Engineering Organisms
Domestication and selective breeding of animals and plants began before recorded history. In fact, historians propose, the shaping of organisms to fit human needs contributed to the rise of settled complex cultures. Until late in the twentieth century, farmers and scientists could breed novel strains only from closely related species or subspecies because the DNA had to be compatible in order to produce offspring that in turn were fertile.
In the late 1970s and early 1980s, molecular biologists learned how to surpass the limitations of selective breeding. They invented procedures for combining the DNA of species as distantly related as microbes, plants, and animals. These organisms carrying the novel heritable genetic material derived from different species using recombinant molecular biology techniques are termed as transgenic or genetically modified organisms (GMO). Genetic engineering makes it possible to design novel organisms for genetic and biochemical research and for medical, agricultural, and ecological innovations. However, commercial use of transgenic organisms created worldwide controversy because of their potential threat to human health and the environment.
Transgenesis seeks to produce an entirely modified organism by incorporating the transgene into all the cells of the mature organism and changing the genome. This is done by transforming not only the somatic (body) cells of the host organism but also the germ cells, so that when the organism reproduces, the transgene will pass to the next generation. Transgenes can block the function of a host gene, replace the host gene with one that codes for a variant protein, or introduce additional proteins.
Transgenic Animals
In recent years the use of transgenic organisms has become widespread and a large variety of animals and plants has been successfully engineered. Some examples of transgenic mammals include mice, rabbits, pigs, sheep, and cows. Birds such as chickens as well as fishes like salmon and trout, and even amphibians like frogs and toads have been made transgenic. Among invertebrates, transgenic fruit flies (
Drosophila melanogaster
) and nematodes (
Caenorhabditis elegans
) have become indispensable for research.
The first transgenic mice were created by Rudolf Jaenisch in 1974, showing that SV40 viral DNA had integrated into mouse genome. In 1982, Richard Palmiter and Ralph Brinster created “supermice” that grew much larger than ordinary mice because these had received the rat growth hormone gene. Most of these transformations were generated by microinjection of DNA directly into cells. Later, scientists were able to deliver foreign genes into hosts by several other methods: incorporating them into retroviruses and then infecting target cells; electroinfusion, whereby an electric current passed the foreign DNA through the relatively flimsy animal cell wall; and biolistics, a means of mechanically
shooting a DNA bullet into cells. Two methods, developed at first for mice, are particularly successful in creating genetically modified animals. The first entails injecting transformed embryonic stem cells into a blastocyst (an early spherical form of an embryo). In the second, the DNA is inserted into the pronucleus of a freshly fertilized egg. The blastocyst or egg is then implanted into a foster mother for gestation.
Initially, the modified transgenic animals were intended for scientific research studies. After disabling a specific gene, scientists could study its effect on the structure, metabolic processes, and health of the mature animal. By 2003, thousands of genes had been tested. Studies on mice transformed with human DNA enabled scientists to identify genes associated with breast and prostate cancers, cystic fibrosis, Alzheimer’s disease, and severe combined immunodeficiency disorder (SCID). In 2001, the first transgenic primate, a rhesus monkey, expressing the green fluorescent protein was created. It took quite a few years before the first transgenic primate model for the human disorder Huntington’s disease, was generated in rhesus macaque in 2008. However, both these animals were unable to give birth to offspring carrying the transgene. In 2009, scientists in the laboratory of Tatsuji Nomura created transgenic marmosets that are the first transgenic primates that were able to pass the foreign gene to their offspring, potentially supplying a research model genetically much more similar to humans than mice.
Beginning in the late 1990s, transgenic animals were developed for production of proteins that can be used in pharmaceutical drugs to treat human disease. Accordingly, they have become known as “pharm animals.” This new technology is known as biopharming and has a potential for producing large quantities of pharmaceutical products and vaccines at much lower costs. A number of companies are developing bioproducts using transgenic domestic lifestock. They include blood clotting factors, malarial antigens for vaccine against malaria, and spider silk protein for fiber development. One example of a transgenic animal is lactating transgenic mice producing tissue plasminogen activator in their milk. Similarly, transgenic sheep supply blood coagulation factor IX and alpha1-antitrypsin, transgenic pigs produce human hemoglobin, and transgenic cows make human lactoferrin. Scientists have also developed transgenic pigs that may supply tissue and organs for transplantation into humans without tissue rejection.
