Why are people so quick to assume the motivations of others for a basic comment?
Posting form this position - Psychopharmacology and neuroscience research to post graduate level. I'm not keen to see a genetic explanation, i'm keen to see the results of research into this area because then we can discuss the extent biology plays a role in relation to socio-economical factors.
There is some research suggesting opiate addicts could be compensating for a dysregualted endogenous opiate system through substance abuse. There is similar work for dopamine with smoking. Looking at things this way could change the way interventions are offered and also potentially reduce stigma for some of those who have addictions.
Some interesting links that have likely already been shared on HN for both socio-economical and biological theories:
Would there not be value in pre-screening patients for SCN9A mutations to predict an increased risk of pain killer addiction? Socioeconomic factors play as role as well, but it doesn't to be so black and white.
> Would there not be value in pre-screening patients for SCN9A mutations to predict an increased risk of pain killer addiction?
Dangers, too. Legitimate pain patients already frequently have to drop through an onerous set of hoops for opiates, and the medical system isn't always good at teasing out "increased risk" from "unacceptable risk". (For example: https://en.wikipedia.org/wiki/Rofecoxib, aka Vioxx)
SCN9A variants have certainly been linked to changes in pain sensitivity (in both directions), but where have they been linked to changes in risk for opiate addiction? Even for the variant identified in this paper, the fact that it was linked to increased pain doesn't necessarily mean that it would put one at an increased risk for opiate addiction; in fact, you could easily imagine the opposite.
Furthermore, in spite of the strong genetic evidence, especially for the cases for congenital pain insensitivity, it has also been hard for the industry to develop Nav1.7 inhibitors, but that could mostly be due to targeting specificity.
As a follow-up for those that have said genetic studies have been fruitful, here's excerpts from the most recent genetic study [1]. This study looked at a link in the μ-opioid receptor gene, which was the only gene that barely reached genome-wide significance in their meta-analysis of 8529 individuals with opioid use disorder (OUD). In contrast, smoking, alcohol use, and education status showed clear effects on OUD.
"Understanding the genetic architecture of OUD might provide clinically useful clues about its biology. However, to our knowledge, only a few risk variants have been identified by GWAS so far, and none has had clear external replication. Several factors contribute to this situation: (1) OUD is a complex psychiatric disease with relatively low heritability, and there is no single variant with a large effect size that can be detected in small cohorts"
Because "genetic causes" will be abused (and arguably is pretty much just a dogwhistle) for racial stereotyping and Untermensch classifications, so you better be damn sure about the accuracy and impact magnitude before talking about it.
Yes. We live in a kind of reflexive terror of a regime that has been dead for the better part of a century and we must not look at certain parts of reality, lest they be true, because those people did something terrible related to that field of inquiry. There comes a time when crouching in silence waiting for a dogwhistle to be blown that nobody else can hear becomes paranoia.
It would be more reasonable and compassionate to identify genetic risk factors so that the people in question could make more informed choices in their lives, but instead we must keep them (and ourselves) ignorant lest, somewhere in the dark, a reel of Triumph of the Will begins spinning all on its own.
> That is hardly a good explanation to avoid scientific research.
I agree it's not, because it's not about research, but rather about science and "science" reporting as well as what ends up in the "news" ("researchers find the addiction gene"). That's why I said it is important to consider the magnitude before talking about it, not before researching it, because obviously you don't know the impact before the research is done.
Yeah it's very tricky given that being able to identify genetic causes could make it easier to identify and help people who may have a higher probability of suffering from some specific issue, such as opt-in screening for Tay-Sachs for people of Ashkenazi Jewish heritage.
I think the line to draw is that for it to be positive it should always be private, voluntary, independent from public policy and strictly for the purposes of improving medical outcomes.
Both are valid searches IMHO. Acknowledging the results of the search is also important.
If we replace the DNA in a human OVA with different DNA we get a different person. I conclude therefore, that DNA plays a role in who and what we are, the extent of which requires honest study.
We like elegant single-variable explanations for observed phenomenon.
See whatever that effect is called where a hundred thousand people collaborate to make something great, and the single person at the top of the organization is given 100% of the credit.
> Researchers have access to only a few Neanderthal genomes, and most of those have been sequenced at a low resolution. This has made it hard to identify mutations that evolved after their lineage split from that of humans some 500,000–750,000 years ago. But in the past few years, Pääbo and his team have generated three high-quality Neanderthal genomes from DNA found in caves in Croatia and Russia.
Can anyone with domain knowledge chime in on this?
