Cloning: People Can. Should They?

By MARY MARKATOU, Kefalonia, Ionian Islands, Greece

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​Bioethics express a plethora of fundamental doubts regarding cloning that tie in to several 'bigger' questions: Should people interfere with nature, especially but not only in terms of human cloning? More thoroughly, should humanity continue the effort of convincing itself that producing livestock in labs with extremely low rates is a much more efficient solution to Earth’s hunger than a political solution? Despite the fact that the practice in question risks the loss of genetic diversity and social balance? And finally, does reproductive human cloning have its roots in human egoism or not?

Introduction

Inserting genetic material of a mammal to an empty egg cell having firstly abstracted its own material and then, putting it into the womb of an other mammal is the advisable way for harvests of apples of discords to crop up, apart from the technique of creating in vitro a being carrying the traits of an already existing or extinct one. An identical copy of it, though, with its own particular individuality, a clone: The first successful mammal cloning brought to life Dolly the sheep -whose stuffed remains are now placed at Edinburg’s Royal Museum- in 1996 and myriads of conflicts apropos of ethical and practical issues making allusion even to a forthcoming demise of the humanity. In the affluent society, nothing hinders the science from generating even duplicates of people except for nature’s laws. But who can affirm that human kind is not apt for dealing with them ignoring the destructive cost in the name of its consuming desires?

What is cloning?

Though known mostly as belonging to the field of biotechnology, cloning, the procedure of generating similar populations of genetically identical individuals is the natural progress for the asexual reproduction of single-celled organisms such as bacteria, of insects or plants. Identical twins are also natural clones with almost identical genetic make-up.

When referring to the biotechnological implementation of cloning, that has to do with copying DNA fragments (molecular cloning), cells (cell cloning) or organisms.  In terms of artificial cloning, somatic-nuclear transfer (SCNT), the nowadays’ most spread cloning method, was first performed by Hans Spemman, owner of the Nobel Prize in Physiology or Medicine (1935) for his work on embryo induction, and his student, Hilde Mangol, with amphibian embryos.

Apart from SCNT, there’s also the less controversial method of embryo twinning, the division of an embryo into two monozygotic twins at the 6- to 8- cell stage in a Petri dish via in Vitro Fertilization and if successful, it gives rise to identical twins. Unlike to IVF, the embryos generated via SCNT are not identical. Apart from the mutations contained in the somatic cells, that’s also because the mitochondrial DNA comes from the mitochondria of egg donor’s cytoplasm while chromosomal DNA is included in the transferred nuclei. That different origin of genomes results in deadly implications for cross-species SCNT due to incompatibilities between the two genomes. Briefly, instead of somatic cell nuclear transfer (SCNT), during induced pluripotent stem cells (iPSCs) practice, a specific set of genes, called reprogramming factors, send signals to a specific adult cell so as to function as a pluripotent stem cell and be able to differentiate into the endoderm (lungs, interior stomach lining, gastrointestinal tract), mesoderm (muscle, bone, blood, urogenital) or ectoderm (epidermal tissues, nervous systems) germ layer. Although reprogramming method (iPSCs) is better studied, SCNT derived from embryonic stem cells (ESCs) happens at a much higher cell production speed making possible its use for medical purposes. Studies are underway to discover faster reprogramming factors in oocytes to increase dramatically not only the speed but also the efficiency of the method.

SCNT

During somatic cell nuclear transfer, a nucleus abstracted from a donor adult cell is transplanted to a host egg cell without genetic material, which means that the genetic material of the somatic cell is transferred into the oocyte with a micropipette. Then, an electric current contributes to the fusion of somatic cell genetic material with the egg in order to end up in a single cell able to grow artificially or in the uterus of a surrogate mother, provided that its division occurs normally.

The three types of artificial cloning

a)    Molecular/Gene cloning
The need for further study on a specific gene raised interest on finding ways to replicate it. In brief, gene cloning develops as following: The DNA fragment of interest is transferred into a self-replicating genetic element, for example, a bacterial plasmid and then, multiple copies of it are generated facilitating researchers’ efforts. Gene cloning has not many similarities to therapeutic and reproductive cloning which share many similar techniques.
Since the early 1960s, molecular biologists have been using this type of cloning with no resistances from public opinion. The lack of contention regarding its use comes from the absence of reproductive intent.

b)    Therapeutic cloning
It refers to the harvest of stem cells for research targeting at replacement of diseased or injured tissues by totally new tissues, after the embryonic stem cells are derived from cloned human embryos in the blastocyst stage of development (five days post-fertilization).
 
c)     Reproductive cloning
If successfully implanted to a uterus of a female- belonging to a closely related species-, the cloned embryo can gestate a naturally fertilized egg. Rise will be given to a biological entity which, thus, will not have the genetic make-up of its genetic predecessor for the afore-mentioned reasons but also as environment plays a crucial role to the expression of the genes.

