Welcome To BMS 1004

Welcome to BMS 1004
Richard A. Stein, M.D., Ph.D.

rastein2018@gmail.com or steinr01@nyu.edu
917-684-9438 cell (for emergencies)
Mondays and Wednesdays

8:30 AM- 9:50 AM
1
Lecture 1: An Introduction to Biology
Key Concepts:
• Principles of Biology and the Levels of

Biological Organization
• Unity and Diversity of Life
• Biology as a Scientific Discipline
Chapter 1
Copyright © 2017 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw- 2
Hill Education.
Principles of Biology
 biology provides an amazing range of organisms to study
 sometimes one can discover (inadvertently) drugs that nobody

thought about
the venom of certain snakes contains a chemical

that lowers blood pressure
3
conotoxins
toxins isolated from marine snails
used for prey capture/defense
several fractions
4
Olivera 1991
conotoxins
assayed toxicity in rodents
5
Clark 1981
conotoxins
very rich in bioactive peptides with various effects
some of them in clinical studies as painkillers
6
Olivera 1991
ziconotide
the first drug based on a conotoxin from cone snails to be made
blocks certain types of calcium channels that neurons use to send pain
signals to the brain
100 times stronger than morphine or gabapentin

unlikely to produce the same addiction response
7
Animal Res Info
plants can communicate with one another
umbrella thorn acacia
emits volatile organic molecules when attacked by herbivores
warn nearby trees that animals are in the area
8
some soil bacteria produce chemical weapons that attack

other (competing) bacteria
developed as antibiotics
9
A Fortunate Accident—Antibiotics
Fleming observed that Penicillium fungus made an antibiotic,
penicillin, that killed S. aureus
1. Cells are the simplest units of life.

2. Living organisms use energy.
3. Living organisms interact with their
environment.
4. Living organisms maintain homeostasis.
5. Living organisms grow and develop.
6. The genetic material provides a blueprint
for reproduction.
Hill Education.
7. Populations of organisms evolve from

one generation to the next.
8. All species (past and present) are related
by an evolutionary history.
9. Structure determines function.
10. New properties of life emerge from
complex interactions.
11. Biology is an experimental science.
12. Biology affects our society.
Hill Education.
1. Cells are the simplest units of life
what are viruses?

are they cells or not?
are they alive or not?
Hill Education.
2. Living organisms use energy
3. Living organisms interact with their environment
Hill Education.
4. Living organisms maintain homeostasis
what are the body temperature levels best for survival?

what is the highest body temperature compatible with survival?
what are the ideal blood glucose levels?
Hill Education.
5. Living organisms grow and develop
development versus growth
Hill Education.
Cell Types in Adult Organisms
development does 2 things
generates cellular diversity and ensures continuity of life across

order within an organism generations
how does a fertilized egg give rise how does an adult body form
to the adult body? another adult body?
Pearson Education, Inc.; ACOG

6. The genetic material provides

a blueprint for reproduction
this is the only function that is not required for the survival
of an individual
but it is required for the survival of the species
Hill Education.
7. Populations of organisms evolve
from one generation to the next
evolution
populations become better adapted to their environment
Hill Education.
Diet and Wisdom Teeth
after we began cooking our food and developed agriculture thousands
of years ago, our diet became softer
this switch to soft grains and starches required less chewing
our jaw muscles didn't grow as strong as they used to
this kept the wisdom teeth beneath the gums at higher risk of
infection
a few thousands of years ago, a mutation emerged
prevented wisdom teeth from growing
one in four people are currently missing at least one wisdom tooth
Hill Education.
Black Death (Plague) and HIV
devastating epidemics in Europe during the Middle Ages
they seem to have left 10% of today’s Europeans resistant to

