As a teen (yes I can still remember that far back) one of my favourite books was “Brave New World” by Aldous Huxley, I haven’t reread it for many years now, but I would still recommend it (and I’m not alone). One of the features of the future dystopian world that Huxley imagined was the creation of different types of human beings, Humans no longer reproduce normally but are created in hatcheries and designed to have certain limitations so that they fit into one caste or another, the betas, deltas and so on. Only the alphas were allowed to develop without any added limitations.
Some ‘advances’ in modern medicine make me think of that book, and the ironic phrase of Shakespeare that the title of Huxley’s book was taken from
How many goodly creatures are there here!
How beauteous mankind is! O brave new world,
That has such people in’t.
Spoken by Miranda in The Tempest.
This study (Haque IS, et al. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA. 2016;316(7):734-42.) was funded by, and 5 of the 6 authors are employees of, “Counsyl’ a company that sells expanded prenatal carrier screening, using a test which screens for anomalies in 110 genes. Over 3 1/2 years, over 340,000 people were tested with one of their two technologies, people who had no specific clinical indication for testing, but decided to be screened to see if they were carriers for an abnormality in one of those 110 genes. 78% of them were women; I guess if the initial screen is negative, then the cost of testing the other parent can be avoided. They are also testing for some X-linked recessive conditions, not just autosomal. Many of the anomalies they are testing for are incredibly rare (with as few as total of 200 cases known in the world). The authors model how many affected fetuses would be detected, using many assumptions, including that the parents are both from the same ethnic group. Overall the predicted rates of affected fetuses vary according to ethnic group, with about 1 affected fetus per 1000 Hispanic patients to about 4 times as many for Ashkenazi Jewish subjects.
An accompanying editorial is worth reading, its written by a specialist in molecular/genomic medicine:
He notes that many of us were taught in medical school that we all carry an average of 6 deleterious recessive gene variants, he specifies that that that number was not based on any apparent actual data, he continues
it is now known from clinical genomic sequencing that each individual carries several hundred potentially harmful gene variants, along with thousands of less characterized coding variants that differ from the so-called reference human genome sequence, and millions more in the noncoding regions of the genome that are largely uninterpretable. In most clinical settings it is unknown whether many of these gene variants result in net harm to patients.
He notes that these extended carrier screens may lead to a diagnosis of abnormalities that may not even cause disease, that they may lead to a diagnosis of diseases (with very good outcomes) that are already screened for in the neonatal period, such as PKU (but don’t necessarily pick up all the hundreds of genetic variants that might cause PKU) and that one of the conditions most commonly picked up is Fragile X syndrome, for which no-one recommends screening, largely because expansion of the triplet repeats into the disease-causing range is uncommon and unpredictable, with uncertain impacts on the family who screens positive, but has no clinical impact.
The criticisms make me wonder why this article was published, as it seems to be mostly a marketing exercise for Counsyl, and as far as I can see the enlarged carrier screening can create almost nothing but heartache. Most positive screens, with a rare gene abnormality will, of course, not be confirmed in a partner in the second stage of testing, and even when the partner is positive, only 1 in 4 of their children will be affected. Who has the expertise, and the time and resources, to explain the implications of every one of the 100 abnormalities being screened for? If the answer is almost no-one, then informed consent is really not being done. We already have many situations where a negative test is mis-interpreted by parents as meaning that the baby will be fine, or where a positive test of uncertain significance leads to incredible stress and soul-searching for no apparent benefit.
What I couldn’t find in this publication is the proportion of initial screens that showed a potential risk, which would then be followed by a partner screen that would almost always not show an anomaly in the same gene. Some of the gene frequencies of individual anomalies can be found in some supplemental material, and many are extremely rare. Only about 20 abnormalities for a gene for Andermann syndrome were detected (among the 340,000 screens), the likelihood of a non-consanguineous couple being both positive for such an anomaly is so vanishingly small, that to include such tests in a carrier screen is ridiculous. Do parents, when they shell out the cash, realize that they are much more likely to win the lottery than to find that they are both carriers for this disease?