>Molecular Biology and Genetic Engineering explained by someone who's done it


This site is dedicated to people like Pim Stemmer who says "People who continue to reject GM will be shown for what they are, non-rational and anti-technology. That's really good."


Last updated Feb 8 2003

Click on the questions to go directly to the relevant commentry:

What is a GMO?
What is DNA?
How many DNA bases are there in a typical organism?
What is a gene?
How many genes does a human have?


What is a protein?
What is genetic engineering?
Why are organisms being genetically engineered?
Does knowing the human genome mean we know all about how a human being works?
What is junk DNA


What are some examples of products made from genetically engineered organisms?
If we eat it, how come we were never asked about this sort of stuff?
Have there been serious mistakes resultant from genetic engineering?
So how is this sort of thing going to effect my life - my coffee will taste the same, won't it?
Any near misses?


There's a group in the Netherlands who, as of May 2001, say they engineered a strain of live HIV which be a good vaccine against AIDS, what's your take on this?
What is substantial similarity?
What sort of people are making the legislative decisions about GMOs?
What was the Flavr Savr tomato?
There's a cow out there which makes spider silk in its milk. Is this a good idea?
What sort of weird GM things have you heard of?


Can give some examples of bad effects a GMO might have in an ecosystem?
Some people say we've been modifying plants for generations and that GMOs are no different. Is this correct?
What sort of modifications are already in the paddocks?
What's a roundup-ready crop?
What effect to glyphosate resistance genes have on the environment?


Some biotech companies say that they didn't add genes in or take genes out, yet they have modified the organism anyway, how does that work?
There's an idea that a protein will do only one task, and that since it only does that task that it can be relied upon only to do that task and therefore is a known quantity. Is this a fair statement?
There's this stuff out there called terminator technology (TT). It is promoted because it stops GM plants from propagating. Does it have any long-term consequences for the stability of the global food supply?
What about terminator technology's effects on the autonomy of farmers?
What's Exorcist technology, how does it work and does it really mean you can have GM-free GM crops?
Are genetically modified crops going to feed the starving millions?
Are genetically modified organisms going to eradicate disease?
Universities are the main institutions where molecular biologists are trained. Do university level courses have any components which inform young scientists about the long term consequences of molecular modification?
There is a concept called "free software" - how does that tie into genetic modification?
You complain a lot about GM, do you think there's anything good about it?



Q: what is a GMO?
A: a GMO (genetically modified organism) is any lifeform which has had its genetic material -DNA - deliberately changed by humans so as to accentuate or minimise particular aspects of a living organism, usually for commercial reasons but also sometimes for research reasons.

Q: what is DNA?
A: DNA is short for deoxyribose nucleic acid. In each cell of a living thing you will find a long, long strand of this stuff, which is a sequence of sugar molecules and phosphate groups. DNA strands usually exist as pairs of these strands, wound around each other like a spiral.

DNA stores the program that tells the cell how to make proteins which can do certain necessary tasks to keep the cell alive and to enable it to do particular jobs, like make new cells or repair damage.

What enables DNA to store this information is the sequence of molecules called bases which are attached to the side of the DNA. Bases on one strand pair up with bases on the other strand. Life on earth uses four different bases, encoded in blocks of three, to encode all the usual amino acids from which we make proteins.

Particular sequences of DNA encode what are called genes.

Q: How many DNA bases are there in a typical organism?
A: It depends, and varies widely (there is no such thing as a typical organism). To encode a bacteria you might need a few hundred thousand base pairs. Brewers yeast has about a million bases. A human usually has about thirty-two thousand million. Some plants have more than this. There is a theoretical limit to how few you need to run a metabolism because there is a requirement for a minimum number of genes to do the biochemistry required to keep something alive. Below this threshold are viruses, which depend on using the metabolism from other organisms to reproduce themselves.

Q: What is a gene?
A: a gene is a sequence of DNA which stores the construction information for the manufacture of a particular protein. A given organism will have some genes in its DNA which are not present in other organisms, but also have genes which are similar to genes in other organisms.

Q: how many genes does a human have?
A: about 30,000. Not all of them are switched on and being used to instruct the manufacture of proteins all the time. Some genes are small, and others are large. Not all genes encode one protein... some encode a precursor peptide which is chopped up or derivitised in different ways (for example, carbohydrate molecules are stuck on them in a process called glycosylation) to produce something distinctly different to what the gene itself encodes. A lot of the immunoglobulins are "differentially spliced" to produce lots of different proteins from one gene.

Q: What is a protein?
A: A protein is a substance which is made according to the specifications of one gene stored in the DNA. For each protein there are a range of possible variants on a given gene, and small changes can have large effects on the correct function of the protein.

All proteins are made of pretty much the same 20 subcomponents. The order in which these subcomponents are strung together differs. The subcomponents are called amino acids, and they are common to all carbon-based biological systems that we know about.

Different proteins have different sequences, so they are shaped differently and can do different structural or chemical tasks. Many of the proteins which do certain jobs are called enzymes and they enable the chemistry of life to operate. Some proteins dont do any chemistry that we know about, and mainly perform a structural role, like stopping your skin from being saggy.

Your hair is made of a protein called keratin. Your blood is red because of a protein called haemoglobin. People who have a gut enzyme called lactase can digest milk with lactose in it. Your tendons are full of a protein called collagen. Some proteins do special jobs like repair DNA damage. Some, like insulin, send signals from one part of the body to another. Most enzymes have ludicrous names... the one most directly responsible for incorporating carbon dioxide into plant sugars is called ribulose-1,6-bisphosphate carboxylase. Egg white is full of a gooey clear protein called albumin. Some proteins do amazingly specific, highly complex jobs, some of these jobs involve specific manipulation of subatomic particles, like hydrogen ions, or electrons. Usually they do tasks at the molecular level, moving whole atoms or groups of atoms arranged in a specific way. They are pretty remarkable things, actually.

Q: What is genetic engineering?
A: DNA occurs in animals, plants, fungi, bacteria, and even viruses (which aren't actually alive). Since DNA is the same across almost all living things, and they all encode proteins the same way in DNA sequences, DNA code from one organism will theoretically do the same thing when put into another organism and modify the biochemical behaviour of the recipient.

Genetic engineers are paid to take DNA from certain organisms and splice it into the DNA code of organisms where it was not originally. Or, they take the original DNA and modify it so it makes a protein which works differently.

The tools used for genetic engineering are usually proteins derived from bacteria, which can do things like assemble individual bases into a sequence, or chop a DNA strand at a particular place.

Q: Why are organisms being genetically engineered?
A: It varies. Sometimes it's for research purposes, since a researcher can often figure out why people get certain inherited diseases by seeing what genes do or dont work in certain ways, and engineering organisms like mice with genetic changes is one way to do this. This gives valuable medical information about things like cancer and birth defects or susceptibility to certain diseases.

But mostly, it's about making money. Companies will tell you they're trying to feed people or cure diseases but make no mistake - those aims are secondary to their main objectives, which are to make people dependant on their products, increase their market share and increase shareholder value.

