Biotechnology, Genetic Engineering and Medicine Biotechnology (define … see text) Biotechnology (define … see text) Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design Drug design Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) and you have them! Evolution’s “mismatched” diseases (not in book) and you have them!

What Is Genetic Engineering? Genetic engineering: 2 options Genetic engineering: 2 options Foreign genes inserted Foreign genes inserted Existing genes altered Existing genes altered Technique Technique Restriction enzymes cut DNA; “excision” Restriction enzymes cut DNA; “excision” Insert new DNA nucleotides (e.g., A,T,C, or G) Insert new DNA nucleotides (e.g., A,T,C, or G) New gene is expressed (via Genetic Code) New gene is expressed (via Genetic Code) Examples Examples Insulin and Starlight Corn Insulin and Starlight Corn Genetically Modified Organisms (GMO’s) Genetically Modified Organisms (GMO’s)

Genetic Counseling using “Gene Chips”

Sequencing of Individual’s 20,000 Genes

Question Biotechnology and genetic engineering focus on ____. A. Specific genes B. Transferring genes from one species to another C. Inserting specific nucleotides into DNA D. Genetically modifying crops and animals E. All of the above

Question One of the stumbling blocks for genetic engineering is that the strands of DNA have to be cut precisely in order to remove or ”excise” nucleotides that are “problematic”; this cutting and removal technology is largely that of a “micro-scissor” operating at the molecular level of the double helix. A. False B. True

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Crime investigations using DNA Crime investigations using DNA Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

What Constitutes a Stem Cell? Unspecialized cells: pluripotent Give rise to more than 250 specialized cells in the body Fetus development Serve as the body’s natural repair system

Utilization of regenerated cell types from stem cells for multiple organs and cell types

Advantages of Stem cells Purpose Therapies for diseases Awaken the natural capacity for self-repair that resides in our genes Example: repairing damaged nerve cells (e.g., spinal cord injuries) Potential results Patients receive own stem cells to treat disease No need for donor match Compare with kidney and heart donor problems

Stems Cell Value: Regeneration of the Eye

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Crime investigations using DNA Crime investigations using DNA Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

DNA Fingerprinting in Criminal Investigations Analysis of DNA in human tissue Analysis of DNA in human tissue Identify criminals/victims Identify criminals/victims Process Process Micro-sample of cells (e.g., tooth brush, hair, blood) Micro-sample of cells (e.g., tooth brush, hair, blood) Analyze DNA sections Analyze DNA sections Compare to individual of interest Compare to individual of interest Each person = a unique DNA fingerprint Each person = a unique DNA fingerprint

Question Stem cells are targets for aggressive R&D in the medical sciences because stem cells are ___ A. pluripotent B. long-lived C. can be transferred to other people D. suitable for computer design E. All of the above

Question One of the great features of stem cells is that your stem cells and my stem cells are identical. A. True B. False

Question The contentious fight over the use of embryonic stem cells has largely abated because scientists have been able to re-establish ____ in many mature cells of humans (e.g., skin cells). A. Cell mitosis B. embryogenesis C. pluripotency D. GMO’s E. Genetic fingerprinting

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

Cancer: A Different Kind of Genetic Disease Normal Cell Normal Cell Genetic “stewardship” Genetic “stewardship” Cancer Cancer Cells reproduce without restraint Cells reproduce without restraint Genetic defect Genetic defect Usually multiple damaged genes Usually multiple damaged genes Collection of diseases Collection of diseases Genetic defects Genetic defects Therapies Therapies Surgery, radiation, chemotherapy Surgery, radiation, chemotherapy Gene therapy Gene therapy

While these are different types of cancer, the root cause of all cancers is the accumulation of un-repaired genetic mutations that lead to uncontrolled growth (i.e., tumors)

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

Gene Therapy Gene therapy Gene therapy Engineer gene with 100% functional DNA (nucleotide excision) Engineer gene with 100% functional DNA (nucleotide excision) Replace defective gene with healthy gene Replace defective gene with healthy gene in vivo (in the body) and in vitro (cell culture) followed by implantation/injection in vivo (in the body) and in vitro (cell culture) followed by implantation/injection in vitro Gene Therapy

DNA Repair in the Cell’s DNA ID “damaged section of DNA Excise DNA strand Remove damaged strand Replace with engineered strand Fix the patch

Question _____ is a disease that occurs in a group of cells that are reproducing without any normal restraints on growth. A. Neuroplasia B. Apotasis C. Ulceration D. Cancer

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) Evolution’s “mismatched” diseases (not in book)

Viruses and Human Diseases Virus Virus No metabolism No metabolism Cannot reproduce on own Cannot reproduce on own Structure Structure Short segment of nucleic acid as “information broker” (DNA or RNA) Short segment of nucleic acid as “information broker” (DNA or RNA) Protein coat Protein coat How it works How it works Taken into cell and takes over cell’s metabolism Taken into cell and takes over cell’s metabolism Your body produces more Your body produces more Kills cell Kills cell Continues to spread – reproduce as a contagion Continues to spread – reproduce as a contagion

HIV Human Immunodeficiency Virus (HIV) Human Immunodeficiency Virus (HIV) Contains RNA as “information broker” (What is your “broker”) Contains RNA as “information broker” (What is your “broker”) Incorporated into you cell’s RNA Incorporated into you cell’s RNA Makes new viruses Makes new viruses Cell dies Cell dies Virus lives to “fight another day” – multiple copies Virus lives to “fight another day” – multiple copies

Influenza Pandemics The Hong Kong Flu in 1968 evolved into H3N2. 750,000 people died of the virus worldwide The Spanish Flu in 1918, killed approximately 50 million people. It was caused by the H1N1 strain of influenza A. The Asian Flu in 1957 was the H2N2 influenza A strain. Worldwide it is estimated that at least one million people died from this virus.

