From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!bcm!cs.utexas.edu!wupost!usc!jarthur!ucivax!orion.oac.uci.edu!unogate!mvb.saic.com!ucsd!celit!cooley From: cooley@fps.com (Jud Cooley) Newsgroups: bionet.molbio.ageing Subject: Re: ageing rates in different species Message-ID: <19606@celit.fps.com> Date: 5 Aug 91 18:13:26 GMT References: <176612@tiger.oxy.edu> <1793@nih-csl.nih.gov> <1991Jul30.193639.12707@mailer.cc.fsu.edu> Sender: daemon@fps.com Organization: FPS Computing Inc., San Diego CA, USA Lines: 19 The recent issue of Scientific American (August, 1991), which has a good article on "Telomeres". Telomeres are the DNA sequences at the end of the double helix. In humans, this sequence is TTAGGG repeated some large number of times. It is on the end of ALL human chromosomes, and on the end of the chromosomes of ALL species studied (appr 100 vertebrate species that have not had a common ancestor for over 400 million years). It has also been noted that cellular DNA replication often "truncates" the DNA molecule. My reference is the article itself, and a report in "Foresight Update No. 10", from the Foresight Institute, which briefly profiles the work of Harley, et al. at McMaster University and Cold Spring Harbor Laboratory (Nature 345:458-460, 31May90) Organisms that do not age have "telomerase" enzymes that "repair" the truncation. Higher organisms have these enzymes as well, but they are only active in the production of reproductive cells. The Foresight Institute article gives an approximation of 180 cell divisions in human somatic cells before the telomeres are exhausted. The speculation, of course, is that this may be the cause of cellular death due to ageing. From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!news.cs.indiana.edu!rutgers!stanford.edu!agate!usenet.ins.cwru.edu!magnus.acs.ohio-state.edu!zaphod.mps.ohio-state.edu!cs.utexas.edu!wupost!uunet!sftwks!bradbury From: bradbury@sftwks.UUCP (Robert Bradbury) Newsgroups: bionet.molbio.ageing,sci.bio,sci.med,sci.econ,talk.philosophy.misc,talk.politics.misc Subject: National health care [was Re: Medical technology and cryonics] Summary: We should adopt a system which provides the greatest overall benefit Keywords: National health care, cryonics, aging, morality, cost-benefit analysis Message-ID: <196@sftwks.UUCP> Date: 4 Jun 92 09:02:04 GMT References: <9205262240.AA01271@rust.zso.dec.com> <1992May27.190122.5638@u.washington.edu> <14856@pitt.UUCP> Followup-To: bionet.molbio.ageing Organization: Softworks Ltd, Seattle, WA Lines: 154 Xref: bionet bionet.molbio.ageing:288 sci.bio:5915 sci.med:27486 sci.econ:9957 talk.philosophy.misc:3975 talk.politics.misc:76344 This discussion started out involving the rights of individuals to spend their money on cryonic preservation and the degree to which limited research funds should be spent on cryobiology. In the bionet.molbio.ageing group there is a consensus (among some of us) that funds should be spent to reduce the overall rate of aging, thereby reducing disease incidence and long term health care costs. This lead to some discussion of the best way to allocate health care resources and a debate over who is entitled to them. This is fundamentally related to the issue of national health care. To enlarge the audience to non-scientists I am cross posting this in the hope that people with other perspectives will contribute. Please delete the first two newsgroups if the discussion strays too far from ageing and its costs. ... entering midstream .... >I wrote: >>The politicians and the medical community need to start >>making it clear to people that if we are going to use "public" monies they >>should be used to provide the greatest benefit to the greatest number of >>people possible. However this in no way should preclude individuals from >>investing/spending their own monies on life preserving/reanimation >>technologies. >> >Gordon Banks replied: >So anyone who is poor and has some rare condition can just go off >in a corner and die, eh? I did not say that. Anyone who is well informed knows that cost effective technologies such as prenatal care for people in inner cities and vaccines are *excellent* uses of public funds. Every dollar spent on prenatal care saves about $3.00 in costs for premature infants. Dollars spent on smoking prevention reduce long term health care costs many times over. These all could be considered providing the "greatest benefit to the greatest number" and would tend to benefit the "poor" more than the "affluent". Rare conditions are a sticky issue. Each and every person probably has defective alleles and I would hate to think that those of us with the worst of them would not receive some medical attention. On the other hand, if you tell me that we can spend $500,000 to keep me alive 10 years and as a result 100,000 children will not be vaccinated or 1000 will not receive prenatal care and as a result a few of them will probably die prematurely, then I have a problem in saving my life at the expense of others. Medical treatments should be subjected to cost-benefit analysis with society deciding exactly how much of their productivity they want to devote to health care (13% of the US GNP and rising) and people knowing up front that their illness cannot be treated cost-effectively then, well, "life is tough". As it is now we are keeping alive large numbers of people who don't even know we are keeping them alive or what it is costing us. This cost is expected to run into the *trillions* in the early part of the next century while the benefit is virtually zero. I challenge all of you who feel that unlimited medical care should be a "right" to explain how you plan to pay for it! >Gordon says: >Thank you, but no thank you. The public doesn't agree with you, fortunately. I submit that if they understood the system and where it is going they would agree with me. National Health Care such as is found in Canada and other countries perform rationing and politically modified cost-benefit tradeoffs but in many cases these "facts" are not clearly explained. The doctor simply says, "This isn't treatable" or "You will have to wait 8 months for treatment" instead of "We cannot afford to treat you." Proposed/enacted changes to the health care systems in Oregon and Vermont seem to indicate that people are discussing and deciding that when funds are limited that 100 of treatment X may be better than 3 of treatment Y. Gerald Phillips wanted to know how old I am. The answer is 35. He also made an extensive case about the productivity of older people and their value to society and how a large amount of medical intervention may necessary to keep some people alive. I agree to a point. I consider productive older individuals who still have their mental capacities at their disposal are a vital national resource. My father is almost 70 and is still teaching. In a time when the world is facing so many potential problems we need people who provide the extensive knowledge and perspective only many years more than mine can offer. I would offer as a counterpoint the elderly couple who live up the street from me who as far as I can determine rarely leave their home and spend their days watching TV. Now, given the relative contributions made to our society by G.P. and the couple I mention, do they deserve the same access to the limited medical resources our society is able to provide? If you want the society to provide you with health care then indicate what you are going to provide to society. Or are you content to be a leech? (Don't flame me on the example, respond to the issue...) This is not a problem which can be resolved by changing from a private insurance based system to a single payer system. That would result in a one time savings which will be consumed in 1-2 years by the increasing numbers of elderly in our society. The real moral issue here is what "right" elderly individuals have to transfer the costs of their health care onto future generations and whether it is just to provide health care for the elderly at the expense of the young. Now, unlike some politicians (and other respondees :)) I will propose an alternative and let you take shots at it. I would argue that it is "morally wrong" to require future individuals to pay for youur choices in life. I would also argue that it is unjust to consume more than your "fair share" of health care. Your fair share would include coverage for those things which can happen equally to all of us (primarily accidents, communicable diseases and genetic defects). These should all be covered under "national health care". Many other diseases (most heart disease, cancer, diabetes) appear to be related to lifestyle decisions (smoking, lack of exercise, poor diet, etc.) because their incidence shows a high correlation with the affluence of the country. For these diseases you would be lumped into a group of people of similar risks (known as assigned risk pools in automobile insurance) and insurance costs would be based on the expected health costs associated with your lifestyle. You and the other individuals within these assigned pools could decide how much coverage you would be willing to pay for. If you could "prove" a genetic cause for these "diseases of affluence" you could receive a reduction in your insurance payments. Companies would be prevented from paying for added insurance costs associated lifestyle risks to allow people to realize the full costs of their "choices" and have an incentive to be more concerned about their personal health. This plan has a number of overall benefits. If national health care has to pay for those health problems which can happen to all of us there would be emphasis on preventing accidents and communicable diseases and finding cures for the most severe genetic diseases. Groups who were assigned to high risk pools would have huge incentives to find cost effective ways of preventing and treating their "illnesses". I could envision groups of people with heart conditions forming and choosing to use less expensive and more effective treatments such as those proposed and proven by Dean Ornish at UCSF instead of the current practices pushed by many cardiologists and drug companies. These groups would be able to command greatly reduced insurance rates. Ultimately the insurance companies could specialize in the effective management of specific pathologies by developing cost effective programs combining patient education with physician specialization which would reduce the costs associated with these diseases. This system would "fair", you are covered for "acts of god" but not for your "addiction" to ice cream, alcohol and TV and you do not get to put your children into debt. Personal responsibility for one's own health and economic benifits (feedback loops) are built into the system. The insurance and medical communities are encouraged to become more cost effective through competition and innovation. If you don't like these ideas then offer some other suggestions as to how you would encourage people to take more responsibility for and actively participate in the care and maintenance of their health. Probably over half of our current health care bill is due to the fact that people have little incentive to adopt behaviors which support their long term health. [This was written last week but news bottlenecks prevented it being posted previously. It may seem out of sequence with of my more recent postings.] -- Robert Bradbury uunet!sftwks!bradbury Death is an imposition on the human race, and no longer acceptable Alan Harrington, The Immortalist (1969) From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!news.cs.indiana.edu!sdd.hp.com!think.com!rpi!usenet.coe.montana.edu!news.u.washington.edu!hardy.u.washington.edu!rbradbur From: rbradbur@hardy.u.washington.edu (Robert Bradbury) Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Summary: Placing limits on health care spending may violate rights. Keywords: health care, wealth, property rights Message-ID: <1992Jun2.094913.11130@u.washington.edu> Date: 2 Jun 92 09:49:13 GMT References: <9206012230.AA26969@rust.zso.dec.com> Sender: news@u.washington.edu (USENET News System) Organization: University of Washington, Seattle Lines: 110 In article <9206012230.AA26969@rust.zso.dec.com> french@RUST.ZSO.DEC.COM writes: >In reply to: Bradbury at sftwks!bradbury@uunet.UU.NET > >> I commented that the wealthy spending money on excessive health care >> might not divert resources from other areas. >Larry replied: > >The point is that shifting a massive amount of resources to the >health care industry will not necessarily improve the quality of >life. Those resources must come from somewhere and, presumably, >the other sectors of the economy serve to improve some facet of the >quality of life. For example, what about the family that raids little >Johny's education fund to pay for grandpa's stay in a nursing home? > You are up against sociological phenomena here. The family could attempt to take care of grandpa at home and avoid the nursing home cost. Some families spend their money to have others take care of grandpa because they are unwilling to do it themselves. Others because they are unable to do it themselves. Now, if the family thinks things through in advance they will set up living wills and determine with grandpa when his quality of life is sufficiently diminished that it should be ended. If that can't be arranged in this country then a family trip to Europe might be required. In any case it shouldn't require dipping into Johnny's college fund to a large degree. (We presume grandpa has a life insurance policy of some kind) Of course problems can arise if one waits too long to make these decisions, but we are talking about how it "should" be setup, are we not? Given what we know about aging process and its potential costs should not every middle-aged child be having these discussions with elderly family members while they are still able to do that? The problem really is that most people do not want to think about death and let it slide until grandpa can't make decisions for himself and then because the family members can't bring themselves to "kill" grandpa (who is already dead) they end up bankrupting themselves or society. >I commented that health care taxes would be unacceptable. >Larry commented: >It would be absurd to tax basic health care - you can buy a lot of good >health care for a reasonable amount of money. What should be taxed is >health care that does not provide good value. This would serve two purposes. >First, it would redirect resources to other areas of the economy that >serve a more important need. And second, it would send a clear message >to the public that not all medical procedures provide an equally good value. > One of the real problems in medicine right now is that we can't figure out what "good value" is. I think I saw a report saying we are already spending $150 million on studies to try and determine what treatments are cost effective. Politicians cannot now enact laws which reflect something which makes correct scientific sense. (Energy spending is in reverse order from what DOE studies show would be the best way to fulfill our energy policy.) Given their record how likely is it they would get the "wasteful treatments" list correct? As others have pointed out, probably all proceedures have a correct use in some cases. How do you vary the tax with the "usefullness" of the proceedure? > >I said: >> You get the money indirectly anyway