Proposal for Human Progeny Testing

Human Genetic Improvement

by Paul VanRaden

Introduction

People differ in their abilities to be happy and in their abilities to lead productive and useful lives. People differ in part because they have been raised in different environments and in part because they have inherited different genes. Despite their differences, all people could probably agree that new babies should receive genes which would lead them to be productive, useful, and happy rather than genes that would cause them grief, if only this were possible. In an abstract sense, then, every reasonable person should be in favor of genetic selection in humans if it could be used to cause his own children to grow up happier while at the same time causing no detrimental effects to anyone else.

For many people, though, the mention of genetic selection in humans brings to mind an image from a few decades ago of a terrible breakdown of society and a very evil dictator making the selections. It is unfortunate that such an event occurred. But people who value freedom should realize that, if given the chance, genetic selection could just as easily be associated with freedom and kindness as with dictatorship and evil.

Individuals now are for the most part limited to giving their children their own genes, whether they are happy with those genes or not. A better system is needed, one that allows individuals who realize they have not inherited the best genes in the world a chance to do something about it. Someone whose own genes have caused him grief might consider it the highest form of morality and of unselfishness to want his children to have the best genes possible, or at least to have genes free of defect, rather than to have his own genes if in fact these are the source of grief.

A purpose of this paper is to argue in favor of giving people the information and the means necessary to make decisions regarding which genes their children will inherit. This could be accomplished by determining which sources of genes actually do cause productiveness, usefulness, and happiness and then by allowing people to choose such genes for their children if they desire.

They could also choose to contribute their own genes, as currently, but for people already unhappy with their genes, the thought of contributing these genes to their children might make them even more unhappy. Practical questions then involve how one measures happiness and how one separates genetic from environmental factors. These questions will be addressed.

The Proposal

The purpose of this paper is to present a program to facilitate genetic selection in humans. Specifically, the topic is how to give people who would rather pass genes other than their own on to their children the means to identify and to obtain the kind of genes which would cause their children to be happy. Formerly, one's only choices were to have or to not have children. It is good that new choices are now becoming available.

Artificial insemination (AI) in humans is already being done on a wide scale in the U. S., with about 20,000 babies being born by this technique each year (Anderson, 1982). This is generally not for couples who have voluntarily decided to give their children genes from someone else but for couples in which the husband is infertile and they have no other choice, save adoption. But whether the choice is voluntary or involuntary, it is difficult to argue that those who use AI would rather give their children genes which they know little about as opposed to genes the effects of which they have studied. Therefore, even if the prospect of couples voluntarily choosing outside genes is ignored, the large number of infertile couples who now resort to AI makes the topic of genetic selection an important one, especially important to those directly involved in raising these children and of course to the future children themselves.

To understand how one might choose a source of genes which would cause one's children to be happy, some background information and genetic theory is needed. A simple method for choosing sources of genes is to rank individuals based on their own measurable traits (phenotypes) and then to choose those that seem most desirable. This is the idea behind the "Nobel sperm bank", which was started in 1980 to provide a source of superior genes for those who want them (Saladin, 1980) and also is the method advocated by Muller (1961). Unfortunately, as has been the case in many animal species, such selection often chooses individuals whose environmental circumstances are very favorable but whose genetic makeup may be much closer to the population average than one would hope.

In animal populations, a very simple method is employed to solve this problem. It is the progeny testing of males. For many traits, determining the value of an individual's genes by looking only at that individual's phenotype is difficult. This is because a large proportion of the differences between individuals may be due to environmental or unexplained factors rather than due to genetic differences. The proportion of variance between individuals likely to be of genetic origin is called heritability or h**2. The heritability to which this paper will refer is the narrow sense heritability, which measures only the amount of genetic variance which parents pass on to their children in a hypothetical random-mating population.