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design Drug design Cancer Cancer Gene therapy Gene therapy Virus and epidemic Virus and epidemic Evolution’s “mismatched” diseases (not in book) and you have it/them! Evolution’s “mismatched” diseases (not in book) and you have it/them!

Evolution’s “Mis-match Diseases”/Maladies “Paleolithic (> 20,000 years before present/YBP) genes in a modern body and modern environment” “Paleolithic (> 20,000 years before present/YBP) genes in a modern body and modern environment” Hypothesis: Hypothesis: Genes in the human body evolved in response to humankind’s 4 million years of evolutionary history in Africa Genes in the human body evolved in response to humankind’s 4 million years of evolutionary history in Africa Many of those genes adapted to the paleolithic era (> 20,000 YBP) and before (millions of years) Many of those genes adapted to the paleolithic era (> 20,000 YBP) and before (millions of years) In today’s world, many of these genes poorly matched to the environment and are a liability In today’s world, many of these genes poorly matched to the environment and are a liability

The Origin of Mismatch Diseases/Maladies Years Before Present 4 M2 M1 M0.5 M 0 M Ardi Lucy H. erectus H. sapiens Genetic adaptations to previous environments poorly adaptive in our contemporary environment These disease are based on genes whose role is “mis-matched” for our lifestyles of today

Some “Mismatched Diseases”/Maladies Dental carries Dental carries Impacted wisdom teeth Impacted wisdom teeth Hypertension (heart) Hypertension (heart) Smallpox Smallpox Flu Flu Measles Measles Mumps Mumps Myopia (short-sightedness) Myopia (short-sightedness) Pertussis/whooping cough Many cancers (reproductive organs in both sexes) Type 2 diabetes Plague Flat feet Obesity Lactose intolerance Total = 50+

“Mis-matched Disease”/Malady: Dental Carries/Cavities Early Paleolithic (> 20,000 YBP) human diet Early Paleolithic (> 20,000 YBP) human diet Mix of fruits, tubers, nuts and occasional meat Mix of fruits, tubers, nuts and occasional meat Very little evidence of dental carries in archaeology Very little evidence of dental carries in archaeology Neolithic (< 5,000 YBP) human diet Neolithic (< 5,000 YBP) human diet Progressive enrichment of carbohydrate-rich foods Progressive enrichment of carbohydrate-rich foods Pervasive evidence for dental carries in archaeology Pervasive evidence for dental carries in archaeology Modern human diet Modern human diet Rich in carbohydrates: sugar + starch Rich in carbohydrates: sugar + starch Action of starch and sugars on dental surfaces Action of starch and sugars on dental surfaces Microbes feast on sugars and excrete enamel-destroying acids Microbes feast on sugars and excrete enamel-destroying acids Enamel erodes and carries/cavities follow Enamel erodes and carries/cavities follow

Differences in Environments: Earlier Humankind vs Present Day Diet Diet Fruits, tubers and occasional meat Fruits, tubers and occasional meat Days w/o adequate caloric intake Days w/o adequate caloric intake ~30% lower sugar intake ~30% lower sugar intake 30-50% less total caloric intake/day 30-50% less total caloric intake/day Stress Stress Less chronic stress Less chronic stress Sleep Sleep ~ 2 hours more per day ~ 2 hours more per day Physical Activity Physical Activity ~30% or more (all demographics and gender) ~30% or more (all demographics and gender) Look in this mirror!

“Mis-matched Disease”/Malady: Myopia/Short Sightedness

“Mis-match Disease”/Malady: Myopia Mechanics of the eye and “sightedness” Mechanics of the eye and “sightedness” Early Paleolithic (> 20,000 YBP) and before environment Early Paleolithic (> 20,000 YBP) and before environment Limited need for shortsightedness Limited need for shortsightedness Diversity of “sightedness” including distances, geometries and colors Diversity of “sightedness” including distances, geometries and colors Beginning in Neolithic (5,000 YBP) coming forward Beginning in Neolithic (5,000 YBP) coming forward Slowly increasing need for short sightedness Slowly increasing need for short sightedness New demands on shortsightedness: accounting, sewing, tool use, etc New demands on shortsightedness: accounting, sewing, tool use, etc Modern eye use Modern eye use Perhaps 50% of time shortsighted (< 18 inches) (e.g., smart phone) Perhaps 50% of time shortsighted (< 18 inches) (e.g., smart phone) Decline in mix of “sightedness” options Decline in mix of “sightedness” options

Question How many “mis-matched” diseases do you already exhibit? A B C D. > 10

Biotechnology, Genetic Engineering and Medicine Biotechnology Biotechnology Genetic engineering Genetic engineering Stem cells and regenerative medicine Stem cells and regenerative medicine Drug design (text) Drug design (text) Cancer Cancer Gene therapy Gene therapy Mitochondrial DNA Mitochondrial DNA Virus and epidemics Virus and epidemics Evolution’s “mismatch” diseases Evolution’s “mismatch” diseases