Gary Gach (ggg) Fri 28 Nov 08 09:27
(Am curious: ever read Science in an Unfree Society by Feyerabend?) Dr Carl Djerassi once told me that if he'd factored in morality he would never have come up with the Pill. I've always been curious how scientific research considers itself morally neutral. Thank you for giving me more grist for the mill, to contemplate.
Gary Greenberg (gberg) Fri 28 Nov 08 09:30
>Dr Carl Djerassi once told me that if he'd factored in morality he >would never have come up with the Pill. Well, I for one am glad he didn't factor in morality.
Steve Silberman (digaman) Fri 28 Nov 08 09:57
Gary, even if you don't think that Ted Kaczynski is schizophrenic, do you believe that schizophrenia can be a medically helpful diagnosis (and not just "helpful" to the preconceptions of the doctors)? What about depression?
Gary Greenberg (gberg) Fri 28 Nov 08 11:04
Yes for both. Someday I think we will find that a certain number of the cases of people who exhibit the symptoms of schizophrenia will turn out to have a common brain chemistry. And I think it is possible that some day drugs or other interventions will be precise enough to target that brain chemistry. For now, we're stuck with major tranquilizers (haldol, thorazine, etc.) and atypical antipsychotics (zyprexa, abilify), whose main effects are pretty imprecise and whose side effects are horrible. Same with depression. There's a pretty clear history, maybe 2500 years or so, of a disease that makes people delusionally guilty, self-loathing, apathetic, and sorrowful to the point that they cannot function. I wouldn't be surprised if this had a relatively discrete biochemistry, one that could be intervened in. (There are cases, byu the way, of people getting deep brain stiumlation for Parkinson's disease who, as soon as the switch is thrown and current flows into the target neuron, become profoundly depressed. So clearly depression can be turned on independent of any psychological events--unless you include having sopmeone drill a hole in your head an dinsert an electrode and then zap you as a psychological event.) So far, the best treatment for that condition, the one that succeeds in the most cases, is shock therapy. But no doubt as the biochemistry is uncovered, more treatments will emerge. But in the case of depression perhaps more than in schizophrenia, the pool of people whose problem proceeds from that characteristic brain chemistry will, I think, be very small--certianly too small to generate a $15 billion a year industry, and to make good the WHO and CDC prevalence projections, which claim that worldwide 20 percent of us will be depressed at some point. With schizophrenia, fewer are afflicted, but there are many people whose symptoms add up on paper to schizophrenia, but who are lacking in some quality, perhaps hard to specify, that makes the diagnosis stick. Obviously, what is missing is the kind of biochemical assay that we have come to expect as the definition of a disease. Without that, you just have clusters of symptoms that comprise the disease, and a disease that is constituted by its symptoms--a logical and nosological circle that should make us all deeploy suspicious of psychiatric diagnosis. None of this means that people who don't have that biochemical signature, who don't qualify for the much more narrowly defined diseases I think would make for a better nosology, shouldn't get treated, with drugs even. I don't think you have to be sick to take drugs that make you feel better, or otherwise alter your consciousness. I do it all the time, and I don't think I'm sick. IN fact, I think you're much better off NOT thinking you have a disease. It opens u[p all sorts of avenues that are closed off if you're just a patient.;
Steve Silberman (digaman) Fri 28 Nov 08 11:26
Thanks for a great answer, Gary. Another provocative issue that you bring up in the book -- which is, I suppose about *nothing but* provocative issues <smile> -- is the leveraging and misuse of the placebo effect in controlled studies by Big Pharma during drug development. You tell the darkly hilarious story of being a relentlessly aware subject in a study of fish oil and depression; I couldn't help but hear an internal chorus of "oy vey!" on both sides of those interactions. And I loved the punch line. I'd be curious to hear a detailed rundown of how the placebo effect is misused in studies, and how that affects us as "end users" of these pharmaceutical products. (I confess that my curosity here is partly self-serving -- we can talk offline about that. Reading those parts of your book were a "plate o'shrimp" experience for me.) What changes should be instituted so that millions of people don't end spending billions of dollars on drugs that are no more effective -- or less! -- than placebo?