Progeny testing allows the genetic merit of an individual to be estimated precisely, the precision being a function of number of offspring and heritability. By evaluating a large number of offspring of many males, those males whose progeny seem most desirable in some sense can be selected to produce additional offspring. The same principle could be applied to females, but at this time females cannot contribute their genes to large numbers of offspring nearly as easily as males can. In the future, embryo transfer may alleviate this problem to some degree.

One of the important principles in progeny testing is randomization of usage. This distributes the progeny of gene sources evenly and fairly across a population so that differences in average merit of progeny reflect only genetic differences of the males tested and not differences in the environments their progeny were raised in or differences in the merit of females who contributed their genes and mothered these progeny. Randomization also ensures that progeny will be raised in a wide variety of environments so that results can be generalized to the population at large.

Objections

People may raise several major objections about the idea of human progeny testing and genetic evaluation. The first objection is one already discussed in the introduction. In most people's minds, the idea of genetic selection in humans is directly associated with the phenomenon of Hitler. Thus, it is wise to see if there are any differences between the ideas of Hitler and those proposed here.

In the current proposal, no individual can force any other individual to reproduce or not reproduce, no one can force another to use their own genes or to use someone else's genes, ideally all children are born to parents who want them, and the government need not and even should not get involved in the process. Genetic selection is controlled by parents deciding to contribute either their own genes or someone else's genes to their children, and if they choose someone else's genes they have the right to use any or all information in deciding whose genes might give their children the largest chance of being happy. Or, they can obtain genes from a random, unevaluated member of the population as is essentially what those who use AI now are forced to do.

A second objection is that the heritabilities of important human traits may be too small and the generation interval may be too long to make genetic selection in humans worthwhile. A counter-argument is that the distress caused to those who inherit genes causing poor health, poor looks, or poor brains is so great that any improvement in their condition is worth the small trouble it takes to achieve it. Realistically, the progress to be gained by genetic selection is not enormous, but then neither is the cost. Surely, if selection programs for animals can yield positive returns on investment, selection in humans should have much higher profitability.

A third objection is that closely related individuals might unknowingly marry each other if large numbers of half sibs are created. This situation would not occur often but could easily be avoided if children conceived by AI were told this fact and were also told some identification number of their genetic father. This identification could be in coded form to prevent a child from actually discovering his genetic father if this were desired. Snowden et al (1983) have studied children conceived by AI and recommend that these children be informed of this fact rather than to keep their genetic origins a secret.

Two related objections are that having a large number of offspring from a single male is too risky in terms of genetic defects and that such a program might result in a substantial reduction of genetic variation and inbreeding. The second of these objections is put to rest very easily when one considers that the number of males contributing genes to the next generation would still be huge even with a very successful AI program. The first objection appears to make sense only when the progeny of a particular male are grouped artificially by themselves. But when one considers the risk to any couple conceiving a child by AI, the risk of genetic defect is no greater than, and in fact is bound to be less than, the risk for a child obtained naturally. This is because those males known to be carriers of genetic defects would be eliminated as donors. When one considers the population as a whole, the average number of genetic defects would also decrease.

Although overall genetic disease rate should decline, incidences of a few rare diseases could happen to increase due to chance heavy usage of some heterozygous individuals. Nevertheless, a big benefit of progeny testing is that it would aid in the process of carrier detection (VanVleck, 1979). Individuals would have many more relatives, so that a larger proportion of suspected carriers could be informed of this fact and greater strides could be made in reducing genetic disease.

A final objection is that the whole idea of genetic improvement of humans is somehow unnatural or immoral, or is playing God. People who feel this way certainly have the right to continue to give birth to children by natural means. But if the option was readily available, many couples might rather play God by giving their children genes from a well-tested source than play roulette by giving their children genes which they know little about, or worse yet, genes which they know to be harmful.

Reasons for Progeny Testing

There are three simple, straightforward reasons for initiating a program of progeny testing and genetic evaluation in humans. They are a) that those couples who cannot or do not wish to pass their own genes to their children will finally have a reliably tested source of genes available for substitution, b) that important questions regarding how much of the variation between individuals is of a genetic origin may finally be answered, and c) that even those couples who continue to reproduce naturally will have a better understanding of what traits they may or may not pass on to their children as a result of information gained in this study.

