Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 20
Part Ia. Emergent Technologies:
Where Do Our Medicines Come From?
© life_edu
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
Kimberly Nelson
OnCampus Live
BCH 190, MIC 190, AFS 190, NRS 190, PLS 190
OnLine BCH 190
A Sweeping General Survey on Life and Biotechnology
A Public Access College Course
The University of Rhode Island
Issues in Biotechnology:
Biotechnology, Our Society and Our Future
life
edu.us
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
BCH 190
Section II.
The Applications of
Biotechnology
A Sweeping General Survey on Life and Biotechnology
© life_edu
The University
of Rhode Island
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 20
Part Ia. Emergent Technologies:
Where Do Our Medicines Come From?
© life_edu
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 21
Part Ib. Emergent Technologies:
DNA-Based Biotechnology and
Pharmaceutical Drug Development
© life_edu
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 22
Part IIa. Pharmaceutical Biotechnology in the
Genomics Era
© life_edu
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 23
Part IIb. Pharmacogenomics and
Personalized Medicine
© life_edu
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch
life edu.us
Pharmaceutical Biotechnology
Lecture 20
Part Ia. Emergent Technologies:
Where Do Our Medicines Come From?
© life_edu
The Problem of Human Suffering
The Problem of Human Suffering
Plato
Epicurus
Socrates
St. Augustine
Martin Luther
Thomas Aquinas
Charles Templeton
Albert Einstein
Bertrand Russell
Mark Twain
John Stuart Mill
Gandhi
John Lennon
Richard Dawkins
How many innocent Iraqi civilians have
died from violent death since the beginning
of the war in 2003?
(A)
(B)
(C)
(D)
(E)
1-5,000
5-10,000
10-50,000
50-150,000
over 5,000.000
Estimates of Iraqi Civilian Deaths Table 1. Iraqi Civilian Deaths Estimates
Iraq Body Count
March 19, 2003 - August 22, 2008
86,661 - 94,558
Iraq Coalition Casualty Count
April 28, 2005 - August 22, 2008
43,099
Brookings Iraq Index
May 2003 - August 14, 2008
113,616
The Associated Press
April 2005 - February 13, 2008
The Iraq Family Health Study (the “WHO study”)
March 2003 - June 2006
Order Code RS22537
Updated August 27, 2008
34,832 dead
40,174 wounded
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 been
undertaken. The first two studies were both conducted by researchers from Johns Hopkins.
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)
(B)
(C)
(D)
(E)
to throw the lever
not to throw the lever
that this is not my problem
stand and watch
turn and walk away
40
35
30
25
20
15
10
5
0
1
2
3
4
5
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)
(B)
(C)
(D)
(E)
to push him
not to push him
that this is not my problem
stand and watch
turn and walk away
30
25
20
15
10
5
0
1
2
3
4
5
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)
(B)
(C)
(D)
(E)
to push him
not to push him
that this is not my problem
stand and watch
turn and walk away
30
25
20
15
10
5
0
1
2
3
4
5
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)
(B)
(C)
(D)
(E)
to push him
not to push him
that this is not my problem
stand and watch
turn and walk away
40
30
20
10
0
1
2
3
4
5
How do we intervene?
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?
• 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?
Drugs and Medicine
The Anthropology
of Medicinals
A History of Pharmacy
• 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
Wild Medicinals
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
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
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.”
Pharmaceutical Giants: Market Leaders in Terms of Sales
Company
Rank
1
Pfizer
2 GSK
3 Novartis
4 Sanofi-Aventis
5 AstraZeneca
6 Hoffmann
7 J&J
8 Merck & Co.
9 Abbott
10 Eli Lilly & Co
11 Amgen
12 Wyeth
13 Teva
14 Bayer
15 Takeda
Sales ($M)
Based/Headquartered
43,363
36,506
36,506
35,642
32,516
30,336
29,425
26,191
19,466
19,140
15,794
15,682
15,274
15,660
13,819
United States
United Kingdom
Switzerland
France
United Kingdom
Switzerland
United States
United States
United States
United States
United States
United States
Israel
Germany
Japan
Who Regulates Drug Safety?
Origin of the FDA
Origin of the FDA
History of the FDA
The 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.
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 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 on
a drug label must include purpose for the drug. Worthless
remedies cannot escape the law by not stating the condition
it 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 Therapies
Alternative Therapies
Herbal Medicine
Homeopathy
Chiropractic
DNA Activation
Etc.
Naturopathy
Osteopathy
Anthroposophical Medicine
Holistic Medicine
Etc.
Alternative Therapies
In 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 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
Alternative Therapies
Many of today’s well accepted drugs were derived from plants
Traditional Herbals (Chinese) have credence and have been
derived from thousands of years experimentation
Many of natural sources (marine) are still untapped
Most alternative therapies are not regulated (warning!)
Alternative Therapies
How Can We Determine if Alternative
Therapies work?
Echinacea had no effect on the duration or severity of the cold
Alternative Therapies
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 Therapies
A question of:
• Efficacy (do they actually work?)
• Reductionist thinking (this herb is for that disease)
• Absence of Science-based results
• Absence of Regulation
• Absence of Accountability
• NEED FOR EVIDENCE BASED STUDIES
Alternative Therapies
Can KILL!!!
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?
• 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?
The History of The Pharmaceutical
Drug Discovery “Pipeline”
Small Molecule Drug Design
Small Molecule Drug Design
Designing small molecules to fit
specific protein sites
Combinatorial 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
Vastly
decreasing
the time
for new drug
discovery and
development
Now small
molecule
design meets
the genomic
era
Small Molecule Drug Design
The Role of Pharmacogenomics
Pharmacogenomics
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
The Role of Pharmacogenomics
Pharmacogenomics is the study of how an individual’s genetic
inheritance affects the body’s response to drugs
Personalized Medicine: Based on patients’ DNA sequence
Sequencing and analysis of the human genome’s six billion base pairs
Drug Metabolism: Based on individual
genomics
A drug that might be good for you might not do anything for
someone else
A drug that might be good for someone else might kill you
Disease Predisposition
Disease Diagnosis
See more on this in the next lecture…
Genes and Behavior
• Brown’s List of Human Universals
• Behavior is a Biological Construct
• Molecular evidence for behavioral diseases
Depression
Bi-polar disorder
ADHD
Schizophrenia
Drugs and Behavior
Drugs and Behavior
SSRIs
Prozac and the Placebo Effect
St. John’s Wort
Drugs and Behavior
Illegal Drugs
Marijuana
Ecstasy
Heroine
Cocaine
Crack
Meth
Prescription Drugs
Drugs of Abuse
Foods and
Alcohol
Supplements
Club Drugs
Cocaine
Coffee
Fentanyl
Chocolate
Heroin
Tea
Inhalants
Alcohol
LSD (Acid)
Sugar
Marijuana
Supplements
MDMA (Ecstasy)
Methamphetamine
Legal Drugs
PCP/Phencyclidine
Prescription Medications
Steroids (Anabolic)
Tobacco Addiction (Nicotine)
Drugs and Behavior
‘This is your brain on drugs’
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”
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)
(B)
(C)
(D)
(E)
1-5 yrs and $10 million
12-15 yrs and over 1,000 million
3-7 yrs and 100 million
3-7 yrs and $20 million
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)
(B)
(C)
(D)
(E)
from the Farm
“drug” or “medicine”
wild plant derivatives
deep biology
wonder cure
6. The FDA is:
(A)
(B)
(C)
(D)
(E)
The Facts on Drugs Administration
The Facts and Defense Administration
The Food and Drug Administration
The Food and Defense Act
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