10 Genetic Modifications Claimed to Enhance Performance
Ever since Francis Crick and James Watson discovered DNA in 1953 and unraveled the genetic code, there has been frantic research activity to find out the function and purpose of different genes found in humans and other animals. The DNA of all living beings on our planet consists of the same kind of structural units, called nucleotides, and all species (including plants, fungi and bacteria) have a similar mechanism how the genetic code is translated to structure of proteins synthesized in the living cells (LINK 1,2).
The elucidation of the whole gene sequence of common fruitfly (Drosophila melanogaster) at the turn of the millennium was an important step towards understanding how living beings work. Not many years later, scientists had also mapped the significantly more complex human genome, in an effort called the Hugo Project. (LINK 3,4)
Together with the elucidation of the function of different genes, there has been a gradual development of biotechnology which now allows us to produce genetically modified animals and plants. A genetically modified organism may lack a gene that is found in normal (wild-type) organisms of the same species, or it may have extra genes that the wild-type species doesn't have. The cells of this kind of modified organisms therefore don't produce a certain protein (gene knockout), or they produce some protein that is not normally found (transgenic organism) (LINK 5).
Gene technology may eventually prove invaluable in the prevention of hereditary diseases, but it also has lots of associated ethical concerns. Many people oppose gene manipulation because of religious views, or believe it has too many risks involved to be safely utilized. Especially difficult ethical questions arise when biotechnology is used as means to improve the physical or mental performance of an organism. For instance, there has already been discussion about the possibility of "gene doping" in sports (LINK 6).
Without taking a position on whether gene technology is a good or a bad thing, this article presents 10 interesting examples of how gene manipulation has been found to improve the performance of laboratory animals in different kinds of tasks, or make them special (e.g. longer-lived) in some other way.
10 Mice with Enhanced Color Vision
Good color vision is not that common in the animal kingdom. Humans have a far better ability to tell apart different colors than many other mammals, such as dogs or cats. However, birds tend to see colors even better than humans (LINK 7). The retina of animals has two kind of cells that detect light, rods and cones. Only the cones can detect different colors, having suitable receptors that react to light in a certain range of wavelengths. Cones can only function in good lighting, and in a dark environment the "color blind" rods are responsible for vision (LINK 8).
The retina of most humans has three different kinds of color receptors, responsible for detecting the three basic colors, red, green and blue. Color blind people usually have only two kinds of receptors, and can not differentiate between red and green colors (there are also forms of total color blindness, where the person sees no colors at all) (LINK 9).
Mice have only two kinds of color receptors in their cone cells, and therefore their vision is duochromatic. However, a team of biologists working in the University of California, Santa Barbara, managed to produce transgenic mice that have been artificially given a human gene that codes the third color receptor protein. These GM mice were able to detect red color, which normal mice are unable to see (LINK 10). Therefore, a relatively simple gene manipulation was able to enhance the visual performance of the animals.
As already mentioned, birds usually have a better color vision than humans. For example, chicken have four kinds of color receptors in their retina, and are able to see four basic colors (tetrachromacy) (LINK 11). Even some people have a mutation that causes them to have four kinds of color receptors. In one case, this kind of a person was actually found to be able to detect an extra basic color (LINK 12).
9 Immunity to Alcohol
Ethyl alcohol is unquestionably the most used intoxicant in Western civilization, and it also causes more costs to society than any illicit drug. Most of us are able to use alcohol in a controlled manner, occasionally having one or two drinks without any problems. However, many people use alcohol in a manner where heavy intoxication is sought after (binge drinking), and the management of the "drunk and disorderly" always causes extra work for the law enforcement (LINK 13).
Alcohol causes its effects with a mechanism similar to inhalation anesthetics like ether or isofluran. It alters the functioning of diffent kinds of receptor proteins that reside on the surface of nerve cells. The most important receptor in this respect seems to be the GABA (gamma-aminobutyric acid) receptor. This causes a general depression of the nervous system, resulting in the typical effects of alcoholic drunkenness (LINK 14).
In 2014, an American research group published a paper in the Journal of Neuroscience, describing a genetically modified Caenorhabditis elegans worm that seemed to be immune to alcohol intoxication, having no signs of poor motor coordination even when exposed to large amounts of alcohol. The worm's nerve cells lacked a functioning version of an ion channel called BK SLO-1, which is known to be an important molecular target that alcohol molecules bind to. Despite having this strange immunity, the worms seemed to be otherwise normally functioning and healthy (LINK 15, 16).
This finding may help scientists in developing an "antidote", that could quickly reverse the effects of alcohol. To date, the only known way to quickly decrease the amount of alcohol intoxication is to put the drunken individual in pressurized (hyperbaric) environment (LINK 17, 18).
