Social and Ethical Issues

A key tool for research on inherited conditions in humans is the family pedigree. To reach conclusions about the genetic basis of a trait, human geneticists need to collect data from as many family members as possible. One way to obtain this data is to ask people affected by a genetic condition about their relatives. However, gaining information in this way may create ethical problems, because these relatives become research subjects without their knowledge or approval. Suppose, for example, that an interviewee mentions that his aunt has had precancerous colon polyps removed. The aunt might consider the dissemination of this information embarrassing, and if the information were to find its way into public databases, she could be subject to discrimination by her employer or insurance company. In 1999, the federal Office for Human Research Protections (OHRP) received a loss-of-privacy complaint for exactly this reason and temporarily shut down a genetic research program as a result. On the other hand, genetic research using human pedigrees might lead to important new therapies and preventive measures. One way to deal with genetic privacy concerns is to require that researchers obtain written informed consent from all family members before a pedigree is published. However, many scientists regard such a requirement as too restrictive: much effort would be required to obtain this consent, and fewer people would enroll in genetic studies if they knew all their relatives had to be contacted. In your opinion, should the right to genetic privacy take precedence over research into human genetic conditions that could benefit a large number of people in the future? If informed consent were not obtained, are there ways to ensure that a person’s genetic information will remain private?

Louise, a single mother with four children, has a job in an aeronautics factory where she is exposed to the element beryllium. Some individuals are susceptible to the damaging effects of this element, developing a respiratory illness called chronic beryllium disease. Workers in the factory were recently tested for susceptibility, and Louise tested positive. She needs the job and wants to continue working at the factory until she finds another job. The company wants her to quit immediately. Should the individual or the company have the right to decide whether a susceptible person continues to work in a potentially damaging environment? If Louise insisted on working in the factory, should she still have the right to sue the company for compensation if she later developed chronic beryllium disease?

John and Nancy’s daughter has a blood test performed by their family doctor. The doctor knows that both John and Nancy have the AB blood type. But when results come back on their daughter’s blood, the doctor discovers that her blood type is O. Neither parent is heterozygous for the Bombay allele. The only conclusion the doctor can reach from this result is that babies must have been switched at the hospital. The doctor is now in an awkward position. John and Nancy and their healthy daughter make a very happy family. If he explains to them the implication of his findings, their lives will be turned upside down. If not, he will be withholding personal information

that one could argue rightly belongs to them. What would you do if you were the doctor?

A man who has committed several violent rapes is on trial, and his lawyer argues that the man cannot help himself because his behavior is the result of his genetic makeup. The man’s father and brother also have a history of committing violent crimes. In defense of this position, the lawyer cites studies reported in 1993 on a small Dutch family indicating that some people inherit a propensity toward violent behavior. Affected individuals in this family have a mutation in the monoamine oxidase gene involved in the breakdown of neurotransmitters. Do you think the sentencing of the man on trial should depend in part on this type of scientific study? Our judicial system is based on the assumption that people act with free will and are therefore responsible for their actions. Are people with known genetic alterations responsible for their actions? Should we make exceptions in the case of genetic predispositions? What role should society play in helping people whose behaviors may be influenced by the alleles they carry?

A teenage girl was diagnosed with chronic myelogenous leukemia, for which the treatment is a bone marrow transplant. Successful tissue transplantation depends on matches with the donor’s alleles of the polymorphic HLA genes. A matching donor could not be found, and her parents decided to have another child, hoping that the younger sibling could serve as a donor of bone marrow for the older child. Is it ethical to conceive a child for the purpose of tissue or organ donation to a sibling? Consider situations in which the donor’s life will be compromised by the donation as well as cases in which the donor’s life will not be compromised.

Gregg and Jennifer are in their late 20s and just had a baby born with cri du chat syndrome. The physical and mental manifestations are microcephaly (small head), mental retardation, and a catlike cry. This dominant condition is due to a loss of a portion of one copy of chromosome 5 and is readily detectable by karyotype analysis. The policy of the health organization to which Gregg and Jennifer belong is to do routine amniocentesis on pregnant women over 35 years of age and on patients from a family with a history of a detectable genetic condition. Jennifer fit into neither category and so was not tested. Jennifer and Gregg feel their doctor was remiss in not ordering the amniocentesis, and they want to bring a malpractice suit against the doctor and the health organization to which they belong. Is there just cause to bring this lawsuit? Should people have a say in which tests they receive? Should doctors be required to give all tests possible? What effect could this have on the cost of health insurance?

Jack and Jessica are going to have a baby, and because Jessica is 38 years old, she had amniocentesis. The karyotype results indicate that the baby has three copies of chromosome 21 (trisomy 21 or Down syndrome). A genetic counselor and doctor have discussed with the couple the potential emotional and financial concerns in raising a Down syndrome child at home versus sending the child to an institution (many of which are state-supported). Jack and Jessica have decided to continue the

pregnancy and raise their child at home. Given their decision to have the child knowing it will be affected, should they be eligible to receive state funds to defray the costs of special educational and therapeutic programs that they may need to raise their child at home? Should society pay for expenses accrued by children with genetic disorders if it is possible to screen for these disorders before birth?

