The History and Ethics of Cloning

What is Cloning?

In biology, cloning is the process of producing an organism with identical genetics to an existing organism.

Why is it important?

In a scientific experiment it is critical to keep as many components exactly the same so that the observed effect can be clearly linked to the one thing that has been altered. For example, to study new cancer drugs you typically take cancer cells, grow them in a lab and treat them with a drug. If the cells die, the new cancer drug is effective. If I used different types of cancers and the drug didn’t kill all of them I might conclude that the drug was NOT an effective cancer drug. Because I didn’t keep the types of cancers the same I might miss the fact that the drug I was testing may infact be extremely effective against a specific cancer. For this reason scientists use bacteria or mice that are identical to ensure that our experimental conclusions are not obscured in differences between the the individual organisms.

Development of the Cloning Process 

1885- Artificial Embryo Twinning
Organism cloned: Sea urchin 
Primary Scientist: Hans Adolf Edward Dreisch
How they did it: Dreisch showed that by merely shaking two-celled sea urchin embryos, it was possible to separate the cells. Once separated, each cell grew into a complete sea urchin.
What they learned: The sea urchin is a simple organism regularly used to study development. This experiment showed that each cell in the early embryo has its own complete set of genes and can grow into a full organism.

1_urchin

1902- Artificial Embryo Twinning Confirmed in Vertebrates
Organism Cloned: Salamander 
Primary Scientist: Hans Spemann
How they did it: Vertebrate embryo cells stick to each other better than the sea urchin embryos. Spemann used a strand of baby hair to separate the embryo into two single cells. Each cell grew into an adult salamander. Interestingly, only salamanders split at an early stage were able to develop into adult salamanders.
What they learned: This experiment showed that embryos from a more-complex animal can also be “twinned” to form multiple identical organisms.

2_salamander

1928- The Cell Nucleus Controls Embryonic Development
Organism Cloned: Salamander 
Primary Scientist: Hans Spemann
How they did it: Spemann, again using a strand of baby hair, temporarily squeezed a fertilized salamander egg to push the nucleus to one side of the cytoplasm. The egg divided into cells—but only on the side with the nucleus. After four cell divisions, which made 16 cells, Spemann loosened the noose, letting the nucleus from one of the cells slide back into the non-dividing side of the egg. He used the noose to separate this “new” cell from the rest of the embryo. The single cell grew into a new salamander embryo, as did the remaining cells that were separated.
What they learned: Essentially the first instance of nuclear transfer, this experiment showed that the nucleus from an early embryonic cell directs the complete growth of a salamander, effectively substituting for the nucleus in a fertilized egg.

3_salamander

1952- The First Successful Nuclear Transfer
Organism Cloned: Frog 
Primary Scientists: Robert Briggs and Thomas King
How they did it: Briggs and King transferred the nucleus from an early tadpole embryo into an enucleated frog egg (a frog egg from which the nucleus had been removed). The resulting cell developed into a tadpole.
What they learned: Few tadpole clones that did survive grew abnormally when cloned with donor nuclei from more advanced embryos. Most importantly, this experiment showed that nuclear transfer was a viable cloning technique. It also reinforced two earlier observations. First, the nucleus directs cell growth and, ultimately, an organism’s development. Second, embryonic cells early in development are better for cloning than cells at later stages.

4_frog

1958- Nuclear Transfer from a Differentiated Cell
Organism Cloned: Frog 
Primary Scientist: John Gurdon
How they did it: Gurdon transplanted the nucleus of a tadpole intestinal cell into an enucleated frog egg and fertilized it. It developed into an average frog.
What they learned: Nuclei from any cell of a fully developed animal could be used for cloning.
Ethical Concerns: Could humans clone themselves?

