The history of the past, present and future is wired indelibly in the merger of the genetic information you inherit from both parents. Within each cell in the human body is located the primal genetic code that will determine everything from hair color, to eye color, to height, to bone structure, to personality, to predisposition or susceptibility to disease. The chromosomes, contained in the nucleus of the cell harbor the nucleic acid DNA - deoxyribonucleic acid, which is the hereditary material of most organisms. The chromosome is divided into units called genes, each gene being responsible for a particular trait. In biochemical terms, each gene is responsible for the manufacture
of the particular protein that is involved in the development of a trait.
If a gene is defective or faulty the mechanism may produce the symptomatology of a genetic disease. Each of the more than 3,000 genetic disorders is comparatively rare, unfortunately collectively they are prevalent as the actuarial information concludes:
· 20 million Americans are carriers of true genetic defects.
There are four mechanisms by which genetic defects may be transmitted from one generation to another: Autosomal dominant inheritance, where the trait is inherited from one parent and from the previous generation, presenting a 50% risk that each child will be symptomatic of the defect, though it may not be evident at birth. There are
about 2,000 confirmed or suspected autosomal dominant disorders. Recessive inherited diseases ironically present parents who are asymptomatic, yet whose double carrier status reinforces the defect and their offspring are each exposed to a 25% risk of manifesting the disease, and a 50% chance of being a clinically normal carrier.
X-linked inheritance in which the gene for the characteristic trait is carried only by the mother and the disease will present itself only in the male offspring. Multifactorial inheritance provides a less intrinsic pattern of transmission, however these
genetic disorders result from the interaction of many genes with other genes or with environmental factors.
These statistics are compounded in populations that maintain an insularity in marrying within the same community, thereby exaggerating the possibility of a carrier marrying a carrier, whereas marrying out of the community may have diluted the impact of carrier status. Such is the case in the Eastern European Ashkenazi Jewish community
that has maintained a very successful intramarriage rate. Ironically by virtue of that commitment, initial mutant genes have been reinforced and have produced a litany of diseases that randomly reappear within the Ashkenazi Jewish population. The roster includes: Tay-Sachs, Gaucher Disease, Niemann-Pick, Canavan's Disease, Fanconi's Anemia, Familial Dysautonomia, etc.
Since the early 1980's Chevra Dor Yeshorim, founded by Rabbi Eckstein, has with Rabbinical endorsements across the spectrum, established a confidential clearinghouse for genetic testing in the Jewish community. Dor Yeshorim currently screens for the recessive diseases: Tay Sachs, Canavan's Disease, Fanconi's Anemia, and cystic fibrosis with a single blood draw. If specifically requested by family members who have determined a family history, screening for Gaucher's, a non-fatal disease, can be arranged as well. Blood samples are forwarded to independent laboratories whose stringent quality control measures and procedural guidelines are routinely reassessed
for accuracy. Dor Yeshorim was initially primarily concerned with screening for Tay-Sachs because of the disproportionate proliferation of carrier status in the Ashkenazi community; 1 in 25 rank as carriers. Traditional Tay-Sachs is a fatal genetic disorder that causes the progressive destruction of the central nervous system due to lack of a crucial enzyme that allows for the breakdown of neurotransmitters so that they don't accumulate in the cells. It results in brain disease that presents itself at about six
months of life with the hallmark failure to thrive, and progresses with mental and motor deterioration. Babies become very floppy and regress to blindness, seizures, muscle weakness and a vegetative state. It is a very prolonged and painful death that squeezes
every last drop of life from the child and every last breath of joy and happiness from the birth of a child, from the parents.
The life expectancy of a Tay-Sachs baby is between 3 and 7 years of heartbreaking agony witnessing a child waste away measure by measure, degree by degree. Before Dor Yeshorim's landmark activism the Tay-Sachs unit of a local hospital was filled to capacity with dying Jewish babies. Dor Yeshorim has nearly eradicated Tay-Sachs
from our vocabulary, and seeks to extrapolate that success to other genetic diseases that plague the Jewish community.
Canavan's disease, also called spongy brain degeneration, destroys myelin, the insulating sheath surrounding nerve cells. The myelin disintegrates so thoroughly that the brain's electrical signals cannot sweep along nerve processes properly, thereby thwarting the development of virtually every function controlled by the nervous system. Such that messages are sent but never received because the bridge is broken. Children with Canavan's cannot sit, walk, or talk and most die before the age of 5. While other parents watch the progress and developmental strides and enjoy the nachas
of the first babblings, the first wary steps, the joy of a smile, parents of children with Canavan's watch their children die.
Cystic fibrosis is the number one genetic killer of children. CF is a debilitating disease inherited from parents with recessive CF genes and results in the body producing atypical amounts of thick, sticky mucus that clog the lungs and pancreas, interfering
with breathing and digestion. Symptomatology is characterized by persistent cough, recurrent wheezing, having pneumonia more than once, excessive appetite but poor weight gain, salty-tasting skin. CF is diagnosed by measuring salt content in sweat. The
recurrence of the CF gene is not reserved to the Ashkenazi population however it is a preponderant disease found among white populations. An estimated 12 million Americans - 1 in 20 - are asymptomatic carriers of the gene that causes CF. The average lifespan is 21 years, however, some victims survive to age thirty-five or so.
