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Lorenzo's Oil

COMPREHENSION TEST

For a printable version of this test suitable to distribute to a class (without suggested answers) click here. This test does not include questions about: (1) genetics (see Lesson Plan -- Predicting Combinations for Alleles in a Zygote Using Punnett Squares); (2) the scientific method, see Lesson Plan -- The Development of Lorenzo's Oil, Strange Twists of Fate, and the Scientific Method); and (3) the medical ethics of clinical trials (for a short quiz on that topic click here).

1.  What does the term VLCSFA stand for? Suggested Response: A saturated fatty acid with a very long hydrocarbon tail.

2.  Focus on a single link in the hydrocarbon tail of a VLCSFA. What are the elements that make up that link and how many atoms of each element are contained in each link? Suggested Response: The elements are hydrogen and carbon and each link has two hydrogen atoms and one carbon atom.

3.  What does the term VLCUFA stand for and how is it different than a VLCSFA? Draw a diagram showing the different linkages. Suggested Response: In VLCSFAs, the links in the hydrocarbon chain are made up of one carbon atom filling the four empty places in its outermost valence shell by sharing one electron with each of two hydrogen atoms and one electron each with the carbon atoms in the adjacent links of the chain. In an unsaturated fat, there is at least one link in the chain in which one carbon atom fills the empty places in its valence shell by double bonding with the carbon atom in an adjacent link. The linkages are shown in the Diagrams of Four Fatty Acids.

4.  What two parts of the body are most damaged by ALD? Suggested Response: The white matter of the brain consisting of the myelin sheaths that surround and insulate nerve fibers and the adrenal gland.

5.  What are the two sources of VLCSFAs in the body? Suggested Response: VLCSFAs come from food and from biosynthesis by the body itself.

6.  Name and describe the part of the cell in which VLCSFAs are synthesized by the body. Suggested Response: The smooth endoplasmic reticulum. This is a highly convoluted membrane within cells which is responsible for the biosynthesis of proteins and lipids.

7.  What are peroxisomes and what is their role in maintaining safe levels of VLCSFAs in normal people? Suggested Response: Peroxisomes are microbodies (organelles) within cells that contain enzymes that oxidize various chemicals in the body, including proteins and lipids. Peroxisomes in liver cells keep the level of VLCSFAs at safe levels by oxidizing excess VLCSFAs.

8.  What do normal people have that ALD patients lack? Suggested Response: ALD patients do not have a transporter protein that moves excess VLCSFAs into the peroxisomes so that they can be degraded through oxidation. Peroxisomes in liver cells contain the enzyme that causes the oxidation of VLCSFAs.

9.  Describe the model that Augusto Odone developed to show the problem of reducing VLCSFAs in Lorenzo's body. Suggested Response: It is a sink with a blocked drain and two faucets. One faucet represents the VLCSFAs from food and the other represents the biosynthesis of VLCSFAs by the body. The drain represents the enzyme activity in the peroxisomes that oxidize VLCSFAs. The plug in the drain represents the failure of the body to transport the VLCSFAs to the peroxisome for destruction. In order to lower the water level (the level of VLCSFAs) both taps had to be turned off. See ALD and Lorenzo's Oil.

10.  What was the contribution of the article by the Polish chemists and where did it leave the Odones? Suggested Response: The paper from the Polish chemists showed that when rats were fed oleic acid their blood levels of VLCSFAs went down. The next question was "why did this occur"?


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11.  Explain how Lorenzo's Oil works to prevent the buildup of VLCSFAs in the body. Suggested Response: It inserts so many unsaturated fatty acids into the body that only a few VLCSFAs are made.

