.::. ÖGGGT .::. Austrian Association for Genetics and Genetic Engineering .::.

ÖGGGT Genetic Engineering

Genetic engineering, genetic modification (GM) and gene splicing are terms for the process of manipulating genes, usually outside the organism's natural reproductive process.

It involves the isolation, manipulation and reintroduction of DNA into cells or model organisms, usually to express a protein. The aim is to introduce new characteristics or attributes physiologically or physically, such as making a crop resistant to a herbicide, introducing a novel trait, or producing a new protein or enzyme, along with altering the organism to produce more of certain traits. Examples can include the production of human insulin through the use of modified bacteria, the production of erythropoietin in Chinese Hamster Ovary cells, and the production of new types of experimental mice such as the OncoMouse (cancer mouse) for research, through genetic redesign.

Applications

The first Genetically Engineered drug was human insulin approved by the USA's FDA in 1982. Another early application of genetic engineering was to create human growth hormone as replacement for a drug that was previously extracted from human cadavers. In 1986 the FDA approved the first genetically engineered vaccine for humans, for hepatitis B. Since these early uses of the technology in medicine, the use of GE has expanded to supply many drugs and vaccines.

One of the best known applications of genetic engineering is that of the creation of genetically modified organisms (GMOs).

There are potentially momentous biotechnological applications of GM, for example oral vaccines produced naturally in fruit, at very low cost.

A radical ambition of some groups is human enhancement via genetics, eventually by molecular engineering. See also: transhumanism.

Genetic engineering and research

Although there has been a tremendous revolution in the biological sciences in the past twenty years, there is still a great deal that remains to be discovered. The completion of the sequencing of the human genome, as well as the genomes of most agriculturally and scientifically important plants and animals, has increased the possibilities of genetic research immeasurably. Expedient and inexpensive access to comprehensive genetic data has become a reality with billions of sequenced nucleotides already online and annotated. Now that the rapid sequencing of arbitrarily large genomes has become a simple, if not trivial affair, a much greater challenge will be elucidating function of the extraordinarily complex web of interacting proteins, dubbed the proteome, that constitutes and powers all living things. Genetic engineering has become the gold standard in protein research, and major research progress has been made using a wide variety of techniques, including:

Loss of function, such as in a knockout experiment, in which an organism is engineered to lack the activity of one or more genes. This allows the experimenter to analyze the defects caused by this mutation, and can be considerably useful in unearthing the function of a gene. It is used especially frequently in developmental biology. A knockout experiment involves the creation and manipulation of a DNA construct in vitro, which, in a simple knockout, consists of a copy of the desired gene which has been slightly altered such as to cripple its function. The construct is then taken up by embryonic stem cells, where the engineered copy of the gene replaces the organism's own gene. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. Another method, useful in organisms such as Drosophila (fruit fly), is to induce mutations in a large population and then screen the progeny for the desired mutation. A similar process can be used in both plants and prokaryotes.

Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently.
'Tracking' experiments, which seek to gain information about the localization and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as Green Fluorescent Protein (GFP) that will allow easy visualization of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences which will serve as binding motifs to monoclonal antibodies.

Bioethics

Bioethics is the ethics of biological science and medicine.

Bioethics is concerned with the ethical questions that arise in the relationships among biology, medicine, cybernetics, politics, law, philosophy, and theology. Disagreement exists about the proper scope for the application of ethical evaluation to questions involving biology. Some bioethicists would narrow ethical evaluation only to the morality of medical treatments or technological innovations, and the timing of medical treatment of humans. Other bioethicists would broaden the scope of ethical evaluation to include the morality of all actions that might help or harm organisms capable of feeling fear and pain. Thus bioethics has a comprehensive scope, including human health, human life, animal and vegetable life; in other words, all issues related to life.