Gary Greenberg (gberg) Fri 28 Nov 08 11:44
Well, for starters, the FDA could make drug companies test drugs against each other instead of against placebo and then demand that new drugs be better than old drugs to justify bringing them to market. That way, the hazards of a new drug--not only the unknown side effects that emerge in the first years of widespread use (and, by the way, you probably sbhouldn't buy a new drug any more eagerly than a new model of auto or a new operating system; it takes some time to work out the bugs, and the first post-approval users are the beta testers), but also the inevitable ramping up of the marketing effort, the attempt to persuade people that htey are sick, the mongering of disease. You might still want to have a placebo group, but with the established antidepressants you don't really need to. THere's so much data now, and it's so easy to aggregate that you can do an easy meta-analysis that shows that antidepressants on average improve people's depression by 10 points on the test used universall in clinical trials. Placebos improve it by 8. Which doesn't only mean that placebos are almost as good as the drugs. It also means that the placebo effect is 80 percent of the drug effect. In other words, eighty percent of what the drug does is due to placebo effects. And it could be more: because of the side effects of the drugs, it's possible that the people getting them have an amplified response, based on their knowledge of what hte drug is supposed to do and their certainty that they are getting the drug. Now if you really wanted to disentangle this further, you';d have four groups. Group 1 would get the drug and be told they were getting the drug. Group 2 would get the drug and be told they're getting placebo. Group 3 would get placebo but told drug, and Group 4 would get placebo and told placebo. Taking the expectancy out of the trial should clarify exactly how much of what is going on is the chemical and how much is the pill. The drug companies don;t want to do this, for the obvious reason.
Gary Greenberg (gberg) Fri 28 Nov 08 11:52
About eight years ago, a UCLA doctor was trying to figure out of he could predict response to particular antidepressants by using quantitative EEG. The idea was that if he could find some kind of brain wave pattern that correlated to a good response to, say, Prozac, and another that went to Paxil, then doctors wouldn't be stuck with trial and error. HE didn't find any QEEG differences between drugs. But he did find a consistent pattern among placebo responders. He published a paper that claimed, more or less, that he could predict who would be a strong placebo responder in clinical trials. The drug companies were soon all over him like white on rice. Why?: Because they would like nothing more than to eliminate placebo responders from their studies. The idea is that some of us are more prone to the effect than others, and it's the strongest responders who realluy make the drugs look bad. So if you get rid of them, your numbers get better. It's totally cooking the books, in other words. But they already do it. MOst clinical trials start with a washout period. Everyone gets placebo, but no one knows that. After a couple of weeks, if you respond strongly to the placebo, you get washed out of hte study. THe QEEG work would only make this strategy easier to implement. Because every clinical trial requires a placebo group, the placebo is the most studied remedy ever. But no one seems to want to actually study it, so all that data has yielded very little knowledge.
Gary Greenberg (gberg) Fri 28 Nov 08 11:58
But the most interesting use of the placebo effect, and the one the drug companies really won't acknowledge, is the way that their advertisign creates the expectation of how a drug is going to make you feel. The direct to consumer advertising doesn't just promise relief, it also tells you what kind of relief you will get. When I was in my clinical trial, they kept telling me I was getting better. And all the time they were doing that, they were asking me these questions--about my sleep and myappetite and my sex life and my self-criticism--that, whatever their manifest intent, served to alert me to what I should be looking for, what improvement actually consisted of. I don't think they think this is mobilizing the placebo effect, but it undoubtedly is.
Sharon Lynne Fisher (slf) Fri 28 Nov 08 12:40
Gary Greenberg (gberg) Fri 28 Nov 08 12:45
I totally agree.
Steve Silberman (digaman) Fri 28 Nov 08 12:46
Gary Greenberg (gberg) Fri 28 Nov 08 12:53
Don't be. It's mnot your fault.
Sharon Lynne Fisher (slf) Fri 28 Nov 08 13:42
http://en.wikipedia.org/wiki/Hawthorne_effect Short version -- people would be likely to show improvement anyway just because people are paying attention to them.
Hugh Watkins (hughw1936uk) Fri 28 Nov 08 15:53
I think it is more because the healthy human brain is self correcting as a matter as survival for example the guru effect in an ashram in other cultures as a substitute for a mental hospital
Steve Silberman (digaman) Fri 28 Nov 08 16:46
Very interesting, Sharon, thanks.