HIV
possibly plague helped protect against HIV

others reported that maybe it was smallpox
how?
Black Death (Plague) and HIV
by increasing the prevalence of a mutation that confers
resistance against HIV
CCR5-Δ32
(emerged ~2500 years ago, long before HIV)
Disease Ecology
8. All species (past and present) are related by

an evolutionary history
Copyright © 2017 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-
Hill Education.
23
9. Structure determines function
Hill Education.
10. New properties of life emerge from complex

interactions
Hill Education.
.
11. Biology is an experimental science
Hill Education.
.
12. Biology affects our society
microorganisms that produce insulin

bacteria that can clean oil spills
Hill Education.
Gene Patents: Benefits and Challenges
Ananda Mohan Chakrabarty

India Medical Times
Diamond v. Chakrabarty
long legal battle

United States Supreme Court case
can genetically modified organisms be patented?
patent was granted by the USPTO on Mar 31, 1981
“A live, human-made micro-organism is patentable…”

Diamond v. Chakrabarty
implications are positive and negative
encourages innovation
not clear what can be patented
entities (people, groups) can “own a life”

BRCA Genes
BRCA1/BRCA2
long, complicated legal battle
BRCA-1 and BRCA-2 mutations linked to breast & ovarian cancers
Vereitasgenetics
NCBI
BRCA Genes
BRCA Genes
BRCA1/BRCA2
Myriad Genetics held the patent
a French company developed a better test but not allowed
to offer it to patients
BRCA Genes
BRCA1/BRCA2 patent invalidated in 2013
“A naturally occurring DNA segment is a product of nature and not

patent eligible merely because it has been isolated”
manipulation of a gene to create something not found in could still be

eligible for patent protection
There are Several Levels of Biological
Organization
35
Organization
1. Atoms 6. Organism
2. Molecules 7. Population
3. Cells 8. Community
4. Tissues 9. Ecosystem
5. Organs 10. Biosphere

Hill Education.
Organization
1. Atoms 6. Organism
2. Molecules 7. Population
3. Cells 8. Community
4. Tissues 9. Ecosystem
5. Organs 10. Biosphere

Hill Education.
Innovation in Science
2D versus 3D
cell cultures
a growing body of evidence has suggested that 3D cell culture systems,

in contrast to the 2D culture system, represent more accurately the
actual microenvironment of cells in tissues
some anti-cancer drugs that work in 2D cultures don’t work well in 3D
some anti-cancer drugs that work in 3D don’t work in 2D (missed?)
Hill Education. Joseph 2018
Unity and Diversity of Life
Unity
 All life displays a common set of characteristics
(principles 1-8)
 United by a shared evolutionary history: organisms have evolved
Diversity
 A diversity of forms of life have evolved in diverse environments
 tropical forests
 oceans
 deserts
Hill Education.
Evolutionary History
 Life began on Earth as primitive cells 3.5-4 billion years ago

 Those primitive cells underwent evolutionary changes to give rise to
the species of today
 Evolutionary history helps us understand the structure and function
of an organism
 Evolutionary change involves modifications of pre-existing
characteristics
 Structures may be modified to serve new purposes
Hill Education.
Evolutionary History
bat’s wings
used for flying
dolphin’s flipper
used for swimming
both structures evolved from a

limb that a pre-existing ancestor
used for walking
41
Two mechanisms of evolutionary change
1. Vertical descent with mutation

2. Horizontal gene transfer
Hill Education.
vertical descent with
mutation
historically evolution has been

studied by examining a
progression of changes in a
series of ancestors
this is called a lineage
part of the lineage that gave

rise to modern horses
Hill Education.
vertical descent with

mutation
vertical evolution
(because it occurs in a lineage)
the ancestors that were much

smaller and gave rise to the
modern horse by the
accumulation of mutations
Hill Education.
new species evolve from pre-

