Deck 19: Applications and Ethics of Genetic Engineering and Biotechnology

Question 1

Ralph , a 57 year old man, was diagnosed with colon cancer/ His oncologist discussed the use of radiation and chemotherapy as treatments for this cancer and explained that each of these therapies kills actively dividing normal and cancer cells, causing debilitating side effects. Ralph decided to carefully review his options and went for a second opinion to a cancer clinic at a major teaching hospital. There he learned that researchers in a synthetic biology program were testing the use of genetically modified E. coli that selectively invade and kill cancer cells, with no effects on normal cells. Ralph decided to participate in this trial , and at an appointment to learn about the details , he was informed that he would be part of a phase III trail, comparing the effects of the modified bacterial cells against conventional chemotherapy. As part of the trail , he would be randomly assigned to receive one or the other treatment , He was disappointed to learn this, because he assumed that he would receive the bacterial therapy.
What are Ralphs options at this point?

Answer 1

Phase III clinical trials are performed on about 1000 to 2000 number of patients of specific diseases to evaluate the efficacy and safety of the new therapeutic approaches. This includes the randomized controlled trains in multiple centers.
This is also known as "pre-marketing studies" because they are conducted to study the patient's response before marketing the drug.
It is given that Ralph is disappointed when he is informed that he will be given either the genetically modified E.coli therapy or some other therapy. In this case, Ralph's requirement is to get the treatment possibly without the treatment.
If he do not get the genetically modified E.coli as a treatment option, he is likely to receive another therapy, which can produce the side effects. So, Ralph must be clearly informed regarding what types of treatments he is going to receive by chance.
Thus, Ralph can either continue with the clinical trials or choose the chemotherapy and radiation therapy if he is convinced with the provided options.

Question 2

In this chapter, we focused on a number of interesting applications of genetic engineering, genomics, and biotechnology. At the same time, we found many opportunities to consider the methods and reasoning by which much of this information was acquired. From the explanations given in the chapter, what answers would you propose to the following fundamental questions:
(a) What experimental evidence confirms that we have introduced a useful gene into a transgenic organism and that it forms as we anticipate?
(b) How can we use DNA analysis to determine that a human fetus has sicke-cell anemia?
(c) How can DNA microarray analysis be used to identify specific genes that are being expressed in a specific tissue?
(d) How are GWAS carried out, and what information do they provide?
(e) What are some of the technical reasons why gene therapy is difficult to carry out effectively?

Answer 2

Not answer

Question 3

Ralph , a 57 year old man, was diagnosed with colon cancer/ His oncologist discussed the use of radiation and chemotherapy as treatments for this cancer and explained that each of these therapies kills actively dividing normal and cancer cells, causing debilitating side effects. Ralph decided to carefully review his options and went for a second opinion to a cancer clinic at a major teaching hospital. There he learned that researchers in a synthetic biology program were testing the use of genetically modified E. coli that selectively invade and kill cancer cells, with no effects on normal cells. Ralph decided to participate in this trial , and at an appointment to learn about the details , he was informed that he would be part of a phase III trail, comparing the effects of the modified bacterial cells against conventional chemotherapy. As part of the trail , he would be randomly assigned to receive one or the other treatment , He was disappointed to learn this, because he assumed that he would receive the bacterial therapy.
Should he reconsider and try radiation and chemotherapy instead?

Answer 3

It is given that Ralph is disappointed when he is informed that he will be given either the genetically modified E.coli therapy or some other therapy. In this case, Ralph's requirement is to get the treatment possibly without the treatment.
If he do not get the genetically modified E.coli as a treatment option, he is likely to receive another therapy, which can produce the side effects.
So, Ralph must be clearly informed regarding what types of treatments he is going to receive by chance. If he is not satisfied with the options and as the genetically modified E. coli therapy is not guaranteed, he can choose radiation and chemotherapy as they produce promising results possibly.

Question 4

Review the chapter concepts list on page 378. Most of these center on applications of genetic technology that are becoming widespread. Write a short essay that summarizes the impacts that genomic applications are having on society and the ethical issues presented by these applications.

Question 5

Ralph , a 57 year old man, was diagnosed with colon cancer/ His oncologist discussed the use of radiation and chemotherapy as treatments for this cancer and explained that each of these therapies kills actively dividing normal and cancer cells, causing debilitating side effects. Ralph decided to carefully review his options and went for a second opinion to a cancer clinic at a major teaching hospital. There he learned that researchers in a synthetic biology program were testing the use of genetically modified E. coli that selectively invade and kill cancer cells, with no effects on normal cells. Ralph decided to participate in this trial , and at an appointment to learn about the details , he was informed that he would be part of a phase III trail, comparing the effects of the modified bacterial cells against conventional chemotherapy. As part of the trail , he would be randomly assigned to receive one or the other treatment , He was disappointed to learn this, because he assumed that he would receive the bacterial therapy.
Or should he enrol on the chance that he would receive therapy using the genetically modified bacteria and that it would be more effective that conventional therapy?

Question 6

Why are most recombinant human proteins produced in animal or plant hosts instead of bacterial host cells?

Question 7

There are more than 1000 cloned farm animals in the United States. In the near future, milk from cloned cows and their off-spring (born naturally) may be available in supermarkets. These cloned animals have not been transgenically modified, and they are no different than identical twins. Should milk from such animals and their natural-born offspring be labeled as coming from cloned cows or their descendants? Why?

