eric@snark.uu.net (Eric S. Raymond) (02/11/89)
In <10276@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes: >Not being a geneticist, I have frequently wondered, but never looked into, >the question of why an infrequent mutation like Tay-Sachs, which has such >a devastating effect on those unfortunates who are homozygous for it, has >such a relatively *high* incidence among Ashkenzaic Jewry (I believe that >1/30 individuals is heterozygous). I think I know the answer to this one, but you're not gonna like it... A good friend of mine at UPenn was a pre-med who came from a family of doctors (as a matter of fact, the fact that his uncle is a senior physician at the medical school's hospital saved his life once, but that's another story). The family was Ashkenazic Jewish, German overachiever subvariety. Harry once told me that one of his doctor cousins had researched this problem and come to some really startling conclusions (which, for reasons which will become obvious, he never got to test conclusively). Everybody know how the sickle-cell trait works in Blacks? If you're homozygotic for it, you lose; it's lethal. But if you're heterozygotic for it, you win -- you're resistent to malaria. A useful adaptation for Blacks in sub-Saharan Africa, so the trait is widespread in the Black population despite its deadliness. Harry's cousin guessed something similar might be true for Tay-Sachs. He figured there had to have been some historically recent advantage to being heterozygotic for the trait, or it'd have been selected right out. So he went looking for a disease or other environmental factor that was endemic to south central Russia and the Pripyet Marshes around the time the ancestors of the Ashkenazim emerged as a distinct population there. Something sufficiently dangerous that resistance to it was a net win over significantly higher infant mortality; something for which no less costly adaptation has been shown in any other human population; and something for which some later suggestion of significant resistance in the Ashkenazim could be found. He found it. A bacterium called `pasteurella pestis' -- the bubonic plague. I don't know if he ever tried controlled in vitro test of this hypothesis; in vivo, of course, would be horribly dangerous. But if true, it would explain an *awful* lot about the tragic history of the Jews in Europe. Perhaps the Ashkenazim really *were* (inadvertent) plague-spreaders. Standard theory about the ghettos escaping the worst effects because of `superior sanitation' always had sounded kind of thin to me. Someday I hope to read a definitive book on epidemiological catastrophies in social history that features details on this one and the ergotism explanation for the late-medieval witchcraft hysterias as star cases. Sadly, it hasn't been written yet. -- Eric S. Raymond (the mad mastermind of TMN-Netnews) Email: eric@snark.uu.net CompuServe: [72037,2306] Post: 22 S. Warren Avenue, Malvern, PA 19355 Phone: (215)-296-5718
ayermish@asylum.SF.CA.US (Aimee Yermish) (02/12/89)
In article <eoig7#1hZTGI=eric@snark.uu.net> eric@snark.uu.net (Eric S. Raymond) writes: >So he went looking for a disease or other environmental factor that was >endemic to south central Russia and the Pripyet Marshes around the time the >ancestors of the Ashkenazim emerged as a distinct population there. Something >sufficiently dangerous that resistance to it was a net win over significantly >higher infant mortality; something for which no less costly adaptation has >been shown in any other human population; and something for which some later >suggestion of significant resistance in the Ashkenazim could be found. > >He found it. A bacterium called `pasteurella pestis' -- the bubonic plague. > >I don't know if he ever tried controlled in vitro test of this hypothesis; in >vivo, of course, would be horribly dangerous. But if true, it would explain >an *awful* lot about the tragic history of the Jews in Europe. Perhaps the >Ashkenazim really *were* (inadvertent) plague-spreaders. Standard theory about >the ghettos escaping the worst effects because of `superior sanitation' always >had sounded kind of thin to me. I wouldn't throw out the idea of superior sanitation so quickly. Yersinia pestis (the name pasteurella is no longer used) is transmitted to humans by flea bites. Bubonic plague manifests, among other things, with serious lymph node swelling especially near the flea bite. In this form, it doesn't transmit between people. In later stages, the lungs can get secondarily infected from the bloodstream, causing "pneumonic plague," which is almost invariably fatal and can in fact spread between people (you cough the bugs into the air and someone else inhales them). I don't recall exact figures, but practically everyone who gets this shows symptoms. If you keep your bodies and homes clean and sanitary, as free as possible of fleas and rats (which is the reservoir of the disease), you don't get bitten by as many fleas and have a lowered probability of getting bitten by one carrying the plague. Also, if you are in a ghetto or other population physically removed from the rest of the population, you minimize your risk of contracting plague via the respiratory route. In any case, the Ashkenazim could not have been spreading the plague a la Typhoid Mary because, as I explained, asymptomatic pneumonic plague is at the very least, extremely rare. Incidentally, the defect in Tay-Sachs is known. (It's an enzyme that produces a certain lipid required in the nervous system) Assuming that rats need the same lipid, with a great deal of effort the in vivo experiment could actually be done. Not an easy one, though. --Aimee -- Aimee Yermish ayermish@asylum.sf.ca.us Program in Cancer Biology ayermish@portia.stanford.edu Stanford University 415-594-9268
