Tag Archives: carrier screening

Albatross

Ah! well a-day! what evil looks
Had I from old and young!
Instead of the cross, the Albatross

About my neck was hung.

And till my ghastly tale is told,

This heart within me burns

He went like one that hath been stunned,
And is of sense forlorn:
A sadder and a wiser man,

He rose the morrow morn.

- Excerpts from The Rime of The Ancient Mariner, by Samuel Taylor Coleridge

Eugenics. I can hear the thud as the collective eyes of genetic counselors roll heavily at the mention of the E-word.  That finger has been wagged in our faces ad infinitum. Alright already, we have learned our lesson from this shameful past. That was like more than half a century ago. Do we have to still keep apologizing for something we never did? Enough with the hand-wringing and perseveration. We’ve smoked this one down to the filter.

Well, no, apparently we are not done. As historian of medical genetics Nathaniel Comfort has pointed out in a recent thoughtful Genotopia blog (with an equally thoughtful commentary by Alex Stern, the biographer of our profession), eugenics discussions are back with us. We need to keep having the discussion because apparently we are not sadder and wiser people this morn. Some even think – with great hubris, in my view – that with our supposedly greater wisdom and technological advances, maybe some version of eugenics is not such a bad idea after all.

I am not going to repeat Nathaniel’s and Alex’s arguments here; visit the Genotopia blog and read the originals. What I want to do is to offer a  framework for thinking about the issues raised by these historians and introduce the concept of genetic discrimination into the mix.

Genetic discrimination, in my definition, is discrimination based on a person’s presumed or actual genotype and it’s presumed or actual phenotypic expression. The word discrimination comes from  the Late Latin discriminationem, meaning “to make distinctions” and can have both negative and positive connotations. Racial and gender discrimination that results in suffering and inequity is bad. But a discriminating person is one who shows great taste for fine things. Not to try to dance too many angels and devils on the head of this pin, but perhaps when discrimination has a negative effect, it could be called dyscrimination.

Eugenics, then, can be viewed as a form of negative genetic discrimination, the goal of which is to improve the genetic health (whatever that means) of future generations.

Prenatal diagnosis, the usual aim of eugenic critiques, is not eugenic because it does not try to alter allele frequencies of future generations. Down syndrome is almost never an inherited disorder, and people with Down syndrome rarely reproduce. Prenatal diagnosis is not an attempt at “the self direction of human evolution,” as the 1921 Second International Eugenics Congress defined eugenics.  But from the standpoint of some, prenatal diagnosis is a form of negative genetic discrimination – fetuses are discriminated against because of their genome and the common but inaccurate perception of the Down syndrome phenotype as a backward child with a heart defect but a pleasant personality. Although the insensitive term mongolism is rare these days, the common image of “the Mongol child” has not evolved as much as it should have.

Pre- or early pregnancy screening of parents for mutation carrier status for various genetic conditions, on the other hand, might rightfully come under eugenic criticism since its explicit goal is to improve the genetic health of future generations and to wipe out genetic diseases by preventing the conception of homozygous recessive offspring. Never mind the nonsense spewed forth on some websites; carrier screening usually has very little to do with improving the health and quality of life of babies who are born with genetic conditions. Carrier screening can result in reduced suffering if fewer children are born with life threatening or medically serious disorders but it rarely improves the health of babies who are born with those conditions. Whether this is a “good” or a “bad” form of eugenics, and how commercial laboratories advertise their product, are questions open to healthy debate.

Newborn screening, as it is currently practiced, is not eugenic because its intent is to improve the health of a child by treating the presumed phenotype based on the genotype. Newborn screening could thus be viewed as a positive form of discrimination, albeit one with flaws that we are not comfortable acknowledging . But newborn screening can also be viewed as negative genetic discrimination, depending on the condition being screened for. Some people who are deaf have raised serious concerns about screening newborns for hearing loss.

Genetic screening for adult onset disorders like Lynch syndrome or familial hypercholesterolemia may be positive genetic discrimination. The goal of this screening is to treat the phenotype based on the genotype with the hope of reducing the incidence of serious, life-threatening diseases or to mitigate their effects. Dietary changes, treatment with statins, high risk cancer screening, and surgery are strategies that are offered to people at increased hereditary risk of developing these diseases. Of course, if there were to be widespread preimplantation or prenatal diagnosis for these conditions, then we should rightly raise eugenic questions.

