Based on his experiments with pea plants, Gregor Mendel, a monk living in the Austro-Hungarian Empire, formulated basic tenets of genetics in 1865. He found that when he crossed a white-flowered and a purpled-flowered plant, the offspring were not all purplish white, or 50% purple and 50% white. Rather, 75% of the offspring were purple, and only 25% were white. Yet when he cross-pollinated the purple plants, 25% of their progeny were white. Thus, he hypothesized that certain traits were controlled by “factors” (later termed “genes”), of which offspring inherited one each from each parent. In addition, genes for traits such as flower color could be dominant or recessive.
Since then, scientists have discovered that in humans and other species, this so-called “classical” Mendelian pattern applies to certain diseases and traits, but not most. Common diseases such as high blood pressure and diabetes may be influenced by multiple genes, as well as by the environment.
We now know that each person has 46 chromosomes—23 from each parent—that consist of deoxyribonucleic acid (DNA). DNA is a double stranded molecule, each strand of which contains a sequence of four different amino acids—adenine, cytosine, thymine, and guanine (abbreviated A, C, T, G). Sequences of these “letters” A C T G form “genes,” each of which constitutes the cellular instructions for a particular function (e.g., making a particular protein). Our chromosomes contain two copies of each of the three billion letters that make us. These letters form approximately 25,000 genes.
Each cell in our body contains these 46 chromosomes. The DNA sequences on the chromosomes in each of us differ from the sequences in anyone else’s body by 0.1%. The only exception is if one is an identical twin (or if one were to have a clone).
Occasionally, as a single fertilized egg or embryo keeps dividing to become a multi-billion cellular mass, a mistake—or mutation—gets made. If the mutation occurs in a cell that becomes an egg or sperm, this mutation could get passed on to our children. Usually, a single such error has no consequences. But sometimes, such an error can cause major problems. A single broken link in the DNA chain can make a protein misfold and dysfunction. Similarly, in retyping text, an occasional error does not ordinarily change the overall meaning. But at times, a single error could lead to problems. King Louis XIV’s diction L’etat c’est moi (“I am the state”) could accidentally become L’etat c’est toi (“You are the state”), completely altering the implications. War and Peace could end up being titled Car and Peace, or Bar and Peace. Similarly, the play Wit concerned ambiguity over whether the poet John Donne meant to use a comma or a semicolon in the last line of one of his Holy Sonnets—the meaning of his poem is different in each instance. (A typo could also change the title of this play to Bit, Hit, or Win).
In the case of HD, BRCA, and Alpha, these mutations can be deadly. Yet these three diseases differ in certain regards. HD follows a so-called Mendelian pattern—one gene is dominant, and is solely responsible for the disease. The mutation actually consists of a few accidental added repeats of the sequence CAG on the gene that makes the Huntington protein. A person who has this error on this gene from either parent will develop this deadly disease. Each child then has a 50% chance of inheriting this defective chromosome (with the mutation), rather than the other, normal chromosome that the ill parent has (and received from his or her healthy parent).
In contrast, breast cancer appears not to follow a classic Mendelian pattern. Rather, multiple factors may be involved. Two mutations have been identified—named BRCA 1 and BRCA 2—that predispose to the disease. The presence of one of these two mutations gives a person a 40%–60% chance of developing the disorder. Yet only approximately 10% of breast cancer is due to one of these two mutations.
In the case of Alpha, a person can inherit the mutation from only one parent (in which case one is a carrier, and may develop some mild symptoms), or from both parents (in which case, one develops a more severe form of the illness).
When did you first find out you were at risk for a genetic disorder, and how did you respond? What are your understandings of what it means to be at risk for a genetic disorder?
Do you feel genetic information is different than other kinds of health information, and if so, how and why?
Do you feel you are “disabled,” or “sick,” or not?
Do you see genetic information as part of your identity, and if so, how?
Has your genetic risk affected you in any way, and if so, how?
PRIVACY AND DISCLOSURE DECISIONS
What do you feel comfortable or uncomfortable having others know about you, and why, concerning genetic or other medical information?
How concerned are you about threats to privacy of genetic information? Of other information?
Who have you decided to tell or not to tell about your genetic risk?
Have you told family members (spouse/significant other, sisters, brothers, parents, children, other extended family members, in-laws), friends, coworkers, employers, neighbors, healthcare professionals (primary physician, other physicians in different contexts), researchers, insurers (health insurers, life insurers, disability insurers), and others? How do you make these decisions?
What have you disclosed, and when and why?
