[Genetic Engineering] Faster, Stronger, Hardier

[Admiral Valdemar]

Hornier?

The mouse that shook the world

It can run for hours at 20 metres per minute without getting tired. It lives longer, has more sex, and eats more without gaining weight. Could the science that created this supermouse be applied to humans?

By Steve Connor, Science Editor
Published: 02 November 2007

Scientists have been astounded by the creation of a genetically modified "supermouse" with extraordinary physical abilities – comparable to the performance of the very best athletes – raising the prospect that the discovery may one day be used to transform people's capacities.

The mouse can run up to six kilometres (3.7 miles) at a speed of 20 metres per minute for five hours or more without stopping. Scientists said that this was equivalent of a man cycling at speed up an Alpine mountain without a break. Although it eats up to 60 per cent more food than an ordinary mouse, the modified mouse does not put on weight. It also lives longer and enjoys an active sex life well into old age – being capable of breeding at three times the normal maximum age.

American scientists who created the mice – they now have a breeding colony of 500 – said that they were stunned by their abilities, especially given that the animals came about as a result of a standard genetic modification to a single metabolism gene shared with humans.

They emphasised that the aim of the research was not to prepare the way to enhance the genes of people. However, they accepted that it may be possible to use the findings to develop new drugs or treatments that could one day be used to "enhance" the natural abilities of athletes.

The professor of biochemistry at Case Western Reserve University at Cleveland in Ohio, Richard Hanson, said that the physical performance of the supermouse can only be compared to supremely fit athletes like the cyclist Lance Armstrong, who won the Tour de France seven consecutive times from 1999 to 2005. The genetic alteration to a gene involved in glucose metabolism appears to stimulate the efficient use of body fat for energy production. At the same time, the mice do not suffer from a build up of lactic acid – which causes muscle cramps – a feature also seen in the best endurance athletes.

Professor Hanson said yesterday: "They are metabolically similar to Lance Armstrong biking up the Pyrenees. They utilise mainly fatty acids for energy and produce very little lactic acid. They are not eating or drinking and yet they can run for four or five hours. They are 10 times more active than ordinary mice in their home cage. They also live longer – up to three years of age – and are reproductively active for almost three years. In short, they are remarkable animals.

"On the downside, they eat twice as much as control mice, but they are half the weight, and are very aggressive. Why this is the case, we are not really sure."

Professor Hanson, who led the 15-strong team of researchers, said that the first supermouse was created about four years ago by injecting a highly active form of a gene for an enzyme called phosphonenolpyruvate carboxykinase (PEPCK-C) into a mouse embryo. The results of studies on the mice are published for the first time today in the Journal of Biological Chemistry.

Professor Hanson said: "We humans have exactly the same gene. But this is not something that you'd do to a human. It's completely wrong. We do not think that this mouse model is an appropriate model for human gene therapy. It is currently not possible to introduce genes into the skeletal muscles of humans and it would not be ethical to even try."

However, it may be possible for pharmaceutical companies to use the findings to develop new drugs that enhance muscle performance, which may benefit certain patients. Professor Hanson accepted that it was possible athletes might misuse any future drug developed in this way.

He said: "It's very possible. It's a different approach to putting a gene into a human. I would only do that to help anyone who suffers from disorders such as cystic fibrosis."

The aim of the research was to gain a greater understanding of the PEPCK-C enzyme, which is present mainly in the liver and kidneys. As a result of the genetic modification, the mighty mice have up to 100 times the concentration of the enzyme in its muscles compared with ordinary mice.

Professor Hanson said: "The purpose of our experiment was to study energy metabolism in the mice and the role that a single, metabolically important enzyme might play in a tissue in which it is not normally expressed at high levels."

He said that the physical and behavioural changes in the modified mice were completely unexpected. Usually, scientists have to carry out blood tests to see if there has been any effect of altering the genes, but these mice were noticeably different at a very early age.