Animal Cloning

Contrary to human cloning, animal cloning is already put into practice across the Globe on a wide variety of animals over the last 50 years. However, it was just 1894 when Hans Driech cloned a sea urchin shaking a beaker of sea water to the point that the contained embryo cleaved into two separate embryos. Eight years later, Hans Spemann did the same with a salamander embryo utilizing a hair of his infant as a noose. In 1928, repeated the salamander’s cloning with nuclear transfer, which was used, in 1951, for cloning of frogs by R. Briggs and T. King. In 1962, after experiments on frogs too, John Gurdon became the first to demonstrate, not in a mammalian system, the possibility of a nucleus from differentiated cells, to develop a whole organism if transplanted into an egg cell without nucleus. Scientific community was surprised by the use of differentiated cells since there was the belief that there was no probability for further differentiation and so, the creation of an entire organism. That’s also why the afore-mentioned had experimented only with undifferentiated embryonic cells. In 1995, at Roslin Institute, Scotland, in grace of Dr. Wilmut and Dr. Campbell, Megan and Morag, two mountain sheep, came successfully to life from embryonic sheep cells. A year later, the same scientists gave rise from a mammary gland cell and named after the clever performer, Dolly Parton, Dolly, a Finn-Dorset ewe. Before Dolly became the first mammal cloned from an adult somatic cell –her genetic predecessor was 6 year old-, in 1979, a mouse clone produced by splitting mouse embryos (IVF) paved the way, for cows, sheep and chickens to obtain a replica with cloning cells from an early embryo. After Dolly’s creation, Japanese researchers achieved the survival of four out of eight calves from a single cow, and then, the list of cloned mammals expands continuously: cattle, sheep, cat, deer, dog, horse, mule, ox, rabbit, cat….
 
Why Animal Cloning? And why not.
Animal cloning seems to have gained a general acceptance presenting important advantages considered to boost global agricultural economy and economy at large. Below, those pluses are listed with references to any expressed hesitations. In this point, it is worthwhile highlight the most important drawbacks in terms of both animal and human cloning in order to emphasize to the ethical issues human cloning arises when time comes to.
 
Animal (and human) cloning cons
At first, the point that research is not sufficient to adopt cloning without a high level of danger is a usual minus to which American Association for the Advancement and Research also drew attention in 2014. Given the high-priced procedures, which, of course, are supposed to decrease as implementations advance,  it’s undeniable that the success rates until now are low enough to justify hesitation. Or not? More thoroughly, 29 successful embryos per 277 fertilized eggs and one surviving lamb out of three at birth were the detected success rates of the first mammalian cloning, while 814 attempts took place for Prometeas, the first cloned horse. The roots of this extremely low efficiency lie in the enormous stresses on the egg cell and the nucleus and as the procedure can still proceed only manually in a microscope, the SCNT method is very resource intensive. In 2014, cloning success levels reported to have risen remarkably to 60-70 % and, this year, Sooam Biotech, a Korean Company, is claimed to be producing 500 cloned embryos per day.

No matter the success rates, adverse health effects in cloned mammals such as augmented birth size and malfunctions of vital organs like liver, heart and brain have been multiply observed by scientists, while more severe possible consequences, including premature aging and inefficient immune system have appeared.  According to researchers, the origin of other potential problems could be the age of cloned cell’s chromosome as explained at the site of National Human Genome Research Institute.

“As cells go through their normal rounds of division, the tips of the chromosomes, called telomeres, shrink. Over time, the telomeres become so short that the cell can no longer divide and, consequently, the cell dies. This is part of the natural aging process that seems to happen in all cell types. As a consequence, clones created from a cell taken from an adult might have chromosomes that are already shorter than normal, which may condemn the clones' cells to a shorter life span. Indeed, Dolly, who was cloned from the cell of a 6-year-old sheep, had chromosomes that were shorter than those of other sheep her age. Dolly died when she was six years old, about half the average sheep's 12-year lifespan.”

