Arguments against routine screening for severe disease genes; food for thought

Yesterday I pointed to an article by New Scientist editor Michael Le Page advocating routine carrier testing for severe disease genes in parents-to-be, followed by IVF and pre-implantation genetic screening of embryos for couples unfortunate enough to both be carrying mutations in the same gene. I asked for well-reasoned objections to this approach from commenters.

Razib responded with a post at Gene Expression. Firstly, he pointed out that well-reasoned objections are not what matters in this debate:

...though reason is the "front side of the house" in this discussion, the
real work is being done by intuition in concert with social consensus
in the kitchen.

and that pragmatic concerns will play a bigger role in building society's view of these technologies than sophisticated moral arguments:

The best way to be on the "right side of history" in this sort of
discussion isn't to argue in bioethics journals, it's to make sure that
the cost of the procedure comes down and its marketing makes it seem
innocuous, or the inverse if that is your position.

I completely agree - I've argued in the past that the current widespread taboo against pre-natal screening will ultimately be eroded by pragmatism, if and when it becomes clear to parents that screening provides a higher probability of good outcomes for their children (a desire that out-weighs virtually any religious proscription). My ambition here is not so much to seek a knock-down argument for universal screening as to convince myself what the appropriate ethical stance is for me to take regarding these technologies.

John Hawks also contributed a long and thoughtful comment pointing out that the cost-benefit equation is not as simplistic as Le Page proposes. Hawks' costs include the financial burden of IVF and the fact that IVF still has a high failure rate relative to normal conception (for fertile couples) - these are perfectly fair, but it's worth noting that under Le Page's proposal only those parents who both carry known disease-causing mutations in the same gene would be encouraged to pursue IVF and PGD. For most couples the only cost would be carrier screening, which could probably be provided at a cost under a thousand dollars using a chip-based assay, including the cost of validation assays for positive results (I'm assuming a substantial cost saving due to volume if the test was offered as routine). The costs of IVF/PGD would then only be borne by couples who were advised that they were both carriers of mutations in the same gene, and who chose to undergo these more arduous screening processes to ensure that they did not carry an embryo with two mutated copies to term.

One of the most interesting impacts of routine genetic screening that Hawks notes (and that I've discussed previously) is the burden of guilt and social condemnation carried by parents who choose not to undergo screening or not to act on information they receive, and then give birth to a disabled child:

The argument also ignores the suffering of people who face the
opprobrium of society for their choice not to have the test performed.
At present, this is considered to be bad luck. The change toward an
attitude of parental negligence has already begun for parents who
choose to complete Down syndrome pregnancies.

There is no question that this will become a very real issue as the availability of severe disease screening increases over the next few years. Whether it serves as a powerful argument against the use of screening, however, is another matter. To return to Le Page's analogy, there are some parents who would prefer to let their child die than to allow them to be "poisoned" by antibiotics, blood transfusions or other modern treatments; does the social condemnation suffered by these parents serve as a good argument against the routine use of antibiotics?

I don't have time to respond right now to several other excellent points made in the comment thread, but hope to get back to them later. For the moment I will simply acknowledge that there is no simple ethical road here, and that it will be crucial (as Hawks points out) to perform a thorough cost-benefit analysis incorporating financial, social and emotional factors. Regarding the financial aspect I recommend a 2006 article by Armand Leroi (pointed to by commenter Carl Shulman) that is well worth a read.

Subscribe to Genetic Future.

More like this

A couple of weeks ago I pointed to an article by bioethicist Jacob Appel arguing that genetic screening for severe disease mutations should be mandatory for parents undergoing IVF, and that not doing so is tantamount to child abuse. Today the same theme is taken up by New Scientist biology editor…
In the last century infant mortality has declined precipitously in the Western world, thanks in large part to the development of antibiotics and vaccination. Yet as the suffering and death from infectious disease has reduced, the burden from genetic disease has become proportionately greater:…
Over at Opposing Views, bioethicist Jacob Appel argues that pre-implantation genetic screening for severe disease mutations should be compulsory for parents undergoing IVF. Appell dodges one obvious criticism of this suggestion - that it unacceptably limits parental autonomy - by pointing out that…
Disclaimer: my wife and I have both received and used free testing kits from Counsyl. Counsyl is a rather enigmatic player in the personal genomics field: apart from a brief mention in Steven Pinker's excellent NY Times piece over a year ago and an even briefer post on a Newsweek blog late last…

Personally, I am of the opinion that going into the very long term, the best option for us is to take charge of our own evolution, and IVF screening is perhaps the most ethical way of doing that. Disease screening seems to me to be about the best way to get started down this path, and it wouldn't be ethical to go further at the current time (because not enough information is available).