existing species by the
accumulation of mutations
when a mutation is beneficial,

it becomes more frequent in
the population due to natural
selection
Hill Education.
horizontal gene transfer
 relatively rare
 genetic exchange between different species
 genes that confer antibiotic resistance are sometimes transferred
between different bacteria species
46
Tree or web of life?
when the time scale is shown as a vertical axis, horizontal
gene transfer is shown as a horizontal line
47
traditionally people used the “tree of life”
focuses on vertical evolution
48
web of life
includes the contribution of horizontal gene transfer
49
Classifying Organisms
5-50 million species on Earth

the need to classify them
species with a recent common ancestor grouped together

species with a distant common ancestor grouped separately
taxonomy
the grouping of species based on common ancestry
Copyright © 2017 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-
Hill Education.
three main groups or domains of life
Bacteria
unicellular prokaryotes
Archaea
Eukarya
have a nucleus
unicellular and multicellular eukaryotes
51
.
Domain Bacteria
mostly unicellular prokaryotes

inhabit many diverse environments on Earth
Hill Education.
.
Domain Archaea
often live in extreme environments, such as hot springs
Hill Education.
Domain Eukarya
unicellular and multicellular organisms
cells with internal compartments that serve various functions
4 kingdoms
Protista, Plantae, Fungi, and Animalia
Hill Education.
taxonomy involves multiple levels
a species is placed into progressively

smaller groups that are more closely related
emphasizes the unity and diversity of different species
Hill Education.
.
56
biologists use a two-part description
binomial nomenclature
genus + species
Genus name capitalized

Species descriptor is not capitalized
Both names are italicized
Amphiprion ocellaris
clownfish
57
Genomes and Proteomes
tools available for evolutionary biologists
genome
the complete genetic makeup of an organism
proteome
the totality of proteins in a cell
58
The Human Genome Project
E. coli genome
~4.6 million base pairs
~4300 genes
human (H. sapiens) genome

~3 billion base pairs
longer ago (1990s) it was predicted
that there are ~120,000 genes in humans
(wrong)
identify genes and mutations that are linked to

disease
several major findings

1. there are “only” ~20,000-25,000 protein-encoding genes
in the human genome
(comparable to the fruit fly and flowering plants)
2. only ~1.5-2% of the genome encodes for proteins (!!!)

Fu 2018
98.5% of the genome does not make

proteins
called “junk DNA”
it attracted more interest than the actual

protein-encoding genes
divides
one cell mitotically
adult
(zygote) organism
Chinnery 2002
a single genome becomes epigenetically programmed to

generate a remarkable multitude of distinct “epigenomes”
>200 different types of cells
CSHL
Epigenetics
first genome of a free-living organism sequenced
in 1995 Haemophilus influenzae
66
some chromosomes are linear
(human)
67
Ponnuraj 2011
(human)
68
Ponnuraj 2011
(human)
69
Ponnuraj 2011
other chromosomes are circular
(most bacteria)
70
Kavenoff 1976; Benza 2012
genomics
techniques used to analyze DNA sequences
comparisons
between genomes of different species
comparative genomics
71
some studies suggest that 50-75% of human disease
genes are conserved in Drosophila
72
73
Crespi 2009
genome-wide association studies (GWAS)
we can sequence entire bacteria/humans nowadays

in a short time (hours-days)
the $1000 genome is a main goal in biotech
Hill Education. KU Leuven
genome-wide association studies (GWAS)
Hill Education. KU Leuven
proteome
the complete complement of proteins of an organism
76
Van den Brink 2016
proteomics
techniques used to analyze the proteins of a species
comparison of proteomes of different species
Hill Education.
the genome carries the information

to make the proteome
genome and proteome analysis

illuminate the evolutionary history
and relatedness of all living organisms
78
Stages of Development in the Gypsy Moth
illustrate how the genome and proteome affect

the traits of an organism
4 different forms as it progresses through

development
79
egg typically laid as an egg
mass on a branch or trunk larva known as caterpillar
of a tree hatches from the egg after ~ 1 month
undergo multiple moltings
develops into an embryo in
the spring
adult moth forms

