What is Genetic Engineering?

Genetic engineering is an umbrella term which can cover a wide range of ways of changing the genetic material - the DNA code - in a living organism. This code contains all the information, stored in a long chain chemical molecule, which determines the nature of the organism - whether it is an amoeba, a pine tree, a robin, an octopus, a cow or a human being - and which characterises the particular individual. Apart from identical twins, your detailed genetic make-up is unique to you. Individual genes are particular sections of this chain, spaced out along it, which determine the characteristics and functions of our body. Defects of individual genes can cause a malfunction in the metabolism of the body, and are the roots of many "genetic" diseases.

Genetic mapping

Our understanding of our genetic makeup is being greatly expanded by a systemmatic mapping process known as the Human Genome Project, carried out internationally with enormous commercial and government funding. Smaller projects are also drawing the genetic map of pigs, chickens and some other organisms. As this work proceeds, individual genes are being identified for various functions and especially for medical conditions. Sometimes it appears that a single gene is responsible, for example in cystic fibrosis, but most conditions seem to be caused by more complex sets of factors, both genetic and environmental. We should make an important distinction between a gene which causes a condition outright, and one that gives one a susceptibilty to it, but which requires other factors to be present as well for the condition to develop. The ability to detect such genes now means we can use the tests for screening, especially pre-natally. This raises some important ethical questions, as we shall see. Screeing for various diseases is not, strictly speaking, the same thing as manipulating or "engineering" them. Some people feel "engineering" is an inappropriate term, with connotations of cold mechanics rather than living things, but it does reflect that manipulating genes has in some cases become a relatively common laboratory technique. We should also put it in context, that genetic engineering has been performed for centuries in animals and plants by selective breeding. This enhances particular genetic traits based on outward appearance, by choosing, for example, which boars to mate which sows to develop, over many generations, leaner pigmeat.

Genetic manipulation

From the early beginnings in the 1970's, however, it has now become possible to manipulate specific genes at a molecular level, using laboratory procedures on material taken from living organisms, which can be replaced in the organism, or put into a different one. It can be likened to taking a long, thin garment with a constantly varying pattern along its length, snipping out a section of pattern (an individual gene), modifying it and putting it back, or putting in a section with a different pattern (gene) taken from another garment. In principle, this ought to be much more specific than selective breeding, but the uptake of the relevant modified gene is often quite low, particularly in animals. It also allows the creation of "transgenic" organisms, where a short section of genetic material from an unrelated species can be introduced into another (N.B. a transgenic animal does not mean a 50-50 mixture!).

Some Uses of Genetic Engineering

But why should we do this manipulation, be it within or across species? The purposes of doing genetic engineering are many and various. A range of them are listed below. These include :

to repair a genetic "defect" (as with the current early trials of gene therapy in humans),
to enhance an effect already natural to that organism (e.g. to increase its growth rate),
to increase resistance to disease or external damage (e.g. crops - blight, cold or drought),
to enable it to do something it would not normally do ...

This is a preview of the whole essay

Some Uses of Genetic Engineering

But why should we do this manipulation, be it within or across species? The purposes of doing genetic engineering are many and various. A range of them are listed below. These include :

to repair a genetic "defect" (as with the current early trials of gene therapy in humans),
to enhance an effect already natural to that organism (e.g. to increase its growth rate),
to increase resistance to disease or external damage (e.g. crops - blight, cold or drought),
to enable it to do something it would not normally do :
e.g. getting a micro-organism to produce human insulin for diabetics, or a sheep to produce a human blood-clotting protein in her milk, in both cases a transgenic method,
e.g. getting a tomato to ripen without going squashy - this can be done simply by taking one of its own genes, turning its "pattern" upside down and putting it back again!

Cloning

On January 8, 2001, scientists at Advanced Cell Technology, Inc., announced the birth of the first clone of an endangered animal, a baby bull gaur (a large wild ox from India and southeast Asia) named Noah. Although Noah died of an infection unrelated to the procedure, the experiment demonstrated that it is possible to save endangered species through cloning.

Cloning is the process of making a genetically identical organism through nonsexual means.

Why Clone?

