Cloning For
Every Man
Timothy G. Standish, Ph. D.
©1999 Timothy G. Standish
“The cloning of mammals . . .
is biologically impossible.”
James McGrath and Davor Solter
Science, Dec. 14, 1984
©1999 Timothy G. Standish
“Our announcement of Dolly’s birth
in February 1997 attracted enormous
press interest, perhaps because Dolly
drew attention to the possibility of
cloning humans. This is an outcome I
hope never comes to pass.”
Ian Wilmut
Scientific American, December, 1998
©1999 Timothy G. Standish
What This Talk Is About
Four Questions:
What is cloning?
How is cloning achieved?
Why Clone? Why would anyone want to
clone an animal or human?
Ethical Considerations? Why should cloning
technology be carefully thought through
before being widely used and particularly
before humans should be cloned?
©1999 Timothy G. Standish
The Code For Life
Organism
.
Tissues
Organ
System
Cell
Nucleus
©1999 Timothy G. Standish
The Code For Life
Chromosome
Big nose
Brown eyes
Nucleus
Straight hair
Genes
©1999 Timothy G. Standish
The Nucleus Contains An
Organism’s Blueprint
Every cell has a nucleus when it is
made
Within every nucleus is a complete
copy of the organism’s genetic code
Differences between cells result from
different genes being “expressed” in
different ways
©1999 Timothy G. Standish
Clones
Clones are two genetically identical organisms
Nature commonly produces clones
Most bacteria reproduce by “binary fission” in
which the mother cell splits in two with a
complete copy of the genetic information
being passed to each daughter cell
Many single-celled eukaryotic organisms
reproduce in a similar way
In higher organisms, clones also occur
naturally, but usually through some more
complex mechanism
©1999 Timothy G. Standish
Plant Clones
Any time that plants are reproduced using
cuttings to produce new separate plants,
they are being cloned
Many commercially important strains of
fruits are produced from clones
Seedless plants can only be reproduced as
clones
©1999 Timothy G. Standish
Animal Clones
Animal clones may result from “budding” as a
way of reproducing
Budding is common in corals and some other
animals
Some vertebrates reproduce via
parthenogenesis
©1999 Timothy G. Standish
Natural Human Clones
Identical twins result from the splitting of an
embryo into two separate cell masses which
both go on to develop into genetically identical
twins
This happens naturally in about 3/1,000 births
Identical twins are genetically identical because
they have identical genes in their nucleus
This does not mean they are truly identical
©1999 Timothy G. Standish
How Is Cloning Done?
Making a clone is, in theory, a very simple
thing
All one has to do is take a cell with the nucleus
of the organism you want to clone, and grow it
into a new organism
The difficulty is that most cells do not readily
grow into whole new organisms
©1999 Timothy G. Standish
Barriers To Cloning Mammals
Most cells seem to have a limit to how many
times they will divide (the Hayflick limit)
A complex interplay between nucleus and
cytoplasm exists that prevents most cells from
producing cells other than their own type
During development, cells differentiate into all
the cell types in the body, but they do not
readily go back to being undifferentiated
The egg and a few early cells in an embryo are
the only cells capable of developing all the cell
types necessary to make a whole mammal
©1999 Timothy G. Standish
Overcoming The Barriers
A nucleus needs the right cytoplasm environment
if it is to become “totipotent”
Eggs provide the correct environment
The nucleus must be “reset” so that it forgets it
was in a differentiated cell
Ian Wilmut learned that starving cells in
culture reset their nucleus
Cells developing from mammal eggs do not seem
to have a limit to the number of times they will
divide
©1999 Timothy G. Standish
Making A Clone
The method for making a clone used by Ian
Wilmut includes 6 steps:
1 Production of quiescent cells containing nuclei
that “forget” the type of cell they are in
2 Collection of the donor nucleus
3 Preparation of an egg lacking genetic material
4 Insertion of the donor nucleus
5 Initiation of development
6 Development of the embryo in a surrogate
mother
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 1
Making Quiescent Cells
Mammary gland cells
Finn Dorset ewe
3.5 months pregnant
Harvest quiescent
cells
Culture mammary cells
Starve cells
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 2
Collecting The Donor Nucleus
Glass pipette
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 2
Collecting The Donor Nucleus
Glass pipette
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 3
Egg Preparation
Egg
Scottish Blackfaced
ewe egg donor
An egg is collected then
placed into a dish where it
can be manipulated
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 3
Egg Preparation
Glass pipette
Egg
Chromosomes
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 3
Egg Preparation
Chromosomes
Glass pipette
Egg
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 4
Inserting The Donor Nucleus
Glass pipette
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 4
Inserting The Donor Nucleus
Glass pipette
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 4
Inserting The Donor Nucleus
Suction
Suction
Pipette
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Initiating Development
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Zygote
Initiating Development
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Initiating Development
Cleavage
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Initiating Development
Cleavage
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Initiating Development
Cleavage
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Initiating Development
Cleavage
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 5
Morula
Initiating Development
©1999 Timothy G. Standish
How Ian Wilmut Made Dolly 6
Development
Morula
Scottish Blackfaced
ewe surrogate
mother
Finn Dorset lamb
Dolly
©1999 Timothy G. Standish
Why Clone?