cannot feed
takes in moisture
female secretes larval structures break
pheromone, attracts down
males pupation
lays eggs
dies within 1 week
80
explained by the fact that different genes are
expressed at some stages but not at others
81
Biology as a Scientific Discipline
science is the observation, identification,
experimental investigation, and theoretical
explanation of natural phenomena
the scientific method is used to test theories
some discoveries also made when scientists gather

information
“fact-finding mission”
82
Biologists investigate life at different levels
different branches of biology study life at different

levels using a variety of tools
ecology, anatomy, physiology, cell biology,

molecular biology
as new tools become available, they allow scientists

to ask new questions
83
.
Hill Education.
.
Hill Education.
systems biology
aims to study systems as a whole
(not just individual components)
an approach in biomedical research to understand the larger

picture by putting its pieces together
at the level of the organism, tissue, or cell
86
systems biology
interactions of
proteins in yeast
87
Xiao 2011
Hypothesis or Theory?
• Hypothesis
A proposed explanation for a natural phenomenon
Based on previous observations or experiments
Hypotheses must make predictions that can be shown
to be correct or incorrect (must be testable)
Additional observations or experiments can
support or reject a hypothesis, but a hypothesis is never
really proven
Example:
“Maple trees drop their leaves in autumn because of
shortened hours of sunlight”
88
Hypothesis or Theory?
 Theory
– Broad explanation of some aspect of the natural world
that is substantiated by a large body of evidence
– Allows us to make many predictions
 Two key attributes of a theory:

1. Consistent with a vast amount of known data
2. Able to make many correct predictions
 Example
– “DNA is the genetic material”
– Overwhelming body of evidence supports this theory
89
Understanding Biology
curiosity is the key
no rigid set of steps
two general approaches
discovery- hypothesis
based science testing
Hill Education.
Discovery-based science
collection and analysis of data without the need for a
preconceived hypothesis
goal is to gather information
 test 1,000,000 drugs to look for action against disease

 sequence genomes and proteomes
often leads to hypothesis testing

91
Hypothesis Testing
 Five steps used to test the validity of a hypothesis

1. Observations are made regarding natural phenomena.
2. These observations lead to a testable hypothesis that tries to
explain the phenomena.
3. Experiments are conducted to determine if the predictions are
correct.
4. The data are analyzed.
5. The hypothesis is accepted or rejected.
 These steps comprise the Scientific Method
Hill Education.
do not change another variable
ex: moisture, temperature, should stay

the same
Hill Education.
Hill Education.
How is Hypothesis Testing Conducted?
data are often collected in parallel
control and experimental groups
positive negative
control control
differ by only a single variable
95
data analysis
apply statistical analysis to determine if the control

and experimental groups are different because of
the single variable that is different
if the two sets are found not to be significantly

different, we must reject our hypothesis
if the two sets of data are significantly different, we

accept our hypothesis (though it is not proven) 96
a lot of debates surrounding
statistical significance
versus
biological relevance
example: link between mutations and diseases

type II diabetes mellitus
>60 risk gene variants (as of 2013) explain only about 10% to
15% of the heritable component
97
The Role of a Control Group
Hill Education.
Hill Education.
The Role of a Control Group: Social Implications of
Flawed Research can be Immense
100
101
Forbes
Flawed Studies that Cause A Huge Mess
102
Forbes
Cystic Fibrosis
affects ~1 in 3,500 Americans
abnormally thick mucus that obstructs the lungs and pancreas
average lifespan is currently in the late 30s
1935
it was determined that cystic fibrosis is a genetic disorder
1989
research groups identified the CFTR gene using genetic
approaches
discovery-based science, not hypothesis-testing, found the

gene
Hill Education.
Hypothesis for function of the CFTR gene
hypothesis testing
once the gene was known, it was possible to compare it with other,
known genes
researchers hypothesized that the protein it encodes probably

transports something across cellular membranes
the gene encodes a protein that transports chloride ions (Cl-) across the
membrane of cells
led to experiments to test normal cells and cells from CF patients for
ability to transport Cl-
104
Hypothesis for function of the CFTR gene
CF cells were found to be defective in chloride transport
transferring a normal CF gene into cells in the lab corrects this
defect
chloride transport hypothesis is accepted 105

