The National Academy of Science defines genetic screening as the systematic search of a population for persons with latent, early, or asymptomatic disease. The term genetic testing is often used interchangeably, but differs in that it only targets those individuals believed to be at high risk for an inherited condition. Genetic screening has a much broader target population. As genetic screening becomes easier, faster, and less expensive, there is a growing debate about who should be tested, what those results should be used for, and who should have access to those results. Before addressing these questions it is necessary to understand the basic processes involved in genetic screening.
The techniques used for genetic screening are based on the recognition of nucleotide sequences in the DNA. The most commonly used method is called restriction fragment length polymorphisms (RFLP). RFLP uses restriction enzymes to cleave the DNA at specific sequences. Cleavage of the DNA generates small restriction fragments of varying length. Electrophoresis is then used to separate the fragments with respect to size and/or charge. The sample is added to an agarose gel plate which is electrically charged for a specific length of time. The smaller and more negatively charged fragments move to the positively charged pole the quickest. A banding pattern with many bands is generated. The bands are then transferred to a nylon membrane by Southern Blot. A radiolabled probe which binds specifically to a sequence of interest is added to the membrane. The banding pattern can now be observed and specific sequences identified. The problems with RFLP are that it is expensive and time consuming. RFLP is the process used for DNA fingerprinting. In this case, probes which are specific for variable number tandem repeats (repeated sequences in the gene) are used because VNTR's are individual specific.
Another technique often used for genetic screening is Polymerase Chain Reaction (PCR). PCR requires only a very small amount of DNA. Theoretically a single molecule could be used. PCR selectively amplifies a specific region of DNA. Initially double-stranded DNA is heated to denature the hydrogen bonds which hold the strands together. Two single-stranded DNA sequences are generated. The strands are rapidly cooled, and an RNA primer which targets the sequence of interest is allowed to bind to the DNA strands. DNA polymerase then copies the strands. The result is two double-stranded DNA molecules. This cycle is repeated, and the amount of DNA is doubled each time. At present, techniques such as RFLP and PCR are still somewhat time consuming and costly, especially when dealing with many sequences, but it is probable that in the near future the cost and effort required will be greatly reduced. Through the use of DNA chip technology, in which strands of DNA are placed on a silicon substrate, a sample could be simultaneously checked for the presence or absence of an almost unlimited number of sequences (Beese). Such a powerful technique raises many ethical and legal questions.
Before genetic screening goes any further, a variety of issues need to be resolved. In order to resolve the problems associated with genetic screening, we must examine both the benefits and dangers inherent to the process. Three majors areas of concern are: (1) discrimination based on genetic screening results; (2) the type of consent required to screen newborns; (3) will gene frequencies of populations change due to people basing reproductive decisions on genetic makeup.
Once an individual is diagnosed with an allele which could lead to a genetic disease, he would have the option to change his lifestyle for the better. That person can take precautions to reduce the severity of the illness. In the case of PKU, something as simple as a modified diet early in life can prevent lifelong mental retardation. If there are no preventative measures to be taken, the person can at least be aware and watch for symptoms of onset of the disease. Early diagnosis of certain diseases can quite often reduce the severity. The problem with diagnosis of disease causing alleles lies in who has access to the information. There is a high potential for discrimination based on genetic makeup. If insurance companies are allowed access to genetic profiles, they could charge higher rates or completely deny insurance to carriers of certain alleles. Many jobs may become unavailable to people with deleterious alleles even if they never develop the disease. If employers are allowed access to genetic information, a large portion of the population could be seen as high liability and unemployable. Some people believe that discrimination will not occur because eventually everyone will be a carrier of some genetic anomaly.
Many hospitals currently screen newborns for certain diseases such as PKU and sickle-cell anemia. The samples that are taken are then archived, and could potentially be used for research on gene structure and population genetics. Although the samples represent a huge wealth of data, the privacy of the individual also needs to be taken into consideration. The requirement of parental consent for research use of the samples could be handled in several different ways: (1) the parent could be required to sign a consent form; (2) the samples could be used anonymously without consent; or (3) the individual could sign a consent form once he is old enough to understand the ramifications of his decision. There is also the question of how to deal with samples that have already been obtained.
Another concern is that people will base decisions of reproduction on genetic makeup. Certain genetic diseases could be eliminated if parents who are carriers decide not to reproduce. The elimination of deleterious alleles may seem like a great idea, but it could prove to be very dangerous if all of the genetic interactions aren't clearly understood. One danger is the elimination of deleterious alleles that provide benefits when present in the heterozygous condition. Another danger would simply be the reduction of genetic diversity in the population. The lower the genetic diversity of a population the less adaptable that population will be to changing conditions. Some people also fear the very extreme "Brave New World" scenario In which people are selectively bred for traits predisposing them to their assigned task in life.
Despite the possible dangers, I feel that it is still valid to use genetic screening. The information gathered by this process would be an extremely useful tool, and could be used to determine how alleles work and control specific traits. The problems associated with screening can be greatly reduced if the information is used and stored in a responsible manner. The highest precautions should be taken to assure that no one has access to the information without the consent of the individual. If the screening results are stored in a computer database, they should be encoded. By limiting access, the potential for people to base judgments on information they are not qualified to interpret will be greatly reduced. If a genetic profile were to fall into the wrong hands, not only would it compromise the welfare of the individual, but also that persons relatives. Because of this danger, harsh penalties should be established for any misuse or unauthorized access of private genetic information.
Consent for use of previously collected samples and newly collected samples for research purposes would have to be handled in different ways. Parental consent should be required for all newly collected samples. The parent should be able to give separate consent for private use of the sample to ensure that the child has no genetic diseases and for research purposes. It could also be broken down further so the parent could allow the sample to be used for certain types of research and not others. In order for this system to work, the consent form would have to be worded very clearly so that parents with no background in genetics could easily understand to what they are agreeing. The samples which have already been collected will have to be treated differently. Ideally all of the parents or individuals themselves would be contacted for consent. Such a task would be extremely impractical if not impossible, therefore previously collected samples should be allowed to be used anonymously for research.
I do not believe that the knowledge of genetic information will affect the decision to reproduce to the extent that alleles will actually be eliminated. Many people will probably not even know their exact genetic makeup. Those who do may decide to have children regardless of the risks. Due to these situations, the elimination of an allele from a human population would be very unlikely. There is also a high likelihood of gene flow occurring between populations because people are highly mobile. Gene flow between populations would act to increase diversity and counteract any reduction of alleles that is taking place.
Genetic screening is a powerful technology. Many risks are involved, but they can be easily reduced by responsible management of information. The information that can be gained with the aid of genetic screening far outweighs the risks.
Southeastern Regional Genetics Group
National Center for Genome Resources