Biotech companies engineer bacteria to make certain molecules, usually proteins, which have some kind of commercial value, for example some antibiotics. Insulin can be manufactured by engineered bacteria, which prevents the need to extract it from dead pigs.

Some companies are engineering existing organisms so that pesticides don't kill them, or so that insects don't eat them, or so that they grow really big really fast... there are lots of modifications that are planned. There is no way they have a clue about the long term impact of these organisms on the ecosystem.

The main motivation for the biotech companies is that they think they can make an astounding amount of money by making organisms make molecules which are profitable. They use living organisms as nanofabrication factories for specialised molecules, because living organisms are very energy efficient at doing this.

Q: The human genome project will give us the sequence of all the DNA in a human being. Doesnt this mean we know all about how a human being works?
A: No.

Knowing the sequence of all the genes doesn't say anything about how they all work or how they all interact. The genome project also only took DNA from a small number of humans, so most varieties (alleles) of human genes are not represented. Much of the sequence data originated from Craig Venter, who, upon the (incomplete) sequencing of the genome by Celera Genomics (which he runs) used the data from his sequenced DNA to diagnose that he had a lipid metabolism problem, for which he now takes corrective medication.

Further, there are functions we need to have which our genes don't encode, like the manufacture of folate, which is made for us to a limited extent by bacteria in our intestines, so in theory, to encode a complete human, it might help to include some of these genes too. Human mitochondria have been sequenced for some time, they were only forty thousand bases long, but they do very important jobs.

Some of our metabolic pathways are broken - we have, for example, some of the genes for the synthesis of ascorbic acid but we can't actually make it ourselves, we have to get it in our diet, by eating plants which make it.

Q: What is junk DNA?
A: DNA which does not encode genes which instruct the building of proteins. I think junk is really a poor label, it simply means we don't know how to figure out what it does.

It obviously plays a role in phosphate, deoxyribose, purine and pyrimidine metabolism, since at the very least this stuff had to be synthesised, and sits around behaving as a kind of storehouse of these materials - if a cell dies or undergoes programmed self-destruction (apoptosis) then all that noncoding DNA is made available for incorporation as raw materials into other cells. It also plays a role in DNA packing and maintaining telomere stability. It worries me that some people are arrogant enough to call it junk DNA and are so readily accepting of the recieved wisdom that simply because it doesn't encode a gene or regulate protein expression, it has no role. Einstein said we only use 10% of our brain but that doesn't mean that people who are missing 90% of their brain (eg: car accident victims, television evangelists, for instance) are fully functional.

I expect there will never be a human which could be engineered so that there was no junk DNA in its genome, or if it was so encoded, the human would be fragile... robust systems have lots of redundancy, things you can damage without serious consequences. This is, by the way, the reason organisms have what is called ploidy - a number of copies of each gene. Humans are diploid (we get one copy of each gene from mum and one from dad, making two copies), some plants are triploid or tetraploid. It means you can have an error in one copy but not be seriously affected because the other copy works fine.

There are arguments about the role of junk as a kind of protective agent amongst which the useful DNA can hide from damage, or the junk can act as a physical scaffold for useful DNA. It has been shown that it does have a role in packing DNA properly. The introns - non coding parts - of some genes, which are spliced out before transcription, intrinsically make it difficult for things like viruses to simply chop out our genes and use them for their own purposes. So I hesitate to assume that just because we don't know what it does, it's useless.

Q: What are some examples of products made from genetically engineered organisms?
A: They're all over the place. Enzymes in washing powder have been engineered so they last longer in the wash. This probably has unforseen consequences in terms of how long these enzymes last, and what they do, when they hit marine life near ocean sewage outfalls, for example.

A lot of antibiotics are made by bacteria with entire suites of genes in them, which enable the bacteria to make the precursors to the antibiotic, and the antibiotic itself, from regular things which the bacteria can eat. These bacteria aren't usually released into the environment, however.

These days a lot of human foodstuffs are derived from plants with non-indigenous genes in them. Some of these genes have never existed until recently, notably the ones which degrade pesticides - mainly because these pesticides didn't exist until recently. We don't know what these genes do out there in the ecosystems into which they are placed.

Q: If we eat it, how come we were never asked about this sort of stuff?
A: Companies have been doing this pretty much without the permission of the public, and the public are being kept pretty much in the dark about it by the mainstream corporate media, whose sound-bite architecture doesn't permit detailed complex information to be distributed to the public. People are interested but the media fail in their task of informing the public because the network bosses and TV moguls think it is more profitable to fill up the bandwidth with inconsequential drivel like olympics and sit-coms.

It is also totally obvious that what is called western democracy is actually a mechanism to prevent the public having a say. You are supposed to exercise your decision making power only very narrowly, as a consumer in the supermarket. That the public has a right to know, or even an interest in the biology of what they eat, or even their own biology, is not even permitted onto the agenda for discussion.

Q: Have there been serious mistakes resultant from genetic engineering?
A: Yeah. They're just the first in what history will reveal to be a string of stupid and preventable screwups. The classical, and tragically stupid, example occurred around 1990. It'll take a little while to explain, it's complex... that's partly why it happened, the complexity is subtle.

I mentioned amino acids and proteins... well, one of the amino acids acids we need is called tryptophan. You usually make it in your own body from a precursor called chorismate. Some people dont make enough of it, so they take it as a dietary supplement.

You could go to all the trouble of using synthetic organic chemistry to make tryptophan, but the reactions are complex, expensive and the yields are low. So generally nobody does that.

Another way to make it in a factory is to get a big vat full of nutrient and grow a certain bacteria in it, a strain called Klebsiella, which happens to make a lot of tryptophan. Usually you let the vat brew for a few days, then rupture all the bacteria, and extract the tryptophan. Humans have been doing this perfectly adequately and safely for decades.

We know what all the genes are which make the proteins which turn chorismate into tryptophan. Usually these genes are turned on and off in a regulated manner by the organism which is making the tryptophan. This makes sense, the organism doesnt make any more tryptophan than it needs, it allocates its resources in an efficient way. The regulation mechanism involves a stretch of DNA just before the genes which encode the proteins which make tryptophan. This stretch of DNA is called a promoter, and is involved in deciding wether or not a protein is going to be made. In klebsiella, the promotors switch the tryptophan-making protein-manufacture machinery on or off as needed. This sort of regulation goes on everywhere in all living things.

In the early 1990s a petrochemicals company called Showa-Denko reckoned that they could make a strain of Klebsiella with all the regular tryptophan-making genes turned on all the time - they replaced the usual promoters with ones which were turned on continuously. This was so bacteria would make loads of tryptophan. It did indeed make loads and loads of tryptophan. It also started making something else, something rather unexpected.