5_frog

1975- First Mammalian Embryo Created by Nuclear Transfer
Organism Cloned:  Rabbit
Primary Scientist: J. Derek Bromhall
How they did it: Mammalian egg cells are much smaller than those of frogs or salamanders, so they are harder to manipulate. Using a glass pipette as a tiny straw, Bromhall transferred the nucleus from a rabbit embryo cell into an enucleated rabbit egg cell. He considered the procedure a success when a morula, or advanced embryo, developed after a couple of days.
What they learned: This experiment showed that mammalian embryos could be created by nuclear transfer. To show that the embryos could continue developing, Bromhall would have had to place them into a mother rabbit’s womb. He never did this experiment.
Ethical Concerns: Were scientists closer to cloning humans?
6_rabbit
1984- First Mammal Created by Nuclear Transfer
Organism Cloned:  Sheep
Primary Scientist: Steen Willadsen
How they did it: Dr. Willadsen used a chemical process to separated one cell from an 8-cell lamb embryo. Then he used a small electrical shock to fuse it to an enucleated egg cell. The embryos were implanted and normal lambs were born.
What they learned: This experiment showed that information in the nucleus of each of the 8 cells in an early mammalian embryo was capable of bringing about a whole organism.
Ethical Concerns: By this time, human in vitro fertilization techniques had been developed, and they had been used successfully to help couples have babies. If the nucleus of one cell could be transferred into an egg and the egg could develop into a normal adult human could parents now try and clone themselves? A second concern was that farmers could use this technology to clone livestock. Would the animals be healthy? Would the meat be safe? Would the animals be able to reproduce?
7_sheep1996- Nuclear Transfer from Laboratory Cells
Organism Cloned:  Sheep
Primary Scientists: Ian Wilmut and Keith Campbell
How they did it: Wilmut and Campbell transferred a nuclei from cells that had been isolated from an adult sheep then multiplied in a petri dish in the lab, into enucleated sheep egg cells. The egg was then implanted and a normal lamb developed.
What they learned: All previous cloning experiments used donor nuclei from cells in early embryos. In this experiment, Wilmut and Campbell demonstrated that nuclei from cells of an adult organisms could be used.
Ethical Concerns: By this time scientists had already learned how to alter genes in cultured cells, this experiment showed that it might be possible to use such modified cells to create transgenic animals. Should there be regulations on what scientists could alter? Again, if farmers could use this technology to clone livestock would the meat be safe?

9_sheep

1996- First Mammal Created by Somatic Cell Nuclear Transfer: Dolly
Organism Cloned:  Sheep
Primary Scientists: Ian Wilmut and Keith Campbell
How they did it: They transferred the nucleus from an adult sheep’s udder cell into an enucleated egg, implanted the early embryos. From 277 cell fusions, 29 early embryos developed and were implanted into 13 surrogate mothers. But only one pregnancy went to full term. That sheep was named Dolly after Dolly Parton. Dolly exhibited early health issues and died young.
What they learned: Every cell’s nucleus contains a complete set of genetic information. However during development different genes are turned off in different cells which causes some cells to be bone cells and some to be brain cells. When an adult cell’s nucleus is used as a donor, its genetic information must be reset to an embryonic state. Often the resetting process is incomplete, and the embryos fail to develop.
Ethical Concerns: This demonstrated that adult individuals could be cloned but also demonstrated that the resulting newborn would likely face health concerns and possibly a shortened lifespan. The publicity that this experiment garnered brought the cloning controversies into the public eye and mainstream media.

10_dolly

1997- First Primate Created by Embryonic Cell Nuclear Transfer
Organism Cloned:  Rhesus Monkey
Primary Scientists: Li Meng, John Ely, Richard Stouffer, and Don Wolf
How they did it: They fused early-stage embryonic cells with enucleated monkey egg cells using a small electrical shock. The resulting embryos were then implanted into surrogate mothers. Out of 29 cloned embryos, two monkeys were born.
What they learned: This experiment showed that primates, humans’ closest relatives, can be cloned.
Ethical Concerns: Primates are good models for studying human beings.  The concern was this would lead directly to human cloning trials.