Is the sample set of genomes enough to suggest these mutations were prevalent in the neanderthal population? And even so, might they have had a completely different effect on neanderthal physiology?
>Can anyone with domain knowledge chime in on this?
Due to the age of the genomes, C's deaminate and are recorded erroneously as T's. The solution is usually to throw out those sites from the sequencing results (which account for a large fraction of the genome in the garbage). By sequencing many different neanderthal individuals you can start to reconstruct some of those lost parts of the genome.
>Is the sample set of genomes enough to suggest these mutations were prevalent in the neanderthal population?
We aren't really at population scale genomics of neanderthals yet. We are still trying to piece together a truely high-quality reference genome (of one individual). Once that is complete, the next step is a population of about 100.
Based on the human genome, the chimpanzee genome, the neanderthal genome and the ancestrally reconstructed most recent common ancestor at each of the nodes in between, we can estimate allele frequencies within the different populations.
First, neanderthals were closely related to Denisovans. In Denisova cave itself, both neanderthals & denisovans were found and even a first generation hybrid. So.. you could call it a denisovan-neanderthal complex with various subpopulations over time and geography.
The altai neanderthals have been suggested as a subspecies/type... so there are differences there.
In europe and the middle east, there's a decent phenotypical distinction between early and late (classical) neanderthals. The earlier type was less distinctively neanderthal... kind of more sapien looking. Later populations developed that distinctively bony face.
..Sapiens too, probably. We descend mostly from a small population of sapiens, but that doesn't mean other populations didn't exist. They just don't have descendants.
For example, modern europeans have a relatively homogenous, low level of neanderthal DNA. At different points of history, certain populations could have ben 25% neanderthal... and genetically distinct from other groups.
This is all normal mammalian population dynamics. Modern Sapiens are the unusual ones. We went through a genetic bottleneck and lost a lot of diversity.
My understanding is that Neanderthals didn't occupy that large of a region. There are ancient human ancestors all over the globe but actual Homo neanderthalensis did not leave modern day Europe.
It is actually thought that this could have contributed to their decline. Compare with modern day humans who explored the whole globe: some ancient dude even paddled his way to Australia! It's hard for a species that widespread to go extinct.
Homo Neanderthalis has been found in europe, the middle east, the altai mountains, armenia and other places. The were widespread, and interbred with sapiens, denisovans and probably other types.
There is even renewed interest in finding American and/or Australian neanderthals and denisovans... As the known range has grown, those seem more plausible.
There is stubbing your toe pain. Watching kids, this does not stop repeat behavior.
Then there is pain that is all you can do to not jump off a cliff to end it. This, tends to change personal behavior.
Then there is pain that is slightly less then jump off a cliff. But it goes on for months, non stop, making every moment a horrible experience.
This has a huge impact on all those around you. Some pity you, some try and help, some wish you would die already. Most avoid you.
Degree makes a massive difference. Wish it was otherwise.
Perhaps it made them more empathetic? When I visited the Museum of Human Evolution in Burgos, Spain, they took us out to the Atapuerca excavation site and told us they’d found evidence of a Neanderthal with a life-threatening tooth abscess. Apparently he would have been in incredible pain and his tribe(?) mates managed to keep him alive by pre-chewing his food for him. They also found evidence of disabled Neanderthals who were helped/kept alive by the group but I can’t recall the specifics of the disability to remember whether any pain may have been involved.
I would think pro-social behaviors like that have a serious evolutionary advantage.
> Because feeling physical pain is vital for survival, CIP is an extremely dangerous condition.[1] It is common for people with the condition to die in childhood due to injuries or illnesses going unnoticed.
I wonder if that implies that neanderthals had greater pain sensitivity in general.
Pure speculation but it would be interesting if that was related to the apparent harshness and difficulty of life at the time. Perhaps it was something selected for survival.
I wonder whether we can infer this, because although the genes might result in nerves that more sensitively detect trauma and transmit that stimulus, we don't know that neanderthal experience of that pain was more intense, maybe their pain experience to a given stimulus was calibrated differently? Or perhaps, these nerves were slightly more sparsely placed in stouter bodies and had to detect injury across a greater region?
It sounds like they had to endure some damage:
I like the wikipedia quote:
'
It has been remarked that Neanderthals showed a frequency of such injuries comparable to that of modern rodeo professionals, showing frequent contact with large, combative mammals. The pattern of fractures, along with the absence of throwing weapons, suggests that they may have hunted by leaping onto their prey and stabbing or even wrestling it to the ground.'
While they didn't survive until today, they did survive for far longer than we have so far managed to, and in incredibly hostile conditions for the most part, which in itself is an enormous feat and makes you wonder, how did they do it?