Anyway, since the tryptophan was manufactured in pretty much the same way as it usually was, it was decided that no special tests be performed on the end product, no labels need be put on the cans it was sold in, and so off it went into general consumption. 36 people were fatally poisoned. About 1500 now have permanent nerve poisoning, a syndrome called eosinophilia-myalgia (EMS)... permanent serious muscle pain and other problems.

So how did that happen?

It turns out that in the engineered klebsiella, the _precursor_ to tryptophan built up to such a high concentration that it formed a dimer - that is, two precursor molecules chemically bonded with each other, to form a molecule called 1-ethylidene-bis-L-tryptophan, or EBT for short. This dimer never occurs in natural organisms, because the promoters switch production off when concentration gets too high. If biochemists were trained in physical chemistry they might have seen this coming, but physical chemistry in living things is hideously complex, and biochemists aren't much trained in physical chem, so they couldn't even begin to try and predict it. Physical chemistry in dead things is pretty complex, too.

EBT is chemically similar to tryptophan (it is just two tryptophans bolted together, after all) so it came through with the tryptophan in the extraction procedure, to about 0.5% contamination by weight. Showa Denko settled out of court for a large sum of money. The dead people are still dead, others EMS victims gradually die off as the years roll on.

Tryptophan became a restricted chemical after that. How can legislators call a molecule restricted if it is a component of most of the proteins in every living thing? What really should have been restricted is the freedom which companies have to spread GM derivatives around the planet.

When I did biochemistry/molecular genetics in 1996-1998, we were told lots about how tryptophan is synthesised in cells and how it is regulated, but not a peep about this screwup, which is a heck of a cautionary tale.

Q: So how is this sort of thing going to effect my life - my coffee will taste the same, won't it?

A: Nobody really knows. Probably not. I read recently that the genes responsible for the synthesis of caffeine in the coffee plant (Arabica robusta) has been identified and some biotech startup thinks there's money to be made by turning that gene off and thereby producing a coffee bean without caffeine in it, which in turn produces a decaffeinated coffee which still has all the full caffeinated coffee flavour in it because the other flavour molecules aren't lost (co-extracted) during the solvent-based caffeine extraction procedure currently employed in industry.

Apart from the zero-diversity problems attendant to having zillions of hectares of identical GM arabica robusta all over the world (the diversity of the coffee tree genome is already pretty restricted) there is no mention of the possible biochemical consequences of this engineering : if you turn off the gene which produces the protein which transforms all the precursors to caffeine into actual caffeine, then what happens to all that precursor? Does it build up to a concentration at which it can biotransform into something poisonous to humans or damaging to the surrounding environ? Does it influence the kinetics of some other part of the plant's biochemistry which renders the crop able or not able to do something else, for example will a GM caffeine incapable plant make more dimethylxanthines instead (gotta do something with all that xanthate precusor, if it can't make caffeine, the plant might increase the synthesis of theobromine or theophylline, the latter of which is toxic to some people). We aren't learning the necessary lessons, we're keeping on making the same fucking stupid mistakes over and over because we aren't learning to ask the questions which we should have asked when we discovered we messed up the first time around.

Q: Any near misses?
A: Absolutely. My god, this one 'll make you dirty your pants, it's so scary. Again, it's a bit of a long story.

A German biotech firm engineered a bacterium  (again, Klebsiella, the particular subtype was called planticula) to help dispose of rotting crop waste on farms. It happpened that when it did this it also produced ethanol, which is in demand as a fuel.

The engineered bacteria was sent off to Oregon State University in the USA, to be tested. Usually when labs test an organism they use sterile soil, basically it's normal dirt which has been processed in such a way as there's nothing left alive in it, which means all the variables are controlled, you don't have earthworms or nematodes or fungi or whatever in the dirt to mess with your results. But that means you're testing it in dirt which is totally unrealistic compared to the dirt in which you typically grow plants in, which is usually packed full of living things.

Anyway a doctoral student named Michael Holmes thought that testing this bacteria in sterile soil was senseless so he did the test in various sorts of living soil with lots of organisms already in it.

He found that every plant put into the living soils with the engineered Klebsiella died.

Why did this happen? It turns out that the Klebsiella interfered with, and often killed, the mycorrhyzal fungi in the dirt, which are responsible for making soil nutrients available so the plant can absorb them in its roots. Plants are dependant on these soil organisms to live.

Think about it. The engineered Kleb was producing ethanol, the stuff  which,  when you drink it in beer, makes you drunk and kills cells in your liver and brain. Ethanol is a widely used biocidal agent, we usually wiped down the benches with it in the  lab where I used to do my research, for this reason. Of COURSE it's gonna kill things in the soil, including the plant roots too, if my experiences in plant biochem lab are anything to go by. The experiment is easy enough to do - pour some ethyl alcohol on the grass outside and come back in a few days, and it'll be dead. Well, duh.

But it gets astoundingly worse.

Suppose this stuff had been tested in sterile soils, and given the OK by the EPA (like the FDA did with tryptophan) to be released, in processed plant waste, onto soil on farms throughout the world. You'd never stop it.  It would adapt to every treatment you'd throw at it. It would be impossible to contain its spread. It would just distribute itself on vehicle tyres, dust storms, the claws of birds which happened to land on the soil. It would spread throughout the planet gradually resulting in the eradication of agriculture and most the plant kingdom as we know it.

(See: Suzuki, Dressel, "Naked Ape to Superspecies" p120-121, Allen and Unwin)

If Holmes hadn't done  his experiments in real dirt, we'd never have known the effects in living soils. The guy deserves a Nobel Prize for bringing these results to light and averting the collapse of the civilised world, which is entirely dependant on agriculture.
 

Q: There's a group in the Netherlands who, as of May 2001, say they genetically engineered a strain of live HIV which might be good as a vaccine against AIDS. What's your take on this?

A: I think I'd rather be shot than take this stuff. They've engineered the virus so it's dependant on the presence of a chemical called doxycycline to permit it to replicate. The theory is that they infect you with this stuff and give you doxycycline and it gives you a very weak form of AIDS for a few days, and then they stop giving you doxycycline and the doxycycline-dependant virus dies out. During which time the immune system learns to recognise the HIV virus and generate antibodies and white cell defences to that virus.

 The people who think live attenuated vaccines are useful as vaccines fail to understand that they are dealing with a dynamically adaptive, self-interested, evolving and replicating data construct - a virus. Viral DNA and RNA replication is *intrinsically* error prone - that's how HIV becomes specific for CD4+ T-cells and macrophages and certain kinds of neurons, it's also how it generates escape mutants to become immune to sodium phosphonoformate, and protease inhibitors, and chain terminators (like AZT and ddI) and even to recently developed error-inducing nucleotide analogues which are supposed to push the virus over its error-catastrophe threshold.

 If you stick live AIDS into someone, even if it's attenuated, it'll become virulent in the long term, period. After all, you've put it on an evolutionary topography where the virus will 1) benefit by not replicating any more of its own RNA than it has to and 2) benefit by losing the gene or promoter which encodes its controllability by doxycycline. Eventually there will be a variety of it which *ignores* the presence of absence of doxycycline and replicates anyway.