by taxes on doctors salaries, hospital >> profits, equipment manufacturers profits, etc.) >Larry replied: >Essentially, you are saying that we should let market forces determine >the price of all goods and the problem of resource allocation will take >care of itself. There is a problem with this policy. What happens when those >who control most of the resources have an uncontrollable desire to spend >those resources in a way that is socially irresponsible? Well, that is the system you have now. The elderly are spending their children's future though government borrowings. The reason things are messed up now is that you don't have "real" markets. Your company or the government pay for the insurance of most people who have it and in this kind of system most people are going to milk it for everything they can get. There is no feedback loop in that system, no disincentive for people to consume less as costs go up (because they don't see the costs). If everyone had "basic" coverage for all of the stuff we cannot avoid and then had to pay for insurance based on their expected consumption (just as people who have a history of accidents pay more for auto insurance) the feedback loop should result in decreased consumption due to people becoming more responsible for their health. [Please note that I am *not* saying that we should require people with genetic diseases or pre-existing conditions to pay more.] If you want to tax something, why don't you tax those things which make us unhealthy? Cigarettes are about $4.00 a pack in Canada now, a drink is something like $8.00 in Sweeden and of course if you really want to make a difference tax fat (milk-fat, meat-fat, oils, butter, etc). These taxes would act as very directly to reduce consumption of those things known to result in high health care expenditures. This would be much easier than trying to tax the "wasteful health care expenditures". > >Is it good policy to allow the elderly to squander their money and their >children's money on expensive health care that provides little or no social >benefit? Perhaps you can't stop someone from squandering their money, but >you can and should tax certain health care procedures as luxuries. > Each of us has property rights to our money. If the elderly person wants to spend it on his/her health care they are free to do so. (I've started having my silver/mercury fillings replaced with gold ones as they wear out for health concern/cost effectiveness reasons -- are you going to tell me that I shouldn't be "wasting" my money on this?!?) None of the children's money should be involved. No family member should be obligated to pay for the health care of another family member. If our laws aren't set up that way in some states then they should be changed. Now, at the same time society should adopt a position that we (collectively) should not be mortgaging our children's future to take care of people who need health care now. For people who are stubborn enough to want a natural death no matter what their condition, society should apply *strong* pressure to ensure that they have insurance to cover that. For those people sensible enough to choose a "graceful exit stage left" when their minds or bodies are in hopeless condition, society should adopt social and medical structures which allow that option. From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!phri!cmcl2!yale.edu!qt.cs.utexas.edu!cs.utexas.edu!usc!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing,alt.individualism,sci.econ Subject: Re: Medical technology Message-ID: <1992Jun2.001632.18780@yang.earlham.edu> Date: 2 Jun 92 05:16:31 GMT References: <9205282308.AA18139@rust.zso.dec.com> <1992May31.104031.18646@yang.e arlham.edu> <50167@mentor.cc.purdue.edu> Followup-To: bionet.molbio.ageing Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 26 Xref: bionet bionet.molbio.ageing:286 alt.individualism:11084 sci.econ:9855 In article <50167@mentor.cc.purdue.edu>, hrubin@pop.stat.purdue.edu (Herman Rubi n) writes: >>In article <9205282308.AA18139@rust.zso.dec.com>, french@RUST.ZSO.DEC.COM writ es >>> In reply to <9205282107.AA23251@inet-gw-1.pa.dec.com> by >>> Gerald M. Phillips (Professor Emeritus) >> Let's let the elderly pay for such technology if they can afford >>it. Don't offer the alcoholic a drink; let him decide to use it and pay >>for it. > >>> A good example is my grandfather. We sold the family farm to pay >>> for his medical expenses. And for what? Due to Alzheimers disease, he >>> could not recognize us. He couldn't even recognize himself! Now the >>> farm that I grew up on, the place where my fondest memories came from, >>> is gone and neither I nor my son will ever be able to enjoy it again. >>> How did this improve the quality of life? > > This has nothing to do with technology. There is little which can be done > for Alzheimer's patients now which could not be done at least 50 years ago. > And this 100% income and property tax before public assistance comes in > for medical care is a political problem, and should be treated as one. > We must recognize that all eligibility rules are taxes, and should be > treated as taxes, not as reasonable restrictions on availability. It's not a tax. It's a user fee. Someone is spending money for a service, and we pay for that service if they're too poor to afford it otherwise (or, which I disagree with, they're older than an arbitrary date). -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!mips!swrinde!zaphod.mps.ohio-state.edu!cis.ohio-state.edu!rutgers!psuvax1!psuvm!dgs4 From: DGS4@psuvm.psu.edu Newsgroups: bionet.molbio.ageing,sci.econ Subject: Re: National health care [was Re: Medical technology and cryonics] Message-ID: <92156.075634DGS4@psuvm.psu.edu> Date: 4 Jun 92 11:56:34 GMT References: <9205262240.AA01271@rust.zso.dec.com> <1992May27.190122.5638@u.washington.edu> <14856@pitt.UUCP> <196@sftwks.UUCP> Organization: Penn State University Lines: 109 Xref: bionet bionet.molbio.ageing:290 sci.econ:9964 In article <196@sftwks.UUCP>, bradbury@sftwks.UUCP (Robert Bradbury) says: > > >I submit that if they understood the system and where it is going they >would agree with me. National Health Care such as is found in Canada >and other countries perform rationing and politically modified cost-benefit >tradeoffs but in many cases these "facts" are not clearly explained. >The doctor simply says, "This isn't treatable" or "You will have to >wait 8 months for treatment" instead of "We cannot afford to treat you." >Proposed/enacted changes to the health care systems in Oregon and Vermont >seem to indicate that people are discussing and deciding that when funds >are limited that 100 of treatment X may be better than 3 of treatment Y. One of the problems with the cost-benefit approach is that it is not technically possible to count the benefits very accurately. That's why Oregon only used it as a guide and focused on a political, democratic decision to determine how they would pay for poor peoples' health care. A second problem is that, in fact, if you use cost-benefit analysis you may find that people place an extraordinarily high value on those final days of life. It makes economic sense. If you only have 10 days to live, a medical treatment that extends your life by 1 or 2 days can be very valuable to you. Thus, there's no guarantee that your cost- benefit approach would reduce the use of high-tech interventions that only extend life marginally. >Now, unlike some politicians (and other respondees :)) I will propose an >alternative and let you take shots at it. I would argue that it is >"morally wrong" to require future individuals to pay for youur choices in >life. I would also argue that it is unjust to consume more than your "fair >share" of health care. Your fair share would include coverage for >those things which can happen equally to all of us (primarily accidents, >communicable diseases and genetic defects). These should all be covered >under "national health care". Many other diseases (most heart disease, >cancer, diabetes) appear to be related to lifestyle decisions (smoking, >lack of exercise, poor diet, etc.) because their incidence shows a high >correlation with the affluence of the country. For these diseases you >would be lumped into a group of people of similar risks (known as assigned >risk pools in automobile insurance) and insurance costs would be based >on the expected health costs associated with your lifestyle. You and >the other individuals within these assigned pools could decide how much >coverage you would be willing to pay for. If you could "prove" a genetic >cause for these "diseases of affluence" you could receive a reduction >in your insurance payments. Companies would be prevented from paying >for added insurance costs associated lifestyle risks to allow people to >realize the full costs of their "choices" and have an incentive to >be more concerned about their personal health. Your proposal is exactly what insurance companies try to do now. There are two main problems with it: 1) It doesn't work. It is impossible to distinguish how much of a person's health problems and health care costs are attributable to behavior, genetics, randomness, provider abuse, etc., etc., etc. We spend about 25% of our total health care dollars trying to determine this now, and we are no closer to figuring it out than 20 years ago, when we spent a far smaller amount. Every dollar we spend trying to find this "health care holy grail" is another dollar we can't spend on medical care, or education, or defense, or anything else we want. 2) To be able to do it, if you could do it, would require an extraordinary invasion of privacy. Obviously, the government or insurer could not trust me to tell the truth about behavior (I would have great incentives to lie), so they would have to keep track of my smoking, drinking, exercise, genetic characteristics, and so on. I really do not want that, and I don't think many other people do. What's the solution? Do what has been proven in other countries and other areas to work. If you want to deter use of unhealthy goods, you use user taxes to raise their relative prices. Look at how smoking has dropped as taxes have increased. User taxes, combined with education (examine the recent drops in smoking among CA youths as a result of a large educational campaign) are a much more humane and effective way of addressing health behavior problems than trying to deter behavior through income mitigated rationing. Don't forget in your model it would be the poor smoker who wouldn't get the lung transplant. the rich smoker could pay for it. If you want to have more equal access to some basic level of health care then you define what that includes through a political process (which might include some of your cost-benefit calcuations) and collect money for it through a progressive income tax. As many nations have shown, you can design your program to fit your nation's particular problems and structure. If you want to control costs, you have global controls on physician and hospital costs, and any other costs that you have included in your NHI system. Within those global controls, those who have the medical expertise, primarily physisicans have to determine how they will allocate the scarce dollars that have been budgeted. The global controls are determined through a national, state, or local political process. This system doesn't give you the perfect health care system, but it works. If we continue wasting our time trying to find the ideal health care system, we'll never get a system that meets basic needs. Economic science tells us that competitive markets can fail, especially when there is uncertainty, information assymmetry, and monolpoly providers. We continue to seek a system that gives people the market signals that identify the costs and beenfits of health behaviors, yet we rest our arguments on the key assumption that those signals are visible. They are not. As Evans and Barer note in a recent article in Health Affairs, once you assume away these distrotions in the competitive environment, "one can use the rhetoric of efficiency to legitimate the competitive ideal." Dennis G. Shea, Penn State <> "I believe that there is social and psychological justification for significant inequalities of incomes and wealth....But it is not necessary....that the game should be played for such high stakes as at present." John Maynard Keynes From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!phri!cmcl2!yale.edu!think.com!mips!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing,alt.individualism Subject: Re: Medical technology Message-ID: <1992Jun2.002621.18782@yang.earlham.edu> Date: 2 Jun 92 05:26:21 GMT References: <9206012230.AA26969@rust.zso.dec.com> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 59 Xref: bionet bionet.molbio.ageing:287 alt.individualism:11085 In article <9206012230.AA26969@rust.zso.dec.com>, french@RUST.ZSO.DEC.COM writes : >> Huh? If the rich are paying for their own medical care why does >> this divert resources from education. Given the structure of >> our society the people that go into medicine and the people that >> go into education are rarely an overlapping set. If anything, >> rich people spending money on medicine will divert money from other >> questionably productive uses for their money (real estate? art?). > > The point is that shifting a massive amount of resources to the > health care industry will not necessarily improve the quality of > life. Those resources must come from somewhere and, presumably, > the other sectors of the economy serve to improve some facet of the > quality of life. For example, what about the family that raids little > Johny's education fund to pay for grandpa's stay in a nursing home? > It isn't the business of anyone else what that family does. It's not anyone else's money. If someone chooses to spend their money on health care, then that isn't anyone else's business except the health care provider's. > >> Putting a sales tax on health care proceedures would be even harder >> to pass than one on food. The public would never sit still for taxes >> on things which are viewed as basic needs. > > It would be absurd to tax basic health care - you can buy a lot of good > health care for a reasonable amount of money. What should be taxed is > health care that does not provide good value. This would serve two purposes. > First, it would redirect resources to other areas of the economy that > serve a more important need. And second, it would send a clear message > to the public that not all medical procedures provide an equally good value. I can see to some degree taxation of non-neccessary health care, just as other services are taxed. In other words, normally sales taxes don't include drugs (nor should they), and some relief from other taxes is found (income taxes, I believe (at least in some states) have a health care deduction). Some medical care may be such (plastic surgery, etc.) that we don't want to make it cheaper by exempting it. > >> You get the money indirectly anyway by taxes on doctors salaries, hospital >> profits, equipment manufacturers profits, etc.) > > Essentially, you are saying that we should let market forces determine > the price of all goods and the problem of resource allocation will take > care of itself. There is a problem with this policy. What happens when those > who control most of the resources have an uncontrollable desire to spend > those resources in a way that is socially irresponsible? It gets spent in a way that you don't like. So? It isn't your money. > > Is it good policy to allow the elderly to squander their money and their > children's money on expensive health care that provides little or no social > benefit? Perhaps you can't stop someone from squandering their money, but > you can and should tax certain health care procedures as luxuries. > I can see this point somewhat, but I would say it isn't a matter of can't stop someone from "squandering" their money. It's a matter of shouldn't be able to stop someone from "squandering" their money, and (if government) shouldn't stop someone from "squandering" their money. Social benefit doesn't matter; it's not society's money. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9206012230.AA26969@rust.zso.dec.com> Date: 1 Jun 92 22:30:21 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 47 In reply to: Bradbury at sftwks!bradbury@uunet.UU.NET > Huh? If the rich are paying for their own medical care why does > this divert resources from education. Given the structure of > our society the people that go into medicine and the people that > go into education are rarely an overlapping set. If anything, > rich people spending money on medicine will divert money from other > questionably productive uses for their money (real estate? art?). The point is that shifting a massive amount of resources to the health care industry will not necessarily improve the quality of life. Those resources must come from somewhere and, presumably, the other sectors of the economy serve to improve some facet of the quality of life. For example, what about the family that raids little Johny's education fund to pay for grandpa's stay in a nursing home? > Putting a sales tax on health care proceedures would be even harder > to pass than one on food. The public would never sit still for taxes > on things which are viewed as basic needs. It would be absurd to tax basic health care - you can buy a lot of good health care for a reasonable amount of money. What should be taxed is health care that does not provide good value. This would serve two purposes. First, it would redirect resources to other areas of the economy that serve a more important need. And second, it would send a clear message to the public that not all medical procedures provide an equally good value. > You get the money indirectly anyway by taxes on doctors salaries, hospital > profits, equipment manufacturers profits, etc.) Essentially, you are saying that we should let market forces determine the price of all goods and the problem of resource allocation will take care of itself. There is a problem with this policy. What happens when those who control most of the resources have an uncontrollable desire to spend those resources in a way that is socially irresponsible? Is it good policy to allow the elderly to squander their money and their children's money on expensive health care that provides little or no social benefit? Perhaps you can't stop someone from squandering their money, but you can and should tax certain health care procedures as luxuries. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!ames!haven.umd.edu!purdue!mentor.cc.purdue.edu!pop.stat.purdue.edu!hrubin From: hrubin@pop.stat.purdue.edu (Herman Rubin) Newsgroups: bionet.molbio.ageing,sci.med Subject: Re: Medical technology Summary: Wrong problem Message-ID: <50167@mentor.cc.purdue.edu> Date: 31 May 92 18:31:58 GMT References: <9205282308.AA18139@rust.zso.dec.com> <1992May31.104031.18646@yang.earlham.edu> Sender: news@mentor.cc.purdue.edu Followup-To: bionet.molbio.ageing Distribution: bionet Organization: Purdue University Statistics Department Lines: 40 Xref: bionet bionet.molbio.ageing:278 sci.med:27191 In article <1992May31.104031.18646@yang.earlham.edu> allens@yang.earlham.edu (Allen Smith) writes: >In article <9205282308.AA18139@rust.zso.dec.com>, french@RUST.ZSO.DEC.COM writes >> In reply to <9205282107.AA23251@inet-gw-1.pa.dec.com> by >> Gerald M. Phillips (Professor Emeritus) >> Is it morale for society to make available an unlimited amount >> of expensive medical technology? This is akin to offering an alcohaulic >> a drink to console his depression. As humans, we crave to care for the >> elderly, but doing so often reduces the overall quality of life for >> everyone involved. Making something available is quite different from either providing it essentially free for everyone or insisting that those with funds pay for it and use it. Yachts are available, and yet I have no desire to spend the money to buy one. I would not use tax money to provide them, nor would I insist that every person with the money to buy one do so. > Let's let the elderly pay for such technology if they can afford >it. Don't offer the alcoholic a drink; let him decide to use it and pay >for it. >> A good example is my grandfather. We sold the family farm to pay >> for his medical expenses. And for what? Due to Alzheimers disease, he >> could not recognize us. He couldn't even recognize himself! Now the >> farm that I grew up on, the place where my fondest memories came from, >> is gone and neither I nor my son will ever be able to enjoy it again. >> How did this improve the quality of life? This has nothing to do with technology. There is little which can be done for Alzheimer's patients now which could not be done at least 50 years ago. And this 100% income and property tax before public assistance comes in for medical care is a political problem, and should be treated as one. We must recognize that all eligibility rules are taxes, and should be treated as taxes, not as reasonable restrictions on availability. -- Herman Rubin, Dept. of Statistics, Purdue Univ., West Lafayette IN47907-1399 Phone: (317)494-6054 hrubin@pop.stat.purdue.edu (Internet, bitnet) {purdue,pur-ee}!pop.stat!hrubin(UUCP) From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!ig!ames!elroy.jpl.nasa.gov!usc!cs.utexas.edu!uunet!pipex!ibmpcug!ibmpcug!george From: george@ibmpcug.co.uk (Michael Veltman) Newsgroups: bionet.molbio.ageing,connect.audit Subject: Re: Life extension now [was Re: Medical technology] Message-ID: <1992Jun01.005939.2128@ibmpcug.co.uk> Date: 1 Jun 92 00:59:39 GMT References: <9205292307.AA24462@genbank.bio.net> <192@sftwks.UUCP> Sender: george@ibmpcug.co.uk (Michael Veltman) Organization: The IBM PC User Group, UK. Lines: 75 Xref: bionet bionet.molbio.ageing:279 X-Disclaimer: The views expressed in this article are those of the author alone and may not represent the views of the IBM PC User Group. In article <192@sftwks.UUCP> bradbury@sftwks.UUCP (Robert Bradbury) writes: >In article <9205292307.AA24462@genbank.bio.net> GMP@PSUVM.PSU.EDU writes: >you need to address the issue within the medical community of, "When and >how may physicians properly assist in the process of dying?". Comfortable >transitions to a state of death probably require the assistance of a doctor. >We came close to allowing "planned death" here in Washington in the last >election, people who view the current situation as an abomination need to >continue these efforts on a state by state basis if necessary. A difficult question... Actually I think your average Vet would know more about comfortable transitions. Serious comment, but I'll probably be flamed for it anyway. >>How many people on respirators ever get weaned off? >>Does a CABG really prolong life? If so, what is the evidence? >>Are anti-depressive drugs really anti-depressive or are they vegetable makers? >>How do you know for sure a person is brain dead? > >People in sci.med are better qualified to answer questions about these >than I am, can the doctors comment? It is true that at the point when >large amounts of "technological intervention" are required to keep you >alive you are living on borrowed time. At that point I would strongly >urge one to start considering cryonics. You have nothing to lose if >it doesn't work and might have another life to gain if it does work. 1. How many people on respirators get weaned off? Depends on the group you define. In terms of routine anaesthetics for surgery, almost everyone. In terms of post arrest, of a non cardiac orign, I think about 5% get out of hospital, although many more than that make it off the respirator. In terms of anything else, the chance is somewhere between these two. 2. Does a CABG really prolong life. Yes, certainly in the right people. Severe disease (Left main or three vessel coronary artery disease sufferers do better to my understanding) 3. Are anti-depressives antidepressives or vegetable makers. If you want to see a vegtable, see a seriously depressed person on no treatment. Honestly, I provide anaesthesia for ECT services and the people are _SERIOUSLY_ depressed when they start, and some of them are better within a week. 4. How do you know if a person is brain dead? That is a hard question, and the problems start with what you define as brain dead (although they dont end with a good definiton). Criteria include loss of any response to painful stimulii, fixed unresponsive pupils, absent reflexes (corneal, lash, "doll's eye", gag, carinal) and loss of spontaneous breathing. Usually it requires more than one doctor to make the diagnosis, bearing in mind the cause of coma and ruling out any reversible causes (eg., low body tempreture, anaesthesia). A flat EEG is confiratory but not always necessary. For more detailed information on brain death I would suggest you talk with someone more knowledgeable than me. Yours, Michael -- Michael Veltman | george@ibmpcug.co.uk | email direct, save | | some bandwidth "At a cardiac arrest, the first step is to take your own pulse" Samuel Shem - The House of GOD - From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!bcm!cs.utexas.edu!usc!wupost!tulane!ames!agate!dog.ee.lbl.gov!network.ucsd.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <1992Jun1.021027.18726@yang.earlham.edu> Date: 1 Jun 92 07:10:27 GMT References: <9205311713.AA12186@genbank.bio.net> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 18 In article <9205311713.AA12186@genbank.bio.net>, GMP@PSUVM.PSU.EDU writes: > Whoever Allen is --- you will get old! You cannot avoid it! It will > happen to you. You haven't the vaguest notion of what the world will > look to you then, nor do you have any idea what the world looks like > to an Alzheimer's patient. You are obviously young. How about spending > the time between now and when you get as old as I am to learn how to > spell simple words in the English language. I am working to avoid getting old, and I disagree that it isn't possible to avoid. I am quite aware of Alzheimer's, although not (obviously) from the perspective of a patient. I am aware from the perspective of a family member (admittedly, there was a disagreement whether it was Alzheimers or simply a series of mini-strokes, but the ultimate effect was approximately the same). Yes, I am young. That doesn't mean I can't think, reason, and come up with valid concepts. That also doesn't mean that I'm immature enough to engage in spelling flames. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9206011519.AA24765@genbank.bio.net> Date: 1 Jun 92 15:19:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 15 Dear Allen: If you are a physician, spelling is quite important. If your pharmacist cannot distinguish Quinidine from Clonidine or Zantac from Xanax, you are in big malpractice trouble. If you are not a physician, enjoy! I would hate to believe that a license to practice medicine is a license illiteracy. As to "flames," that was not! Language happens to be my profession. I take it seriously and honestly believe its integrity should be respected. GMP@PSUVM Gerald M. Phillips (Professor Emeritus) Speech Communication Pennsylvania State University From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9206011858.AA22253@rust.zso.dec.com> Date: 1 Jun 92 18:58:08 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 42 In reply to: Phillips at GMP@PSUVM.PSU.EDU > How many people on respirators ever get weaned off? > Does a CABG really prolong life? If so, what is the evidence? > Are anti-depressive drugs really anti-depressive or are they vegetable makers? > How do you know for sure a person is brain dead? Regretfully, I am not an expert on gerontology and can not answer your questions. Hopefully, someone else on the newsgroup can answer these questions. > I regard your speculation about gene tampering as science fiction, at the > moment. Science fiction? Yes, and no. Yes, it will a long time before we will be able to engineer better error-correction mechanisms into the human genome. However, the need for doing so has important implications for the way medicine is practiced today. For example, lets assume that medical procedures were available to fix all possible complications caused by broken genes. Since gene breakage increases exponentally at the rate of X^5 as we age, then the number of medical procedures required to maintain one's health would also increase exponentially with age. Clearly, there exists a point where the life-extension value provided by certain medical procedures is not worth the cost. This begs the question of how will we decide which medical procedures are not worth it. Are current medical procedures a good value? Are the elderly consuming an unreasonable proportion of the countries resources and so on? Hopefully, our politicans and the medical community will be responsible enough to make the choices that must be made. Ultimately, it is in the best self-interest of the medical community to limit itself to avoid the backlash that will occur if things continue on the the current track. