Gene Choices and Genetic Information
Introduction
Test your Intuition
Welcome to lesson 4. We are going to be introduced to a new topic today: genetic choices and genetic information. In this lesson, we face yet another case of modern technology outpacing our conventional moral practice. If you have been following the news, you may know that the Nobel Prize in Chemistry in 2020 has been awarded to the two scientists in the pictures. Do you happen to know their contribution?
Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna won the Nobel Prize for the development of a powerful way to change DNA. They transformed an obscure bacterial immune mechanism, commonly called CRISPR, into a tool that can simply and cheaply edit the genomes of everything from wheat, mosquitoes, to humans.
Human Genome Project and Moral Questions
Let’s start by learning about the Human Genome Project (HGP). The Human Genome Project was one of the great feats of exploration in history. Rather than an outward exploration of the planet or the cosmos, the HGP was an inward voyage of discovery led by an international team of researchers seeking to sequence and map all of the genes (the fundamental unit of biological inheritance)— together known as the genome (an organism’s entire complement of DNA)—of members of our species, Homo sapiens. Onscreen is an image of the monument to the laboratory mouse in Novosibirsk, Russia. It commemorates the sacrifice of the mice in genetic research used to understand biological and physiological mechanisms for developing new drugs and curing of diseases. Beginning on October 1, 1990, and completed in April 2003, through the HGP, we are able to, for the first time, read nature's complete genetic blueprint for building a human being. The length and breadth of the human genome, determining the exact sequence of a human being’s 3 billion letters of DNA code, all grouped into 20,000 to 25,000 genes.
Now, scientists are rapidly pinpointing genetic factors that cause or contribute to diseases, developing tests to identify and predict (even before conception) specific human conditions, researching ways to alter genes to affect cures or devise treatments, enabling parents to have control over the genetic makeup of their children, and peering into the future with the power to change profoundly the human genome itself.
At each step, moral questions press in, and they intersect with almost every major ethical concern in this text: paternalism, autonomy, beneficence, rights, confidentiality, abortion, killing, personhood, reproductive technology, justice in providing health care, research ethics, and more. Science has once again outpaced conventional moral understanding as genetics inserts a host of raw, hard questions into our lives: Should genetic testing be used to identify or predict diseases even when no treatment is available? Do carriers of a deadly genetic disease that is likely to be passed on to their children have a duty to warn those children of the risk? Who should control genetic information about a person, and what is a physician’s duty regarding truth-telling and confidentiality? Is it “playing God” to alter someone’s genes to treat diseases or prevent them in future generations? We will explore some of these issues in this lesson.
The Limits of Genetic Testing
We are going to discuss a number of issues relating to the use of information or technology related to genes. We will start from genetic testing, then move to the two types of gene therapy.
The first thing we need to know about genetic testing is that it almost never yields conclusive answers; genetic testing can only give us probabilities of developing a disease. In other words, genetic testing is not an accurate prediction in a deterministic world where things are bound to happen. A positive result only predicts the likelihood of developing a certain disease, whereas a negative result does not guarantee a disease-free future either. Popular culture sometimes likes to exaggerate the power of (and threat posed by) new technologies, but we must know their limitations.
Cannot predict how severe symptoms will be, or when they will appear
May not be able to do anything about the prediction of the likelihood of having a certain disease
In addition, gene testing also cannot predict how severe the symptoms are going to be, or when they will appear. In other words, we are privy to less information as many believed us to be. That being said, the power to identify and predict genetic disorders has outpaced our ability to do anything about them. We may not be able to do anything about the prediction—the likelihood of having a certain disease. It is thus perfectly understandable that some of us do not want to know the information genetic tests could provide. It is good to keep in mind these limitations as we move forward.
Genetic Testing: Moral Issues
Divulging Information
For example, since the disease-causing gene is likely shared amongst the patient’s family members and not just limited to this individual, does a health care professional (HCP) have a duty to inform the patient’s family members of this gene that they may be carrying? On one hand, it is in the family members’ interests to know, and they may even have a right to know, as this information is crucial to their own health. On the other hand, the patient’s confidentiality with the HCP will be compromised if the HCP communicates this information with the family members.
