Genes, Technology and Policy/Applications in Medicine

What are the applications of modern biotechnology in the medical field?
In medicine, modern biotechnology finds promising applications in:


 * Pharmacogenomics
 * Drug Production
 * Genetic Testing
 * Gene Therapy

What is pharmacogenomics? What are its anticipated benefits?
Pharmacogenomics is the study of how the genetic inheritance of an individual affects his/her body’s response to drugs. It is a coined word derived from the words “pharmacology” and “genomics”. It is therefore the study of the relationship between pharmaceuticals and genetics. The vision of pharmacogenomics is to be able to design and produce drugs that are adapted to each person’s genetic makeup.

Pharmacogenomics results in the following benefits:

1. Development of tailor-made medicines. Using pharmacogenomics, pharmaceutical companies can create drugs based on the proteins, enzymes and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize therapeutic effects but also to decrease damage to nearby healthy cells.

2. More accurate methods of determining appropriate drug dosages. Knowing a patient’s genetics will enable doctors to determine how well his/ her body can process and metabolize a medicine. This will maximize the value of the medicine and decrease the likelihood of overdose.

3.Improvements in the drug discovery and approval process. The discovery of potential therapies will be made easier using genome targets. Genes have been associated with numerous diseases and disorders. With modern biotechnology, these genes can be used as targets for the development of effective new therapies, which could significantly shorten the drug discovery process.

4. Better vaccines. Safer vaccines can be designed and produced by organisms transformed by means of genetic engineering. These vaccines will elicit the immune response without the attendant risks of infection. They will be inexpensive, stable, easy to store, and capable of being engineered to carry several strains of pathogen at once.

''Box 2. Selected Recombinant Products for Disorders Affecting Large Patient Populations''

Figure 5 Source: Feldbaum, C. (8 February 2002). Some History Should Be Repeated, 295 SCIENCE, at 975

How does biotechnology contribute to drug production?
Modern biotechnology can be used to manufacture existing drugs more easily and cheaply. The first genetically engineered products were medicines designed to combat human diseases. To cite one example, in 1978 Genentech joined a gene for insulin and a plasmid vector and put the resulting gene into a bacterium called Escherichia coli. Insulin, widely used for the treatment of diabetes, was previously extracted from sheep and pigs. It was very expensive and often elicited unwanted allergic responses. The resulting genetically engineered bacterium enabled the production of vast quantities of human insulin at low cost.

Since then modern biotechnology has made it possible to produce more easily and cheaply the human growth hormone, clotting factors for hemophiliacs, fertility drugs, erythropoietin and other drugs. Most drugs today are based on about 500 molecular targets. Genomic knowledge of the genes involved in diseases, disease pathways, and drug-response sites are expected to lead to the discovery of thousands more new targets.

What is genetic testing?
Genetic testing involves the direct examination of the DNA molecule itself. A scientist scans a patient’s DNA sample for mutated sequences.

There are two major types of gene tests. In the first type, a researcher may design short pieces of DNA (“probes”) whose sequences are complementary to the mutated sequences. These probes will seek their complement among the base pairs of an individual’s genome. If the mutated sequence is present in the patient’s genome, the probe will bind to it and flag the mutation. In the second type, a researcher may conduct the gene test by comparing the sequence of DNA bases in a patient’s gene to a normal version of the gene.

What are the potential uses of genetic testing?
Genetic testing can be used to:


 * Diagnose a disease.


 * Confirm a diagnosis.


 * Provide prognostic information about the course of a disease.


 * Confirm the existence of a disease in individuals.


 * With varying degrees of accuracy, predict the risk of future disease in healthy individuals or their progeny.

