Lorenzo’s Oil

1. Lorenzo’s Oil An exploration of Genetics and the Scientific Method

2. Bell Ringer (10min) 1. Define the term “zygote”. 2. Define the term “allele” and tell us what the difference is between a gene and an allele. 3. Define the terms “homozygous” and “heterozygous”. 4. Define the term “autosomal chromosome”. 5. What is the role of the Y chromosome? 6. When do you describe a person as carrier for a specific genetic trait?

3. Bell Ringer Responses 1. A zygote is the cell formed by the union of the sperm and the egg. 2. An allele is any one of two or more genes that may occur alternatively at a given site on a chromosome. Another way to put it is that alleles are different versions of the same gene. There is no difference between a gene and an allele. 3. As to a trait, an individual whose alleles are identical is homozygous and a person whose alleles are different is heterozygous. 4. One of the 22 non-sex chromosomes. 5. It carries the genes that encode/transmit the characteristics necessary to become a male. 6. When the person is a heterozygote, i.e., a person for whom one allele is recessive and the other allele is dominant. This person does not express the recessive trait but may transmit it to his or her offspring. In recessive sex-linked genetic diseases such as ALD, the carrier will always be a female.

4. Introduction • This lesson provides a mental exercise in applying the scientific method and developing hypotheses in an interesting real world situation. • -- We will be watching “Lorenzo’s Oil”; • -- about family with wonderful five year old by who gets ALD; • -- rare genetic disease causes deterioration of myelin sheath; • -- myelin white matter of brain; insulation around nerve cells; • -- no cure; no treatment; • -- parents go on a hunt to find a cure; • -- to help understand the movie, we need to understand a few concepts.

5. O C O H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H Cerotic Acid (C26:0) This is one of the VLCSFAs implicated in ALD C C C C C C C C C C C C C C C C C C C C C C C C C C Vocabulary words • Saturated fats: • -- we’ve all heard of them; • -- same fats that cause plaque to build up and clog arteries; cause heart attacks; • VLCSFAs: Very Long Chain Saturated Fatty Acids; The body gets VLCSFAs in two ways: food and it makes its own. • Unsaturated fats: • -- good fats; don’t clog arteries; • VLCUFAs: Very Long Chain Unsaturated Fatty Acids; -- apparently not harmful.

6. Vocabulary words • Enzyme: • -- biochemical catalyst produced by an organism; • -- causes a specific chemical reaction involving molecules of other substances without the enzyme itself being destroyed or changed; • Endoplasmic reticulum: • -- production of VLCSFAs and VLCUSFAs occurs here; • -- enzymes add carbohydrate links to chains of fatty acids. • Peroxisomes are organelles within cells that: • -- regulates VLCSFA levels; • -- oxidize and break down various proteins and lipids; • -- peroxisomes in liver cells oxidize and degrade excess VLCSFAs.

7. Vocabulary words • Anomaly: • -- in scientific research, an unusual result which appears to be specific to only one or a few subjects; • Anecdotal evidence: • -- evidence collected in circumstances in which there were no scientific controls present. Anecdotal evidence is of very limited value to scientists. • Symposium: • -- meeting in which the scientists exchange information and theories. • Clinical trial: • -- medical research trying out new treatments on people; • -- strict ethical guidelines for clinical trials; • -- need to be careful not to hurt people; • -- must be reviewed and approved by various committees of scientists before they can be started.

8. Competitive inhibition • -- biological process in which more than one substance is competing for the active sites of one enzyme; the substance that has a higher concentration will have more access to the enzyme sites and more of that substance will be modified by the enzyme; • In other words, both the bad guys and the good guys compete for the attention of the same enzymatic complex.

9. Adrenoleukodystrophy (ALD): • -- Rare recessive X linked genetic disease; • -- Body does not make the protein that transports excess VLCSFAs into the peroxisomes to be degraded into harmless substances through oxidation; • -- VLCSFAs build up in the body. • -- Only 35% of boys with ALD genetic defect develop the aggressive early childhood form of the disease; 65% of boys with ALD genetic defect develop usually milder symptoms later in life.

10. ALD Researchers need to follow rules: 1. Have a master plan called a protocol, run by PI (principal investigator) 2. Include only participants who fit the patient traits for that study. 3. Use Clinical Trial Phases (small groups first, followed by larger groups of participants) 4. Avoid Bias 5. Have a control group 6. Randomization: assigning patients to different comparison groups by chance, rather than choice. 7. Use "masking" : not telling the clinical trial participants which treatment they're getting in order to also avoid Bias.

11. Movie: Part 1 • Silently watch Part 1 of Lorenzo’s Oil. • Take any notes you feel necessary. • Absolutely NO cellphones or electronics allowed! • If caught using an electronic teacher will NOT interrupt movie to reprimand you. Teacher will silently mark down your name and points will be deducted from your grade.

12. Lorenzo’s Oil Day 2

13. Bell Ringer 10 Min 1. What is a rare disease? Do you know anyone that has one? 2. How many rare diseases are there and how many million Americans are affected? 3. What do scientists believe causes a rare disease? (*hint, think about our DNA unit!) 4. Name 3 examples of rare diseases. (Yes, you can use Google)

14. Bell Ringer Answers 1. A rare disease is a disease that affects fewer than 200,000 people in the United States at any given time. Sometimes called orphan diseases. 2. There are more than 6,800 rare diseases. They affect an estimated 25 million to 300 million Americans. 3. The exact causes remains unknown but scientists can trace a significant portion of the problem to mutations (changes) in a single gene.

15. Bell Ringer Answers 4. Some examples of rare diseases (Cystic Fibrosis – affects the respiratory and digestive systems, Huntington's Disease – affects the brain and nervous system, Muscular Dystrophy – affects the muscles)

16. False Michaela didn’t slap her husband or kick her sister out of the house. The people in the ALD Foundation were unhelpful. Dr. Nikolais was not a “bad guy.” Lorenzo’s Oil is a good therapy for boys suffering from ALD. True The couple reportedly were supportive of one another, fighting together to try and find a cure for their son. The people in the ALD Foundation were helpful to the couple. Dr. Nikolais ended up being one of the heroes, as 10 years later, he discovered that Lorenzo’s Oil could be a treatment/cure for boys that had the disorder but had not yet developed any symptoms. In Lorenzo’s case, his results were found to be an anomaly. Movie’s True and False statements:

17. Clogged sink model • A model for the situation was a sink with two water taps and a defective drain. •    level of water  =   level of VLCSFAs   water taps        =   sources of VLCSFAs – diet and biosynthesis   drain               =   oxidizing enzymes in peroxisome   clog in drain    =   lack of VLCSFA transporter enzyme to take • VLCFSAs to the location of the oxidizing enzymes • Unless both taps were turned off, water would continue to accumulate in the sink, i.e. the VLCSFAs in the body would increase to dangerous levels.

18. Lorenzo’s Oil found to work • Dr. Moser embarked on a ten year study and in late 2002, he published research that showed that Lorenzo's Oil was in fact effective for many children who had not yet developed symptoms. 76% of the 68 boys who strictly adhered to a diet that limited VLCSFA consumption and took Lorenzo’s Oil were still healthy and produced normal MRI scans of the brain. For the control group, 36 boys who did not take Lorenzo’s Oil, no more than about one in three remained free of symptoms.

19. Movie: Part 2 • Silently watch Part 2 of Lorenzo’s Oil. • Take any notes you feel necessary. • Absolutely NO cellphones or electronics allowed! • If caught using an electronic teacher will NOT interrupt movie to reprimand you. Teacher will silently mark down your name and points will be deducted from your grade.