They also never completely vanished; I have a number Neanderthal-specific alleles (more than most), as have pretty much all people of not exclusively subsaharan descent, and these alleles seem to have some pretty profound effects, some of them quite negative. That may be because these alleles evolved to work in concert with others that we haven't inherited, or for some other reason, but that would be quite valuable knowledge for a huge lot of people.
Besides, they're also a fascinating part of our collective history. They apparently had a unique and rich culture of their own; they are thought to have produced works of art before we even arrived in Europe[0] and they built pretty big structures out of stalagmites that appear to have no obvious practical purpose, in Bruniquel cave[1], about 176,000 years ago; by comparison, our ancestors seem to have started doing comparable things only ~60-50ka ago.
> They also never completely vanished; I have a number Neanderthal-specific alleles (more than most), as have pretty much all people of not exclusively subsaharan descent, and these alleles seem to have some pretty profound effects, some of them quite negative.
I wouldn't say entirely that they "didn't survive" considering we're talking about their genes existing within humans today.
Also, long term survival of a species has a lot more to do with luck than you'd think. e.g If cooling temperatures killed off their primary food source and forced them to migrate into human controlled territory where they didn't have experience, they'd be at a disadvantage. But if they lived in a temperature warming era, we may be having the opposite conversation right now. "Guns, Germs, and Steel" is a good summary of this hypothesis.
If we get wiped out in a nuclear war or because of global warming in the next 10k years, Homo Sapiens would have been around for less time than Neanderthals. Thus Neanderthals would have been better at surviving than us.
According to wikipedia Homo Sapiens have been around for 300 to 400 thousand years, while Neanderthals existed for 315 thousand to more than 800 thousand years.
You don't need to prove the the timespan left for a species in order to prove that the species is better at surviving, assuming better at surviving means surviving for more years.
In regards to Homo Sapiens and Neanderthals you just have to wait until Homo Sapiens goes extinct or has been around for a number of years that exceeds that of Neanderthals. Then you can conclude which species was better at surviving.
That's my original point. You can't say whether Neandethals are better or worse at surviving until 10-400k years in the future.
Also, I don't agree that a conjecture has to be experimentally proven during your personal lifetime in oder to be falsifiable. E.g. that would make gravity waves unfalsifiable, since they were predicted by Einstein in 1916 but weren't observed until 2016; 61 years after his death.
I just observed that they are extinct and we are not, despite coexisting for a substantial period. Their overall adaptation couldn't be that much better than ours.
Einstein's theories were falsifiable in multiple ways, with earliest confirming experiments in 1920s. Still, 61 years is within a lifetime. 10k years requires a time machine and makes your proposition pointless. As good as waiting for second coming to see if Bible's right.
> They didn't survive, so not sure what that says.
It says nothing because we cannot yet conclude that Homo Sapiens will survive for longer.
> Still, 61 years is within a lifetime. 10k years requires a time machine and makes your proposition pointless.
Interesting! So when does an experiment become pointless? When it takes a 100 years to prove? 200 years? 500 years? 1000 years?
> As good as waiting for second coming to see if Bible's right.
That's not the same. The second coming might never happen, Homo Sapiens will go extinct. In a million years, you can conclude which species survived the longest, but you'd probably still by waiting for the second coming.
That immediately came to my mind also. Apparently it's due to a variation of the MC1R gene which according to what I've read here, fourth paragraph [0], both developed independently of one another. Fascinating.
Also it's not necessarily the reception of pain itself that's different, as someone else said, but the perception or anticipation of it [1] that changes the degree of anesthetization required.
It's been found that Neanderthals didn't even carry the gene linked to "modern" red hair[1]. Also, I believe them having red hair was actually about as rare as it is nowadays.
I didn't know about their feeling more pain, but I know they require higher doses of anesthetic to knock them out for surgery (as in, anesthesiologists are taught this as a matter or course).
I wish dentists were, I (as a proud ginger man) have had to explain carefully that I'll need more local to several dentists, a few of whom didn't believe me.
We're also apparently less sensitive to electrical pain than others, so can we call that a superpower?
i wonder if that somehow is connected to the huge neuro diversity we see in the expression of the neurotransmitters. and the huge range of different types of intelligence. very cool. thanks for sharing.
Ironically, given that people of African descent have the least Neanderthal DNA, this study actually bolsters a supposedly discredited, baseless stereotype that they are less sensitive to pain:
"People of African descent" have the highest genetic diversity among all human subgroups. That fact alone makes making generalizations based on supposed genetic make-up preposterous.