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205311713.AA12186@genbank.bio.net> Date: 31 May 92 17:13:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 17 Whoever Allen is --- you will get old! You cannot avoid it! It will happen to you. You haven't the vaguest notion of what the world will look to you then, nor do you have any idea what the world looks like to an Alzheimer's patient. You are obviously young. How about spending the time between now and when you get as old as I am to learn how to spell simple words in the English language. Yes, a great many people oppose usenets, largely because it features such inane discussions as this one. I am sorry I started it. I will withdraw, tail between my legs, and caress my mutual funds and wish all you young folks do as well. GMP@PSUVM Gerald M. Phillips (Professor Emeritus) Speech Communication Pennsylvania State University From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!bcm!cs.utexas.edu!uunet!sftwks!bradbury From: bradbury@sftwks.UUCP (Robert Bradbury) Newsgroups: sci.bio,bionet.molbio.ageing Subject: Longevity in vertebrates and other species Summary: longevity tables for various species Keywords: maximum longevity Message-ID: <193@sftwks.UUCP> Date: 31 May 92 21:20:31 GMT References: <1992May28.150102@aifh.ed.ac.uk> Followup-To: sci.bio Organization: Softworks Ltd, Seattle, WA Lines: 46 Xref: bionet sci.bio:5825 bionet.molbio.ageing:280 In article <1992May28.150102@aifh.ed.ac.uk> bridget@aifh.ed.ac.uk (Bridget Hallam) writes: > >I want to know the vertebrate species with maximum and >minimum expected lifespans, for writing up a project about >robots. Can anyone out there help? I'm not sure there is a concept of "minimum expected lifespan". The maximum expected lifespans for a variety of species are: species tmax, years Plants Bristlecone pine > 5,000 Conifers and deciduous trees 300-1,500 Bamboo (Phyllostachys) <= 120 Century plant (Agave) > 100 Puya raimondii 150 Invertebrates Lobster > 50-100 Quahog > 200 Vertebrates Sturgeon (Acipenser fulvescens) 152 Tortoise > 150 Rockfish > 120 Homo sapiens > 110 Dogfish 70 Elephant > 60 Pilot whales > 50 Rinosceros unicornis > 50 Hippopotamous amphibius > 45 Chimpanzee (Pan troglodytes) > 40 Ringed seal (Phoca hispida) 35 Eels (Anguilla) 10-15 Eels (Anguilla, spawning prevented) 60-80 There are many more. The definitive reference on this is: Longevity, Senescence and the Genome (1990) by Caleb E Finch. It is an amazing book with 680 pages of text and 160 pages of bibliography. Well worth reading for anyone interested in the evolution of ageing. -- Robert Bradbury uunet!sftwks!bradbury Death is an imposition on the human race, and no longer acceptable Alan Harrington, The Immortalist (1969) From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205292203.AA03905@rust.zso.dec.com> Date: 29 May 92 22:03:02 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 53 In reply to article <9205290120.AA10093@inet-gw-1.pa.dec.com> by GERALD M. PHILLIPS > I have three vessel inoperable heart disease. I was given a year to live > in 1984. I have had no operations. I do take about 9 different drugs, > half to counteract the side effects of the other half. I am functional > and since my death sentence, I have published seven books and 25 articles > ... Clearly, your life has been very productive and, hopefully, you will continue to be so for many years to come. However, you are the exception to the rule. For each extraordinary person, like you, there are many non-productive elderly people who require a great deal of expensive medical care. In the not too distant future, we will face the prospect of being able to keep such elderly people alive and kickiing for as long as we are willing to pay for the health care. Yet the cost of health care is now at the point where any large increase will signifigantly lower the quality of life for the general public. The problem runs deeper than limiting the amount of public funds spent on health care. For example, if the rich have unlimited access to any medical technology they are willing to pay for, then a great deal of resources will be diverted away from areas such as education and so on. Furthermore, we are all subject to the survival instinct and few of us are capable of acting in the best public interest when it involves a matter of life and death. The best solution that I can envision is to limit public funds spent on health care to a fixed percentage of GNP and to heavily tax health care procedures that add little value to the quality of life for the general public. > I urge those of you who are looking to science for the fountain of > youth to consider the despair of uselessness and make sure you have > room for the old people you are saving. The foutain of youth, that I hope for, would greatly extend the robust period of our lives and shorten the length of time that we are enfeebled. If such technology were available, one would have to endure the feelings of despair and uselessness that traditionally accompany old age for a relatively short period of time. I believe that the path to such a foutain of youth lies in making our DNA more durable by introducing error correction mechanisms into our genome. The catch is that it is a far more difficult to run the genetic clock backwards than it is to stop it. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Ageing, Genetics and Population Message-ID: <9205292220.AA04141@rust.zso.dec.com> Date: 29 May 92 22:20:23 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 22 > How do we handle population problems ( like the one we > will confront) when the birth rate is high and death > rate is low? We currently handle this problem by allowing the elderly to gradually become enfeebled, and then go through the hell of dying from cancer, Alzheimers, or any number of other diseases that accompany old age. I'd prefer to spend my entire life in a vigorous, robust state and then, when my time came, end it by taking a pill and going into the good night as was done in "Soylent Green." Of course, this begs the question of how you are going to get all those people to ignore their survival instinct and peacefully check out of this world at the appropriate time. Whatever the solution is, I think that it will be better than what is done today. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!uwm.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing Subject: Re: Ageing, Genetics and Population Message-ID: <1992May31.104437.18647@yang.earlham.edu> Date: 31 May 92 15:44:37 GMT References: <9205290118.AA13421@genbank.bio.net> <36147@darkstar.ucsc.edu> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 24 In article <36147@darkstar.ucsc.edu>, stephen@orchid.UCSC.EDU writes: > I find it odd that we strive so hard to see if we can > continue life indefinitely ( or at least a lot longer > than 100 years ). > > How do we handle population problems ( like the one we > will confront) when the birth rate is high and death > rate is low? Given that such medical technology is mainly available in developed countries, it's probable that these will not result in overpopulation. If they're exported through government "charity" to underdeveloped nations without adequate birth control, then there will certainly be problems. > > What if birth rate drops or goes negative and the death > rate drops towards zero? What about the gene pool and > the reduction of mixing? As far as I can tell, the most probable means of significant life-extension will involve applied molecular genetics. Given that, the gene pool isn't as much of a concern, especially if germ line gene therapy is allowed (as it should be). -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!ames!sun-barr!cs.utexas.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing,sci.med Subject: Re: Medical technology Message-ID: <1992May31.104654.18648@yang.earlham.edu> Date: 31 May 92 15:46:54 GMT References: <9205292203.AA03905@rust.zso.dec.com> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 23 Xref: bionet bionet.molbio.ageing:275 sci.med:27185 In article <9205292203.AA03905@rust.zso.dec.com>, french@RUST.ZSO.DEC.COM writes : > In reply to article <9205290120.AA10093@inet-gw-1.pa.dec.com> by > GERALD M. PHILLIPS > > In the not too distant future, we will face the prospect of being able > to keep such elderly people alive and kickiing for as long as we are > willing to pay for the health care. Yet the cost of health care is > now at the point where any large increase will signifigantly lower the > quality of life for the general public. > > The problem runs deeper than limiting the amount of public funds > spent on health care. For example, if the rich have unlimited > access to any medical technology they are willing to pay for, then > a great deal of resources will be diverted away from areas such > as education and so on. Furthermore, we are all subject to the > survival instinct and few of us are capable of acting in the best > public interest when it involves a matter of life and death. People are going to spend money on things that aren't productive. For instance, I suspect most people would regard USENET as an unproductive waste of time, money, etc. But that doesn't mean that they should be able to restrict or ban USENET. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!ames!sun-barr!cs.utexas.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing,sci.med Subject: Re: Medical technology Message-ID: <1992May31.104031.18646@yang.earlham.edu> Date: 31 May 92 15:40:31 GMT References: <9205282308.AA18139@rust.zso.dec.com> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 46 Xref: bionet bionet.molbio.ageing:274 sci.med:27184 In article <9205282308.AA18139@rust.zso.dec.com>, french@RUST.ZSO.DEC.COM writes : > In reply to <9205282107.AA23251@inet-gw-1.pa.dec.com> by > Gerald M. Phillips (Professor Emeritus) > > Is it morale for society to make available an unlimited amount > of expensive medical technology? This is akin to offering an alcohaulic > a drink to console his depression. As humans, we crave to care for the > elderly, but doing so often reduces the overall quality of life for > everyone involved. Let's let the elderly pay for such technology if they can afford it. Don't offer the alcoholic a drink; let him decide to use it and pay for it. > > A good example is my grandfather. We sold the family farm to pay > for his medical expenses. And for what? Due to Alzheimers disease, he > could not recognize us. He couldn't even recognize himself! Now the > farm that I grew up on, the place where my fondest memories came from, > is gone and neither I nor my son will ever be able to enjoy it again. > How did this improve the quality of life? > > I regret that the expensive medical technology and health care that > kept my grandfather alive in an enfeebled state for a few extra years > was available. I'm sure that my grandfather would have agreed if only > he could have forseen the suffering that my family would experience. Definitely, the right to die and living wills should be more achnowledged. But that doesn't mean that a family shouldn't be able to make the decision to pay for further medical treatment, unless the person had said beforehand that they didn't want such treatment. > > >> As a retiree, I fear the world looks very different to me than it does >> to them. > > I'd like to hear what the world looks like from your perspective. Should > the elderly have unlimited access to health care even if the costs are > increasing exponentially? Should there be a cut off age? > > What would the ideal health care system for the elderly be like? > Let them pay for it. If they're too poor, and are sick through no fault of their own (not through smoking, etc.), then government payments may be appropriate- and such payments may be limited by what is appropriate, such as a cutoff for total dollar amount. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Life extension now [was Re: Medical technology] Message-ID: <9205311445.AA09567@genbank.bio.net> Date: 31 May 92 14:45:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 60 Interesting comments by Mr. Bradbury. I am, also, not a doctor. However, I am a medical writer and work in medical environments. The recommendations Mr. Bradbury makes are quite cogent if, and only if, they are begun around age five. (Try telling them to any pizza eating, hamburger scarfing kid!) The data on angioplasty is quite accurate. I have been watching, with interest, the record on laser and roto-rooter applications of angioplasty. They do not seem to improve on things. CABG is a debatable proposition. With advances in thrombolytic therapy, CABG may well decline in importance in the years ahead. Transplant therapy is showing some real advance. My question still has to do with where to draw the line. I don't like the phrase "quality of life." Life is no bargain: most of the world's work is done by people who don't feel very well. Everyone tries to compensate for physical miseries with psychological gratifications (which accounts for smoking, drinking, and drug use.) As a matter of fact, "productivity of life" would probably lead us to a better set of criteria than "quality of life." Are you thinking of a triage system like that suggested by the former Gov. Love of Colorado or are you thinking of rationing as in Canada or Oregon. Basic research directed at prolonging life has been going on for decades. We must deal now with critical issues of soaring medical costs and the skewed proportion of medical resources utilized by the elderly. Much of this comes through the courtesy of taxpayers (I am, at the moment, paying my for my life sustaining care)> But suppose you had to pay part of my $12,000 medical bill for 1991? How much would you want me to produce to justify your expenditure? If you take a position that all life is sacred, forget I asked -- the question cannot be answered rationally from that position. Remember, when you answer the question you set a precedent for questions about resources for treatment and care of the challenged; saving the lives of preemies, etc. The question was initially posed in the modern world by Adolph Eichmann and Josef Goebbels when they attempted to assess the relative value of Jews and gypsies and decided on the "final solution." You see, this debate about aging takes you (ethically speaking) far beyond medical parameters. So --- back to my question. What do I have to do to earn my $12,000 for payment of my medical bills. (I am ambulatory, working full time, and probably outearning many of you --- right now. But, suppose I got a cardiac myopathy and my insurance wouldn't pay for a mechanical heart. I sell my house, cash my mutual funds, and I am still $50k short. Now how much am I worth). I worked on the P.I. team on an artificial heart project and believe me, this question came up. I also worked, back in 1962 on the Swedish hospital problem where they only had two kidney dialysis machines and decisions had to be made on what patients would live and which would die. Interesting issue, eh. Check my article (G. M. Phillips, "The Kidney Machine Problem." Pfeifer and Jones, HANDBOOK FOR GROUP FACILITATORS. La Jolla, CA: 1974.) for details of the decision making process. In the local nursing home, top quality facility, there is a semi-violent, vituperative, raging and dangerous, but completely non compis mentis male, aged 80 whose children are paying the bills. He takes a lot of care. In the next room there is an 85 year old man, semi blind, deaf, semi-ambulatory, affable, who is able, at times, when he remembers what day it is, to joke with the nurses. He rarely bothers them. But he is almost out of money. When he runs out he must go on Medicaid and this facility does not take Medicaid so he will be chucked out and warehoused where they can find a cubicle. (This was purposely phrased in inflammatory language). Should we preserve the life of an S.O.B. who can pay and take the life of a gentle old man? Can you think of another way to ask the question? From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!ig!ames!elroy.jpl.nasa.gov!swrinde!cs.utexas.edu!uunet!sftwks!bradbury From: bradbury@sftwks.UUCP (Robert Bradbury) Newsgroups: bionet.molbio.ageing,sci.med Subject: Life extension now [was Re: Medical technology] Summary: Methods for extending life now and in the future. Keywords: life extension, planned death, cryonics Message-ID: <192@sftwks.UUCP> Date: 31 May 92 00:23:33 GMT References: <9205292307.AA24462@genbank.bio.net> Followup-To: bionet.molbio.ageing Organization: Softworks Ltd, Seattle, WA Lines: 118 Xref: bionet bionet.molbio.ageing:272 sci.med:27179 In article <9205292307.AA24462@genbank.bio.net> GMP@PSUVM.PSU.EDU writes: > ... comments on the degradation associated with aging and nursing homes ... > This is the sad part of this problem. We live in a society where we either lock up the old people or have caregivers who are literally killing themselves caring for the elderly. These are problems that psychologists and sociologists need to address. The first question one needs to answer is, "When does your quality of life diminish to the point where it makes no sense to continue living?". We as a society should encourage individuals to answer this question for themselves. Then