Over at Genetic Future Dr. Daniel MacArthur has a measured response to a Nature commentary by David Goldstein, Growth of genome screening needs debate. As Dr. MacArthur notes an excessive portion of Goldstein’s piece is taken up with inferences derived from assuming that the model of rare variants causing most diseases is correct, when that is an issue currently in scientific contention (and this is a debate where Goldstein is a primary player on one side). But the last two paragraphs of the piece is where the real action is, no matter the details of genetic architecture of diseases:
One potential problem with this is that numerous genetic risk factors will have diverse and unexpected effects — sometimes causing disease, sometimes being harmless and sometimes perhaps being associated with behaviours or characteristics that society deems positive. Even for simpler Mendelian diseases, up to 30% of the mutations originally termed pathogenic have turned out to be apparently harmless…Wholesale elimination of variants associated with disease could end up influencing unexpected traits — increasing the vulnerability of populations to infectious diseases, for instance, or depleting people’s creativity.
There are no clear-cut answers to the questions of what should be screened for and to what end, but we must at least begin the debate.
There’s nothing that I can find objectionable at all about the last sentence. We’re really close to the “we have the technology” moment. Seeing as how more and more of the higher socioeconomic strata are delaying having children you are going to have a phenomenon where those with disposable income are going to “want to make it count,” so to speak. Especially since children born to older parents already have a higher likelihood of having medical issues.
The specific point which Dr. MacArthur brings to light is that we need to balance social consequences with individual incentives. Consider something which is more clear-cut than diseases: sex selection. Intuitively we understand that humans flourish best in circumstances when the ratio between the sexes is balanced. Imbalances tend to lead in a skewing of social dynamics. But in many societies there are strong incentives toward having children of one particular sex. Therefore on an individual level the rational calculus is one where you make the choice which is totally irrational when everyone else makes the same choice. I have pointed out before that the reality is that male sex bias in both Japan and Korea have shifted toward a female sex bias (first in Japan, and now in Korea). So just like biological sex ratios cultural pressures tend toward equilibrium. Eventually. But, that equilibration may take a generation, and between now and then the social phenomena which we are confident will eventually fade may not be so positive, whether in the individual happiness of the excess sex, or in the aggregate functioning of a well balanced society. An average stable point can still manifest as uncomfortable swings and transitions for human beings living their lives.
In relation to preimplanation genetic diagnosis the moral and ethical dilemma is somewhat different. Overall there is a boundary condition where most might agree that genetic screening of some sort is preferred. The issue is that when price points decrease it is inevitable that instead of preventing Tay-Sachs, parents will want to prevent the birth of a brown eyed child. The latter is a pretty plausible candidate for selection; readers of this weblog who have brown eyes but one blue eyed parent have expressed the wish to load the die so that their children might be homozyogte for the allele which tends* to produce blue eyes. Or going to an example which is less Eurocentric, there are large effect genes segregating within South Asian populations which are responsible for the great amount of within population and family range in complexion. It is entirely plausible that South Asian parents, who are already major practitioners of sex selection, will be open engaging in diagnostic screening so that biological children are as “fair and lovely” as possible out of the potential range (skin color has huge life implications in India, especially for women, so sex selection and complexion selection may actually have opposite effects in that the latter may diminish the “need” for the former).
I jumped straight to cosmetic issues because I’m rather skeptical that governments or cultural elites will be able to prevent a lot of discretionary genetic screening for possible disease alleles. Unless we mandate that the whole society raises children and is responsible for their needs through mass transfer of payments in terms of a cradle-to-grave welfare state I think the demand will be strong enough that any debate of ethical concerns will be rendered moot and pushed to the margins of the anti-biotech movements of the Right and Left. A more interesting issue to me is the implication by Goldstein that we “need” more genetic diversity which might have negative byproducts for creativity.
There are ~7 billion people alive today. In raw absolute terms we’ve got a lot more summed up genetic variation than we did 100 years ago, let alone 1,000 years ago. Is there no point of diminishing marginal returns on absolute variation levels? In other words I suspect that in terms of creativity and the downside risks of removing some of the positive externalities of “oddballs” who are weird and unexpected we’ve got a lot of slack with our huge population. There are always going to be large groups of people who will refuse to manipulate the nature of their offspring, or constrain the parameters excessively. Large perhaps not in a proportional sense, but we’ve got a huge census size now. My own suspicion is that there are limits to how many creative types a society can absorb. Most people are going to be more conventional, or going to have to be more conventional, because much economic and social productivity is driven by workaday behaviors. PGD is going to “perfect” these workaday types. I don’t see a problem with that. There will be huge numbers of Leftist Deep Ecology types and Rightist Roman Catholics who will let nature or god decide for them. These will be the cultural creatives if deviation from the genetic ideal is strongly correlated with creativity.**
* ~75% of the variation in the European population in blue vs. brown eyes is accounted for by a few SNPs around the HERC2-OCA2 locus…but, the prediction algorithm isn’t perfect, so a parent might not get their heart’s desire.
** With widespread whole genome sequencing I’m assuming we’ll actually have time to see if this is true. That is, genetic oddballs are more creative.