One goal, two approaches: Tay Sachs disease case study

When looking at the interactions between science, medicine, technology, and society, the domain of genetics is an abundantly fertile ground for reflection. In this post I would like to focus on Tay-Sachs Disease screening as a first step into this domain.

It is a striking story where genetics meet society and (personal) ethics, which I learned about via an online course on genomics.

Tay-Sachs disease (TSD) is a fatal genetic disorder, most commonly occurring in children, that results in progressive destruction of the nervous system. …

In children, the destructive process begins in the fetus early in pregnancy. However, a baby with Tay-Sachs disease appears normal until about six months of age when its development slows. By about two years of age, most children experience recurrent seizures and diminishing mental function. The infant gradually regresses, and is eventually unable to crawl, turn over, sit or reach out. Eventually, the child becomes blind, cognitively impaired, paralyzed and non-responsive. By the time a child with Tay-Sachs is three or four years old, the nervous system is so badly affected that death usually results by age five.

A much rarer form of Tay-Sachs, Late-Onset Tay-Sachs disease, affects adults and causes neurological and intellectual impairment. Only recently identified, the disease has not been extensively described. As for the childhood form of Tay-Sachs, there is no cure [although researchers are pursuing several approaches to find a cure]. Treatment involves managing the symptoms of the disease.

National Human Genome Research Institute

I chose TSD as a first step into genetics and screening for two reasons. First, it is the “longest-running, population based program designed to prevent a lethal genetic disease”, and often presented in such terms as “the major success story in terms of carrier screening programs” (Genome News Network). As such, it is an obvious place to start, and indeed often is used as an introductory case study when looking at genetics and society.

Second, it seems to be that people agreed and still agree that this disease is a terrible ordeal for both parents and the child to go through, without hope. There is a lot of material for debate with other diseases/disabilities/conditions, however with TSD, all children die young after losing most capabilities, and people generally agree that this should be prevented (as far as I have understood from research).

A key fact to this story is that Eastern European/ Ashkenazi Jews are more likely to be TSD carriers than other populations. “In the early 1970s, there were 100 children per year afflicted with Tay-Sachs disease in North America, 85 of whom were of Eastern European (Ashkenazi) Jewish ancestry”. Dr. Michael Kaback led the efforts leading leading to the first community-based TSD screening in 1971. Of this he said, “this wasn’t an epidemic as only one in 3,000 Jewish children carried the disease. We just wanted to give them sufficient information so they could make an informed decision.” (source)

1,800 young Jewish adults in Bethesda, Md. participated in the first screening program in 1971. “Within two years, similar screenings were conducted in cities across North America, and California began the first statewide program in 1973.”

Together with prenatal screening for PKU and carrier screening for sickle cell disease, these TSD carrier screening programs are considered the first steps in modern screening (note – my initial sources on this are North American, I would be interested to learn whether other regions of the world had a similar experience or maybe other/ earlier steps).

How does the ‘traditional’ TSD screening take place? Dr. Kaback, together with John O’Brien, wanted to create “a simple, accurate blood test that would detect the disease gene in adults and the presence of disease in early fetuses”. In the first screening programs:

The test was both inexpensive and reliable and was soon widely adopted; 1.3 million people were tested, and nearly 50,000 carriers of the gene were identified within a few years. When both prospective parents were identified as carriers, pregnancies were tested … to determine whether the child had Tay-Sachs. Out of the 604 cases where the diagnosis was confirmed, 583 couples chose to abort the fetus. Almost all of the remaining children were born with Tay-Sachs and died in early childhood.

– p.13 of Biotechnology and Genetic Engineering by Kathy Wilson Peacock (2010), accessed via Google Books

The resulting drastic decrease of TDS incidence among the Jewish population is what characterizes the program as a success (the way the program was implemented should also be mentioned as part of this success – with the close involvement of many stakeholders in the community). However the means to this end – abortion – is a debated topic in many communities, including the Jewish community. Indeed, for the “religious” or Orthodox Jewish community, prenatal screening/diagnosis is not feasible as abortion is not permitted. Even carrier screening poses challenges, as birth control is not acceptable, and artificial insemination by a donor not an option either. So if both members of a couple are identified as carriers, they still cannot take action to prevent conceiving and giving birth to children with a high probability of TSD.

