19.6 Biotechnology Harnesses the Power of Molecular Genetics

In addition to providing valuable new information about the nature and function of genes, molecular genetics techniques have many practical applications, including the production of pharmaceutical products and other chemicals, specialized bacteria, agriculturally important plants, and genetically engineered farm animals. The technology is also used extensively in medical testing and, in a few cases, is even used to correct human genetic defects. Hundreds of companies now specialize in developing products through genetic engineering, and many large multinational corporations have invested enormous sums of money in molecular genetics research. As discussed earlier, the analysis of DNA is also used in criminal investigations and for the identification of human remains.

Pharmaceutical Products

The first commercial products to be developed with the use of genetic engineering were pharmaceutical products used in the treatment of human diseases and disorders. In 1979, the Eli Lilly corporation began selling human insulin produced with the use of recombinant DNA technology. The gene for human insulin was inserted into plasmids and transferred to bacteria that then produced human insulin. Previously, insulin was isolated from pig and cow pancreases; a few diabetics developed allergic reactions to this foreign protein. Recombinant insulin has the advantage of being the same as that produced in the human body. Other pharmaceutical products produced through recombinant DNA technology include human growth hormone (for children with growth deficiencies), clotting factors (for hemophiliacs), and tissue plasminogen activator (used to dissolve blood clots in heart-attack patients).

Specialized Bacteria

Bacteria play an important role in many industrial processes, including the production of ethanol from plant material, the leaching of minerals from ore, and the treatment of sewage and other wastes. The bacteria used in these processes are modified by genetic engineering so that they work more efficiently. New strains of technologically useful bacteria are being developed that will break down toxic chemicals and pollutants, enhance oil recovery, increase nitrogen uptake by plants, and inhibit the growth of pathogenic bacteria and fungi.

Agricultural Products

Recombinant DNA technology has had a major effect on agriculture, where it is now used to create crop plants and domestic animals with valuable traits. For many years, plant pathologists had recognized that plants infected with mild strains of viruses are resistant to infection by virulent strains. Using this knowledge, geneticists created viral resistance in plants by transferring genes for viral proteins to the plant cells. A genetically engineered squash, called Freedom II, carries genes from the watermelon mosaic virus 2 and the zucchini yellow mosaic virus, which protect the squash against viral infections.

Another objective has been to genetically engineer pest resistance into plants to reduce dependence on chemical pesticides. As discussed earlier in the chapter, a gene from the bacterium Bacillus thuringiensis that produces an insecticidal toxin has been transferred into corn, tomato, potato, cotton, and other plants. These Bt crops are now grown worldwide. Other genes that confer resistance to viruses and herbicides have been introduced into a number of crop plants. During 2011, 16.7 million farmers worldwide planted 160 million hectares of genetically engineered crops. In the United States, 88% of all corn, 94% of all cotton, and 93% of all soybeans grown in 2012 were genetically engineered.

Recombinant DNA techniques are also applied to domestic animals. For example, the gene for growth hormone was isolated from cattle and cloned in E. coli; these bacteria produce large quantities of bovine growth hormone, which is administered to dairy cattle to increase milk production. Transgenic animals are being developed to carry genes that encode pharmaceutical products; some eukaryotic proteins must be modified after translation, and only other eukaryotes (but not bacteria) are capable of carrying out the modifications. For example, a gene for human clotting factor VIII was attached to the regulatory region of the sheep gene for β-lactoglobulin, a milk protein. The fused gene was injected in sheep embryos, creating transgenic sheep that produced in their milk the human clotting factor, which is used to treat hemophiliacs. Transgenic salmon have been created that carry a foreign growth hormone gene and promoter; the transgenic fish grow year round instead of just during warm months, reaching market size more quickly and with less feed than wild salmon. And through genetic engineering scientists have created transgenic chickens that express a small RNA that blocks infection of avian influenza virus.

The genetic engineering of agricultural products is controversial. One area of concern focuses on the potential effects of releasing novel organisms produced by genetic engineering into the environment. There are many examples in which nonnative organisms released into a new environment have caused ecological disruption because they are free of predators and other natural control mechanisms. Genetic engineering normally transfers only small sequences of DNA, relative to the large genetic differences that often exist between species, but even small genetic differences may alter ecologically important traits that might affect the ecosystem.