For heaven's sake, viruses lose virulence genes when you passage them in cell culture, *because* it's more efficient for the virus to do that in the context in which it finds itself - a cell culture context where it does not need to be virulent. Over a few generations of infecting cultured cells in a sealed environment in which its every need is catered for, the virus throws its virulence genes away because it doesn't need them, Any virlogist with half a clue knows that.

Q: What is substantial similarity?
A: It's a term which signifies that the GM food crop regulatory authorities and legislators have absolutely no idea about molecular genetics. They pass legislation which says "if a GM plant is substantially similar to the natural plant, then they can be treated as if they are the same."

This is absolute crap piled on top of arrogant stupidity. I guess it is to be expected, since most of the people who write these laws are economists or lawyers, business types who haven't the slightest idea about how real living systems work.

Ok, yes, technically, chimpanzees are substantially similar to humans... mainly humans who write this kind of legislation. There are lots of examples in nature where the tiniest little difference can have massive, often fatal differences.

There's a protein I mentioned earlier, haemoglobin. Its main job is to sit around in red blood cells, pick up oxygen in the lungs and dump it in the other tissues. There are two genes which encode the subcomponent proteins in haemoglobin. Regular haemoglobin molecules float around independantly inside the red blood cell, so the red blood cells can squeeze through tiny blood vessels, called capillaries.

Some people have a blood disorder called sickle cell anaemia. This occurs because the amino acid sequence in the haemoglobin has changed slightly, which in turn occurs because ONE DNA BASE has changed. The consequence of this is that the haemoglobin molecules stick together, and form rods, which turn red blood cells into a kind of stretched curved donut shape, which stops them from going through capillaries easily, and this starves your flesh of oxygen.

At a DNA level you might be substantially similar, but at a functional living being level you've got serious problems if this single base is changed ... one base in 3 billion. Basically because you multiply that error in ALL of your red cells.

There's a load of other examples... genes which predispose you to getting cancer... genes which, because they dont work, mean that you bleed for days when you get a tiny cut... all substantially similar, but nevertheless different to the usual version which most humans have.

Q: What sort of people are making the legislative decisions about GMOs?
A: I don't know, but they aren't the people who use or understand the technology. I went to a public forum at NSW state parliament in 1999 about this, sat and listened to the suits at the front, and to the questions asked by the journalists. I stood up and said, "Is there anyone in this room, aside from me, who actually does molecular genetics, uses restriction enzymes, can sequence and clone a gene, or has any idea how this genetic technology works?" I was the only person, in a room with five hundred people in it, who had ever actually gloved-up and gowned-up and done molecular genetics.

This isn't actually surprising. Molecular biology takes a while to learn, it's hard stuff. Also most gene jockeys who have jobs are employed by biotech firms, which would sack them instantly if they said anything about what they do... non-disclosure agreements are a part of getting employed. So they shut up. Most of the ones I've worked with don't actually have a clue about the distributed interactivity of the ecosystem, 'cos they are confined to a narrow specialty. I can talk about this 'cos I get paid to be a computer geek.

Most journalists don't even know what are the right questions to ask.

They focus on wether or not the GM crops are safe to eat. My bet is, after it's been killed and processed and frozen and seasoned and oven roasted, it's probably safe to eat, but really we just don't know until some people die because of some wierdo interaction we didn't know about. The Showa Denko lesson is there for the learning, if you look for it.

Food safety is peripheral to the main questions, which are: Is it safe to have this casually modified molecular software running our global food supply? Is it stable for the next few million years? Is it diverse enough to be robust? (If it crashes as often as most commercially available software, we're in deep shit, soon). Should it be owned by a few large, unaccountable, immortal transnational companies, who employ biology-clueless accountants to decide about "how to manage" it for maximum profit?

Currently I think the respective answers are no, no, no and no. I am unlikely to change this stance in the forseeable future.

The stake we should be interested in is long-term survival, that is what you play for when you're playing a game called Darwinian Selection. Species too stupid to realise this are eventually edited from the gene pool. This is a fate for which I think h.sapiens is a prime candidate.

Besides which, we already HAVE safe, not-modified food plants, which have a track record of centuries of safety. Let's eat 'em while we can still get them.

Q: What was the flavr savr tomato?
A: Tomatos rot because there are genes which turn on when the tomato ripens, which make enzymes which dissolve the structural components of the cells in the tomato.

The idea was that to make tomatos last longer on the supermarket shelf, you just turned these genes off. Anyway this was done and it produced a tomato which was more fragile than the ones already on the shelf. They were then used to make tomato soup since they're easier to process than regular tomatos. I don't know if they tasted any better.

While we're on the subject of tomatos, the ones we get look really red and juicy, and are firm as tennis balls, but taste like wet cardboard. These were not genetically engineered to be that way... farmers and consumers bred them that way. How?

For years grocery and supermarket managers complained that soft, mushy tomatos (which also tasted good) were not profitable. Shoppers would judge their tomato by the firmness and the look of it. Tomatos which allocated their resources to making flavour molecules, were mushy and were easily bruised and looked unattractive on the shelves, so shoppers didn't buy them even if they probably tasted good.

The call went out, we want firmer tomatos. So tomato growers started to select strains which were physically tougher. A plant which allocates resources to structural strength is not allocating them to making itself tasty. Over several decades we have arrived at a tomato which is optimised for profitable supermarket distribution, is as red, firm and shiny as a cricket ball and tastes about as good, too. They don't even go splat when you drop them. We brought this on ourselves without GMOs.

Q: There's a cow which has been engineered to make spider silk in its milk udder. Is this a good idea?
A: Well, we don't know. It probably isn't going to help any calves the cow might have, when they try and grow up drinking milk with spider silk proteins dissolved in it. In any case, again, nobody is sure what this gene (fibroin) will do in all the other cells in the cow, if it gets expressed; I'm yet to hear wether the cow has immunologically reacted against the fibroin or its derivatives.

Why is this being done? Well, it's for the fibre. Cows are going to get a lot of modifications, I suspect, since that udder of theirs is a convenient thing from which to extract all sorts of engineered protein products, because the technology for it already exists (automated cow milking machines). But, it's being plugged right into the nutrient supply of the new calf. This isn't a very clever thing to do, I think.

I heard in 2003, someone has engineered cows so they make more than twice the normal amount of casein in their milk. They used multiple copies of the normal cow genes for casein, so it's the same two proteins beta-casein and kapa-casein, which cows usually secrete into their milk, but the engineered cow makes 2 times more kappa-casein and 1.7 times more beta-casein - they're not in their usual proportion. These cows also have a genetic marker for resistance to an antibiotic engineered into them too, as an artefact of the cell selection procedure used to select the individual engineered cells from which these cows originate. It hasn't been mentioned if all the cow's cells express proteins which destroy a particular antibiotic, but if they do, and the cow gets a bacterial infection, there's at least one antibiotic you can't use to help the cow recover from any infections it might get, because its cells just destroy it. I'm sure veterinarians aren't going to like that.