The ethics and practice of abortion are a different topic. I would simply like to acknowledge the complex sensitivity and emotions that the topic gives rise to, without going into further detail in this post.

Here, what I would like to focus on is that a community and individuals agreed that TSD was better prevented, but did not agree in the available means of prevention.

Their answer lay in another feature of this community, which is the facilitation of arranged marriages:

… prenatal screening is not acceptable for Orthodox and Chassidic Jews because abortion, artificial insemination and birth control are not options. In 1982, Chevra Dor Yeshorim was established to provide compatibility testing, i.e., genetic screening prior to “matches.” As of 2006, over 200,000 individuals were tested and over 800 proposed matches of carriers were averted. This model has already been transferred to the Saudi Arabian population where matches are made and certain recessive disorders are frequent.

Looking back, this story is almost too neat, too elegant. I have found some further sources which I will expand on in a next post, looking a bit more at the experience of the individuals who undergo screening, at sources from Australia and Canada rather than just the United States, as well as how the model was applied in Saudi Arabia. I will also look at how these successes co-existed with messier experiences such as the sickle cell screening programs, and how together they set the stage for the next steps in genetic (carrier) screening programs.

However what I wanted to emphasize here is not the positive outcome of genetic carrier screening. Rather it is how two communities used the same science and technology to achieve the same goal, but by two different methods according to their different values.

Science and technology continue and will continue to progress. However their progression doesn’t – shouldn’t – dictate society. That doesn’t mean avoiding technology – but rather thinking and making choices about how we apply these tools – from genetics, to smartphones, to social media, etc. I find that this first introduction to the carrier screening programmes of TSD is a good illustration of how societies can actively consider and make choices about how to use available technologies.

Additional sources for this post:


March 19th post-scriptum

I’m doing some research for a follow-up post, and finding some information that may be a good complement to this post.

Here’s another introductory presentation of TSD:

Tay-Sachs disease (TSD), a fatal condition, is a neurodegenerative lysosomal sphingolipid storage disorder. TSD is caused by mutations of HEXA (MIM *606869, gene map locus 15q23-q24). The HEXA gene product was identified in 1969 as the α-subunit of β-hexosaminidase enzyme (HEXA). The normal function of HEXA is to degrade GM2 gangliosides in central nervous system cell lysosomes.1,2 In TSD, neuronal accumulation of sphingolipid GM2 gangliosides results in progressive loss of central nervous system function. Most infants with TSD appear healthy at birth. After a period of normal development, affected individuals experience slow neurological decline and death in infancy (infantile TSD) or early childhood (intermediate TSD). A still milder form of TSD exists where individuals survive into adulthood. No cure or effective treatment to slow the progression of the disease is known.3 TSD has autosomal recessive inheritance, with TSD carriers being unaffected. In the case of carrier couples, 25% of pregnancies will be affected by TSD. TSD is a rare disease, with an incidence of one in 320,000 births in general populations (carrier frequency one in 250). The specific populations at a higher risk of TSD are: Ashkenazi Jewish (AJ), French Canadian, Irish, Pennsylvania Dutch, and Cajun communities. All populations exhibit specific HEXAfounder mutations at high allelic frequencies.4

Tay-Sachs Disease, current perspectives from Australia (2015)

One point that strikes me here is the milder form of TSD where individuals survive into adulthood. Perhaps this weakens what seemed to me like a broad consensus whereby, considering the inevitability of early death following neurological decline, most people would agree that it is a condition worth preventing.

Some additional summary figures on TSD carrier screening since 1971:

TSD incidence in unscreened Jewish populations is one in 3,900 births.5 The first TSD carrier screening program was introduced in the USA in 1971, representing a precedent for population genetic screening for inherited diseases.6 By the year 2000, over 51,000 TSD carriers, including more than 1,400 at-risk couples, had been identified via TSD screening programs around the world.7 Internationally, screening has reduced the incidence of Ashkenazi Jews with TSD-affected children by more than 90%.5

Tay-Sachs Disease, current perspectives from Australia (2015)


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