HLTH 103 Biological Determinants of Health Genomics - Presentation Notes

HLTH 103 – Biological Determinants of Health Genomics Module 06: Outline of Topics  PART A: Case Study: Carrie Buck & Eugenics  Gene Therapy  Risks, Benefits, Ethics, Challenges & Other Considerations  PART B: Stem Cells  Applications  Risks, Benefits, Ethics, Challenges & Other Consider...

HLTH 103 – Biological Determinants of Health Genomics Module 06: Outline of Topics  PART A: Case Study: Carrie Buck & Eugenics  Gene Therapy  Risks, Benefits, Ethics, Challenges & Other Considerations  PART B: Stem Cells  Applications  Risks, Benefits, Ethics, Challenges & Other Considerations  PART C: Biotechnology (Chp 7: 7.3 – 7.7): Case Study: Golden Rice  Genetic Engineering  Risks, Benefits, Ethics, Challenges & Other Considerations Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study - Carrie Buck & Eugenics  Carrie Buck was sent to live with the Dobbs when her mother Emma was committed to the Colony for Epileptics and Feebleminded in 1920. She was neither epileptic nor feebleminded, but spent the rest of her life in this colony.  Carrie was removed from school by the Dobbs to do more housework and was “loaned” her out to other households.  Carrie got pregnant at 17 when she claimed she was raped.  The Dobbses did not believe her and had her committed.  Carrie was the test case of the new eugenics law.  The way to improve “human stock” is to prevent biologically defective people from having children.  The law stated that a person could be sterilized for “the good of society.” Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study - Carrie Buck & Eugenics  Carrie’s child Vivien was examined to see whether she was feebleminded, and it was determined that she was.  The Supreme Court heard the case and Justice Oliver Wendell Holmes wrote “…Three generations of imbeciles are enough.”  The law was upheld, and Carrie was sterilized.  Her child Vivien died at age 8, but she was making the honor roll at school. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetics, Genomics & Human Characteristics  Genetic essentialism: the notion that being human means having a human genome (all the genes in an organism).  Genetic determinism: the idea that our genes determine, direct, or cause everything about us.  A significant amount of evidence shows that genetic determinism is largely incorrect. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy  Many diseases can be attributed to mutations in specific genes.  Prenatal screening allows us to potentially “weed out” certain traits.  Gene therapy attempts to be able to cure these types of diseases.  Two types:  Somatic Gene Therapy  Germ-line therapy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy: Somatic Gene Therapy  Somatic gene therapy: attempts to cure a genetic disorder by inserting a normally functioning gene(s) into patients.  First success was in 1990 to help children with severe combined immunodeficiency (SCID).  In SCID, lymphocytes (a type of white blood cell) are missing an enzyme  Enzyme ADA = adenosine deaminase  Therapy consisted of using a virus (phage) to insert the gene of the missing enzyme. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy: Somatic Gene Therapy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy Example:  Loss-of-function  Factor VIII  Hemophilia Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy Example:  Gain of function  Sickle cell Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy: Risks, Precautions & Benefits  Somatic gene therapy: attempts to cure a genetic disorder by inserting a normally functioning gene.  Germ-line therapy aims to correct genetic problems in the germ line (sperm and eggs) so that mutations cannot be passed on.  The ethical challenges of these two are not the same, nor are the benefits and risks.  Some arguments against this therapy:  Effectiveness will depend on the type of disease: loss-of-function disease or gain- of-function disease.  Other ethical issues surrounding germ-line therapy: Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy: Risks, Precautions & Benefits  Some arguments against this therapy:  Not safe, may not be effective, expensive, and we should not “play God.”  These same arguments have been made every time a new therapy is developed (blood transfusions, vaccines, and surgeries).  Effectiveness will depend on the type of disease: loss-of-function disease or gain-of-function disease.  Counter-arguments  Expensive: as are all new medical technologies, especially when they are first developed.  “Playing God”: one could argue that everything done to heal, treat, or overcome illness is playing God.  Mistakes are permanent and would affect more than one person.  We are not sure which genes are “good” and which are “bad.”  We must distinguish between medical treatment vs. enhancement. (What if parents wanted a taller child?)  Germ-line therapy could potentially alter how we feel about the sick and disabled. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Gene Therapy Some traits are influenced by multiple genes  example: skin & eye color Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Life Application: Sex Selection  Male children are preferred in many cultures.  In these areas, many more boys are being born than girls.  The same trend is found in U.S.-born children of parents originally from these areas.  Selective abortion of females has created a shift in the gender ratio.  Efforts are underway to rebalance sex ratios for future generations, though it will take decades. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells  Gene therapy is not the only technology being developed to permanently alter the genes of an individual.  Stem cells - cells that can renew themselves and give rise to other cells - come from different sources and have different capabilities - one source is from the adult, called adult stem cells - adult stem cells are limited in flexibility Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells  Gene therapy is not the only technology being developed to permanently alter the genes of an individual.  Stem cells - cells that can renew themselves and give rise to other cells - come from different sources and have different capabilities - one source is from the adult, called adult stem cells - adult stem cells are limited in flexibility Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Fertilization, Development & Differentiation Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Stem cells are Stem cells multiply and located in red become specialized Mature blood cells bone marrow Erythrocyte Erythroblast (red blood cell) Nucleus lost Neutrophil Granular Eosinophil leukocytes Myeloblast White Basophil blood cells Stem cell Monoblast Monocyte Agranular leukocytes Lymphocyte Lymphoblast MegakaryoblastMegakaryocyte Platelets Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Figure 7.5  O2 availability Increase Set point Decrease O2-sensitive cells in kidneys respond to a decline in O2 availability by increasing erythropoietin production Increased number of RBCs returns O2 availability to normal Erythropoietin stimulates increased RBC production by stem cells in bone marrow Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Figure 7.6 Stem Cells  TOTIPOTENT: once a zygote forms and starts dividing, it is still capable of producing any of the cells in an embryo.  