you must ask, "Is there any way to convince religious leaders that suicide is not sinful?". Without addressing this issue you will have large numbers of people in our society who will not choose to die when it might otherwise be appropriate to do so. Then finally, you need to address the issue within the medical community of, "When and how may physicians properly assist in the process of dying?". Comfortable transitions to a state of death probably require the assistance of a doctor. We came close to allowing "planned death" here in Washington in the last election, people who view the current situation as an abomination need to continue these efforts on a state by state basis if necessary. > >I regard your speculation about gene tampering as science fiction, at the >moment. What I want is your knowledge about contemporary methodology. >... >Please tell me the effectiveness of the technological means that are >currently being used to prolong life. > >How many people on respirators ever get weaned off? >Does a CABG really prolong life? If so, what is the evidence? >Are anti-depressive drugs really anti-depressive or are they vegetable makers? >How do you know for sure a person is brain dead? People in sci.med are better qualified to answer questions about these than I am, can the doctors comment? It is true that at the point when large amounts of "technological intervention" are required to keep you alive you are living on borrowed time. At that point I would strongly urge one to start considering cryonics. You have nothing to lose if it doesn't work and might have another life to gain if it does work. (One should make an informed decision regarding the potential of reanimation against leaving one's money to charity, children, etc.) I will offer the following set of proposals for getting the most out of life based on the research I have done. 1) Don't smoke, eat a low fat diet (<20% of calories), exercise, avoid stress Most of the diseases we associate with aging (heart disease, diabetes, high blood pressure, etc.) are primarily due to our lifestyles. [See: The Pritican Program (1979), The Pritican Promise (1983), N Pritican; The Paleolithic Prescription (1988), SB Eaton MD, M Konnder, MD, PhD; The New American Diet System (1991), SL Connor MS, RD, WE Connor MD] 2) Eat plenty of fiber, fruits and veggies (esp. broccoli). Take vitamin supplements, particularly vit. E, C and beta-carotene. Very few people consume enough fiber and only 9% of the population eats the recommended amounts of fruits & veggies which is probably the major cause of cancer in our society after smoking. This is especially important for the elderly who may have problems absorbing nutrients. [See: Formula for Life (1989), E Kronhausen et al; American J. Clincal Nutrition (1991) 53(Sup. 1), many articles] 3) Get vaccinations, for Hepatitis if you travel and Human Papilloma Virus when it becomes available. Viruses are a major cause of cancer world wide. 4) Restrict your calorie intake by 30% while maintaining nutrient intake. This is for the real diehards . It extends life by 20-40% in fish, insects and several small mammal species. The primate study is underway but results will not be available for years and even then may not be conclusive due to the low numbers of animals involved. If it works you will add 10-30 excellent years to your life. [See: The 120 Year Diet (1986) and Maximum Life Span (1983), Roy Walford, MD The Retardation of Aging and Disease by Dietary Restriction (1988), R Weindruch, PhD, R Walford, MD] 5) Make a major effort to reduce factors associated with accidents and cancer. This includes things like: cars with air bags and antilock brakes, fire sensors in your home, carcinogens in your diet/environment (alcohol, secondary smoke, charcoal broiled meats, nitrates, peanut butter, asbestos, formaldehyde, etc.) and radiation exposure from X-rays, radon high altitude flying and fireplace ashes from wood the eastern US). [See: Science 236 (1987), 267-285, several articles; In Search of Safety (1988), JD Graham, LC Green, MJ Roberts] Also, support the reduction of environmental pollution. [See, The Betrayal of Health, (1991), Ch 5,6, JD Beasley, MD] 6) People whom are afflicted with a non-genetic disease, perhaps age related, should redouble their efforts on 1 and 2. [See: Reversing Heart Disease (1991), D Ornish; Immune for Life (1989), A Fox, MD, B Fox] [For those people who dislike some of my recomendations please cite references if possible when responding.] A proper lifestyle should allow you to make it into your 90's as an active vital human being unless you have a bad set of genes. The odds for this vary from 1 in 500 for heart disease to perhaps 1 in 5-10 for cancer to maybe 1 in 3-5 for Alzheimers). Calorie restriction might push you to 110-120. After that the only hopes are genetic therapy or cryonics. I'm not sure if this addresses Gerald's comments. I would only recommend that if I were an elderly person with a "fatal disease of aging" I would spend some time with Medline and find myself the physicians who seem to be getting the best results and go visit them. I would determine if the additional life they could offer me justified the time, pain and expense which would have to be invested and make a decision regarding treatment. I would also get a second and third opinion. Medicine is an inexact science. For example, doctors do 300,000 balloon angioplasties every year. I had a pathologist at the Univ. of Washington who stood in front of a class and said that he personally would never undergo angioplasty because the damage caused by the process is almost guaranteed to cause vessel blockage to reoccur. Why undergo an expensive, potentially life threatening treatment if it only provides a short (1-2 yr) solution?!? (I think people would try other less expensive solutions first if they were paying the bills rather than the insurance companies or the government.) [Note: I am not a doctor and all of the above is not "medical advice".] [Note2: If you are sick see a doctor. If you are well and want to live a long time, educate yourself and stay away from them... :-)] Death is an imposition on the human race, and no longer acceptable Alan Harrington, The Immortalist (1969) There are many virtues to growing old. [Long pause.] I am just trying to think of what they are. Somerset Maugham at eighty Robert Bradbury uunet!sftwks!bradbury From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205292307.AA24462@genbank.bio.net> Date: 29 May 92 23:07:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 27 Meanwhile, Larry, you have to deal with realities. You can't put us on ice floes and float us out to sea. I have visited enough nursing homes to know the degradation that comes along with aging. Just for fun, you are obviously a professional. Give me the up to date assessment of the use of medical technology. How many people on respirators ever get weaned off? Does a CABG really prolong life? If so, what is the evidence? Are anti-depressive drugs really anti-depressive or are they vegetable makers? How do you know for sure a person is brain dead? I regard your speculation about gene tampering as science fiction, at the moment. What I want is your knowledge about contemporary methodology. And let me know if I can quote you, Larry. I am writing a book -- my partner is a dying physician, another man who got a death sentence at age 57. He is now 64 and on the short list for the Nobel. Help us frail old guys out, kid. I'm not kidding. Please tell me the effectiveness of the technological means that are currently being used to prolong life. GERALD M. PHILLIPS GMP at PSUVM "Everyone should get exactly what he/she deserves -- real hard!" From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!usenet.ins.cwru.edu!gatech!pitt!geb From: geb@dsl.pitt.edu (gordon e. banks) Newsgroups: sci.med,bionet.molbio.ageing Subject: Re: Tortoises; was: Re: cryonics & rationalizatio Message-ID: <14881@pitt.UUCP> Date: 28 May 92 16:39:37 GMT References: <14773@pitt.UUCP> <1992May27.222932.18525@yang.earlham.edu> Sender: news@cs.pitt.edu Followup-To: sci.med Organization: Decision Systems Laboratory, Univ. of Pittsburgh, PA. Lines: 16 Xref: bionet sci.med:27004 bionet.molbio.ageing:262 In article <1992May27.222932.18525@yang.earlham.edu> allens@yang.earlham.edu (Allen Smith) writes: >> reach 100 without being quite "absent minded". >> > However, are such changes due to brain cell loss, or psychological >changes? I'd suspect the former. Cell loss and connection loss. It is doubtful that "psychology" plays much of a role at all in this. -- ---------------------------------------------------------------------------- Gordon Banks N3JXP | "Skepticism is the chastity of the intellect, and geb@cadre.dsl.pitt.edu | it is shameful to surrender it too soon." ---------------------------------------------------------------------------- From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!ig!ames!agate!darkstar!orchid.UCSC.EDU!stephen From: stephen@orchid.UCSC.EDU Newsgroups: bionet.molbio.ageing Subject: Ageing, Genetics and Population Message-ID: <36147@darkstar.ucsc.edu> Date: 29 May 92 05:23:38 GMT References: <9205290118.AA13421@genbank.bio.net> Sender: usenet@darkstar.ucsc.edu Distribution: bionet Organization: University of California, Santa Cruz Lines: 31 I find it odd that we strive so hard to see if we can continue life indefinitely ( or at least a lot longer than 100 years ). How do we handle population problems ( like the one we will confront) when the birth rate is high and death rate is low? What if birth rate drops or goes negative and the death rate drops towards zero? What about the gene pool and the reduction of mixing? All of us, to a degree, want to survive forever, or cannot really think of 'dying'- maybe it is not a final as we think. Just some thoughts. ___________________________________________________________ | Stephen Hauskins | | University of California, Santa Cruz | | Departments of Biology and Chemistry | | Santa Cruz, CA 95064 | | | | internet: (1) hauskins@biology.ucsc.edu | | (2) hauskins@chemistry.ucsc.edu | |___________________________________________________________| | Use everything as though it were the only one. - me ;-> | |___________________________________________________________| From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Medical technology Message-ID: <9205281936.AA14446@rust.zso.dec.com> Date: 28 May 92 19:36:51 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 33 > So anyone who is poor and has some rare condition can just go off > in a corner and die, eh? Thank you, but no thank you. The public > doesn't agree with you, fortunately. I doubt if anyone would enjoy sending someone off to a corner to die, but the simple fact of the matter is that the costs of keeping a person alive increase exponentially with age. With new, and often more expensive medical procedures becoming available at an ever increasing rate, how long can we continue giving the best that medical technology has to offer to all those in need? The crux of the problem is that, currently, medicine targets fixing specific things that break rather than changing the rate at which they break. The first apprach works fine if the rate at which things break increases linearly but not if it increases exponentially. It follows that the greatest benifit to mankind will come from changing the shape of the curve by genetically engineering more durable humans. As for whether or not it is humane to deny health care to the elderly, consider this... My grandfather, who suffered from Alzheimers disease, was confined to a nursing home for an extended period of time. To pay for medical expenses we sold our farm that had been in the family for four generations. And my grandfather couldn't even recognize us. So what was accomplished? Did it improve the quality of life? Was it humane? - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205290118.AA13421@genbank.bio.net> Date: 29 May 92 01:18:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 42 Good questions, Mr. French. I have three vessel inoperable heart disease. I was given a year to live in 1984. I have had no operations. I do take about 9 different drugs, half to counteract the side effects of the other half. I am functional and since my death sentence, I have published seven books and 25 articles. I have two more books coming out this year and contracts for books for the next five years. I have run a successful consulting business from my home and am an active speech writer for a major presidential candidate. I also have a living will and am a member of the Hemlock society. I am, frankly, kept alive by the efforts of the pharmaceutical industry. Now, how much do I want? I want enough to keep me going and sentient. I will take my nitro when my chest hurts and I will take a nap when I see double. But I am still outproducing most 35 year olds. Cut me off when I can't function and am not aware that I am not functioning. That's a subtle point, but there are a lot of old people who could be useful within defined parameters, who despair because they are not useful. They are not dying of disease, but of boredom. I call your attention to the Canadian medical system. The heavy duty surgery is rationed and treatment is triaged. I could tolerate that in the U.S. I don't believe in keeping people alive who are brain dead and I suspect hopeless neurological cases and Alzheimer's patients should be allowed their choice of a way out. Remember the film "Soylent Green," the way Edward G. Robinson died, with the movie and Beethoven's Sixth and the pill and he gently went into that good night. I intend to go when it is my turn, but I want the choice. My legatees have durable power of attorney. I urge those of you who are looking to science for the fountain of youth to consider the despair of uselessness and make sure you have room for the old people you are saving. For now, I'll fight you for room. Next year, maybe not. Five years from now, I suspect I'm out of here. Just give me the choice. GERALD M. PHILLIPS GMP at PSUVM "Everyone should get exactly what he/she deserves -- real hard!" From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: A question of philosophy on aging. Message-ID: <9205290034.AA20228@rust.zso.dec.com> Date: 29 May 92 00:34:44 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 10 Are not the elderly just as addicted to expensive medical technology as a heroine addict is addicted to his drug? Likewise, why does society have any more of an obligation to support one habit than it does the other? Perhaps the main distinction is that we all expect to grow old, but few of us expect to become heroine addicts. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205282308.AA18139@rust.zso.dec.com> Date: 28 May 92 23:08:10 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 45 In reply to <9205282107.AA23251@inet-gw-1.pa.dec.com> by Gerald M. Phillips (Professor Emeritus) > Would the writers of these recent pieces please state their ages along > with their I.D. As a retiree, I fear the world looks very different to > me than it does to them. I am 35, and I realize that my previous posts may sound very uncaring and callous with respect to the elderly. Actually, the opposite it true. I have a deep respect for my elderly parents and will do everything within my means to care for them in their old age. Is it morale for society to make available an unlimited amount of expensive medical technology? This is akin to offering an alcohaulic a drink to console his depression. As humans, we crave to care for the elderly, but doing so often reduces the overall quality of life for everyone involved. A good example is my grandfather. We sold the family farm to pay for his medical expenses. And for what? Due to Alzheimers disease, he could not recognize us. He couldn't even recognize himself! Now the farm that I grew up on, the place where my fondest memories came from, is gone and neither I nor my son will ever be able to enjoy it again. How did this improve the quality of life? I regret that the expensive medical technology and health care that kept my grandfather alive in an enfeebled state for a few extra years was available. I'm sure that my grandfather would have agreed if only he could have forseen the suffering that my family would experience. > As a retiree, I fear the world looks very different to me than it does > to them. I'd like to hear what the world looks like from your perspective. Should the elderly have unlimited access to health care even if the costs are increasing exponentially? Should there be a cut off age? What would the ideal health care system for the elderly be like? - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!PSUVM.PSU.EDU!GMP From: GMP@PSUVM.PSU.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Medical technology Message-ID: <9205282105.AA20242@genbank.bio.net> Date: 28 May 92 21:05:00 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 9 Would the writers of these recent pieces please state their ages along with their I.D. As a retiree, I fear the world looks very different to me than it does to them. GMP@PSUVM Gerald M. Phillips (Professor Emeritus) Speech Communication Pennsylvania State University From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!ames!sun-barr!cs.utexas.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: sci.med,bionet.molbio.ageing Subject: Re: Tortoises; was: Re: cryonics & rationalizatio Message-ID: <1992May27.222932.18525@yang.earlham.edu> Date: 28 May 92 03:29:31 GMT References: <1992May18.192342.2084@athena.cs.uga.edu> <1992May21.111046.19673@cs .yale.edu> <14773@pitt.UUCP> Organization: Earlham College, Richmond, Indiana Lines: 18 Xref: bionet sci.med:26968 bionet.molbio.ageing:261 In article <14773@pitt.UUCP>, geb@dsl.pitt.edu (gordon e. banks) writes: > In article pmetzger@shearson.com w rites: > >> >>What strikes me as being the most interesting question is this: is >>there any limit to how long human minds can last? Given that >>truly healthy hundred year olds often show no signs of any mental >>incapacity, I would guess that at the very least the human mind could >>last unmodified for a lot longer than simply a century and a half, but >>unfortunately, we have no data to go on yet. > > The cognitive changes that occur with aging are well documented, > occur in almost everyone, start quite early, and rarely does anyone > reach 100 without being quite "absent minded". > However, are such changes due to brain cell loss, or psychological changes? I'd suspect the former. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!caen!kuhub.cc.ukans.edu!husc-news.harvard.edu!husc10!robison1 From: robison1@husc10.harvard.edu (Keith Robison) Newsgroups: bionet.molbio.ageing Subject: Re: DNA error rates Keywords: DNA error rate, autosomal mutations Message-ID: Date: 19 May 92 17:08:26 GMT References: <9205121706.AA07357@rust.zso.dec.com> <190@sftwks.UUCP> <1992May18.190400.5502@u.washington.edu> Lines: 24 Nntp-Posting-Host: husc10.harvard.edu rbradbur@hardy.u.washington.edu (Robert Bradbury) writes: >Now, looking at the "Parameters of the Human Genome", NE Morton, PNAS 88:7474-6 >we can see the X chromosome is 5.1% of the genome. Assuming that we have >100,000 genes and that one in 10 are "active" in a cell, we must have 500 >active genes on the X chromosome. Going back to my 2.2*10^-5 mutation rate >we get 1 in 100 cells with a broken X-chromosome gene. Two qualifiers: Don't forget, not all genes on the X are unpaired with the Y. A region called the "pseudoautosomal" region contains paired genes. Most of these genes escape X-inactivation. Also, a few genes which do pair are not X-inactivated, so in 1/2 the population those genes have extra copies. Keith Robison Harvard University Program in Biochemistry, Molecular, Cellular, and Developmental Biology robison@ribo.harvard.edu From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!uwm.edu!rpi!gatech!pitt!geb From: geb@dsl.pitt.edu (gordon e. banks) Newsgroups: bionet.molbio.ageing,sci.med Subject: Re: Cryopreservation in life extension [was Re: Tortoises & cryonics] Keywords: cryonics, life extension, genetic engineering Message-ID: <14856@pitt.UUCP> Date: 27 May 92 21:04:44 GMT References: <1992May25.173240.18386@yang.earlham.edu> <9205262240.AA01271@rust.zso.dec.com> <1992May27.190122.5638@u.washington.edu> Sender: news@cs.pitt.edu Followup-To: bionet.molbio.ageing Organization: Decision Systems Laboratory, Univ. of Pittsburgh, PA. Lines: 29 Xref: bionet bionet.molbio.ageing:260 sci.med:26925 In article <1992May27.190122.5638@u.washington.edu> rbradbur@hardy.u.washington.edu (Robert Bradbury) writes: >as good economics). The politicians and the medical community need to start >making it clear to people that if we are going to use "public" monies they >should be used to provide the greatest benifit to the greatest number of >people possible. However this in no way should preclude individuals from >investing/spending their own monies on life preserving/reanimation >technologies. > So anyone who is poor and has some rare condition can just go off in a corner and die, eh? Thank you, but no thank you. The public doesn't agree with you, fortunately. >This makes me think that the current "flaw" in the whole cryonics >preservation game is that of preserving only the quiescent heads. >These non-talking heads :) will have to wait much longer for reanimation >than those who go the whole body route. In Orson Scott Card's "Wyrms", the King kept his best counsellors alive as "talking heads" for up to a millenium. The heads desired nothing more than death, but were, of course, impotent to bring it about. -- ---------------------------------------------------------------------------- Gordon Banks N3JXP | "Skepticism is the chastity of the intellect, and geb@cadre.dsl.pitt.edu | it is shameful to surrender it too soon." ---------------------------------------------------------------------------- From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!caen!uakari.primate.wisc.edu!usenet.coe.montana.edu!news.u.washington.edu!hardy.u.washington.edu!rbradbur From: rbradbur@hardy.u.washington.edu (Robert Bradbury) Newsgroups: sci.med,bionet.molbio.ageing Subject: Cryopreservation in life extension [was Re: Tortoises & cryonics] Summary: Medical techniques to preserve tissue are important to life extension. Keywords: cryonics, life extension, genetic engineering Message-ID: <1992May27.190122.5638@u.washington.edu> Date: 27 May 92 19:01:22 GMT References: <1992May18.192342.2084@athena.cs.uga.edu> <1992May21.111046.1967 3@cs.yale.edu> <1992May25.173240.18386@yang.earlham.edu> <9205262240.AA01271@rust.zso.dec.com> Sender: news@u.washington.edu (USENET News System) Followup-To: bionet.molbio.ageing Organization: University of Washington, Seattle Lines: 89 Xref: bionet sci.med:26918 bionet.molbio.ageing:259 In article <9205262240.AA01271@rust.zso.dec.com> french@RUST.ZSO.DEC.COM writes: > >In article <14813@pitt.UUCP> Gordon Banks writes: >> There is a good chance that within a century or so we will have the >> capabilities of engineering germ cell lines to the point that almost >> any characteristic could be programmed into the individual. It is here >> that the most likely promise of "immortality" lies, not in cryonics. >> By the time the technology to revive these frozen fossils is in place >> (if ever), those who would be doing the reviving may look upon the >> frozen specimens as genetically hopeless and have no desire to resurrect >> such poor specimens. > >Yes, any approach to immortality other than improving the germ line by >introducing improved repair and error correction mechanisms into our >DNA is an exercise in futility! Once this is understood, one begins >to question the current direction of medical research which, at best, >will extend our lives by only a few years. > I agree with Larry that our current medical research (most of it) is misdirected. This is because as he points out it increases our life for only a few years and most importantly increases those years at an ever increasing cost per additional unit of lifetime. This reaches the point (as it did with my grandmother) where the final years of her life cost society (the state of Massachusetts) more than she made in her entire lifetime. Another example would be the recent case, I think it was in Pennsylvania, where a man in his 30's or 40's was about to undergo his 3rd transplant operation (due to failures of the first two). In that case I would bet his health care costs would exceed his future lifetime potential earnings. In my opinion medical research funding and health care coverage should be directed directly towards efforts which will provide the greatest benifit for the lowest cost (invoking the principle of utilitarianism as well as good economics). The politicians and the medical community need to start making it clear to people that if we are going to use "public" monies they should be used to provide the greatest benifit to the greatest number of people possible. However this in no way should preclude individuals from investing/spending their own monies on life preserving/reanimation technologies. Now, one must ask where cryonics fits in. If one accepts that in the long term we will engineer ourselves to have longer lives then one has to agree that the major cause of unplanned death will be accidents. In situations such as this the ability to lower the body temperature to allow extended microsurgery, to pull replacement organs out of a freezer or keep a person in a "suspended state" while a new organ is cloned and grown will play critical roles in preserving life when it would otherwise be impossible. The only way around this is to argue that we can engineer "instantaneous" regrowth of vital organs or we will have replacement "machines" for all bodily functions. I have to believe that the first is unlikely and the second would probably be more expensive and less effective than "real organs". So one can see an important place for cold storage of tissues with varying degrees of "aliveness" in the general scheme of life preservation. This leads us to look at where cryonics funding is today. If people go down to their health sciences library and pull out "Cryobiology" they will find many articles done by "real" scientists researching things like blood and organ preservation and the effects of cold storage on tissue samples preserved for long term research. The HIV labs at major research centers have large numbers of lymphocytes from patients preserved in LN for the purpose of studying disease progression and drug efficacy. To argue that funding for this type of research is irrelevant is to ignore the threat posed by HIV. Research in cryobiology is progressing rapidly considering how little funding there actually is for it. Lymphocytes properly frozen can be preserved for years and thawed out with 70%-80% viability. Obviously these will need to be improved for nerve tissue but numbers in this range are probably fine for young liver, kidney and muscle tissue given that one probably loses 20-30% or more of these cells over a normal lifetime anyway. It is also worth noting that this type of research will end up lowering the costs of blood and organs by allowing their long term storage. So to argue that cryopreservation is "irrelevant" or "futile" is to ignore the current uses for the technology and the pace at which it has advanced over the last 20 years. To argue we shouldn't be doing this type of research one needs to offer alternate forms of research which would provide equivalent benifits at a lower cost. And finally to argue that cryonic preservation of human tissue with its potential reanimation is never going to work is akin to arguing that we will never get 1 billion transistors on a chip. From where I stand (a moderatly well informed programmer/biologist) I would guess freezing organs by 2000 and the 1 billion transistor chip by 2005. The cloning of an individual may not be until 2030+ and the ability to realize brain transplants/nanotechnology 2050-2100(?). This makes me think that the current "flaw" in the whole cryonics preservation game is that of preserving only the quiescent heads. These non-talking heads :) will have to wait much longer for reanimation than those who go the whole body route. From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Re: Tortoises; Message-ID: <9205262240.AA01271@rust.zso.dec.com> Date: 26 May 92 22:40:39 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 20 > There is a good chance that within a century or so we will have the > capabilities of engineering germ cell lines to the point that almost > any characteristic could be programmed into the individual. It is here > that the most likely promise of "immortality" lies, not in cryonics. > By the time the technology to revive these frozen fossils is in place > (if ever), those who would be doing the reviving may look upon the > frozen specimens as genetically hopeless and have no desire to resurrect > such poor specimens. Yes, any approach to immortality other than improving the germ line by introducing improved repair and error correction mechanisms into our DNA is an exercise in futility! Once this is understood, one begins to question the current direction of medical research which, at best, will extend our lives by only a few years. Perhaps the time is ripe for a national effort to tackle the foutain-of- youth problem! - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!yale.edu!qt.cs.utexas.edu!cs.utexas.edu!swrinde!gatech!pitt!geb From: geb@dsl.pitt.edu (gordon e. banks) Newsgroups: sci.med,bionet.molbio.ageing Subject: Re: Tortoises; was: Re: cryonics & rationalizatio Message-ID: <14813@pitt.UUCP> Date: 26 May 92 18:45:55 GMT References: <1992May18.192342.2084@athena.cs.uga.edu> <1992May21.111046.1967 3@cs.yale.edu> <1992May25.173240.18386@yang.earlham.edu> Sender: news@cs.pitt.edu Followup-To: sci.med Organization: Decision Systems Laboratory, Univ. of Pittsburgh, PA. Lines: 26 Xref: bionet sci.med:26851 bionet.molbio.ageing:257 In article <1992May25.173240.18386@yang.earlham.edu> allens@yang.earlham.edu (Allen Smith) writes: >> > Are you counting molecular genetics under the category of >nanotechnology? I wouldn't, and it's what I see as the most helpful >possibility. Admittedly, I'm biased; I'm going into molecular genetics. If you really want to talk about something that has both moral, philosophical and medical implications, and isn't purely science fiction, one should talk about genetic enhancement rather than cryonics. There is a good chance that within a century or so we will have the capabilities of engineering germ cell lines to the point that almost any characteristic could be programmed into the individual. It is here that the most likely promise of "immortality" lies, not in cryonics. By the time the technology to revive these frozen fossils is in place (if ever), those who would be doing the reviving may look upon the frozen specimens as genetically hopeless and have no desire to resurrect such poor specimens. -- ---------------------------------------------------------------------------- Gordon Banks N3JXP | "Skepticism is the chastity of the intellect, and geb@cadre.dsl.pitt.edu | it is shameful to surrender it too soon." ---------------------------------------------------------------------------- From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!cs.utexas.