He said: "We could spot them at just a few weeks after birth. They popped around the cage like popcorn. We found that they were about 10 times as active as ordinary mice."

Further research on the mice could shed light on the link between high-calorie diets and cancer, and low-calorie diets and longevity. He said: "Our animals live longer and eat almost twice as much as ordinary mice – this is a model to study."

A risky business: previous attempts at genetic modification

Genetic modification is a 30-year-old technology that has been used extensively on a range of animals for basic research and the production of agricultural or pharmaceutical products. It involves inserting an extra gene or modifying the expression of an existing gene within the DNA of the animal. Famous examples of GM animals include:

The Beltsville pig

An early experiment involving the insertion of a gene for human growth hormone into pigs to make them grow faster. They suffered severe bone and joint problems and could not walk properly without pain.

Oncomouse

Created by scientists at Harvard. Engineered to develop cancer, it enabled researchers to use it as a model of the disease. It was involved in one of the earliest patent applications on an animal.

Knock-out mice

Probably the most common use of genetically modified animals. The mice have a gene modified or destroyed so that scientists can study the outcome. Has created a revolution in the understanding of mammalian genes.

Spider-silk goats

Spider-silk protein gene is inserted into goats to extract the substance from their milk. The silk is stronger than steel, so could be used in industry.

Spinach pigs

Japanese scientists have created pigs with an added gene from spinach. They say it cuts fat – making them healthier to eat.

Humanised cattle

A range of experiments have tried to introduce important human genes into cattle so that pharmaceutical proteins can be extracted from their milk.

The green pig

Scientists are trying to introduce a bacterial gene into pigs that will make their faeces less toxic, cutting farm pollution.

I've been following such GM organisms for years now, but ones like this catch my eye. It may not apply to humans and it may have a horrible side-effect yet to be fully realised (okay, ultra violent tendencies is bad and overeating too). One cannot help but be amazed at what else we could probably do with even better knowledge. And this is simply tinkering with a simple metabolic pathway. We've not even touched the likes of re-engineering whole organ systems or delving into starting from scratch with second rate evolved mechanisms or the brain.

[K. A. Pital]

These achievements will be used for consequently super-soldier, super-sportsman and super-worker production. Maybe super-intellectuals too, but that's a little fast forward.

[lazerus]

Impressive! And the implications for human applications are fascinating, to say the least. Though I can see why the scientists were so leery about saying as much: There's a bit gap between mice and a side-effects-free version for humans. To quote "Cancer has been cured in mice several times."

[DavidEC]

I, for one, welcome our new overlord Mighty Mice.

[DarthShady]

I, for one, welcome our new overlord Mighty Mice.

I second that.

It seems this type of research is progressing a lot.Maybe the next generations can become super humans.
But such experiments are dangerous and unpredictable.Although in time this research may become extremely useful.

[Sea Skimmer]

I’m willing to bet they also get super cancer super fast

[Lord of the Abyss]

I’m willing to bet they also get super cancer super fast

Given that they also live longer according to the quoted article, apparently not.

[Mayabird]

It seems to me that the reason they don't gain weight is that their metabolisms are on speed. If they don't eat that much, they'll probably die very quickly. How that's a benefit, I don't really know. I'd hate to have to constantly stuff my face to live.

Although I do find it interesting that they can live longer while still having these overdrive metabolisms.

[Admiral Valdemar]

I’m willing to bet they also get super cancer super fast

Like they say, they've cured cancer in mice. Though if it's any consolation, they did go ahead and make a whole new strain for getting cancer anyway.

A fast metabolism does not necessarily mean more chances of cancer, since cancer is really more an environmental effect and the failure of certain cellular machinery that we take for granted. The number of humans on Earth vs. the number who get cancer is testament enough to how tough we can be against it, not that there isn't room for improvement.

It seems to me that the reason they don't gain weight is that their metabolisms are on speed. If they don't eat that much, they'll probably die very quickly. How that's a benefit, I don't really know. I'd hate to have to constantly stuff my face to live.