After it continues dividing, it forms two populations of cells:  Trophoblast: forms support structures like the placenta.  Inner cell mass (ICM): forms the embryo and is the source of embryonic stem cells.  PLURIPOTENT: capable of producing any of the cells of the body.  Cloning can be divided into two categories: therapeutic cloning and reproductive cloning.  Therapeutic cloning produces embryos as sources of healthy stem cells for the medical treatment of individuals.  Reproductive cloning creates an ideal embryo that will develop into offspring. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells  Daniel Kaufman Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells  Cloning can be divided into two categories:  therapeutic cloning and reproductive cloning.  Therapeutic cloning produces embryos as sources of healthy stem cells for the medical treatment of individuals.  To avoid rejection, somatic cell nuclear transfer (SCNT) is used.  SCNT takes a nucleus from a healthy cell in a patient’s body and is placed into an egg that has had its own nucleus removed. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells  In reproductive cloning, the goal is to create embryos that will develop into offspring.  A nucleus is taken from a “parent” and placed into an egg that has had its nucleus removed.  The embryo that results is implanted into a surrogate mother.  The offspring produced will be genetically identical to the parent that donated the nucleus.  Although some states ban reproductive cloning, there are no federal laws that ban this practice. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells Benefits:  Research has shown promising results, including the regeneration of neurons in the brains of rats with a Parkinson’s-like disease.  We can learn how development and birth defects occur.  By altering specific genes of embryonic stem cells, we can create human disease models.  Drugs would be able to be tested on embryonic stem cell cultures. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Stem Cells Risks:  It’s not yet completely safe: transplanted stem cells are not always perfectly matched, so rejection can still occur.  To get the large number of eggs required for this, women who wish to donate their eggs must undergo hormone treatments that could lead to complications.  Could be used for enhancements rather than for medical purposes.  Could also extend the human life span beyond what is beneficial to society. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Medical Technology & Other Challenges  Privacy: the ability to identify disease genes creates a new body of information. Who should be allowed to access this information?  Accessibility: to people of all economic backgrounds?  Danger of new eugenic movement: if we are deciding what is desirable, how are we any different than the case study involving Carrie Buck? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Golden Rice  Vitamin A deficiency can lead to blindness  Found in fresh produce, meat, and milk  Not available in developing countries  Two German scientists genetically engineered Golden Rice:  They inserted a gene from another species that produces the precursor.  This precursor can be converted by the human body into vitamin A Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Golden Rice  Ancient people selectively bred teosinte into maize  Easier to grow and more nutritious  Lacks hard outer case, easier to digest Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants  Genetically modified organisms (GMOs) have altered genetic material  Golden rice was humanitarian effort, but GMOs are big business in the U.S.  More than half the corn, cotton, soybeans, and alfalfa sprouts grown in the U.S. are genetically modified  Purpose of genetically modifying plants:  Pesticide production  Herbicide resistance  Nutritional value Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants Pesticide Production  Bacillus thuringiensis (Bt) produces toxins that kill insects  GMO crops produce this toxin, making their own pesticide  No apparent harm to pollinating insects or humans results Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants Herbicide Resistance  Glyphosate (found in Round Up) is broad-spectrum herbicide  Agrobacterium have an enzyme that is resistant to glyphosate  Plants that are genetically altered to produce this enzyme are resistant to this herbicide Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants: Increased Nutritional Value Examples:  Golden rice: beta-carotene, which is converted to vitamin A  Soybeans and canola: omega-3 fatty acids, reduce risk of heart attack and stroke  More edible potatoes  Slowly ripening tomatoes  Apples that don’t brown Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants: how to steps Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants: how to steps Define the Problem:  Rice plants do not make vitamin A in their endosperm (the part we eat)  Missing two enzymes (psy and crt1)  Need to insert working copies of psy and crt1 into endosperm Clone the genes  Identified psy gene from daffodils and crt1 from soil bacterium  Biochemically isolated these genes and made billions of copies through cloning Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering in Plants: how to steps Package the Genes  Extra DNA added to beginning and end of gene to ensure insertion  Start and stop sections added for gene transcription Transform the Cell  Transformation: cell takes in and uses DNA from a foreign source  Agrobacterium infects plants by inserting DNA  Scientists inserted psy and crt1 into the bacteria and allowed them to infect rice cells Confirm the Strain  Rice plant fragments were isolated and allowed to grow  Plants that made beta-carotene were separated and interbred to produce a true- breeding strain of golden rice Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering: Example: INSULIN  Insulin: first drug produced by a genetic engineering  Bacteria are used to make genetically engineered human insulin  They grow quickly and are easy to transform  Other compounds: human growth factor, clotting factors, erythropoietin Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Novelty / Other Genetic Engineering: Other Applications Industry: Bioremediation: bacteria engineered to clean up oil spills  Bioleaching: bacteria engineered to dissolve metals from ore Research Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Genetic Engineering and Our Environment  Horizontal gene transfer: genes transferred between individuals of the same generation  Bacteria and plants undergo horizontal gene transfer naturally  What are the potential consequences of the “spreading” of these genetically engineered genes in the environment? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Risks, Benefits, Ethics, Challenges & Other Considerations Course discussion the impacts of genetic engineering  RISKS: What Are the Risks of Genetic Engineering?  SAFETY: How do we know this is safe and how is this evaluated?  ECONOMICS: Can low-income farmers afford GMO seeds?  ETHICS:  What happens when GMOs are released into the environment?  Will humans use genetic engineering wisely?  EFFECTIVENESS:  How do we know the approach is effective? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press