For the long-term, when we start selecting based upon desirable traits instead of just eliminating certain disease traits, the only ethical way to proceed is to make this sort of screening available to everybody, or, if it's too expensive, to a random subset of the population unrelated to economic status.

By Jason Dick (not verified) on 23 Mar 2009 #permalink

I'm glad people have found the article thought-provoking. Of course in such a short article there were many points I had to skip.

Here I just wanted to say that, while I've no doubt John Hawks' maths is far better than mine, I think his quick cost-benefit analysis of using IVF-PGD to prevent cystic fibrosis is misleading.

Firstly, as you point out above, you don't have to offer IVF-PGD to the whole country, just those parents who both have the CF variant. Let's say the initial genetic screening of parents costs $50 per couple (you only need to test one parent to start with).

Using Hawks' figures, if 1/2500 children are born with CF in the US, then (very crudely) for every 2500 couples screened one couple would be at risk of having a child with CF. That's an initial screening cost of $125,000. Include the IVF-PGD, and the total cost is $126,000 per case prevented.

Those figures are looking rather better even before we come to the second mistake I think Hawks' has made: ignoring the lifetime cost of CF.

If the annual cost of treating someone with CF is $10,000, that means the lifetime cost is over $330,000, given an average survival of 33 years. So preventing one case might cost $126,000 but it'd save $330,000 over the next three decades.

A very quick search for formal cost-benefit analyses of using IVF-PGD to prevent CF didn't reveal any up-to-date studies but it does suggest that another point made by John Hawks is also wrong.

I found a 2007 study that concluded that IVF-PGD is much more cost-effective than prenatal screening followed by elective abortion for preventing cystic fibrosis (

What's more, we can be pretty sure that in the future a) the cost of genetic screening (and IVF-PGD) will fall and b) the cost of treating genetic diseases like CF will soar as new drugs like PTC124 become available.

"The argument also ignores the suffering of people who face the opprobrium of society for their choice not to have the test performed. At present, this is considered to be bad luck. The change toward an attitude of parental negligence has already begun for parents who choose to complete Down syndrome pregnancies."

This is true; but I don't see why it is a bad thing. The whole point of the original essay was that, given the technology to avoid various horrid diseases, not avoiding them is arguably unethical. People who do unethical things deserve social opprobrium.

Today's BBC News website covers (via the US's Centers for Disease Control and Prevention and the UK's Human Fertilisation and Embryology Authority) a story that IVF raises the risk of "birth defects" by "up to 30%":

The UK National Screening Committee publish the criteria on which they would consider introducing a new test:

which suggests that the assessment of risk vs benefit is at least as important as cost vs benefit.

These criteria are based on those by Wilson & Jungner - see e.g.:…

The full list may be of interest:

1. The condition being screened for should be an important health problem
2. The natural history of the condition should be well understood
3. There should be a detectable early stage
4. Treatment at an early stage should be of more benefit than at a later stage
5. A suitable test should be devised for the early stage
6. The test should be acceptable
7. Intervals for repeating the test should be determined
8. Adequate health service provision should be made for the extra clinical workload resulting from screening
9. The risks, both physical and psychological, should be less than the benefits
10. The costs should be balanced against the benefits

I'd like to weigh in on the specifics of determining appropriate methodology to inhibit the propagation of genetic disease. My background is in both molecular and quantitative genetics, and I have worked in labs that contribute significantly to increasing knowledge of various evolutionary processes.