8 Resistance to Parkinson's Disease
Parkinson's is a neurological disease in which dopamine-releasing cells in the so called nigrostriatal dopamine pathway of the brain are gradually destroyed, causing tremors, slowness, rigidity and other problems in moving. The disease can be caused by genetic vulnerability or by toxins such as carbon monoxide, MPTP or manganese (LINK 19, 20, 21).
One theory attempts to explain the development of Parkinson's disease by claiming that it is produced by some toxin that is generated by the human body itself, and that this toxic substance is produced by an enzyme called MAO-B (monoamine oxidase B). This theory is supported by the fact that a MAO-B inhibiting drug, selegiline (Deprenyl) can prevent dopaminergic cell destruction by the neurotoxin MPTP, and it also slows down the progression of Parkinson's in people who have not gotten it as a result of any poisoning (LINK 22).
In 1999, Asian researchers published data on experiments that they made with laboratory mice that were genetically modified to lack the MAO-B enzyme altogether. The mice were immune to MPTP neurotoxicity, as can be expected, and their behavior was otherwise fairly normal (expect that they were more stress-sensitive than wild-type mice). It remains unknown whether this kind of modification can also protect an animal against Parkinson's disease (LINK 23).
Interestingly, chronic administration of the MAO-B inhibitor seleginine has been found to extend the lifespan of laboratory animals (LINK 24). It remains unknown whether the mice totally lacking MAO-B enzyme live longer than wild-type mice, too.
7 Lack of Receptor Makes Animals Smarter
Melatonin is a hormone that is released from the pineal gland of the brain, and its main functions are the regulation of sleep-wake rhythm and to some extent the regulation of sex hormone production. Many are familiar with its use as a supplement to promote sleep, and it has also been claimed to have other beneficial effects, but the evidence on its effectiveness is not very convincing (LINK 25).
Melatonin causes its effects on our cells by binding to two kinds of melatonin receptors, called MT1 and MT2 (LINK 26). A paper published in Neuroscience in 2014 describes an experiment where experimental animals were genetically modified to lack the two kinds of melatonin receptors. This was done to find out what effects of melatonin are caused by binding to these receptors and what are caused by some other mechanism. A surprising finding in this experiment was that the performance of these MT knockout animals in tasks measuring cognitive and motor abilities was significantly enhanced compared to animals without this genetic modification (LINK 27). It remains unclear whether this modification had any undesirable side effects.
Cognitive enhancement is one of the favorite subjects of people who support transhumanism, an ideology that states that technology should be used to improve us beyond normal human limitations. The finding described here is an example of research that could get us closer to accomplishing that goal (LINK 28).
6 Another Way to Make Mice Smarter
So, removing the melatonin receptors had a cognitive enhancing effect, what about other receptors? The GABA-A receptor, one of the receptor types that bind a neurotransmitter called gamma-aminobutyric acid, is important in medicine because anti-anxiety drugs like Valium or Klonopin exert their effects by binding to it (LINK 29). In item 9 of this list, the effect of alcohol on this receptor was already mentioned.
Common side effects of the sedative anti-anxiety drugs are sleepiness, loss of memory and cognitive impairment. In fact, it has been found out that the GABA-A receptors are composed of several different kinds of protein subunits, which are named with combinations of Greek letters and numbers. Different GABA-A receptors are built from different sets of these subunits. The anti-anxiety effect of Valium is mostly caused by its binding to alpha3 subunit containing receptor, while the cognitive impairing effects are related to the alpha1 and alpha5 subunits (LINK 30).
So it seems that these alpha1 and alpha5 proteins have something to do with being dumb and slow. What about removing the genes that produce them? In fact, disruption of the alpha5-producing gene has been shown to enhance the performance of mice in tests measuring memory and learning ability (LINK 31). Also, it's not necessary to remove the gene to benefit from this finding. Blocking the alpha5 subunit containing receptors with an experimental drug named RO4938581 (developed by Hoffmann-La Roche) has a similar cognitive-enhancing effect, and this kind of compounds may one day be used as a medication for dementia or other mentally deteriorating conditions (LINK 32).
5 Pigs that Digest Cellulose
As you may know, some animals have the ability to eat and digest wood, which is impossible for us humans. If you've had a pet rabbit, you may have had problems with it damaging wooden furniture by chewing (LINK 33). The main component of wood is cellulose, a polymeric compound that is formed from large amounts of glucose molecules bound together. Glucose is the simplest carbohydrate (sugar), and there's always glucose in our blood because brain cells need a constant supply of it to function normally (LINK 34, 35).
