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Brainstorming: The Science and Politics of Opiate Research by Solomon
Snyder, Harvard UP, pp 200, Pounds sterling 17.95

Anatomy of a Scientific Discovery by Jeff Goldberg, Bantam Books, pp
228, Pounds sterling 4.99 pbk

OPIATE receptors and endogenous opiates were buzz words in the 1970s.
The first are sites in the body to which morphine and other opiates (ligands)
bind strongly (with high affinity) and in proportion to their known potency
as analgesics (painkillers). Solomon Snyder’s claim to fame is that he (‘I
never do laboratory experiments myself’) and his research students at the
Johns Hopkins School of Medicine at Baltimore were the first to demonstrate
the existence of opiate receptors.

Unbeknown to them, however, John Hughes and Hans Kosterlitz at Aberdeen
University had already gone one stage further. Persuaded by the selectivity
of the opiate antagonists nalorphine and naloxone that specific receptors
existed, they were trying to isolate from pig brain a naturally occurring
substance with effects like morphine that were blocked by the antagonists.
Their work is given pride of place in Goldberg’s book which is based on
interviews with all the protagonists in the drama.

When ‘Richard Nixon officially declared a war on drugs’ in June 1971,
Snyder tells us: ‘I had not conducted any research on opiates. I was not
alone. Opiates were definitely not one of the glamour fields of brain research.’
As his czar in the war (all this jargon is getting a new airing under George
Bush), Nixon appointed psychiatrist Jerome Jaffe, who was experienced as
a pioneer in the treatment of heroin addicts.

‘Though I hardly knew heroin from horseradish, I did know Jerry Jaffe,’
Snyder says. His own mentor, the Nobel laureate Julius Axelrod was, furthermore,
one of the group of medical researchers at the US National Institutes of
Health (NIH) called in ‘to brainstorm ways of efficiently using Federal
monies to solve the important underlying scientific questions in drug abuse’.
By late 1971, moreover, Snyder ‘was becoming quite bored with amphetamines’,
a field of ‘bonafide, respectable, and predictably successful drug-abuse
research’, in which he had several publications.

In response to ‘Jerry Jaffe’s almost messianic exhortations to ‘give
me a hand’, Snyder demonstrated his skill in ‘grantsmanship’. He submitted
an application for support to continue his amphetamine work, which the referees
applauded as ‘real solid stuff’ and funded it fully . . . Once the ($300
000 to $400 000) grant was awarded, with a starting date of 1 June, 1972,
I dropped the amphe tamine work and commenced attempts to find the opiate
°ù±ð³¦±ð±è³Ù´Ç°ù.’

In this he made two key changes to the technique used earlier by Avram
Goldstein, professor of pharmacology at Stanford University. First, he used
as ligands tritium-labelled substances with one thousand times the radioactivity
per molecule and at much lower con centration in his incubation mixture;
and secondly, instead of spinning down the mixture in a centrifuge (he had
a most unfortunate experience with one in his first week as a graduate student),
Snyder got his student to use simple filtration under vacuum, washing the
filtrate rapidly to eliminate low affinity bonding, and only then doing
the bound radioactivity counts.

They were successful. On 2 March 1973, their paper The Opiate Receptor:
Demonstration in Nervous Tissue appeared in the American journal Science
to wide acclaim for him and his research student Candace Pert. His achievement
was recognised in 1978 with the coveted Lasker award which, Goldberg writes,
Pert made known she felt she should have shared – an aspect of politics
on which Snyder is strangely silent. ‘The highest honour accorded an Ameri
can scientist, short of a Nobel Prize’, membership of the US National Academy
of Sciences, also came his way. His neuroscience department at Johns Hopkins
University went on to identify other receptors for neurotransmitters produced
in the brain.

Snyder’s book is more than an engrossing description of the development
of his group’s ideas and experiments. He has a thumbnail history of opium,
starting at 4000BC, and of addiction to it ranges over the problems of treating
mental illness; and has provoking thoughts about the relationship between
research student and supervisor. His account of the origin of the drug receptor
concept and its influence on the thinking of pharmacologists is partly redeemed
by the concise summary of the experimental evidence that supports it.

While Goldberg’s book complements Snyder’s in interesting ways, the
hype that all too often characterises popular press treatment of science
is intrusive. A passing reference to ‘the fertility (!) drug Thalidomide’,
and elsewhere to ‘ergot progtomine . . . a wonder drug for migraine’ betrays
a lack of attention to fact that weakens confidence. But similarities of
style and subject far outweigh differences.

This is particularly true of the discussion of competition and rivalry,
as reflected in the frequent references to the Nobel Prize. In his final
chapter Snyder poses the question: Who will make the discoveries? He answers:
‘The best way to predict who will make a discovery worthy of a Nobel Prize
is simply to examine who trained whom . . . Just how do mentors influence
their laboratory students? I can speak only from my own experience. I spent
two years with Julius Axelrod in a small laboratory immediately adjacent
to his. We would talk about research several times every day. I soaked him
up through all the pores of my being.

‘Julie was more concerned with dreaming up new ideas than with the technical
virtuosity of experimentation . . . New methodologies played a key role
in his Nobel-Prize-winning discoveries.’

Goldberg believes the row with Candace Pert over the Lasker award for
the discoveries described has relegated to the future a possible Nobel award
for them. These books, meantime, will amuse the cognoscenti.