The speed at which technology is developing completely outstrips our understanding of the ethical and psychosocial issues that come with it. Most genetic testing has been done on adults; little is known about the psychological effects of childhood genetic testing.
For now, genetic screening of newborns is mainly done for research purposes, so that doctors can follow children with a particular genetic predisposition over time.
It's important that such research include psychologists as researchers need to understand how parents react to the news of their child's genetic predisposition to a disease, because that reaction can affect whether children remain in the study.
There are so many questions testing raises, like the impact on family members' psychological state, behaviour and risk communication. And, as the children age, it will be important to examine the impact on their own emotional status, self-esteem and health behaviours.
Prospective Assessment of Newborns for Diabetes Autoimmunity (PANDA). PANDA researchers have tested more than 4,000 newborns at several University of Florida-affiliated hospitals for specific genes-HLA-DQB1 alleles-that are associated with a higher-than-average risk of developing diabetes. The goal of the study is to follow children with the genes until age 15 to determine what environmental factors influence whether they eventually develop the disease.
The researchers interviewed 435 mothers whose children were identified as having a moderate (approximately 2%), high (5-10%), or extremely high (20-25%) risk of developing diabetes. They talked to the mothers one month and three months after the mothers learned the screening results.
At the one-month interview, 73% of mothers remembered their child's risk level correctly, while 13% underestimated risk, 3% overestimated risk and 10% could not remember at all.
Two months after that, however, only 62% remembered the correct estimate, and 24% underestimated risk. The results, Carmichael says, are consistent with previous studies of genetic testing on adults, which have shown that people tend to minimize risk as a coping mechanism.
Ever since Watson and Crick deciphered the biological code of life, scientists have been busy unraveling the mysteries of life.
A recent development in the area of genetic research has been the Human Genome Project (HGP). The HGP is a massive international effort to map and sequence the entire human genetic code.
The primary goal of this research is to link certain diseases with abnormal genes that may be possessed by certain people. This would allow researchers the ability to screen individuals for certain diseases.
In 1972 scientists first isolated a DNA segment from a virus and combined it with a piece of bacterial DNA. When this gene was placed into a plasmid and introduced into a bacterium, the introduced gene functioned normally. Thus was born the biotechnology of recombinant DNA, the foundation of genetic engineering.
This has already been a success with a number of conditions. PKU is a condition that causes severe retardation in children if nothing is done to prevent it, but by genetically screening the infants, doctors are able to tell who has the disease (Davis 1990).
By simply altering the diet of these children, the mental retardation effects of the disease can be prevented. In addition, diseases such as Huntington’s disease, breast cancer, and muscular dystrophy are presently being screened for in humans (Jaroff, 1996).
New developments have given researchers the ability to decipher the genetic code of organisms. Some of the techniques that researchers use are RFLP (restriction fragment length polymorphism) analysis and DNA probes.
RFLP analysis utilizes enzymes from bacteria that are thought to be used as defense mechanisms against invading viral DNA. The enzymes fragment foreign DNA at specific locations depending on the base sequence (Griffiths, 1996).
In order to analyze an organism’s genome a researcher will add a certain restriction enzyme to DNA. This produces small restriction fragments of DNA that vary in length. Electrophoresis is then used to separate out the various fragments of DNA.
This is accomplished by subjecting the fragmented DNA to an electrical charge after it has been placed onto an agarose gel plate. Due to differences in length, the DNA restriction fragments will be separated in the gel plate.
DNA probes are used to locate and identify genes. Probes utilize the complementary base pairing structure of DNA. The two complementary strands of DNA can denature (separate) and rejoin in exactly the same se¬quence. A free- floating single DNA strand binds only to the appropriate complementary sequence.
Single-stranded DNA fragments can be "labeled" to exhibit color (biotinylated), light (fluorescence), radioactivity, or resistance to antibiotics. When these fragments bind to their complement, the "label " iden¬tifies the target DNA sequence.
From previous research and " DNA libraries" molecular biologists know that certain probes bind to human DNA near certain genes. When used in combination with RFLP analysis, DNA probes can pin¬point mutations or identify parents.
Embryo and fetal screening
The ability of scientists to screen humans for certain genetic abnormalities has led to four situations in which the ethics of genetic screening come into play.
They are embryo and fetal screening, neonatal screening, carrier screening, and testing for economic reasons.
