>Though today Benjy and most of the Fugate family descendants have lost their blue coloring, the tint still comes out in their skin when they are cold or flush with anger.
I wish they had included at least one photograph of this.
Makes sense, seems like in the 1960s they came up with a solution for removing the blue color, so most likely if they have the recessive gene, they are taking those pills.
> Using research collected from studies of isolated Alaskan Eskimo populations, Cawein was able to conclude that the Fugates carried a rare hereditary blood disorder that causes excessive levels of methemoglobin in their blood.
> Cawein devised a cure for this disorder: more blue. Counterintuitively, the best chemical for activating the body’s process of turning methemoglobin to hemoglobin is methylene blue dye. The Fugates he treated ingested this dye and within a few minutes, the blue coloration of their skin disappeared, and their skin turned pink.
> As long as they kept ingesting pills of the substance regularly, these blue people of Kentucky could live their lives normally.
Very well could be. I'd never heard of it at the time I knew them, so didn't know to look or even ask.
I can't confirm they are direct lineage or anything, though. I only know they were Fugate from eastern KY. It's not a particularly common name, nor is eastern KY particularly well populated so figure they are related in some manner.
He doesn't look too blue at all, that is true. They say that most of the color faded as he got older. If you look closely you can see a tinge of blue on his face.
This article touches on something that remains very true today: if you want to study genetic disorders you look at closely-related populations. If the condition you want to study is linked to a recessive gene, you want to find (or create) an isolated population with that gene.
In animals/plants this is why inbreeding can serve a useful function. If you want to detect a recessive gene, but either don't have access to genetic testing or are not sure which gene is involved, you in-breed until you see individuals who express the recessive gene. These individuals inherited the recessive gene from both parents. You then know which parental lines carry the gene, which lets you select for or against it.
My country of origin, Faroe Islands, has worked on this precisely because the population is small and very closely related. So there's a lot of recessive genes being expressed. Also, they've kept meticulous population records for centuries, so traits can be accurately traced back through several generations. I just looked up my own records in the national registry and traced one of my branches back to a named person born in the year 1170.
Many, many species of plants are inbreeders. In the plant world, inbreeding and outbreeding seem to both be successful techniques with their own benefits and drawbacks.
Inbreeding gets a bad reputation in humans because we have poor genetic diversity and endless recessive diseases due to going through at least two near-extinction events (population bottlenecks) that took us down to 2000 and 55000 humans.
https://gizmodo.com/extinction-events-that-almost-wiped-out-...
Many animals can inbreed with much less downside.
There are lab mice that are entirely homozygous (inbred until every gene they have is identical). They're not quite as prolific as normal mice, but they survive.
The discovery of the treatment in the methylene blue dye is quite fascinating. How exactly did someone figure that out for such a rare condition? And imagine being deep blue all your life and everyone knowing you as blue, then you take this blue pill and bam, you're pink as can be. Must have seemed like practical magic.
Methylene blue was widely used in malaria treatment, and after its relative safety was figured out, ease of access meant doctors went nuts trying it out on all sorts of conditions. And it worked as a treatment for all sorts of things, and was issued to soldiers in the field through wwii. It's a MAOI and shows up in nootropic stacks and discussions all the time.
Makes you pee blue, can treat effects of carbon monoxide poisoning, etc. There were lots of opportunities for someone with blue skin to have encountered the stuff.
Methylene blue has a fascinating history in medicine. It was already well known as a treatment for methemoglobinemia however. It's a ready electron acceptor. It's used for a few other conditions today, without a lot of evidence.
The general condition of methemoglobinemia isn't as rare as this family's particular genetic condition, so the methylene blue treatment was already known. I'm not sure when they first discovered that methylene blue can treat methemoglobinemia - methylene blue was discovered in 1876, but it does all sorts of things.
> And imagine being deep blue all your life and everyone knowing you as blue, then you take this blue pill and bam, you're pink as can be. Must have seemed like practical magic.
Almost sounds like homeopathy, without the dilution, that actually works.
Not really. This isn't like cures like. This is triggering a biological system to do something. There is a buildup of a substance that he body could break down but doesn't. So you do something to trigger the system into action. This is more like hydrating someone in order to trigger their kidneys to work harder and thereby flush out some other toxin.