11_monkey

1997- Nuclear Transfer from Genetically Engineered Laboratory Cells
Organism Cloned:  Sheep
Primary Scientists: Angelika Schnieke, Keith Campbell, Ian Wilmut
How they did it: This experiment was an exciting combination of findings from earlier work. Campbell and Wilmut had already created a clone using the nucleus of a cultured cell. This time, the researchers introduced the human Factor IX (“factor nine”) gene into the genome of sheep skin cells grown in a laboratory dish. Factor IX codes for a protein that helps blood clot, and it’s used to treat hemophilia, a genetic disorder where blood doesn’t form proper clots.To create the transgenic sheep, the scientists performed nuclear transfer using donor DNA from the cultured transgenic cells. The result was Polly, a sheep that produced Factor IX protein in her milk.
What they learned: This experiment showed that sheep could be engineered to make therapeutic and other useful proteins in their milk, highlighting the potential medical and commercial uses for cloning.
Ethical Concerns: Would such medicine be safe?
12_tgsheep.jpg
2001- Endangered Animals cloned by Somatic Cell Transfer
Organisms Cloned:  Gaur and Mouflon 
Primary Scientists: Many
How they did it: They isolated the nucleus from an adult Gaur and Mouflon cell and transferred them to the enucleated egg cell from a domestic cattle and sheep, respectively.  What they learned: Due to their limited success they determined that this was not a feasible way to repopulate endangered animals.
Ethical Concerns: How much would it alter the species if the animals were generated using a different organism as the egg and surrogate source?

14_cowgoat

2007- Primate Embryonic Stem Cells Created by Somatic Cell Nuclear Transfer
Organism Cloned:  Rhesus Monkey
Primary Scientist: Shoukhrat Mitalipov
How they did it: Mitalipov took a cell from an adult monkey and fused it with an enucleated human? Monkey? egg cell. The embryo was allowed to develop for a time, then its cells were grown in a culture dish. These cells, because they can differentiate to form any cell type, are called embryonic stem cells.
What they learned: Nuclear transfer in a primate, which researchers had tried for years without success, was possible.
Ethical Concerns: Because of the  genetic similarities between humans and the rhesus monkey, the embryonic stem cells generated by this procedure are a more accurate model to study human development while minimizing the ethical concerns that would arise from generating human embryonic stem cells

15_monkey

2013- Human Embryonic Stem Cells Created by Somatic Cell Nuclear Transfer
Organism Cloned:  Human
Primary Scientist: Shoukhrat Mitalipov
How they did it: Mitalipov took a skin cell from the patient and fused it with a donated egg cell. Key to the success of the experiment were modifications to the culture liquid in which the procedure was done and to the series of electrical pulses used to stimulate the egg to begin dividing.
What they learned: Human cloning is possible. Currently scientists and physicians have proposed using this method to cultivate stem cells that could be use for treatments like wound healing. Because the cells originally came from the patient they would have the same DNA as the patient. This would eliminate the risk of rejection.
Ethical Concerns: We now know humans could be cloned. Each of those eggs has the potential to be a full human being. We learned from Dolly the Sheep that a mammalian clone brought about using DNA from a developed individual will likely have health issues and a reduced life span. There is also the issue that since these embryos originate in the lab scientists have the capabilities to alter the genes.

16_human

 

2016- British Scientists given governmental approval to genetically alter human embryos
Organism Cloned: Human
Primary Scientist: Kathy Niakan
Ethical concerns: Across the globe scientists have been hesitant to attempt human cloning. Niakan has been restricted to working with embryos up to the 250 cell stage (the first 7 days of development). She has also been restricted to using already stored embryos that are left after patients complete in vitro fertilization. This british group is not the first, in fact, in April of 2015, scientists in China became the first in the world to edit a gene that causes a blood disorder. Meanwhile the U.S. National Institutes of Health released a statement saying it would not fund gene editing technologies in human embryos. There is great hope that this type of research could shed light on human development and miscarriage. There are mixed feelings about what this research could mean if scientists are allowed to implant edited embryos and allow them to fully develop. It is possible that this research could be used to screen for and cure embryos with genetic disorders. It is also possible that this technology could be used to alter other, non disease-associated, genes. It is this possibility that is at the center of most of the current ethical debates.

 

Christina
Morra_ACEs_AvatarChristina is a Ph.D. candidate studying the interactions between gut bacteria and the human intestine. She is pursuing a career teaching undergraduates.

All photos obtained from: here.

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