Genetic Discrimination
Further, genetic information, when collected and stored electronically, may be made available to parties other than the HCP (for example, insurance companies). They may use this information to calculate the likely costs of a person’s medical expenses in the future and refuse to provide service or provide service to them at a higher cost. Disclosing genetic information leads us to the issue of possible discrimination based on people’s genomes.
Genetic Screening and Abortions
Another important fact is that through gene screening, prospective parents may choose to abort fetuses with undesirable features or disabilities. This is alarming. This is met with criticism from the ethicists and community of people with disabilities. We will discuss one’s right to reproduction shortly in the lesson discussing reproductive freedom and reproductive rights; we will learn that no one is entitled to an “ideal” baby despite our reproductive rights.
Somatic Gene Therapy
Overview
Now that we have talked about genetic testing, let us review gene therapy. We will talk about two types of gene therapies: somatic and germline gene therapy. They are very different from each other, please keep this in mind as we go forward to discuss somatic gene therapy in this section. We will explore germline gene therapy in the next section. Somatic gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient‘s cells instead of using drugs or surgery. Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease.
How it Works
Somatic gene therapy replaces a faulty gene or adds a new gene in an attempt to cure a disease or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia, and acquired immunodeficiency syndrome (AIDS).
Procedures
Researchers are still studying how and when to use gene therapy. Currently, in the United States, gene therapy is available only as part of a clinical trial. There are currently a number of ways to do this:
Replacing a missing or defective gene with a normal one
Repairing a faulty gene so it will function properly
Activating or deactivating a gene (switching it on or off)
Delivery Method
Gene therapy has some potential risks. A gene can't easily be inserted directly into your cells. Rather, it is usually delivered using a carrier, called a vector.
The most common gene therapy vectors are viruses. They are good vectors because they can recognize certain cells and carry genetic material into the cells' genes. Of course, we know viruses can cause diseases themselves, so researchers remove the original disease-causing genes from the viruses (for example for a cold virus, the genetic material that causes cold), replacing them with the genes needed to stop the patient’s disease. Now, through the manipulation, the viruses researchers cultivate no longer cause the disease that’s typically associated with this type of virus (e.g., cold for cold virus); instead, they carry the genes to cure an existing disease in the patient.
Risks of Somatic Gene Therapy
The technique of somatic gene therapy presents a number of risks. There are four types of them.
Unwanted immune system reaction
Targeting the wrong cells
Infection caused by the virus
Possibility of causing a tumour
First, unwanted immune system reaction: Your body’s immune system may see the newly introduced viruses as intruders and attack them. This may cause inflammation and, in severe cases, organ failure. Second, targeting the wrong cells: Because viruses can affect more than one type of cells, it's possible that the altered viruses may infect additional cells—not just the targeted cells containing mutated genes. If this happens, healthy cells may be damaged, causing other illnesses or diseases, such as cancer. Third, infection caused by the virus: It's possible that once introduced into the body, the viruses may recover their original ability to cause disease. Fourth, possibility of causing a tumor: If the new genes get inserted in the wrong spot in your DNA, there is a chance that the insertion might lead to tumor formation.
Patient Cases
Jesse Gelsinger
For a first patient case, please review the articles on Jesse Gelsinger’s case (called Death but one unintended consequence of gene-therapy trial; and also in Case 4 Jesse Gelsinger: Research Conflicts and Ethical Review), found in your Readings list. This is a significant event that has been frequently discussed in light of the safety of gene therapy.
Jesse Gelsinger had ornithine transcarbamoylase (OTC) deficiency and was considered an ideal candidate for the experimental trial, led by Dr. James Wilson, director of the Institute for Human Gene Therapy at the University of Pennsylvania. On September 13, 1999, the 18 years old Gelsinger who was a student at University of Pennsylvania, was given an infusion of corrective OTC gene encased in a dose of attenuated cold virus, a recombinant adenoviral vector. Gelsinger experienced a severe immune reaction to the vector—the gene's delivery vehicle—and died 4 days after receiving the injection. The major question surrounding his death involves informed consent. A lawyer retained by his family says Gelsinger was not told that several other patients had experienced serious side effects from the therapy, or that 3 monkeys had died of a clotting disorder and severe liver inflammation after being injected.