A natural instinct in all parents is to have perfect children. All parents would like to have children that are free from diseases. This has led to screening of children before they are born.
Fetal screening involves taking tissues from a fetus inside the mother’s womb and screening the fetal tissues for genetic abnormalities.
Some of the abnormalities that are tested for are PKU, down’s syndrome, and turner syndrome. The first condition, PKU, is tested for because early detection and treatment prevent the onset of sever retardation in children positive for PKU. The other syndromes are screened for in order to allow the parent to accept the fact that their child may not be normal.
Embryo and fetal screening
The advent of in vitro fertilization has had a tremendous impact on fetal screening. In vitro fertilization technology allows doctors to fertilize a human egg outside the mother.
Cells from the early zygote can then be pulled off and screened for certain genetic abnormalities. Parents now have the ability to have multiple eggs fertilized and have each one screened for abnormalities.
The parents can then choose which zygotes they would like to have implanted into the uterus. This can be viewed as a form of eugenics.
Neonatal screening is similar to fetal screening in that the purpose is to identify genetic abnormalities in which an early treatment could prevent the symptoms of the disease.
PKU is again a good example for what doctors are looking for. Neonatal screening is also done in order to confirm diagnosis in children such as down’s syndrome and turner syndrome.
Screening people to determine if they are a carrier for certain genetic defects. One of the genes that is important in this instance is the gene that codes for Cystic Fibrosis.
People would want to know if they were a carrier for this gene in case they were planning to have a child. If a couple found out that they were both carriers, then they would have to weigh the risks for themselves. Do we want to take the risk of bringing a child with a devastating disease into this world?
Testing for economic reasons
Testing for economic reasons is different from the previous subjects in that it would not benefit the individual in any way.
This would be genetic information that would be used by insurance companies and employers in order to make a profit. Insurance companies would like to have the ability to screen customers in order to determine their dispositions for certain diseases.
They then could charge the individual with a high risk an inflated premium or deny them entirely. Employers would use genetic information to determine which workers would suit their jobs.
Arguments against genetic screening
There are two good arguments that go against genetic screening.
Some feel that genetic screening would lead to discrimination of those individuals, which possess "inferior" genes. Second, people fear that genetic screening will lead to reproductive decisions being based on the genetics of their child.
Discrimination is a very real prospect, now that humans posses the technology to analyze genetic contents.
As discussed previously, insurance companies and employers would like to be able to determine insurance rates and employment statuses based on the genetic composition of people. Individuals may be prevented from obtaining insurance due to a high risk factor for a certain disease. In addition, some diseases such as sickle-cell anemia are predominant among those who are of African American heritage and therefore could lead to racism (Reich, 1995).
Arguments against genetic screening
Many people fear that genetic screening will change the way humans reproduce. Instead of allowing reproduction to occur naturally, people could use fetal and embryonic genetic screening in order to select for a better child.
Secondly, abortion also becomes an issue, because if the parents of an unborn child find out that their child has a certain genetic defect, they may decide to end the pregnancy. In addition, some religions consider any interference with the natural act of reproduction to be immoral. In the Roman Catholic view, any act of reproduction that is not performed by the natural way as immoral (Smith, 1989).
Thirdly, what would happen to individuals who were carriers for genetic abnormalities? Would they be encouraged not to reproduce? In this situation it seems as though the individual would be better off not knowing about their condition.
Arguments for genetic screening
The first argument is that by screening for genetic abnormalities, a doctor can prescribe an early treatment that would allow the person to live a longer more productive life.
If an individual was found to be positive for a cancer-causing gene, then the individual could modify their behaviors in order to prevent the expression of the gene. There is an argument that an individual would probably not want to know if they were predisposed for a condition that was untreatable
. This may be true, but on the other hand, if an individual knows their fate they would be able to make adjustments in their life in order to deal with their condition rather than learning about their condition later on in life. In the case of cystic fibrosis, which is chronic and incurable, the number of patients screened for this disease has risen from 9,000 in 199 to 63,000 in 1992 (Grace, 1997). Therefore people must want to know their fates if the rate of screening for an incurable disease are going up.
Arguments for genetic screening
The obvious argument here is the wonders it could do for medicine.
The procedure that will probably follow genetic screening will probably be genetic engineering.
Mayeux and Schupf state that, "Molecular genetics promises a greater and more precise understanding of how genetic factors influence disease." (1995).
