Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/General information on Science and its interface with society/Human genetic engineering

Human genetic engineering is the genetic engineering of humans by modifying the genotype of the unborn individual to control what traits it will possess when born.

Humans do not need gene therapy to survive, though it may prove helpful to treat certain diseases. Special gene modification research has been carried out on groups such as the 'bubble children' - those whose immune systems do not protect them from the bacteria and irritants all around them. The first clinical trial of human gene therapy began in 1990, but (as of 2008) is still experimental. Other forms of human genetic engineering are still theoretical, or restricted to fiction stories. Recombinant DNA research is usually performed to study gene expression and various human diseases. Some drastic demonstrations of gene modification have been made with mice and other animals, however; testing on humans is generally considered off-limits. In some instances changes are usually brought about by removing genetic material from one organism and transferring them into another species.

There are two main types of genetic engineering. Somatic modifications involve adding genes to cells other than egg or sperm cells. For example, if a person had a disease caused by a defective gene, a healthy gene could be added to the affected cells to treat the disorder. The distinguishing characteristic of somatic engineering is that it is non-inheritable, e.g. the new gene would not be passed to the recipient’s offspring.

Germline engineering would change genes in eggs, sperm, or very early embryos. This type of engineering is inheritable, meaning that the modified genes would appear not only in any children that resulted from the procedure, but in all succeeding generations. This application is by far the more consequential as it could open the door to the perpetual and irreversible alteration of the human species.

There are two techniques researchers are currently experimenting with:

• Viruses are good at injecting their DNA payload into human cells and reproducing it. By adding the desired DNA to the DNA of non-pathogenic virus, a small amount of virus will reproduce the desired DNA and spread it all over the body.
• Manufacture large quantities of DNA, and somehow package it to induce the target cells to accept it, either as an addition to one of the original 23 chromosomes, or as an independent 24th human artificial chromosome.

Human genetic engineering means that some part of the genes or DNA of a person are changed. It is possible that through engineering, people could be given more arms, bigger brains or other structural alterations if desired. A more common type of change would be finding the genes of extraordinary people, such as those for intelligence, stamina, longevity, and incorporating those in embryos.

Human genetic engineering holds the promise of being able to cure diseases and increasing the immunity of people to viruses. An example of such a disease is cystic fibrosis, a genetic disease that affects lungs and other organs.

Researchers are currently trying to map out and assign genes to different body functions or disease. When the genes or DNA sequence responsible for a disease is found, theoretically gene therapy should be able to fix the disease and eliminate it permanently.

However, with the complexity of interaction between genes and gene triggers, gene research is currently in its infancy. Computer modeling and expression technology could be used in the future to create people from scratch. This would work by taking existing DNA knowledge and inserting DNA of "superior" body expressions from people, such as a bigger heart, stronger muscles, etc. and implanting this within an egg to be inserted into a female womb. The visual modeling of this process may be very much like the videogame Spore, where people are able to manipulate the physical attributes of creatures and then "release them" in the digital world.

The possibilities of physical changes are endless. Strength, speed, endurance and so on can be enhanced. The baby can be made taller, more beautiful, the changes possible are really up to the imagination, and the ability of the techniques employed by future gene manipulators. Certain people have been identified with extraordinary physical abilities, (such as athletes, geniuses, physical and mental event record holders) and their genes could be identified and replaced into the target embryo. There is also the possibility that science will advance so much that people will create genes not identified or discovered in nature (or people) and implant these into the human body as artificial genes.

Corresponding gene function to intelligence or mental aptitude in various fields is much harder because while researchers are finding out which sections of the brain light up when used through MRI imaging, corresponding genes to manipulate and/or expand intelligence are harder to map. The brain seems to be the last great medical mystery because unlike a muscle, it transfers information and handles complex processes like a computer, but without any logical process discernible to researchers. However, in certain individuals that have a higher aptitude at certain tasks, the history of their family having done the same work seems to show that either through practice, teaching, or gene expressions these individuals find tasks such as composing music or mathematics much easier than the average member of the population.

Methods and technology

Current technology

One of the types is gene manipulation through virus insertion. The main mechanism by which this operates is a fairly standard one; one is taking DNA throughout the host’s body. Problems with this approach may be:

Randomness of the insertion of the DNA fragment wanted (this might lead, for instance, to a cell turning cancerous, or being more subtly disrupted),

Possible lack of control over the immune response to the "retrovirus", and

Possible problems getting complete transformation of the target cell population.

Another approach is to take advantage of the cell's endogenous ability to undergo homologous recombination wherein an exogenous DNA fragment with ends matching an endogenous gene replaces the target gene by action of enzymes called recombinases. This is the technology used for "knockouts" and "knock-ins" and generally cannot be performed on an intact organism and is therefore only a candidate for germline (i.e. single cell) genetic manipulation. This technology has very widespread usage in mouse genetics wherein genetically altered embryos are grown in a surrogate mother. This could easily be extended to humans in the very near future as there are no major additional technological hurdles remaining to engineer humans versus mice (though minor hurdles certainly remain). The primary hurdle is ethical, as the efficiency of this process can be quite poor and many embryos would be sacrificed in order to produce one genetically modified offspring.

Future technology

There are limitations to what current technology can do. Research scientists want to get finer control on how DNA sequences might be added to a host cell. Technologies that could offer this sort of control might well result from a merger of highly engineered/modified viruses with micromechanical technologies, modified to migrate to a particular specified N nucleotide sequence in the host DNA for N significantly large to minimize targeting errors, then precisely and efficiently insert the desired snippet in the correct position in the host. Evidently it would be desirable to allow such a device/organism to feed on available resources in the host in order to migrate from cell to cell and perform this process until a significant proportion of host cells had been transformed; it would then be desirable for the device to disable itself. Also it would be desirable for the device to understand when it had finished with a cell (e.g. after levels of a desired protein reach a critical threshold, though this would be perhaps too slow, i.e. movement via measurement of some sort of chemical gradient) so that it could move on. Certainly such devices could not be user controlled for a large population; they would need to be autonomous.