In 1965, a study on mentally subnormal males with violent tendencies in a Scottish institution was published; it indicated that 7 of 197, or 3.5%, had the karyotype XYY. These individuals were, on average, 6 inches taller than the XY males in the institution. This percentage (3.5%) of XYY males in this institution seemed abnormally high when compared with that seen in the general population (about 0.1%). A large-scale study was initiated in 1968 in Boston to screen newborns for the XYY karyotype and to follow up on the development of these boys. In 1974, a group of scientists opposed this study, feeling that it was based on preliminary observations and could be damaging to the boys involved. A major concern was that the boys would be unfairly branded as abnormal and violent. In addition, the parents had not been fully informed of the purpose of the testing. What is a fair way to approach the scientific question of the effects of an extra Y chromosome in humans? Can one separate social and cultural impacts from biological impacts of an extra Y chromosome?

In the initial stages of gene mapping, researchers find DNA markers that are linked to a disease gene. It is possible to use such linked DNA markers to test for the presence of a disease-causing allele in a fetus, although these tests are by definition inaccurate. For example, if the distance between the disease gene and the DNA marker is 5 m.u., then 5% of fetuses diagnosed with the disease-causing allele would actually be false positives, while 5% of the fetuses considered free of the disease-causing allele would be false negatives and actually have the disease. How accurate must a genetic test be to be used on patients? To what extent does this decision depend upon the severity of the genetic condition? How should one balance the costs and risks of the diagnostic procedure? (For example, there is a very low but apparently real risk of miscarriage when amniocentesis is performed to obtain fetal DNA. Are most patients intellectually and emotionally prepared to deal with a genetic diagnosis that is less than certain?

In 1996, evidence was presented for linkage of a marker to a predisposition to prostate cancer. Using 66 families in which at least three males had prostate cancer, a genetic marker was found that is inherited with high frequency in those men with prostate cancer. Linked to this marker, somewhere in a region of about 10 million base pairs, is a gene that predisposes to prostate cancer. The estimate is that this genetic region is involved in about 3% of the total cases of prostate cancer. National newspapers announced these findings with the following headlines:

Social and Ethical Issues“Scientists Find Proof That Mutant Gene Can Increase Risk of Prostate Cancer”“Prostate Cancer Gene Evidence Found”“Scientists Zero in on Gene Tied to Prostate Cancer”

Do these headlines accurately represent the situation? Could they be misleading in any way? What would you use as a headline for an article on this study? What is the responsibility of the press in presenting new findings? Consider the responsibility of journalists/reporters to their employers (newspapers), their profession, and to the public.

In 1990, researchers reported the recovery and amplification of a small fragment of DNA from a fossilized leaf that was 20 million years old. Subsequent studies suggested that all samples of purported million-year old DNA may actually be the result of unintentional contamination from contemporary organisms. Nevertheless, the recovery of small bits of ancient DNA inspired Michael Crichton to write the best-selling novel Jurassic Park. In his story, researchers re-create dinosaurs by isolating and piecing together bits of DNA. The necessity of recovering enough intact long stretches of dinosaur DNA make this a highly improbable scenario, yet the movie portrayed this work with an aura of authenticity. Does a science fiction writer have a responsibility to indicate what is truly possible and where the line between science and fiction is likely to lie? Does this become more of an imperative when a book is made into a movie that reaches a mass audience? Can the reality of what is currently possible be conveyed within the framework of science fiction?

Eleanor has just been diagnosed with breast cancer at age 45. An analysis of her DNA shows that a mutant form of the BRCA1 gene is responsible for the cancer. Mendelian genetics tells us that there is a 50% chance that Eleanor’s 18-year-old daughter Erin inherited this mutation from her mother. We also know that the mutation is not completely penetrant—only 70% of women with the mutation develop breast cancer by the age of 60. But a radical bilateral mastectomy, which removes all currently healthy breast tissue, can dramatically decrease or eliminate the possibility of developing breast cancer in the future. Many women feel conflicted about receiving a mastectomy when the possibility also exists that their breast tissue could be healthy for the rest of their lives. Some with a family history of breast cancer choose not to learn whether they actually carry a BRCA1 mutation. Who should decide whether Erin takes a DNA test that could detect the BRCA1 mutation? Erin, her parents, or their family physician? Should government regulations mandate that Eleanor and Erin receive specific information about the connection between genotype and phenotype before they make their decision? At what age does a person become competent to make this kind of decision for herself? Should Erin’s physician wait until she turns 21 before allowing her to take the test? (Erin’s chances of getting cancer before the age of 21 are very low, but if she puts off the decision beyond that age, the probability increases continuously.)