A final reason for starting such a program is that similar programs with domestic animals, for instance, dairy cattle, have been very successful and economically rewarding. It always seemed wrong to me as I grew up that I and my fellow farmers could spend such time and effort searching for the right genes to put into our next generation of crops and livestock, and yet when it came time for us to contribute genes to the next generation of people, each person was expected to contribute his own genes to his child unthinkingly, whether or not he was happy with those genes himself and whether or not he knew that there were better genes easily available. It didn't make sense then, and still doesn't.

Practical Problems to Overcome

Several problems must be overcome if large-scale progeny testing is to become a reality. Sufficient numbers of couples must be found among those coming to AI clinics who will agree to be part of a progeny-test study. This means they must agree to have data collected from their child throughout the child's early life, say until the age of 18. Data collection even after this age would be desirable, but then would be subject to consent of the child. Couples who wish to keep their involvement with AI a secret may not wish to cooperate with data collection. However, with the recommendation now that children be informed of their genetic origins (Snowden et al,1983), agreement for data collection may be easier to obtain.

If progeny-test results are to be reliable and believable, randomization of donor to couple must be done. Ideally, one would like usage of all donors to be completely random, but couples are not likely to agree to this. Some grouping would have to be done and then donors chosen randomly from within the group. Grouping could be on race and on certain visible body characteristics, for instance.

Currently, donors are matched to couples based on resemblance of the donor to the husband. If randomization within groups is used, matching of donors to husbands could not be done quite as accurately. Nevertheless, if couples do not intend to keep AI a secret, it is probably less critical to have the child look like the husband.

A big problem might be just to decide what traits or how many traits to measure on the resulting offspring. General categories of traits to measure might include physical characteristics, abnormalities, athletic ability, looks, intelligence, personality, and interests, but one could think of hundreds of ways to measure such traits and there would be many individual components within each trait. Much research is needed to determine which traits are important and how to best measure them. Obviously, the more traits that are measured, the more information is gained, but also the more unwilling that couples would be to have their children subject to such detailed scrutiny.

A sufficient number of long term semen donors would need to be secured. Agreement to supply semen for, say, 40 or 50 initial progeny for the test would not be sufficient. The idea is that, once progeny-test results are available, semen from the top ranking males would be in large demand. Thus, it would make sense for all males in the progeny test to continue banking semen in frozen storage during this waiting time. Finding males to agree to provide semen over many years should not be difficult, however, if they are allowed to profit from their efforts. It is not difficult to imagine progeny-tested human males earning $100,000 or more per year from semen sales alone. Progeny-tested bulls can earn much more than this and their progeny are only cows, not people.

For the best progeny-tested males to really have an impact, much more efficient usage of semen is required. Problems to overcome in this area are timing the insemination to coincide with ovulation and placing the semen in the uterus or cervix rather than the vagina. Research on both of these topics is progressing. Ovulation can now be detected by chemical, temperature, or ultrasound methods and intrauterine insemination can usually be carried out without complication although success rates are still low as compared with animal species.

Some national system of identification of donors would be needed so that progeny of AI could verify, when they married, that they were in fact not marrying a half sib by chance. Such potential marriages would be rare even if large groups of paternal half sibs existed, because the children of one male would likely be distributed over the entire country and would constitute only a very small proportion of the total population. Nevertheless, for peace of mind of those involved, it would be good to compare identification of genetic fathers. Perhaps something simple like social security number of donor would work without making it too easy for children to contact the donor if he did not wish to be contacted.

Collection of data itself could be a difficult task. One might want to obtain peer evaluations for a trait such as "niceness" or "easy-to-get-along-with-ness" for instance, but such information would be difficult to obtain without singling the child out or making the child feel awkward. School records and results from certain standardized tests could be used, but this might require contacting a different school for each child in the study, which could be expensive. Keeping track of addresses for couples and their children would also require some effort.

