Inkwell: Authors and Artists

    
(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.
  

    
>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.
  

    
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?
  

    
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.;
  

    
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?
  

    
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. 
  

    
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.
  

    
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.
  

    
Hawthorne
  

    
I totally agree.
  

    
Sorry?
  

    
Don't be. It's mnot your fault.
  

    
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.
  

    
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
  

    
Very interesting, Sharon, thanks.
  

    
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?
  

    
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.
  

    
"working," not "workly," sorry.
  

    
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.  
  

    
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, 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.
  

    
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.
  

    
>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.)
  

    
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. 
  

    
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."