Although I do find it interesting that they can live longer while still having these overdrive metabolisms.

Frankly, given the world's populace today, I don't think that's a problem. Anorexia is not a problem in this country.

[[R_H]]

Why would people have any objections to this kind of genetic engineering?

Professor Hanson said: "We humans have exactly the same gene. But this is not something that you'd do to a human. It's completely wrong. We do not think that this mouse model is an appropriate model for human gene therapy. It is currently not possible to introduce genes into the skeletal muscles of humans and it would not be ethical to even try."

However, it may be possible for pharmaceutical companies to use the findings to develop new drugs that enhance muscle performance, which may benefit certain patients. Professor Hanson accepted that it was possible athletes might misuse any future drug developed in this way.

He said: "It's very possible. It's a different approach to putting a gene into a human. I would only do that to help anyone who suffers from disorders such as cystic fibrosis."

These three paragraphs are unclear to me. Why is he saying it's wrong and unethical? Because negative sides effects of doing so aren't know? Or because genetic engineering shouldn't be preformed on human beings? Same goes for "I would only do that to help anyone who suffers from disorders such as cystic fibrosis.

Admiral Valdemar, is there any ongoing genetic engineering research into making mammilian organisms less susceptible to cancer, and geriatric related illnesses (sorry if I'm not expressing myself clearly, I'm not that well informed about genetic engineering, and biology in general)?

Thanks

[Admiral Valdemar]

Bioethics is a touchy subject and this article came with one such diatribe against tinkering with the genes in the print edition of the paper from the president of GeneWatch. It's only the same as with any other fractious subject in society, given we still debate the use of abortion or embryonic stem cells despite all their notable advantages to us.

There is always ongoing research into ways to rid us of cancer; how much is genetic modification I can't say, because I mainly see stuff relating to novel compounds rather than gene therapy which is far less well understood and more expensive to R&D. A recent problem with a treatment in France which involved the death of a child who was meant to be undergoing therapy via a retroviral product line shook the industry quite a bit. Now do you carry on and accept the risks or losing people in the name of refining medical science for the greater good, or do you make all such experiments verboten because "playing God" is not ethically sound, no matter the benefits?

[hongi]

I sincerely hope they lock that mice up very tight. I wouldn't want those genes to spread into the general mice population.

[Broomstick]

These three paragraphs are unclear to me. Why is he saying it's wrong and unethical? Because negative sides effects of doing so aren't know? Or because genetic engineering shouldn't be preformed on human beings? Same goes for "I would only do that to help anyone who suffers from disorders such as cystic fibrosis.

I'd just like to point out that attempts to use gene therapy in humans have already had some "negative side effects" - it wasn't that long ago that a young man in a trial of gene therapy for a liver disorder died, and while I'm not sure if a determination was ever made there was certainly the question of the treatment causing his death.

The thing is - if you screw up with a mouse or a pig you can just euthanize it. And a LOT of lab animals were euthanized on the way to producing the current strains of useful lab rats. With people... screw up a human and you've got a whole different problem because society values people a whole lot differently than mice and pigs.

The cystic fibrosis reference is probably related to the idea that it's ethical to use risky treatments for terminal illnesses where it would not be ethical to do so for minor illnesses or cosmetic purposes or for enhancement of natural and adequate abilities.

I will also point out that yes, in many ways this mutation seems optimal for current conditions but animals - including people - evolved to fit conditions in which famine occurred from at least time to time, and sometimes periodically. A mutation granting improved strength and endurance is useless if a side effect is ease of starving to death. Likewise, although increased activity is good in some circumstances it's a bad thing when you need to hide from a predator or other danger. Humanity Mark I may be lacking compared to Humanity Mark II in some ways, but may have more survivability in changing environments.

[Stark]

Gee, expensive technology for making people better: why could anyone have any problem with that? Nobody should be afraid of elites, right? However irrational it might be in any given case, people are often resistant to anything that widens the gap between rich and poor. Being gengineering, just wait for the first rich guy who demands his son marry properly to maintain the awesome genetics he bought for his family.