Victoria Gray
We will revisit this case again in the lesson discussing Research with Human Subjects. The second case is a more positive report of Victoria Gray, who underwent the gene therapy for sickle cell disease. Please review the article in your Readings list (called A Year In, 1st Patient To Get Gene Editing For Sickle Cell Disease Is Thriving).
Germline Gene Therapy
Overview
As mentioned, there are actually two types of gene therapies: somatic cell and germline cell therapy. In the previous component, we only discussed somatic cell gene therapy. These two types have some key differences that results very different moral considerations. As we have discussed for somatic genome editing, there are four risk types for the patient. With germline genome editing, however, it is even more complicated and may affect people other than the patient; in other words, the risks are not limited to the patient, which is why scientists and philosophers are very concerned about the use of it.
Somatic vs. Germline
Somatic gene therapy involves altering genes in a person’s somatic (body) cells, such as liver or muscle cells, to treat an existing disorder. The alterations can help the person suffering from the disease but are not inheritable — they cannot be passed on to the person’s offspring. They affect the person’s genome but not the genomes of subsequent generations.
Germline gene therapy entails modifying genes in germline cells (egg and sperm cells) and zygotes — these alterations are inheritable. Currently, the scientific focus is on somatic cell gene therapy, with most research evaluating treatments for cancer, heart disease, and infectious diseases.
Effects on Genome
Germline human genome editing alters the genome of a human embryo at its earliest stages. This may affect every cell of the body, including their gametes, which means it has an impact not only on the person, but possibly on their descendants. There are, therefore, substantial restrictions on its use.
Considerations
Manipulation of germline cells
Desire to cure a disease for all future generations
Fabrication of “designer” babies
Risk of introducing errors into the collective human genome
Gene therapy in germline cells is not yet feasible. But the ability to manipulate germline cells evokes both the dream of eradicating mutations from future generations (and thus cure or prevent a disease for all future generations) and the nightmare of fabricating “designer” babies or introducing horrible errors into the collective human genome.
Germline Genome Editing Case
Now, let us review a very relevant event: the CRISPR-baby scandal. A scientist named Dr. He Jiankui, at an international summit on genome editing, announced on November 26th, 2018, that he and his team had helped produce genetically edited twins, to make the twins‘ cells resistant to infection by human immunodeficiency virus (HIV). This was met with criticism from the scientific community worldwide and he was later sentenced to prison for three years for conducting “illegal medical practice.” For more information on this case, select the first link, “Researcher defends CRISPR twins work.” For additional information, select the second link, “The CRISPR-baby scandal.” 7. Germline
He Jiankui’s irresponsible behavior has called out attention to the lack of regulation in germline genome editing. While scientists agree that it could be potentially beneficial and seem to provide a cure for families who have watched their children suffer from devastating genetic diseases, the risks are too high and too hard to predict. “Diversity” is our survival strategy when it comes to evolution. Having diverse genes ensures that humankind can adapt to environmental changes. If future generations are engineered to have certain traits that we deem desirable today, in the future, with the changes to the environment we live in, those “desirable traits” may turn into risky liabilities — the risks are really hard to predict.
Wrap-Up
In this lesson, we have discussed:
limitations of gene testing
Promises and pitfalls of gene therapy
Two types of gene therapy:
Somatic gene editing
Germline gene editing
A number of issues in relation to the ethical challenges brought to us by the development of gene technology. We have discussed the limitations of the helpful tool, gene testing. We also discussed the promises and pitfalls of gene therapy. We also have talked about, importantly, the two types of gene therapy, namely the somatic gene editing which targets single cells in patients and is not inheritable and the germline gene editing which changes the germline cells and are inheritable. I hope by now, we have a better understanding of the ethical complications revolving around gene testing and gene editing.