Anatomy of a Scientific Discovery: The Race to Find the Body's Own Morphine

191 Pages·2013·1.29 MB·English

by  Jeff Goldberg

Copyright © 1988, 2013 by Jeff Goldberg All Rights Reserved. No part of this book may be
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T C
ABLE OF ONTENTS
Introduction to the Twenty-Fifth Anniversary Edition
Slaughterhouse Days
Brain Soup
Locks and Keys
Substance X
Breaking the Code
Alpha, Beta, Gamma
The Madness Factor
The Endorphin Business
Families
Rats and Runners
The Symphony and the Orchestra
Index
I T -F A
NTRODUCTION TO THE WENTY IFTH NNIVERSARY
E
DITION
In the mid-1970s, the discovery of a family of molecules in the body called
endorphins, which behaved exactly like narcotic drugs, captivated the popular as
well as the scientific imaginations. Yet, it wasn’t just what was discovered that
made it remarkable; it was how the discovery was made. The work by Hans
Kosterlitz and John Hughes, in a small, dusty laboratory in Aberdeen, Scotland,
was great science but hardly big science. It evolved not from massive funding or
modern laboratories filled with high-tech equipment but from single-minded
dedication, keen intelligence, and the ability to make the most of limited tools.
Their discovery epitomized the same kind of low-budget, garage-style innovation
that would lead to the computer revolution a decade later.
Twenty-five years have passed since this book was published, and so have
some of the central figures. Hans Kosterlitz, chief of the Aberdeen lab, died in
1996 at age ninety-three. He was already seventy-three when his assay, using a
tiny bit of twitching nerve tissue from the lower intestine of guinea pigs,
demonstrated that there was opiate activity in a chemical fragment distilled from
pig brains by his colleague John Hughes. And Avram Goldstein, the discoverer of
dynorphin, the most powerful endorphin, died in 2012. He was ninety-two. But,
the “younger” generation of endorphin investigators are all still at work.
Solomon Snyder was only thirty-six when he and his twenty-nine-year-old
postdoc Candace Pert discovered molecular receptors in the brain that fit opiates
exactly like a lock fits a key. Today, at seventy-one, Snyder continues his research
juggernaut at Johns Hopkins, where, with more than a thousand publications to
his credit, he’s investigating the effects on memory of a brain-produced gas
called nitric oxide. Always unconventional, Candace Pert, meanwhile, is the only
one of the original endorphin researchers with a Facebook page and a blog
devoted to a new age theme of Healing the Hurting, Shining the Light. She’s also
working in private industry on an AIDS vaccine. John Hughes was thirty-five
when he identified the formula for Met-enkephalin, the first of the endorphins.
Now seventy-one, after retiring as director of the Parke-Davis Neuroscience
Research Centre, he continues his scientific work at Wolfson College,
Cambridge, when he’s not in his garden or on the golf course.
The word “endorphins” has entered the common vernacular, meaning any
one of a number of mood-related chemicals that have been found in the body.
But the style of science that brought this deeply hidden secret of human nature
into the light may indeed be a thing of the past.
Today, big science is the standard: big budgets, big staffs, big equipment. With
the ability to exchange data instantly over the Internet, collaborations between
dozens of scientists in multiple research centers (often scattered over the globe)
are the norm and are considered necessary to gain ever-tightening research
funding. It would be almost impossible for the small, slow, and steady to win any
scientific race in 2013.
A case in point is the discovery of a sodium ion channel in nerve cells called
NaV1.7 in the mid-1990s by a small group of researchers at Stony Brook
University. NaV1.7 appeared to be a crucial gateway for pain signals. It was an
intriguing finding, but it took a massive collaboration between nineteen
scientists in five countries, funded by the drug giant Pfizer Pharmaceuticals, to
reveal the molecular gate’s true potential. The multinational research team
analyzed the DNA of children born with a congenital insensitivity to pain. These
children, who typically suffer severe burns and other grave injuries without
knowing it, had once been thought to have a defect in their endorphin pathways.
Instead, they were discovered to have nonfunctioning NaV1.7 channels. As a
result, pain messages were completely shut down; the children were in a
permanent state of local anesthesia.
Imagine if pain could be blocked as effectively in people suffering from
disease or injury. Pfizer and Icagen, a rival pharmaceutical company, are hard at
work developing drugs based on this discovery, in hopes of finding a non-
addictive painkiller—the holy grain of a “stingless bee” that was also one of the
underlying motivations of endorphin researchers. That is, until hopes for an
endorphin pill evaporated within a few years of the initial discovery.
While Pfizer and Icagen battle it out for the next blockbuster analgesic, other
