© life_edu lecture 20 part ia. emergent technologies: where do our medicines come from? issues in...
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© life_edu
Lecture 20
Part Ia. Emergent Technologies: Where Do Our Medicines Come From?
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Issues in Biotechnology:Biotechnology, Our Society and Our Future
OnCampus LiveOnCampus LiveBCH 190, MIC 190, AFS 190, NRS 190, PLS 190BCH 190, MIC 190, AFS 190, NRS 190, PLS 190
OnLine BCH 190OnLine BCH 190
A Sweeping General Survey on Life and BiotechnologyA Public Access College Course
The University of Rhode Island
Kimberly Nelson
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
© life_edu
A Sweeping General Survey on Life and Biotechnology
The University of Rhode Island
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
BCH 190BCH 190 Section II.
The Applications of Biotechnology
© life_edu
Lecture 20
Part Ia. Emergent Technologies: Where Do Our Medicines Come From?
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
© life_edu
Lecture 21
Part Ib. Emergent Technologies: DNA-Based Biotechnology and
Pharmaceutical Drug Development
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
© life_edu
Lecture 22
Part IIa. Pharmaceutical Biotechnology in the Genomics Era
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
© life_edu
Lecture 23
Part IIb. Pharmacogenomics and Personalized Medicine
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
© life_edu
Lecture 20
Part Ia. Emergent Technologies: Where Do Our Medicines Come From?
Issues in Biotechnology:The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
The Problem of Human Suffering
The Problem of Human Suffering
Plato Albert EinsteinEpicurus Bertrand RussellSocrates Mark TwainSt. Augustine John Stuart MillMartin Luther GandhiThomas Aquinas John LennonCharles Templeton Richard Dawkins
How many innocent Iraqi civilians have died from violent death since the beginning of the war in 2003?
(A) 1-5,000(B) 5-10,000(C) 10-50,000(D) 50-150,000(E) over 5,000.000
Estimates of Iraqi Civilian Deaths Table 1. Iraqi Civilian Deaths Estimates
Iraq Body CountMarch 19, 2003 - August 22, 2008 86,661 - 94,558
Iraq Coalition Casualty CountApril 28, 2005 - August 22, 2008 43,099
Brookings Iraq IndexMay 2003 - August 14, 2008 113,616
The Associated PressApril 2005 - February 13, 2008 34,832 dead
40,174 woundedThe Iraq Family Health Study (the “WHO study”)
March 2003 - June 2006 151,000
The Lancet Studies, Johns Hopkins University“Mortality after the 2003 Invasion of Iraq”
March 19, 2003 - July 31, 2006 426,369 - 793,663
Source: Prepared by CRS with data from noted sources.The lancet studies comprise three cluster studies of violence-related mortality in Iraq that have recently beenundertaken. The first two studies were both conducted by researchers from Johns Hopkins.
Order Code RS22537Updated August 27, 2008
When do we intervene?
Is empathy uniquely human?
How do we intervene?
Imagine that again you are standing on a train platform. A train is coming down the track and you can again see the conductor through the window, frantically waving his arms and indicating that there are no brakes. When you look down the tracks, you see five men working where the abuts the end of the tracks and that they will be crushed by the incoming train. You quickly notice that there is a lever, which if you throw it, will divert the train to another track, saving the lives of the five men. However, there is a man working on that track who will certainly be killed.
You Decide:
(A) to throw the lever(B) not to throw the lever(C) that this is not my problem(D) stand and watch(E) turn and walk away
Imagine that again you are standing on the same train platform. The same train is coming again and you can again see the conductor through the window, frantically waving and indicating that there are no brakes, and again when you look down the tracks, and you see five men working, who will be crushed by the incoming train. This time however, there is no lever to divert the train, but there is a very large man next to you reading a newspaper, unaware of the situation. You are not large enough to stop the train, but he is. If you push him, or drop kick him, onto the tracks his body will stop the train, saving the five men.
You Decide:
(A) to push him(B) not to push him (C) that this is not my problem(D) stand and watch(E) turn and walk away
Imagine that again you are standing on the same train platform. The same train is coming again and you can again see the conductor through the window, frantically waving and indicating that there are no brakes, and again when you look down the tracks, and you see five men working, who will be crushed by the incoming train. This time however, there is no lever to divert the train, but there is a very large man next to you reading a newspaper, unaware of the situation. You are not large enough to stop the train, but he is. If you push him, or drop kick him, onto the tracks you will stop the train, saving the five men. You happen to know that he is a Nobel Prize Laureate.
