Genetic engineering, or bioengineering, is currently one of the most exciting and publicized branches of biotechnology. Since the development of sophisticated gene spicing in the mid-1970s, a technique known as recombinant DNA, scientists have been able to remove and add genetic material to a cell's DNA. By impregnating the genetic material of plants and animals with "helpful" genes taken from the DNA of other organisms, biotechnologists are creating new kinds of foods, including some that you may soon see on the shelves of your local grocery stores.
The United States Department of Agriculture frequently issues permits to companies across the country allowing them to field-test genetically engineered crops. Many bioengineered foods have already been developed, and more are in process.
High-yield agriculture in recent decades has involved the use of vast amounts of fertilizer and pesticide chemicals. These toxic chemicals have a devastating effect on the environment and are extremely costly to farmers. Biotechnologists hope to reduce the need for fertilizers and pesticides by creating plants that can repel pests and help to fertilize themselves. Agronomists also are using genetic engineering to strengthen plants against diseases and harmful environmental conditions such as soil salinity, drought, alkaline, earth metals, and soil that lacks air.
Some of the genetically engineered foods that are currently being tested are a type of rice that has greater protein content, wheat that can help fertilize it-self by producing its own nitrogen, tomatoes that have more pulp and less water, and potatoes that absorb less fat when fried. Biotechnologists also are experimenting with using gene splicing to make chickens bigger, pigs leaner, and crops such as straw berries and tomatoes resistant to frost damage.
While the possibilities of genetic engineering seem virtually limitless, there are legitimate concerns about this new branch of biotechnology. The power of bioengineering has tremendous potential for good; however, it can just as easily be used irresponsibly. For example, some of the agricultural research currently being conducted is aimed at creating plants with greater resistance to the harmful effects of pesticides. Such crops would still require the use of pesticides and perhaps even encourage greater pesticide usage because of their increased tolerance. Why create plants that can better withstand pesticides when it is possible to create plants that can repel pests themselves, eliminating the need for pesticides? The answer is that chemical companies that sell pesticides want to ensure that farmers will continue to buy their products.
Environmentalists are concerned about what will happen when genetically engineered plants and animals enter earth's delicate ecosystem and food chain. Many people predict that creating genetically altered organisms will further reduce the earth's biological diversity, result in "super-weeds" that will threaten current plant species, and produce unforeseen allergens and toxins in the foods we eat. Other people question the morality of manipulating the genetic makeup of animals. What will stop people from using biotechnological methods to manipulate human DNA, controlling who and what will be born?
From a scientific standpoint, bioengineering is an extremely exciting field; however, it has raised difficult questions. Scientists and students interested in this branch of biotechnology will need to consider the social, ethical, and environmental implications of genetic manipulation before attempting to utilize its power.
MONOCLONAL ANTIBODY TECHNOLOGY
Another facet of biotechnology is monoclonal antibody technology. Substances foreign to the body such as viruses, disease causing bacteria and other infectious agents have structural features jutting from their surfaces. These features, called antigens, are recognized by the body's immune system as invaders. Our natural defenses against these infectious agents are antibodies, proteins that seek out the anti gens and help to destroy them.
Antibodies have two very useful characteristics. First, they are extremely specific; that is, each antibody binds to and attacks one particular antigen. Second, some antibodies, once activated by the occurrence of a disease, continue to offer resistance against that disease. For example, once you have had the chicken pox, you should never have it again. That second characteristic of antibodies makes it possible to create vaccines. A vaccine is a preparation of killed or weakened bacteria or viruses that, when introduced into the body, stimulates the production of antibodies against the antigens it contains.
It is the first trait of antibodies, their specific nature that makes monoclonal antibody technology so valuable. Recent Developments in Biotechnology has proved that antibodies can not only be used therapeutically to protect against disease, but can also help to diagnose a wide variety of illnesses. Furthermore, they can detect the presence of drugs, viral and bacterial products, and other unusual or abnormal substances in the blood.
Because there is such a diversity of uses for these disease-fighting substances, their production in pure quantities has long been the focus of scientific investigation. The conventional method had been to inject a laboratory animal with an antigen and then, when antibodies had been formed, collect those antibodies from the blood serum. There are two problems with this method. It yields antiserum (an antibody containing blood serum), which is comprised of undesired substances. Also, it provides a very small amount of usable antibody.