The main reason to clone plants or animals is to mass produce organisms with desired qualities, such as a prize-winning orchid or a genetically engineered animal -- for instance, sheep have been engineered to produce human insulin. If you had to rely on sexual reproduction (breeding) alone to mass produce these animals, then you would run the risk of breeding out the desired traits because sexual reproduction reshuffles the genetic deck of cards.

Other reasons for cloning might include replacing lost or deceased family pets and repopulating endangered or even extinct species. Whatever the reasons, the new cloning technologies have sparked many ethical debates among scientists, politicians and the general public. Several governments have considered or enacted legislation to slow down, limit or ban cloning experiments outright. It is clear that cloning will be a part of our lives in the future, but the course of this technology has yet to be determined.

If human cloning proceeds, one method scientists can use is somatic cell nuclear transfer, which is the same procedure that was used to create Dolly the sheep. Somatic cell nuclear transfer begins when doctors take the egg from a donor and remove the nucleus of the egg, creating an enucleated egg. A cell, which contains DNA, is then taken from the person who is being cloned. The enucleated egg is then fused together with the cloning subject's cell using electricity. This creates an embryo, which is implanted into a surrogate mother through in vitro fertilization. If the procedure is successful, then the surrogate mother will give birth to a baby that is a clone of the cloning subject at the end of a normal gestation period. Of course, the success rate is only about one or two out of 100 embryos. It took 277 attempts to create Dolly. Take a look at the graphic below to see how the somatic cell nuclear transfer cloning process works.

Selective Breeding

Breeders of animals and plants in today's world are looking to produce organisms that will possess desirable characteristics, such as high crop yields, resistance to disease, high growth rate and many other phenotypical characteristics that will benefit the organism and species in the long term.

This is usually done by crossing two members of the same species which possess dominant alleles for particular genes, such as long life and quick metabolism in one organism crossed with another organism possessing genes for fast growth and high yield. Since both these organisms have dominant genes for these desirable characteristics, when they are crossed they will produce at least some offspring that will show ALL of these desirable characteristics. When such a cross occurs, the offspring is termed a hybrid, produced from two genetically dissimilar parents which usually produces offspring with more desirable qualities. Breeders continuously track which characteristics are possessed by each organism so when the breeding season comes once again, they can selectively breed the organisms to produce more favourable qualities in the offspring.

The offspring will become heterozygous, meaning the allele for each characteristic will possess one dominant and one recessive gene. Most professional breeders have a true breeding cross (ie AAbb with AAbb) so that they will produce a gene bank of these qualities that can be crossed with aaBB to produce heterozygous offspring. This way the dominant features are retained in the first breeding group and can be passed on to offspring in the second instance.

This process of selecting parents is called artificial selection or selective breeding, and poses no threat to nature from man manipulating the the course of nature. It has allowed our species to increase the efficiency of the animals and plants we breed, such as increasing milk yield from cows by continuously breeding selected cows with one another to produce a hybrid.

Selective Breeding Methods

Isolation. There must be a period in which the members of the group are relatively fixed, so that no new genetic material comes in. Without genetic isolation of the group, the differentiation that creates a new breed cannot take place.
Artificial selection. Breeders must prevent random mating from coming about, and limit mating to those individuals who exhibit desired characteristics. One logical consequence of this isolation is the next characteristic: inbreeding.
Inbreeding. Ordinarily those who are controlling the artificial breeding will find it necessary at some stage to employ a degree of linebreeding (mating within one bloodline, or strain) or inbreeding (mating closely related individuals), to facilitate the weeding-out of undesired characteristics and the fixation of desired traits. Inbreeding and linebreeding are controversial aspects of artificial selection, but have been practiced for centuries

Human Genome Project

Completed in 2003, the Human Genome Project (HGP) was a 13-year project coordinated by the U.S. Department of Energy and the National Institutes of Health. During the early years of the HGP, the Wellcome Trust (U.K.) became a major partner; additional contributions came from Japan, France, Germany, China, and others. See our history page for more information.

Project goals were to

identify all the approximately 20,000-25,000 genes in human DNA,
determine the sequences of the 3 billion chemical base pairs that make up human DNA,
store this information in databases,
improve tools for data analysis,
transfer related technologies to the private sector, and
address the ethical, legal, and social issues (ELSI) that may arise from the project.