Why make these distinctions? Because the word eugenics has become an angry accusation that ends discussions. The social effects of genetic medicine and genetic counseling should always be open to vigorous scrutiny but the criticism needs to be accurate and sensitive to nuance. Maybe some of what we genetic counselors do is eugenic, and maybe under certain situations, this may not be as terrible as it sounds. And maybe some of what we do is dyscriminatory but not eugenic; we need to understand why it is dyscriminatory so we can do something about it. And maybe lots of what we do is very helpful for many people and not particularly eugenic. To cram all of medical genetics into a eugenic framework prevents any progress from ever being made. The two sides start to resemble Democrats and Republikans in a dysfunctional Congress, never able to engage in meaningful debate. Let’s get this albatross off our necks.

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Screening Everyone For Everything: A Changing Model of Screening For Carrier Status of Genetic Diseases?

The heterozygote carrier screening paradigm  is  starting to shift from ancestry based screening  for carriers of a single or a few genetic diseases to pan-ethnic screening for carriers of a wide range of genetic diseases. New techniques of DNA sequencing make it possible to test a single sample to determine carrier status for dozens of genetic conditions at prices that make carrier screening panels (CSPs) very tempting to healthcare providers and patients. Since carrier screening for one or another genetic disease – cystic fibrosis, Tay-Sachs, hemoglobinopathies – is already offered to essentially all women who are pregnant or planning a pregnancy, why not “screen everyone for everything” at no greater up front cost? And it doesn’t even require a blood sample; a less intimidating buccal sample works just fine.

Part of the understandable justification to move beyond targeted carrier screening programs is the futility of trying to classify people into distinct ancestry/racial/ethnic categories. Gene mutations and genetic diseases have a pesky habit of flowing fluidly between populations, and cultural heritages can be lost through assimilation (See Interesting Digression* below).

People

So why object to CSPs? After all, don’t people have a right to “know their DNA” and to understand what health and reproductive risks they face?

I am not suggesting that we should stand in the way of anyone’s wishes to “know their DNA.” If someone chooses to acquire that knowledge without the benefit of meeting with a genetic counselor, well, I may disagree with that decision but I respect it. But whether people decide to undergo carrier testing through a genetic counselor or through an online testing company, they need information that is forthright, complete, and transparent; they do not need subtly biased sales pitches. Private companies do not have a vested interest in talking people out of genetic testing.

Before we examine how some labs “objectively” describe carrier screening to patients, we must acknowledge an ethically uncomfortable truth. Carrier screening does not consistently lead to better treatments,  encourage greater tolerance of disabilities,  stimulate research into cures, or improve psychosocial adaptation to genetic disease. The only compelling reason to devote economic and medical resources to carrier screening is to reduce disease incidence. For better or worse, that is the measure of success of Tay-Sachs screening in Ashkenazi Jews and thalassemia screening on Cyprus.

Three strategies can reduce the incidence of genetic disease. One is mate selection based on carrier status, which is rare except in select populations such as Ultra-orthodox Jews (Hey Single Women out there, when was the last time you met potential Mr. Right and said “Er, you can buy me a drink but do you mind if I take a pedigree and a cheek swab from you before I give you my phone number?”). A second approach is preimplantation genetic diagnosis, but it is available to only a miniscule percentage of the population. The third and only realistic option for most patients is the elephant in the room – prenatal diagnosis with termination of affected fetuses.

Bar

Take a look at the  web sites of companies such as Counsyl or 23andMe and you get a different narrative. The word “abortion” does not appear. Instead, you read about sperm/ovum donation, preimplantation diagnosis, mental preparation, watchful waiting, and early treatment. No mention is made that early treatment requires testing the baby anyway and that some treatment is available for only a handful of the screened conditions. The websites do not bring up the point that there are no large-scale studies that have shown better familial adaptation to genetic disease when parents have prenatal awareness of their carrier status, so couples really cannot know if testing really will result in mental preparedness. And I am still not sure what watchful waiting is, and how it differs from mental preparedness.

waiting

A second concern is that screening for very rare conditions plays on the emotionally vulnerable state of many pregnant women and the difficulty almost anyone has in understanding very, very small numbers in a psychologically meaningful way. Take for example, a condition that has an incidence of 1/100,000 births with a 75% carrier detection rate. Before carrier testing, a couple would have an ~99.9999% of NOT having an affected child; after carrier testing that probability would increase to ~99.99999%. Really, who can tell the difference between those two statistics? It’s difficult just trying to count the number of nines in those numbers. But read about the condition’s severe intellectual disabilities and physical birth defects, and, damn the statistics, give me that test.