Dolly, for example, had encountered many pathological problems akin to accelerated aging until 2003, year of her death which was attributed to the shortening of telomeres. Other scientists, with Ian Wilmut among them, state that any deficiencies with the cloning progress have nothing to do with the respiratory infection which led Dolly to death. In 2013, the idea of not irreversibly aged found support when Japanese researchers created 25 generations of  healthy cloned mice with normal lifespan after 8 years of research.
Another disadvantage is that reproductive cloning may be the reason for terminal deceases. The strongest point against it is the possibility of new illnesses to arise as it is widely known that the activity on new forms of genes may result this way. At the same time, cloning could offer the opportunity to problematic corners that fester in a particular DNA to expand and, as an aftermath, cause massive pathological problems. It’s taken for granted that cloning accompanied by less varieties of characteristics, it poses the survival of our kind or any other kind at threat delaying evolution.
 
Animal cloning pros

Catering to the needs of medical purposes, cloning can be utilized to generate animal models of disease such as mice, models engineered to carry disease-causing genetic mutations.  The creation of these transgenic animals could dramatically reduce the demanded time for research: Research based on trial and error and requiring the breeding of several generations demands lot of valuable time. Most important, those animals will be genetically identical which increases researches’ quality, fact that emerges another application of animal cloning, that of drug testing, as clones are supposed to response uniformly to drugs.  Drug production is also a worthwhile viewpoint. To give an example and not emphasize to genetic engineering, the Scottish researchers who cloned Dolly managed to brought to life an other sheep genetically modified for production of milk containing a human protein responsible for human clotting. This method allows the gene to pass to the species’ off springs and then, affect a whole herd to produce that milk. It would be afterward in science’s responsibility to isolate and purify this essential protein.

An other service of animal cloning would be the reviving of extinct or endangered species. Of course, it’s practically impossible for dinosaurs to return to Earth due to the damages time has caused to the available DNA, though, there are projects, one of them aspiring to clone wooly mammoth, as there are well-preserved tissue samples. The first almost successful resurrection of animal took place in 2009 when the bucardo, a wild mountain goat, was cloned with goats as egg donors. However, even the best clone survival ended soon after birth, not to mention that the frozen tissue belonging to female can produce only females. Scientists, of course, have the solution: replacement of a X chromosome by a Y. Cloning of endangered species, on the other hand, is much more feasible occurring with living cells and so, replicas of mouflon sheep, deer, bison and coyotes and two relatives of cattle, quar and bateng, have been made. Many scientists state that the adoption of this practice will lead to loss of genetic diversity, result of sexual reproduction, which means posing an even more serious threat to endangered species. Before risking disabling species to face   environmental changes, there is emerging need to face the problem in its roots which are habitat destruction and hunting. Undoubtedly, cloning must remain in the toolkit of nowadays’ science when it comes to protect biodiversity.

In 2008, after detailed assessments in collaboration with independent experts across the Globe, the U.S. Food and Drug Administration (FDA) acknowledged cloned animals’ meat and products as safe as those from non-cloned ones. Given that the cost of the procedure, if followed, is extremely high, food products’ arrival to supermarkets is supposed to happen in far future. Nevertheless, cloning agricultural animals with the desired traits aims at using animals as breeding stock rather than for consumption. It’s widely known that male beef cattle, for example, undergoes a removal of its testes only a few days after its birth. A solution to this is cloning cells from a high quality carcass to create a fertile animal. A gelded racing horse has also a not sterile clone for breeding. It’s notable that milk production of some cloned cows is twice the average.

Imagine that you have just lost your beloved pet, cloning could give it back to you. Not exactly how it was… as both the traits and personality of an organism is the outcome of its genes’ expression on which environment has an important impact. A striking example is that of Rainbow and CC (copy cat), Rainbow’s clone and first cloned feline. CC was born at the College of Veterinary Medicine at Texas A&M University,  at the cadre of a program funded by the Californian company “Genetic Savings and Clone” (2004-2006), which provided to grieving pet owners their sick or deceased pets. However, CC (left) was apparently identical to Rainbow.  According to the explanation of the site  Learn. Genetics:
 
“The answer lies in the X chromosome. In cats, a gene that helps determine coat color resides on this chromosome. Both CC and Rainbow, being females, have two X chromosome. Since the two cats have the exact same X chromosomes, they have the same two coat color genes, one specifying black and the other specifying orange. Very early in her development, each of Rainbow's cells "turned off" one entire X chromosome, thereby turning off either the black or the orange color gene. This process, called X-inactivation, happens normally in females, in order to prevent them from having twice as much X-chromosome activity as males. It also happens randomly, meaning that different cells turn off different X chromosomes.So like all female mammals, Rainbow developed as a mosaic. Each cell that underwent X-inactivation gave rise to a patch of cells that had oneor the other coat color gene inactivated. Some patches specified black,other patches specified orange, and still others specified white, due to more complex genetic events. This is how all calico cats, like Rainbow, get their markings. CC looks different because she was made from a somatic cell from Rainbow in which the X-chromosome with the orange gene had been inactivated; only the black gene was active. What's interesting is that, as CC developed, her cells did not change the inactivation pattern. Therefore, unlike Rainbow, CC developed without any cells that specified orange coat color. The result is CC's black and white tiger-tabby coat.”
 