Monoclonal antibody technology allows scientists to produce large amounts of pure antibodies.
Like other applications of biotechnology, modem bioprocess technology is an extension of ancient techniques for developing useful products by taking advantage of natural biological activities. When our early ancestors made alcoholic beverages, they used a bio process the combination of yeast cells and cereal grains. This combination formed a fermentation system in which the organisms consumed the grain for their own growth and, while doing so, produced by-products (alcohol and carbon dioxide gas) that helped to make the beverage. Although certainly more advanced, today's bioprocess technology is based upon the same principle: combining living matter (whole organisms or enzymes) with nutrients under the conditions necessary to make the desired end product.
Bioprocesses have become widely used in several areas of commercial biotechnology. These include the production of enzymes used for such things as food processing, waste management, and antibodies.
As techniques and instrumentation are refined, bioprocesses may have applications in other areas where chemical processes are now used. They offer several advantages over the latter: bioprocesses require lower temperature, pressure, and pH (a measure of acidity); they can use renewable resources as raw materials; and greater quantities can be produced with less energy consumption.
AIDS (Acquired Immune Deficiency Syndrome) is one of the most serious health threats presently facing modem society. Since AIDS was first recognized as a disease in 1983, millions of people around the world have been infected with the human immunodeficiency virus (HIV) that causes AIDS. Too many will die of AIDS unless a cure is found.
Biotechnology has played a crucial role in preventing the spread of AIDS, as well as treating it. Using monoclonal antibody technology, biomedical researchers have developed a laboratory test that shows whether blood has been contaminated with the HIV virus. This has helped slow the spread of AIDS by informing people if they are HIV carriers and enabling hospitals to screen donated blood.
Scientists have experimented in recent years with genetically engineered proteins as possible treatments for HIV and the infectious diseases that accompany it. HIV infection destroys T-4 lymphocytes, which make up an important part of the body's immune system. Without these lymphocytes, the body is vulnerable to a wide range of diseases that it would normally ward off without difficulty. A natural protein called CD4 is found on the surface of the body's T-4 cells and acts as a gate, allowing the virus to enter the cells. By introducing bioengineered CD4 protein into the bloodstream as a decoy, scientists hope that the HIV virus will attack it instead of T-4 cells.
Scientists also are using biotechnology techniques in an effort to develop an AIDS vaccine. Traditionally, vaccines have been made from a dead or weakened virus, which stimulates the body's natural defenses while not actually producing disease. If the immunized person is later infected with the natural virus, his or her stimulated immune system is ready to destroy the invader. A weakened or killed HIV virus, however, can become reactivated and cause AIDS rather than produce immunity. Several biotechnology companies are investigating the idea of using part of the HIV virus to create a vaccine that cannot become reactivated and lead to AIDS. Efforts to develop a vaccine have been thus far unsuccessful, mainly because the virus itself is changing so quickly. Because HIV occurs in several different forms, it is unlikely that a single vaccine will be effective against all of them.
Biotechnologists are also involved in the fight against disease-both treating and avoiding it. First, they determine what specific drugs are required. Then they plan their de sign. Experts predict another "explosion" of discoveries leading to many new pharmaceutical products that will far exceed the substantial growth in drug development over the last fifty years.
Professionals in the health field, as well as their patients, already owe much to biotechnology. Vitamin B12, steroids, and many birth control pills originate from biotechnological sources. Human insulin was the first recombinant DNA derived product to become commercially available. It was first marketed in 1982.
The Biotechnology Industry Organization reports other important studies biotechnologists are making to keep us healthy, including the following:
FIGHTING HEART DISEASE
Heart attacks may occur in people whose arteries have been narrowed by the accumulation of cholesterol. If a blood clot enters one of the coronary arteries, which supply blood to the heart muscle, it can become lodged in a narrowed section of the artery, cutting off blood flow to a portion of the heart muscle. Without quick and effective treatment, the heart can be damaged permanently.
Each year, 1.1 million people suffer heart attacks. More than 400,000 of those attacks are fatal. Many of these patients can be saved from death or permanent disability with a genetically engineered drug called tissue plasminogen activator, or TPA.