You Decide:
(A) to push him(B) not to push him (C) that this is not my problem(D) stand and watch(E) turn and walk away
Imagine that again you are standing on the same train platform. The same train is coming again and you can again see the conductor through the window, frantically waving and indicating that there are no brakes, and again when you look down the tracks, and you see five men working, who will be crushed by the incoming train. This time however, there is no lever to divert the train, but there is a very large man next to you reading a newspaper, unaware of the situation. You are not large enough to stop the train, but he is. If you push him, or drop kick him, onto the tracks you will stop the train, saving the five men, one of whom is your father. You happen to know that he is a convicted pedophile.
You Decide:
(A) to push him(B) not to push him (C) that this is not my problem(D) stand and watch(E) turn and walk away
How do we intervene?
• Where do our Medicines come from?• History• Alternative Therapies and Science
• How is DNA-based biotechnology used in current pharmaceutical drug development improvement?
• Small Molecule Drug Design• Vaccine Development and Production• Recombinant DNA Drugs
• How is it done?• What are the goals?• What as been done so far?• What is in the future?
• What are the controversies and concerns?
Pharmaceutical Biotechnology What is it?
• Where do our Medicines come from?• History• Alternative Therapies and Science
• How is DNA-based biotechnology used in current pharmaceutical drug development improvement?
• Small Molecule Drug Design• Vaccine Development and Production• Recombinant DNA Drugs
• How is it done?• What are the goals?• What as been done so far?• What is in the future?
• What are the controversies and concerns?
Pharmaceutical Biotechnology What is it?
Drugs and MedicineDrugs and Medicine
• Where did our early ‘drugs’ come from?• How do animals ‘know’ which plants to eat to alleviate unpleasant symptoms?
• Did humans acquire knowledge through observation and experimentation?
• Herbal Medicinal Botanicals
The Anthropology of Medicinals
A History of Pharmacy
Animals self-medicate: Many mammals (including gorillas, chimps, and elephants) as well as certain indigenous tribes, eat clay rich soils that contain essential minerals, but also bind plant toxins and stop diarrhea. Kaolinite clay Kaopectate
Animals partake in certain stimulating refreshments:
• Coffee is reputed to have been discovered 1500 yrs ago when a goatherd noticed his goats became excessively energetic after feeding on red berries of a small shrub
• Ancient Peruvian Indians observed that their lamas chewed coca leaves when carrying heavy loads on long journeys, and took up the habit themselves
Wild Medicinals
Humans not the only animals to enjoy behavioral modification through ingestion
of plant, fungal and microbial based compounds
Animals and birds have a strong predilection for alcohol which they obtain from fermented fruit
They often are observed to over indulge, despite the associated risks (accidents and predation), perhaps because alcohol is rich in calories and a stress reducer
Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs. The word derives from the Greek: φάρμακον (pharmakon), meaning “drug” or “medicine.”
Pharmacy
Company Sales ($M) Based/Headquartered
1 Pfizer 43,363 United States2 GSK 36,506 United Kingdom3 Novartis 36,506 Switzerland4 Sanofi-Aventis 35,642 France5 AstraZeneca 32,516 United Kingdom6 Hoffmann 30,336 Switzerland7 J&J 29,425 United States8 Merck & Co. 26,191 United States9 Abbott 19,466 United States10 Eli Lilly & Co 19,140 United States11 Amgen 15,794 United States12 Wyeth 15,682 United States13 Teva 15,274 Israel14 Bayer 15,660 Germany15 Takeda 13,819 Japan
Rank
Pharmaceutical Giants: Market Leaders in Terms of Sales
Origin of the FDA
Who Regulates Drug Safety?