Question 8

One of the major causes of sickness, death, and economic loss in the cattle industry is Mannheimia haemolytica , which causes bovine pasteurellosis, or shipping fever. Noninvasive delivery of a vaccine using transgenic plants expressing immunogens would reduce labor costs and trauma to livestock. An early step toward developing an edible vaccine is to determine whether an injected version of an antigen (usually a derivative of the pathogen) is capable of stimulating the development of antibodies in a test organism. The following table assesses the ability of a transgenic portion of a toxin (Lkt) of M. haemolytica to stimulate development of specific antibodies in rabbits.
(a) What general conclusion can you draw from the data?
(b) With regards to development of a usable edible vaccine, what work remains to be done?
* Lkt50 is a smaller derivative of Lkt that lacks all hydrophobic regions. + indicates at least 50 percent neutralization of toxicity of Lkt; - indicates no neutralization activity.
Source: Modified from Lee et al. 2001. Infect. and Immunity 69: 5786-5793.

Question 9

Describe how the team from the J. Craig Venter Institute created a synthetic genome. How did they demonstrate that the genome converted the recipient strain of bacteria into a different strain?

Question 10

Sequencing the human genome and the development of microarray technology promises to improve our understanding of normal and abnormal cell behavior. How are microarrays dramatically changing our understanding of complex diseases such as cancer?

Question 11

A couple with European ancestry seeks genetic counseling before having children because of a history of cystic fibrosis (CF) in the husband's family. ASO testing for CF reveals that the husband is heterozygous for the ? 508 mutation and that the wife is heterozygous for the R117 mutation. You are the couple's genetic counselor. When consulting with you, they express their conviction that they are not at risk for having an affected child because they each carry different mutations and cannot have a child who is homozygous for either mutation. What would you say to them?

Question 12

When genome scanning technologies become widespread, medical records will contain the results of such testing. Who should have access to this information? Should employers, potential employers, or insurance companies be allowed to have this information? Would you favor or oppose having the government establish and maintain a central database containing the results of individuals' genome scans?

Question 13

What limits the use of differences in restriction enzyme sites as a way of detecting point mutations in human genes?

Question 14

Might it make sense someday to sequence every newborns genome at the time of birth? What are the potential advantages and concerns of this approach?

Question 15

What is the main purpose of genome-wide association studies (GWAS) How can information from GWAS be used to inform scientists and physicians about genetic diseases?

Question 16

The family of a sixth grade boy in palo alto, California , was informed by school administrators that he would have to transfer out of his middle school because they believed his mutation of the CFTR , which does not produce any symptoms associated with cystic fibrosis, posed a risk to other students at the school, a settlement was reached to have the boy return to school. Based on what you know about GINA, the genetic information Non discrimination Act , what ethical problems might you associate with this example?

Question 17

Dominant mutations can be categorized according to whether they increase or decrease the overall activity of a gene or gene product. Although a loss-of-function mutation (a mutation that inactivates the gene product) is usually recessive, for some genes, one dose of the normal gene product, encoded by the normal allele, is not sufficient to produce a normal phenotype. In this case, a loss-of-function mutation in the gene will be dominant, and the gene is said to be haploinsufficient. A second category of dominant mutation is the gain-of-function mutation, which results in a new activity or an increased activity or expression of a gene or gene product. The gene therapy technique currently used in clinical trials involves the "addition" to somatic cells of a normal copy of a gene. In other words, a normal copy of the gene is inserted into the genome of the mutant somatic cell, but the mutated copy of the gene is not removed or replaced. Will this strategy work for either of the two aforementioned types of dominant mutations?

Question 18

In 2013 the actress Angelina Jolie elected to have prophylactic double -mastectomy surgery to prevent breast cancer based on a positive test for mutation of the BRCA1 gene , What are some potential positive and negative consequences of this high profile example of acting on the results of genetic test?

Question 19

The Genetic Testing Registry is intended to provide better information to patients, but companies involved in genetic testing are not required to participate. Should company participation be mandatory? Why or why not? Explain your answers.

Question 20

Should the FDA regulate direct-to-consumer genetic tests, or should these tests be available as a "buyer beware" product?

Question 21

Would you have your genome sequenced, if the price was affordable ? why or why not? If you answered yes , would you make your genome sequence publicly available ? How might such information be misused?

Question 22

Following the tragic shooting of 20 children at a school in New town, Connecticut, in 2012, connecticuts state medical examiner requested a full genetic analysis of the killers genome. What do you think investigators might be looking for? What might they expect to find? Might this analysis lead to oversimplified analysis of the cause of the tragedy/

Question 23

Private companies are now offering personal DNA sequencing along with interpretation. What services do they offer? Do you think that these services should be regulated, and if so in what way ? Investigate one such company , 23 and Me, at http:// www.23and Me.com.

Question 24

Yeager , M., et al. (Nature genetics 39: 645- 649,2007) and sladek , R. et al ,(Nature 445:881 - 885, 2007 )have used single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS)to identify novel risk loci for prostate cancer and Type2 diabetes mellitus respectively. Each study suggests that disease test genes can be identified that significantly contribute to the disease state. Given your understanding of such complex diseases , what would you consider as reasonable factors to consider when interpreting the results of GWAS studies?

Question 25

In March 2010, Judge R. Sweet ruled to invalidate Myriad Genetics' patents on the BRCA1 and BRCA2 genes. Sweet wrote that since the genes are part of the natural world, they are not patentable. Myriad Genetics also holds patents on the development of a direct-to-consumer test for the BRCA1 and BRCA2 genes. Judge Sweet's ruling was subsequently reversed.
(a) Would you agree with Judge Sweet's ruling to invalidate the patenting of the BRCA1 and BRCA2 genes? If you were asked to judge the patenting of the direct-to-consumer test for the BRCA1 and BRCA2 genes, how would you rule?
(b) J. Craig Venter has filed a patent application for his "firstever human made life form." This patent is designed to cover the genome of M. genitalium. Would your ruling for Venter's "organism" be different from Judge Sweet's ruling on patenting of the BRCA1 and BRCA2 genes?