Cloning - What It Is And Isn't

by Anders Sandberg <asa@nada.kth.se>
Published in Homo Excelsior #2 1997.

What is a clone? Webster's dictionary defines clone as:

clone n. 1. A group of genetically identical cells descended from a single common ancestor. 2. One or more organisms descended asexually from a single ancestor. 3. One that is an exact replica of another.-v. cloned, clon-ing, clones.-intr. To create a genetic duplicate of an individual organism
A well known and natural form of clones are identical twins; during early development the the spherical cluster of cells that will eventually develop into an embryo splits for some reason, forming two different individuals sharing the same genes.

Cloning is a commonplace process in biotechnology and genetic engineering, where it is used to create cultures of identical cells for study. Cloning higher animals; however, is more tricky. The reason is that as the cells of the embryo divide, they differentiate: despite starting out with an identical genetic composition they specialize into specific cell types such as neurons, muscle fibers, skeleton or sex cells. This process is still not entirely understood, but seems to involve chemical signals telling different cells to choose different "careers" in the body. In their nuclei, genetic switches toggle genetic programs depending on the signals, changing the way the cells act and grows. Their descendants will retain the settings of the genetic switches, remaining differentiated into neurons or skin cells despite the fact that each carry the full genome of the entire person.

Experiments have been done on amphibians where nuclei from adults have been induced to grow into tadpoles, but so far the tadpoles have failed to grow into adults. Many people believed that the genetic switches of adult cells prevented them from returning to the embryonic stage; to achieve cloning of an adult animal they would have to be reset somehow, a very complex problem.

The Day of the Lambs

Cloning an entire organism, as portrayed in movies, is technically impossible, for now and for the long term future. This is because humans and animals start as one cell that divide into millions of cells with different functions. Copying all the different types of cells that make a cloned human or animal is out of the realm of possibility for now.
Media Images of Cloning, Genetic Odyssey January 7 1997
This week all that changed. On February 27 I. Wilmut, A.E. Schnieke, J. McWhir, A.J. Kind and H.S. Campbell of the Roslin Institute in Edinburgh published a paper in nature titled Viable offspring derived from fetal and adult mammalian cells. They removed the nucleus from a cell in the udder of an adult ewe, implanted it into an unfertilized oocyte whose nucleus had been removed, and then transferred into a surrogate mother. After a normal pregnancy Dolly, as the lamb was called, was born.

The result is dramatic, not just because it achieved cloning of an adult animal, but also because it shows that the oocyte could somehow reprogram the udder cell into becoming totiopotent, able to grow into an apparently normal lamb. Exactly how and why this happens remains to be seen, but it most likely involves timing the cell cycles of the donor and recipient cells. Normally a cell moves through a cycle of growth and reproduction accompanied with characteristic changes in biochemistry and genetic activity. The researchers found that the transfer of nuclei worked best if the donor cells were in a quiescent phase, perhaps giving factors in the oocyte cytoplasm time to reprogram the donated nucleus before division.

Of course, this method is not unproblematical. Of the 834 fused couplets 156 developed well enough to be transferred into surrogate mothers. Approximately 62% of the fetuses in the experiment (which involved clones from both an adult ewe, a 9-day embryo and a 26-day fetus) were lost, which is significantly above the ordinary 6%. Finally, 8 lambs were born of which one was descended from an adult cell. Obviously the technique has to be developed further before it can become truly useful for anything, but it has demonstrated the possibility of cloning from adult cells.

What Cloning Isn't

There are many myths about cloning, often based on bad treatment in science fiction or B-movies.

One of the most common myths is that a clone is an identical copy of the donor, with identical body, personality, skills and memories. This is obviously untrue, since the clone would be a new-born infant, not an xerox copy of the donor. In time the clone may grow up into the donor's younger twin brother, but that is as close as they will ever get. While they will most likely be quite similar in many respects, both are individual and unique. In fact, it appears that the growth of the brain is highly individual and the brains of identical twins actually differ from each other in macroscopic structure; in the case of clones the different environments during pregnancy and childhood will most likely make the brains even more different between the donor and the clone.

Another common myth is that cloning involves "force-growing" the clone into an adult. This would require extensive control over the developmental process and most likely an artificial womb, two things we are incapable of yet. While it might be possible in the future to increase the growth rate of cells, there are strict limits due to the efficiencies of enzymes, the diffusion of chemicals, rate of reactions in the cell and removal of waste products and heat. To make an adult clone, something like advanced nanotechnology would be necessary.

To sum up, a newborn clone of any species is indistinguishable from any other newborn. It has the same needs and capabilities as others, and cannot be identified in any way. The only thing that is different is that it has a much older twin. When it grows up it will become just as individual as everyone else.

Reference

I. Wilmut, A.E. Schnieke, J. McWhir, A.J. Kind & H.S. Campbell, Viable offspring derived from fetal and adult mammalian cells, Nature Vol 385, 810-813, February 27, 1997
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