Genetics of Original Sin (21 page)

This astonishing return to virginity by a transplanted nucleus was first observed in the 1970s, in amphibians, by the British biologist John Gurdon, who is the true “father” of animal cloning. Shortly afterward, a Swiss investigator claimed to have accomplished the same result on mice but later had to retreat in some confusion—perhaps unjustly in view of what is now known of the hazards of the technique—because his findings could not be reproduced. As a consequence of this unfortunate incident, mammalian cloning fell into disrepute, until Dolly was produced by Wilmut and his team, who obviously belonged to those who “didn't know it couldn't be done and so went ahead and did it.”

Cloning can be used for several purposes (
fig. 15.2
). One form, called
reproductive
cloning, aims at creating a younger, quasi-identical twin of the donor of the transplanted nucleus. This method can be used, for example, to perpetuate valuable stock.

In so-called
therapeutic
cloning, the resulting early embryo is sacrificed, to provide totipotential stem cells that are kept for possible future use in the repair of damaged tissues in the donor of the nucleus. The advantage of this technique is
that, because of their genetic kinship with the cells of the donor, such stem cells are not immunologically rejected by the host, as would be the case with foreign grafts.

Fig. 15.2. Different kinds of cloning. The somatic cell nucleus destined to be transplanted into the enucleated oocyte is inserted as such (1), or after modification by genetic engineering (2). The renucleated oocyte is either implanted to develop into an individual (3, reproductive cloning) or used for the generation of stem cells (4, therapeutic cloning). Combination of steps 2 and 3 is used to create genetically modified (transgenic) animals.

In a particularly important form of cloning, which could be called
engineering,
the transplanted nuclei have been subjected to some genetic modification, leading to the creation of genetically modified organisms (GMOs), also called “transgenic.” This procedure is now widely used in research, where it has allowed a host of important discoveries. There are also many industrial applications of this technique, used, for in
stance, to generate animals that manufacture valuable human proteins in their milk or to endow animals with new, useful properties, such as the ability to subsist on new kinds of foods, enhanced productivity, or lower harmfulness to the environment. Thus, pigs have been equipped with a bacterial enzyme that renders the animals able to digest an important phosphorus-containing component of their food that is normally excreted unbroken and is a major source of pollution of streams and lakes in the neighborhood of pig farms, where it favors eutrophication, an excessive proliferation of algae that stifles other forms of life. These animals have been called “enviropigs” because of their beneficial effect on the environment. Genetically modified plants are also produced on a large scale, by a different procedure, which I describe in
chapter 18
.

So far, no authenticated instance of human reproductive cloning has been reported. But this is due mainly to ethical constraints that most countries impose on such attempts. There is no reason to suspect that the technology would not be applicable to human cells. Certainly, this possibility has already inspired innumerable conjectures and debates. Creating a younger copy of oneself or replacing a lost child have been cited as possible applications of human reproductive cloning, a procedure that is, at present, prohibited by most legislatures around the world.

Human therapeutic cloning is allowed in many countries but fiercely opposed in others, including the United States, where prolife advocates condemn the destruction of a potential human embryo inherent in the technique. Because of this opposition, an immense research effort is aimed at obtaining
stem cells without cloning. Possible sources are umbilical cord blood or, if some genetic commitment is acceptable, differentiated tissues, most of which are now known to contain pluripotential (though not totipotential) stem cells. Special hope is put in a recently achieved procedure claimed to turn back the clock in a fully differentiated cell by the modification of only four genes.

As to engineering cloning, its envisaged human applications are restricted to the medical correction of some specific gene defect already identified. The use of this technique to produce “designer babies” has, however, been much evoked, hotly discussed, and mostly rejected.

Production of designer babies would require considerable improvement of present cloning methods. In today's state of the art, the percentage of failures remains too high to allow an ethically acceptable use of human material. The number of “failed” embryos and their fate would create unmanageable situations. Should safe procedures someday become available and should the ethical ban against human reproductive cloning be lifted, this technique could conceivably be used to engineer genetically modified humans, by knocking out or otherwise mutating certain genes or by inserting new ones.

The main problem, if such manipulations were to become possible and ethically acceptable, would be the choice of the genes to be manipulated or inserted. We would need to know much more than we know now about the genetic control of human qualities. This is a major unsettled issue. Experts even disagree on the extent to which certain characteristics are genetically determined, let alone agreeing on more specific relationships. It does, however, seem probable that complex psychological traits or talents do not depend on single genes. It is unlikely that one could engineer the production of a new
young Mozart or Einstein or Martina Navratilova by simple genetic manipulation.

Even if the necessary knowledge of genetics should one day be available, one still would have to agree on what qualities to aim for. If some central authority were in charge, the threat of a
Brave New World
would loom. In order to avoid this dangerous difficulty, some have proposed formation of a genetic “supermarket,” in which prospective parents would choose the qualities of their offspring à la carte. This idea may seem grotesque, but it could arguably be viewed as an improvement over the present lottery, in which the genetic makeup of children is decided by pure chance among a huge number of combinations of parental genes. Remember that, because of the genetic reshuffling that takes place in the course of germ cell maturation, oocytes and, especially, spermatozoa come in a large number of different genetic varieties. The genome of a fertilized egg depends on whichever of the millions of spermatozoa contained in an ejaculate succeeds in entering the available oocyte first. Substituting reasoned choice for such a blind game could be seen as desirable.

