The Reason I’m Alive

For a variety of reasons I’ve always considered myself to have been exceptionally lucky, but last week I got news that increased still further the extent of this sense of good fortune. I hesitated before putting anything about this on here because it is rather personal and there are details I’m going to leave out about how I came by the information.

Over a month ago I posted some thoughts about the TV series It’s A Sin based on my own experiences back in the 1980s. That post ended with this:

… a question that often troubles me returned once again to my mind: why am I still alive, when so many people I knew back then are not?

In response to this a former colleague of mine suggested I get my DNA sequenced to see if I had any innate resistance to HIV infection. I wasn’t sure how to go about doing this but one of the advantages of having worked in several different universities is that I know people in several bioscience and biomedical departments, including people who work on the data science aspects of genetics. After emailing around for advice I eventually ended up talking to a very distinguished scientist in that field to whom I explained the situation.

Since I didn’t really want to have a copy of my entire genome sequence – that’s a lot of data most of which I wouldn’t understand – but just wanted to know the answer to one question it seemed a waste of money to have this done commercially (although at around €1000 it’s not enormously expensive). Instead a plan emerged in which I would offer my (suitably anonymized) DNA as part of a scientific study in return for the small piece of information I wanted.

After a few days I received a kit for taking oral swabs, a medical questionnaire and quite a lot of paperwork to do with ethical considerations and data protection. I sent everything back by return post. Last week the results came back. There was some general info about my genetic make-up – which shows a considerable dollop of Scandinavian ancestry – alongside the answer the question I had asked.

The full DNA sequence of my genome reveals that I have the CCR5-Δ32 genetic mutation. Not just that. I have it twice (i.e. it’s homozygous), which means that I inherited it from both parents.

Of order 1% of the European population has this mutation, which is thought to have arisen in a single Scandinavian individual at some stage during the Viking era and subsequently propagated through mainly Northern Europe where about 10% have one copy, and about 1% have two.

Here is a map of the geographical distribution in Europe (from this paper) :

It’s nowhere near as prevalent in Asia or African populations.

So what does this mean?

Heterozygotic CCR5-Δ32 (i.e. one mutated gene) confers some protection against HIV infection but the homozygotic CCR5-Δ32 mutation involving both copies confers virtually total immunity. I was terrified of AIDS in the 1980s but it turns out I was immune all the time without knowing it. This explains why to my great surprise the HIV test I took in the 1980s came back negative despite my sexual history and behaviour.

As a friend told me when I passed this news on: “you’re a f**king lucky bugger”. Indeed I am. I already considered myself to have been very lucky but this absolutely takes the biscuit.

P.S. My immediate “reward” for having this genetic peculiarity is to take part in further scientific study on it, which I am of course very happy to do.

19 Responses to “The Reason I’m Alive”

  1. According to the same article, there seem to be some potential costs:

    CCR5 Δ32 can be beneficial to the host in some infections (e.g., HIV-1, possibly smallpox), but detrimental in others (e.g., tick-borne encephalitis, West Nile virus). Whether CCR5 function is helpful or harmful in the context of a given infection depends on a complex interplay between the immune system and the pathogen.

    In general, research suggests that the CCR5 Δ32 mutation may play a deleterious role in post-infection inflammatory processes, which can injure tissue and create further pathology.[67] The best evidence for this proposed antagonistic pleiotropy is found in flavivirus infections. In general many viral infections are asymptomatic or produce only mild symptoms in the vast majority of the population. However, certain unlucky individuals experience a particularly destructive clinical course, which is otherwise unexplained but appears to be genetically mediated. Patients homozygous for CCR5 Δ32 were found to be at higher risk for a neuroinvasive form of tick-borne encephalitis (a flavivirus).[68] In addition, functional CCR5 may be required to prevent symptomatic disease after infection with West Nile virus, another flavivirus; CCR5 Δ32 was associated with early symptom development and more pronounced clinical manifestations after infection with West Nile virus.[69]

    This finding in humans confirmed a previously observed experiment in an animal model of CCR5 Δ32 homozygosity. After infection with West Nile Virus, CCR5 Δ32 mice had markedly increased viral titers in the central nervous system and had increased mortality[70] compared with that of wild-type mice, thus suggesting that CCR5 expression was necessary to mount a strong host defense against West Nile virus.