Now, the cheesemakers are saying this casein overexpression is a great idea, they get more cheese from milk, more money per cow, etc. But think about it for a moment... by changing the promoters for the expression of these casein genes, they have altered the animal's normal tissue-specific allocation of amino acids. All animals have a daily amino-acid budget, and these cows are now allocating a hell of a lot more of their amino acid pool, to excretory casein synthesis than they normally would. In addition they will be depleting their amino-acid pool most severely of the exact same amino-acids which will now be used up in the process of making lots of casein - not all amino-acids are depleted equally. Normal cows make as much secretory casein as their body thinks is necessary, and these ones have been engineered to make heaps, in an unregulated way. Are these cows going to experience illness as a result of amino-acid deficiencies elsewhere in their system as a result of placing all their resources into their milk glands? Nobody knows yet.

It should also be noted here that since this animal has several copies of casein engineered into it, that this animal is no longer totally a diploid mammal any more - the ploidy for the casein genes is much higher than the ploidy of the genes for the rest of the animal. Generally if you have changes in ploidy you get odd changes in the physiology of the animal; when humans get ploidy changes they exhibit things like Klinefelter's syndrome or Turner's Syndrome - which are brough about by excessive copies of things like the genes on X chromosomes.

Q: What sort of weird GM things have you heard of?
A: Someone's trying to develop blue roses. You can, from certain research institutions, get hairless mice which faintly glow green in the dark, they have been engineered with genes from bioluminescent organisms. There's also a mouse which has been engineered with its pigmentation synthesis genes placed under the control of the bacterial lac operon, so it'll change the colour of its growing coat-hair depending on wether or not you feed it a particular material (IPTG). I imagine these sorts of things will eventually become available for sale, and pollute our ecosystem even more than it is already, just because someone thinks there's a buck to be made and no legislator will have the nouse or guts to prevent it.

Another whacky one is, someone has engineered potatos to glow in the dark when they're in need of water (using the same luciferase genes, but different promoters, to the ones spliced into the mouse mentioned above) . Um, can't people just look at them and see if they're wilting, like we did for a few thousand years? More recent examples of utterly idiotic GM projects include engineering grass so it doesn't grow so fast, therefore needs less frequent attention with a lawnmower (I'm not kidding... instead of planting something other than grass, our solution to lawn maintenance is evidently to engineer grass to be slow-growing... you're still going to have to waste resources growing it and you'll still have to mow it!) - and there's an Israeli chap engineering chickens to have no feathers. I don't suppose it ever occurred to this guy that feathers actually do useful things for chickens, like say, keep them warm, and provide abrasion resistance, waterproofing, and so on? I imagine someone will get the idea that it might be good to engineer humans to have 12 fingers, so they can type faster, play the piano better, etc - and when it eventually happens it will never be asked why evolution decided, after millions of years of testing, on five digits per hand.

Just because we can do these sorts of things does not mean they're a good idea. It concerns me that living organisms are being engineered to suit the requirements of sometimes demonstrably stupid sales droids and marketing analysts.

Q: Can you give some examples of bad effects a GMO might have in an ecosystem?
A: Yeah. There's a cotton crop you can get with a bacterial enzyme engineered into it. This enzyme (from Bacillus Thuringiensis) attacks the internal structure of insects, so when the insects eat the plant, the enzyme attacks the insect, which kinda dissolves into mush from the inside out, in a day or so.

This means that the crop is protected, but it also means that the dead insect isn't out there doing its particular job in the ecosystem. It might be that it had other jobs like pollenating nearby plants, or becoming food for local bird life. Obviously if it has dissolved into brown sludge from the inside out, it can't perform those roles any more. Sometimes these roles are critical. Say your engineered plants also slowly kill every bee in the district... where will the beekeepers go? Where will the new saplings germinate?

There's an additional consequence to doing this - you set the scene for the evolution of insect pests which are resistant to attack by this enzyme. So over the years, the organic farmers who use bacillus thuringiensis as a natural pesticide of last resort are going to find that it doesn't work any more. And, in the very long term, the adapted insects will just eat the engineered crop anyway, so the farmer will have to get the same crop but engineered to have a different poison in it.

Some additional things go wrong with the crop, like sometimes its leaves are warped, or the toxin doesn't actually work against pest weevils (they have resistance, maybe?), or the plant has very little foliage so it doesn't grow very quickly, or the cotton bolls on it were shaped stragely and yielded no fibre. Whatever the Bt gene was doing, we didn't completely know about it.

Here's some other examples; there's genes for various lectins implicated in actually raising the susceptibility of potatos to sucking insects, because these GM-introduced protein are thought to be responsible for decreasing the amount of glycoalkaloids produced when expressed in genetically engineered potatos, and glycoalkaloids are what potatos use naturally to repel sucking insects. (See: Annals of Applied Biology Vol 140 p143). It's known also that when Pioneer-Hi-Bred engineered Soybeans to express a methionine-rich Brazil nut protein in 1996, the protein was later shown to cause allergies in the people eating it (the idea here was to make the food more methionine-rich). There's various people also engineering the genes controlling the process of synthesis for lignin in trees, so they are more easily able to be processed into paper... who knows what this modified lignin will turn into when the organisms responsible for breaking it down try and eat it, or what structural effects it will have on the trees growing it? (See Nature Biotechnology Vol 20 p607).

By 2003 a gene encoding an enzyme called Cystatin has been inserted into many of the world's banana crops. Cystatin originates in a totally different plant, namely rice, and blocks the action of an enzyme called cysteine proteinase. Cysteine proteinase chops up proteins which possess an amino acid called cysteine. The idea behind this is that cystatin expressed by engineered bananas prevents nematodes, which are a worm which eats banana plants, from completing their life cycle by preventing the nematodes from digesting the banana flesh (by blocking the nematode's cysteine proteinase which is part of the way nematodes chop up banana proteins during their digestion). Does anyone know if the engineered inhibition of cysteine proteinase changes anything else, like the way we digest bananas, or the function of the hundreds of kinds of bacteria in our gut, or the way bananas run their own internal cysteine proteinase biochemistry? What about cystatin... does it interfere with anything else? What happens if all the nematodes die out where these engineered banana crops are planted? What are we going to do if the nematodes don't die out, but instead become resistant to the effects of cystatin? What about all the other things which live on bananas... fungi, bacteria ... what will cystatin do to them?

Carson wrote Silent Spring what, thirty years ago? What happens when the only organism which survives in an ecosystem is the one which has eliminated all the neighbours with engineered molecular trickery?

If you plant vast areas with the same identical plant, you have a monoculture, and anything that damages it will damage the entire crop because there is no variation. Diversity creates robustness. If you have a crop with 5 strains of wheat, a frost might kill some of it, a drought might kill some of it, a flood might kill some of it, an insect might kill some of it, a fungus might kill some of it, but any one of those will only kill 20% of your crop. A crop with one strain of wheat is uniformly vulnerable, and that's exactly what the GM plants are - pretty much genetically identical.

