Understanding cloning

Q: We do not understand cloning.  How does it work?  How is it done? Can you explain it?  (Vernon, Walla Walla, Washington)

A: The basic idea of cloning is simple:  copying biological stuff.  Human identical twins, plants grown from a clipping and fresh-water sponges are all naturally occurring biological copies — clones.

An over wintering body of the freshwater sponge spongilla — a natural clone.  Image courtesy of J. Houseman; BIODIAC

These days, however, "cloning" normally means artificially creating an organism (like a sheep) that is genetically identical to another organism. The waters muddy somewhat, though, because we use the same term, "cloning" for three different technologies:

• reproductive cloning (for making an animal or plant with the same nuclear DNA as another animal or plant). 
• therapeutic cloning (for making a reserve of "spare parts" of cells with the same nuclear DNA as a particular human or animal)
• recombinant DNA cloning (for making many copies of a gene).

DNA (DeoxyriboNucleic Acid) is the molecule that encodes genetic information in the nucleus of cells.  It determines the structure and function of the cell.  Genetic information determines heredity.

Reproductive and therapeutic cloning.

Reproductive and therapeutic cloning is done in almost the same way.  In both cases, we begin with a parent's cell (shown in the figure as a gray circle) that contains the nucleus (red dot) that we want to copy.  A cell's nucleus, by the way, has the complete instructions coded in its DNA for making another identical cell. 

This figure shows the procedure common to reproductive and therapeutic cloning.  Both processes replace the nucleus (green dot in the figure) of a donated egg cell (yellow circle) with the desired nucleus (red dot) of a cell (gray circle) from the parent organism. This results in an egg containing the desired nucleus (yellow circle with red dot).  The egg divides to produce a cloned embryo (bunch of red dots). Drawing courtesy of Wikipedia and modified by the author.

First we extract the desired nucleus from the parent's cell.  Then, we obtain an egg cell (yellow circle) from another animal that is the same species as the one we wish to copy.  We discard the egg's nucleus (green dot), and replace it with the desired nucleus.  The drawing illustrates the result:  an egg (yellow circle) containing the desired nucleus (red dot).  Then we stimulate the modified egg with a chemical or an electrical shock to start it dividing.  The egg divides to form a cloned embryo (yellow circles enclosing red dots). 

The figure shows how reproductive and therapeutic cloning procedures differ. Top image illustrates reproductive cloning; the bottom,  therapeutic.  Drawing courtesy of Wikipedia, modified by the author.

At this point, the cloning processes differ.  For reproductive cloning, we transfer the cloned embryo into the womb of a surrogate mother and let the embryo develop.  After the gestation period, the surrogate mother gives birth to the clone. 

Whereas, for therapeutic cloning, we halt the embryo's further development by removing some of the cells, which we cultivate in the lab (represented in the figure by the petri dish).   The resulting specialized cells are then available to treat diseases or injuries, says reproductive physiologist and embryologist Lannett Edwards with the University of Tennessee Institute of Agriculture.

You can make your own virtual clone by visiting the University of Utah's cool Click and Clone site. 

In 1952, biologists Robert Briggs and Thomas J. King, of the Institute for Cancer Research in Philadelphia, cloned the first animal:  a tadpole.  Since then, we have cloned hundreds of animals, including a frog (1952), carp (1963), sheep (the first mammal, 1996), Rhesus monkey (2000), cattle (2001), cat (2001), mule (2003), horse (2003) and a dog (2005).

Unfortunately, the process leads to many failures — Dolly, the sheep, was the only success out of 277 tries.  Perhaps someday, when the success rate improves, we can clone extinct animals, such as the Wooly mammoth (so far unsuccessful).  We have managed to clone an endangered cattle species, the Asian gaur, but the calf died after two days.

Dipping a bladder-shaped scaffold seeded with human bladder cells into a growing solution. The research team cloned 1.5 billion bladder cells for growing new bladders for seven patients.  Courtesy of Brian Walker, AP.

Therapeutic cloning, on the other hand, is advancing at a more rapid rate, says Edwards.  Already, we've grown skin and bone tissue from patients' own cells and transplanted them successfully.    

Between 1999 and 2001, Anthony Atala, at that time a team leader at the Children's Hospital in Boston, replaced diseased bladders of seven young people with bladder tissue grown from their own bladder and muscle cells.  Thus, the team cloned the first complex organ — a bladder.  Self-cloned bladder cells work well because the patient's body should not reject them.  So far, the young people have retained the bladders.

Moreover, therapeutic cloning may lead to other wonderful feats — growing a new heart, liver or kidneys to replace a failing organ or regenerate damaged spinal cord tissue.  

Recombinant DNA technology or gene cloning. 

First, why clone genes?  To get many copies so we can work on a particular gene.  A gene is a part of a DNA molecule;  it controls part of an organism's traits and physical characteristics, as illustrated in this Human Genome Project image.  The pictures depicts the relationship between a gene and the entire DNA molecule, and, for that matter, chromosomes.

"Gene cloning has been an integral part of identifying genes responsible for inherited diseases," says geneticist Louisa Stark, director of the Genetic Science Learning Center at the University of Utah.  "Researchers often report that they have 'cloned a gene' for a disease like cystic fibrosis or breast cancer.  In this context, cloning simply means that a researcher has used cloning and recombinant DNA technologies to isolate a gene involved in an inherited disease."

Cloning a gene. Drawing courtesy of University of Utah, modified by the author.

Now, how do we clone a gene?  From the genome (all the DNA in all of the cells of the human or organism), we isolate the one gene (shown as red segment in the figure) that we're interested in.  Then we put the gene into a simple self-replicating DNA molecule (called a plasmid), which is circular in shape (shown in the figure as part of a blue circle). 

Plasmids occur naturally in bacteria.  The gene joins the plasmid DNA molecule; the new modified molecule is called a "recombinant DNA molecule" (blue circle with red segment). Then we stick this new recombinant DNA molecule into bacteria host cells (yellow blobs).  The host cells reproduce the recombinant DNA molecule along with the host cell DNA.  The host cells thus become biological factories that crank out many copies of the gene — the cloned genes.

We are experimenting in clinical trials with using gene cloning to treat genetic conditions by inserting normal copies of faulty genes into cells of the person being treated.  Another application is to mass produce human protein needed to treat a disease.  For example, we insert the human insulin gene into bacteria, which then mass produce human insulin, which diabetic patients then use to treat their disease.  Also, gene clones allow us to genetically engineer food crops in order to improve their taste or resistance to pests or disease.  Gene cloning has also helped decipher and map entire genomes.

Further Reading:

Cloning in focus by Louisa Stark, the University of Utah Genetic Science

Cloning Fact Sheet, Human Genome Project Information, DOE

Cloning, Wikipedia

DNA: Yes, Snuppy is definitely a clone, PhysOrg.com

Organ re-engineered for the first time in bladder transplants by Jeff Donn, USATODAY.com

(Answered May 16, 2006)