Another area of concern is the effect of genetically engineered crops on biodiversity. In the largest field test of genetically engineered plants ever conducted, scientists cultivated beets, corn, and rapeseed that were genetically engineered to resist herbicide along with traditional crops on 200 test plots throughout the United Kingdom. They then measured the biodiversity of native plants and animals in the agricultural fields. They found that the genetically engineered plants were highly successful in the suppression of weeds; however, plots with genetically engineered beets and rapeseed have significantly fewer insects that feed on weeds. For example, plots with genetically engineered rapeseed had 24% fewer butterflies than did plots with traditional crops.

There is also concern that transgenic organisms may hybridize with native organisms and transfer their genetically engineered traits. For example, herbicide resistance engineered into crop plants might be transferred to weeds, which would then be resistant to the herbicides that are now used for their control. Some studies have detected hybridization between genetically engineered crops and wild populations of plants. For example, evidence suggests that transgenic rapeseed (Brassica napus) has hybridized with the weed Brassica rapa in Canada. Other concerns focus on health-safety matters associated with the presence of engineered products in natural foods; some critics have advocated required labeling of all genetically engineered foods that contain transgenic DNA or protein. Such labeling is required in countries of the European Union but not in the United States.

On the other hand, the use of genetically engineered crops and domestic animals has potential benefits. Genetically engineered crops that are pest resistant have the potential to reduce the use of environmentally harmful chemicals, and research findings indicate that lower amounts of pesticides are used in the United States as a result of the adoption of transgenic plants. Studies conducted in China show that when Bt crops are used farmers spray less chemical insecticides, allowing more predatory insects to survive, and creating more natural pest control. Transgenic crops also increase yields, providing more food per acre, which reduces the amount of land that must be used for agriculture. Genetically engineered plants offer the potential for greater yields that may be necessary to feed the world’s future population.

Genetic Testing

The identification and cloning of many important disease-causing human genes have allowed the development of probes for detecting disease-causing mutations. Prenatal testing is already available for many genetic disorders (see Chapter 6). Additionally, presymptomatic genetic tests for adults and children are available for an increasing number of disorders. A number of genetic tests are now being offered directly to consumers, without requiring the participation of a health-care provider. Usually offered over the Internet, these direct-to-consumer genetic tests are available for testing a large and growing array of genetic conditions, everything from single-gene disorders such as cystic fibrosis to multifactorial conditions such as obesity, cardiovascular disease, athletic performance, and predisposition to nicotine addiction.

The growing availability of genetic tests raises a number of ethical and social questions. For example, is it ethical to test for genetic diseases for which there is no cure or treatment? Other ethical and legal questions concern the confidentiality of test results. Who should have access to the results of genetic testing? Should relatives who also might be at risk be informed of the results of genetic testing?

Another set of concerns is related to the accuracy of genetic tests. For many genetic diseases, the only predictive tests available are those that identify a predisposing mutation in DNA, but many genetic diseases may be caused by dozens or hundreds of different mutations. Probes that detect common mutations can be developed, but they won’t detect rare mutations and may give a false negative result. Short of sequencing the entire gene—which is expensive and time consuming—there is no way to identify all predisposed persons. These questions and concerns are currently the focus of intense debate by ethicists, physicians, scientists, and patients.

Gene Therapy

Perhaps the ultimate application of recombinant DNA technology is gene therapy, the direct transfer of genes into humans to treat disease. Today, thousands of patients have received gene therapy, and many clinical trials are underway. Gene therapy has been used as an experimental treatment for genetic diseases, cancer, heart disease, and even some infectious diseases such as AIDS. A number of different methods for transferring genes into human cells are currently under development. Commonly used vectors include genetically modified retroviruses, adenoviruses, and adeno-associated viruses (Table 19.4).

In spite of the growing number of clinical trials for gene therapy, significant problems remain in transferring foreign genes into human cells, getting them expressed, and limiting immune responses to the gene products and the vectors used to transfer the genes to the cells. There are also concerns about safety. In 1999, a patient participating in a gene-therapy trial had a fatal immune reaction after he was injected with a viral vector carrying a gene to treat his metabolic disorder. In addition, five children who underwent gene therapy for severe combined immunodeficiency disease developed leukemia that appeared to be directly related to the insertion of the retroviral gene vectors into cancer-causing genes. Despite these setbacks, gene-therapy research has moved ahead. Unequivocal results demonstrating positive benefits from gene therapy for several different diseases have now been published (see the introduction to this chapter).

Gene therapy conducted to date has targeted only non-reproductive, or somatic, cells. Correcting a genetic defect in these cells (termed somatic gene therapy) may provide positive benefits to patients but will not affect the genes of future generations. Gene therapy that alters reproductive, or germ-line, cells (termed germ-line gene therapy) is technically possible but raises a number of significant ethical issues because it has the capacity to alter the gene pool of future generations.