Unit Three. The Continuity of Life


13. The New Biology


13.4. Genetic Engineering and Medicine


Much of the excitement about genetic engineering has focused on its potential to improve medicine—to aid in curing and preventing illness. Major advances have been made in the production of proteins used to treat illness, and in the creation of new vaccines to combat infections.


Making "Magic Bullets"

Many illnesses occur because of gene defects that prevent our bodies from making critical proteins. Juvenile diabetes is such an illness. The body is unable to control levels of sugar in the blood because a critical protein, insulin, cannot be made. This failure can be overcome if the body can be supplied with the protein it lacks. The donated protein is in a very real sense a “magic bullet” to combat the body’s inability to regulate itself.

Until recently, the principal problem with using regulatory proteins as drugs was in manufacturing the protein. Proteins that regulate the body’s functions are typically present in the body in very low amounts, and this makes them difficult and expensive to obtain in quantity. With genetic engineering techniques, the problem of obtaining large amounts of rare proteins has been largely overcome. The cDNA of genes encoding medically important proteins are now introduced into bacteria (table 13.2). Because the host bacteria can be grown cheaply, large amounts of the desired protein can be easily isolated. In 1982, the U.S. Food and Drug Administration approved the use of human insulin produced from genetically engineered bacteria, the first commercial product of genetic engineering.





Effects and Uses


Involved in dissolving blood clots; used to treat heart attack patients

Colony-stimulating factors

Stimulate white blood cell production; used to treat infections and immune system deficiencies


Stimulates red blood cell production; used to treat anemia in individuals with kidney disorders


Promotes blood clotting; used to treat hemophilia

Growth factors

Stimulate differentiation and growth of various cell types; used to aid wound healing

Human growth hormone

Used to treat dwarfism


Involved in controlling blood sugar levels; used in treating diabetes


Disrupt the reproduction of viruses; used to treat some cancers


Activate and stimulate white blood cells; used to treat wounds, HIV infections, cancer, immune deficiencies


The use of genetic engineering techniques in bacteria has provided ample sources of therapeutic proteins, but the application extends beyond bacteria. Today hundreds of pharmaceutical companies around the world are busy producing other medically important proteins, expanding the use of these genetic engineering techniques. A gene added to the DNA of the mouse on the right in figure 13.8 produces human growth hormone, allowing the mouse to grow larger than its twin.




Figure 13.8. Genetically engineered human growth hormone.

These two mice are genetically identical, but the large one has one extra gene: the gene encoding human growth hormone. The gene was added to the mouse's genome by genetic engineers and is now a stable part of the mouse's genetic make-up. In humans, growth hormone is used to treat various forms of dwarfism.


The advantage of using genetic engineering is clearly seen with factor VIII, a protein that promotes blood clotting. A deficiency in factor VIII leads to hemophilia, an inherited disorder (discussed in chapter 10) that is characterized by prolonged bleeding. For a long time, hemophiliacs received blood factor VIII that had been isolated from donated blood. Unfortunately, some of the donated blood had been infected with viruses such as HIV and hepatitis B, which were then unknowingly transmitted to those people who received blood transfusions. Today the use of genetically engineered factor VIII produced in the laboratory eliminates the risks associated with blood products obtained from other individuals.


Piggyback Vaccines

Another area of potential significance involves the use of genetic engineering to produce subunit vaccines against viruses such as those that cause herpes and hepatitis. Genes encoding part of the protein-polysaccharide coat of the herpes simplex virus or hepatitis B virus are spliced into a fragment of the vaccinia (cowpox) virus genome. The vaccinia virus, which is essentially harmless to humans and was used by British physician Edward Jenner more than 200 years ago in his pioneering vaccinations against smallpox, is now used as a vector to carry a viral coat gene into cultured mammalian cells. As shown in figure 13.9, the steps in constructing a subunit vaccine for herpes simplex begin with 1 extracting the herpes simplex viral DNA and 2 isolating a gene that codes for a protein on the surface of the virus. The cowpox viral DNA is extracted and cleaved 3, and the herpes gene is then combined with the cowpox DNA 4. The recombinant DNA is inserted into a cowpox virus. Many copies of the recombinant virus, which have the outside coat of a herpes virus, are produced. When this recombinant virus is injected into a human 5, the immune system produces antibodies directed against the coat ofthe recombinant virus 6. The person therefore develops an immunity to the virus. Vaccines produced in this way, also known as piggyback vaccines, are harmless because the vaccinia virus is benign, and only a small fragment of the DNA from the disease-causing virus is introduced via the recombinant virus.



Figure 13.9. Constructing a subunit, or piggyback, vaccine for the herpes simplex virus.


In 1995, the first clinical trial began of a new kind of vaccine, called a DNA vaccine. DNA containing a viral gene is injected and taken up by cells of the body, where the gene is expressed. The infected cells trigger a cellular immune response, in which blood cells known as killer T cells attack the infected cells. The first DNA vaccines spliced an influenza virus gene encoding an internal nucleoprotein into a plasmid, which was then injected into mice. The mice developed strong cellular immune responses against influenza. The approach offers great promise.

In 2010, the first effective cancer vaccines were announced. A cancer vaccine is therapeutic rather than preventive, stimulating the immune system to attack a tumor in the same way invading microbes are attacked. The first cancer vaccine approved for clinical use employs proteins from prostate cancer cells to induce the immune system to attack prostate cancer tumors. Another cancer vaccine, very effective in mice but not yet approved for humans, uses a protein called alpha-lactalbumin to trigger an attack on breast cancer cells. The protein is not found on normal breast cancer cells except when women are breast-feeding. As 96% of the lifetime risk of a woman for breast cancer is after child-bearing years, post-menopausal use of this vaccine may prove to be a powerful therapy against early undetected breast cancers.


Key Learning Outcome 13.4. Genetic engineering has facilitated the production of medically important proteins and led to novel vaccines.