A third concern is the lack of complete information about test sensitivity on the information portion of the website. For example, a patient with normal carrier test results might understandably think they would not have to be concerned about having a child with Bardet Biedl syndrome. What the site does not indicate however is that BBS1 and BBS10, the two loci included in the  panel, account for less than half of patients with Bardet Biedl syndrome, and that the dozen or so other genes that can cause Bardet Biedl syndrome are not included in the test panel.

A fourth, and maybe the greatest, concern is the ethical difficulty of deciding which conditions to include on a CSP. Tay-Sachs screening among Ashkenazi Jews and thalassemia screening in Cyprus developed with significant input from families, medical professionals, and community and religious leaders. There was widespread agreement in those communities that these were serious diseases and that carrier screening, mate selection, or prenatal diagnosis were ethically acceptable ways of reducing disease incidence. Very little community dialogue has taken place over CSPs. Do we really believe that the world is a better place if we screen for carriers of a common form of hereditary deafness or, God help us, red hair color?

Redhead

And ruminate on this: a study of 3 million cystic fibrosis carrier tests performed at a single US lab found that 25,000 CF carrier screens needed to be performed to detect one affected fetus. And this is for a relatively common genetic condition with a frequency of about 1/4000 US newborns and  a screening program whose success remains debatable. How many carrier screens will need to be performed to detect a fetus or newborn with a rare disorder like isovaleric academia, with a frequency of 1/250,000 births?

It could be that I am just the last of the old wave of genetic counselors who are out of touch with new technologies and changing ethical values, the proverbial last leaf on the tree. Maybe I am a 20th century genetic counselor in a  21st century world in which private industry will become the primary mode for the delivery of medical genetic services. Perhaps when I retire in a decade or so the genetic counseling community will issue a collective sigh of relief. But sometimes Old School cranks have a point.

MR900400816

* – Interesting Digression: I recently learned about the Jews of Acadiana, Jewish merchants who settled among, and who were often culturally and reproductively assimilated into, Louisiana’s Cajuns (although the Cajun Tay-Sachs mutations stem from their French Canadian origins and predates the Ashkenazi admixture). Also, an exploration of why Tay-Sachs screening caught on among Ashkenazi Jews but not among Cajuns would make for  an interesting socio-medical-historical study. If a  large scale  Tay-Sachs screening program were to be introduced among Cajuns, perhaps its motto would be Laissez les bon genes roulez.

Accordion

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Resistance Is Futile: A New Paradigm for Genetic Counseling?

For with this detection there arises new lines of approach in the field of preventive medicine, and the sociological consequences may be far-reaching.

- James V. Neel, from his 1948 plenary lecture, “The Detection of The Genetic Carriers of Hereditary Disease”, delivered at the first annual conference of the Human Genetics Society of America (which eventually changed its name to the American Society of Human Genetics)

The technical advances in genetic testing over the last 5 years have been stunning. Much of what I thought of as Not Going To Happen For A Long Time  has now happened yesterday. Along with these breakthroughs is the unstated but increasingly common suggestion that everyone should taste the fruit of testing in Gregor’s Genetic Garden of Eden.

In the old days (like a year or two ago) only a small portion of the patient population were thought to be candidates for genetic testing, those for whom it made medical sense and who were emotionally ready for the ramifications of the knowledge. Genetic counselors used their skills to help patients select the appropriate test and to guide them through the clinically, emotionally, and financially complicated decision-making process. Some chose to undergo testing while others delayed or declined it. We did not really care what patients chose to do; our role was to go through the wringer with them.

Now, though, this model of genetic testing only for the select few may be replaced in the near future by the idea that everyone – healthy, sick, high risk, low risk – should have genetic testing. Population scale genetic testing, with its promises of personally tailored medical care and better health outcomes, assumes that everyone – except for a handful of Luddites, people who do not own mobile phones or have Twitter accounts, Flower Children, and conspiracy theorists – will incorporate DNA into their routine medical care. Genetic testing becomes a foregone conclusion, not an ethically and emotionally weighty matter to be carefully explored and considered. If everyone has a genetic test and everyone carries gene mutations, doesn’t that make everyone a patient?

