THE REAL SCOPE.



a. Optimizing the Performance of Human Genes by Verle E. Headings, MD.
b. Cloning.



OPTIMIZING THE PERFORMANCE OF HUMAN GENES.


On Friday, April 21, 1972 a Symposium was held on Ethical and Social Problems in Human Biology in the Conference Theater, Norton Union, of the State University of New York in Buffalo. The symposium started at 9 am. After the introduction by Dr. Gelbaum, the Vice President for Academic Affairs, and the first talk by Dr. Daniel Callahan from the Hastings Center, the audience was asked if anyone would like to make a comment at this time or make some suggestions as to the proceedings. A young man stood up and walked up to the reader, and began to give an account on the progress of the Communist Party on campus, which had nothing to do with the Symposium. Since he had within reach all the controls and could not be stopped, the whole assembly stood up and walked out into another less glamorous auditorium. We lost enough time, however, to postpone the next talk to be given in the afternoon by Verle E. Headings MD from Howard University College of Medicine on "Developing the Potential of Human Genes."

Before that took place we had lunch. The loudspeakers were blasting away rock music at such volume that the food seemed to want to come out through my ears instead of going down. Suddenly there was total silence and then a voice came on saying, "Today is Friday. Don't forget your contraceptives. Booth twenty two. Today is Friday." Then the music came back on at full blast. I said to myself, "What kind of a hellhole is this place?"
There was some talk about the shocking proposals made in genetic engineering and the need for control to prevent possible abuses as if those plans and abuses were for real. I had the impression: here we go again about Frankenstein’s monster, or here we are peering into a black box and making decisions not really knowing what is really going on.

Bat all was forgotten once I heard Verle Headings' presentation. His major thesis was that it is much more effective to achieve results in genetic engineering if, instead of trying to manipulate the genes themselves, we should provide for whatever is genetically given the optimum environment for development. First, he reduced all the fanfare and upset on genetic engineering to what is real by presenting genetic engineering today in three sets of practices and research.

SELECTION OF OFFSPRING
Selective and restricted mating
Artificial insemination
Selective abortion
In vitro fertilization
Negative eugenics
Cloning
GENE THERAPY
Cell transformation with DNA
Gene transduction by virus
Gene regulation
Cell hybridization by recombination
Gene excision
Selective mutation
OPTIMUM ENVIRONMENT
Replace deficient gene products
Restrict intake of specific factors
Restrict exposure to specific factors
Provide developmental opportunity

The first lot, referring to selection of offspring, is a rather mixed bag of tricks. It includes a number of atrocities, such as slave breeding practices by a large rubber company in Brazil. They were killing off native indians in the rain forest and bred slave labor selectively as recently as in the early 1970s. (First hand account of such practices are scattered among more than 2,000 narratives in B.A. Botkin’s Slave narratives, vol. 1-17, Washington: The Library of congress, 1941. Also check N. Lewis, Brazil’s dead indians: The killing of an unwanted race. Atlas, January p. 22. 1970.) The company’s practices have been stopped since. Artificial insemination and in vitro fertilization are medical techniques to resolve certain forms of infertility. These techniques are there to help people, although in vitro fertilization opens the way to human cloning. Negative eugenics is discussed as a special topic in the section on Eugenics where it is shown that in both, aim and method it is based more on hatred and ignorance than on realities of benefit. Cloning is also discussed as a special topic at the end of this section.
The second lot includes front line biomedical research where neither techniques nor the hoped for results are in really well worked out in some practical form. The exception is the DNA recombinant technology, or in other words, cell hybridization by recombination. In this line of research the methods have been well worked out and the results are most promising. This is also discussed as a special topic in the section on The recombinant DNA scenario.
Headings emphasized the importance of the environment in genetic engineering, since the phenotype is never determined by the genes alone. There is always interaction between the genetic and the environmental factors during development in addition to some random events. So why not make use of this fact and modify the gene effect via the much more accessible environment. Here are a few examples:

Replacing deficient gene products: Human insulin is produced by the pancreas. Certain types of diabetes are hereditary and result in an insufficient or not well functioning insulin. The needed insulin is then provided orally or as an injection from other sources than the diabetic person. (Note: Today we can mass manufacture human insulin using the recombinant DNA techniques.)

Restrict intake of specific factors. Galactosemia is an inherited metabolic disorder. The galactosemic infant is unable to metabolize galactose, the sugar in milk. The result is a slow poisoning of the nervous system, mental retardation, coma, and death. But if we provide a special milk for the infant which contains any other sugar but galactose, the disorder will not be manifested and the child develops normally. Amniocentesis is recommended to prepare the parents to provide the proper diet for the child right at the beginning.

