On Fri, 23 Jul 2010 17:36:40 -0500 (CDT), Joan Warmbold wrote: > I find Mike's analogy between Alzheimer's and Huntington's quite > inappropriate.
Frankly, I do not understand Joan's complaints but will play along since there some issues that she raises that need clarification. > We have known for eons that Huntington is caused by one > dominant gene and if that gene is in one's genotype, it will be in their > phenotype, period. First, let me reproduce Michael Sylvester's original questions/statements: Michael Sylvester previously wrote: >>Recently there have been speculations about detecting Alzeimers, >>autism,and other pathologies as early in life as possible. >>Re Alzheimers,researchers think that there are biological markers >>that can be detected very early in life and preventative treatment can be >>applied.I find this idea crazy. I don't know what releveance Joan's comments have to these statements but my use of Huntington's disease was to show that we can indeed use biological markers that can detect disease very early in life and preventative treatment, if available, can be applied. A condition like Phenylketenuria (PKU) is another example but its manifestation, unlikely Alzheimers and late onset Huntington's, can be treated very early in life, as soon as the condition is known to exist by changing the child's diet. For more on PKU, see: http://en.wikipedia.org/wiki/Phenylketonuria As for the comments "we have known for eons that Huntington is caused by one dominant gene...", I don't really see the relevance of this since the original issue raised by Sylvester was being able to detect illnesses very early in life. But perhaps a little history is appropriate; quoting from the Wikipedia entry on Huntington disease: |The first thorough description of the disease was by George Huntington |in 1872 [NOTE: Alzheimers was first described in 1906]. Examining |the combined medical history of several generations of a family exhibiting |similar symptoms, he realized their conditions must be linked; he |presented his detailed and accurate definition of the disease as his first |paper. Unknowingly, Huntington described the exact pattern of inheritance |of autosomal dominant disease years before the rediscovery of Mendelian |inheritance. "Of its hereditary nature. When either or both the parents have |shown manifestations of the disease ..., one or more of the offspring |almost invariably suffer from the disease ... But if by any chance these |children go through life without it, the thread is broken and the grandchildren |and great-grandchildren of the original shakers may rest assured that |they are free from the disease.".[60][64] [snip] | |During the rediscovery of Mendelian inheritance at the turn of the 20th |century, HD was used tentatively as an example of autosomal dominant |inheritance.[61] The English biologist William Bateson used the pedigrees |of affected families to establish that HD did have an autosomal dominant |inheritance pattern.[62] The strong inheritance pattern prompted several |researchers to attempt to trace and connect family members of previous |studies, one of whom was Smith Ely Jelliffe.[61] Jelliffe collected information |from across New York State and published several articles regarding the |genealogy of HD in New England.[66] Jelliffe's research roused the interest |of his college friend, Charles Davenport, who commissioned Elizabeth |Muncey to produce the first field study of families with HD, and construct |their pedigrees, on the East Coast of the United States.[67] Davenport |used this information to document the variable age of onset and range of |symptoms of HD and make the claim that most cases of HD in the USA |could be traced back to a handful of individuals.[67] This research was |further embellished in 1932 by P. R. Vessie, who popularised the idea |that three brothers who left England in 1630, bound for Boston were the |progenators of HD in the USA.[68] [snip] | |Research into the disorder continued steadily through the 20th century, |reaching a major breakthrough in 1983 when the US-Venezuela Huntington's |Disease Collaborative Research Project discovered the approximate |location of a causal gene.[57] This was the result of an extensive study |begun in 1979, focusing on the populations of two isolated Venezuelan |villages, Barranquitas and Lagunetas, where there was an unusually high | prevalence of the disease. Among other innovations, the project developed |DNA marking methods which were an important step in making the Human |Genome Project possible.[71] In 1993 the research group isolated the precise |causal gene at 4p16.3,[72] making this the first autosomal disease locus |found using genetic linkage analysis.[72][73] In the same time frame, key |discoveries concerning the mechanisms of the disorder were being made, |including the findings by Anita Harding's research group on the effects of |the gene's length.[74] | |Modelling the disease in various types of animals, such as the transgenic |mouse developed in 1996, enabled larger scale experiments. As these |animals have faster metabolisms and much shorter lifespans than humans, |results from experiments are received sooner, speeding research.[75][76] |The 1997 discovery that mHtt fragments misfold led to the discovery |of the nuclear inclusions they cause.[77] These advances have led to |increasingly extensive research into the proteins involved with the disease, |potential drug treatments, care methods, and the gene itself.