Analysis of the data should not be a problem if randomization is carried out properly. Statistical procedures for ranking sires are already well developed from animal data. Unfortunately, much precision is gained in animal data by having progeny of several of the sires to be evaluated all raised together in a common environment, such as a herd. This would be difficult to do in humans, but in its place certain variables on the parents such as education and income could be collected to correct for environmental differences somewhat.

Implementation of the Program

Starting a national or even regional program of human progeny testing and genetic evaluation would require much coordination of effort. Nevertheless, since similar programs are already operating profitably in animal populations, the task cannot be that great. One might think that a single national program carried out under the guidelines of a governmental or independent agency would be most effective. A government program probably also has largest chance of being abused. An alternative would be for competing private firms to design their own programs. Obviously, competing firms could still agree to coordinate their data collection and data analysis efforts. The competition would then focus on which firm could most efficiently find and deliver the kind of genes people would like their children to have.

AI clinics are already in place and doing substantial business. What is required is to organize the usage of particular males in such a way that their genetic merits for various traits can be accurately determined. This would require finding couples who agree not only to use the particular males of the study as donors, which should not be difficult, but to allow data collection on the resulting children. For couples to give prior agreement, they would probably want to know exactly what sorts of data will be collected and they might also want the option of allowing some variables to be collected while refusing others.

Funding for data collection could be a problem unless only already-recorded variables such as school grades or results of standard tests are to be used as traits of the study. Traits which require a researcher to visit each child would be somewhat more expensive to measure, but these traits include some of the most interesting and some which have never been studied before, such as a most important trait, looks. Data collection expenses could be charged against later revenues from sales of semen. This would require only some venture capital.

Example of Intended Results

Suppose, for example, that 100 males are progeny tested initially and that they obtain an average of 50 progeny each. After approximately 18 years, assuming that data are collected on all progeny, a summary could be produced which might look something like Tables 1 and 2.

Table 1. Gene sources ranked on overall index.

Estimated Transmitting Abilities¹	6593	Gene sources 4816	5702	etc.
Overall Index²	129	126	124
Looks	+1.31	+.83	+.58
Intelligence	+.20	+1.19	+1.91
Athletic Ability	+1.50	-.35	+.35
Peer Evaluation	+.44	+.72	-.09
Childhood Happiness	-.26	+.22	+.19
Artistic Ability	+.00	+.05	-.96

¹ Expected differences of this source's progeny from the average source's progeny. All traits except overall index have standard deviation of 2.

² Computed as 100 + 10*(looks + intelligence + peer evaluation + .7*athletic ability + .4*childhood happiness + .3*artistic ability)

Table 2. Additional traits of gene sources.

Trait	6593	Gene sources 4816	5702	etc.
Eye color alleles	brown, brown	blue, blue	brown, green
Hair color alleles	black, brown	brown, blonde	brown, red
RH factor	+ +	+ -	+ +
ABO blood type	o, o	A, o	o, o
Height (inches)	+.74	+.28	-2.11
Weight (lbs)	-5.3	+2.5	-8.1
Ease of birth (s.d. = 2)	+.61	-.10	+.94
Price¹	$30,000	$22,000	$21,000

¹ Price per pregnancy in U. S. dollars. If no pregnancy occurs after 10 inseminations, 1/2 payment is refunded and agreement cancelled. Prices also available for per- insemination service.

This is just one approach for presenting the results. Many people might not wish to be confronted with such detailed information about the sources of genes available to them. Nevertheless, the purpose of the tables is to stimulate discussion about what traits are important to human happiness and how sources of genes which contribute happiness might be selected and distributed.