Have you told your offspring, and if so, when?
Have you told healthcare professionals or institutions? Why or why not?
Have you ever had to hide the fact that you are at risk of, or have a genetic or other disorder?
Have other family members ever told you that you may be at risk of a genetic disorder? If so, what was said and when?
Have your views about whom to tell changed over time, and if so, how?
What is it like to face these decisions?
Have you ever experienced limitations on privacy?
Have you ever encountered stigma or discrimination as a result of a diagnosis? How do you view these?
Have you ever not disclosed potentially relevant information to physicians, and if so, what kind of information, when, and why?
Have physicians ever discussed with you limitations on confidentiality or risks of genetic discrimination, and if so, what was said?
How do you feel about healthcare professionals and institutions having access to private aspects of yourself?
Are there differences in doctors having access to personal information, medical history, or laboratory tests (including DNA), and if so, how?
Have you ever requested or considered requesting that certain information not be included in your record, or ever delayed or avoided treatment because of privacy concerns? How have you made these decisions?
Have privacy concerns affected your use of the Internet in any way, and if so, how?
Have concerns about privacy of genetic information affected you in other ways, and if so, how?
Has your health information ever “leaked out” or led to discrimination, and if so, how?
Do you feel employers have access to health information, or would under new laws?
Do you feel your employer has ever used health information in work decisions (e.g., hiring or promotions) with employees?
Do you know of others who have faced discrimination or stigma as a result of genetic or other health information? What experiences have these others had?
Have you ever disclosed that you are at risk of or have a genetic or other disorder to individuals who then in turn communicated that information to others?
HEALTH BEHAVIORS, TESTING, AND TREATMENT
Have any family members considered or sought testing? How did they make their decisions? What factors were involved? Have these experiences affected your views in any way?
How have you made decisions concerning testing?
Have you made any decisions about treatment of a genetic condition? If so, what?
VIEWS OF TRADEOFFS AND POLICY ISSUES
How do you weigh privacy against other concerns or benefits in choosing to have tests or treatment?
How do you balance individual rights to privacy with other concerns?
Do you feel you would be more likely to take tests if better treatment were available? How effective would the treatment have to be?
Do you feel third parties have a right to some types of information, and if so, what or when? What if you would risk losing health insurance coverage or other benefits if you did not grant permission?
What do you feel should be done when it may not be possible to request such consent (e.g., on records collected in the past)?
Do you feel it should ever be permissible to share such information when authorization cannot be obtained?
Would you be willing to pay additional costs to protect privacy? Why or why not?
What factors would you take into account in deciding whether to consent or not to your genetic information being shared?
What do you think doctors should do if patients with a genetic disorder do not inform family members who may be at risk? Do you think the physician has a “duty to warn” family members?
Do you feel loss of privacy is inevitable? Have you felt coerced to accept such limitations?
How do you feel such decisions concerning privacy safeguards should be made?
Do you have any other thoughts about these issues?
Chapter 1 presents a brief overview of the methods. More fully, I had the interviews transcribed, and analyzed them during the period I was conducting them. I conducted interviews until I reached “saturation”—that is, until the major and minor themes became clear.
I tried to recruit additional African Americans and Latinos, but to do so proved difficult in part because Caucasians undergo genetic testing far more than these other groups do. These different rates of testing result from various reasons including finances and wariness, given the history of eugenics in the United States. Nonetheless, several African Americans and Latinos agreed to participate.
I analyzed the interviews, informed by grounded theory.1 Once the full set of interviews was conducted, subsequent analyses were conducted in two additional phases, by myself and research assistants who had social science training. We independently examined a subset of interviews to assess factors that shaped participants’ experiences, identifying categories of recurrent themes and issues to which we subsequently gave codes. We assessed similarities and differences between participants, examining categories that emerged, ranges of variation within categories, and variables that may be involved. We thus developed a coding manual and examined areas of disagreement until reaching consensus. We discussed new themes that did not fit into the original coding framework, and then modified the manual when appropriate. In phase two of the analysis, we refined and merged subdivided categories into secondary or sub-codes, when suggested by associations, or overlap in the data. We then used these codes and sub-codes in analyzing of all of the interviews. To ensure reliability, two coders analyzed all interviews. We triangulated methods, referring to anecdotal reports and prior literature.
The Columbia University Department of Psychiatry Institutional Review Board approved the study.
1. Strauss, A, and Corbin, J. Basics of Qualitative Research—Techniques and Procedures for Developing Grounded Theory. Thousand Oaks, CA: Sage Publications, 1990.