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BIO155
How Genes are Controlled
&
Cloning
Chapter 11
Reminders
• HW7 due tonight/ HW8 due Monday 13th
• Quiz 4 on Wednesday
• Rubric for Centro Romero due Friday
Learning Objectives
• Regulation of Gene Expression
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Every cell in your body (except gametes) are clones
Not every cell in your body does the same job, how is this possible?
Most cells only express 20% of genes at any one time
Understanding regulation of genes helps understand processes of cloning and cancer
• Cloning
➢ Reproductive cloning can be used to make copies of organisms
➢ Therapeutic cloning can be used to make embryonic stem cells for therapies
Overview
•
Cellular differentiation is possible due to
regulation of gene expression
•
Reproductive and therapeutic cloning
Why are genes regulated?
• Every cell carries the same genes
• Different genes are expressed in different cells =
different cell types
• This regulation of gene expression results in cellular
differentiation
Kidney cells
DNA
From
genotype to
phenotype
Gene Expression
1. Transcription
1
2. Exit from nucleus
mRNA
3. Translation
NUCLEUS
CYTOPLASM
mRNA
2
Ribosome
3
Polypeptide
Amino
acids
Patterns of
Gene
Expression
Housekeeping Genes
•Typical human cell expresses 20% of its genes at any one time
Go over cellular differentiation..
Reproductive Cloning in Pop Culture
Society’s View on Cloning
Clonaid, 2002
Reproductive Cloning in the Media
Reproductive Cloning
•
Method for cloning a whole organism from
a single cell
•
The result is an organism that is an exact
copy (a CLONE) of one that already exists or
has existed
Reproductive Cloning
•
Applications of this technique include:
1. Repopulation of endangered/extinct animals
2. Production of organisms with specific
characteristics, such as drug-producing animals,
pigs for organs
3. Control animals for research
Reproductive Cloning of Mammals
Cloning for medical use
In a First, Man Receives a Heart From a Genetically Altered Pig (lived 61 days)
The breakthrough may lead one day to new supplies of animal organs for transplant into human patients.
NYT, 10 January 2022
•
•
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In 2021, over 40,000 patients received transplanted organs
2022, According to organdonor.gov, there are over 106,000 people waiting for organ transplants
17 people die each day waiting for an organ transplant
Reproductive Cloning
Baby Banteng,
first healthy
clone of
endangered
species 2003
Little Nicky
First ever
commercially
produced
cloned pet
2004 cost
$50,000
2018- first primates ever
to be cloned: Zhong
Zhong and Hua Hua
Pyrenean Ibex, the first species to
be brought back into existence via
cloning. Extinct in 2000. Cloned in
2009 but short lived.
Cloning a Woolly Mammoth
The Mission to Resurrect the Woolly Mammoth
Think-Pair-Share Questions on
Cloning
• Why do you think scientists are trying to clone
woolly mammoth? Should they?
• Do you think it is right to bring back animals
from extinction? What are the risks/benefits?
• What are your thoughts on cloning
Neanderthals?
Cloning Timeline
• 1880s Hans Dreich credited with first cloning of an
animal (sea urchin)
• 1950s Cloning carrot plant and amphibians
• ………
Cloning of amphibians using
somatic cell nuclear transfer
(SCNT)
Cloning Timeline
• 1984 first successful cloning of mammal, sheep.
Donor DNA was taken from eight-cell embryo
• 1987 first cloning of cows. Success low: 2 live clones
out of 558 attempts
• 1996 Dolly is born. The first mammalian clone using
a differentiated cell as the DNA donor. Dolly was the
only survivor out of 277 attempts
Cloning a mammal
using a nucleus from
differentiated cell
TECHNIQUE
Mammary
cell donor
Egg cell
donor
2
1
3 Cells fused
Cultured
mammary cells 3
4 Grown in
Nucleus
removed
Nucleus from
mammary cell
culture
Early embryo
5 Implanted
in uterus
of a third
sheep
Surrogate
mother
6 Embryonic
development
RESULTS
Lamb (“Dolly”)
genetically identical to
mammary cell donor
Cloning Timeline
• 1998-2005 cloning of cattle, mice, goats, rats, cats, horses etc
• 2005 First cloned dog, Snuppy. Earned the 2005 Invention of
the Year award by Time
Cloning Timeline
• 2007 First cloned non-human primate (therapeutic cloning)
• 2014 Therapeutic cloning of humans achieved
• 2018 First non-human primates cloned
• Human cloning next??