Bioethics involves many public policy questions that are sometimes politicized and used to mobilize political constituencies, hence the emergence of biopolitics and its techno-progressive/bioconservative branches. For this reason, some biologists and others involved in the development of technology have come to see any mention of "bioethics" as an attempt to derail their work and react to it as such. Some biologists can be inclined to this line of thought, as they see their work as inherently ethical, and attacks on it as misguided.

The questions begged by the idea of bioethics as a distinct area of academic inquiry (why must it exist apart from philosophy? isn't everyone an 'ethicist'?) are largely answered by the needs of institutions. Bioethicists today are not hired or engaged in conversation (and thus "named") because of their opinions or because they have special skills of reasoning, but because they know and can put to work the enormous body of research and history of discussions about bioethics in a fair, honest and intelligent way.

Genetically modified food

A genetically modified food is a product developed from a different genetically modified organism (GMO) such as a crop plant, animal or microorganisms, such as snails. Genetically modified foods produced by genetic engineering have been available since the 1990s. The principal GM foods derived from plants are soybean, maize, canola, cocoa beans, and cotton seed oil.

Development and application

The general principle of producing a GMO is to add novel genetic material into an organism's genome to cause both new and useful traits. The origins of this genetic engineering were a series of sequential scientific advances from the discovery of DNA to the production of the first recombinant bacteria (E .coli) expressing a frog gene in 1973. This led to concerns in the scientific community about the possible risks from genetic engineering and led to biologists meeting at the Asilomar Conference in Pacific Grove, California. The recommendations laid out from this conference were that government oversight of recombinant DNA research should be established until the technology was deemed safe. Herbert Boyer then founded the first company to use recombinant DNA technology, Genentech, and in 1978 the company announced that it had produced a strain of E. coli that could produce the human protein (insulin).

First crops

The first commercially grown genetically modified food crop was a tomato created by California company Calgene called the FlavrSavr.This tomato was made more resistant to rotting, by adding an antisense gene which interferes with the production of the enzyme polygalacturonase. Calgene submitted it to the U.S. Food and Drug Administration (FDA) for assessment in 1992; the agency determined that the FlavrSavr was in fact a tomato, did not constitute a health hazard, and did not need special labeling. Calgene was allowed to release it into the market in 1994, where it was welcomed by consumers who purchased the fruit at two to five times the price of standard tomatoes. However, production problems, and competition from a conventionally bred Long-Shelf-Life (LSL) variety prevented the product from becoming profitable, and Calgene was bought by Monsanto in 1995. A variant of the FlavrSavr was used by Zeneca to produce tomato paste which was sold in Europe during the summer of 1996. Its labelling and pricing were designed as a marketing experiment which proved that, at the time, European consumers would accept genetically engineered foods. This attitude would be drastically changed after outbreaks of Mad cow disease weakened consumer trust in government regulators, and protesters rallied against the introduction of Monsanto's Roundup-Ready soybeans.

The next GM crops included insect protected cotton, introduced into the United States and Australia in 1997, and herbicide tolerant soybeans. These crops have been widely adopted both in the United States, and in countries that (unlike the European Union) depend heavily on unsubsidised farming (e.g. the Australian cotton industry). They have also been extensively planted in several developing countries (Argentina, Brazil, South Africa, India, and China) where agriculture is a major part of the total economy. Other successful GM crops include insect protected maize and herbicide tolerant maize cotton and rapeseed varieties.

Commercial crops

Transgenic crops; plants that possess a gene or genes that have been transferred from a different species, are grown commercially or in field trials in over 40 countries and on 6 continents. In 2000, about 109.2 million acres (442,000 km²) were planted with transgenic crops, the principal ones being herbicide- and insecticide-resistant soybeans, corn, cotton, and canola. Other crops grown commercially or field-tested are a sweet potato resistant to a US strain of a virus that affects one out of the more than 89 different varieties of sweet potato grown in Africa, rice with increased iron and vitamins such as golden rice, maize with enhanced levels of the essential nutrient lysine which provides better quality protein for animal feeds, and a variety of plants able to better tolerate non-biological stresses which are commonly encountered in a normal growing season, such as water, and nitrogen limitation, or survive extreme growing conditions, such as high-salinity or acidic soils, or hot weather. Such traits can provide more reliable crop performance over an extended period of cultivation.