And - a field full of some GM crop is a field with no natural crop in it. So what happens when the planet is planted with this? Where does the diversity of heirloom strains go? They go extinct, that's where. Extinct is for a long, long time. Its software we can't afford to lose.

Q: Some people say we've been modifying plants for generations and that GMOs are no different. Is this correct?
A: No. What we're doing is taking genes and inserting them into organisms in which they did not evolve. Genes and proteins do not come with an instruction manual. Suppose there is a strain of wheat which has been selected over centuries for its resistance to frost. The particular makeup of that plant is is full of genes which evolved entirely in wheat, and is going to be more predictable in the long term than say, a genetically modified wheat plant which has had a gene from, say, a jellyfish engineered into it to improve frost resistance. We have no way of knowing what the jellyfish gene will do in the metabolism of the wheat, or in the ecosystem local to the wheat crop.... it evolved in the ocean, after all. Who knows what it could do in the paddocks?

Q: what sort of modifications are already in the paddocks?
A: I'm finding it hard to keep track of them all. A chap named Herrera-Estrella from Mexico is engineering crops to tolerate droughts by making them synthesise sugars (for instance, trehalose) which tend to make it easier for the plant to retain water (this trick is widely practised in a lot of natural succulent plants like the cacti). Yeasts will ferment trehalose, so are we looking at accidentally engineering the plant so that its relatively moist, sugary products rot faster in storage silos?

Tobacco is being engineered with proteins which enable the roots to pump salt out of the plant, which enables the plant to grow in soils otherwise rendered useless by salinity. I suspect this might be a good way to engineer a salt-tolerant weed, but anyway, what *are* we growing tobacco for - it causes millions of people to die painful deaths every year, many of them become a drain on government resources when they're busy being treated in hospital.  Tobacco doesn't feed anyone except the tobacco company shareholders.

But wait, there's more. Someone's engineering cats so they are non-allergenic to humans... but there's no discussion amongst the proponents that cats might be secreting their allergenic protein for a good reason. Someone else is planning to engineer bacteria that convert your sweat into pheromones. This isn't going to feed anyone either.

Some other bunch of people are in the process of engineering cattle to be immune to trypanosomes, which would have the undesirable long term effect that feral cattle in Africa would undergo a population explosion in that country because trypanosomiasis is one of the major things keeping them in check. But they never talk about that scenario.

I've heard of engineered plants which lower the pH of the soil around them, which makes it easier for them to extract phosphate ions from the dirt. Too bad if you're a soil organism and you prefer not to have your environmental acidity increased.

Somewhere else rice has been engineered to contain more precursors to vitamin A. It's been given away free to impoverished nations supposedly to prevent blindness due to vitamin A deficiency. It's called Golden Rice. It's causing some problems already. People aren't getting visual defects from vitamin A deficiency like they used to but now they're getting vitamin A toxicity, you only need about 33 milligrams of this per day in your diet before you start to exhibit poisoning, it's a lipid-soluble vitamin so it's not like Vitamin C any excess of which you can excrete in your urine. The way to fix this is to eat less vitamin A by eating less of the engineered rice, but uhhh, they can't do that, they were offered it for free and planted all their fields with it and it's their staple diet and they cant afford to buy rice from anywhere else. Brilliant, not.

There's potatos which have been engineered to be resistant to various viruses, too, but I can't see why in the long term the viruses won't adapt to the engineered crop, as has been the experience with other pest organisms. I can't see why when the spuds eventualy flower (as, the variety Lemhi Russet will do) they won't spread this gene around amongst other spuds.

I brew my own beer, and I have heard a rumour which I have not been able to pin down concerning the engineered strains of yeast (saccharomyces cerevisiae) used in commercial breweries. I don't know yet but it wouldn't surpise me, yeast are an industrial workhorse and modified strains exist in laboratories all over the world.

Q: What's a roundup ready crop?
A: A crop which has been engineered with enzymes which protect it from being poisoned by glyphosate sodium, which is a plant poison and widely used weedkiller. The company which has the patents on these plants also owns the patents on the roundup herbicide. They engineer crops so they cant be killed by glyphos, so you can spray a crop and it will only kill the weeds.

Q: What effect do glyphosate resistance genes have on the ecosystem?
A: Certainly their presence encourages farmers to spray more glyphos on weed plants, which increases the amount of residue in the overall crop, and also in the soil.

If you look on a drum of Monsanto Roundup, it says that "glyphosate breaks down on contact with soil" ...which is not completely true. It doesn't all break down instantly, which means that the label is misleading. It has a half life of several months. So it builds up from repeated application. Check the Merck Index entry for it.

It isn't known if these genes have spread into other plants, but it wouldn't be surprising, given that all lifeforms want to do is to spread their genes around, after all, that's what they evolved to do. Do we need weeds which are resistant to weedkiller? I think not.

Q: Some biotech companies say that they didn't add genes in or take genes out, yet they have modified the organism anyway, how does that work?
A: Word-play. You can have all the original genes, just driven under different promotors - genes which are usually switched on or off are engineered to be permanently turned off or on, or made to turn on/off under different circumstances to the ones under which they used to turn on or off, and this has a significant effect on the behaviour of the organism. Or, a gene is reinserted backwards so the protein it encodes doesn't get made. The effects of this aren't known, but you can say "we didn't take out or add any _genes_." Its like saying glyphos breaks down on contact with soil. Its a half-truth, they rely on people not to ask anything else. Usually it works because they don't know what to ask.

Q: There's an idea that a protein will do only one task, and that since it only does that task that it can be relied upon only to do that task and therefore is a known quantity. Is this a fair statement?

A: No. All complex proteins have an evolutionary history. For example, we have a protein in our liver called alcohol dehydrogenase, it breaks down ethanol (which is produced by our gut bacteria). It happens that a protein in the lens of human eyes, called crystallin, will also break down ethanol. This is probably because crystallin evolved over billions of years from the same sequences of DNA which encode alcohol dehydrogenase. Check out their genes, they're pretty similar. Other proteins and enzymes probably used to do other jobs millions of years ago, but we don't know what they did because we don't even know how to look. Their behaviour is very context dependant.

Q: There's this stuff out there called terminator technology (TT). It is promoted because it stops GM plants from propagating. Does it have any long-term consequences for the stability of the global food supply?
A: Yes. TT makes crops produce seeds which can't germinate. It generally works by inserting into the plant genome a gene encoding a protein which interferes with germination (and there are several ways to do this) and putting this protein under the control of a DNA promotor sequence which is activated during seed germination. So the seed starts to germinate and then poisons its own germination process.

If the company which makes the F1 (parent) crop suddenly can't provide new seeds to the farmers each year, then the result is shortage of crops because the farmers can't grow next years crops from the seeds they have already from the last years harvest. The word "crippleware" applies here. Destabilising the software which feeds you is uh, suicidally insane if you're interested in long-term survival.