TPA is a natural human protein that dissolves blood clots. It occurs naturally in the blood, but in amounts too small to stop a heart attack.
When a heart attack strikes, doctors may inject genetically engineered TPA into the patient's blood. The protein travels to the clot, breaking it up within minutes and restoring blood flow to the heart muscle. By quickly restoring blood flow, TPA helps prevent life-threatening damage to the heart muscle.
The U.S. Food and Drug Administration approved TPA in 1987, and it is available in most hospitals. Eventually, the drug may be used by ambulance crews-or heart patients themselves-to stop heart attacks before the patient even reaches the hospital.
NEW WEAPONS FOR THE WAR ON CANCER
Cancer is an error in cell development. Normal cells grow and reproduce rapidly when they are young and then slow down or stop reproducing when they mature. Somehow cancer cells get tricked into staying immature, and they reproduce wildly.
Despite the nation's war on cancer since the early 1970s, cancer is still second only to heart disease as a killer. Each year, more than one million Americans develop cancer, and more than five hundred thousand people die from the disease. Biotechnology is used to treat cancer in three ways. Some genetically engineered proteins, called lymphokines, appear to attack cancer cells directly, or they may trigger the body's immune system to attack the cancer. Other genetically engineered proteins, called growth factors, appear to push cancer cells to maturity, slowing the rampant reproduction. And monoclonal antibodies armed with radioactive material, cancer drugs, or other poisons search out and destroy cancer cells.
One genetically engineered lymphokine, alpha-interferon, is used to treat people with hairy cell leukemia, a cancer that several hundred Americans develop each year.
Before alpha-interferon came along, a diagnosis of hairy cell leukemia was a death sentence. People with the disease required frequent blood transfusions and became highly susceptible to infections. There were no effective long-term treatments.
Now, alpha-interferon can restore people with hairy cell leukemia to normal health. The protein appears to bind to the surface of the cancer cell, halting its growth.
In addition to alpha-interferon, doctors are looking to other genetically engineered lymphokines to treat cancer patients. Interleukin-2 activates special white blood cells, called killer cells that can destroy cancer cells. These activated killer cells may prove to be an effective treatment for people with advanced skin and kidney cancers.
Another group of proteins, called colony stimulating factors, trigger the production and activity of cells of the immune system. Colony stimulating factors may prove useful in marshaling the body's defenses against cancer and AIDS. They may also help restore normal blood production in patients with severe anemia or undergoing bone marrow transplantation.
OTHER DISEASES
Heart disease, cancer, AIDS, and diabetes are just some of the diseases biotechnology will help to treat in the coming years. Here is a sample of some of the other conditions for which biotechnology products are available or under development:
- Dwarfism. Children lacking sufficient growth hormone cannot grow to normal height without regular injections of human growth hormone. Traditionally, these children were treated with limited supplies of growth hormone from cadavers. But in 1985, cadaver-derived hormone was removed from the market after several children died from a rare virus that contaminates it. Unlike cadaver derived hormone, genetically engineered growth hormone is a safe therapy for treating dwarfism.
- Hemophilia. Hemophiliacs are constantly at risk of internal bleeding because their bodies cannot produce enough of a protein called Factor VIII, which controls blood clotting. Transfusions of Factor VIII from human blood can control the disorder, but these transfusions contain only I percent Factor VIII and can transmit viral diseases. Some hemophiliacs were infected with the HIV from transfusions in the early 1980s, and they can still get hepatitis from contaminated Factor VIII.
- Now, monoclonal antibody technology is being used to make Factor VIII that is 99 percent pure. And studies are underway with genetically engineered Factor VIII, which is completely pure and incapable of transmitting disease.
- Anemia. Hundreds of thousands of people suffer each year from anemia associated with a variety of conditions, such as chronic renal failure and AIDS. A person on kidney dialysis or undergoing cancer therapy generally suffers from anemia and must receive blood transfusions. As with hemophiliacs, transfusions carry the risk of infectious disease. Several biotechnology companies have developed genetically engineered erythropoietin, a natural human hormone that stimulates the production of red blood cells and may be useful in treating anemia and reducing the need for transfusions.