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: sci.med,bionet.molbio.ageing Subject: Re: Tortoises; was: Re: cryonics & rationalizatio Message-ID: <1992May25.173240.18386@yang.earlham.edu> Date: 25 May 92 22:32:40 GMT References: <1992May16.094807.12967@cs.yale.edu> <1992May18.192342.2084@athena.cs.uga.edu> <1992May21.111046.1967 3@cs.yale.edu> Organization: Earlham College, Richmond, Indiana Lines: 17 Xref: bionet sci.med:26812 bionet.molbio.ageing:256 In article <1992May21.111046.19673@cs.yale.edu>, horne-scott@CS.YALE.EDU (Scott Horne) writes: > In article <1992May18.192342.2084@athena.cs.uga.edu>, mcovingt@athena.cs.uga.e du (Michael A. Covington) writes: > pmetzger@shearson.com writes: > < > <>Some tortoises last for at least three to four centuries. > < > > On Easter Island, I think. Anyway, this is irrelevant. The human body, > no matter how well maintained, simply cannot last for much more than one > hundred years (I think someone proposed a cap of 115 years) (barring, > of course, any so-called "nanotechnology"). > Are you counting molecular genetics under the category of nanotechnology? I wouldn't, and it's what I see as the most helpful possibility. Admittedly, I'm biased; I'm going into molecular genetics. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!caen!kuhub.cc.ukans.edu!husc-news.harvard.edu!husc10!robison1 From: robison1@husc10.harvard.edu (Keith Robison) Newsgroups: bionet.molbio.ageing Subject: Re: Speculation on error correction [Re: The fountain of youth.] Keywords: DNA damage Message-ID: Date: 19 May 92 17:11:52 GMT References: <9205111852.AA24470@rust.zso.dec.com> <1992May14.205658.18282@sci.ccny.cuny.edu> <1992May18.192430.7063@u.washington.edu> Lines: 27 Nntp-Posting-Host: husc10.harvard.edu rbradbur@hardy.u.washington.edu (Robert Bradbury) writes: >In article <1992May14.205658.18282@sci.ccny.cuny.edu> dac@sci.ccny.cuny.edu > (David A Cooke) writes: >> I refuse to believe that the prime cause of aging is DNA damage, >>no matter how many times you repeat it, Larry. Until I see some actual >>scientific evidence for that, I think the question of replacing the human >>genome is moot. >Ask and you shall receive.... I must confess to being a complete doubter -- until yesterday morning. I did a MEDLINE search on progeria, a syndrome marked by hyperaccelerated aging. Much to my surprise, several references had found reduced DNA repair activity in cells from progeria paper. Not a smoking gun, but quite suggestive (I didn't save the references -- sorry). Keith Robison Harvard University Program in Biochemistry, Molecular, Cellular, and Developmental Biology robison@ribo.harvard.edu From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!samsung!uakari.primate.wisc.edu!usenet.coe.montana.edu!nntp.uoregon.edu!news.u.washington.edu!hardy.u.washington.edu!rbradbur From: rbradbur@hardy.u.washington.edu (Robert Bradbury) Newsgroups: bionet.molbio.ageing Subject: Re: Speculation on error correction [Re: The fountain of youth.] Summary: DNA damage and ageing Keywords: DNA damage Message-ID: <1992May18.192430.7063@u.washington.edu> Date: 18 May 92 19:24:30 GMT References: <9205111852.AA24470@rust.zso.dec.com> <1992May14.205658.18282@sci.ccny.cuny.edu> Sender: news@u.washington.edu (USENET News System) Organization: University of Washington, Seattle Lines: 30 In article <1992May14.205658.18282@sci.ccny.cuny.edu> dac@sci.ccny.cuny.edu (David A Cooke) writes: > I refuse to believe that the prime cause of aging is DNA damage, >no matter how many times you repeat it, Larry. Until I see some actual >scientific evidence for that, I think the question of replacing the human >genome is moot. Ask and you shall receive.... For all the DNA damage doubters I'd suggest you go read: PNAS 1988 85:6465-7, C Richter, J-W Park, BN Ames Normal oxidative damage to mitochondrial and nuclear DNA is extensive PNAS 1990 87:4533-7, C Fraga, et al (inc BN Ames) Oxidative damage to DNA during aging: 8-Hydroxy-2'-deoxyguanosine in rat organ DNA and urine. These articles document amounts of DNA damage and its age related increase, particularly in organs which show some of the greatest cell loss with aging. I'll give you the 3 main arguments that I find compelling: 1) Ames & co. can measure the damaged DNA bases both in vivo and in the urine of animals and its increase with age. 2) Albertini and others have documeted the base changes resulting from DNA damage in several different genes and the increase with age. 3) Cancer rates increase with age^5 and are known to involve mutations in specific genes. Colon cancer requires mutations within 4 or 5 genes. (Care to figure the probability of mutations in 4 or 5 specific genes only? I cannot convince myself that mutations happen to tumor suppressor genes or oncogenes and leave other genes in pristine condition....) From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!agate!spool.mu.edu!caen!uakari.primate.wisc.edu!usenet.coe.montana.edu!news.u.washington.edu!hardy.u.washington.edu!rbradbur From: rbradbur@hardy.u.washington.edu (Robert Bradbury) Newsgroups: bionet.molbio.ageing Subject: Re: DNA error rates Summary: Autosomal gene vs. sex-linked gene mutation rates. Keywords: DNA error rate, autosomal mutations Message-ID: <1992May18.190400.5502@u.washington.edu> Date: 18 May 92 19:04:00 GMT References: <9205121706.AA07357@rust.zso.dec.com> <190@sftwks.UUCP> Sender: news@u.washington.edu (USENET News System) Organization: University of Washington, Seattle Lines: 47 In article robison1@husc10.harvard.edu (Keith Robison) writes: > >Go back to stat class. If the probability of losing one copy of SOD >is 2*10^-5, then the probability of losing both copies is that value >_SQUARED_, not halved! So your final fraction is 4*10^-10 (a mighty >small number). I don't have the figures in front of me, but 1 in >40 trillion would be much less than 1 cell/person. > Keith is right. Probability is not my strong point, my misadventures at roulette tables due to my inability to comprehend the laws of probability are ample testimony to this fact. :-) At least someone understands the argument enough to correct my errors. However, 4*10^-10 as an two allele SOD knockout rate is about 1 in 2.5 *billion*. I'm fairly sure we have many times that many cells. (Does anyone have a good ref. for the #'s of cells in various organs in the body??) However this does bring to light the glaring difference between the effects of mutations in the X or Y chromosome vs. mutations in the autosomes if we presume that everyone has 2 good copies of all their autosomal genes. Now I suspect that this assumption is very iffy for several reasons. there are a large number of known genetic diseases (4000+ and counting). Some significant portion of these must be recessive diseases meaning we can have lots of carriers in the population. The carrier level of CF is one in 25 whites. I've seen figures for others in the 1 in 100's to 1 in 1000's. (Anyone have a list of carrier frequencies?) If you add all of these up there may be quite a few of our autosomal genes for which we do not have 2 "working" copies. Now, looking at the "Parameters of the Human Genome", NE Morton, PNAS 88:7474-6 we can see the X chromosome is 5.1% of the genome. Assuming that we have 100,000 genes and that one in 10 are "active" in a cell, we must have 500 active genes on the X chromosome. Going back to my 2.2*10^-5 mutation rate we get 1 in 100 cells with a broken X-chromosome gene. Not my initial one broken gene / cell claim but this doesn't include any mutations in autosomal genes for which you don't have two good copies. Aging is closely associated with the loss of cells in many tissue types. While at 80, the loss may only be 20-30% (except as has been pointed out in Parkinsons where it is 80% in the SN) it is a downhill slide with the numbers reaching into the 50%+ range in many tissues around 150. Now given the observed cell death increase and given the observed mutation rates and the mutation rate increase with age, I want someone who doesn't believe that DNA damage is a big factor in aging to explain why. From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!uwm.edu!zaphod.mps.ohio-state.edu!news.acns.nwu.edu!uicvm.uic.edu!yang.earlham.edu!allens From: allens@yang.earlham.edu (Allen Smith) Newsgroups: bionet.molbio.ageing Subject: Re: Speculation on error correction [Re: The fountain of youth.] Message-ID: <1992May16.065030.17939@yang.earlham.edu> Date: 16 May 92 11:50:30 GMT References: <9205111852.AA24470@rust.zso.dec.com> <1992May14.205658.18282@sci.cc ny.cuny.edu> Distribution: bionet Organization: Earlham College, Richmond, Indiana Lines: 54 In article <1992May14.205658.18282@sci.ccny.cuny.edu>, dac@sci.ccny.cuny.edu (Da vid A Cooke) writes: >> >>> Once gene therapy is an off the shelf process you will be able >>> to replace any of your alleles with the "optimal" one for your >>> lifestyle ... >> >>How can broken genes be replaced without also messing up the gene >>expression state of somatic cells? For example, if my insullin >>producing gene is broken, I want to replace it and have the >>new gene turned on in my pancreas but turned off elsewhere. > > Unless a damaged gene is producing a product that is a problem in and > of itself (e.g the mutant hemoglobin produced in people carrying the sickle > cell trait), there is no reason to turn off the old gene. A functional copy > of the gene can be inserted under the appropriate promoter and enhancer, > and it should be expressed normally. If the defective gene product itself > is a problem, antisense therapy might be an option, though granted the > technique will require a lot more development before that can be considered. > As far as targeted expression, there are a number of ways to do > that. In many cases, the promoters and enhancers on the gene will produce > tissue-specific expression, so the transfection need not be selective. > Another approach is the use of engineered viral vectors that are specific > to cell type. A number of natural viruses (most notably AIDS) have this sort > of specificity; with some clever genetic manipulation they could probably > be used for this sort of therapeutic purpose. A third option, already being > used in human experimental trials, exists for certain types of cells, such > as marrow-derived cells. The marrow can be removed, transfected with the > desired DNA, and replaced. The cells subsequently produced from this marrow > will carry the desired trait. A fourth, and perhaps simpler, solution may > involve using foreign cells. A paper published in Science earlier this year > described curing Type I diabetes in rats by implanting foreign insulin- > producing cells in nonbiological cylinders into the rats abdomen. The > cylinders shielded the cells from the host immune responses, but allowedd > them to exchange nutrients and wastes with the blood, as well as release > of insulin. The result was that these rats produced insulin in a normal > regulated manner and were cured of diabetes, all without tissue rejection. Has much work been done with the idea of taking cells out, doing gene therapy on them, then implanting them back in- where they aren't normally? For instance, most if not all the side effects of testosterone and somatotropin, when used for body-building, are due to their travelling places other than the muscles and similarly beneficial spots. An idea I've had was to take cells from other portions of the body, modify them to produce a short-lived form of testosterone or growth hormone (this would be the hardest part, admittedly; but I'd think that in researching artificial forms of testosterone that at least a few short-lived forms would have been come across, although implementing them in a biological system might be difficult), then implant them into the muscles and other areas. If one is simply trying to target the effects of a drug or hormone, then it needn't neccessarily be the cells that normally produce it that get altered. Just alter some cells from the person (avoiding immunological problems) and implant them in the correct location. -Allen From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!s.u-tokyo!ccut!wnoc-tyo-news!sh.wide!sun-barr!cs.utexas.edu!swrinde!mips!think.com!news.bbn.com!hsdndev!husc-news.harvard.edu!husc10!robison1 From: robison1@husc10.harvard.edu (Keith Robison) Newsgroups: bionet.molbio.ageing Subject: Re: DNA error rates Keywords: DNA error rate, degenerate code, superoxide dismutase Message-ID: Date: 16 May 92 16:02:59 GMT References: <9205121706.AA07357@rust.zso.dec.com> <190@sftwks.UUCP> Distribution: bionet Lines: 79 Nntp-Posting-Host: husc10.harvard.edu bradbury@sftwks.UUCP (Robert Bradbury) writes: >In article <9205121706.AA07357@rust.zso.dec.com> french@RUST.ZSO.DEC.COM writes: >>In article <9205071432.AA10616@genbank.bio.net> >>rbradbur@hardy.u.washington.edu (Robert Bradbury) >> >>> >>> This means by the time you hit 80, your mutation frequency is >>> 2.2 x 10^-5 in a single gene. Multiply by 5000 active >>> genes per cell and you have 1 in 10 cells with a broken gene... >>> >>> Hmmmm, so damaging .2% of a gene makes it non-functional. Due to the >>> degenerate code from DNA to proteins and the large portions of proteins >>> which aren't critical to structure/function you can make a case that a >>> large fraction of the DNA for a protein can be damaged without harming the >>> protein. ... >>> >>> If we say that 10x the critical active area is important for >>> general functioning then every cell in the body has a gene suffering a >>> loss of function due to DNA damage! >> >>If the DNA coding sequences really are redundant, wouldn't you divide >>the mutation frequency by 10 instead of multiplying it by 10? If so, >>then by age 80 only 1 in 100 cells would be suffering loss of function >>due to DNA damage. This defect rate appears to be too low to account >>for the effects of aging. >> >I should probably try to be more complete but I worry about the bandwith >problem. Proteins are complex in terms of what is important and what >isn't. Proteins which are enzymes (as opposed to structural components) >have one or more active sites where they do their dirty work. These sites >have a small number (2-10?) of amino acids which are critical to the >catalytic activity of the enzyme. Change one of these and the enzyme >is broken! There are a number of other sites which are involve in the >protein maintaining its shape and in aligning molecules properly for >catalysis to occur, these are perhaps a much larger fraction (10-30%?). >And there may be additional places which are normally unimportant to >the functioning of the protein but if you stick something wrong (large >amino acid replaces small amino acid, hydrophobic replaces hydrophilic, >etc) in that location things are impacted as well. >Now, we are lucky that we have repair processes that keep things from >changing very much. And when they do the redundancy of the code keeps >things from becoming too messed up. If I read my RNA codon->Protein >chart correctly, you can change the 1st, 2nd and 3rd bases of a codon >3.1%, 1.6% and 81% of the time respectively without changing the protein. >So if we were to assume base mutations all occur with equal frequency >(which is untrue) then about 29% of the time a base change does not >affect the protein. >So, to take a real (perhaps extreme) example this time. In CuZn superoxide >dismutase, 38 out of 151 (25%) of the amino acids are conserved across 19 >species (from bacteria to plants and mammals). Such a high conservation >rate would argue that all of the a.a. are critical. If we take the numbers >from my previous article for 4x10^-8 for the mutation rate of the amino >acid responsible for sickle cell anemia, estimate 1 order of magnitude >increase due to age (quibble here if you want) gives you 4x10^-7 times >38 / 2 copies per cell gives a mutation rate in critical amino acids of >SOD at approx. 