Princeton University - Council of Science & Technology

POPE PRIZE

Essay 1
Should I Give my DNA Away?
Lara C. Atwater

Essay 2
Excerpts from novella: "Dreams of Ingrid Capac-Nolasco"
Nicholas R. Lilly

Essay 3
From Greening to Curing: Cornelia Liu Trimble, M.D.
Monica H. Wojcik

Honorable Mention
Neir Eshel

Should I Give my DNA Away?

People in my family have a condition called Charcot-Marie Tooth (CMT) disease. Around age forty, my father started developing numbness in his extremities and lost feeling and muscle control in his hands and lower legs. Currently, he has trouble reading his own handwriting, can no longer run, and does not feel it when his shoe falls off while he’s walking across the hot asphalt of a parking lot. A few months ago, I went to the neurologist to initiate testing for CMT because I have begun to have numbness sensations in my feet. In addition to the periodic tingling, I also have the extremely high arches and the “hammer” toes characteristic of individuals with this condition. About half the people in my father’s family are symptomatic, but the onset and presentation is different for every person. The neurologist confirmed that I likely have CMT, based not only on my symptoms and family history but also on nerve conduction studies he performed. I am certainly not alone. CMT is one of the most common inherited neurological disorders in the U.S., affecting approximately 1 in 2,500 Americans. Named for the three physicians who discovered it in 1886, CMT affects nerves in the muscles and sensory organs of the limbs rather than the brain or spinal chord (central nervous system (CNS)). CMT patients have low or non-functioning peripheral nerves that usually help the brain communicate with the limbs via electrical signals. Nerve structures called axons (responsible for conducting these signals) and myelin sheaths (which insulate axons) usually help conduct the electrical message, but these do not function properly in CMT patients because their bodies do not have the correct genetic information to manufacture the proper balance of proteins necessary for these nerve structures to function appropriately. The proteins are incorrectly manufactured based on genetic abnormalities, which ultimately cause CMT disease. These mutations can take many different forms and occur on many different chromosomes, but CMT ultimately describes a failure of peripheral nerves to communicate with the CNS, which leads to atrophy, loss of motor function, and numbness. Although it seems likely that I have CMT, my diagnosis will not be certain until I develop more symptoms or decide to take a genetic test that detects the various known mutations involved in CMT. In general, “genetic testing” is the laboratory analysis of DNA, RNA, or chromosomes, and can also include examination of proteins that are the products of genes. CMT comes in many varieties, including autosomal recessive, autosomal dominant and X-linked forms. Many, but not all members of my family have symptoms of CMT but have them in varying degrees, it is possible that our form of CMT is autosomal dominant with incomplete penetrance, meaning that it does not skip generations but manifests a range of symptom severity. My family may also have a mulltifactorial form of the disease, meaning it is caused by many genes rather than one that can be traced easily in a family pedigree. There is no cure for CMT, so a positive genetic test would not affect my prognosis. Additionally, I am anxious that I may be denied health insurance, as companies will ask for my medical records before granting me a policy. I want to know if health insurers are likely to refuse me coverage or charge me a higher premium, despite the fact that my condition has no impact on the length of my life. Are my fears of genetic discrimination well-founded and common to other patients? I wanted to find out. The existence of genetic tests and how they influence insurance discrimination is the subject of this paper. Do others share my fear? As the number of verifiable genetic diseases increases, so does the number of genetic tests. There are now over 15,500 recognized genetic disorders impacting over thirteen million Americans. Since 1997, the number of diseases with corresponding genetic tests has mushroomed from 169 to 1,221 conditions, an increase of over 600%. Formerly limited to newborn screenings and patients with rare disorders such as Huntington’s disease, there are now tests for genetic abnormalities linked to common conditions such as breast cancer, Alzheimer’s disease and heart disease. These tests are used not only for patients with existing symptoms, but also to gauge individual “risk” for future diseases that can be treated preemptively using drugs or lifestyle changes. As more genetic tests become available, so do patient fears that this information could be used discriminately. For example, a recent survey reported the percentage of respondents not wanting their employers to have access to their genetic information rose from 85% in 2002 to 92% in 2004. In that same period, the percentage of respondents wanting their genetic information kept secret from insurers rose from 69% to 80%. Medical professionals suggest this fear is legitimate. For example, The American Medical Association’s Institute for Ethics has advised that physicians who recommend genetic testing should also inform patients of the possibility of discrimination. Even more telling, a recent congressional survey of genetic counselors revealed that 68% would opt not to share their own personal genetic information with insurance providers out of fear it might be misused. 