[w0mbat]

The gene that causes sickle cell anaemia actually provides partial immunity to malaria, which is why this gene has not been bred out of the population over time.

[lostlogin]

> which is why this gene has not been bred out of the population over time.

Is that why? Or is it just the people with it aren’t sick enough to die before procreating?

[CobrastanJorji]

It's a recessive/heterozygous thing. If you get the gene from neither parent, you're vulnerable to malaria. If you get the gene from either parent, you're immune to malaria and don't get sickle cell. If you get the gene from both parents, you get sickle cell. A hypothetical future person who's going to be born in an area with a lot of malaria would really want exactly one parent with sickle cell and one parent lacking the gene completely to guarantee the best personal outcome, or they'd want exactly one heterozygous parent (for a 50% chance of being immune to malaria with no downside), or they might settle for the gamble of two heterozygous parents (50% chance of immunity, 25% chance of sickle cell).

[vidarh]

Without access to modern hospital treatments it is fairly normal to die very young from sickle cell disease - it causes 100k+ deaths a year.

An in-law of an ex has it, and regularly spends days in hospital during crises. Without access to a high quality hospital he'd have been dead a long time ago.

The average life expectancy for someone with sickle-cell disease in developed countries is 40-60 years, and serious crises tend to start from childhood.

That said, it's recessive, and so it's likely the reverse of what you think: It's not primarily the people with full-blown disease who contributes most to the long term survival of the trait, but that the trait alone confers fairly significant advantage in regions where Malaria is huge killer mostly without causing health problems. So across the combined set of carriers and those with the full disease, the life expectancy in Malaria stricken areas tends to be higher.

Pattern of change of the prevalence of the trait correlating with changes in prevalence of Malaria has been observed many places. E.g. the prevalence among US black people is significantly lower and dropping than in the areas their ancestors came from.

[SoftTalker]

Malaria often kills people before they reach the age of being able to procreate.

[ls612]

No the important part is that the mutation is recessive, but being heterozygous for it is enough to confer malaria resistance.

[freeone3000]

In regions where malaria was endemic, this mutation was selected for, as malaria kills children.

[graphe]

Africa wasn't colonized by Europe until vaccines and treatments were invented because of malaria and other tropical diseases. Quinine was one of the last ingredients needed to conquer Africa.

[robwwilliams]

Good point and thanks for being on-topic. Humans have three variants of the HBB gene and having sickling mutations in the variant expressed in adult is causal to SC disease.

The FDA-approved treatments reactivate the fetal HBB gene in adults and this change in gene expression control effectively prevents SCD.

Very cool and transformative work. Now we have to get the price tag down from seven figures to four or five figures so that it will be used widely. That may be a few decades. Let’s hope that more efficient alternatives are developed soon.

[firejake308]

From an efficiency standpoint, I think having to harvest and modify the patient's stem cells is probably the biggest choke point, right? I would imagine that if you could inject something once and be done with it (I'm thinking like Zolgensma), you could mass produce it more effectively

[firejake308]

Correct, but if we have good treatments for malaria (e.g. hydroxychloroquine, atorvaquinone) then I would argue that we no longer need that partial immunity

[imtringued]

That is true but even the unreliable malaria vaccines that are out there are more effective and reliable against malaria than sickle blood cells.