By linking genes to diseases scientists will be able to develop treatments for diseases. The genetic knowledge of the disease process will create a revolution in how medicine is performed.
Many adult-onset genetic disorders are progressive (meaning that they get worse over time) and have long-term health consequences.
Thus, when a person is at risk for such a disorder, he or she may consider undergoing genetic testing.
When the consequences of the specific disorder in question are treatable, most people would agree that genetic testing makes sense. But what about disorders for which no preventative measures or treatments are available? What happens, for instance, when a young adult is found to have the mutation that causes a fatal disorder?
Would such a person still be able to buy insurance or get the job promotion he or she applied for? How would this information affect his or her family and social life? As these questions illustrate, genetic testing for potentially lethal disorders is an area fraught with ethical, legal, and social concerns.
One devastating genetic disorder that exemplifies these difficult ethical and social concerns is Huntington's disease (HD).
Symptoms of HD, which include uncontrolled movements, loss of mental abilities, and emotional disturbances, are caused by the progressive death of neurons in certain areas of the brain.
Death from related complications usually occurs 10 to 30 years following onset of symptoms. There is currently no treatment for this disease, nor is there anything an affected person can do to prevent the inevitable onset of symptoms.
Huntingdon's Disease cont.
HD is an autosomal dominant disorder with complete penetrance; therefore, any child of a person with HD has a 50% chance of developing the disease.
The genetic basis of Huntington's, discovered in 1992, is an expansion of a trinucleotide repeat within the coding region of the huntingtin gene (La Spada et al., 1992; Huntington's Disease Collaborative Research Group, 1993)
Normally, this gene contains between 7 and 35 CAG repeats. In a person with HD, however, the gene contains more than 35 repeats. The age of onset of symptoms is inversely related to the number of repeats; generally, the more repeats that are present, the earlier the age of onset.
A person with 40 CAG repeats can expect the onset of symptoms to occur anywhere from 40 to 70 years of age.
Huntingdon's Disease cont.
HD presents many unique challenges to affected families. Given the age of onset of symptoms, many individuals have already passed the disease to their children before their own diagnosis.
Also, many people with HD have had the experience of seeing a parent, grandparent, or other family member suffer with the condition, due to the high penetrance and founder effect (meaning that de novo mutations are very rare) of HD.
Genetic testing is available to those at risk for the disease and can indicate with certainty whether an individual is affected, but many people opt not to be tested.
Creighton et al (2003) revealed that only 3% to 24% of at-risk individuals get predictive testing. This percentage is surprisingly low, especially given the fact that surveys taken shortly after predictive testing for HD became available indicated that between 66% and 79% of individuals at risk for the disorder would seek genetic testing to determine their status (Mastromauro et al, 1987).
Reproductive and Other Familial Concerns
The decision to undergo genetic testing for an inherited disease is an intensely personal choice, influenced by the perceived treatability and preventability of the disorder, as well as various reproductive implications.
In the case of HD, although there is no way to treat or prevent this condition, knowing one's status could influence many life decisions. For example, if you learned you had inherited the HD mutation, would you decide to have children of your own and risk passing the gene on to your children?
Perhaps you would consider using assisted reproductive technology (ART), such as preimplantation genetic diagnosis, to make sure only unaffected embryos were allowed to develop to term. But what if you already had children?
Would you still get tested? What if test results indicated that you were likely to begin showing symptoms at age 40? How might this affect the way you live your life? Conversely, what if testing revealed that you had not inherited the mutation, but that your siblings and their children had?
Reproductive and Other Familial Concerns
Feelings of guilt and depression are not uncommon in these situations. Finally, what if you chose not to get tested at all?
Research has shown that individuals with a family history of genetic disorders who know they are at risk but choose not to get tested can have difficulties in social interactions (McConkie-Rosell et al., 2008).
Each scenario is complex, especially given the incurable nature of HD.
The decision to undergo genetic testing can only be made by the individual at risk for a disorder. Once a test has been conducted and the results are known, however, a new, family-related ethical dilemma is born: Should a carrier of a known genetic risk be obligated to tell his or her relatives (Forrest et al., 2007; Gaff et al., 2007)?
Reproductive and Other Familial Concerns
This very question has begun to challenge the well-established medicolegal principles of confidentiality and privacy.