25% even said they would use a false name. Fear of genetic discrimination not only prevents individuals from seeking testing, but also continues to worry patients after tests are performed. A study of women testing positive for deleterious “BRCA” mutation (which predisposes women to breast cancer) revealed that cancer-free carriers of the gene had serious concerns about insurance discrimination, despite the fact they were perfectly healthy. Have others’ fears come true? Although many people have genetic tests and do not encounter discrimination, there is widespread anecdotal evidence that it occurs. Genetic Alliance, a genetic-rights advocacy group, receives multiple calls each week from people who have been denied health coverage because of genetic information. Additionally, the Council for Responsible Genetics has documented more than 500 cases of genetic discrimination. Kentucky resident Heidi Williams claimed that her health provider, Humana, refused to cover her two children when told that they carried the allele (gene variety) for alpha-1 antitrypsin deficiency. An autosomal recessive disorder that causes emphysema and liver diseases, it only occurs when children inherit the abnormal allele from both parents. Although the children were healthy and did not have the two copies necessary to make them sick, Humana refused to cover them until Williams won a year-long battle with the help of genetic rights’ advocates, lawyers, and medical researchers. In 2002, the Burlington Northern Santa Fe railroad allegedly forced 18 of its employees to undergo genetic testing for a chromosome 17 deletion or be fired. These employees had filed workers’ compensation claims for carpal tunnel syndrome (a stress injury), and the company hoped to avoid paying compensation by proving their injuries resulted from a genetic condition rather than a work-related injury. The most frightening anecdote I came across, however, was a CMT patient complaining on a group-support website that health insurers refused to cover her because of CMT. She had lost her job and consequently lost the group health insurance coverage provided by her employer, and was denied individual health coverage due to her CMT diagnosis. There are also justifiable worries that genetic information is especially prone stigma and misinterpretation by insurance companies. Genetic tests have great potential to improve healthcare, but at present, most are significantly limited in their ability to predict diseases. For example, a test might not be able to pinpoint every mutation in a gene (which may have changes in one or many of its hundreds of base pairs) and therefore might not be able to confirm an aberration even if it exists. Additionally, DNA tests cannot measure the influence of environmental factors on a person’s genotype, an interaction that affects the onset of most diseases. A positive test for a genetic abnormality does not mean an individual will develop the correlated disease, it only indicates a certain estimated risk, and with many polygenic diseases (diseases involving more than one gene) or multifactorial diseases (diseases that are affected by factors in addition to genes such as environmental influences), it is oftentimes difficult for scientists and doctors to predict a person’s future health. Thus, it is understandably worrisome that health insurers may misinterpret this essential nuance of genetic testing. In the words of concerned Congresswomen Louise Slaughter, “Expecting a human resources professional to interpret a genetic test accurately is about as realistic as asking them to predict the weather for May 2009.” Also disconcerting to those worried about the misuse of genetic information is that there is no federal agency explicitly responsible for assuring the validity of genetic tests. This would include verification that the tests consistently produce correct answers and also target genetic variations with legitimate links to a person’s health. Many of these tests are marketed directly to consumers, who can demand them through their doctors or even order them online or through the mail. If many well-established tests predict the incidence of disease with less than 100% accuracy, it is frightening to imagine genetic discrimination being based on tests that are popular due to successful marketing rather than demonstrated predictive value in standardized tests. Additionally, “genetic” disease conditions can carry more negative stigma than other disease conditions, not only for patients but for health insurers. For example, one study documented insurance discrimination against patients with the genetic conditions hemochromatosis, phenylketonuria (PKU), Huntington’s disease, and mucopolysaccharidoses (MPS). Individuals with any of these four conditions reported difficulty obtaining health insurance due to perceived “genetic risk,” regardless of whether they had actual symptoms or had a disease (such as hemochromatosis) that carries no association with excess mortality or morbidity when managed correctly. , Additionally, a 2007 study found that patients with single-gene disorders (e.g., cystic fibrosis or sickle cell disease), were more than twice as likely to be denied health insurance or have it offered at prohibitively high rates than those with “non-genetic” conditions (defined within the study as diseases with “complex” etiologies including diabetes, HIV, breast cancer, and colon cancer). Does the federal government