Human cloning
 
1998: Advanced Cell Technology created the first hybrid human clone.
The truth is that the numerous conflicts human cloning seems to have raised among the whole fabric of society have extensively suspended the operation of such methods since mid-1960s when human cloning was rendered a hot debate topic. According to 2015 assumptions, about 70 countries have banned human cloning claiming it as a serious threat to human dignity. To the question if human baby have ever been cloned and existed, there will be not any references to not solid claims even highly publicized. The common sense is that human cloning is limited to human embryos destroyed shortly after their creation. Last year, scientists in Massachusetts stated that they have cloned the first human embryo for medical purposes which passed away after three days. This year, Chinese researchers, using egg cells from patients at a fertility clinic, claimed to have cloned embryos also for medical purposes but all the embryos were destroyed after three days.
Both for pharmaceutical and reproductive human cloning, there is a strong obstruction called hesitation whether an intervention to natural processes can yield benefits instead of triggering dangers. This fact is absolutely normal given that humanity always hesitates in face of radical changes in any field. In any case, it’s sure that human cloning is much more complicated than many other mammals’ cloning as the two spindle proteins, essential for cell division, are too close to chromosomes in primate eggs so they are easily removed along with the egg’s nucleus.
 
Arguments in favor of reproductive human cloning

 An argument in favor of reproductive cloning is that infertile couples or homosexual couples will stand a fair chance to give birth to a child with qualities of both partners through genetic cloning, a method claimed as safer than the conventional ones by lots of specialists. For example, a couple incapable to generate an adequate number of embryos from IVF procedures can be facilitated by cloning via artificially induced embryo twinning until the desirable quantity of embryos. Even if the male partner is not able to produce viable sperm, cloning of his genetic material through SCNT with the contribution of the prospective mother’s ovum could be a solution for both prospective parents to offer chromosomal and mitochondrial DNA to their offspring, instead of seeking a sperm donor. The same method can be used for female homosexual parents as they can both contribute both types of DNA. Thus, for both cases, the proportion is different from that of natural conception.

Many people would fain make a replica of their child as a savior sibling, who would save the older brother from death through donating bodily fluids, umbilical cord blood,  non-vital organ or tissue, totally compatible as the two siblings would have nearly the genetic make-up of monozygotic twins. Compensating a loss along with giving an insight on the world regenerating brilliant minds or at least,  the genesis of people with the desired genome are also  main positions of arduous reproductive cloning supporters.
 
Arguments against human cloning and responses

To address to the first argument for cloning, one could say that Western political culture has established procreative liberty as an undoubted right. Can, although, this right overwhelm the truth that, until today at least, a clone is more likely to present adverse health effects to a point that the cloned human’s life becomes intolerable? Taking Dolly’s example, even if there is no solid evidence that her premature death occurred as a result of her artificial conception, arthritis, the disease from which it suffered to death, was uncommon for lambs of her age, probably a symptom resembling to accelerated aging. Someone could respond that even natural conception is dangerous and inefficient to a certain degree, as many couples with genetic abnormalities decide to reproduce and there is no prohibition for that, while 73% of fertilized eggs do not survive to 6 weeks gestation and 2-3% of newborn infants have congenital abnormalities. If the risk of cloning, once, approaches that of conventional conception, then, the cloning could be much more reliable to be adopted for procreation.

A drawback resulting from the first argument has a social basis: the clone will be the twin sibling of her genetic predecessor, in other words, the twin sibling of her social mother and the genetic daughter of her social grandmother. It’s apparent that familial roles become ambiguous with the distortion of generational boundaries. A response to this could be that, if adopted children that have no genetic relationship with their adoptive parents do not suffer from detrimental effects and their social parents conceive parenthood the same important as if they have given rise to their child, being a clone would not be that disastrous as genetic ties would have nothing to do with social roles.

The issue of savior siblings, in addition, creates grounds to fear about a possible devaluation of life, even if the savior sibling was willing to give her consent. In other words: Of course, human life is of uncountable value, though, that does not prevent people from the negation to accept this fact and isolate those people due to the laboratory way they came to life. That means new divisions and, hence, new types of discriminations.

There’s also the pessimistic viewpoint according to which clones will have trouble even in assuring their own rights and the ownership of themselves. The right of uniqueness will be violated as they will be, mostly, the recreation of an existing genetic code. However, taking the example of Rainbow and CC’s, clones cannot be completely identical not only due to mentioned factors: Their character will be absolutely unique, shaped by experiences and the irreversible impact of the zeitgeist them.