Since DNA sequences vary from individual to individual, and individuals may even be chimeras, also required would be the capability to sequence individual genomes, the ability to target fixes to particular parts of a chimera population, and finally a good understanding of how to avoid disruptive edits- that is, edits that do not disrupt the functioning of some other process in the cell. This requires some level of mastery of the area of proteomics, that is, the understanding of a lifeform's proteome.

Computers

The future most likely lies in a process that is automated by a wide repository of knowledge, a method of combining that knowledge into an embryo, and a design system such as a computer program that is easily represented to human individuals. The researcher is able to pick and choose what characteristics the "soon to be created human" should have, such as high intelligence, high strength, 20/20 or above vision, etc., and then tells the computer to create that person. This designer baby machine would then search through current research on these genes, put them into the proper places of the DNA mode through an accurate DNA modification method, enter it into an egg (created or taken from a female), and then insert the egg into a female or a mechanical womb.

Nanotechnology

Nanotechnology could be used to implement gene changes. Nanotechnology is an expression of ultra small devices or machines that are able to operate at the nanoscale level.

When to make changes

Changes at conception

Genetic engineering is most easily accomplished by making changes just after the egg and sperm have melded but before first division. In this way, the gene will be expressed throughout and will affect the recipients children, grandchildren, and all subsequent generations. Germline engineering is controversial because there is insufficient knowledge about DNA expression to accurately judge what result these changes will have.

Changes after birth

As of now, this is likely to take the form of gene therapy. This would not be hereditary unless the sex cells are engineered.

Positive and Negative Distinction

Two types of genetic engineering exist when applied to humans. Positive and negative. The former enhances humans and the latter removes genetic disorders.

Negative genetic engineering

When treating problems that arise from genetic disorder, one solution is gene therapy, also known as negative genetic engineering. A genetic disorder is a condition caused by the genetic code of the individual, such as spina bifida or autism. When this happens, genes may be expressed in unfavorable ways or not at all, and this generally leads to further complications.

The idea of gene therapy is that a non-pathogenic virus or other delivery system can be used to insert a piece of DNA--a good copy of the gene--into cells of the living individual. The modified cells would divide as normal and each division would produce cells that express the desired trait. The result would be that he/she would then have the ability to express the trait that was previously absent at least partially. This form of genetic engineering could help alleviate many problems, such as diabetes, cystic fibrosis, or other genetic diseases.

Positive genetic engineering

The potential of genetic engineering to cure medical conditions opens the question of exactly what such a condition is. Some view aging and death as medical conditions and therefore potential targets for engineering solutions. They see human genetic engineering potentially as a key tool in this. The difference between cure and enhancement from this perspective is merely one of degree. Theoretically genetic engineering could be used to drastically change people's genomes, which could enable people to regrow limbs and other organs, perhaps even extremely complex ones such as the spine. It could also be used to make people stronger, faster, smarter, or to increase the capacity of the lungs, among other things. If a gene exists in nature, it could be brought over to a human cell. In this view, there is no qualitative difference (only a quantitative one) between, for instance, a genetic intervention to cure muscular dystrophy, and a genetic intervention to improve muscle function even when those muscles are functioning at or around the human average (since there is also an average muscle function for those with a particular type of dystrophy, which the treatment would improve upon).

Others feel that there is an important distinction between using genetic technologies to treat those who are suffering and to make those who are already healthy superior to the average. There is widespread agreement that germline engineering should not currently be allowed for either therapeutic and enhancement applications, as evidenced by a recent report by the American Association for the Advancement of Science. Though theory and speculation suggest that genetic engineering could be used to make people stronger, faster, smarter, or to increase lung capacity, the AAAS report finds that there is little evidence that this can currently be done without very unsafe and therefore unethical human experiments. Because different cells have different tasks, changing one cell to do a different job will not only affect that one task, it can affect many others too.

Controversy

Ethics

The genetic engineering of humans has raised many controversial ethical issues. With the release of the 1997 cult film Gattaca, human genetic engineering has been widely debated. While negative genetic engineering (gene therapy) does indeed raise a debate, the use of genetic engineering for human enhancement arouses the strongest feelings on both sides.

Social considerations

Individuals may benefit from non-therapeutic genetic engineering, but some claim that there may be adverse social implications. Few resources – particularly those related to medicine and health care – are available to everyone, and allowing the most privileged to engineer themselves or their children to have special capabilities could lead to what some call a genetic aristocracy. Numerous enhancements via genetic engineering have been proposed, including increased memory, intelligence, and less need for sleep, in addition to some peoples’ desires to alter their physical appearance. The advantages created by genetic engineering, either real or perceived, could lead to new forms of inequality between those with genetic enhancements and those without while also exacerbating current inequalities between the rich and poor.

This isn't to say that the poor would never have access to such technologies - there is no theoretical limit on how much retrovirus can be cultured in a bioreactor. But the likely high costs would probably require harsh financing plans. Genetic mortgages of the future could go hand in hand with student loans, spelling disaster for dropouts and increasing the risks of a first-class education for a middle or lower class citizen. Many people view genetic engineering as just a way to cure diseases.

On the other hand society could get to the point where the government pays for everyone to undergo genetic engineering. There would also be a point where patents on specific treatments run out, allowing cheaper access to the majority population after a decade or two of high cost. This may actually decrease inequalities, because natural differences in ability would be nearly eliminated leaving socioeconomic success or failure entirely to the environment and personal choice.