by Charles Baum
“Hi, Bob!” he said, with his usual big smile, his thick black mus-
tache and curly black hair making him seem younger than his years.
(“It comes from drinking lots of good red wine,” he’d say.) Piles of
manuscripts and journals covered most of his desk and surrounding
tables; banks of neatly labeled filing cabinets hinted that he had the
upper hand on entropy. Glenn leaned back in his chair, hands behind
his head—a characteristic gesture I’d soon come to learn. “What’s up?”
I described the chirality experiments and their implications for
origins research in as sexy a way as I could. Glenn nodded often, but
his smile slowly faded. When I had finished, he launched into an in-
timidating list of his own amino acid projects already underway.
Glenn’s research exploited the fact that although almost all of life’s
amino acids are left-handed, as soon as an organism dies, a slow, in-
exorable process called racemization—the random flipping of mol-
ecules from L to D and vice versa—begins. Eventually, after a few tens of
thousands of years, an organism’s amino acids will have completely
randomized to a 50:50 mixture. This tendency for the D:L ratio of
amino acids to change over time provides a powerful dating technique:
The older the shell or bone, the closer its amino acids will be to a 50:50
mix. Other factors—notably the average water temperature, the acid-
ity, and the salinity—also affect the rate of racemization; the D:L ratio
in a fossil can thus provide evidence for changes in ancient environ-
ments. Glenn was one of the world’s experts in determining that cru-
cial ratio, so scientists from all over asked for his help. In one ongoing
collaboration, he determined the ages of fossil eggshells from Austra-
lia, to help understand long-term changes in the continent’s vegeta-
tion. Another project used clam shells to measure recent changes in the
salinity of the Venetian Lagoon. He also was studying amino acids in
fossil shells from the Baja Peninsula of Mexico to deduce patterns of
climate change.
But his biggest and boldest effort was his long-term collaboration
with Harvard paleontologist Stephen Jay Gould on the evolution of
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Cerion, a beautiful little Bahamian land snail. Glenn had helped to col-
lect countless thousands of these inch-long shells from deep pits dug
into remote sand dunes. The major part of the collection was exhumed
from a deserted stretch of Long Island in the Bahamas. Glenn’s Cerion
specimens displayed remarkable variations, even though all were mem-
bers of a single species. Some shells were elongated, while others were
almost round; some richly decorated, others almost smooth. These and
several dozen other morphological characteristics provided Gould with
a perfect species to test his provocative theories of evolutionary change.
Glenn’s job was to provide the critical dating by analyzing D:L ratios
from thousands of individual shells. Once supplied with enough dif-
ferently shaped shells, their ages, and the DNA analyses performed by
another colleague, Gould hoped to tease out the evolutionary path-
ways of gradual morphological change. Years, maybe decades, of work
lay ahead.
Given these commitments, Glenn was certainly too busy to take
on a new project. Yet he was also intrigued. Chiral selection was a new
challenge for his analytical system, and he knew a good project when
he saw it.
“Looks like it’s about time for lunch!” he said, abruptly changing
the subject.
“Let me take you.” I sensed a setup, but I would have done just
about anything to secure his help.
“There’s a nice little place a couple of blocks from here. Kinkead’s.”
It wasn’t a question.
“Sure, let’s go.”
Kinkead’s specializes in seafood, to which Glenn was deathly aller-
gic; he even had to wear protective gloves when handling his favorite
Cerion shells. But Kinkead’s had a great wine list, and Glenn had a
passion for good red wines. Glenn ordered glasses of two different
wines and extra glasses for each of us, so we could compare and con-
trast. Some months later, I learned that Kinkead’s was a kind of test;
had I balked at the noontime diversion, our collaboration might never
have happened.
Evidently I passed. “OK,” he said, and paused. “You’ll have to
derivatize the samples, but I’ll do the analyses.” So I would have to do a
bit of chemical prep work, but I was in business.
Glenn had to maintain his analytical facility in the same large room
as the undergraduate anthropology lab at George Washington. The first
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thing you notice on entering is the inordinate number of bones—doz-
ens of human skulls, legs, ribs, and hip bones in wooden trays and
glass display cases. A fully mounted human skeleton (lacking only the
odd digit and forelimb) presides slack-jawed over the unsettling scene.
A long, black-topped table surrounded by two dozen padded stools
occupied the center of the 25 × 40-foot space. Glenn had a cramped 3-
foot-square chemical hood on one side of the room and his arsenal of
state-of-the-art gas chromatographs along the opposite wall, where any
undergraduate might inadvertently bump into them. How could any-
one work effectively under these conditions, I wondered? And yet one
quickly learns to focus only on the diminutive vials and their secrets.