I get their point, homeopathy has two bs gimmicks. The first is to use a substance that causes the ailment as a cure, the second is to replace that substance with water/sugar and the idea of the substance.
Using a blue substance to cure someone who's blue is similar to the first gimmick, but here they actually use the substance and medically tested it.
For the sake of clarity: I will not stand on the side of homeopathy, ever. It's placebo effect marketing rather than evidence-based science and hence not worth my money.
What about when placebo-based medicine offers better patient outcomes, for certain disorders? E.g., for sleep medicine without side effects? We used homeopathy for my daughters car sickness and it worked great.
Did you know stretching before a car trip prevents all but the worst car sickness? Both my chiropractor and my acupuncturist recommended it and I haven't suffered from car sickness since.
There, I saved you the cost of the water pills. You don't need costly, potentially dangerous additive laced medicine if you're just looking for the placebo effect.
Some of the pills are made using toxic fillers. It's not enough I'd panic over, you can get the placebo effect without ingesting anything shady/expensive.
I can't find specifics about homeopathic fillers, but any pill not regulated by the FDA is likely to use cheap fillers that are often toxic. Vitamins are where you commonly hear about this, see https://en.wikipedia.org/wiki/Regulation_of_food_and_dietary...
Placebo is very powerful and is actually validated by scientific research.
So when the conditions are here, as they seemingly were for your daughters, it's great.
Yet, homeopathy, when considered as a potent product, didn't help, because it is not potent. The conditions enabling the placebo effect did. And no one would complain about that :)
The problem arises when homeopathy is sold and marketed as potent _per se_.
Maybe the old term for European aristocrat, blue blood, along with its inbreeding connotations, is more literal than history gives it credence. It's usually attributed to pale skin but perhaps methemoglobinemia was on display.
If people had been quite literally blue, it would have been widely written about. You're talking about an era giving people nicknames based on their countenance and using any slight deformity for propaganda was quite common.
Some oxiditation (1%) of Hb (Fe 2+) to metHb (Fe 3+) is normal, it gets reduced back by the enzyme Cytochrome b5 reductase. So far so good.
But since metHb is dysfunctional and cannot bind oxygen and you need levels of at least 10% metHb to be visible as cyanosis: Why didn't they exhibit oxygen-deficit related symptoms?
Or can your body compensate with other mechanism if it's congenital?
At least when it is visibly induced you most certainly will also suffer from symptoms like shortness of breath etc.
Comically, the author used a stock image to explain how recessive genes work, where the unaffected individual is blue, and the affected is red. It serves more to confuse than explain.
The patho is different. Fugates’ skin was due to methemoglobin. Argyria is the result of the accumulation of silver nanoparticles in body tissues. Argyria is not reversible.
I would imagine the actual hue of the blueness would be different.
Other than the one person marrying their aunt, the closest connection I can see is a second cousin marrying, something I believe is legal, healthy, and very common in that period. I'd bet portions of your family tree from two hundred years ago would look similar.
That tree's focused on only one person, Ben Stacy; his ancestors. The entire tree sounds a lot more connected:
> However, by the early 1960s, some members of the Fugate clan had begun to resent their cobalt-tinted skin. Not only did their skin mark them as different, but by that time, people had already begun to associate their skin color with the family’s history of inbreeding.
It’s called pedigree collapse. Your family tree grows exponentially to the second power with each generation. So a mere 50 generations ago, which is to say roughly 1000-1500 years ago, you had 1,125,899,906,842,624 slots in your family tree. Needless to say the vast majority of those slots don't have a unique person in them.
Mine certainly does. One quarter of my ancestry comes from an area of Lancashire which had three wealthy families -- the Cleggs, the Mercers, and the Taylors. Those three families intermarried almost exclusively from ca. 1400 until ca. 1850.
Hi exDM69, you posted in April about a proto (https://news.ycombinator.com/item?id=22977095) that you might share. I am interested on how you did: "cache (sizeof(node) == cache line), no recursion, no memory allocation, no unbounded loops, no system calls, etc."
Can you share please github name: lazalong
Maybe that particular family had it much worse but I don't think I'd ever see someone with it and think "they're blue." Though if it's like poor circulation, it'd looks a bit more blue in person.
I wish they had included at least one photograph of this.