Transgenic Plants
Plant cells present greater difficulties for transformation because their cell walls are sturdier than animal cell walls. Microinjection and biolistics are possible, but tricky and slow. A breakthrough for plant transgenesis came in 1983, when three separate teams of scientists used plasmids as vectors (carrier molecules) to infect plants with foreign DNA. The achievement came about because of research into plant tumors caused by crown gall disease. The pathogen, the soil bacterium Agrobacterium tumefaciens, caused the disease by ferrying bits of its own DNA into the genome of plants via plasmids, circular bits of extranuclear DNA. Scientists found that they could take the same plasmid, cut out bits of its DNA with enzymes and insert transgenes, and then use the altered plasmids as vectors to transform plants. Subsequently, scientists discovered that liposomes can be vectors. A liposome is a tiny ball of lipids that binds
readily to a cell wall, opens a passage, and delivers any DNA that has been put inside it.
A great variety of transgenic plants have been designed for agriculture to produce genetically modified (GM) foods. The first to be marketed was a strain of tomato that ripened slowly so that it gained flavor by staying longer on the vine and remained ripe longer on supermarket shelves. However this Flavr Savr tomato was not a commercial success. Other crops have been made resistant to herbicides so that weeds can be easily killed without harming the food plants. Corn, cotton, soybeans, potatoes, and papayas received a gene from the bacterium Bacillus thuringiensis (Bt) that enables them to make a caterpillar-killing toxin; these are frequently referred to as Bt crops. Herbicide resistant (HT) soybeans were cultivated in 94 percent of the total US soybean acreage in 2014, according to the US Department of Agriculture. Other transgenic crops such as pest-resistant (Bt) cotton was grown in 84 percent of cotton acreage while Bt corn was grown in 80 percent of the total corn acreage. Despite the expanding acreage, the diversity of crop types and traits in commercial production is tightly regulated by government agencies.
Like transgenic animals, some transgenic crops promise to deliver pharmaceuticals at lower costs and more conveniently than factory-made drugs. In 2000, scientists reported invention of rice and wheat strains that produce anticancer antibodies. Golden rice, a transgenic strain that contains vitamin A, was developed to ward off blindness from vitamin A deficiency, which is a problem in countries that subsist largely on rice. Another strain has elevated iron levels to combat anemia. Also in a bid to reduce the health risk from smoking, a tobacco company developed a strain free of nicotine. In recent years, maize, potato, soybean, and tomato have been used to produce vaccines for both humans and animals against pneumonic and bubonic plague. A vaccine for hepatitis B has been developed in transgenic potatoes that raises an immunological response in humans. Also edible rice-based vaccine targeted to allergic diseases such as asthma, seasonal allergies, and atopic dermatitis has been developed.
The Debate over Transgenesis
Transgenic organisms offer great benefits to humankind: deeper understanding of the genetic component in disease and aids in diagnosis; new, cheaper, more easily produced drugs; and crops that could help alleviate the growing hunger in the world. Yet during the 1990s protests against transgenesis began that are as contentious as any since the controversy over the pesticide DDT during the 1960s.
Some opponents object to the very fact that organisms are modified strictly for human benefit. They find such manipulations of life’s essential code blasphemous and arrogant, or at the very least unethical and reckless. Furthermore, animal rights groups regard the production of transgenic pharm and research animals as cruel and in violation of the natural rights of other species.
The greater portion of opponents, however, are concerned with specific dangers that transgenic organism may pose. Many consumers, most noticeably those in Europe, worry that GM foods contain hidden health risks. After transgenes were found to escape from crops and become part of wild plants, environmentalists proposed that there could be unforeseen and harmful ecological consequences, especially in the destruction of natural species and reduction of biodiversity.
Even those who welcome the creation of transgenic animals and plants are concerned about the legal and social effects. Principally, because biotechnology corporations can patent transgenic organisms, they potentially have great influence on agribusiness, perhaps to the detriment of small farmers and consumers.
Therefore, as with the development of any new technology, it is critical to conduct extensive studies and peer reviewed research for harnessing the power of genetic engineering. The close scrutiny and appropriate policies would allow the human society to reap its immense benefits without compromising biodiversity or creating environmental imbalance.
Key terms
genome
:
the complete genetic material carried by an individual
plasmid
:
a circular piece of bacterial DNA that is often used as a vector
transformation
:
integration of foreign DNA into a cell
transgene
:
the foreign gene incorporated into a cell’s DNA during transformation
vector
:
a carrier molecule that introduces foreign genetic materials into a cell
Bibliography
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