Whether such manipulations will ever be attempted or accomplished cannot be predicted at the present time. They certainly are not among the measures that can be contemplated today as a solution to the present pressing problems of humankind. Even if one knew what to do and how to do it, the question would remain: Who should benefit from the improvement? Changing six billion individuals hardly seems feasible. Starting with a small group destined to become the new
Herrenvolk
is too reminiscent of Nazism to even be thinkable today. Letting selection be based on the ability to pay for the very expensive procedures involved, as proposed by the American biologist Lee Silver in his book
Remaking Eden
(1997), would be consistent with laissez-faire, though not with most people's concept of democracy or social fairness. It will be up to future generations to make the appropriate decisions if they are ever able to produce viable genetically modified humans. The problem does not presently exist, but it may well some day.

C
orrecting the flaw is not the only solution to our genetic predicament. Genes can be overruled by education. This message comes to us from neurobiology, which tells us that some among our most decisive traits are
epigenetic.
I use this adjective in the original meaning given to it in the 1930s by the British evolutionist Conrad Waddington (1905–1975) to qualify traits that are not genetically transmitted and are acquired later in life, under genetic control but in response to outside factors. In recent literature, as we have seen in
chapter 8
, the noun “epigenetics” designates a new kind of genetics involving transmissible traits that are not encoded in DNA sequences but accompany the DNA. The two definitions are thus contradictory in terms of heredity.

The wiring of the human brain is a striking case of epigenetics in the Waddington sense. Only the general features of the
brain are genetically determined. Its detailed wiring is superimposed upon the genetic blueprint, it is epigenetic. It couldn't be otherwise. The human brain contains about one hundred billion neurons, each of which is connected with some ten thousand other neurons, adding up to about one million billion interneuronal connections. Our genome contains only about three billion bases, not nearly enough to determine that many interneuronal connections, even if—which is hardly conceivable—each base should code for a connection. This fact opens hopes for the future, offering a way for us to escape the possible fatality of genetic determinism. This escape is particularly meaningful, as it concerns the brain, the organ through which we make decisions and perform actions.

The way the wiring of the brain is established epigenetically has been elucidated by the investigations of Jean-Pierre Changeux, in France, and Gerald Edelman, in the United States. According to these scientists, growing neurons continually send out projections in all directions. Acting like “feelers,” these projections, upon chance encounters with each other, form transient connections that quickly come apart again if they are not used. If a stimulus repeatedly goes through such a connection, it becomes stabilized into a synapse. Both of these scientists have stressed the analogy between this mechanism and Darwinian selection. Chance offers a vast array of possible connections among which a small number get selected by use. Edelman calls it “neural Darwinism.”

The implications of this epigenetic process are critical. The human brain is shaped to a large extent by the impulses to which it is exposed during the first years after birth, even, perhaps, while in the womb. The process continues all life long, by education, training, and learning. Even an old brain can make new connections. But the first years are crucial. Children de
prived of contact with other humans for the first years of life are permanently stunted psychologically.

These findings have a profound significance for the topic of this chapter. If we wish to take advantage of the plasticity of the brain to counter the defects imprinted in us by natural selection and escape the tyranny of our genes, we must start in the cradle and continue afterward in the early educational environment to which a child is exposed, in a nursery, kindergarten, or primary school, or at play with peers or parents and other grown-ups. In other words, for children to be changed, their parents and teachers must first be changed.

This looks like an impossibility. It requires parents and teachers to be changed in adulthood. Furthermore, in order to be effective on a global scale, the change would have to affect hundreds of millions of largely illiterate parents, as well as their children's elementary schoolteachers. Instant change, over a single generation, is clearly impossible. Evolution, step by step, toward the desired situation is a more realistic ambition. Even if started on a small scale, such a movement, if sufficiently contagious, could snowball into worldwide enlightenment.

Many such attempts have been made in the course of history. Think of pacifist religious groups, the Amish and Quakers, the advocates of nonviolence, from Christ to Buddha to Gandhi, conscientious objectors, the communes and flower children of recent years, “make love, not war,” and so on. None of these movements has snowballed. Some have even degenerated into violent defense of nonviolence. But this is no reason for despair. With increasing awareness of the disaster we are
facing if we do not change course, future initiatives could meet with greater success.

Even a large-scale movement is not unthinkable. History shows that mass indoctrination of adults by single individuals is possible. Political leaders have done so repeatedly, but mostly within the confines of national borders and with aims that were far from pacifistic. But some philosophers and, especially, religious leaders have managed to influence huge masses across national boundaries. They, more than anybody else, are in a position to help spread the epigenetic changes needed to save the world.