The perpetrator of a serious crime has left behind a few hairs, which contain enough DNA to allow detection of specific sequences using a technique called PCR. The

police arrested a number of suspects and required them to provide DNA samples so that technicians can determine whether any of their sequences match DNA retrieved from the crime scene. After completed comparisons reveal that the suspects’ samples don’t match sequences from the crime scene, should the police or other governmental agencies be allowed to store the DNA from these individuals indefinitely, or should they be required to destroy the samples?

A decade ago, researchers collected DNA samples from 100 volunteers who gave them permission to use the samples in a specific study aimed at identifying a gene involved in a particular disease. With new discoveries made since the samples were collected, the researchers have become aware that samples from this particular group of 100 people would be very useful in the analysis of another, unrelated disease. Since the volunteers never gave the researchers permission to use their samples in this unexpected manner, the researchers try to contact them to see if they will agree to participate (indirectly) in the new experiment. Unfortunately, 30 of the people cannot be found, but their DNA samples are crucial to the collection of sufficient data for obtaining a significant experimental result. Is it ethical for the researchers to use the DNA from these “lost” people in this particular experiment without permission? Should the answer depend in any way on how important the potential results would be in curing a disease that affects many other people, or is this consideration irrelevant to an ethical decision?

Chemicals that are mutagenic are identified by the Ames test, which measures the level of mutagenesis in bacteria. The susceptibility of humans to mutagenic chemicals may vary depending on the genetic makeup of the individual. The dose that affects one person may be different from that which affects another. However, there are few, if any, reliable tests that determine a person’s level of susceptibility. If this is true, is it a good idea to translate the results of the Ames test of mutability in bacteria to a prediction of carcinogenicity in humans? Often, reports of Ames test results on a chemical make newspaper headlines. Is this a useful and honest way to report findings that could affect human health, or do people need to consider other variables to make an informed decision?

Mr. and Mrs. Aswari have a child with fragile X syndrome. They want to have a second child but are considering egg donation because genetic screening has indicated that Mrs. Aswari carries a premutation allele with 120 CGG repeats. If you were the Aswari’s genetic counselor, what would you tell them about their risk of having a second child with fragile X syndrome? What are the ethical issues related to genetic screening when (1) a result indicates no risk, (2) a result indicates that the phenotype being screened for will be exhibited, and (3) an intermediary result does not clearly fall into either category?

An ethnobotanist who works with native peoples of Peru approached a large pharmaceutical corporation, hoping to get some benefits for the native Peruvians as compensation for conveying knowledge on medicinal plants of the rain forest to the company. Scientists in the company found several potential plant-based drugs using

information from the indigenous peoples. However, when they tried to purify the drugs from the plants, they found that their yield was low. As an alternative, chemists in the company began to synthesize the drugs. Because the chemists are synthesizing these compounds, the company says it owes neither the native peoples nor the country of Peru anything. Is this a responsible policy for the company? Consider the responsibility the company has to the ethnobotanist, to its stockholders, to the native peoples, and to Peru.

In sub-Saharan Africa, where more than 34 million people are infected with HIV, more than 2 million individuals die of AIDS each year. The current treatment for HIV is a “cocktail” of several drugs that costs about $10,000 per year in the United States, an amount that is unaffordable for most Africans. In response, several pharmaceutical companies have relaxed the rules for licensing their patent rights to allow African companies to produce anti-HIV drugs at a decreased cost. Is this type of “corporate philanthropy” an obligation that a pharmaceutical company owes society? If so, how can these companies recoup the $800 million dollars that is, on average, required to develop a new drug? Should the World Health Organization or the governments of more-developed countries share the costs of this philanthropy? Should mechanisms be instituted to prevent the importation of cheaper versions of the drug back into the developed countries? As a general principle, is it fair to index the price of a drug to the ability of a patient to pay?

In 1992, the biotechnology company Calgene applied for approval of their rot-resistant tomato, the FlavrSavr® tomato. They had engineered the tomato plant by introducing a copy of the gene encoding a softening enzyme downstream of, and in reverse orientation to, a strong promoter active in the fruit. When the engineered gene is transcribed, an “antisense RNA,” complementary in sequence to the softening enzyme mRNA, is produced. The antisense RNA binds to the normal mRNA and blocks translation of the softening enzyme so the tomatoes stay ripe longer. The FDA approved the sale of the tomato without any additional labeling because the DNA that had been introduced into the tomato was tomato DNA. (The FDA’s policy on bioengineered foods is to label food as genetically engineered only when a new substance has been introduced that could cause an allergy or when there has been a change in the food’s nutritional value.) Several consumer groups were upset by the FDA’s action and wanted to see labeling about genetic modification appear on the tomatoes in the stores. Their protest significantly stalled the sale of these tomatoes. Were the consumer groups’ actions, which blocked an advance that people might have wanted, warranted? Are these groups important watchdogs of everyone’s well-being, or are they hindering progress?