In terms of individuality, scientists are, also, talking about augmentation of crime rate since the guilt will be able to fall underneath rules using the identity of her law-abiding human counterpart. Changing identity could be done also as an effect of syndromes in which people pretend to be another person. In general, psychological problems will turn out to be a customary phenomenon as people will then get born to make other people’s expectations. As a personality is formed by the various circumstances and experiences-twins are a typical example-how could feel a person with Einstein’s DNA but with no trace of his talent? But let’s take the example of a clone born to “replace” a deceased child. To what point, will the child be capable of posing and making its own targets rather than following a life programmed to continue the life than once stopped shattering dreams and hopes? Anyway, it seems genetic determinism to believe that one can revive a human (or not) being by reproducing her genetic material: The challenges a human clone will encounter will totally differ so as to open up totally different opportunities leading to a totally different lifeline.

It must be seriously considered that parents could utilize biotechnology to designate their off springs, apart from replicating an existing DNA. This fact poses many people under the impression that a massive production of modified clones could happen relegating children to the status of mere possessions produced to serve to the needs of consumers, parents. People, then, could be used as a mean for others to obtain status rather than for enjoying their existence. This actuality could, also, involve despotic parents as the DNA choosing alone could compose a symptom of such a tendency. There’s also the feeling that those children will receive less love, a feeling not shared by many though. As many children were born with the use of artificial methods and their parents loved them enough to resort to expensive, time-intensive scientific methods in order to have them. Meanwhile, it was not love but chance what led to the natural genesis of uncountable children. However, in cloning, there is not genetic material from both parents involved. In my opinion, what should fairly trigger uncertainty are the military uses of biotechnology at large including the mass-manufacturing of soldiers susceptible to the idea of sacrifice seem to threaten peace.
 
Therapeutic cloning

The practical drawback of therapeutic cloning is that both stem and cancer cells proliferate indefinitely with stem cells accumulating terminal mutation after 60 cycles of cell division, as research has shown. Prerequisite for safe stem research is the clarification of their relationship. The social problem has emerged from those who recognize the embryo as bearer of moral rights, so oppose to the embryo experimentation which needs massive destruction of embryos. Comparing, though, to human cloning, the resistances appear to lessen due to the plethora of advantages.

The expansion of cloning as a common practice increases the potentials for a medical advancement boom accompanied with the advent of effective medicines and innovative cures for terminal deceases. Molecular causes of diseases can be detected with the assistance of stem cell research, which, in its turn, in grace of cloning, can work on stem cell lines from cloned embryos.  New therapeutic drugs can, additionally, be tested with the usage of differentiated tissues from embryonic stem  cells.

Tissue harvesting, with the development of stem cells, is supposed to decrease the side-effects of cosmic surgery, even, boost the lifespan spiraling, as someone could have his/her young cell cloned in order to have access to renaissance if need be. Genetics have surely found the way to overcome the major problem of heart attacks from which the whole planet is suffering: cultivation of cordial cells and replacement of the damaged ones. Similarly, their valuable plasticity permits embryonic stem cells to differentiate in all type of cells, allowing researchers to grow any kind of tissue in laboratory.

Last but not least, significant is organ harvesting by multiplying a small amount of somatic cells. As there would be no need for waiting in long donors lists for organ transplant, it doesn’t allow of ambiguity that millions of people would not pass on in expectation of a donor or being a donor at their own or not while the success rate would be much higher due to the –not 100%- assured compatibility.  

​Conclusion

Humans have the ability to interfere with nature. They – we – have fairly gained the self-estimation of an adequate knowledge, they would fain take as signal of access to nature’s mystery, genetics, the similarity of  DNA molecule throughout all known kinds of flora and fauna. There is one thing missing: Willingness. But it’s not necessary to get always theirs.  Bioethics express a plethora of fundamental doubts on that  and, especially, regarding cloning, they express them so loudly and fast, that even the most clear mind could be set in a challenging mental aberration thriving to the actual question: Should people interfere with nature especially in terms of human cloning? More thoroughly: Should humanity continue the effort of convincing itself that producing livestock in labs with extremely low rates is a much more sufficient solution to Earth’s hunger than a political solution? Risking genetic diversity and social balances? And, as generally as referred, has reproductive human cloning its roots in human egoism or not?
                 
Potential further research
·       Mitochondrial vs Chromosomal DNA
·       Environment vs Genes
·       Resistance of genetic material-Ways to protect it
·       Procreative ethics
·       Destructive political strategies

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