- Organ rejection. When a patient receives a kidney or other transplanted organ, the patient's immune system may recognize it as an invader and attack it. Such rejection can cause a transplant to fail, and in some cases, the rejection can be fatal. Using monoclonal antibodies, doctors can eliminate T cells, elements of the immune system responsible for organ rejection.
- Common cold. Medicine has conquered many common bacterial diseases with antibiotics. But antibiotics are useless against viral diseases, such as the common cold. The lymphokine interferon-referred to earlier as the treatment for hairy cell leukemia-may be effective against the virus that causes 40 percent of all colds.
All of these powerful new therapies would be of little use if doctors could not accurately determine which diseases or other conditions their patients have. In addition to providing new drugs, biotechnology has added to the physician's trove of diagnostic tools.
A number of biotechnology companies are using mono clonal antibodies in diagnostic tests. Because monoclonal antibodies bind specifically to certain targets, they are generally more effective than conventional diagnostic tools in identifying the cause and location of disease. To cite just a few examples, monoclonal antibodies are used in diagnostic procedures for hepatitis, venereal disease, and bacterial infections. They are also used in home pregnancy test kits.
Doctors can use monoclonal antibodies to "see" into the Human body with clarity unimaginable a decade ago. A physician injects a patient with monoclonal antibodies that carry minute amounts of radioactive material. The antibodies then attach to their target, such as a tumor or heart muscle damaged by a heart attack. The doctor uses a computerized scanning device to locate and study the diseased tissue so that an appropriate course of therapy can be planned.
Recombinant DNA technology allows physicians to identify specific genes, enabling the doctors to diagnose genetic disorders such as cystic fibrosis. Recombinant techniques also are used to detect HIV infection and may someday be used to diagnose a variety of infectious diseases, including cancer.
THE NEXT FRONTIER: DISEASE PREVENTION
As amazing as some of the therapeutic and diagnostic uses of biotechnology may seem today, they may someday appear crude. The real promise of the new biology is in helping scientists understand the cause of disease, so that health care professionals will better be able to prevent most diseases.
Biotechnology companies and pharmaceutical firms are developing vaccines against a host of infectious diseases, in addition to AIDS. Doctors now have a genetically engineered vaccine against hepatitis B, for instance, a viral disease that more than two hundred thousand people contract each year.
Genetically engineered vaccines will have the greatest impact in developing nations, where millions die or suffer chronic illness from viral and parasitic diseases such as malaria and schistosomiasis. Scientists may be able to use genetic engineering to mix the genes of many infectious agents, producing a single vaccine that could be used to immunize people in the world's developing countries against a wide range of diseases.
Disease prevention is also an important issue in developed countries. Death from heart disease, for example, can be greatly reduced by lowering the amount of cholesterol-laden food people consume. The risk of cancer can be reduced with a low-fat, high-fiber diet. Biotechnology companies are using genetic engineering to develop foods and food ingredients that are more healthful but still tasty.
Biotechnology also presents the possibility of correcting genetic disorders. Caused by an insufficient amount of a single protein, severe combined immune deficiency is the hereditary disorder brought to public attention by David, the boy in the plastic bubble. Children with this disease cannot fight off simple infections, and they rarely survive the first two years of life. The condition may be cured by replacing the gene that codes for the deficient protein.
Replacing missing or defective genes in a person with a genetic disorder would restore normal function to the individual, but the person could still pass the genetic defect on to his or her children. Some doctors have proposed eliminating genetic defects in reproductive cells to prevent offspring from inheriting the disorder. This step, however, raises ethical questions about who will decide which genes should be passed to future generations.
John Fletcher, Ph.D., professor of biomedical ethics and religious studies at The University of Virginia School of Medicine, Charlottesville, believes human gene therapy can be used without violating ethical principles.
"If you had the power not only to prevent a genetic disorder, but to protect the next generation, would you want to take that step? Most people would say 'yes,'" Fletcher said. But Fletcher also said that doctors and patients must "keep the line drawn between treating real diseases that cause death and pain and suffering, and trying to engineer perfect people."
Briefly summarizing the feats of a young and robust science is a challenging task. For one thing, new accomplishments come along at a rapid pace. We are living at a time when some of the answers to elusive questions about fundamental biological processes soon may be found with the help of biotechnology. Using more powerful methods than ever before, many of which were only dreamed of a short time ago, biotechnologists are changing our world.