Thousands of years ago, people living in the Middle East discovered that when they added a tiny quantity of an extract from the inner lining of the fourth stomach of a freshly killed calf to cow’s milk, the milk turned to cheese. In the twentieth century, biochemists isolated and characterized the responsible agent: an enzyme named chymosin. The enzyme is encoded by a single gene that is expressed only in animals that chew their cud and only before weaning. Until just two decades ago, cheese

makers had to use this animal product as an essential component of the cheese-making process. Then, using the tools of recombinant DNA technology, biotechnologists cloned the cow chymosin gene in a bacterial expression vector, making it possible to produce fully functional chymosin in a culture of cloned bacteria. In 1990, chymosin produced in this way became the first approved product of recombinant DNA technology to enter the U.S. food market. Unlike calf chymosin, recombinant cow chymosin can be standarized; it can also be inexpensively produced, and it doesn’t require the killing of any animals. Purified calf chymosin and bacterially produced chymosin are indistinguishable in their structure and enzymatic activities. By 2004, over 90% of the cheeses on supermarket shelves in the United States, Europe, and most other countries around the globe were produced using recombinant chymosin.

a. Chr. Hansen, the Danish company that produces recombinantchymosin under the trademark of ChyMax, claims in their promotional literature that it is “nature’s own enzyme for clotting milk,” and a “natural ingredient for the food industry.” What is the definition of the term natural? Is it appropriate for a company to use this term to describe a protein made from a mammalian-specific gene inside bacterial cells? Does it matter that the purified chymosin proteins from a calf’s stomach and from cloned bacteria are structurally and functionally identical? How important is the process relative to the product in assessing something’s naturalness?

b. Some people do not want to eat food produced through genetic engineering, and they have called on the FDA to require a “genetically engineered” label on all such products. Food manufacturers argue that since biotech-produced cheese and traditionally produced cheese are indistinguishable, FDA regulations say that they don’t have to put special labels on their products to this effect. Both sides are fully aware of survey results showing that 50% or more of Americans would refuse to buy a product carrying a “genetically engineered” label. Do you think that food made with recombinant DNA technology should be labeled as such? What are the benefits and harms of requiring or not requiring such labels?

c. Acting in response to a request from the organic farmers trade organization, the FDA included in its regulation of organic food labeling the stipulation that no product of recombinant DNA technology was allowable at any point in the food production process. Consequently, cheese produced with the use of Chy-Max cannot be labeled “organic.” However, “organic” cheese produced by the traditional method requires the use of an animal ingredient and is, therefore, unsuitable for consumption by vegetarians. This means that dedicated vegetarians who eat only organic food cannot eat any cheese. (Some dairy products that do not require chymosin—such as cream cheese—have cheese in their name but are not true cheeses, according to the accepted definition of that food term.) Do you think organic cheese producers should be required to attach a label stating “contains animal products” so that vegetarians can be forewarned? What are the benefits and harms of requiring or not requiring such labels?

Pigs are a major cause of environmental pollution, as anyone who walks past a pig farm knows. Most of the pollution occurs because the animals are biologically unable to process the organic phosphorus present naturally in feed or grain; as a result, they require mineral phosphorous as an essential growth supplement. Unfortunately, most of the phosphorus in grain passes unabsorbed through the pig gut and into their manure, which is then used by organic farmers to fertilize crops. When it rains, the phosphorus-rich manure runs off into streams and other waterways where it causes eutrophication, algal blooms, depletion of oxygen, dead fish, and greenhouse gases. Natural human gut bacteria contain an enzyme called phytase that allows the biological processing of naturally occurring organic phosphorus. And in a reversal of the genetic engineering process, scientists have inserted a recombinant DNA molecule containing the bacterial phytase gene into a pig genome. Animals engineered with genes from other species are called transgenic, and the genes themselves are called transgenes. The recombinant phytase transgene is attached to a special promoter that causes the animal to produce the enzyme only in its salivary secretions. Except for this one difference, transgenic pigs are physiologically indistinguishable from nontransgenic pigs. Transgenic phytase-producing pigs benefit farmers financially because the pig growers no longer have to supplement pig feed with mineral phosphorus. Of greater importance is the fact that the transgenic pigs release 75% less polluting phosphorus in their manure.

a. Once transgenic-phytase pigs are available commercially, do you think the Environmental Protection Agency should require, or encourage, pig farmers to purchase them in place of traditional animals in order to reduce environmental harm?

b. As a result of self-formulated regulations, organic pig farmers cannot raise transgenic pigs and cannot use manure from transgenic pigs as fertilizer for crops. Consequently once transgenic-phytase pigs predominate in nonorganic pork production, organic pig farms will become more polluting than the corresponding nonorganic farms. What do you think would be the appropriate course of regulatory action in this situation?