Although some people feel that an individual who is found to carry a dominant gene for Huntington's disease has an ethical obligation to disclose that fact to his or her siblings, there currently is no legal requirement to do so.
In fact, requiring someone to communicate his or her own genetic risk to family members who are therefore also at risk is considered by many to be ethically dubious.
Genetic Testing and Privacy Concerns
Another important consideration when deciding whether to undergo genetic testing is the possibility that if someone knows you are likely to develop a genetic disorder in the future, he or she could use that information against you.
For example, if an employer knows that an employee is likely to be diagnosed with cancer or HD, the employer might not want to retain that employee. Similarly, a person who is known to have a high risk for a genetic condition may have difficulty obtaining insurance because he or she is likely to run up medical bills that would be costly to the insurance company.
Because we cannot control our genes, it is unfair to discriminate against a person's genetic predispositions. In the United States, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) was the first federal law to provide protections against genetic discrimination, but its intentions fell short.
Genetic Testing and Privacy Concerns
Specifically, under HIPAA, insurance companies were not prevented from charging higher rates to customers based on genetic information, nor were they prevented from collecting genetic data or requiring applicants to undergo genetic testing. Thus, a more comprehensive federal measure, the Genetic Information Nondiscrimination Act (GINA), was signed into law in May 2008 (Allison, 2008).
GINA, spearheaded by members of Congress like Representative Louise Slaughter, GINA took ten years to pass. Ideally, now that the legislation is law, the protections provided by this act will foster an atmosphere in which Americans feel safe to take advantage of appropriate genetic testing, as well as to share test results with any other at-risk family members.
Genetic Testing is a Matter of Individual Choice
In summary, the choice to undergo genetic testing is a highly personal one. A person's decision depends on various factors, including the perceived preventability and treatability of the disorder and one's ability to make constructive life changes with the information one gains from testing.
On one hand, testing can help people make family planning decisions and other life choices, like when to retire or how much money to put away for the future. However, finding out that you are at a higher risk for developing treatable diseases such as cancer or that you carry a gene for an untreatable, fatal disorder such as HD can have negative social consequences.
Moreover, it can open the door for potential discrimination. Hopefully, with the recent passage of GINA in the U.S., more Americans will feel comfortable working with physicians and genetic counselors to undergo any genetic tests that contribute to better management of their health care and health choices.
There is probably no force in a society more powerful than the acquisition of information. The very essence of genetics is, of course, information (genotype and phenotype) on individuals and their families. As modern genetics probes deeper and deeper into the essence of the human genome, the science of genetics will come to possess an information base with power and opportunity for use undreamed of only a few years ago.
Along with this power and opportunity comes responsibility. Genetic intervention techniques such as genetic engineering, human gene therapy, and genetic screening raise many questions. Since these techniques change the flow of information at the level of molecules, the level of individuals, and at the level of societies it is wise to consider to what extent we want to apply these technologies and to reflect on what changes we are seeking. A pertinent question to ask might be whether a technology should be used just because it is available. We need to exercise judgment in our pursuit of these technologies. We also need to understand the options the new genetic technologies will offer so that we can make informed decisions at the individual, local, state, national, and international levels.
The majority of researchers and ethicists agree on the importance of diagnosing a disease such as Lesch-Nyhan syndrome, which strikes soon after birth and produces a short, brutally painful life characterized by severe retardation, violence, and self-mutilation. Few ethicists see a problem in prenatal screening for such conditions as long as abortion is a legally obtainable option. But the issues are different in diagnosing a disorder such as familial Alzheimer's disease which produces no symptoms until it s trikes as early as age 45, or in the case of polycystic kidney disease which produces no symptoms until adulthood and even then progresses slowly. This ability to detect presymptomatic genetic conditions, susceptibility to genetic diseases such as hyperchlosterol or alcoholism, or the ability to identify carriers of recessively inherited conditions such as cystic fibrosis, poses new challenges to the ethical frameworks that had previously been established to deal with controversial detection programs.
Eugenics. Social or political pressure may be applied to people to make childbearing decisions on the basis of genetic information. Mating between those with valued genes may be encouraged while mating between two people with dangerous recessive traits may be prohibited. Women carrying fetuses with genetic abnormalities may be encouraged to abort.