12.  In the movie, the Odones were confronted with a number of questions that they had to answer. An early question was why Lorenzo's VLCSFA levels went up even when the VLCSFAs were eliminated from his diet. Hopefully, by looking at the sink model you know the answer. (It is that VLCSFAs were still being made by biosynthesis.) Another question the Odones had to answer was why biosynthesis of saturated fats was reduced when Lorenzo was given oleic acid, an unsaturated fat. Why did that occur? Suggested Response: Scientists had previously thought that the harmful VLCSFAs were produced by one enzyme and that the harmless VLCUFAs were produced by another enzyme. Augusto Odone hypothesized that one enzyme added hydrocarbon chains to both saturated fatty acids and unsaturated fatty acids. If there were only a limited number of sites at which this enzyme was located, then as the amount of unsaturated fatty acids in the body increased, the opportunity for VLCSFAs to be created would be decreased. This way of manipulating enzyme activity is called "competitive inhibition."

13.  Does Lorenzo's Oil correct the damage done by VLCSFA's? Suggested Response: No. It does not restore the myelin sheath.

14.  When do symptoms of ALD appear and how many boys with the defective ALD gene will actually get the disease and show symptoms during that period? Suggested Response: Symptoms appear between the ages of 4 and 8. Approximately 35% of boys who have the defective gene get ALD and show symptoms at ages 4 to 8.

15.  Name five symptoms of ALD. Suggested Response: Symptoms include (1) poor memory; (2) loss of emotional control; (3) dementia; (4) muscle weakness; (5) difficulty in walking; (6) spasticity; (7) deficiencies with hearing; (8) problems with speech; (9) problems with vision; (10) deteriorated muscle tone; (11) difficulty swallowing; and (12) coma.

16.  What is the prognosis for patients with untreated ALD? Suggested Response: Very poor. The disease, untreated, results in increasing disability and then death.

17.  What is the earliest point at which ALD can be diagnosed with modern medical techniques? Suggested Response: Early during pregnancy.

18.  Name two current treatments for ALD. Suggested Response: There are four: (1) Lorenzo's Oil (really a preventive treatment); (2) Adrenal steroid replacement therapy; (3) Bone marrow transplantation; and (4) symptomatic and supportive treatments such as physical therapy, psychological support, and special education.

19.  Are excessive levels of VLCSFAs part of the cause of the deterioration of the myelin sheath in ALD sufferers or is it a mere byproduct of that process? How do we know this? Suggested Response: An excessive level of VLCSFAs is part of the cause of the deterioration of the myelin sheath. We know this because when VLCSFAs are kept at normal levels in asymptomatic boys with the ALD gene, the vast majority do not suffer loss of their myelin sheath.

20.  What is adrenomyelonueropathy (AMN), how does it relate to ALD, and who gets it? Suggested Response: It is the adult form of ALD. It is much milder than ALD and afflicts men between the ages of 21 and 35.

21.  EXTRA CREDIT: The Odones were very lucky in their effort to find a way to arrest the progress of ALD in their son. One of the reasons that the scientists were reluctant to immediately publish the remarkable drop in the level of VLCSFAs in Lorenzo's blood was that they had no idea of what Lorenzo's Oil would do to the human body. Focus on the different possible effects of competitive inhibition and describe a possible scenario for damage that could have been caused by the ingestion of Lorenzo's Oil. Suggested Response: There is no one right response to this question. Look for scenarios which are logically possible. Examples are: (1) The enzyme process by which VLCSFAs and VLCUFAs are made could also make other compounds which are necessary for life. By crowding them all out with large amounts of unsaturated fatty acids, not only would the production of VLCSFAs be reduced but the production of these other necessary compounds could be reduced or eliminated. Lorenzo could have died or suffered a severe injury as a result. (2) The level of VLCUFAs could be driven so high that they became toxic and caused some other potentially fatal disease.

QUESTIONS ON MEDICAL ETHICS    
(These questions can be used as a test. Click here for a Microsoft Word version without answers.)

1.  What risks did the Odones take by giving a combination of oleic acid and erucic acid to Lorenzo? Suggested Response: The risks were that the additional fatty acids would cause Lorenzo to have some other illness and that it would even make the ALD disease worse. Animals studies had shown the erucic acid caused heart disease in rats. Lorenzo's ability to metabolize fats was already compromised. It was possible that he couldn't metabolize large amounts of VLCUFAs. (Note that Lorenzo's Oil does have side effects. For example, it reduces platelet count.) However, the Odones thought that it was worth the risk because it was the only way that had any chance of reducing the level of VLCSFAs in Lorenzo's body. They were lucky.