In the long term you can't guarantee a mutation won't enable the TT engineered crop (and any other genes it might have) to propagate, because you're dealing with a living organism. _All_ it wants to do is spread its genes around. Say a TT crop pollenates a nearby wild type crop. Does that mean that the wild crop's progeny is now not going to germinate? This is like a self-destruct sequence but with a distribution mechanism. The epidemiological analogy with a plague disease is exact.

Q: What about terminator technology's effects on the autonomy of farmers?
A: it induces dependancy on the GM crop because farmers can't grow their crop from seeds they might have adapted to their particular environment over decades. They become dependant on an agribusiness co for their annual seed supply, for which they pay a lot of money, and they used to get it for free.

Q: There's a new technology (2002) called Exorcist. How does it work and does it really mean you can have a GM but GM-free plant?
A: Supposing you had modified a plant genome to include a transgene like, say, one which encoded a protein which made the GM plant herbicide resistant.. Once that gene has been transcribed into mRNA and the protein has been produced, the GM technology has done its work, but after that, the "Exorcist" is a neat way of chopping that gene out of the plant's genome - in fact it will chop the transgene out, and also most of the DNA which has been spliced into the plant genome to enable the Exorcist mechanism to work.

Naturally, Exorcist itself is a genetic modification which leaves traces of itself behind after it has done its work (which includes chopping itself out of the genome of the modified plant), and these traces remain both in the modified plant genomic material. Also, the chopped-out sections encoding foreign genes are not reliably destroyed, they sometimes remain after excision, floating around in the cell, doing whatever it is they do when they're chopped out (which isn't known).

The "Exorcist" protein is called Cre, which is actually a (bacterial) virus recombinase enzyme which chops out anything between two specific DNA sequences (called loxP, 34 bases long) then re-joins the cut loxP ends, between which the rest of the GM DNA is deliberately placed. An engineered-in recognition sequence remains in the genome wherever it was initially placed, because the two of them initially present are not completely chopped out.

Once the Exorcist, its promotor section, and the other modified genes under their control have done their work, you'll *STILL* have a modified plant, the metabolism of which was doing engineered processes during the period when the intended-for-removal transgenic gene, and its protein were still there in the plant cell, doing whatever nonstandard biochemistry they were doing (rather like a worn sock is still a worn sock even though you've taken your foot out of it).

You might have much less of a chance of identifying that it was a modified plant. If there was a remnant loxP site there, which didn't exist in the wild-type plant, you'd be able to say "this is a modified plant." However, if there was such a loxP site in the wild-type plant, you'd be dealing with an organism which would behave unpredictably when engineered with the Exorcist system since the Cre protein would probably make an attempt at chopping out DNA which just happened to fit Cre's recognition requirement, but you couldn't say definately the plant had this loxP site due to engineering or not if you didn't know it was engineered... because the transgenes have been chopped out and might not remain in a condition which a PCR search could recognise.

We don't know the recognition error rates for the Cre recombinase, nor what else it might do in organisms where it didn't evolve, nor wether the loxP sequences Cre works on also occur naturally elsewhere in the plant to be engineered. To me, having a foreign recombinase running around in your plant's genetic material, chopping-out whatever it happens to find between the required sequences, is a brilliant way to destabilise the genome of the organism. It might be worth asking, too, why develop a means to chop out an engineered gene, if these things we're engineering in there in the first place are supposedly safe? Doesn't it seem like Exorcist is a fix-up for a mess we should not have created in the first place?

There's someone else out there saying that if you do engineering on the DNA of the chloroplasts in plants (the photosynthetic sub-component of plant cells) that it's ok since that DNA can't spread ... well, again, even if you have engineered the plant chloroplasts to behave differently for few weeks, the effects of those engineered chloroplasts can remain for a very long time. I think the no-spread claim is dubious anyway, since chloroplasts and mitochondria have to be passed down the generations along with normal nuclear material, so if the plants with engineered chloroplasts can reproduce, their chloroplasts probably will find a way to do so too.

Q: Are genetically modified crops going to feed the starving millions?

A: No. This is because the starving millions don't have the money to pay the agribusinesses for the privelage of using them. Simple and callous as that. This is peripheral to the question of wether we need more people on a planet with six billion humans on it, which I think we definately do not. Or the question of where to get the hydrocarbons and synthetic fertilisers to run our mechanised mono-agriculture for the next century. Or the question of where to get land to grow enough crops to feed so many people.

Did the last green revolution feed everyone? Well, actually, no.

If there is a plague organism on this planet, we're it. We need distributed immunocontraception. Maybe genetic engineering will provide that in one form or another. If history is any guide, it will happen by accident. Probably something stupid like we woke up to the sudden realisation that we engineered all our food crops to die out after one season with terminator technology and planted it everywhere so the wild types pretty much became extinct, creating widespread famine. Sheer genius.

Q: Are genetically modified organisms going to eradicate disease?

A: No.

Problems of resistance aside, enough people won't be able to get access to things like engineered vaccines, because they won't be able to afford them, so there will be persistent reservoir populations of pathogenic organisms in hosts, and probably resistant ones evolving everywhere.

Similarly, many diseases which are inborn errors of metabolism and which dont have many sufferers or a sexy media profile, will largely lose out in the competition for research funds. We've already got one GMO which _causes_ a disease (vitamin A poisoning, see above).

There are some GM crops which have in them proteins from disease causing organisms, and the idea here is that people eat these crops, and their immune system learns to recognise the pathogen protein, so they get immunity to that disease. I think that's a good idea except the disease organism only needs to slightly change and the immune system won't recognise it, necessitating a new release of a newly modified crop.

The crops are often modified with no consideration about how the plants are processed in the societies where they are eaten : someone released a potato with a gene encoding a bacterial protein from a disease-causing bacteria in it, but since the locals always cooked their potatoes before eating them, the protein was denatured by heat before the immune system ever got a change to recognise it. OF COURSE they did. Potato rinds are poisonous, they contain things like prussic acid. You yourself probably don't eat potatos raw either.

Again we dont know what viral proteins will do in food crops, for reasons I already mentioned. In any case, some companies think this is a bad idea because they make money out of selling cures, and this sort of prevention strategy is bad for their profitability.

Q: Universities are the main institutions where molecular biologists are trained. Do university level courses have any components which inform young scientists about the long term consequences of molecular modification?
A: Universities are not places where the molecular biologists of the future are informed of the consequences of their interference with the genomes of organisms. They are places where you are trained to use the tools, but not to have any understanding of the consequences of application of those tools. It is the same as it was with training people in the 1930s to synthesise pesticides, or hormones, which turned out to be oestrogen analogues which induced unusual vaginal cancers and male mammal infertility decades later at parts-per-million concentration and which we only became aware of in the 1960s and 1970s.

Modification of organisms is something which doesnt go away, once you release an organism it stays released, and uaully evolves into something else. Australia has a history of this... feral rabbits, foxes, cats, birds, grasses, trees, and to a significant extent, humans who did not evolve locally. Australia is never going to be rid of them and they aren't even genetically modified. Our successes with smallpox and prickly pear are aberrations.