As we consider these questions it would be wise to remember that less than half of all disease and disability is thought to be caused by genetic factors. Each human is also thought to carry about five recessive genes for lethal disorders. We will probably discover that all of us carry a large number of genes that predispose us to various conditions. We all share the human condition. We will, all of us, become ill at various times. We all will, with certainty, grow old and die. Perhaps this fact alone will temper our judgment about who will be screened for genetic disease for we might find ourselves weighed in the balance.
Cancer is a heterogeneous disease that will claim more than 560,000
lives in our country this year. Lung cancer is the most common fatal cancer in men (31%), followed by prostate cancer (10%), and colon & rectum cancer (10%). In women, lung (27%), breast (15%), and colon & rectum (10%) are the leading sites of cancer death.
Cancer is not a single disease.Rather, any cancer may involve: multiple tissue lineages or an aberrant expression of genes with a variety of cellular functions.
Variation in the number of deregulated genes cancer is a genetic disease.
All cancers involve genetic changes in somatic cells, the germ line, or both.
Cancer Genes Most gene mutations in cancer occur in somatic cells and are acquired (multifactorial etiology). However, some mutations do occur in the germline and may be inherited and passed on to future generations.
Individuals genetically predisposed to cancer account for 5-10% of the cancer population.
Features suggesting an inherited predisposition to cancer: Two or more close relatives affected, an early age of onset, cancers of a specific type occurring together (breast and ovary) and multiple or bilateral cancers occurring in one person.
Two major susceptibility genes for breast cancer, BRCA1 and BRCA2 have been identified. Mutations in these genes account for 3-5% of all breast cancers.
Breast cancer can be prevented with nedication such as tamoxifen, aromatase-inhibitors and with oral contraceptives.
Invasive procedures can be undertaken such as prophylactic surgery- i.e. prophylactic mastectomy reduces risk by 90% and prophylactic salpingo-oophorectomy reduces risk by 96%.
Genetic testing for cancer susceptibility is an application of biotechnology that has the potential both to improve the psychosocial and physical wellbeing of the population and to cause significant psychosocial and physical harms.'
Both the benefits and harms of these tests lie not as much in the tests themselves, as in their power to predict or alter the future.
First, the voluntary and optional nature of testing should be emphasized. Second,
participants should be told about the limitations of testing as well as the potential benefits. These limitations include the accuracy of current diagnostic technologies,
the fact that test results cannot provide definitive information about whether or when cancer will develop (for example, incomplete penetrance), and limitations in available options for prevention and surveillance.
Discussion of risks should include the potential for anxiety, altered family relationships, stigmatization, and discrimination.'" But, characterizing these social risks, qualitatively and quantitatively, in a consent process is challenging.
For example, the disclosure of the presence of a BRCAl mutation to a physician
may be necessary for obtaining earlier or more frequent mammograms. There was consensus that participants should be informed that such discussions may result in information being recorded in their medical records and that such recording would increase the chances of third parties gaining access to test results.
Additionally, even if the information is not placed in medical records, in most states,
insurers or others are not prohibited from requesting this information directly from individuals.
When participants want to disclose this information to family members, they may be uncertain about how to proceed. Thus, one important part of counseling may be
to discuss possible strategies for effective communication with family members about test results. It may be useful to develop pamphlets or letters that give suggestions to participants about how to communicate this information, as well as to provide specific pamphlets or letters that could be given to relatives.
Requests for testing of children
A consensus is emerging that genetic testing for adult-onset diseases should generally be deferred until adulthood.^"
Children cannot provide consent, so they must rely on surrogate decision-makers. Children may be uniquely vulnerable to the psychosocial risks of testing because they are undergoing the developmental processes of acquiring a selfimage and independence.
The central issue is whether the potential benefits of testing outweigh the potential harms. Although parents are usually in the best position to make such determinations, there are little data about the impact of such information on children and their families.
What is a cancer genetic susceptibility test? It is a test involving analysis of DNA for mutations in one or more specific genes that confer a susceptibility to a given type of cancer.
It is generally performed on a blood sample, but sometimes can be performed
on surgical or autopsy material if blood is not available.
Who should consider testing?
Generally only a person with a family history of a specific type of cancer or cancer syndrome. The person tested may or may not have had cancer. For example, a family history of breast or ovarian cancer may prompt BRCA testing, whereas a family history of colorectal cancer may lead to testing for hereditary nonpolyposis colorectal cancer or familial polyposis.
There are currently about a dozen familial cancer susceptibility syndromes for which DNA testing is commercially available.