Humans are not able to digest cellulose, because we don't have a cellulase enzyme that is able to break cellulose molecules into their constituent glucose units. Pigs don't have cellulase either, and providing appropriate food for the animals is one important factor affecting the cost of factory farming. Recently, it has been proposed that transgenic pigs that have a cellulase-producing gene expressed in their pancreas (the organ that secretes digestive enzymes to the small intestine) could be farmed more inexpensively, because they could utilize the calories in dietary fibers that are usually left undigested (LINK 36, 37).
4 Genetic Modification Makes Cattle More Muscular
Athletes and other people interested in enhancing their physique have a large variety of pharmaceutical products to choose from, if they decide to dabble in the somewhat immoral business of chemical performance enhancement. These drugs include anabolic-androgenic steroids, growth hormone, EPO and beta-2-agonists to name a few. All of these can cause negative side effects, and there are always some risks involved in their use (LINK 38).
New performance-enhancing drugs are constantly being developed, and the authorities sometimes have hard time keeping the drug testing up to date with the new developments. One of the newest causes of concern is the possible use of gene therapy to enhance muscle growth (LINK 39).
Farm animals that have been genetically modified to have more lean muscle have already been developed. The best known example of this is the Belgian Blue Beef cattle, which lacks the so called myostatin gene. Pigs with a similar mutation have also been developed (LINK 40). These animals have a really hulky, even somewhat disturbing appearance. Only time will show whether this kind of bioengineering will some day be used on humans.
3 Resistance to Cancer
Cancer is one of the most common causes of death in modern society. About 50% of people get it at some point of their life, and 25% of us die from it. Research on cancer and the cytostatic medications used against it is one of the most active research topics in medicine and pharmacology. Unfortunately, all effective cancer medications still have bad side effects that would be totally unacceptable in the treatment of some less serious disease. (LINK 41, 42)
One of the things that are being investigated in cancer research is the involvement of genes in tumor development. Cancer risk seems to run in families to some extent, and the risk to develop some kinds of cancers seems to depend on a relatively small number of genes.
A promising result in cancer research was obtained when scientists from the University of Kentucky reported in 2007 that they had produced a strain of transgenic mice that were given an extra gene called Par-4, which seemed to make the animals more resistant to carcinogenic toxins and less prone to develop tumors spontaneously (LINK 43, 44).
2 Leaner Mice that Live Longer
Life extention is an interesting subject, and futuristic views of its possibilities have been presented by figures such as Nick Bostrom and Aubrey de Grey. To date, however, there is no scientific consensus on how to extend human lifespan, except the obvious things everyone already knows, which include avoiding smoking and controlling one's diet to prevent obesity. In lab experiments, the most effective way to make animals live longer is to put them on a restricted diet that contains all necessary nutrients, but has a low amount of calories and keeps them constantly a little hungry and underweight (LINK 45).
The life-extending potential of the drug selegiline (Deprenyl) was already mentioned in item 8 of this list. There are also some known genetic modifications that lenghten the lifespan of lab mice. One of these modifications is the overexpression of a gene that codes the so called ATG5 protein. This protein is important in a process called autophagy, which is a kind of a physiological waste management system, destroying useless proteins and damaged cell organelles in the body and recycling the useful amino acids they are made of (LINK 46).
According to Korean researchers, ATG5 overexpressing mice lived approximately 17% longer than the wild-type mice and had 12% lower body weight with significantly lower body fat percentage (LINK 47).
1 Aging without Intellectual Dulling
The intellect of people tends to be sharpest at young age. When intelligence is measured with classical IQ tests, the performance in pure logical reasoning such as mental calculation seems to peak in the 20s or 30s, and after that it slowly declines. Some aspects of intelligence, however, may continue developing until advanced age (LINK 48, 49).
Age-related dementia is a public health problem that causes costs to society and psychological stress to the family members and other caregivers of the affected people. As the population of western countries is getting older, the problem is getting even more significant (LINK 50).
There are several pharmacological ways to reduce the risk of dementia, including low dose NSAIDs (aspirin-like drugs), estrogen therapy for women and management of blood cholesterol levels with statins (LINK 51).
Recently, a genetic experiment perfomed by Canadian researchers shed some more light on the mechanism of intellectual decline. GM mice that didn't have a gene coding a protein called prodynorphin (Pdyn), seemed to have no observable decline in their cognitive abilities, measured with diffent kinds of spatial and recognition tasks, as they got older. On the other hand, genetically normal control mice that had the gene, had significant memory deficits by the time they were near the end of their lifespan. Removal of the Pdyn gene also seemed to make the animals less prone to anxiety (LINK 52, 53). This finding may eventually help in the development of more effective drugs against Alzheimer's and other forms of dementia.