I showed up there mid-morning of the following week to prepare
my amino acid samples for analysis. The aspartic acid had to be chemi-
cally modified so that the D- and L-amino acids could be separated
more efficiently by gas chromatography. The amino acid molecules,
which normally dry to a white powder, had to be treated so that they
evaporated to a gas at high temperature. Under Glenn’s guidance, I
made sure each sample was completely dried down, then added a mil-
liliter of thionyl chloride, an orange-tinged toxic liquid, and tightly
capped the vials under a stream of nitrogen gas. Then we cooked the
samples, two dozen at a time, in the oven.
I have never watched a scientist more meticulous in his procedures
than Glenn, who proved to be one of the most exacting, finicky experi-
mentalists I’d ever met. Like a master chef, he prepared amino acid
samples for analysis the same way every time. He heated them at 100°C
for one hour in a small, squat oven, instructing me to open the oven
door quickly and place the tray of vials on the shelf in one swift ges-
ture. Close the door within 4 seconds to keep the temperature at the
proper level. If the temperature dropped even 0.2°C, he recorded it in
his lab notebook.
An hour later, to the second, I had to remove the samples from the
oven with a similar smooth motion. If I was 10 or 15 seconds late, his
mustache would twitch and the discrepancy went into the notebook.
One secret to Glenn’s success was his absolute, rigorous reproducible
procedures.
Once th
e rows of vials had cooled, I opened each one, dried them
under a vacuum, added a second chemical (trifluoroacetic acid anhy-
dride), sealed the vials, and heated them again for exactly five minutes.
At the end of this process, each amino acid sample had been modified
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GENESIS
to a volatile form that was ready to analyze. We transferred a small
volume from each into glass autosampler vials, loaded up the gas chro-
matograph, and set it to run overnight.
Glenn and I were paranoid about the potential for unconscious
bias. We knew exactly the chiral effects we were looking for—certain
faces should select L-molecules and others D-molecules, while the frac-
ture surfaces should display no preference. So I randomly renumbered
the samples and Glenn renumbered them again in his own notebook.
That way, neither of us would know which sample came from which
face until after we’d completed all the analyses and compared num-
bers. It’s all too easy to see what you want to see in random data. Once
the samples were prepared, we had only to wait for the automated ma-
chine to do the analyses. Glenn promised to call me the next day with
our first results.
“Hi, Bob. Looks like we have some data,” he reported the next af-
ternoon. “Got a pen?” I scribbled down a long list of specimen num-
bers and D:L ratios. Quite a few of the numbers were close to 1.00—no
effect. But there were also several values significantly higher and lower:
0.958, 1.031, 0.965, and other numbers that pointed to a possible chiral
effect.
“Of course we’ll have to repeat all these analyses a couple more
times,” Glenn added. I was to learn that performing analyses in tripli-
cate (at a minimum) was one of his trademarks.
“What sorts of reproducibility do we have?”
“Looks like about plus-or-minus half a percent. Not bad.” I was
amazed. Errors smaller than 1 percent were almost unheard of in this
business.
As soon as I had sorted out which analysis went with which face, a
clear and compelling story began to emerge from the data. Left-handed
calcite faces almost universally displayed D:L ratios a few percent less
than 1.00. These faces preferentially retained L-aspartic acid. The right-
handed calcite crystal faces displayed an equal and opposite affinity for
D-aspartic acid. Equally important, all of the nonchiral fracture
surfaces, which served as our experiment’s internal control yielded
D:L ratios indistinguishable from 1.00. Glenn’s repeat analyses of each
sample over the next week reinforced the story.
We wrote up the results quickly and submitted the short manu-
script to the Proceedings of the National Academy of Sciences, with Hat
Yoder serving as the sponsoring Academy member. The discovery that
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chiral crystal faces of calcite selectively adsorb D- and L-amino acids
suggested not only a plausible chiral environment on the early Earth,
but also a possible mechanism for making functional biological mac-
romolecules. If adsorbed L-amino acids lined up sequentially on the
crystal surface, then they might be poised to link to each other, form-
ing a protein-like polymer of amino acids. Perhaps in this way mineral
surfaces selected, organized, and assembled the first homochiral
biomolecules.
As we had hoped, a few workers in the origin-of-life community
noticed our results. What we had not anticipated was significant inter-
est from chemical engineers engaged in the design and purification of
chiral pharmaceuticals. Our work on chiral mineral surfaces had
opened the door to a host of possible industrial applications in the
$100-billion-a-year chiral drug business.