Genetic testing is now used for:


 * carrier screening, or the identification of unaffected individuals who carry one copy of a gene for a disease that requires two copies for the disease to manifest


 * prenatal diagnostic screening


 * newborn screening


 * presymptomatic testing for predicting adult-onset disorders


 * presymptomatic testing for estimating the risk of developing adult-onset cancers


 * confirmational diagnosis of symptomatic individuals


 * forensic/identity testing

Are genetic tests now available in the market?
Some genetic tests are already available, although most of them are used in developed countries. The tests currently available can detect mutations associated with rare genetic disorders like cystic fibrosis, sickle cell anemia, and Huntington’s disease. Recently, tests have been developed to detect mutation for a handful of more complex conditions such as breast, ovarian, and colon cancers. However, gene tests may not detect every mutation associated with a particular condition because many are as yet undiscovered, and the ones they do detect may present different risks to different people and populations.

What is gene therapy?
Gene therapy may be used for treating, or even curing, genetic and acquired diseases like cancer and AIDS by using normal genes to supplement or replace defective genes or to bolster a normal function such as immunity. It can be used to target somatic (i.e., body) or germ (i.e., egg and sperm) cells. In somatic gene therapy, the genome of the recipient is changed, but this change is not passed along to the next generation. In contrast, in germline gene therapy, the egg and sperm cells of the parents are changed for the purpose of passing on the changes to their offspring.

How is gene therapy done?
There are basically two ways of implementing a gene therapy treatment:

1. Ex vivo, which means “outside the body” – Cells from the patient’s blood or bone marrow are removed and grown in the laboratory. They are then exposed to the virus carrying the desired gene. The virus enters the cells, and the desired gene becomes part of the DNA of the cells. The cells are allowed to grow in the laboratory before being returned to the patient by injection into a vein.

2. In vivo, which means “inside the body” – No cells are removed from the patient’s body. Instead, vectors are used to deliver the desired gene to cells in the patient’s body.

How extensive is the use of gene therapy?
Currently, gene therapy use is limited. Somatic gene therapy is primarily at the experimental stage. Germline therapy is the subject of much discussion but it is not being actively investigated in larger animals and human beings.

As of June 2001, more than 500 clinical gene-therapy trials involving about 3,500 patients have been identified worldwide. Around 78% of these are in the United States, with Europe having 18%. These trials focus on various types of cancer, although other multigenic diseases are being studied as well. Recently, two children born with severe combined immunodeficiency disorder (“SCID”) were reported to have been cured after being given genetically engineered cells.

What are the obstacles to the widespread use of gene therapy techniques to treat patients?
Gene therapy faces many obstacles before it can become a practical approach for treating disease. At least four of these obstacles are as follows:

1. Gene delivery tools. Genes are inserted into the body using gene carriers called vectors. The most common vectors now are viruses, which have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists manipulate the genome of the virus by removing the disease-causing genes and inserting the therapeutic genes. However, while viruses are effective, they can introduce problems like toxicity, immune and inflammatory responses, and gene control and targeting issues.

2. Limited knowledge of the functions of genes. Scientists currently know the functions of only a few genes. Hence, gene therapy can address only some genes that cause a particular disease. Worse, it is not known exactly whether genes have more than one function, which creates uncertainty as to whether replacing such genes is indeed desirable.

3. Multigene disorders and effect of environment. Most genetic disorders involve more than one gene. Moreover, most diseases involve the interaction of several genes and the environment. For example, many people with cancer not only inherit the disease gene for the disorder, but may have also failed to inherit specific tumor suppressor genes. Diet, exercise, smoking and other environmental factors may have also contributed to their disease.

4. High costs. Since gene therapy is relatively new and at an experimental stage, it is an expensive treatment to undertake. This explains why current studies are focused on illnesses commonly found in developed countries, where more people can afford to pay for treatment. It may take decades before developing countries can take advantage of this technology.

What is the Human Genome Project?
The Human Genome Project is an initiative of the U.S. Department of Energy (“DOE”) that aims to generate a high-quality reference sequence for the entire human genome and identify all the human genes.