In Fanconi's anemia the bone marrow produces severely reduced amounts of red and white blood cells. Additionally, the disease may progressively mutate to leukemia and lymphoma. At present, the sole effective long-term treatment for the disease is a bone
marrow transplant available only to relatively few FA victims with a sibling whose bone marrow provides an identical match.
Niemann-Pick resembles Tay-Sachs symptomatology and in early findings was mistaken for Tay-Sachs, however it presents itself in infancy and results in an enlarged liver and spleen, enlarged lymph glands, swelling and a darkening of the skin and face. Brain and nervous impairment, and a maximum life expectancy of 2-3 years herald
the grim prognosis.
The plethora of screening prerogatives attempts to prevent the potential heartbreak of the pairing of incompatible carriers. When we survey the dating/shidduch scene it poses another consideration rather than obstacle in the determination of a successful shidduch. "It is no different than immunizing children or than using science to cure deadly diseases," explains Dr. Yaakov Friedman, Chairman of Critical Care Medicine at Providence Hospital in Chicago, and Chicago liason for Dor Yeshorim. Though as Dr. Friedman confides, there is a very slim, nearly singular, minority of Rabbi/s who prefer not to affix their endorsement to the Dor Yeshorim program
because they insist that "how do you know Moshiach won't come from one of these unfortunate pairings of incompatible carriers?". Most couples don't presume to play G-d, however most don't presume to gamble against these very terrifying odds.
As Dr. Friedman confirms, "Unfortunately, some couples wait till the last minute to confirm their compatibility. They'll call in their confidential numbers when they're on the verge of announcing their engagement and have invested a significant emotional attachment. Then they're under stress and we're under duress. It's not fair and occasionally very painful. Recently a couple who were about to confirm their engagement, broke it off instead. They were informed they were incompatible. The 'are you sure's' went back and forth for days. Eventually they decided to go for independent lab testing which only confirmed their fears. If they had checked their numbers
in a timely manner, at the latest after the first or second date before any emotional bonds are activated, they would have been spared much anguish." Startlingly, another couple who were confirmed incompatible and were stringently advised to break their engagement, refused to do so and were married, intentionally putting
themselves in harm's way.
Geneticists and doctors are pondering corresponding ethical dilemmas in the proliferation of genetic screening options that have besieged the medical consumer. Previously, the objective of genetic screening was only to provide those who were thinking of having a family with an informed choice. However, over the past decade geneticists have excavated a hoard of genes responsible for human ailments.
As genetic testing becomes largely available to the public, nearly mainstreamed, the moral and ethical considerations coincide with the infinite potential of the findings.
Currently there are testing options available that screen for mutations that may raise the risk of breast, colon and thyroid cancers and melanoma, a virulent skin malignancy, as well as Alzheimer's disease, diabetes, cardiovascular disease, etc. Contending that
information is power that would contribute to more vigilant monitoring of affected individuals, proponents have foisted their arguments on the Ashkenazi community with the discovery of BRCA1, the breast cancer gene that seems to recur predominantly in Ashkenazi Jewish women. A study of 858 healthy Ashkenzai women published one year
ago found that eight carried the same mutation in BRCA1. Given that the more than 100 mutations identified in the gene vary significantly from family to family, the statistics are remarkable. To add insult to injury researchers recently divulged that at least 3 in 1,000
Ashkenazi Jews might carry a specific alteration in BRCA2, the other gene indicted in breast cancer. However, medical and legal specialists caution that the new tests have generated a quagmire of ethical quandries.
Studies indicate that individuals who present with BRCA1 have an 85% chance of developing the disease by age 85. The risk in the general population bottoms out at 10%. Furthermore, the findings profess that BRCA1 mutations seem to inflate the lifetime risk of ovarian cancer to nearly 50%, as opposed to the 1% risk in
the general population. Experts are concerned about the application of these statistics. In classic genetic disorders involving a mutation in a single gene, the presence of said gene virtually confirms the diagnosis. However, conventional medical wisdom indicates
that the most common killers such as cancer and Alzheimer's disease are resultant from the interplay of mutations or flaws in various genes and environmental factors. It follows, that inheriting a singular flawed gene related to these diseases does not confirm
or deny its potential ramifications. Generally, the genetic alterations linked to cancer do impact significantly on a carrier's risk, however, we've discerned the test before the cure or the treatment. How can we in good conscience inform an individual of a predisposition to a disease that he may never develop, and for which no preventive
medicine has been assigned?
There is another crucial issue that we must examine, that of confidentiality. Dor Yeshorim circumnavigates the destructive peripherals of adverse genetic information by insisting on the most stringent anonymity. Individuals are not informed of their carrier status rather they submit anonymous I.D. codes for comparitive analysis, and unless
they have been confirmed as incompatible, and dual carrier status is obvious, no one individual will be informed of his individual carrier status. Unfortunately, the information gleaned from other genetic testing, lacking confidentiality, could conceivably come
to be appraised by employers and insurance companies to your detriment, much the same way every minute detail of your credit report is available to mortgage lenders, loan officers, credit card companies, etc.