Origin of the FDA
Harvey Washington Wiley, Head of the Division of Chemistry of the U.S. Department of Agriculture,
predecessor of the FDA, in 1899
with his technical staff
History of the FDAThe Food and Drug Administration is the
oldest comprehensive consumer protection agency in the U. S. federal government. Its origins can be traced back to the appointment of Lewis Caleb Beck in the Patent Office around 1848 to carry out chemical analyses of agricultural products, a function that the newly created Department of Agriculture inherited in 1862. Although it was not known by its present name until 1930, FDA’s modern regulatory functions began with the passage of the 1906 Pure Food and Drugs Act, a law a quarter-century in the making that prohibited interstate commerce in adulterated and misbranded food and drugs. Harvey Washington Wiley, Chief Chemist of the Bureau of Chemistry in the Department of Agriculture, had been the driving force behind this law and headed its enforcement in the early years, providing basic elements of protection that consumers had never known before that time.
History of Drug Regulation
• In 1902 The US BIOLOGICS CONTROL ACT is passed to ensure purity and safety of serums, vaccines, and similar products used to prevent or treat diseases in humans.
• In 1962 THALIDOMIDE, a new sleeping pill, was found to have caused birth defects in thousands of babies born in western Europe. News reports on the role of Dr. Frances Kelsey, FDA medical officer, in keeping the drug off the U.S. market, arouse public support for stronger drug regulation.
Significant Dates in U.S. Food and Drug Law History
1820 Eleven physicians meet in Washington, D.C. establish the U.S. Pharmacopeia, the first compendium of standard drugs for the United States.
1862 Lincoln appoints Charles M. Wetherill, to serve in the new Dept of Ag. the predecessor of the Food and Drug Administration.
1883 Dr. Harvey W. Wiley Father of the Pure Food and Drugs Act.
1902 The Biologics Control Act is passed to ensure purity and safety of serums, vaccines, and similar products used to prevent or treat diseases in humans.
1906 The original Food and Drugs Act prohibits interstate commerce in
misbranded and adulterated foods, drinks and drugs. The Meat Inspection Act is
passed the same day. 1907 First Certified Color Regulations.
1927 Food, Drug, and Insecticide Administration.
1938 The Federal Food, Drug and Cosmetic (FDC) Act of 1938.
1939 First Food Standards issued.
1950 Alberty Food Products Co. v. U.S. ,directions for use ona drug label must include purpose for the drug. Worthless remedies cannot escape the law by not stating the conditionit is supposed to treat.
Significant Dates in U.S. Food and Drug Law History
1954 Miller Pesticide Amendment sets safety limits for pesticide residues on raw agricultural commodities.
1958 Food Additives Amendment requires new food additives safety; Delaney proviso prohibits any food additive shown to induce cancer in humans or animals.
1962 Thalidomide, a new sleeping pill, is found to have caused birth defects in thousands of babies born in western Europe; arouses public support for stronger drug regulation. Kefauver-Harris Drug Amendments passed to ensure drug efficacy and greater drug safety.
1965 Drug Abuse Control Amendments are enacted to deal with problems caused by abuse of depressants, stimulants and hallucinogens.
1968 FDA Bureau of Drug Abuse Control.
1970 The Comprehensive Drug Abuse Prevention and Control Act replaces previous laws and categorizes drugs based on abuse and addiction potential compared to their therapeutic value.
1985 AIDS test for blood approved by FDA.
1992 Nutrition facts, basic per-serving nutritional information, are required on foods under the Nutrition Labeling and Education Act.
Significant Dates in U.S. Food and Drug Law History
1995 FDA declares cigarettes to be drug delivery devices.
2002 The Best Pharmaceuticals for Children Act improves safety and efficacy of patented and off-patent medicines for children.
2004 Project BioShield Act of 2004 FDA to expedite countermeasures to chemical, biological, and nuclear agents that may be used in a terrorist attack against the US.
2005 Food Allergy Labeling and Consumer Protection Act requires the labeling of any food that, account for the vast majority of food allergies: peanuts, soybeans, cow’s milk, eggs, fish, crustacean shellfish, tree nuts, and wheat.
2009 President Obama signs the Family Smoking Prevention and Tobacco Control Act into law.
2010 FDA Center for Tobacco Products established. FDA announced a ban on cigarettes with flavors characterizing fruit, candy, or clove.
Alternative TherapiesAlternative Therapies
Herbal MedicineHomeopathyChiropracticDNA ActivationEtc.