[Civil War Man]

40k fanboys rejoice, the human race is now one step closer towards being able to field the God-Emperor's first Space Marine batallions.

[wolveraptor]

Not to mention the fact that the tinkering seemed to cause the mice to behave aggressively. The last thing we need is an aggressive super-human, though I suppose that could be adjusted by some form of depressants.

Shit, it sounds like a Sci-Fi plot. A futuristic society of gene-modded humans that need their daily dosage of soma in order to not be a danger to those around them.

[Admiral Valdemar]

Actually, having just come back from 30 Days Of Night, the first thing I thought was "There's your supermouse gene in humans".

[NeoGoomba]

I don't care how "super" the supersoldiers we get from these treatments eventually are, they'll still get their asses kicked by 13 year olds at Team Fortress 2.

[Jadeite]

I, for one, welcome our new overlord Mighty Mice.

This stopped being funny years ago.

Anyway, hopefully they can get the aggression under control, this would be awesome if it became viable for humans. This could be an important first step in the war against death and nature.

[Admiral Valdemar]

This stopped being funny years ago.

Anyway, hopefully they can get the aggression under control, this would be awesome if it became viable for humans. This could be an important first step in the war against death and nature.

Many more longer lived, unstoppable human beings on the planet with violent tendencies? I can think of better things to solve the ravages of the Four Horsemen. One of them being less humans.

[DavidEC]

This stopped being funny years ago.

I did for the obligatory factor more than anything else.

[Gullible Jones]

I don't know, the "60% more kcals required" catch doesn't sound very good. In the event of some kind of major social collapse, it would not be good for our survivability.

(No, the Bene Gesserit do not approve.)

Also, the long distance running thing might be more problematic than it sounds. IIRC there's some recent evidence indicating that "the burn" isn't a buildup of lactic acid in the muscle tissue, but your central nervous system taking measures to keep you from depleting all your glycogen (and preventing the resultant coma, brain damage, and probably death). Umm, let's see... here it is. According to the article:

At the same time, the mice do not suffer from a build up of lactic acid – which causes muscle cramps – a feature also seen in the best endurance athletes.

So if the mice suddenly start showing stroke-like symptoms after a workout, we probably know what the problem is already.

[Shroom Man 777]

Although I do find it interesting that they can live longer while still having these overdrive metabolisms.

They're lab rats, no doubt they're well fed. Unless the scientists got a supermouse and a normal mouse, starved them, and observed which mouse died first.

Shit, it sounds like a Sci-Fi plot. A futuristic society of gene-modded humans that need their daily dosage of soma in order to not be a danger to those around them.

Just like that B-movie I once saw. It had a giant rat commanding an army of not-giant rats that ate people. The giant rat ended up attacking a hooker. That hooker's fake-blooded face was screaming for, like, an hour (of bad acting). The fundies might support supermouse genetic research if only for the purposes of developing whore-eating super-rats.

Another possible B-movie plot: an escaped (neo)Nazi supersoldier with superstrength, supermetabolism, and the ability of supersex. And it's up to this team of prudish Mossad agents, who are Jews (duh, and one is a rabbi), to stop the Nazi superman from fucking hundreds blue-eyed blondes to spread his SuperAryan genes. It'd be like Species, crossed over with Munich.

Our entertaining duo of Mossad agents would, aside from keeping an eye on brothels, also stake out fast food restaurants and would have a humorous exchange on what food is kosher and not.

[Lord of the Abyss]

Actually, having just come back from 30 Days Of Night, the first thing I thought was "There's your supermouse gene in humans".

Actually, my first thought was of the various genetically enhanced humans in the Honor Harrington books. Stronger, live longer, but needs to eat more and increased aggression.

[Ritterin Sophia]

Whelp, I"ve got to prepare measures that will follow through after I'm dead to kill my most hated anime character. No one's going to miss Kira Yamato, right?