For our part, Glenn and I saw the aspartic acid study as the begin-
ning of a long and fruitful collaboration. Next on the agenda were simi-
lar experiments with D- and L-glutamic acid, another amino acid that
binds readily to calcite. We also plotted out new experiments with left-
and right-handed quartz crystals. As our friendship grew, so did my
interest in his other research projects, and he signed up my wife and
me as field hands for his next Bahamain field season the following
December.
It was during these new experiments that Glenn, uncharacteristi-
cally, began to complain of an incessant pain in his jaw. A drug-resistant
tooth infection had gradually spread through his mouth and into his
sinuses. Worse than the pain, the disease numbed Glenn’s sense of taste.
He began to lose weight rapidly. He stopped drinking wine. In March
of 2002, the antibiotic Cipro seemed to turn the tide. Glenn rallied and
he even agreed to visit a favorite lunch spot, Pizza Paradiso, where for
the first time in weeks he managed to eat most of his lunch. We talked
optimistically of our December trip to the Bahamas.
Though weakened, Glenn returned to his lab and began to
recalibrate the sensitive analytical machines that had sat idle for so
long. On March 27th, we enjoyed a brief, sobering visit from Steve
Gould, whose magnum opus, On the Structure of Evolutionary Theory,
had just appeared in print. Steve talked optimistically about the
upcoming fieldwork, but he had just been diagnosed with a fast-
spreading cancer and he tired quickly. During much of the visit, he sat
in front of piles of his beloved Cerion, picking up one after another,
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GENESIS
pointing out unusual features. He kept saying “I need another 20 years.
I just need another 20 years.” [Plate 8]
But it was not to be. Stephen Jay Gould died of cancer on May
20th, fewer than two months later.
By the end of May, Glenn’s infection had returned with increased
virulence, spreading to his brain, confusing his thoughts. During our
last halting conversation, in early October, he fretted about the long
hiatus in his research. He spoke eagerly of the December field trip to
the Bahamas, as if in another few weeks he’d be well again. In his de-
lirium, he anticipated meeting Steve Gould on the island.
Glenn Goodfriend died on October 15, 2002, at the age of 51. The
chance to know and work with him was one of the greatest gifts of my
career, and his decline and death one of the saddest events I’ve ever
had to experience. For months I was paralyzed by the loss. Asking any-
one else to fill Glenn’s shoes seemed disrespectful, like marrying again
too soon after the death of a spouse. Colorful crystals lay idle in my lab.
More than a hundred vials of amino acids sat unanalyzed. Only gradu-
ally, with the help of new collaborators, did the chiral-selection project
get back on track.
Scientists don’t know for certain—and may never know for certain—
how life’s homochirality emerged from the random prebiotic milieu,
but we have targeted an expanded repertoire of promising local chiral
environments. Perhaps life’s molecules self-select for handedness. Or
perhaps they spontaneously assemble on chiral mineral surfaces. What-
ev
er the answer, these ideas offer years of opportunities for origin-of-
life researchers (and chemical engineers, as well).
What we can say for sure at this stage is that mineral surfaces are
remarkably successful at selecting, concentrating, and organizing or-
ganic compounds. Thanks to quartz, calcite, and a growing list of other
crystals, the mystery of the emergence of organized molecular systems
from the complex prebiotic soup seems a lot closer to being solved. It
would appear that minerals played a far more central role in the origin
of life than previously imagined. Armed with that understanding,
chemists, biologists, and geologists are embracing a more integrated
approach to one of science’s oldest questions.
Interlude—Where Are the Women?
Reading your manuscript is really depressing.
Where are the women?
Sara Seager, 2004
Even a cursory scan of this book reveals a field that has been
overwhelmingly dominated by white males. Why should this
be? Who’s to blame?
The answer certainly isn’t in the nature of the discipline. A
few scientific subjects, like field geology and high-pressure re-
search, require extraordinary physical exertion and carry a level
of risk that provided a convenient excuse for decades of almost
exclusive male domination. But no such hardships are associated
with research on life’s origins, a field that holds intrinsic fascina-
tion for men and women alike. Yet hardly a single female ap-
peared as coauthor on any origins paper in the three decades
following Stanley Miller’s 1953 landmark article.
I don’t know why, but I suspect that two factors played a sig-
nificant role in this unfortunate, embarrassing bias.
First, the origin-of-life field is small, and by simple bad for-
tune several of the most prominent leaders during the 1950s
through the 1970s were male professors who were at best
unsupportive of women students (if not downright misogynistic).
All young scientists need the encouragement of mentors and the
inspiration of role models. Lacking this support system, women
felt excluded from the origins club. Only within the past decade
has the research environment changed enough to provide women
with a more conducive environment in which to excel.
Second, the best and brightest women scientists may have