Think I am overstating my case? Perhaps. Then again, recall the many professional and popular articles you have read that are variations on this theme: The time is near when you will walk into your doctor’s office with an inexpensive DNA Chip that contains your entire genome and that will guide your doctor in choosing the best medications for you and select the most effective screening tests. You will live to be 100, enjoy a lusty sex life, and have healthy children. While the $1000 genome may not be a shining example of truth in advertising, affordable genetic testing is upon us.

A second case in point is the introduction of cheap carrier testing for a huge number of mostly obscure genetic conditions, what has come to be called Universal Carrier Screening. I will risk stating the obvious and point out that the word “universal” implies that the test is for everyone. At $99, it is hard to say no.

A third case in point is newborn screening, which is as close as it gets to universal genetic testing. The conditions screened for with those heel sticks continues to increase but the primary justification is not “treatment before symptoms develop.” Rather, testing is predicated on reducing the number of families caught in The Diagnostic Odyssey, that emotionally and financially draining parental journey to find out what medical disorder their child may have. Based on this premise, there is no logical stopping point for including disorders in a newborn panel. Every genetic disease is a potential source of a diagnostic odyssey. In fact, the rarer the syndrome, the better it is for inclusion in newborn screening since uncommon conditions are less likely to be diagnosed by most practitioners.

Another area of pervasive genetic testing is the recommendation for universal fetal aneuploidy screening during pregnancy, made even more tempting by high detection/low false positive non-invasive tests.

Genetic screening is offered to everyone prior to conception, during pregnancy, and at birth. Testing all adults allows the rest of the camel into the tent.

Genetic counselors are not the driving force behind universal genetic testing, although undoubtedly we have some complicated role. As I have discussed elsewhere, we probably have less influence on patients’ decisions than we  think. Larger social, economic, and ethical forces are at play, in much the same way that the introduction of amniocentesis, newborn and carrier screening, and the birth of the genetic counseling profession were all products of their times.

The role of genetic counseling when it comes to genetic testing, then, may no longer be primarily to help patients make decisions. Instead, genetic counselors may become Phenotype Counselors who interpret and integrate results of genetic tests that were run – and possibly chosen through online services – before patients walked into our offices.

Ilana Löwy’s book “Preventive Strikes: Women, Precancer, and Prophylactic Surgery”

If I am right, genetic counselors are likely to encounter controversies and dilemmas. Ethical values like nondirectiveness and autonomy become less forceful if individually tailored health strategies can help prevent or attenuate serious illness. Think of how many  oncologists consider their high risk cancer patients crazy for not having BRCA testing or believe that known BRCA mutation carriers are making poor choices for not undergoing risk-reducing surgeries.

Eugenic concerns, the voice and dignity of the disability community, the psychological sequelae of coping with test results, and worries about the other downsides of genetic testing may be pushed to the wayside by the power of the still unproven assumption that medical spending will become more cost-effective, clinical decisions will be wiser, and everyone will be healthier if their genomes are analyzed. In fact, people with disabilities themselves will likely see some treatment and diagnostic benefits from genomic testing. And because laboratories and lab-based counselors will likely play critical roles, defining and protecting against conflict of interest becomes even more critical and complex.

Both good and bad will come out of universal DNA testing, though it is difficult to predict what measure of each. But so much genetic information available on so many people must give one pause. The history of genetics demonstrates that every advance in genetics is fraught with social complexity and dangers. We may have a more sophisticated knowledge of genetics than our predecessors, but we are neither wiser nor more ethical.

I  close by reminding you that knowing our past helps us better understand why we are here and what may happen if we go there. To that end, let me bring to your attention two recently published books about the history of genetic counseling and the history of medical genetics: Telling Genes: The Story of Genetic Counseling in America by Alex Stern (The Johns Hopkins Univ. Press, 2012) and The Science of Human Perfection: How Genes Became the Heart of American Medicine by Nathaniel Comfort (Yale Univ. Press, 2012). The authors, my good friends and colleagues, provide an informed and critical historical understanding of  genetic counseling and genetic medicine. Everyone should read these books. It will do your souls – and your counseling philosophy – good.

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