Restrict exposure to specific factors. Albinism is a disorder of phenylalanine metabolism. Because of defective enzymes no melanin pigment can be formed from phenylalanine. The result is that the skin, hair, iris and retina are all devoid of pigment. The eyes are pink and extremely sensitive to sunlight, the skin and hair are white, and the skin has no protection against sunburn. In addition the nasal mucosa is also missing its pigment, which impairs considerably the sense of smell. Avoiding direct sun, and using dark glasses prevent the exposure to harmful factors.

The most important insight of Headings was that we should try to provide an optimal environment to any given genotype so that each child, whatever be the genetic endowment, will develop to the best possible phenotype.
It has been known that many Down syndrome children (21 trisomy) are most receptive to a loving, caring, and stimulating environment, and given the opportunity, they may develop well mentally, and in many cases they may even overlap the normal in their IQ distribution. I recommend to check out such documentaries as the movie, Educating Peter, presented by the Home Box Office from the National Down Syndrome Congress, State of the Art Inc. (800-232-NDSC)

For all children, irrespective of their genetic endowment, the benefits of optimizing developmental opportunities has been recognized. Today toy manufacturers will gear their product to certain ages when they are the most beneficial as development enhancers. Many TV programs for preschool children, such as Mr. Rogers' Neighborhood, and Sesame Street, have the same idea of enriching the child's environment and enhancing developmental opportunities. I believe this is most practical and beneficial approach to genetic engineering today, in spite of the glamor of the unusual.

There have been some abuses in the applications of genetic engineering, but on the whole both, research and use of knowledge, are aimed at real benefits for all concerned. Science fiction is for entertainment only.



CLONING.



Cloning is for real, but mostly in agriculture. Its purpose is to safeguard and multiply a rare genotype. The technology of cloning is relatively simple. The unfertilized ovum is enucleated by pulling the nucleus out via a fine glass pipette. The same is done to a somatic cell of an adult organism and the diploid nucleus obtained from the somatic cell is then inserted into the enucleated egg cell. The damaged cell membrane of the now diploid "zygote" closes up and repairs itself. All this maneuvering is followed by normal mitotic divisions of the cloned egg cell and as it goes through all the stages of normal development an adult is produced whose genetic make-up is identical to that of the somatic donor.

Of course, cloning is only possible if development after the in vitro technique described above is possible. Among plants the first cloned cells were that of a carrot. In animals the first cloned cells belonged to anamniotic amphibians because fertilization being external their eggs are easily accessible and development takes place in water, without the need of any kind of artificial life support. Among amniotes the first mammal cloned by Ian Wilmut and colleagues at Roslin Institute in Edinburgh in 1997 was a Finn Dorset ewe named Dolly. The choice was probably influenced by the fact that the connection between maternal and embryonic circulations in ruminants is not too intimate, the placenta being syndesmo-chorial. This means that the zygote may be brought to full term in a completely artificial environment. The same would apply to Perissodactyls (horses, donkeys, zebras) where the placenta is epithelio-choreal. Here the intimacy between the maternal and fetal circulations is even less intimate than among the ruminants. In the human situation, where the placenta is of the hemo-chorial type, the intimacy is so close that as of to date no artificial means are adequate enough to bring development to completion from the in vitro beginning to end. Here the implantation of the cloned egg cell into a properly prepared surrogate mother would be needed. This was the method used by the Japanese researcher Ryuzo Yanagimachi who cloned mice during a period from 1998 to 1999.

Until quite recently, human cloning has not been done, and for good reasons. It is a very expensive procedure, and it has no morally acceptable practical benefits. Many would rightly object against cloning a human fetus as part of an experiment, or as a source to supply human embryonic stem cells or human organs and body parts for whatever reason. The process of human development forms a self-completing unity where at no moment in time can the understanding of being human be replaced by the idea of becoming human from a non-human entity. The old, medieval concept of ensoulment at so many days during embryonic development (St. Thomas Aquinas) has no biological meaning in the continuum of development. Human development is the present outcome of millions of years long evolutionary process and it is not the recapitulation of this process within the span of nine months justifying such ideas that at this or that moment in time during development there is anything other than a uniquely individual human being in a process of differentiation and growth.

There are some dangers of cloning from an evolutionary perspective. Suppose that a rare combination of genes resulted in some specially useful trait in corn, maze or some other agricultural product. Sexual reproduction would destroy the rare gene combination and the trait would be lost. First cloning and then sexually inbreeding the clones obtained can result in large population and may be of great benefit. The members of the group of clones, however, being isogenic, will have no genetic variation and will become immune to natural selection. In a changing environment such situation invariably leads to extinction. That is why in agricultural products it is always useful to maintain the original genetic variation, at least in seed banks, while spreading out and making use of clones.

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