Several companies were formed in the 1990s with the purpose of sequencing portions of the human genome and using this information to devise new drugs. These companies sought to patent each bit of DNA sequence that they decoded even if they did not know whether it encoded a gene product. Their justification was to ensure that any use of the sequence would yield payback for their research. This strategy failed as shown by the failure of most of these companies. Do you think patents should be granted for each partial gene sequence that has been determined? Do you think patents should be granted for entire gene sequences even if we do not know what the gene does? What criteria do you think are compatible with facilitating private-industry drug development, encouraging research, and protecting intellectual property?

Researchers who have similar interests and complementary expertise often collaborate on projects. The Johnston lab has recently started a collaboration with a lab in San Francisco to use a unique tissue culture cell line that the San Francisco lab established. At a scientific meeting, a graduate student from the San Francisco lab heard Marcus Johnston give a seminar talk in which he discussed future work and described this cell line, but he did not mention where it came from. Johnston also did not describe it accurately. The graduate student was very upset with this but then thought perhaps she was being too sensitive and when the work was done and publication occurred, appropriate credit would be given to the San Francisco lab. Should the student speak up at the end of the talk to correct misinformation? Should she approach Johnston later? Should she wait and talk with her advisor first? Should she do nothing and assume the misinformation will be corrected by someone else?

a. As a result of the new molecular genotyping and positional cloning tools described in this chapter, it has become possible to identify currently healthy individuals who are predisposed to—but may never express— a host of diseases and other deleterious traits. Insurance companies could use this information as the basis for charging people different rates according to the genotypes they’ve inherited. Most Americans are opposed to genetic discrimination by insurance companies, and several states have passed laws against the practice. The response from the insurance industry is that they have always used family histories—a weak form of genetic information—to set rates and that laws against the use of genetic information would require them to charge nonpredisposed people more than they would otherwise. Do you think insurance companies should be allowed to set rates according to genetic predisposition or resistance to a relevant trait?

b. One form of genetic discrimination is already practiced by all American auto insurance companies who charge hundreds of dollars more per year to insure a person between the ages of 18 and 25 who happens to carry the SRY gene. The presence of this particular gene predisposes a young person to engage in reckless driving and costly accidents, although most SRY-positive individuals drive safely. Should auto insurance discrimination based on SRY be allowed to continue? (SRY, of course, is the male-determining gene on the Y chromosome.)

Mary is a 25-year-old woman who has a good job with a company where she has room to advance in her career. When she accepted her job at the age of 22, she signed a contract that stipulated that she would tell her supervisor of any change that occurred in her health status. A footnote in the contract stated explicitly that a change in health status was defined not only as a symptomatic change but also as a prognostic change. This footnote was meant to include persons who tested positive for HIV even when they did not yet exhibit the symptoms of AIDS. It seemed clear to Mary that the purpose of this stipulation was to provide the company with grounds for dismissal. Three years after the beginning of Mary’s employment, Mary’s 56-year-old mother Elizabeth was diagnosed with breast cancer. Because several other women in the family had breast cancer, there is a high probability that there is an inherited predisposition to breast cancer in the family. Tests indicated that her mother does

carry a mutant allele of the BRCA1 gene, and therefore, Mary has a 50% chance of having a BRCA1 allele that predisposes her to breast cancer. The counselor encouraged Mary to take the test since there are preventative measures that can be taken if she finds out she is positive. But, if she takes the test and the result shows that she carries the BRCA1 mutation, she believes that she will have to tell her boss and possibly lose her job. On the other hand, if the test shows that she doesn’t have the mutation, a large load will be taken off her mind as she realizes her risk of disease is no more than that of other women without the BRCA1 mutation. What would you do if you were Mary?

Both members of a married couple express the trait of achondroplasia, the dominant inherited form of dwarfism. (The parents are heterozygous for the achondroplasia allele. Homozygous individuals die before age one of severe skeletal abnormalities.) The parents want to have a baby and they have told the genetic counselor at the testing clinic that they will abort a fetus if it does not carry a mutant achondroplasia allele. The prospective parents are concerned that they would not be able to discipline a child who became, at a young age, much taller than they are. Who should decide whether it is appropriate for this couple to select a child with achondroplasia—the government, the physicians at the testing clinic, or the couple themselves? According to the 1973 Supreme Court decision in the case of Roe v. Wade, a woman has the right to obtain an abortion for any reason during the first two trimesters of pregnancy. Even if it is legal, do you think it is ethical to abort a fetus simply because it does not carry a particular allele that most members of our society consider to be a mutation?

Antoine and Naomi’s first child has cystic fibrosis. They would like to have a second child but want to make sure the child does not have cystic fibrosis. After in vitro fertilization, seven embryos are screened for the presence of the disease. Of the seven, two are determined to have the disease. Prior to preimplantation, Antoine and Naomi asked the doctor to screen the remaining “healthy” five embryos for gender as they want to have only one more child, and they want that child to be a boy to carry on the family name. What would you tell the couple if you were the doctor? Is there a difference, in your opinion, between screening for a genetic disease and gender? If a genetic test for a phenotype exists, should the screening be available (e.g., if Antoine and Naomi asked to select an embryo carrying the genes to express blue eyes and blond hair, should they be able to do so)? What are some potential implications of selecting for alleles that do not have an impact on survival? What types of genetic screening, if any, should be available?