drug companies are instead spending millions of dollars frantically looking for
ways to make conventional narcotics uncrushable, unsnortable, uninjectable, and
generally unlikeable when tested on drug addicts. Clearly, big science doesn’t
always yield big results, especially in drug research. And when big science comes
up short, who knows? Maybe that’s when the next John Hughes will again peddle
his push-crate bicycle through the predawn streets in quest of fresh pig brains.
S D
LAUGHTERHOUSE AYS
In Aberdeen, on the northeast coast of Scotland, winter begins in early October
and does not let up until May, or so it seems. On most days it rains.
In the fall of 1973 the old fishing and textile manufacturing city was being
transformed into a kind of American frontier town by the discovery of offshore
oil. Texas oilmen roamed the streets in ten-gallon hats and cowboy boots, and
the young men who worked the rigs came into town on the weekends like
western movie extras, their pockets stuffed with cash, to drink and brawl
themselves into oblivion. Oil was bringing prosperity and development to
Aberdeen; new office buildings and shops were springing up among the grim
granite edifices.
All the buildings in and around Aberdeen were made of granite mined from a
nearby quarry—the building code of the “granite city” is still very strict in this
regard. The stone sparkled with silica when the sun was shining, but on Union
Street, Aberdeen’s historic main street, it was dull, dark, and gray at four o’clock
in the morning.
The sidewalks were wet and empty, the store windows unlit and gated, as John
Hughes rolled through the predawn blackness, pedaling a push-crate bicycle that
resembled an ice cream vendor’s.
Hughes was thirty years old, a short, slight, bespectacled man, who was
booking-looking except for his swollen hands, which looked like the hands of a
boxer or a murderer—flecks of blood had crusted under the cuticles and faintly
stained his knuckles and fingertips. Most of his head was obscured by an orange
woolen balaclava helmet that his wife, Mandy, had given him on the Christmas
past.
Hughes turned left on Broad Street into the shadows of Marishal College,
where he stopped, slipped into the building, and silently made his way to his
third-floor laboratory to collect what he needed: a supply of small plastic ziplock
bags, a white lab coat, a gore-splotched hacksaw and hatchet, a short wooden-
handled knife purchased at Woolworth’s, and a bottle of Scotch whisky.
With everything safely stowed in the crate on the front of his bicycle, he
pedaled toward the Market Street docks. The wind bit at his face, and his glasses
misted as he jolted over the wet cobblestones. The fishing fleet was casting off, so
Prince Edward quay was a site of bustling activity in the otherwise sleeping city.
Gulls swooped in the wake of the boats and fought over the leavings of
yesterday’s catch.
Hughes stopped his bike at a warehouse, the owner of which reluctantly sold
him a single block of dry ice, which normally could only be purchased in lots of
ten. Hughes loaded the dry ice into the crate and pedaled slowly uphill, back past
the Marks & Spencer department store on George Street. His final destination
was still a mile away.
In 1908 the “killin” house on the corner of George and Hutchinson streets
first opened for business. The date was inscribed in the high granite walls above a
wooden gate, along with the crest of the Butchers Guild—an axe, three knives, a
castle—and its motto, Virtute vivo: “I live virtuously.” This was the place where
local farmers brought their pigs and sheep for slaughter, and the place John
Hughes had come to collect his pig brains. The stone holding pens, pits, and the
shelters for the workers had been constructed at the turn of the century, as had
the floor of stone tiles—which covered part of the open field—and the system of
drains and sewers beneath them, which washed away the blood. The chains and
pulleys and meathooks on overhead tracks were a more recent addition. There
was no roof, and from the second floor windows on George Street the
slaughtering process, as it proceeded through the morning, was inescapably
visible.
Animals shuffled restlessly inside their wooden stalls while the butchers stood
in groups near the warming wood fires, on which cauldrons of water boiled.
They talked in thick Scots accents, smoked cigarettes, and drank coffee; Hughes
knew he must have seemed a weird bird to them: the little man who arrived every
couple of days on a push-crate bicycle, put on a white lab coat, and spent the
morning packing pig brains in dry ice.
To Hughes the pig brains were an absolute necessity. He needed a lot of them,
and here they were free. He had tried explaining to the butchers that he was
looking for a chemical in those pig brains, a chemical that resembled drugs
derived from the opium poppy—a natural “morphine” produced from within the
animal’s own body that might, someday, unlock the mysteries of safe relief for
human pain. A few of the butchers pretended to catch on, but Hughes quickly