Also, you have to be absurdly blind to the history of scientific racism to not understand that the stereotype of being less sensitive to pain has a historical origin in justifying abusing slaves by dehumanizing them.
I am NOT approaching this from any kind of racial stereotyping, but merely from a genetic point of view, but reading the article I had the same thought.
I had previously understood, that native domestic sub-Saharan Africans (i.e. those living on the continent, with clear African based heritage) did not have any Neanderthal DNA, as Neanderthals were further down the evolutionary line of the first emigration out of Africa, and were primarily European based. Therefore those with purely African genetic history would never had interbred with them.
Is this still true, or have I been walking around with a massive misunderstanding here?
As a footnote, We need to still be able to ask these questions without being afraid of the racism response. We are all different, we should embrace that and not let it affect scientific discussion or discovery.
As is usually the case, reality is to messy for simple explanations like this to be completely correct. Europe and Africa are pretty close, so there has been a lot of migration to and fro, some of it bringing Neanderthal DNA into Africa: https://www.sciencemag.org/news/2020/01/africans-carry-surpr...
- "modern Europeans and East Asians apparently inherited about 2% of their DNA from Neanderthals"
- "African individuals on average had [...] more Neanderthal DNA than previously thought—about [...] 0.3% of their genome."
So the article seems to confirm a 10x difference in Neanderthals DNA, which might be significant.
It's also unclear what they mean by "Africans, did the same include,
e.g. Egyptians of Greek descent?
Fascinating revelation. What still puzzles me is how Asian populations have a slightly higher average proportion of Neanderthal DNA when their range was predominantly over the European part of Eurasia.
> "People of African descent" have the highest genetic diversity among all human subgroups.
Yes, but that has nothing to do with Neanderthal interbreeding.
Sub-Saharan Africans have less Neanderthal DNA that other humans from outside of Africa because interbreeding occurred when we left Africa and met Neanderthals in Eurasia.
Based on that it is not crazy to formulate the hypothesis that any traits we may have inherited from Neanderthals might be less pronounced in sub-Saharan Africans, though obviously hypotheses are not facts and one has to be very prudent, and even more so when calling on racial stereotypes...
Slavery is much older than the period that the term "scientific racism" refers to. Older slave holders had no trouble justifying slavery.
Interestingly, the many slave rebellions of antiquity (and after) by and large did not seek to abolish slavery, only to switch who's a slave, and who's a slave holder.
> Romans (or whatever) did not treat their slaves as sub-humans
I mean, that's pushing it. Obviously, their concept of slavery wasn't really based on ethnicity, and manumission was generally more common and socially acceptable than it was in American slavery. But the treatment of slaves in Ancient Rome was certainly inhuman by modern standards.
The Romans also had mechanisms to, in practice, suppress the political power of descendants of slaves; in practice almost all freedmen went into one of the urban tribes (the very wealthy could buy into a rural tribe), making their votes largely irrelevant, for instance. It's reasonable to view New World slavery as a special evil, but Roman slavery was Pretty Bad, too.
> The Romans also had mechanisms to, in practice, suppress the political power of descendants of slaves; in practice almost all freedmen went into one of the urban tribes (the very wealthy could buy into a rural tribe), making their votes largely irrelevant, for instance. It's reasonable to view New World slavery as a special evil, but Roman slavery was Pretty Bad, too.
Those mechanisms sound a lot like present day gerrymandering[1][2] coupled with redlining[3][2].
Look at it the other way around: white people have higher pain sensitivity. You don't have to make a generalisation about all peoples from Africa, you can just make a generalisation about white people. We know there was a genetic bottleneck.
Comments like being "absurdly blind" are stupid. Are you going to discredit current science because of some loosely related historical events?
If we resume the finding this in term of skin color: "some middle-aged people (mostly 'white') have higher pain sensitivity than other middle-aged people (mostly 'white')
From the article:
> About 0.4% of participants in the UK Biobank, a genome database of half a million British people, who reported on their pain symptoms had one copy of the mutated gene. No one had two, like Neanderthals. Participants with the mutated version of the gene were about 7% more likely to report pain in their lives than were people without it.
About UK Biobank:
> The study is following about 500,000 volunteers in the UK, enrolled at ages from 40 to 69. Initial enrollment took place over four years from 2006, and the volunteers will be followed for at least 30 years thereafter.
0.4% of people who _were already reporting on their pain_ (likely a group who are plausibly more likely to have some sort of pain issues than the general population) had this gene. That is, this is extremely rare. And the effect was small. It shouldn't bolster any stereotypes.