Recent evidence has shown that the ends of chromosomes (telomeres) get shorter as somatic cells age because of a lack of the enzyme telomerase, which maintains the ends and length of chromosomes. In contrast, cancer cells that are “immortal” and divide rapidly have telomerase activity. Whether the lack of telomeres in older cells is a cause or a result of aging is still under investigation. A proposal that included experimentation on telomerase has been submitted to the National Institutes of Health. A stated goal of the proposal was exploration of ways to extend the human life span. Is this a valid way to spend federal research monies given that many

commercial companies are already exploring ways to use these findings to extend the human life span? What are the consequences for society if people live longer? What do you think of the goal of a longer life?

A city school board put forward a proposal to screen school children with learning disabilities for the fragile X mutation. Fragile X is the most common form of inherited mental retardation and is caused by an unusual expansion of a triplet nucleotide repeat in a gene on the X chromosome. (The triplet expansion is extreme enough to be seen as a cytological abnormality as well as by DNA sequence analysis.) The extent of mental impairment and other abnormal phenotypes varies with the size of the repeat. The proposal was well intended; the school board hoped to use the screening to identify students with potential disabilities and give them extra help and consideration. However, many parents and professionals opposed the testing. How could selection for testing harm a child? How could identification of fragile X harm a child? What are the benefits of such testing?

With available data on the DNA sequence of the human genome, what has changed about the information that a researcher might choose to share with other researchers? For example, a scientist who has worked for two years on identifying a particular human disease gene recently determined the 10 Mb region of a chromosome where the gene is located. The next steps are to use genomic sequence information to identify potential gene candidates and determine which of the candidates is altered by disease-causing mutations. The scientist hesitates to talk about his finding because he thinks many other researchers will immediately use the data and design PCR primers to investigate the potential genes and mutations in affected individuals. Does he have a right to withhold the information until he has completed his analysis of mutants? Does the answer to this question depend on whether his work is supported by public (government) funding agencies or by a private biotechnology company?

Until recently, female athletes were gender tested to confirm they were female, using the Barr body test. In 1985, the Spanish hurdler Maria Patinez failed the Barr body test. She was encouraged by her coaches to fake an injury, quietly withdraw from the race, and retire from competition. Maria, indignant that someone suggested she was not a woman, spoke out against the testing policy. What are the problems scientifically with the Barr body test for gender identification? What do you think is a reasonable, accurate way to ascertain the sex of an individual? How should sex be defined? By karyotype? By examination of external genitalia? By internal gonadal structure?

Gary is a livestock farmer and has 2000 head of cattle. An outbreak of bacterial infection would be devastating to his livelihood, so he uses feed that contains antibiotics. Recently he heard a report indicating that the use of antibiotics in livestock food was contributing to the increase in antibiotic resistance in bacteria that infect humans. (The antibiotic resistance genes are contained on transposable elements that can be transferred from one bacterium to another.) Being a conscientious citizen, Gary is now considering eliminating the use of antibiotic feed.

Will discontinuing the use of this feed make enough of a difference to justify the risk he takes? What should he do? What are the stakes for him and for the public in this issue?

Jason and Sylvia received some unsettling news from the amniocentesis of their fetus. Karyotype analysis showed a partial trisomy in which one chromosome 8 homolog carried a duplication of a particular region. However, this specific partial trisomy had not been reported before, and its observation led to considerable uncertainty because some partial trisomies lead to developmental abnormalities, while others do not. The parents decided to continue the pregnancy. Their doctor alerted other medical colleagues who now would like to follow the progress of this child after birth in order to understand the consequences of this chromosomal rearrangement. Jason and Sylvia would prefer not to have their child subjected to any unnecessary medical scrutiny and are upset that their doctor gave information without their permission. Should the doctor have obtained permission before sharing the details with colleagues? Do Jason and Sylvia have a responsibility to provide information on the medical progress of their child so others in the future will know what to expect if the same duplication occurs?

Bacteria have now been engineered to break down components of oil, potentially providing a biological way to clean up an oil spill. Many environmentalists have been upset by and are opposed to this action. Why would they be disturbed by this action? How widespread do you think the effects of seeding a spill site with oil-eating bacteria might be? Who would have to approve this type of action in cleaning up an oil spill? What characteristics might you want to engineer into these bacteria to make them safer for the environment?

Sarah has been using Southern blot analysis to determine whether genes homologous to specific ones found in E. coli are present in a rare thermophilic (heat-loving) bacterium. Since she had very little of the bacterial DNA, she was able to make only one filter, and she had to reprobe that filter several times. After many months of work, she is getting her answer on what genes are present. The final blot that she does gives a large smudge in an important lane, but she feels she can still tell where there are bands and where there are not bands. The blot is not of high enough quality for reproduction in a publication. Sarah knows that reviewers and editors would probably reject it, but she thinks she could refer to this piece of evidence in her paper without showing a photo of the blot (listed as data not shown in the paper). It would take several months to again grow enough of the bacteria to repeat the experiment, and she knows there are competitors with similar experiments to report. Should she go ahead and submit the paper for publication even though most people would say the data are messy?