The fragmented data could thus prove hazardous to your insurability and your employability. Who would want to hire an employee who may develop early-onset Alzheimer's, or potentially be laid up for months at a time from cancer treatments? Though you may be absolutely asymptomatic and totally well, knowledge of your gene
status would put you in a high risk category. Genetic discrimination is very real and very dangerous. If you've recently applied for life insurance you are well aware of the physical you must undergo, and the blood sample you must provide, in addition to the comprehensive medical and family history. You must include any surgical procedures
you're parents have had within the last three years, etc. What if insurers could test your blood for objectionable genes, as well, to better determine their risk? What if health insurers could deny acceptance, not for preexisting conditions, but for
postexisting diseases that may never present themselves? In the worst case scenario genetic screening could create the emergence of an underclass of marked "untouchables" who would be genetically inferior, a remarkably potent consideration for the international Jewish community which was plagued by Hitler's
purported scientific analysis of the genetics of race. And what about the emotional factor? How does a patient emotionally reconcile an 85% risk of developing a disease? Ironically a negative result for the BRCA1 and BRCA2 markers does not conclude that you are risk-free. Inherited breast cancers account for only 5-10% of
all diseased findings.
Much of the current trends in genetic screening provide circumstantial evidence at best. The fact that a woman from a family with a history of cancer tests positive for one of the cancer-linked DNA variants does not mean that she will definitely have a tumor, even though her lifetime risk of breast cancer may be as high as 85%. With an increasing number of the "hows" of tumor development addressed, researchers are confused by the "whys". Cancer is basically 100% a genetic disease, but it's not 100% a hereditary disease, but lifestyle and diet seem to play a major role, as
well as exposure to chemically hazardous compounds. Defining exact causes is supremely challenging the research community.
Further contributing to the witches' brew of confusion is data submitted at the annual meeting of the American Society for Human Genetics in Minneapolis last year, where scientists challenged the standards and accuracy of the laboratories conducting genetic
tests. The practices of laboratories that provide genetic testing concern geneticits, according to Science News. In a study of 463 commercial and nonprofit laboratories that offer or are developing genetic tests nearly 90% are registered under the Clinical Laboratories Improvement Act of 1988, which sets forth regulatory standards for medical tests. Yet 41% of commercial laboratories are using testing methods without the oversight required by the Food and Drug Administration. Nearly 30% of both commercial and noncommercial labs use home brews, reagents prepared inhouse whose validity
has never been confirmed by an outside source.
Governor Pataki recently signed legislation requiring that couples seeking a marriage license be provided with the pertinent information relating to genetic diseases. The program goes into effect September 1, and will include information on Tay-Sachs and cystic fibrosis. On the horizon scientists expectantly foresee genetic screening
for heart disease, diabetes, osteoporosis, allergies, and asthma. Conceivably these could be included as factors for pre-marital genetic screening. "I hope not," alerts Mrs. T. "When my son was diagnosed with asthma, the pediatrician took a family history. Neither of us recalled any asthma in the family, however
we are both highly allergic and suffer in varying degrees from eczema. The doctor took one look at my husband and me and said, 'I don't know how the two of you ended up together. With your history each of your children has a 75% chance of having asthma,
and the boys have a 90% chance of having asthma. I flashed back to the ten year old girl I knew who died of an asthma attack, five years earlier, in the school where I worked, and a teacher's brother who died of it years earlier as well. My son was diagnosed at age 2 and we lived through years of stress and anxiety that
I wouldn't wish on anyone. At night he would wake up coughing horrendously and we'd rock him and try to keep him from pulling off the mask from his nebulizer. When my next son was born the doctor warned us that we'd likely be in for the same deal. In
the interim we took my older son to specialists, and there were remarkable advances in the treatment of asthma. The treatment worked remarkably and my older son outgrew his asthma by age seven. And Baruch Hashem my little one didn't get it. But I have no doubt that had I known that as a couple my husband and I would have children with a 75% chance of having asthma, I would have never married my husband. I'm glad I never knew."
Nevertheless, a clear distinction must be appreciated in that asthma is potentially fatal if not appropriately controlled and supervised. Recessive genetic diseases such as Tay-Sachs, Neimann-Pick, cystic fibrosis, Fanconi's anemia, Canavan's, etc. can neither
be controlled by medication nor supervised, and are always fatal. Mrs. T concedes the point, "Asthma isn't Tay-Sachs, and I'll tell you this. When it's time for my children to get married, I don't want them tested for asthma, but I definitely want them
tested for Tay-Sachs, cystic fibrosis, Fanconi's anemia, etc."
· One out of every three babies or young children admitted to a hospital is there because of a genetic problem.
· 12 to 15 million Americans have a genetic disorder of one kind or another.
· One out of every 250 newborn babies has a genetic disorder.
· Each of us carries an average of between four and seven
abnormal recessive genes.
"COUNTRY YOSSI"