Steve Silberman (digaman) Fri 28 Nov 08 17:45
Gary, how have your considerations of brain death and the efforts of the people in your book to attain cryo-enabled immortality altered your feelings about your own mortality, if at all?
Steve Silberman (digaman) Fri 28 Nov 08 18:16
Four years ago, my dad had a heart attack in a union meeting. The EMTs arrived 20 minutes later and then revived him. The 10 days that followed were... well, there are really no words. One of the climaxes of the psychedelically horrible ordeal was when my father "woke up" out of his coma and began convulsing and grimacing, as if he was in the worst pain imaginable -- he looked like he was trying to climb out of his body -- and I told the nurse that he should be given morphine. The next morning, he was clearly in no better shape, and when I found the nurse again, she told me, "Your father does not have enough brain tissue to feel pain." That's the kind of moment when the ideas you write about in your book become realer than real. My father's kidneys were also damaged, and because our little family left me in the position to decide what to do at that point, I declined dialysis, and my father died a few days after. I can't imagine what families go through when their loved one is in the condition my father was in and don't have the "easy way out" of kidney failure. It was a very strange moment indeed when I was standing with my mother beside the warm body of my dad at 1am and I was suddenly called out of the room for a phone call. A kind-sounding guy on the other end of the line asked me if we would consider organ donation. Until I read your book, Gary, I didn't even really know who that guy was, or how he would have known that my dad had just died. Unfortunately, my mom wouldn't hear of it, and I didn't feel like pressing the issue when the body of her soulmate was right in front of us. The whole experience certainly made me realize how many delicate systems must be workly perfectly and in tandem for us to simply look around the room, have a coherent thought, and appreciate the sunlight in the window.
Steve Silberman (digaman) Fri 28 Nov 08 18:22
"working," not "workly," sorry.
Kurt Sigmon (kdsigmon) Fri 28 Nov 08 21:35
I'm curious now what Gary would have chosen for a subtitle, for a marketing plan, for all the things the publisher chose for his book. How would you present the book to the world? I read science books and tend to expect clear answers or at least a clear point where 'we don't know' is the last statement. I don't see that so much in this book. Things happen, they are presented to the reader, whatever conclusions there are come from the reader. It reminds me a little of (what I know of) therapy.
Gary Greenberg (gberg) Sat 29 Nov 08 07:32
I don't know about subtitles, but what I think my book is about is the relationship between truth and certainty, and how very often the more you ahve of one the less you have of the otehr. >I don't see that so much in this book. Things happen, they are >presented to the reader, whatever conclusions]there are come from >the reader. It reminds me a little of (what I know of) therapy. I thikn that's a fair summary. I mean, I never thought about the boook (or my approach to its subjects) that way, but that feels about right. The problem with the kind of diagnoses I write about is that they represent an assertion of the scientist/doctor's authority in a realm where it really can't be the coin. Or, to put that better, that they encourage people to think that the question is settled in the same way that the question of gravity has been settled. That kind of certainty doesn't stand up well to the truth.
Gary Greenberg (gberg) Sat 29 Nov 08 07:42
>Gary, how have your considerations of brain death and the efforts of the people in your book to attain cryo-enabled immortality altered your feelings about your own mortality, if at all? Well, first of all, the real lesson about these things is in your very moving story about your father. I remember when you were in the middle of that, and writing about it on the Well--how painful it seemed, and how clearly your love for your dad shined through your deliberation and your suffering. But I didn't get that on top of everything else there was confusion and friction about withdrawal of support and organ donation issues. I can't imagine what that phone call (they couldn't show up in person?) from the organ donor people was like for you, but I know what it would have been like for me, and it's not a pretty picture. So much of the pseudoscience around disorders of consciousness (brain death, persistent vegetative state, minimally conscious state) seems designed to ward off the accusation that doctors are vultures. But once the machine starts to churn, that's exactly what some people feel. It's the return of the repressed, and it's no accident that the guy whose views on this subject I respect the most, Stuart Youngner, was, before he became a medical ethicist, a psychoanalytically trained psychiatrist. Anyway, the thing I learned from the many stories I heard and was in the middle of when I did stories on persistent vegetative states and brain death was that it is absolutely necessary to make your wishes clear in advance, and that the boilerplate advance directives and living wills are only the first step. The most important thing is letting the people most likely to be speaking for you what you actually mean, to speak from the heart about this, so that they aren't stuck wishing for kidney failure, or feeling guilty that they pulled the plug. That, and that you should put on your helmet as soon as you get out of bed and leave it on till you get back in.