10^-5 or one in 100,000 cells have broken SOD genes. Go back to stat class. If the probability of losing one copy of SOD is 2*10^-5, then the probability of losing both copies is that value _SQUARED_, not halved! So your final fraction is 4*10^-10 (a mighty small number). I don't have the figures in front of me, but 1 in 40 trillion would be much less than 1 cell/person. >-- >Robert Bradbury uunet!sftwks!bradbury Keith Robison Harvard University Program in Biochemistry, Molecular, Cellular, and Developmental Biology robison@ribo.harvard.edu From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!cs.utexas.edu!uunet!sftwks!bradbury From: bradbury@sftwks.UUCP (Robert Bradbury) Newsgroups: bionet.molbio.ageing Subject: Re: DNA error rates Summary: DNA errors which alter protein function Keywords: DNA error rate, degenerate code, superoxide dismutase Message-ID: <190@sftwks.UUCP> Date: 14 May 92 14:44:14 GMT References: <9205121706.AA07357@rust.zso.dec.com> Distribution: bionet Organization: Softworks Ltd, Seattle, WA Lines: 88 In article <9205121706.AA07357@rust.zso.dec.com> french@RUST.ZSO.DEC.COM writes: >In article <9205071432.AA10616@genbank.bio.net> >rbradbur@hardy.u.washington.edu (Robert Bradbury) > >> >> This means by the time you hit 80, your mutation frequency is >> 2.2 x 10^-5 in a single gene. Multiply by 5000 active >> genes per cell and you have 1 in 10 cells with a broken gene... >> >> Hmmmm, so damaging .2% of a gene makes it non-functional. Due to the >> degenerate code from DNA to proteins and the large portions of proteins >> which aren't critical to structure/function you can make a case that a >> large fraction of the DNA for a protein can be damaged without harming the >> protein. ... >> >> If we say that 10x the critical active area is important for >> general functioning then every cell in the body has a gene suffering a >> loss of function due to DNA damage! > >If the DNA coding sequences really are redundant, wouldn't you divide >the mutation frequency by 10 instead of multiplying it by 10? If so, >then by age 80 only 1 in 100 cells would be suffering loss of function >due to DNA damage. This defect rate appears to be too low to account >for the effects of aging. > I should probably try to be more complete but I worry about the bandwith problem. Proteins are complex in terms of what is important and what isn't. Proteins which are enzymes (as opposed to structural components) have one or more active sites where they do their dirty work. These sites have a small number (2-10?) of amino acids which are critical to the catalytic activity of the enzyme. Change one of these and the enzyme is broken! There are a number of other sites which are involve in the protein maintaining its shape and in aligning molecules properly for catalysis to occur, these are perhaps a much larger fraction (10-30%?). And there may be additional places which are normally unimportant to the functioning of the protein but if you stick something wrong (large amino acid replaces small amino acid, hydrophobic replaces hydrophilic, etc) in that location things are impacted as well. Now, we are lucky that we have repair processes that keep things from changing very much. And when they do the redundancy of the code keeps things from becoming too messed up. If I read my RNA codon->Protein chart correctly, you can change the 1st, 2nd and 3rd bases of a codon 3.1%, 1.6% and 81% of the time respectively without changing the protein. So if we were to assume base mutations all occur with equal frequency (which is untrue) then about 29% of the time a base change does not affect the protein. So, to take a real (perhaps extreme) example this time. In CuZn superoxide dismutase, 38 out of 151 (25%) of the amino acids are conserved across 19 species (from bacteria to plants and mammals). Such a high conservation rate would argue that all of the a.a. are critical. If we take the numbers from my previous article for 4x10^-8 for the mutation rate of the amino acid responsible for sickle cell anemia, estimate 1 order of magnitude increase due to age (quibble here if you want) gives you 4x10^-7 times 38 / 2 copies per cell gives a mutation rate in critical amino acids of SOD at approx. 10^-5 or one in 100,000 cells have broken SOD genes. Well, you say that's not bad but realize that if you break the SOD genes the mutation rate of every other gene in those cells goes up significantly. (my crystal ball says I see cancer in your future.... :-)). Now, given 5,000-10,000 active genes, a higher mutation rate among those that aren't often turned on and allowing for defective alleles that you do not normally see because they are masked by the "normal" allele but that you will see if the "normal" allele is broken and you start to have a good case for mutated genes in every cell. Now, back to Larry's question. The 10x in the original posting was the factor going from .2% of the gene being critical to function (break this and the gene doesn't work) to 2% of the gene being "useful" to function (break this and the enzyme works more slowly). Damaging any of the amino acids involved in useful function impacts the function which is why I multiply by 10. If you correct (roughly) for the degenerate code as I indicate above you need to divide by 3 and then by 2 to correct for those genes for which you have 2 active copies. But then if you use the "critical" region of SOD as typical (25% vs. 2%) then you need to multiply by 10 again so you end up roughly back where you started. I emphasize the back-of-the-envelope nature of these calculations. Someone needs to do some work on how critical various enzymes are to the cell and what fraction of those amino acids are "critical" and what the mutation rate is for those amino acids. Then we could have a complete picture. But as my calculation above shows you can damage a critical gene in a few cells and start them on a very rapid downhill slide which leads to very unpleasant disease consequences. -- Robert Bradbury uunet!sftwks!bradbury From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!rutgers!uwm.edu!cs.utexas.edu!uunet!sftwks!bradbury From: bradbury@sftwks.UUCP (Robert Bradbury) Newsgroups: bionet.molbio.ageing Subject: Gene replacement and DNA repair [was Re: The fountain of youth.] Summary: Methods for replacing genes will be very specific. Keywords: gene therapy, viruses Message-ID: <189@sftwks.UUCP> Date: 14 May 92 13:50:33 GMT References: <9205111852.AA24470@rust.zso.dec.com> Organization: Softworks Ltd, Seattle, WA Lines: 95 In article <9205111852.AA24470@rust.zso.dec.com> french@RUST.ZSO.DEC.COM writes: > >> Once gene therapy is an off the shelf process you will be able >> to replace any of your alleles with the "optimal" one for your >> lifestyle ... > >How can broken genes be replaced without also messing up the gene >expression state of somatic cells? For example, if my insullin >producing gene is broken, I want to replace it and have the >new gene turned on in my pancreas but turned off elsewhere. > The current model on which much gene therapy is based is to take the gene and stick into a retrovirus vector which contains the retrovial packaging sequences but not the retroviral genes themselves. This is usually done in a specially designed cell line. The result is a virus package which will transfer the gene to only those cell types which have certain receptors. The reverse transcriptase from the virus converts the viral RNA to DNA which integrates somewhere in the host DNA. People have in the past been worried about this integration transforming the cells but that doesn't seem to happen at a very high rate. This is great for something like diabetes, you only need a "working" insulin gene with its normal promoters, you don't need to replace the defective insulin gene. It is not good for some tumors where you need to replace a gene which is promoting cell division or Alzheimer's where you may need a substitute for a defective protein. There are several approaches to this. One would be to develop DNA viral vectors packaged with proteins which mediate homologous recombination between the DNA in the viral package and your defective gene. Another would be to add a gene generating anti-sense mRNA to disable the defective gene and then add the defective gene seperately. You avoid much of the regulatory problem by using viral vectors which target only the cell types which are defective and you try as much as one can given our limited knowledge to include promoters/repressors which are only active in those cell types. >In any event, you would probably have to replace all of your genes >periodically (assuming that every cell in the human body contains >a broken gene by age 80). I find it difficult to see how it would >be possible to replace your entire genome without also disrupting >the gene expression state of your somatic cells. > You don't need to replace the entire genome, you only need to replace the specific "active" genes in the cells in which they are important. I envision the point where we will develop "pseudo-artificial mini chromosomes" which contain complete biochemical pathways under common regulatory control which are packaged in such a way so as to be delivered to specific cell types. You don't have to mess with a person's normal DNA, you simply need to add those genes which do the proper thing when detecting specific signals in specific cells. Now, if you favor the disdifferentiation theory of aging (that aging is caused in part or whole because cells lose their differentiation) we are going to have to come up with a way to keep genes which are normally off off. But the anti-sense RNA I mentioned above give you one way to do this, I'm sure that others will be developed as we understand the normal means by which cells turn off genes during development. >Furthermore, I suspect that the easier route to immortality will be >to prevent DNA errors from accumulating by building more sophisticated >error correction machinery into our cells. > Yes, of course, but this doesn't help the people who are alive now and may be in need of "renewed" DNA when they are elderly and the techniques become available to provide this. >Meiosis seems to provide the right model for how we might engineer >such a DNA repair mechanism. The following excerpts on >recombinatorial repair and meiosis from the text "Aging, Sex, and >DNA Repair" are interesting: > ... book excerpts from pgs 255, 259 Yes, there are certainly very active repair process in mitosis during S and G2, during meiosis in gamete production and during early development when metabolic rates are very high. The key thing about mitosis and meiosis is not so much that they have higher DNA repair activity but that they make all of the DNA available for DNA repair to occur which is something that doesn't happen in non-dividing cells where much of the DNA is turned off by being packed into protective structures. There is a distinct difference in the speed with which different species repair "inactive" DNA. Longer lived species seem to be faster at making inactive DNA available to repair proteins. This makes sense if you think of aging as a process whereby DNA damage is occuring to genes which are "normally" off but are sometimes required by a cell. (In aging one thing that consistantly happens is you lose your ability to respond to stress and you take longer to return to homeostasis). It would appear that to have a long lifespan you want to do a better job repairing inactive genes for those times when they are called into action. It doesn't do you much good to turn on a burned out lightbulb! -- Robert Bradbury uunet!sftwks!bradbury From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Speculation on error correction [Re: The fountain of youth.] Message-ID: <9205150034.AA26742@rust.zso.dec.com> Date: 15 May 92 00:34:47 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 23 In article <9205142126.AA06934@genbank.bio.net> > Unless a damaged gene is producing a product that is a problem in and > of itself (e.g the mutant hemoglobin produced in people carrying the sickle > cell trait), there is no reason to turn off the old gene. A functional copy > of the gene can be inserted under the appropriate promoter and enhancer, > and it should be expressed normally. If the defective gene product itself > is a problem, antisense therapy might be an option, though granted the > technique will require a lot more development before that can be considered. Replacing genes one by one, as we age and our genes break, is bound to be a failed strategy. It's like trying to prevent a house made of sand from falling down by replacing each individual grain as it tumbles down. Why not prevent the grains from tumbling down in the first place by adding cement to the sand? However, I have to admit that replacing genes one by one will be immensely profitable and, no doubt, the medical-industrial complex will pursue that line of research. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Speculation on error correction [Re: The fountain of youth.] Message-ID: <9205150033.AA26732@rust.zso.dec.com> Date: 15 May 92 00:33:23 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 15 In article <9205142126.AA06934@genbank.bio.net> dac@sci.ccny.cuny.edu (David A Cooke) > I refuse to believe that the prime cause of aging is DNA damage, > no matter how many times you repeat it, Larry. I too find it difficult to believe that programmed aging is not THE primary mechanism involved in aging. However, a large body of evidence indicates that DNA damage does play a signifigant role in aging. Apparently there are two problems that must be solved before we can reach the foutain of youth. - Larry French From owner-ageing@net.bio.net Sun Sep 27 23:00:00 1992 Path: bionet!RUST.ZSO.DEC.COM!french From: french@RUST.ZSO.DEC.COM Newsgroups: bionet.molbio.ageing Subject: Speculation on error correction [Re: The fountain of youth.] Message-ID: <9205150014.AA26282@rust.zso.dec.com> Date: 15 May 92 00:14:51 GMT Sender: daemon@genbank.bio.net Distribution: bionet Lines: 58 In article <9205142126.AA06934@genbank.bio.net> dac@sci.ccny.cuny.edu (David A Cooke) > As I have posted before, spontaneous abortion provides a very > effective quality-control process that does not require rewriting of > DNA by some magical repair mechanism. First of all, recombinatorial DNA repair is a reasonably well understood mechanism documented in the text "Aging, Sex, and DNA Repair" by Bernstein and Bernstein. It is a fact and not "some magical repair m