  2. Over a month ago I posted some thoughts about the TV series It’s A Sin based on my own experiences back in the 1980s.

    I know what you mean, but that could be parsed as the series being based on your experiences.

    Finding the correct antecedent of a relative pronoun (understood to be “which” in the above sentence) is a good test for artificial intelligence, machine translation, and so on as one really has to understand the sentence in order to get it right every time.

  3. Strange that there is no data from Sweden.

  4. Anton Garrett Says:

    So it seems that the Vikings really did go south along the great rivers of Russia, a claim which is disputed by some. Also, the ‘Normans’ were Northmen who picked up Catholicism in Northern France and were the driving force behind the Crusades, getting all over the eastern Mediterranean (although the prevalence of this gene in Israel is clearly due to 20th century Jewish migration; it would be interesting to see the statistics for Gaza and the West Bank, which are Arab).

    On the other hand, I might be indulging in circular logic, if the evidence for a Norse origin of the gene is what I have just stated…

    It helps to be from the north-east, which took the full brunt of the Viking raids!

    • telescoper Says:

      Although I was born in the North-East not all my immediate family history is from there so it’s not as simple as that!

      • Anton Garrett Says:

        Understood!

        Continuing my theme nevertheless, the Byzantines had an elite unit, the Varangian Guard which bodyguarded the Emperor, consisting of Vikings (once they had taken up Christianity) and then Normans. King Harald Hardrada of Norway, who died in an attempt to invade England days before William the Conqueror’s success, had served in it. And earlier, the Vikings has sailed up the Seine under Rollo and sacked Paris.

        I should have added that the Jews who brought this gene to Israel had picked it up most likely from rape at the hands of Europeans.

        Is it known *how* this gene protects against HIV?

      • telescoper Says:

        Yes, I believe it is quite simple as these things go. The HIV virus enters a CD4 immune cell via the CCR5 co-receptor which usually sticks out from the cell and allows the virus to bind to it. The mutation causes the CCR5 to be smaller than usual and no longer sit outside of the cell. This closes the door on the virus which is unable to enter these cells.

      • telescoper Says:

        It’s interesting that the numbers for Ireland are just as large as those for Denmark. Data from Sweden are not in the figure I showed but it is believed that Sweden has the highest fraction in Europe of the delta-32 mutation.

      • Anton Garrett Says:

        And no mutation of HIV, which mutates like blazes, has got round that?

        I’ve been educating myself as best I can on the difference between the various SARS-CoV-2 vaccines, and also trying to read the literature on its origins based on sequencing. We physicists have it easy!

      • telescoper Says:

        I think it must be such a basic part of the way HIV works that no mutation has succeeded in circumventing it. It is easy to image how the mutation also affects the ability of immune cells to deal with other things though…

        By the way here’s an article about genetic immunity in the context of both HIV and SARS-COV-2.

        https://www.bbc.com/future/article/20210219-the-covid-resistant-patients-e-the-viruss-weak-spots

      • Of course, as the name implies, the Normans were Northmen just a generation or two before.

    • Mostly Vikings from Sweden went to Russia, while those from Denmark and Norway went west.

      • Anton Garrett Says:

        Some were sensible enough to go south; they got round Spain into the Mediterranean and their ships were spotted by Charlemagne, who rightly saw trouble ahead. This according to his biographer one generation later, Notker the Stammerer.

  5. […] 10,000 years ago; before that happened no humans had blue eyes. Having blue eyes myself, and in light of a recent discovery that I have a different mutation that arose more recently, I find that […]

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