NaturopathyOsteopathyAnthroposophical Medicine Holistic MedicineEtc.
Alternative TherapiesAlternative Therapies
Alternative TherapiesAlternative TherapiesIn 2011, 60 million Americans had used one or more complementary or alternative therapies to address health issues
The research found that those having used alternative medicine tended to have higher education or report poorer health status
The majority of alternative medicine users appear to be doing so largely because:
“they find these healthcare alternatives to be more congruent with their own values, beliefs, and philosophical orientations toward health and life”
Alternative TherapiesAlternative Therapies
A majority of alternative medicine use was in conjunction with standard medical treatments
Approximately 4.4 percent of those studied used alternative medicine as a replacement for conventional medicine
Popularity linked to low level of scientific literacy among the public at large
Many of today’s well accepted drugs were derived from plants
Traditional Herbals (Chinese) have credence and have beenderived from thousands of years experimentation
Many of natural sources (marine) are still untapped
Most alternative therapies are not regulated (warning!)
Alternative TherapiesAlternative Therapies
Alternative TherapiesAlternative Therapies
How Can We Determine if Alternative Therapies work?
Echinacea had no effect on the duration or severity of the cold
Seek a Balanced view
You are an experiment of one data point
There are good reasons to use ‘purified’ medicines
Life expectancy is up world wide in past 100 yrs
Alternative TherapiesAlternative Therapies
A question of:A question of:
• Efficacy Efficacy (do they actually work?)(do they actually work?)
• Reductionist thinking Reductionist thinking (this herb is (this herb is forfor that disease) that disease)
• Absence of Science-based resultsAbsence of Science-based results• Absence of RegulationAbsence of Regulation• Absence of AccountabilityAbsence of Accountability
• NEED FOR EVIDENCE BASED STUDIESNEED FOR EVIDENCE BASED STUDIES
Alternative TherapiesAlternative Therapies
Alternative TherapiesAlternative Therapies
Can KILL!!!
• Where do our Medicines come from?• History• Alternative Therapies and Science
• How is DNA-based biotechnology used in current pharmaceutical drug development improvement?
• Small Molecule Drug Design• Vaccine Development and Production• Recombinant DNA Drugs
• How is it done?• What are the goals?• What as been done so far?• What is in the future?
• What are the controversies and concerns?
Pharmaceutical Biotechnology What is it?
• Where do our Medicines come from?• History• Alternative Therapies and Science
• How is DNA-based biotechnology used in current pharmaceutical drug development improvement?
• Small Molecule Drug Design• Vaccine Development and Production• Recombinant DNA Drugs
• How is it done?• What are the goals?• What as been done so far?• What is in the future?
• What are the controversies and concerns?
Pharmaceutical Biotechnology What is it?
The History of The Pharmaceutical Drug Discovery “Pipeline”
Small Molecule Drug DesignSmall Molecule Drug Design
Small Molecule Drug DesignSmall Molecule Drug Design
Designing small molecules to fit Designing small molecules to fit specific protein sitesspecific protein sites
Combinatorial chemistryCombinatorial chemistry
Historical Perspective:
Combinatorial chemistry, also known as test-tube evolution or applied molecular evolution, owes its origins to the arrival of the principles of molecular evolution almost 30 years ago, when RNA evolution experiments and theories on the self-organization of biopolymers suggested how it was possible to “evolve” by iteration successive generations of biopolymers from previous generations, with different properties
VastlyVastlydecreasing decreasing the timethe timefor new drugfor new drugdiscovery anddiscovery anddevelopmentdevelopment
Now small Now small molecule molecule design meetsdesign meetsthe genomicthe genomiceraera
The Role of PharmacogenomicsThe Role of Pharmacogenomics
Small Molecule Drug DesignSmall Molecule Drug Design
Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms (SNPs) with a drug’s efficacy or toxicity
PharmacogenomicsPharmacogenomics
The Role of PharmacogenomicsThe Role of PharmacogenomicsPharmacogenomics is the study of how an individual’s genetic
inheritance affects the body’s response to drugs
Personalized Medicine:Personalized Medicine: Based on patients Based on patients’’ DNA sequence DNA sequenceSequencing and analysis of the human genome’s six billion base pairs