Human Cloning
Reproductive Cloning
Somatic Cell
Nuclear Transfer
Cloning by Nuclear Transplantation
Therapeutic Cloning
•
Involves creating a cloned embryo for the sole
purpose of producing embryonic stem cells (ESTs)
with the same DNA as the donor cell.
•
ESTs can be used in experiments aimed at
understanding disease
•
ESTs can be used to create organs matched to the
patient (cell replacement therapy)
Stem Cell Origin
• Embryonic*
• Adult (bone marrow, dental pulp)*
• Umbilical cord
• Induced pluripotent- reprogrammed adult cells
Stem cell Potency
• Totipotent cells are able to produce every cell type in
an embryo; can produce viable organism
• Pluripotent cells can differentiate into nearly all cells
(NOT placental cells)
• Multipotent cells can differentiate into a number of
cells that are closely related
Embryonic Stem Cell
• Unspecialized
• Can reproduce indefinitely (self-renewal)
• Can differentiate into specialized cells (pluripotent)
• Isolated from embryos at blastula stage (blastocyst=
approx. 100 cells)
• Controversial (isolated from embryos)
Ethical Issues
Obtaining the human embryos for research
• Unused frozen embryos from fertility clinics
(somewhat controversial)
• Cloning human embryos for the the sole purpose of
harvesting stem cells (most controversial)
• Current Laws and Legislations on Human Cloning: No
worldwide consensus!
In 2005 UN called for a global ban on all human embryo
cloning- it’s not legally binding
In 2015, 70 countries reportedly banned human cloning, but
some make exceptions for therapeutic research, for example
UK and Australia
• USA: NO FEDERAL LAWS THAT BAN CLONING COMPLETELY.
• 10 states ban human reproductive cloning (CA, IL, MA).
These states also allow the use of tax dollars to fund embryo
research (‘clone and kill’ laws)
• 8 states ban cloning for any purpose (AR, AZ, ND)
• 29 states promote the use of umbilical cord/adult stem cells
for research
Stem Cell Research in the Media
Adult Stem Cells
• They generate replacements for non-dividing
differentiated cells
• Partly specialized
• Usually give rise to only a few cell types
(multipotent)
• Not controversial- lots of research/trials carried out
Application of Adult Stem Cells: To Treat Burns
Stem Cell Derived “Clean Meat”
Attracts Billionaires* (2022)
•
“By 2040, a projected 60% of the meat we eat will be created from muscle cells
grown within laboratory bioreactors. These products will be sold in grocery stories
under names such as cultured meat, clean meat, lab-grown meat, and potentially,
meat produced via cellular agriculture”
•
“The first FDA-approved cultured meat is expected to be launched in 2023 and the
global market is predicted to be approximately $18.3 million in 2023, with a
potential to display exponential growth by 2030.”
•
*https://bioinformant.com/clean-meat-market/
Stem cells In the Food Industry
First restaurant to serve lab-grown chicken in Singapore,
2021
Summary
Stem Cells
Embryonic stem cells
Adult stem cells
Early human embryo
at blastocyst stage
(mammalian equivalent of blastula)
From bone marrow
in this example
Cells generating
all embryonic
cell types
Cells generating
some cell types
Cultured
stem cells
Different
culture
conditions
Different
types of
differentiated
cells
Liver cells
Nerve cells
Blood cells
Summary: Benefits of Stem Cells
•
Used in experiments aimed at understanding disease
•
Repair damaged tissue; No more waiting for organs
•
Designer clones using patient’s DNA will avoid rejection
•
Revolutionize meat production
Summary for Cloning
• Reproductive cloning of animals to make identical
copies of animals
• Controversy- low success rate and health of clones
• Therapeutic cloning for the purpose of making stem
cells
• Controversy over stem cells: embryonic vs. adult
ADDITIONAL VIDEOS
Why we still haven’t cloned humans- it’s
not just ethics (Business Insider)
‘Scientists want to resurrect the woolly mammoth. They just got $15
million to make it happen’
CNN, September 2022
Proponents say bringing back the mammoth in an altered form could help restore the fragile Arctic tundra ecosystem,
combat the climate crisis, and preserve the endangered Asian elephant, to whom the woolly mammoth is most closely
related. However, it’s a bold plan fraught with ethical issues.
The goal isn’t to clone a mammoth – the DNA that scientists have managed to extract from woolly mammoth remains
frozen in permafrost is far too fragmented and degraded – but to create, through genetic engineering, a living, walking
elephant-mammoth hybrid that would be visually indistinguishable from its extinct forerunner.
“Our goal is to have our first calves in the next four to six years,” said tech entrepreneur Ben Lamm, who with Church
has cofounded Colossal, a bioscience and genetics company to back the project.
https://colossal.com/mammoth/
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