Genetic engineering

Genetic engineering is the term applied to techniques that alter the genes (hereditary material) or combination of genes in an organism. The cells of all living organisms contain genes. Genes carry chemical information that determines the organism’s characteristics. By changing an organism’s genes, scientists can give the organism and its descendants different traits.

Genetically engineered mouse
Genetically engineered mouse

For thousands of years, breeders of plants and animals have used breeding methods to produce favorable combinations of genes. These “genetic engineers” have produced most of the economically important varieties of flowers, vegetables, grains, cows, horses, dogs, and cats. Beginning in the 1970’s, scientists developed ways to reintroduce individual genes into cells or into plants, animals, or other organisms. Such techniques alter the heredity of the cells or organisms.

How genes are reintroduced into cells.

Genes lie within cells on tiny, threadlike structures called chromosomes. Each chromosome contains a single long molecule of a chemical substance called DNA (deoxyribonucleic acid). A molecule of DNA may contain thousands of genes. DNA stores within its chemical structure the information that determines an organism’s hereditary properties.

The physical structure of DNA is much the same in all organisms. The DNA molecule is shaped like a twisted rope ladder, called a double helix. The “rungs” of the ladder are made of four chemical compounds called bases. A pair of bases forms each rung. Most genes consist of several thousand base pairs. The order of the bases, or the base sequence, provides the information necessary for a cell to make a specific protein. The form and function of a cell depend on the proteins it produces. Thus, the base sequences of an organism’s DNA make the organism different from all other living things.

In addition to storing information, the DNA molecule’s structure allows for easy replication (duplication) of the molecule. Before a cell divides, enzymes split the DNA ladder lengthwise, separating the base pairs. Then, the base sequence in each half ladder directs the production of a new matching half. In this way, each of the two new ladders becomes a duplicate of the original ladder. See Heredity (Replication).

To alter the genetic makeup of DNA, scientists use a technique called gene splicing. In this technique, a gene-sized fragment of DNA is taken from one organism and joined to a DNA molecule from another organism or from the same organism. Gene-sized DNA fragments are isolated by means of restriction enzymes. These enzymes react chemically with a specific base sequence in the DNA molecule and break the molecule at that point. This point is called the cleavage site. The gene-sized DNA fragment can then be spliced (joined) to another DNA molecule by using an enzyme called ligase. The hybrid molecule formed is called recombinant DNA.

When recombinant DNA is mixed with specially prepared cells, a few of the cells will take up the recombinant DNA in a process called transformation. This mixture of cells is then placed on a special culture medium that allows only the “transformed” cells to grow. Each of the transformed cells with the newly added genetic information grows overnight into a colony of millions of cells. This colony represents a clone—that is, a group of genetically identical cells.

Another genetic engineering technique commonly referred to as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) was developed in 2012. It is derived from a process that scientists first observed occurring naturally in bacteria in 1987. The technique uses a protein designated Cas9, which is obtained from bacteria, to break DNA at highly specific locations. Scientists can manipulate the CRISPR/Cas9 process to delete, alter, or replace a gene with great accuracy. See CRISPR.

Compared to older gene-splicing techniques, CRISPR is extremely precise and efficient. Scientists point out that the technique could be used to eliminate many human diseases caused by a single malfunctioning gene, including cystic fibrosis, Huntington’s disease, sickle cell anemia, and Tay-Sachs disease. However, ethics experts worry that the technique could be abused to create genetically modified “designer babies” with made-to-order characteristics.

Uses of genetic engineering.

Researchers have found important uses for genetic engineering in such fields as medicine, industry, and agriculture. Many new uses are predicted for the future.

In medicine.

A number of human illnesses are caused by the failure of certain genes in the body to make specific proteins. For example, the failure of genes in the pancreas to make insulin causes diabetes. Scientists can produce large quantities of insulin in bacterial “factories” by splicing the insulin gene isolated from human cells to plasmids from cells of Escherichia coli bacteria. The insulin is then given to patients who need it. Researchers also have engineered E. coli to make proteins called interferons. These proteins are normally produced by body cells in response to viral infections. They have been tested against many diseases. See Interferon.

Many people suffer from diseases caused by genetic defects. Using recombinant DNA techniques, scientists can test DNA isolated from cells of unborn babies to learn whether the babies will have a disease. Also, researchers have investigated methods of gene therapy in an effort to cure diseases. See Gene therapy.

Doctors first used gene therapy to treat a patient in 1990. The patient suffered from a weak immune system. Since then, many clinical trials using gene therapy on people have been undertaken.

In one approach, the DNA of viruses is modified by replacing disease-causing genes with normal human genes. The modified viruses become vehicles to replace defective genes in patients’ cells with normal genes. This method may help doctors treat cystic fibrosis and various liver diseases. In another technique, researchers are introducing genes into cancer cells to make them more vulnerable to drugs that can kill them.

In industry.

