral Vitamin D supplements are in the form of Vitamin D3. Neither is physiologically active until it's been hydroxylated by the liver and kidney (to 25-hydroxyD3 or 1,25-dihydroxyD3). Sunlight does not allow the human body to bypass the activation step in the liver.

None of the major medical societies in the US, UK or Canada recommend sunlight or artificial UV light as a treatment for Vitamin D deficiencies; all of the above recommend oral supplementation. (here's some links: Request Rejected, National Guideline Clearinghouse | Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline., Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. - PubMed - NCBI)

If you're worried about vitamin D deficiency, for God's sake take a Vitamin D supplement. They're cheap and completely safe. Don't seek out a sunburn or tanning bed, or waste money on "UV selective" sunscreen.

The ever-popular websites and Internet rumors that attribute amazing health benefits to UV light exposure are, to a large extent, sponsored by the tanning-bed industry and by companies selling highly expensive and useless "vitamin D tests". If you believe everything you read on them, you might as well believe in 1950s Marlboro ads claiming that cigarettes prevent arthritis and toothaches.

 

[JoGunnar]

Hey Ed. The answer to my question might seem obvious to you, but can full grown animals' or humans' genes be altered? Or does that have to be done before the animal/human is born?
I tried to look for the answer on the internet, but couldn't find a clear answer. Thanks!

 

[Dave]

Gene therapy uses a vrius to introduce genes into multiple cells, so the answer would be yes. However, I doubt you could change every single cell in the body that way. It is used to cure genetic diseases which usually cause a problem in a single or in several body organs rather than in every cell. Also, that wouldn't change cells that produce sperm and ova, so, you cure a person, but their offspring still have the genetic disorder - I think anyway. If anyone knows better then I'm happy to be corrected, and interested too.

 

[Ed Ryder]

As Dave said, it depends if you are trying to change a particular tissue, organ or every cell. There's been successful gene therapy on cystic fibrosis (eg Gene therapy breakthrough for cystic fibrosis - Health News - NHS Choices - hey I can post links now!) reported, but until recently it's been a bit hit and miss in the clinic. There's also the issue of deployment which may be different depending on what you want to change.
It's usually easiest (in animal models anyway) to do the editing at the earliest possible time, either at the one-cell fertilised egg or introducing altered stem cells at the blastocyst stage of early development.

Cells in animals are either somatic (most cells in the body and changes are not passed on to the next generation) or germ line (form eggs or sperm, changes are passed on), so you'd have to change the germ cells too in order for any changes to be inherited. Germline editing is a major ethical hotbed at the moment and many people are against it, fearing a GATTACA-style future of designer babies.

With the new CRISPR/Cas9 gene editing technology, however, the whole concept of gene therapy just got a whole lot easier , eg http://www.sciencemag.org/news/2015/12/crispr-helps-heal-mice-muscular-dystrophy the groups managed to make a change in a large number of muscle cells and gives real hope for people who suffer from this dreadful disease.
The new tech is the molecular biology equivalent of going from the horse-drawn carriage to an F1 car in one step, and we're only just at the beginning of that adventure. These are exciting times!

 

[Ed Ryder]

It's usually easiest (in animal models anyway) to do the editing at the earliest possible time, either at the one-cell fertilised egg or introducing altered stem cells at the blastocyst stage of early development.

s/animal/mammalian - can't edit it now for some reason

 

[JoGunnar]

Thanks! That makes sense that you would want to make the changes as early as possible. I've heard about CRISPR.
Like if scientists wanted to make a baby have blue eyes instead of some other color that could only be done in the early stages, it couldn't happen after the baby was born, right?

 

[Dave]

Like if scientists wanted to make a baby have blue eyes instead of some other color that could only be done in the early stages, it couldn't happen after the baby was born, right?

That can't be done at the present, but Ed, do you think that might be possible in the near future: To take a pill and get a different eye colour. I find that idea really creepy for reasons that I don't quite understand.

Is one of the reasons these things don't work because adult cells age fast and are kind of worn out? This is why we get Cancer, but also why Cloning doesn't work - everyone made a big deal about Dolly the Sheep but she had accelerated aging and died very early. If we can actually solve that problem then we will have found the Elixer of Life that people have searched for since time began. So, it is probably a long way off, if ever possible.

 

[Ed Ryder]

To be honest I don't know much about the specifics of eye colour genetics so I looked it up on t'internet (good old Wikipedia Eye color - Wikipedia, the free encyclopedia ) and apparently there are quite a few genes involved, so you'd have to change a lot of things all at once for it to work which would be very difficult. There's also the delivery method - I supposed you could inject something directly into your eyes but you'd have to *really* want a different eye colour for that! I suppose if you lived in a regime where anyone with blue eyes was shot at the age of five for example it would be a good reason to. Slightly less dramatic though for a pill you'd have to explain how the therapy method would home in and only target the cells you were interested in.
The good news is that the pigment is recycled, so I guess if you could get over all of the massive hurdles from the first two issues then it could be done, but it would take a while to kick in. In all though, it's probably easier to get coloured contacts fitted

Is one of the reasons these things don't work because adult cells age fast and are kind of worn out? This is why we get Cancer, but also why Cloning doesn't work - everyone made a big deal about Dolly the Sheep but she had accelerated aging and died very early.

The difference is editing a cell vs using it to make a whole new animal. If you're editing an existing cell and then just letting it carry on as it was then that's fine - the main issue there is if you accidentally break something else while you're doing it (off-target effects) which then causes problems like cancer later on. This is one of the main unknowns and ethical dilemmas at the moment.
With Dolly they used an adult skin cell or similar, deprogrammed it and then used that as the starting point for a developing embryo. The problem is that the cell had gone through many divisions previously and the telomeres (caps at the ends of chromosomes effectively) which get smaller each time, couldn't handle another load of divisions required by development. The result, which was probably compounded by other things such as DNA damage and the natural accumulation of small mutations through the cell's life, was premature ageing and lots of health issues. I don't really follow the literature on animal cloning so I don't know if they've managed to solve or reduce those issues subsequently, but the success rate was very low originally.
Personally I don't see the point of cloning animals or people, especially animals as pets. There are plenty of cats and dogs needing homes as it is, and even if you clone your dog it won't be the same dog because genetics is just a small part of what makes them what they are. Ditto for people. My cats are tortoiseshells and so wouldn't even look the same!

If you wanted a clone to be longer lasting, you could wait until the embryo is in early development, take a cell from there and store it until you needed it to act as a basis for the next clone. You'd have to know in advance of course what you wanted to clone so that's a bit of a catch-22

 

[Locrian]

Yeah people make a big deal about human cloning being unethical, but it's also pretty pointless unless all you are doing is cloning organs in vitro. Things that are pointless and difficult tend not to happen.