E. coli strain O157 is a unique strain of this bacterial species that has caused serious outbreaks of human illness, in some cases leading to the death of small children. Yet E. coli is part of the normal flora of the gut of all individuals, and researchers work on harmless laboratory strains all the time. In a college microbiology course in a large

university, one student got upset at the prospect of working with E. coli in the lab. Even with an explanation of the difference between the toxic and nontoxic bacteria, he was not convinced that his safety was ensured. He says he will not do the lab work himself but will do analysis of the lab data obtained by his partner. The laboratory is a required part of the course and accounts for 25% of the final grade. What should and/or could the professor do with this student? Should the student have to forfeit the laboratory points in the course? How far should the professor or university go to accommodate his needs?

A researcher has promising results that could lead to a treatment for a neurodegenerative mitochondrial disease. When she applies for a grant from a federal agency, the reviewers respond that the research proposed is more applied than basic in nature and therefore should be funded by a commercial pharmaceutical company. When the researcher approaches drug companies with her proposal, she finds they are not interested in developing a drug that would have a rather limited market. Should the government create mechanisms to cover the expenses of development and clinical trials for drugs of relatively low use that do not have a potential for producing a profit but that will nonetheless greatly benefit affected people?

During repressive political regimes in many countries, children often are separated from their parents and/or become orphaned. Human rights groups have been in the forefront of assisting in the identification and reunion of relatives using genetic markers such as mitochondrial DNA. Should the government of the country in which the atrocities were committed be obligated to pay some or all of the costs of these searches, even if the current regime is far removed in political ideology and action from the repressive regime?

It has been suggested that a databank consisting of DNA fingerprints of previously convicted felons be established. Both nuclear and mitochondrial fingerprints would be included to accommodate situations in which the nuclear DNA was too degraded to be used. Who should have access to such a database? Law enforcers? Psychologists? Sociologists? Is this an invasion of privacy or a protection for the public?

The bacterium Bacillus thuringiensis (Bt) produces a toxin capable of killing many insects that attack crop plants. For more than 20 years, Bt has served as a biological pesticide that is sprayed on crops. The constant spraying, however, has led to the development of resistant insect strains in the field. A cloned version of Bt toxin consists of the toxin gene fused to a regulatory region that allows expression of the toxin only when crops carrying the gene are under stress—as in an insect infestation. Should farmers be forced to plant the transgenic crops rather than spray their fields so that this biological pesticide will remain effective? Are there ways to enforce this policy in the United States or worldwide?

Many scientists who are employed as professors at universities have become involved in biotechnology ventures outside the university. Companies often set up their

laboratories near universities to take advantage of the intellectual resources there. Industries that develop near universities employ nonscientists in the community as well as scientists and are generally looked upon as an asset to the community. The president of a major state university is encouraging faculty members to become active in the development of associated industries, viewing their mission as academics to include community-related activities. But legislators and the public, whose tax dollars fund the university, believe that the professors should concentrate on teaching. Should faculty be encouraged to participate in outside ventures because it is a service to the community and potentially to humankind through development of new biotechnology, or should they be held more strictly to a solely academic, teaching mission?

In studying virulence in bacteria, a group of researchers stumbled on ways of modifying a particular bacterial species in a way that increased the virulence. While their finding helped them understand the mechanism of virulence better, the group of researchers were split on whether to publish their findings or not. Some fear that this new information could be misused in developing biological warfare. Do scientists have a responsibility to withhold information if it could be used in a harmful way?

Since the cloning of the human growth hormone gene (HGH), the hormone has become available as a drug and is prescribed for children with growth hormone defects. Fred and Susannah’s 12-year-old son Sam is below average in height, and his parents want the family doctor to prescribe growth hormone. They feel that Sam is suffering socially because of his small size and that his height will have a lasting psychological impact on him. The doctor believes that medicine with a lifelong effect is only appropriate when actual disease is present, and he does not consider Sam to have a disease. Who should set the limits for the use of HGH to treat potential growth problems in children— a governmental agency, the child’s physician, or the parents? If a governmental agency or an individual physician regulates the use of HGH, how should they decide on a cutoff height at which to begin treatment, and how should they determine a final height at which treatment should end? In thinking about these questions, take into consideration the fact that different human populations have different distributions of height, with mean values that can differ by as much as 7 inches.