Genetically engineered microbes have been used to improve the efficiency of food production. For example, rennin, an enzyme used in making cheese, is produced naturally in the stomachs of calves. By means of gene splicing, rennin can be obtained more cheaply. Genetic engineering also has potential in controlling pollution. Researchers are working to develop genetically engineered microorganisms that break down garbage, toxic substances, and other wastes.

Researchers are also developing genetically engineered protein enzymes that can carry out chemical reactions in extremely harsh conditions. For example, these protein enzymes can function at high temperatures or in solutions that do not contain water. Such enzymes may become important components in the manufacture of antibiotic drugs and other products.

In agriculture.

Scientists have developed numerous genetically engineered plants. Thousands of genetically engineered plant hormones have been safely field tested under conditions approved by the U.S. Department of Agriculture. Special genes have been engineered into tomato plants to enable them to produce tomatoes with increased flavor and shelf life. Small plants have been genetically engineered to produce small amounts of a biodegradable plastic. Such crops as cotton, corn, soybeans, papaya, and squash have been engineered to resist disease or injury from herbicides, insects, or viruses. Other genetically engineered plants are used to produce antibodies, for potential use in medicines. See Agriculture (The development of modern agriculture).

St. Louis researchers examine soybean plants
St. Louis researchers examine soybean plants

Large amounts of a growth hormone found in cows have been obtained from genetically engineered bacteria. When treated with this hormone, dairy cows produce more milk, and beef cattle have leaner meat. Similarly, a genetically engineered pig hormone causes hogs to grow faster and decreases fat content in pork.

In 1996, a group of scientists in Scotland, led by British biologist Ian Wilmut, achieved the first successful cloning of a mammal from the cells of an adult animal (see Wilmut, Ian). They produced a clone of a sheep, which they named Dolly. Cloning may provide numerous benefits for human beings. For example, livestock of superior quality could be cloned for farmers. Such livestock would yield higher quality meat, milk, and wool. People could also clone animals that produce human proteins and other substances used in medical drugs. See Cloning.

Dolly the Sheep
Dolly the Sheep

History.

Genetic engineering is based on genetics, a science begun in the early 1900’s but based on experiments done in the mid-1800’s by the Austrian monk Gregor Mendel. See Mendel, Gregor Johann.

Techniques for isolating and altering genes were first developed by American geneticists during the early 1970’s. During the late 1970’s, researchers used recombinant DNA techniques to engineer bacteria to produce small quantities of insulin and interferon. By the early 1980’s, methods of genetic engineering had been adapted to large-scale production of these substances. In 1982, bacterially produced insulin became the first recombinant DNA drug approved by the Food and Drug Administration (FDA) for use on people.

Also in the early 1980’s, geneticists made progress in using genetic engineering techniques to add genes to higher organisms. Researchers inserted a human growth-hormone gene into mice, and the mice grew to twice their normal size. In 1982, researchers succeeded in transferring a gene from one species of fruit fly to another. That same year, geneticists proved genes can be transferred between plant species. In 1987, scientists introduced a gene from a bacterial cell into tomato plants, making the plants resistant to caterpillars.

In 1986, the U.S. Patent and Trademark Office issued the first patent on a plant produced through genetic engineering—a variety of corn with increased nutritional value. In 1988, the first U.S. patent on a genetically engineered higher animal was issued. The animal, a type of mouse, was developed for use in cancer research. In 1990, the FDA approved rennin as the first genetically engineered gene product. In 1996, Ian Wilmut and his colleagues pioneered the technique of cloning mammals from the cells of adult animals. The following year, Japanese and American scientists in Hawaii used a similar technique to produce clones of mice.

Genetically modified corn
Genetically modified corn

Concerns about genetic engineering.

Despite its many benefits, genetic engineering has caused concern among some people. Some oppose genetic engineering because they fear that harmful, uncontrollable bacteria might be produced accidentally. Others worry about possible environmental damage by the deliberate introduction of organisms whose heredity has been altered. Some people also question the morality of manipulating the genetic material of living creatures. In addition, the successful cloning of mammals has led many to debate the possible benefits and drawbacks of human cloning.

In 1976, the National Institutes of Health (NIH) issued safety guidelines to control laboratory procedures for gene splicing. These guidelines have been gradually relaxed because such research was proved safe. In 1985, the NIH approved experimental guidelines for treatment in which genes are transplanted to correct hereditary defects in human beings. In 1987, a committee of the National Academy of Sciences concluded that transferring genes between species of organisms posed no serious environmental hazards.

In 1997, the USDA amended its regulations on genetically engineered plants. Once plant breeders have shown that a genetically altered plant has no risk for becoming a pest, they can apply to the USDA to obtain nonregulated status for that plant.

In 2018, a Chinese scientist announced that he had used the CRISPR technique to alter the DNA of human embryos produced through in-vitro fertilization. The embryos were successfully implanted and resulted in the live birth of twin girls. The scientist used CRISPR to remove a gene called CCR5 from the embryos. Removing this gene is thought to make individuals more resistant to infection by HIV, the virus that causes AIDS. Scientific authorities throughout the world considered the experiment to be a serious violation of scientific ethics and codes of conduct.