[61][78][79] I have no idea where Joan get the idea that we've knows the nature of Huntington's genetic character for "eons" (perhaps decades would have been a better choice of words) but it is clear that the specific genetic nature of Huntington's really starts in the 1980s. Again, this is somewhat besides the point because the original statement by Sylvester was: >>researchers think that there are biological markers >>that can be detected very early in life and preventative treatment can be >>applied.I find this idea crazy. Well, I think that the Huntington's disease cases shows that this is not so crazy an idea. Alzheimer's may be much more complex but I don't believe that Joan wants to claim that early life tests for Alzheimers and effective treatments are impossible. > In contrast, the factors that contribute to the > development of Alzheimer's are not nearly as clear-cut. For example, as > well as genetic susceptibility, there is clear evidence that factors in > one's life experiences, as level of academic achievement, keeping very > active, having a very supportive social network and maintaining a healthy > diet high in lycopene and folic acid are associated with low levels of > Alzheimer's (see Nun's > Study: http://www.stpt.usf.edu/~jsokolov/agealzh2.htm ) Again, the issue was can biomarkers and other information be obtained at an early age, provide a diagnosis of the condition (i.e., what type of dementia is likely to develop), its probable course, and what treatments are currently available, what treatments are in the pharmaceutical pipeline, and what novel reconceptions of Alzheimers may lead to new treatments. > Also as Dr. Pimplikar states in his NYT's op-ed piece, the tests for > Alzheimer's, as the search for biomarkers, PET Scan and spinal tap are not > yet able to predict well who will and who will not get this disease. > > http://www.nytimes.com/2010/07/20/opinion/20pimplikar.html And? What is the point? That such tests are in principle impossible? The fact does we do not have such tests now does not make research on developing such tests "crazy". You seem to think that I have said that we have such tests now instead my saying that there is the promise of such tests. > I'm totally baffled at the inclusion of HIV that is clearly caused by > sexual patterns and general health--who believes that HIV has a genetic > cause?! To clarify: (1) HIV is a virus and AIDS is the clinical manifestion of infection with HIV. The development of AIDS depends in part on the immune system of the infected person. The average amount of time between HIV infection and the manifestion of AIDS symptoms is estimated to be about 10 years. That's the average, and there are a group of people that appear not to develop AIDS, referred to as nonprogressive HIV infection. (2) One of the first reports on nonprogressive HIV infection was by Buchbinder et al in *1994*; see: http://www.ncbi.nlm.nih.gov/pubmed/7986410 Nonprogressive HIV infection have been studied since then and one explanation for why this occurs is that humans can produce antibodies that can keep the infection in check, as recently reported by NIH; see: http://www.niaid.nih.gov/news/newsreleases/2010/Pages/HIVantibodies.aspx (the research report summarized here appears in Science, circa July 8, 2010) (3) The ability to make such antibodies naturally should have a genetic basis which is why this research may finally lead to an effective AIDS vaccine. So, HIV is a virus; AIDS is the clinical manifestation of HIV infection. There are a number of viruses and bacteria that many people are infected with but do not manifest clinical signs unless some other condition (e.g., leading to immunosuppression) initiates clinical manifestation; Human herpesvirus 6 (HHV6) is one such bug which it is estimated that about 95% of adults have been infected with and have developed antibodies to; see: http://www.ncbi.nlm.nih.gov/pubmed/9227865 > But the more important issue here is the idea genetic tests can > provide people with a clear idea of their chances of getting Alzheimer's > when such is not the case at all. Where did I claim that we currently have this capability? I said: >> As these disorders become better understood and the basis >> for why they occur, especially genetic, is identified, it will >> become easier to predict who is at risk and what strategies >> to follow to deal with the condition. This has been done in >> that past and will be a useful strategy to follow in the future I have an optimistic view of the power of science and believe that we can solve the problem of understanding these illnesses. > I feel that the medical establishment > is showing their ongoing tendency to push for tests and more tests > regardless of the long-term impact on the patient. I really have no idea what you're talking about here outside of the interpretation that you don't believe that scientific medical research can in fact provide useful and beneficial tests and treatments. Why you seem to believe this is beyond me. -Mike Palij New York University mp262nyu.edu --- You are currently subscribed to tips as: [email protected]. To unsubscribe click here: http://fsulist.frostburg.edu/u?id=13090.68da6e6e5325aa33287ff385b70df5d5&n=T&l=tips&o=3788 or send a blank email to leave-3788-13090.68da6e6e5325aa33287ff385b70df...@fsulist.frostburg.edu
