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cloning

The Dionne sisters, born in 1934, are the first quintuplets known to have survived beyond infancy.

By Elof Axel Carlson

Elof Axel Carlson

Cloning is a fancy word for making identical twins. Another fancy word is calling twins monozygotic, meaning that the two (or more) identical twins arose from a single fertilization of an egg that produced a mass of cells that split into two or more batches of cells, each batch forming an individual.

The Dionne sisters in Canada (five of them) were the most famous set of identical twins. Artificial cloning, or making twins in animals, began with the work of Hans Driesch in the 1890s.  He used sea urchins to separate cells after fertilization, and the individual cells became identical twins. 

A more surprising technique was developed by Robert Briggs and Thomas King in the 1950s; they used cell nuclei from early embryos to insert into enucleated eggs and make clones of frogs.

Ian Wilmut made Dolly in 1996, the first cloned sheep from a cell nucleus taken from the breast of an adult female sheep. Since then lots of animals have been cloned, including pet dogs and cats.

The leaders in this effort to commercialize animal cloning have been South Korea and China.  China has now taken the lead of combining gene editing (replacing one gene with another by microsurgical techniques called CRISPR-9). They believe this will change how research in human diseases will be done. They cloned a beagle after editing one of its donor cells to produce a medical condition of a form of blood vessel damage that leads to heart attacks and strokes.

The arguments for this are based on human welfare. By having a healthy dog as a control and its altered clone with  the culprit gene to be followed in the course of disease, they have dogs differing in only one known gene. They can try methods to regulate that gene, isolate its gene product or functions as it creates a disease later in that dog or they can try using agents that might block the gene from acting or block the product of the inserted gene so it does not lead to heart disease or strokes.

Some people feel medical experimentation should never be done on animals, only on consenting humans. Some feel it is cruel to be created not as a loved pet but as a “thing” to be used in research. Much of human conflict has been based not on conflicts of good versus evil but on the perceived goods of one faction against the perceived goods of a different faction.

I suspect that American (and some other countries) pharmaceutical companies wanting to avoid legislation banning animal cloning  will just have that research done in China or other countries that do not recognize the rights of animals.

Living with contradictions is part of being human.  We claim “thou shall not kill” is mandated to us, but we allow killing by intent in war, self-defense,  execution of condemned prisoners and by neglect (low wages and a government that assumes health is a private matter and not the responsibility of government beneficence).

We could do the same with “thou shall not covet” and apply it to making money. Are not billionaires coveting money when they use lobbyists to change inheritance tax laws and place their money where it cannot be taxed and is shielded by legal loopholes?    

The combination of gene editing and artificial cloning by nuclear transplantation will have major benefits in medicine for those diseases that have identified genes. For single gene defects this is about 2000 known birth defects and other conditions most parents would not wish to have afflicted on their children.

If humans do not prevent diseases by medical research, nature will take its toll in reaping the sick and disabled as it did for centuries until the era of modern medicine began with the germ theory, public health movements and the shift of medicine from an art to a science.

I much prefer having had my cataracts removed so I can now drive without eyeglasses than to find myself unable to read books and articles or be a menace on the road.   

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

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Dolly the sheep. File photo

By Elof Axel Carlson

Dolly was a Dorset Finn breed of sheep born in 1996 in Scotland. She was conceived from a nucleus taken from a breast cell of an adult healthy sheep that was transferred into the cytoplasm of an egg of a different breed whose nucleus had been removed.

Dolly was the first successful live-born lamb out of about 250 tries. She was named for Dolly Parton. Ian Wilmut and Keith Campbell were the scientists who constructed her. Dolly began developing arthritis at age 5 and died a year later showing signs of old age. Normal life expectancy for a Dorset sheep is 12 years. It was thought that the cloning nucleus from the donor Dorset sheep passed on its age to Dolly at birth and that this led to her premature aging. That turned out to be false.

Kevin Sinclair, a developmental biologist in England, obtained four live clones from the breast tissue that was used to make Dolly. The successful live-born sheep were named Debbie, Diana, Daisy and Denise. They are now (2016) 9 years old and in perfect health.

Cloning is still inefficient and more failures (mostly during early embryonic stages) occur than successes. Success with dogs in Japan has led some pet owners to pay for a cloned twin of a favored aging pet. In Dolly’s case an electric shock was used after the transfer of the nucleus to stimulate the cell to divide. For some embryologists a series of transfers to fresh enucleated eggs is required to achieve success.

Why most fail is not known, but the field of epigenetics may supply some of the answers. Genes are coated chemically by the organism in body tissues. Normally, in males and females these coatings, which regulate whether genes are on or off, are removed in the testes or ovaries where reproductive cells are made. I do not doubt that in a decade or so scientists will learn to do that in a test tube or Petri dish. Will that technology be used commercially? Very likely. Prize race horses and beef or milk cattle could be cloned if the success rate was about 70 percent. It will probably not be better than that because natural fertilization fails in about one third of fertilized eggs, a substantial part of that being extra or missing chromosomes when sperm or egg nuclei are produced.

Living things are very complex and the chance of getting almost 100 percent “perfect” cells is virtually impossible to achieve. That is why many couples attempting to have children often take months or years before they become pregnant or seek help from an in vitro fertilization clinic.

The success of Dolly’s cloned sibling sheep worries some medical ethicists that, if applied to humans, this could be abused by narcissistic personalities who want to clone themselves. So far that hasn’t happened and many countries (and states in the U.S.) have banned cloning using human tissues. For those who enjoy watching (and betting on) horses, it raises an interesting idea. If races were eventually done with cloned champions, it would favor the training over the breeding as the basis for who wins. Imagine a field of a dozen cloned Seabiscuits and trying to figure out whose training was the best.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.