Ethical determinations are not based solely upon the practical. Rather, valuation must be placed (by the society, informed by the mores of the individual citizens) upon the various goods affected by any particular ethical issue. In the situation of genetic disease, this includes life, health, quality of life, and societal benefit. Different ethical theories incorporate different relative ranks for each of these goods (highest to lowest):

utilitarian (act and rule)= societal benefit, life, quality of life, health

materialist: quality of life, health, societal benefit, life

natural law: life, societal benefit, health, quality of life

There are other ethical systems, and these are just a sample.

What people need to consider when they choose to state practical cost benefit analyses as the sole rationale for a mode of action is that many ethical norms of good have unquantifiable costs and benefits. For example, is it better to avoid increased taxes and healthcare costs to care for those with genetic diseases or is it better to utilize a eugenic approach to attempt erradication of such diseases? One problem with a eugenic approach is that it is so difficult to call a halt to determining which individuals will be sanctioned: just those with the disease itself (ie: terminated pregnancies due to genetic disease), those who are carriers for the disease (through prohibition against propagation, through testing and selective embryo emplantation, or carrier termination), or anyone with a family history of the disease, regardless of how far back it may be in the geneology. Clearly, if the ultimate goal is to eradicate genetic disease, it would be best to optimize that goal (from a purely practical perspective) by removing all possibility of that disease being propagated (maybe by forced sterilization).

Recall that most diseases that assail the human population are not due to a single gene effect (ie: easy to test for), but rather are influenced by a combination of multiple genes and genetic architecture, environmental influences, and gene-by-environment interactions. There are also concerns of pleiotropy (one gene influencing multiple traits), epistasis (gene-by-gene interactions, on the order of two, three, or greater interactions), dominance, and relative phenotype-by-phenotype interactions (rQTLs). All of these contribute to the genetic variability acted upon in evolution.

I thought that someone should point out the scientific and ethical/philosophical complexity involved in this issue. I also wanted to reiterate (and expand upon) the point raised by Jason Dick, above, about our lack of information in relation to genetic variability, evolution, and human disease. Removal of extreme disease is a laudable goal. Removal of genetic variation is not. Where do you draw the line?

I think there's confusion in many readers of the Michael le Page article about the type of generic diagnosis offered. My original reading made me think of the genetic diagnosis we were offered when my son was concieved 12 years ago - CVS or amniocentesis, looking for Down's Syndrone, with a greater probability of causing a miscarriage than of the problem being present. Actually the article proposes testing the parents (and missing Down's Syndrome), not the embryo/foetus, but I missed that at first reading.

Many people don't want to risk killing an embryo/foetus to reduce a genetic risk. I think this is legitimate.
Many people don't want to abort an established pregnancy, except for fatal problems in the baby, or serious danger to the mother (all preganancies has some danger to the mother).
Some don't want to ever kill any fertilized ova at any stage, even 16 cell pre-implantation. IVF with PGD inevitably does this. Personally I think this is too early for us to have the strong moral responsibilities these people see.

Another reason for distrust of this proposal is distrust in the quality of the underlying technologies - Is the parental genetic testing accurate? Is the PGD accurate? Is the IVF actually as good for the children? How bad is IVF for the mother ? The hazards and unpleasantness of IVF for the mother are a cost of the proposal that is not mentioned by Michael le Page.

My God! You are almost as appalling a human being as Michael LePage. This soulless, cold discussion of "cost-benefit analysis" and pragmatism tells me that you are a socially mal-formed, morally vacuous, probably utterly repulsive human being. Yes, let's kill all the babies who would have been born with diabetes or that might get breast cancer. I'm surprised no one has uttered the H-word in this discussion, as it sounds like you and Hitler would have been swell pals. You are a vile, bad human being, and the only reason you don't recognize this is because you are isolated in some ivory tower--excuse me, ivory dungeon--filled with people who suffer from the same mental, emotional, and social shortcomings that probably made you turn to science in the first place.

On a less grave note, please do me the courtesy of removing the unnecessary comma from your profile sentence: "I write about the genetic and evolutionary basis of human variation, and the companies trying to sell you information about your genome." These are not two independent clauses, so the comma is neither necessary nor proper.

Perhaps if we find the gene for grammatical idiocay (you are clearly displaying that phenotype), we could offer parents the option of killing babies that possess it much as you advocate killing babies that possess genes that might lead to unpleasant diseases. After all, the "undesireability" of a gene is truly in the eye of the beholder.