Q: There is a concept called "free software" - how does that tie into genetic modification?
A: Living organisms run molecular transformation programs which are encoded in their DNA, and executed by proteins. This molecular information, which is actually "software" is free... it is available to benefit all organisms. For example, you have three billion base-pairs of DNA in each of your cells, and this is the software which tells them how to run. You inherit this software from your parents, for free - they both contribute to your genome and when they concieve you are effectively contributing their working code to a collaborative software development project - you. They donate this code without copyrights attached to it, and you as a human being don't have to pay them a license fee for running their code in your metabolism. There are no laws against you giving your code to other people - once people reach a certain age they are legally allowed to share their genomic data to whomever they choose, provided the other party consents to share as well. Currently there is no law against you sequencing parts or all of your own DNA. The only things which stand between you and modifying your own DNA are technical hindrances, such as, how good are you at molecular biology lab technique.

Lots of agribiotech businesses take this kind of software from say, a plant, modify it slightly and then claim the entire plant as theirs. This is, technically, on most electronic platforms, software piracy. It is exactly like micro$oft taking an open standard and modifying it so it becomes proprietary to them.

The planetary genome should remain free software. It is too important to have it any other way. I recommend a look at GNU.org for some essays about Free Software. Stallman's comments about electronic data apply very much to biological data.


You complain a lot about GM, do you think there's anything good about it?

Sure. DNA vaccination is a very good thing, so far, though it has helped the human population explode. Recombinant insulin is a good thing, so far, and there are a lot of diabetics alive today who would otherwise be dead (the pigs from which insulin used to be extracted are probably still processed into bacon and pork roasts, however, so they have not been so lucky). I think these are examples of what good there is to be had from GM technology. Provided everyone is being fed adequately, and the number of humans on earth isn't adversely affecting the ecosystem, these sorts of life-preserving and life-extending things are a really good idea. The food-and-population problems are not going to be solved by GM technology, they're social problems, artefacts of how our corporate-run society is operated.

I think cloning humans is sort of pointless, since it already happens in nature to some extent (homozygotic twins). It's certainly cheaper and easier, at the moment anyway, to make humans the same way we have been making them for several hundred thousand years. If it is applied on a large scale to animals which currently reproduce sexually, we'll have the same monoculture problem we have with a lot of plants, which is, they're genetically all the same and hence all vulnerable to the same diseases. (Bananas and coffee plants are examples of plants with restricted variety because mostly they're clones - they need specialised attention and things like fungicides and pesticides frequently applied.)

The cloning mostly happening at the moment is from somatic cells, which are damaged. Cloning will work when expeimenters begin with fresh embryonic stem cells. People are now preserving their kids stem cells at birth.

Now, on the other hand if I could clone my own organs, that would be kind of useful, but I expect that organ cloning is going to give rise to a new class of individual in society - the more-or-less-immortals, who can afford a couple of million bucks for a new lungs, livers, hearts, spleens, skins, and other replacable organs every few decades. Does the rest of society really want sly corporate CEOs and government dictators and so on to live longer than they do already?

I can think of a pile of modifications I'd like to try on myself. More resources allocated to things like free radical scavenging, DNA error correction, cytochrome P450 optimisation to degrade the new and wierd poisons I absorb because I live in an industrial society. An immune system which was better at spotting metaplastic cells before they became tumors. Ability to synthesise my own vitamin C and folate and essential amino and fatty acids. More melanocytes so I don't get sunburnt so easily. CNS neurons which could metabolise lipids (they currently can only metabolise ketones and glucose) for energy. That's molecular stuff. I don't know if any of it would work, or perhaps drastically skew my metabolic resource allocation so I died.

I caught myself thinking the other day that I could modify my visual pigment, rhodopsin, so I could see shorter or longer wavelength photons that is, see in the ultraviolet or infrared parts of the spectrum. But there are problems... - as with all the preceding screwups, I cannot just modify one gene and expect it to work. If I modified it so I could detect infrared, I'd have to have my eyes located somewhere other than in a big skull full of metabolically active (and therefore very warm) brains (on stalks, maybe?!) otherwise I'd just percieve a blank wall of the same temperature because of all the waste heat being dumped into my eyeballs. If I had visual pigment which could detect short wavelength radiation, how is it going to get through my cornea and aqueous humour, which absorb in the UV to a considerable extent? I'd need to do an awful lot of serious and extensive modification to my basic embryology and biochemistry to do these things.

With some of these modifications we could live a very long time, however, currently I do not think the long term consequnces of my being able to live to 190 years of age are being planned for in the social infrastructure sense. It means I would consume lots more food, energy, resources; more of the disposable, designed-to-break junk which is sold to us by profiteering corporations. I'd rather die than live 190 years of wage slavery.

At the organ level, how about otoliths which regenerate so my hearing doesn't degrade? No loss of skin's ability to synthesise collagen so I don't get saggy as I age? What about a new set of natural teeth every thirty years? Nerves which correctly knit when severed?

What about things like heavy structural modifications ... redundant fingers, redundant organs, backs which aren't so prone to blowing a herniated disc, nerves routed away from impact sensitive locations, more anastamosed arteries. Bigger pelves to enable less traumatic delivery of neonates with bigger heads and brains? Bigger brains are metabolically costly to run, is that a good idea? Brains which are optimised for certain abilities... are we engineering a species which consists of people so standardised for obediently working in an office environment that we lose the philosophers, the radicals, the visionaries?

(I wonder if we're not breeding that civil disobedience out of ourselves already.)

I do not think these sorts of things should be inflicted upon neonates. Maybe if you could prevent a child from suffering some kind of genetically inherited disorder, you might want to do that. I do not think that interfering with the neurochemical or developmental architecture of our brains is likely to be optimal for us in the long term, simply because the direction this will take will fit the social whim of the day... we shouldn't try to engineer humans to fit some trendy social model, or the diversity which we absolutely depend on to run our social organism will go away. People conventionally considered stupid or ugly or insane have contributed to what we call the human experience.

None of us asked for the bodies we are born in or the brains in which our personalities operate. Neither will any humans who grow up to discover that they've had their genome tinkered with. Hopefully they won't curse us for giving them a gene which was fashionable ten years ago but which is now though of as a social stigma. Would male pattern baldness become a thing sported proudly, which says "I run wild type human DNA - a bunch of software proven stable over thousands of years"?

Every conception is an experiment in applied embryology and, as gynaecologists will tell you, nature is the ultimate eugenicist - lots of embryos are spontaneously aborted, some before they get out of the first trimester, many of these are just intrinsically not viable at a molecular biology level, something went awry with some serious part of the developmental process. It won't be very different with germinal modifications. I'd tend to not tinker with crucial things I don't understand. I hope biotech firms learn this posture before they rob us of our own indentities.

Q: sheesh, can I go now?
A: Certainly.
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