Drug MetabolismDrug Metabolism: Based on individual genomics: Based on individual genomics A drug that might be good for you might not do anything for A drug that might be good for you might not do anything for someone elsesomeone else A drug that might be good for someone else might kill youA drug that might be good for someone else might kill you
Disease PredispositionDisease Predisposition
Disease DiagnosisDisease Diagnosis
See more on this in the next lecture…
• Brown’s List of Human Universals
• Behavior is a Biological Construct
• Molecular evidence for behavioral diseasesDepressionBi-polar disorderADHD
Schizophrenia
Genes and BehaviorGenes and Behavior
Drugs and BehaviorDrugs and Behavior
SSRIsProzac and the Placebo Effect
St. John’s Wort
Drugs and BehaviorDrugs and Behavior
Illegal Drugs
MarijuanaEcstasyHeroineCocaineCrackMeth
Drugs of AbuseAlcohol Club Drugs Cocaine Fentanyl Heroin Inhalants LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine PCP/Phencyclidine Prescription Medications Steroids (Anabolic) Tobacco Addiction (Nicotine)
Legal DrugsPrescription Drugs
Foods and Supplements
CoffeeChocolateTeaAlcoholSugarSupplements
Drugs and BehaviorDrugs and Behavior
‘This is your brain on drugs’
Drugs and BehaviorDrugs and Behavior
If you knew your genome, and it revealed that you have a genetic recessive genes for schizophrenia (you do not have the disease) and your spouse has the same diagnosis, would you want a prenatal screen for your children?
(A) yes(B) no(C) uncertain
What Are The Emerging Technologies
That Will Impact Pharma R&D
“Bench to Bedside” “Bench to Bedside”
Takes ~$1 billion and up 12 Years with a 1:5000 Rate of Success
Takes ~$1 billion and up 12 Years with a 1:5000 Rate of Success
Pharmaceutical Companies invest significant $ amounts in R&D
Free market strongly selects for drug targets, not health or efficacy
1. An approximate time and cost from “Bench to Bedside” for the development of a new pharmaceutical product would be in the range of: (A) 1-5 yrs and $10 million (B) 12-15 yrs and over 1,000 million (C) 3-7 yrs and 100 million (D) 3-7 yrs and $20 million (E) 1-5 yrs and $500 million
2. Alternative therapies, such as herbal medicines, DNA Activation, and homeopathy have all raised suspicion and scientific concerns because: (A) they are not regulated by the FDA(B) they have not been rigorously tested in clinical trials (C) they active ingredient(s) or mode(s) of action have not been elucidated or determined in peer-reviewed scientific publications(D) their results are highly variable(E) all of answers are correct
3. Pharmacy is the health profession that links the health sciences with the chemical sciences and: (A) is a relatively new profession developed with the advent of synthetic insulin(B) produce compounds that cannot be rigorously tested in clinical trials (C) it is charged with ensuring the safe and effective use of pharmaceutical drugs (D) therefore cannot be regulated by the FDA(E) all of answers are correct
4. Personalized Medicine: (A) is what is in your medicine chest at home(B) is based on individual genomes indicating appropriate drug prescriptions and diagnostics of disease susceptibilities(C) is an alternative therapy allowing patients their right of choice for their own treatment(D) is part of the Obama Health Care Bill of 2010 requiring health care and pharmaceuticals for all people regardless of income(E) is individualized hands on health care required now for all end of life patients
5. Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs. The word Pharmacy derives from the Greek: φάρμακον (pharmakon), meaning:
(A) from the Farm(B) “drug” or “medicine”(C) wild plant derivatives(D) deep biology(E) wonder cure
6. The FDA is:
(A) The Facts on Drugs Administration(B) The Facts and Defense Administration(C) The Food and Drug Administration(D) The Food and Defense Act(E) The Finance on Drugs Act
7. Alternative therapies including; Herbal Medicine, Homeopathy, Chiropractic Medicine, DNA Activation, Naturopathy, Osteopathy, Anthroposophical Medicine and Holistic Medicine often lack extensive evidence based studies for support raising questions about:
(A) their efficacy (do they actually work?)(B) reductionist thinking (i.e. this herb is for that disease)(C) their absence of science-based results(D) their absence of regulation and accountability(E) all of the factors shown apply to our questions about alternative therapies