The publication today of the detailed sequencing and mapping papers of the Human Genome Project (HGP) shows that the "book of humankind" is even more wonderful, and mysterious, than previously thought.

The HGP papers, published in Nature alongside associated papers from other academic groups that have already been using the data, reveal that the human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution.

The appearance of the HGP papers with the simultaneous publication of a paper in Science from Celera allows for the first time an open comparison of the two projects.

The papers published today give us for the first time a near complete set of human genes, which will form the basis for innumerable future investigations. It is estimated that there are only 30,000 to 40,000 genes, confirming the predictions made from the sequencing of chromosome 22, which was completed by the Sanger Institute in December 1999. This number, lower than once thought, is only twice as many genes as found in much simpler animals such as worms and flies. Many of the new genes in humans seem to be involved in organising how other genes work.

The Finished Human Genome

The Wellcome Trust Sanger Institute, which was the only British organisation involved in the project, carried out nearly one-third of the work, making it the biggest contributor

Less than three years ago the international team announced the original working draft of the three billion letters that make up the code of life. However, the finished sequence, announced today, is essential for growth of research worldwide to produce further medical advances

Anticipating this valuable resource, the Welcome Trust Sanger Institute has already established programmes to tackle many of our common diseases. These have already led to new medical insights, such as a mutation that causes malignant melanoma.

Professor Allan Bradley, Director of The Welcome Trust Sanger Institute, said: "Completing the human genome is a vital step on a long road but the eventual health benefits could be phenomenal.

"Just one part of this work - the sequencing of chromosome 20 - has already accelerated the search for genes involved in diabetes, leukaemia and childhood eczema.

"We shouldn't expect immediate major breakthroughs but there is no doubt we have embarked on one of the most exciting chapters of the book of life."

Human genome data has attracted a huge number of enquiries from researchers around the world, with weekly hits on the Ensemble website - co-run by the Welcome Trust Sanger Institute - rising from 30,000 in June 2000, when the draft sequence was announced, to almost 600,000 today. Scientists from more than 120 countries have made use of this valuable resource.

Access to comprehensive genomic data is powering drug discovery research in academic and commercial organizations. More than 350 biomedical advances have reached clinical trial stage, although experts point out it will be many years before new drugs emanating from the genome are produced.

The sequence of the human genome will underpin biomedical research for decades: one of the demands of the research community was that the reference human sequence should be finished to the highest standards possible. The Sanger Institute is achieving an accuracy rating of 99.999%

Dr. Jane Rogers, Head of Sequencing at the Welcome Trust Sanger Institute said: "We have reached the limits we set on this project, achieving tremendously high standards of quality much more quickly than we hoped.

"The working draft allowed researchers to kick-start a multitude of biomedical projects. Now they have a highly polished end product which will assist them even more. It's a bit like moving on from a first-attempt demo music tape to a classic CD."

The accurate genome sequence will allow researchers to identify genes involved in more complex diseases including cancer and diabetes.

Professor Kay Davies, Department of Human Anatomy and Genetics, University of Oxford, said: "One of the great benefits to spring from the Human Genome Project is the full catalogue of genes, which gives us a clearer route to therapies. We now have a better navigating system. Using this, we have found genes that may compensate for the defect in muscular dystrophy using entirely novel methods, which could have implications for thousands of people."

Before the sequencing project began it could take researchers months or even years to find one gene. Now the same task can be completed in hours or days.

Professor William Cookson, Senior Clinical Fellow at the Welcome Trust Centre for Human Genetics, Oxford, said: "The completed sequence will greatly help in the mapping of disease genes from the unfinished chromosomes. Dealing with the fragmentary information provided by the draft was better than dealing with no information at all, but the finished sequence will make our lives as disease gene hunters much easier."

In the last ten years, The Welcome Trust Sanger Institute has grown from 17 staff to 650 today and is a world leader, not only in sequencing DNA, but also in understanding the messages in our genes to improve human health. The achievement of a finished human genome sequence comes 50 years after James Watson and Francis Crick first elucidated the double-helical structure of DNA.

What is Genetic Engineering?