2.  What did the Odones do that no ethical scientist would do? Suggested Response: The Odones gave a human being an untested therapy which had caused disease in laboratory animals without reviews and approvals by panels of physicians. See Medical Ethics.

3.  What is a clinical trial? Why are there such strict rules regulating clinical trials? Suggested Response: A clinical trial is the testing of unproven treatments on human beings. The rules are strict because research scientists have a built in conflict of interest between their personal interests in professional advancement and financial gain and the safety of their patients. While most researchers are ethical and would put the interests of the patient first, the lure of professional recognition or fortune could lead susceptible scientists astray.

4.  What are anecdotal results and why are research doctors suspicious of them? Give an example of an anecdotal result from the movie. Suggested Response: Anecdotal results are observations of one or a few individuals. Researchers are suspicious of such information because it could be the result of unknown factors or an incorrect observation. Lorenzo's positive reaction to the Oil is a perfect example. The result was misleading because other children with ALD did not get better when they took Lorenzo's Oil. Except for Lorenzo, Lorenzo's Oil works only on children who take it before they develop symptoms.

5.  Why don't drug companies usually develop drugs for diseases like ALD? Do you fault them for this? Suggested Response: There is no one right answer to this question. A good answer would include the following concepts: Since so few people get ALD, there is no chance for the drug companies to make back the money they would have to invest in discovering a cure. However, drug companies are generally, as a group, the most profitable industry sector in the U.S. economy. An argument can be made that they should be required to invest some of those profits in research on the "orphan diseases." Then again, wouldn't a better use of their profits be to subsidize research on diseases that affect more people or AIDs treatment for people who can't otherwise afford it?

6.  What was different about the Odone's situation that justified their willingness to take the risks despite the objections of the physicians? Suggested Response: ALD is invariably fatal in a short period of time, and the Odones had no conflict of interest that a normal scientist would have. The conflict is between the interests of patients in clinical trials and the interests of the doctor in professional recognition and financial gain. The Odones only had Lorenzo's interests at heart.

7.  Why is ALD called an "orphan disease"? Suggested Response: ALD is an "orphan" disease because there are so few people with the disease that finding a cure was not a priority for the government, the drug companies, or the scientific community. In addition, there was no large organization of patients and their families to publicize the need for a cure or treatment.

8.  What is the goal of the Myelin Project, the foundation started by the Odones? Suggested Response: To stimulate scientific research to find a way to remyelinate nerve cells. An alternative acceptable response would refer to the goal of The Myelin Project to provide a "framework in which researchers can cooperate effectively, by giving scientists adequate, prompt financing and by continuously interacting with them. ... To counter researchers' endemic conservative stance...."

9.  Do you think that female carriers of ALD should have children? What about the boys who, because of Lorenzo's Oil and careful medical treatment, survive to adulthood and get married? Should they have children? Suggested Response: There is no one right answer. A good answer will refer to: (1) adoption as a good alternative; (2) the 50% chance with any carrier and with any male who has the ALD defect who survives to childbearing years, that the defective gene will be transmitted to succeeding generations; and (3) the serious impact on that having the genetic defect will have on a person's life.

10.  Do you think that the leaders of the ALD society (Mr. and Mrs. Muscatine) as portrayed in the movie acted in the way that leaders of a support group should act? Suggested Response: First, note that Dr. Moser contends that the parents support group (The American Leukodystrophy Association), were helpful and that the scene of the meeting in which the parents demanded access to Lorenzo's Oil never occurred. This question refers to the actions of the fictional characters and the fictional organization portrayed in the film. There is no one correct answer. A good answer will note the following concepts: Leaders of citizen groups interested in helping families with diseases such as ALD have a multi-faceted role. They are advocates for their members, the victims of the disease and their families. They also help their members interact with the medical community. In many, probably most, situations the position taken by the organization in the movie would have been correct, i.e., the best thing to do is to follow the doctors' advice and follow standard procedures. Depending upon their beliefs, some families may think that it is better to let the afflicted child escape his misery. In this case it wasn't, but that was because of unusual luck and the perseverance of the Odones and Dr. Moser.