Gary Greenberg (gberg) Sat 29 Nov 08 07:56
As for mortality itself, I came away half-convinced that immortality is a distant but distinct possibility, most likely in the form of some kind of digitization of consciousness. The notion that we are born and have to die is one of those certainties that may not have as much truth as we think. But I also learned that it's not for me. Maybe that is because the folks I met who are into it are, by and large, the most selfish and narcissistic people I've been around. I don't think this is an accident. To think that to preserve your little life, you are entitled to continue to consume resources (and hold onto your money; a big part of the cryonics thing is wealth preservation, which they teach you about in a seminar called "You can take it with you") even after you're dead, and that when you are revived the people of the society that revives you will want you around, that you have the right to live in their world, that they won't just use you as a slave or for target practice--well, it doesn't get much more solipsistic than this. When I got back to the home of the immortalist who nearly killed me by his reckless boating and met his wife and kids, spent a few hours and had a meal with them, I was really struck by the way that he sort of floated on the surface of his family life, more or less oblivious to the music of it. And by the way his wife, a pediatrician, was not-so-secretly appalled by his attraction to cryonics. What she wanted to talk about was the power of those end-of-life moments, what Steve calls the psychedelically horrible ordeal, and how mysterious they are, and how important. When I left, she gave me a hug of titanic proportions (which ended with her slipping her hand down onto my ass, which I really really liked). I took that as a sign of her feeling thaqt we had connected deeply (which we had), and my guess is that this was very hard with her husband, who has his eyes on a much more distant horizon. Plus I have a much nicer ass. Of course, there are immortalists and transhumanists and cryonicists who are not walled off from the rest of humanity, whose wish to be preserved until they can be healed from wahtever killed them is not born of resentment of the people who will beneift from future medical advances, who do not live in a cloud of resentment of their descendants, a sort of nostalgia for the future. But that was not the norm. So if it's a choice, I'm choosing mortality.
Gary Greenberg (gberg) Sat 29 Nov 08 08:03
>next morning, he was clearly in no better shape, and when I found the nurse again, she told me, "Your father does not have enough brain tissue to feel pain." An excellent, if disturbing and sad, example of how medical people are certain of things they can't possibly know. HOw mudh brain tissue does it take to feel pain? No one knows the answer to that qwuestion, and as far as we know it could be zero. Maybe pain is felt in the spinal cord. Maybe experience is possible in the absence of what looks to our machines like brain activity. Just because blood isn't flowing in your brain and electrical activity has ceased, that doesn't mean that you have no consciousness. It's a guess, and there's no reason to treat a person as if it is a fact. That's why her refusal to give him morphine is unconscionable. What, she was worried he'd get addicted? ANd it's a really good example of what to talk about in that ocnversation with your loved ones. About how much pain medication you want, how haqrd you want them to fight for it, whether you want enough to kill you. (Under the principle of dual effect, if you need so much morphine to ease yoru pain that it will stop your breathing, the person who administers it is not guilty of murder.)
Mr. Death is coming after you, too (divinea) Sat 29 Nov 08 08:10
I had a similar argument with a twenty year old nurse when my dad was dying. I was reduced to bellowing at her till she produced a supervisor who gave him the gd meds. We know so much more than we used to about pain management and palliative/end of life care; the sad thing is that this knowledge has not necessarily trickled down to the floor. Because of where I live, the whole rightie pseudochristian God's will thing also comes into play. I actually asked one nurse why she thought God gave us pharmacology, if not for use to relieve the pain of the dying.
Sharon Lynne Fisher (slf) Sat 29 Nov 08 09:45
When my dad, who had COPD, was dying of liver cancer and had gotten morphine, I had more than one person ask me disapprovingly why they'd given him morphine when he was having trouble breathing. What was I supposed to say? "Oh, we were trying to kill him off, but you caught us." "Just trying to turn him into a junkie, I guess."
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