The DOE and its predecessor agencies were assigned by the U.S. Congress to develop new energy resources and technologies and to pursue a deeper understanding of potential health and environmental risks posed by their production and use. In 1986, the DOE announced its Human Genome Initiative. Shortly thereafter, the DOE and National Institutes of Health developed a plan for a joint Human Genome Project (“HGP”), which officially began in 1990.

The HGP was originally planned to last 15 years. However, rapid technological advances and worldwide participation have accelerated the expected completion date to 2003. In June 2000, scientists announced the generation of a working draft sequence of the entire human genome. The draft provides a road map to an estimated 90% of genes on every human chromosome. Already it has enabled gene hunters to pinpoint genes associated with more than 30 disorders.

What is human cloning?
Human cloning is one of the techniques of modern biotechnology. It involves the removal of the nucleus from one cell and its placement in an unfertilized egg cell whose nucleus has either been deactivated or removed.

There are two types of cloning:

1. Reproductive cloning. After a few divisions, the egg cell is placed into a uterus where it is allowed to develop into a fetus that is genetically identical to the donor of the original nucleus.

2. Therapeutic cloning. The egg is placed into a Petri dish where it develops into embryonic stem cells, which have shown potentials for treating several ailments.

The major differences between these two types are shown in Figure 6.

In February 1997, cloning became the focus of media attention when Ian Wilmut and his colleagues at the Roslin Institute announced the successful cloning of a sheep, named Dolly, from the mammary glands of an adult female. The cloning of Dolly made it apparent to many that the techniques used to produce her could someday be used to clone human beings. This stirred a lot of controversy because of its ethical implications.

Figure 6. Comparison of Therapeutic Cloning and Human Reproductive Cloning

What are the concerns regarding the use of modern biotechnology techniques in medicine?
Several issues have been raised regarding the use of modern biotechnology in the medical sector. Many of these issues are similar to those facing any new technology that is viewed as powerful and far-reaching. Some of these issues are:

1. Absence of cure. There is still a lack of effective treatment or preventive measures for many diseases and conditions now being diagnosed or predicted using gene tests. Thus, revealing information about risk of a future disease that has no existing cure presents an ethical dilemma for medical practitioners.

2. Ownership and control of genetic information. Who will own and control genetic information, or information about genes, gene products, or inherited characteristics derived from an individual or a group of people like indigenous communities? At the macro level, there is a possibility of a genetic divide, with developing countries that do not have access to medical applications of biotechnology being deprived of benefits accruing from products derived from genes obtained from their own people. Moreover, genetic information can pose a risk for minority population groups as it can lead to group stigmatization.

At the individual level, the absence of privacy and anti-discrimination legal protections in most countries can lead to discrimination in employment or insurance or other misuse of personal genetic information. This raises questions like, is genetic privacy different from medical privacy?

3. Reproductive issues. These include the use of genetic information in reproductive decision-making and the possibility of genetically altering reproductive cells that may be passed on to future generations. For example, germline therapy forever changes the genetic make-up of an individual’s descendants. Thus, any error in technology or judgment may have far-reaching consequences. Ethical issues like designer babies and human cloning have also given rise to controversies between and among scientists and bioethicists, especially in the light of past abuses with eugenics.

4. Clinical issues. These center on the capabilities and limitations of doctors and other health-service providers, people identified with genetic conditions, and the general public in dealing with genetic information. For instance, how should the public be prepared to make informed choices based on the results of genetic tests? How will genetic tests be evaluated and regulated for accuracy, reliability, and usefulness?

5. Effects on social institutions.Genetic tests reveal information about individuals and their families. Thus, test results can affect the dynamics within social institutions, particularly the family.

6. Conceptual and philosophical implications regarding human responsibility, free will vis-à-vis genetic determinism, and the concepts of health and disease. Do genes influence human behavior? If so, does genetic testing mean controlling human behavior? What is considered acceptable diversity? What is normal and what is a disability or disorder, and who decides these matters? Are disabilities diseases that need to be cured or prevented? Where should the line between medical treatment and enhancement be drawn? Who will have access to gene therapy?