dplatt@coherent.com (Dave Platt) (02/12/89)
In article <eoig7#1hZTGI=eric@snark.uu.net> eric@snark.uu.net (Eric S. Raymond) writes: > I don't know if he ever tried controlled in vitro test of this > hypothesis; in vivo, of course, would be horribly dangerous. But if > true, it would explain an *awful* lot about the tragic history of the > Jews in Europe. Perhaps the Ashkenazim really *were* (inadvertent) > plague-spreaders. Standard theory about the ghettos escaping the worst > effects because of `superior sanitation' always had sounded kind of thin > to me. Your "perhaps" doesn't seem to follow from the hypothesis. Even if it's true that the Tay-Sachs gene confers some immunity against the plague bacillus, it isn't necessary to infer that the Ashkenazim were even inadvertent plague-spreaders. The mechanisms by which plague spreads seem to be very well understood (rats, etc.). The very fact that the Ashkenazim weren't as commonly or as seriously affected by the plague would be reason enough (in the eyes of superstitious and anti-Semitic Christians) to throw suspicion on the Jews. -- Dave Platt FIDONET: Dave Platt on 1:204/444 VOICE: (415) 493-8805 UUCP: ...!{ames,sun,uunet}!coherent!dplatt DOMAIN: dplatt@coherent.com INTERNET: coherent!dplatt@ames.arpa, ...@sun.com, ...@uunet.uu.net USNAIL: Coherent Thought Inc. 3350 West Bayshore #205 Palo Alto CA 94303
kanov@bimacs.BITNET (Mechael Kanovsky) (02/12/89)
In article <eoig7#1hZTGI=eric@snark.uu.net> eric@snark.uu.net (Eric S. Raymond) writes: >In <10276@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes: >>Not being a geneticist, I have frequently wondered, but never looked into, >>the question of why an infrequent mutation like Tay-Sachs, which has such >>a devastating effect on those unfortunates who are homozygous for it, has >>such a relatively *high* incidence among Ashkenzaic Jewry (I believe that >>1/30 individuals is heterozygous). > I think that the answer is much simpler. If we take into account that the jews lived in Shtetles i.e. small villages and there was alot of intermarrying like first cousins marrying one another then the chances of the defective gene becoming hozygotis is much higher than in a population where there is a larger gene pool and people marry non-relatives. -- Mechael Kanovsky : BITNET kanov@bimacs.bitnet Math & CS Dept. : UUCP uunet!mcvax!humus!bimacs!kanov Bar-Ilan University : ARPA kanov%bimacs.bitnet@cunyvm.cuny.edu Ramat-Gan Israel : CSNET kanov%bimacs.bitnet%cunyvm.cuny.edu@csnet-relay ! You can't propel yourself forward ! ! by patting yourself on the back !
werner@aecom.YU.EDU (Craig Werner) (02/13/89)
In article <789@bimacs.BITNET>, kanov@bimacs.BITNET (Mechael Kanovsky) writes: > > In article <eoig7#1hZTGI=eric@snark.uu.net> eric@snark.uu.net (Eric S. Raymond) writes: > >In <10276@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes: > >>Not being a geneticist, I have frequently wondered, but never looked into, > >>the question of why an infrequent mutation like Tay-Sachs, which has such > >>a devastating effect on those unfortunates who are homozygous for it, has > >>such a relatively *high* incidence among Ashkenzaic Jewry (I believe that > >>1/30 individuals is heterozygous). > > > The plot thickens even more when you consider that the Tay-Sachs mutation actually arose at least four separate times independently (that is, there are four distinct gene patterns, all distinguishable from one another by standard molecular genetic techniques that cause a defect in the same enzyme, and thus create the Tay-Sachs trait. This is quite a large number when you consider that Sickle Cell seems only to have arisen twice. Now some persons on the net have suggested that the selecting force for the mutation was the Black Plague, Yersinia pestis. That's one I hadn't heard before, but I certainly can't refute it. However, a theory which does seem to have some support, although one that is by no means proven, is that the selection was rather the Great White Plague, namely that disease endemic to cities until the 20th century, Tuberculosis. -- Craig Werner (future MD/PhD, 4 years down, 3 to go) werner@aecom.YU.EDU -- Albert Einstein College of Medicine (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "Until it's on daytime television, it's impossible, and that's the final word."
ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) (02/14/89)
In article <eoig7#1hZTGI=eric@snark.uu.net>, eric@snark.uu.net (Eric S. Raymond) writes: > In <10276@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes: > >Not being a geneticist, I have frequently wondered, but never looked into, > >the question of why an infrequent mutation like Tay-Sachs, which has such > >a devastating effect on those unfortunates who are homozygous for it, has > >such a relatively *high* incidence among Ashkenzaic Jewry (I believe that > >1/30 individuals is heterozygous). > > So he went looking for a disease or other environmental factor that was > endemic to south central Russia and the Pripyet Marshes around the time the > ancestors of the Ashkenazim emerged as a distinct population there. .... > He found it. A bacterium called `pasteurella pestis' -- the bubonic plague. A fascinating idea, although fairly similar to the earlier suggestion about TB. However, I vaguely recall that there are two other rarer genetic diseases among the ashkenazim that produce similar metabolic effects in heterozygous individuals. (Did another poster mention this? Perhaps they could post a few more details.) In any case, the plague was widespread in Europe for quite a while. Why did the Ashkenazim come up with three genetic adaptations and other groups come up with none? Coincidence? Maybe other mutations occurred in the general population but were so diluted as to be indistinguishable from the effects of intermarrying with Jews? -- I'm not afraid of dying Ethan Vishniac, Dept of Astronomy, Univ. of Texas I just don't want to be {charm,ut-sally,ut-emx,noao}!utastro!ethan there when it happens. (arpanet) ethan@astro.AS.UTEXAS.EDU - Woody Allen (bitnet) ethan%astro.as.utexas.edu@CUNYVM.CUNY.EDU These must be my opinions. Who else would bother?
berleant@cs.utexas.edu (Dan Berleant) (02/15/89)
In article <eoig7#1hZTGI=eric@snark.uu.net> eric@snark.uu.net (Eric S. Raymond) writes: >In <10276@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes: <>>... I have... never looked into, the question of why... Tay-Sachs... has <>>such a relatively *high* incidence among Ashkenzaic Jewry (I believe that <>>1/30 individuals is heterozygous). < <>[someone] went looking for a disease or other environmental factor that was <>endemic to south central Russia and the Pripyet Marshes around the time the <>ancestors of the Ashkenazim emerged as a distinct population there. Something <>sufficiently dangerous that resistance to it was a net win over significantly <>higher infant mortality; something for which no less costly adaptation has <>been shown in any other human population; and something for which some later <>suggestion of significant resistance in the Ashkenazim could be found. <> <>He found it. A bacterium called `pasteurella pestis' -- the bubonic plague. <> <>I don't know if he ever tried controlled in vitro test of this hypothesis; in <>vivo, of course, would be horribly dangerous. But if true, it would explain <>an *awful* lot about the tragic history of the Jews in Europe. Perhaps the <>Ashkenazim really *were* (inadvertent) plague-spreaders. Standard theory about <>the ghettos escaping the worst effects because of `superior sanitation' always <>had sounded kind of thin to me. This could certainly explain the high incidence of the Tay-Sachs gene among Ashkenazim. But it wouldn't explain why Jewish ghettoes escaped the worst of the plague, because if only 1/30 of the population was resistant, that still leaves a whopping 29/30 (about 97%) who were presumably as vulnerable as the gentile population. Superior sanitation might actually be reasonable. I think Bubonic plague is carried by rats, and anything that would discourage rats would tend to reduce the amount of plague among the people in the area. Dan
hkhenson@cup.portal.com (H Keith Henson) (02/24/89)
In a privious posting Eric S. Raymond writes of the possibility that plague might have a selective effect on the incidence of Tay-Sachs. Maybe, but if my memory of plague is correct, it has only intermittantly broken out among the rodent populations, with hundreds of years between episodes. This is quite unlike the pressure that malaria puts on human gene selection. An alternate way the gene could have become widespread is that a lot of people are desended from someone in which the mutation occured. When a people moves into a relatively unpopulated area, that happens. Keith Henson hkhenson@cup.portal.com