Cloning provides opportunities in four major
areas
1 Study of development
Production of genetically identical organisms that can be
studied in different environments has the potential to
dramatically advance our understanding of development
2
3
4
5
Propagation of valuable organisms
Control over reproduction
Production of recombinant organisms
Production of engineered organs
©1999 Timothy G. Standish
Propagation Of Valuable Organisms
There are limits to the possibility of
reproducing valuable combinations of traits
using traditional breeding techniques
For example, race horses are regularly bred to
produce fast offspring, but occasionally an
excellent combination of traits if produced that
cannot be repeated even when the same parents
are used
Cloning could produce many copies of Pharlap
or other valuable horses
©1999 Timothy G. Standish
Control Over Reproduction
Production of a clone allows very precise
predictions about the results of a pregnancy
Cloning offers the potential to produce
genetically related offspring from sterile
organisms
Before cloning cells can be engineered to
remove genetic defects, or introduce desired
traits
©1999 Timothy G. Standish
Production Of
Recombinant Organisms
Cloned organisms can be made from cultured
cells
It is relatively easy to introduce new genes into
cell cultures
Cells from recombinant cell cultures can be
used as nucleus donors for clone production
This technique has already been used by
researchers at the Roslin Institute to produce
recombinant sheep that make human factor IX
Factor IX is used to treat hemophilia B
©1999 Timothy G. Standish
Production Of Engineered Organs
The potential exists to engineer organisms that
produce organs which will not be rejected when
introduced into humans or other needy
recipients
To do this, animals would be produced that do
not make the proteins and other chemicals on
cell surfaces that tell the immune system they
do not belong in a human body
©1999 Timothy G. Standish
Why Clone Humans?
Production of genetically related offspring by
infertile couples for whom other reproductive
technologies have failed
Narcissism
Replacement of lost loved ones
Production of genetically “improved” humans
(custom-built babies)
Production of spare parts for those needing
replacement organs
©1999 Timothy G. Standish
Ethical Considerations
All new technologies have unforeseen effects.
We cannot expect that cloning will be without
unexpected benefits and problems
Is any reproductive technology tampering with
the way God made nature to work?
Are we “playing God” when we create
organisms “designed” by humans?
Will there be abuses of the ability to produce
engineered organisms . . . ?
©1999 Timothy G. Standish
Ethical Considerations
Production of large numbers of clones would
lower genetic diversity
Cloning technology makes other technologies
more practical:
Production of cloned body parts requires the
production of embryos that are then used as a
source of stem cells
©1999 Timothy G. Standish
The Ethics Of Human Cloning
Would cloning be in the best interest of the
child?
– How would a child react to knowing how they will
develop in the future?
– What expectations would society put on cloned
children?
Is it ethical to produce a life/potential life for
the purpose of saving or enhancing the life of a
living person?
Is producing a clone as a source of stem cells,
then discarding the remaining parts, equivalent
to abortion?
©1999 Timothy G. Standish
Who Owns A Person’s
Genetic Potential?
It would be immoral to take the gametes of a
person and, without their consent, use them to
produce offspring
Cloning offers the potential of making genetic
copies of anyone -- With or without their
consent
©1999 Timothy G. Standish
Recent Developments In Cloning
1999 - A number of cloned cows and other organisms
have died without explanation. In general clones are less
healthy than offspring produced using other methods
(Lancet, U.S. News and World Report, May 24, 1999)
Dolly has chromosomes with telomeres shorter than those
of other ewes her age. Dolly’s lambs have telomeres that
are normal in length for sheep their age (Nature, May 27,
1999)
The first male has been cloned from adult cells, named
Fibro by Yanagimachi’s group in Hawaii, cells from an
adult mouse tail were used as the source of 274 nuclei,
one of which developed to adulthood and fathered two
normal litters (Nature Genetics, May or June 1999)
©1999 Timothy G. Standish
Recent Developments In Cloning
1999 - Discovery of a frozen woolly mammoth in Siberia
has presented the possibility of cloning mammoths using
a mammoth nucleus and elephant eggs
(http://cnn.com/NATURE/9907/23/mammoth.reut/)
1999 - A group in New Zealand has approved the cloning
of the extinct Hula bird using preserved materials
(http://cnn.com/NATURE/9907/20/cloning.enn/)
1999 - Dolly is shown to have different mtDNA than the
ewe from whom she was cloned, but the same mtDNA as
the mother who donated the egg (Eric Schon, Ian Wilmut
et al., September 1999 Nature Genetics)
©1999 Timothy G. Standish
Cloning Humans Using Cow Eggs
June 17, 1999 American Cell Technology (ACT) announce
they had made a human clone during November 1998
The clone was made by inserting a human nucleus from
skin on a man’s leg into an enucleated cow’s egg
After developing for 14 days the clone was destroyed
(Researches said before 14 days it “was not human”)
Clones of this type may be potential sources of stem cells
and perfect tissue matches for those needing transplants
According to the BBC, Lord
Robert Winston, a British fertility
expert, said the research was
"totally ethical”
The first documented human clone
– This information came from the BBC web page
news.bbc.co.uk/hi/english/sci/tech/newsid_37100
0/371378.stm
©1999 Timothy G. Standish
“None of the suggested uses of
cloning for making copies of existing
people is ethically acceptable to my
way of thinking.”
Ian Wilmut
Scientific American, December, 1998
©1999 Timothy G. Standish
©1999 Timothy G. Standish