It may appear that the weights in the index for ranking gene sources are somewhat arbitrary. This is, of course, true. Each person might have his own feelings about which traits should be included in the index and what their relative emphasis should be. Nevertheless, an overall index can be designed to reflect the average person's views and is just an aid for condensing the many numbers which might appear for each gene source down into one useful number. Anyone whose views differ substantially from those of this overall index would be encouraged to construct their own index and rank gene sources on it.

The overall index should include those traits for which the optimum is in one direction and which most people would agree are important. Other traits exist with intermediate optima, for instance weight, which individuals on either end of the distribution might be concerned about but which, on the average, the population may not wish to change. Traits which are expressed earlier in life could be given higher emphasis relative to those not expressed for many years because inexpensive non-genetic solutions may be found to cure problems caused by genes, for instance, plastic surgery to correct problems of appearance.

The prices in Table 2 are, of course, pure guesses. Still, it is reasonable that couples might regard that giving their child a proper set of genes is about of the same value as giving the child a college education. The quantity of semen available from the best gene sources will greatly influence price. It might be that 100 children per year could result from each male, but if this figure is too high or too low, prices would be affected inversely. In other species, for instance cattle, the best males now sire many more than 10,000 progeny per year but such rates are not likely with humans for some time.

Many people might, upon seeing the prices in Table 2, complain that the program would benefit the rich and do nothing for the poor, whose children could benefit most from having an improved sample of genes. Table 2, however, reflects only the uppermost prices, which there would be few of. Semen from most of the remaining males would be available at much more reasonable prices, and semen from males evaluated to be below average probably would be discarded. Anyone who could afford to raise children could probably also afford AI.

Conclusions

A program of progeny testing and genetic evaluation should be initiated in humans, because it would be profitable, because it would answer important questions about the inheritance of many traits, and because it would provide a source of reliably tested genetic material to those concerned about what genes they pass on to their children. In a democratic nation which stresses individual freedoms and an abundance of choices, such a program could provide a large amount of happiness with little chance of abuse. It would give to parents the option of not having to pass poor genes on to one's children if one was not so happy with those genes himself.

This program would not need, and would not tolerate, a dictator or some mad scientists deciding who should reproduce or what genes should be reproduced. Rather, it would require only that parents consider, when creating a new child, whether that child would be happiest with their genes or with the genes of someone else, and if someone else, who that someone should be. A voluntary program like this would be hard to abuse in a society where individual consent is required for almost every decision, and obviously consent would continue to be required for such a personal decision regarding reproduction. Besides, laws prohibiting the natural production of children would be very hard to enforce, even for the most dedicated police state.

A more likely possibility for abuse comes from those who would, through legislation, force others to accept their own ideas that babies should always have their parents genes rather than having the best genes possible, or force them to accept that random selection of donors is preferable to actually finding out which donors have the best chance to donate happiness.

Artificial insemination with donor semen is already a common phenomenon, with many thousands of babies conceived in this way each year. It would be nice to think that the parents of these children, and indeed all parents, would be concerned enough about their children's futures to at least wonder whether the genes their children receive will cause them to be happy or sad. It is time to begin questioning some traditional ideas about reproduction and to begin demanding more information about how the genes we give our children affect their abilities to lead happy lives. Genetic selection is not an entirely new concept, but it is surely a concept worth a second evaluation.

References

Anderson, J. K. 1982. Genetic engineering. Zondervan Corp., Grand Rapids, MI.

Muller, H.J. 1961. Human evolution by voluntary choice of germ plasm. Science 134:643.

Saladin, K. S. 1980. The Nobel sperm bank: an affront to humanism. Humanist 40:61.

Snowden, R., G. D. Mitchell, and E. M. Snowden. 1983. Artificial reproduction: a social investigation. George Allen and Unwin, London.

VanVleck, L. D. 1979. Notes on the theory and application of selection principles for the genetic improvement of animals. Dept. of Animal Sci., Cornell University, Ithaca, NY.

"Proposal for Human Progeny Testing" was written in Ames, Iowa in 1985 while I was a graduate student studying animal breeding.

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