QUESTIONS RELATING TO CRITICAL VIEWING SKILLS

1.  Describe two scenes in which a sense of foreboding in the music is contrasted with a scene of normal life. Suggested Response: (1) The scene just before Lorenzo falls from his bike and (2) Lorenzo's birthday party.

2.  Name two archetypal storylines which are used to add depth to the film. Suggested Response: Here are three: (1) The Christ story of someone who suffers for the benefit of others; (2) The struggle of people against a heartless nature; (3) the struggle of powerless people against a large institution in society.

3.  Describe two scenes or cinematic effects in which Lorenzo is associated with the Christ child. Suggested Response: Here are four. There are several more. (1) the religious sounding music; (2) images of Lorenzo and his mother are contrasted with a statue of the Madonna and Child; (3) the scene in which Augusto Odone asks his wife "Do you ever think that maybe all this trouble has been for somebody else's kid?"; (4) the scene near the end of the film, just before the testimonials, which shows a ceiling of a church with frescoes of angels.

4.  Name two myths of American culture that are fostered by this film. Suggested Response: There are three. The first is that a cure can be found for any illness if only the bureaucracy and red tape will get out of the way. People want desperately to believe this. The second is a strong belief that perseverance, hard work and love can conquer any ailment. In fact this is not true, as is demonstrated by the many people who have exhausted themselves and compromised their health by caring for an injured child or loved one. The third is the theme that mainstream science is indifferent to the suffering of patients and their families.

5.  A few emotional scenes in the film are spoken in Italian, with subtitles. Why did the director use this device? Suggested Response: Putting the words in a beautiful foreign language with the translation in text on the screen insulates us from these emotions and make it easier to dealt with them. The Italian makes the scenes both poignant and more memorable. We know that Mr. Odone is speaking from the depths of his heart when he lapses into Italian.

OTHER DISCUSSION QUESTIONS

1.  Think of the theme of the film that relates to man battling a harsh and uncaring natural world. What is ironic about this theme in its application to the experience of Lorenzo and Michaela Odone? Suggested Response: The agent of the harsh and uncaring nature was their own genes.

2.  Do you think that the Odones were arrogant as the head of the Foundation claimed? Suggested Response: There is no one right answer to this question. A good answer would include the concept that any amazing accomplishment can be said to be arrogant.

3.  What was the role of luck in the Odones' search for a way to stop the deterioration of Lorenzo's condition? Suggested Response: Phenomenal. They were very lucky to have found two oils that helped some children with ALD and that did not have devastating side effects. They were lucky that the Oil had any positive effect on Lorenzo, when it didn't help other children with ALD who had already developed symptoms.

4.  What happens when scientists work in isolation and don't communicate with each other? Suggested Response: Opportunities for putting different ideas together and finding a good result are lost.

5.  What does this movie demonstrate about the role of scientific symposia in the process of advancing scientific knowledge? Suggested Response: The movie shows the exchange of knowledge in person to person conversations and seminars that can lead to scientific breakthroughs. The government and foundations supporting scientific research spend hundreds thousands of dollars on symposia each year, paying scientists to travel all over the world to attend meetings and talk with each other. The purpose of these trips is exemplified in the value of the symposium to the Odones.

6.  What is "modeling" in scientific research and how does it help scientists make new discoveries? Suggested Response: It provides a way to visualize a problem or a natural phenomenon, so that scientists can focus on a solution and come up with new ideas about hypotheses to test.

Social-Emotional Learning Discussion Questions:

FAMILIES IN CRISIS - MARRIAGE - PARENTING

1.  Compare the reaction of this family to the other families with children who had the same illness. Could every family have reacted in the way that the Odones did? Suggested Response: The Odones had a particular combination of intelligence, drive and independence which caused them to look on their own for a therapy. In addition, the library of the National Institutes of Health was within driving distance from their home. The Odones didn't stand in awe of the doctors as other ALD parents did.

