HUM-MOLGEN archive: ETHI: Multiplex screening

Three more interesting responses on the issue of multiplex screening. Hans Goerl ETHI Editor ***************************************************************************** **** 1.From Jim Cummins. "E. ALLEN SMITH" <EALLENSMITH@MBCL.RUTGERS.EDU> wrote: > > > In regard to Mr. Goerl's interesting questions on the >multiplex gene detection system, I would like to propose two >possible legitimate uses of such tests, beyond the other ones he >mentioned. These services are sperm banks and diagnostic work. I agree that there is a need to screen sperm donors. There's also a pressing need to screen men being treated for severe infertility where there is a tenfold increase in associated chromosomal anomalies. In particular, men with congenital absence of the vas deferens are highly likely to be carriers of cystic fibrosis mutations - in these cases the wife needs screening too. See our paper "Concerns and Recommendations for ICSI Treatment" on http://Numbat.murdoch.edu.au/spermatology/androl90s_ToC.html Jim "Spermatology rules o~ o~ o~ o~" Cummins Associate Professor in Veterinary Anatomy Murdoch University, Western Australia 6150 Tel +61-9-360 2668, Fax +61-9-310 4144 E mail <cummins@possum.murdoch.edu.au> URL <http://Numbat.murdoch.edu.au/spermatology/spermhp.html> The Penultimate Law "All general statements are false. ***************************************************************************** ******** 2.From: Kenneth Krul <PandaGroup@AOL.COM> What fascinates me about the possibility of multiplex screening is that there is a good possibility that we will find that each and every one of us carries one or more negative alleles. I mean, with so many genes, so many base sequences, I find it hard to believe that those of us who do not show recognizable clinical manifestations are "perfect" genetically. How many of us may contain susceptibility genes to this, that, or the other thing that never manifest clinically because of our environment? Are these susceptibility genes to be considered "negative?" A person of, say, African or Indonesian extract, may contain a gene that causes problems indigenous to those regions, but because they and their family have lived in Milwaukee, where the triggering mechanism for that gene's pathological condition does not exist, do we consider this a negative allele? How many recessive genes do each of us carry but, because they are so rare within the population, the chance of our mating with another carrier of that recessive gene is virtually nil. Somehow, we've gotten into the mindset that there will be _a_ model human genome ... base pair by base pair. We already know that any amino acid can be coded for be a number of different nucleotide triplets. Isn't this enough to give somebody the idea that the diversity of the system may be too great to provide anything but a "less than razor sharp" definition? Somehow, I don't think I'm the first and only person to realize this. But those who are uninitiated in the science won't grasp this ... and I'm including a lot, not all, of clinicians in that group. As for there being a very large market for multiplex screening of children ... (a) I doubt it, and (b) why? I doubt it because there have been surveys of genetically at-risk individuals (the most memorable being that of Huntington's families) who were asked if they would want to be tested if such a test as that for their familial condition were available. In large majorities they answered in the affirmative. In very small minorities they reported for testing when such testing became available. As for "Why?" ... "Why?" If there's nothing that can be done about it ... or the interpretation of the data can be so broad as to be meaningless (such as in susceptibility genes or the really rare recessive genes postulated above) why do it? Look, this stuff is complicated enough as it is for those who are immersed in it. A genetic cousellor may help a family along the way ... but that's not necessarily the answer. It's difficult to get people to understand a picture in subtle tones of grey when their frame of reference is largely black and white. Some of the best educated people I know, who have little or no experience in the sciences, can just get to a basic understanding of genetics ... and this is without throwing them any curve balls. The more detail you add, the more it will just serve to confuse them. The more you'll tell them, the more they'll want to do something about something nothing can be done about. Which brings me to the point that we can't now, or for the foreseeable future, do a doggone thing about any of these conditions. Why have there never been any broad-based viral diagnostics on the market? Because we've never had any specific viral therapeutics ... period. Even tests for viral hepatitis B or C are there primarily for screening and prevention ... not therapeutics. Diagnostics follow therapeutics ... So what about multiplex genetic screening? I'm not against responsibly-used genetic testing. But for its use to be responsible, it's got to end in some positive result for the individual being tested. Just to have genetic information on a person for what is, essentially, just to have the information is ridiculous. Frankly, I think multiplex genetic screening, as it is presented today, is just a nice song and dance that people do to get venture capitalists and other investors to pony up tons of cash so some people can live very nice lives ... and then the concept will later come crashing down around their ears ... or around somebody's ears. The inherent promise is that "Someday we'll be able to do something about all of this." Yeah! And maybe someday frogs will fly, but the number of steps and stages that need to be traversed before we'll be able to "do something about all of this" and frogs can fly is probably about the same .. and so is the complexity. Multiplex genetic testing is selling "razor sharp" results in a world of fog. As such, I think it can be used more for ill than for good. Dr. Ken Krul ***************************************************************************** ****** 3. From: Paulo Freitas Tavares <pftavares@TELEPAC.PT> > >From: "E. ALLEN SMITH" <EALLENSMITH@MBCL.RUTGERS.EDU> > > > It is useful for sperm banks to screen their prospective >donors for alleles that may cause disease in their descendents. >This usage would be useful regarding both carrier status and >alleles of which the phenotypic expression does not clearly appear >at the donor's age (i.e., Alzheimer's). Given the probable >commonness of carrier status, it may be most useful also to screen >prospective clients to inform them whose sperm it would be >inadvisable for them to use. This argument is strengthened by that >it is better to know about possible carrier status due to a >detectable allele than due to a currently undetectable one. The >screening out of donors with alleles with incomplete or complete >dominance and delayed negative effects is an obvious benefit. This argument seems at first sight both moral and scientific correct, however, it isn't either. We all know that many disease genes bring beneficts and survival advantage when carried in heterozigoty. That's the case of the Hemoglobin S gene and Malaria resistance. That seems to be the case of some Diabetes gene and food deprivation resistance. We had million years for nature to select good and harmful genes. If some genes give us trouble nowadays there was surely a good reason for them not to have been eliminated by natural selection. I am not a geneticist but an hemato-oncologist. I am both aware of my own ignorance on genetics and of the fact that my job is actively fighting against natural selection and am very proud of it. I do however have a profound respect for nature and its ways of doing things over time. Can someone today say for sure that Alzheimer's or some other disease genes (alone or in combination) don't give for example AIDS resistance? And what about future mankind plagues or climatic changes? I think that it's too early to begin purging our "genome bank" based on our so poor actual knowledge. That does not mean that I am against early abortion of sure cases of serious diseases diagnosed by genetic techniques. I just don't agree on sistematic elimination of potential healthy carriers based on today's classification of good and bad genes. Paulo Tavares, MD ***************************************************************************** **************** "