Science is social
• Within a lab, students, postdocs, technicians, and the PI

work together
• Different labs often collaborate
• At meetings, scientists discuss new data – and debate!
• You can discuss science without having “all the answers”
• Science is a never-ending series of questions
Hill Education.
Thalidomide
used to treat morning sickness
1957-1961
“wonder drug”
>46 countries
did not cause any toxic effects or lethality even in so-

called "suicide-doses”
(14 g/animal)
107
Thalidomide
thalidomide
phocomelia
>12,000 children
one tablet enough to have a

child with all four limbs
deformed
108
Thalidomide
period of susceptibility described
Hill Education.
Thalidomide
Molecular Basis of Teratogenicity

Only Understood in 2010
Hill Education.
Science and Public Health
“multilayered deception”
casting doubt on studies showing that smoking is hazardous
funding research to counter and contradict those reports
concealing industry involvement through multiple

mechanisms
deleting inconvenient research findings
influencing medical professionals
manipulating the hospitality industry to oppose and prevent

smoke-free environments
asking funding agencies to stop funding scientists who

published inconvenient results
Hill Education.
Vinpocetine
Hill Education.
Vinpocetine

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Welcome to BMS 1004

Richard A. Stein, M.D., Ph.D.

Mondays and Wednesdays

• Principles of Biology and the Levels of

 sometimes one can discover (inadvertently) drugs that nobody

the venom of certain snakes contains a chemical

100 times stronger than morphine or gabapentin

warn nearby trees that animals are in the area

some soil bacteria produce chemical weapons that attack

1. Cells are the simplest units of life.

7. Populations of organisms evolve from

what are viruses?

3. Living organisms interact with their environment

what are the body temperature levels best for survival?

5. Living organisms grow and develop

development versus growth

development does 2 things

generates cellular diversity and ensures continuity of life across

Pearson Education, Inc.; ACOG

6. The genetic material provides

but it is required for the survival of the species

this switch to soft grains and starches required less chewing

our jaw muscles didn't grow as strong as they used to

a few thousands of years ago, a mutation emerged

prevented wisdom teeth from growing

devastating epidemics in Europe during the Middle Ages

they seem to have left 10% of today’s Europeans resistant to

possibly plague helped protect against HIV

8. All species (past and present) are related by

10. New properties of life emerge from complex

11. Biology is an experimental science

12. Biology affects our society

microorganisms that produce insulin

Ananda Mohan Chakrabarty

long legal battle

can genetically modified organisms be patented?

patent was granted by the USPTO on Mar 31, 1981

“A live, human-made micro-organism is patentable…”

implications are positive and negative

not clear what can be patented

entities (people, groups) can “own a life”

long, complicated legal battle

BRCA-1 and BRCA-2 mutations linked to breast & ovarian cancers

BRCA1/BRCA2 patent invalidated in 2013

“A naturally occurring DNA segment is a product of nature and not

manipulation of a gene to create something not found in could still be

5. Organs 10. Biosphere

5. Organs 10. Biosphere

a growing body of evidence has suggested that 3D cell culture systems,

some anti-cancer drugs that work in 2D cultures don’t work well in 3D

some anti-cancer drugs that work in 3D don’t work in 2D (missed?)

 Life began on Earth as primitive cells 3.5-4 billion years ago

both structures evolved from a

1. Vertical descent with mutation

historically evolution has been

this is called a lineage

part of the lineage that gave

vertical descent with

the ancestors that were much

new species evolve from pre-

when a mutation is beneficial,

5-50 million species on Earth

species with a recent common ancestor grouped together