Statins are a class of drugs that lower the level of a harmful form of cholesterol called LDL, which plays a significant role in atherosclerosis, a form of heart disease. The drug acts by inhibiting the liver enzyme HMG-CoA reductase, which converts HMG-CoA to mevalonate, an early step in the biosynthetic pathway for cholesterol. Unfortunately, in some people, some forms of the drug can cause grossly elevated levels of the muscle enzyme creatine kinase, leading to muscle failure and even, rarely, death. Sean has borderline high levels of LDL and wants to begin taking statins. His doctor thinks that the side effects of the drug are not well enough known, and she doesn’t want to prescribe the drug to Sean. Should Sean listen to his doctor, or should he try to find another doctor who is more willing to prescribe the drug?

Experimentation has shown that fetal tissue can be used to treat conditions such as the neurological disorder of Parkinson disease. However, because the fetal tissue is at a relatively early stage in development, it could contain many proteins that will affect the expression of genes in the tissue into which it is transplanted. If this is an experimental technology, should the individuals taking part in the trials be obliged to undergo testing that monitors changes in their physiology, or should they be able to choose which follow-up studies they want to participate in?

Taxol is a chemical produced in the bark of Pacific yew trees. In experimental trials, taxol reduced ovarian tumors in up to 50% of terminally ill patients. When this effect was first discovered, ovarian cancer patients were extremely anxious to get the drug. Unfortunately, the Pacific yew tree is a slow-growing tree found in old growth forests of the Pacific Northwestern United States. For a series of treatments, each patient would require the bark of approximately three trees. Because of the scarcity of trees and the difficulty in obtaining taxol from the bark, the expense was high. In 1993, the cost of production by the National Cancer Institute was $1200 for the 2 grams needed for each patient. When a drug is scarce, who should get the drug? The clinical trials involved patients for whom no other treatment had worked. Is this the best use of limited resources of a potentially powerful anticancer drug? Who should decide who gets the drug? On what basis should they make their decision?

In 1976, cancer patient John Moore had his spleen removed at a university teaching hospital as a treatment for the hairy cell leukemia from which he suffered. Some of his spleen cells were cultured at that time. During subsequent treatment other cell types were removed from the same patient and preserved in culture. Researchers eventually used some of these cells to establish a very useful T-cell line. The cell line produced the lymphokine GM-CSF, used in treating cancers and AIDS. A patent, granted to the university and the doctors for the cell line, was sold to two biotechnology companies. Moore filed a claim against the doctors, companies, and the university stating that he was entitled to some of the profits and that there had been a lack of informed consent. He had signed a consent form but was never informed of the potential for commercial exploitation. Several questions arise from the landmark legal case, Moore v. Regents of California. To what extent must a doctor disclose interests in a commercial venture to a patient? Does a person own the rights to cells that have been removed from his or her body?

Suitable animal models for the effects of exposure to radiation on humans are not available. Only tests on humans can make it possible to evaluate the dangers of chromosome damage and cancer resulting from various types of exposure. Under these circumstances, is human experimentation acceptable? Who should participate in human trials? Volunteers who are well apprised of the risks? Prisoners on death row? Are there valid alternatives?

The cost of medicine is rising faster than the rate of inflation. Some argue that because of this, we should not continue with expensive medical research. Yet the systems approach will in all likelihood decrease the cost of medicine. Here are some

of the reasons why. First, predictive and preventive medicine are less expensive than the diagnosis and therapy of reactive medicine. Second, the tools of predictive, preventive, and personalized medicine (for example, for sequencing human genomes and measuring proteins in the blood) will be far less expensive and more effective than the current less precise methods for measuring the parameters of health and disease. Third, systems approaches to the discovery of drug targets will diminish the cost of new drug development. The drug industry now spends about $1 billion per new drug; in the future, companies should be able to spend 20 times less than that. Do you think that the potential future savings related to the application of systems approaches to medicine are worth the current cost of clinical and basic research? In formulating your response, consider the potential for less expensive medical services in developing nations and the possibility of providing insurance to the 45 million uninsured people now living in the United States.

The digitization of medicine over the next 10 years may have a far greater impact on society than the digitization of information technology has already had. First, digitized medical records and tests are easy to transfer from one place to another. As a result, they can be made in one place, read by an expert in another, and returned to the patient and care provider in yet another. Second, digitized tools for extracting information from single molecules (such as proteins) and single cells (such as cancerous cells) will make it possible to rapidly and inexpensively compare normal and diseased cells taken by biopsy from the same patient; delineate the diseaseperturbed networks; and correlate them with molecular fingerprints in the blood. Accurate diagnosis (including disease stratification), efficient selection of the optimal treatment, and the ability to monitor a patient’s progress with a high degree of accuracy will follow. The digitization of information technology and communications has led to big revolutions in the lifestyles of both the developed and developing countries. The digitization of medicine will essentially make it possible to practice predictive, preventive, and personalized medicine inexpensively on a very large scale. Suggest some of the revolutions in health care that will come from the digitization of medicine. How will these changes be similar to or distinct from those which emerged from the digitization of information technology and communications? Compare the advantages of digitization with its potential drawbacks and describe what you consider to be the most effective way to implement the digitization of medicine.