2.  Were there any special attributes that the Odone family possessed which permitted them to find a way to stop the deterioration of their son's health? Suggested Response: Determination, intelligence, education and sufficient assets to devote money to the effort of finding a cure.

3.  Should Michaela have felt guilty that it was her genes that contained the defect that caused Lorenzo to have ALD? Suggested Response: No. She had no control over it. The disease was only first described ten years before, and no one had warned her that she needed genetic counseling.

ILLNESS - DISABILITIES

4.  Before the discovery of Lorenzo's Oil, was it better to simply allow children with the ALD defect to die? Suggested Response: This is a highly emotionally charged question, and for some, it raises important religious issues. The main point is that no matter how strongly people feel about it in their own lives and based on their own religions, reasonable and ethical minds will disagree. There is no one right answer to this question. Good answers will deal with some of the following issues of the ethics of giving up on a life: the fact that if the Odones hadn't tried so hard, Lorenzo's Oil would never have been invented; the trade-off of resources (resources spent on helping the few children suffering from ALD could be better used helping thousands (or more) children suffering from less complicated diseases or starving); the cost to the Odones' lives of their single minded devotion to Lorenzo; and the quality of Lorenzo's life.

5.  Michaela Odone devoted herself to caring for Lorenzo and gave up most other parts of her life. She exhausted herself in caring for him. Her husband believes that it hastened her death. Do you think that she reacted in the right way to her son's illness? What would you have done? Suggested Response: There is no one right answer to this question. A good answer will discuss the issues raised in the answer to the preceding question and note that people all over the world exhaust themselves caring for a sick loved one.

6.  What did you think about Dr. Nikolais? Was he a good doctor or not? Suggested Response: Dr. Nikolais is depicted as a caring physician who is unwilling to go outside of the ethical rules of his profession to save Lorenzo's life. Note that even though he won't participate in the erucic acid trial on Lorenzo he gives advice to Mr. Odone as to the dosage. Dr. Nikolais is used in the film to represent the medical research establishment and a major theme of the film is the difficulty that medical researchers have in responding to a disease such as ALD. However, as shown in the section on Medical Ethics there are important and valid reasons to protect the human subjects of clinical research.

SISTERS

7.  Describe the relationship between Michaela Odone and her sister. Suggested Response: Deirdre was a caring sister who only wanted to help. Michaela's anger at her was part of Michaela's "mother tiger" response that everyone needed to care for Lorenzo and treat him as if he had a mind. Michaela's faith, it turns out, was justified.

Discussion Questions on Morality and Ethics
Using
The Six Pillars of Character

Discussion Questions Relating to Ethical Issues will facilitate the use of this film to teach ethical principles and critical viewing. Additional questions are set out below.

RESPONSIBILITY

(Do what you are supposed to do; Persevere: keep on trying!; Always do your best; Use self-control; Be self-disciplined; Think before you act -- consider the consequences; Be accountable for your choices)


1.  The movie starts with the following passage on the screen:

Life has meaning only in the struggle.
Triumph or defeat is in the hands of the Gods . . .
So let us celebrate the struggle!

            --   Swahili Warrior Song.

What are the filmmakers trying to tell us by putting this quote at the beginning of the movie? Suggested Response: There is no one right answer to this question. A good answer will demonstrate sober reflection. Samples of two good answers are: (1) the experience of the Odone family ennobled them despite the fact that Lorenzo is still disabled; and (2) it means that it is how you live your life that gives it meaning, not how successful you may be.

2.  Is there a difference between fulfilling a responsibility (doing what you are supposed to do, persevering, and always doing your best) and what the Odones did for Lorenzo? Suggested Response: The Odones could have done a lot less for Lorenzo and still have complied with the duties imposed on them by their love for Lorenzo and by their ethical responsibilities.

See questions in Illness-Disabilities section above.
CARING

(Be kind; Be compassionate and show you care; Express gratitude; Forgive others; Help people in need)


3.  Does everyone need people to help them out at certain times? Where would Lorenzo be without those who cared for him? Where would you be if, in your times of need, people had not helped you out? Suggested Response: Everyone needs help at many points in their lives.


Last updated February 5, 2008.




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