think protection of genetic information is warranted? The government seems to have realized that genetic information protection is becoming a larger issue as more genetic tests are developed. A handful of laws passed in the past decade touch upon the issue of genetic information protection with regard to insurance providers (as well as employers). The Health Insurance Portability and Accountability Act (HIPAA) of 1996 prohibits health insurers from using genetic information to determine patient eligibility. However, Health and Human Services’ attempts to enforce HIPAA’s genetic privacy provision have been criticized as “confused and contentious.” The executive branch showed support for genetic privacy in 2000, when President Clinton issued Executive Order 13145 protecting federal employees from genetic discrimination in the workplace. The U.S. judiciary also ruled that the aforementioned Burlington Northern Santa Fe Railroad acted in violation of the Americans with Disabilities Act when it ordered genetic tests for employees filing for workers compensation. Many states have enacted laws designed to prevent genetic discrimination. However, they vary widely in direction and scope and are often limited in their capacity to protect workers against health insurer discrimination because self-insured employee benefit plans are usually exempt from state laws. , Due to the patchwork nature of state regulations and the difficult task of interpreting and enforcing non-centralized federal regulations, significant numbers of scientific and public health professionals have complained about the lack of an explicit federal law addressing genetic privacy. For example, the Secretary’s Advisory Committee on Genetics, Health, and Society at the Department of Health and Human Services recently conducted an analysis of the ability of current law to protect against genetic discrimination. The committee found many holes in government protection, and determined that “current law does not adequately protect against discrimination based on genetic predisposition.” Esteemed scientist Dr. Francis S. Collins, director of the National Human Genome Research Institute at the National Institute of Health, has been urging Congress to pass definitive legislation protecting against genetic discrimination since 1995. He contends that lack of legal protection makes patients less willing to participate in research studies involving genetic testing. Since this time, there have been genetic information nondiscrimination bills proposed in each session of Congress in both the House and Senate. Each House measure has been delayed in subcommittee although often it has been approved unanimously by the Senate and has strong support from the Bush Administration. Representatives curbing the bill’s progress are allegedly influenced by business groups who argue that it would add more cost for business without affording significant consumer protection. In the meantime, patient anxiety about the privacy of genetic information is having a significant effect on both the personal health of individuals and on the advancement of scientific knowledge. Fearing misuse of genetic information, many individuals elect not to test themselves despite knowledge that the results may help their doctor prevent diseases. Recognizing possible harm to the patient, some U.S. insurance companies have made an effort to promote genetic testing for their members because they know that consumers who feel comfortable consenting to genetic tests may benefit from preemptive healthcare solutions, which stave off expensive adverse health events and ultimately reduce insurers’ costs. In the case of many cancers, for example, genetic screening and early detection in combination with prophylactic surgery can save insurance companies money on expensive chemotherapy regimens and complicated surgeries to remove cancers that may otherwise result. Additionally, patient anxiety about genetic privacy has had a “huge chilling effect” on genetic research, and the NIH confirms that a growing number of people refuse to participate in studies for this reason. “As a society, we are all going to suffer if the wheels of research stop turning,” mused one mother whose two children suffered from a rare disease in dire need of research. Conclusion For the moment, I am going to postpone being tested. I feel guilty that my case is not making a contribution to genetic research, but available tests are unlikely to be able to confirm my family’s multifactorial variety of CMT (every three to four years, my father undergoes the latest genetic tests but has never tested positive). Even with a definitive result, there is no preemptive treatment for my disease and risking discrimination seems foolish until I have steady health insurance and employment. However, I am hopeful that as genetic disease links and tests become more prevalent, stigma against genetic aberrations will decrease. After all, calculations based on the number of genes in the human genome suggest that each of us is likely to carry around 200 mutant alleles. Not all of these have high penetrance as in breast cancer or Huntington’s disease, but eventually society will realize that penalizing everyone for having a few genetic abnormalities will mean there will be no one left to insure or employ. Laws and responsible insurers can help in the meantime, but I look forward to an era when genetic information is looked at no differently than a family history. After all, family histories were doctors’ original genetic tests.