Transgenic rice has been developed by a Californian company to improve oral rehydration therapy for diarrhea. In sub-Saharan Africa and parts of Latin America and Asia, diarrhea is the number-two infectious killer of children under the age of five, accounting for some two million deaths a year. Recent 2005-6 trials in a Peruvian Hospital have demonstrated that specialized milk proteins lactoferrin and lysozyme made in transgenic rice plants improve the effectiveness of oral rehydration solution used to treat diarrhea.

Abundance of GM crops

Between 1996 and 2005, the total surface area of land cultivated with GMOs had increased by a factor of 50, from 17,000 km² (4.2 million acres) to 900,000 km² (222 million acres), of which 55% were in the United States. Within the next ten years millions more will be added.

Although most GM crops are grown in North America, in recent years there has been rapid growth in the area sown in developing countries. For instance in 2005 the largest increase in crop area planted to GM crops (soybeans) was in Brazil (94,000 km² in 2005 versus 50,000 km² in 2004. There has also been rapid and continuing expansion of GM cotton varieties in India since 2002. (Cotton is a major source of vegetable cooking oil and animal feed.) It is predicted that in 2006/7 32,000 km² of GM cotton will be harvested in India (up more than 100% from the previous season).

Indian national average cotton yields have been boosted to close 50% above the long term average yield during this period. The publicity given to transgenic trait Bt insect resistance has encouraged the adoption of better performing hybrid cotton varieties, and the Bt trait has substantially reduced losses to insect predation. Economic and environmental benefits of GM cotton in India to the individual farmer have been documented.

In 2005 the crops were grown by 8.5 million farmers in 21 countries, 90% of whom were resource-poor farmers from developing countries, and 60% of global soybean area, 28% cotton, 18% canola, and 14% global maize were sown to genetically modified varieties. The area sown in 2002 was 145 million acres (587,000 km²) and for 2003 was 167 million acres (676,000 km²). In 2004, the value was about 200 million acres (809,000 km²).

Four countries represent 99% of total GM surface in 2001: United States (68%), Argentina (22%), Canada (6%) and China (3%). It is estimated that 70% of products on U.S. grocery shelves include GM-derived ingredients. In particular, Bt corn, which produces the pesticide within the plant itself is widely grown, as are soybeans genetically designed to tolerate glyphosate herbicides. These constitute "input-traits" that financially benefit the producers, yet have only indirect environmental and marginal cost benefits to consumers.

In the US, by 2006 89% of the planted area of soybeans, 83% of cotton, and 61% maize was genetically modified varieties. Genetically modified soybeans carried herbicide tolerant traits only, but maize and cotton carried both herbicide tolerance and insect protection traits (the latter largely the Bacillus thuringiensus Bt insecticidal protein). In the period 2002 to 2006, there were significant increases in the area planted to Bt protected cotton and maize, and herbicide tolerant maize also increased in sown area. The Grocery Manufacturers of America estimate that 75% of all processed foods in the U.S. contain a GM ingredient.

Future developments

Future envisaged applications of GMOs are diverse and include drugs in food, bananas that produce human vaccines against infectious diseases such as Hepatitis B, metabolically engineered fish that mature more quickly, fruit and nut trees that yield years earlier, and plants that produce new plastics with unique properties. While their practicality or efficacy in commercial production has yet to be fully tested, the next decade may see exponential increases in GM product development as researchers gain increasing access to genomic resources that are applicable to organisms beyond the scope of individual projects. Safety testing of these products will also at the same time be necessary to ensure that the perceived benefits will indeed outweigh the perceived and hidden costs of development.

.::. ÖGGGT .::. Austrian Association for Genetics and Genetic Engineering .::.