Water provides the universal medium for life. All known cells are mostly water on the inside, and most are surrounded by water on the outside. That aquatic lifestyle poses a problem, however, because water is one of the best solvents. You don’t want your body’s cells to dissolve every time you take a bath. Life had to develop an insoluble protective membrane, but what chemical to use?

Lipid molecules, which feature hydrocarbon chains (a row of carbon atoms surrounded by hydrogen atoms), provide the perfect answer to the problem. Lipids, including various fats, oils, and waxes, are characterized by their insolubility in water—oil and water don’t mix. The special phospholipid molecules that form most modern cell membranes are no exception. Each of these molecules is shaped something like a tiny bobby pin, with two long hydrocarbon chains of atoms attached to a rounded end. The two exposed hydrocarbon chains are hydrophobic (“water hating”), so most of the elongated molecule is water-repellent. By contrast, the rounded end incorporates a phosphate group (phosphorus and oxygen atoms); that hydrophilic (“water loving”) end attracts water. Such molecules, with both hydrophobic and hydrophilic regions, are called amphiphiles.

When placed in water, amphiphilic lipids deal with their love-hate relationship in a remarkable way. All natural systems tend to rearrange

themselves to reduce their total energy content: A tightly stretched elastic band snaps, a precariously perched boulder tumbles to the valley below, a firecracker explodes. By the same token, a solution of lipid molecules searches for a state of lower energy in which only the hydrophilic phosphate ends contact water. In the early 1960s, Alec Bangham, a biophysicist from Cambridge, England, discovered that lipids that were extracted from egg yolk and immersed in water spontaneously organized themselves into tiny spheres—structures now known as vesicles.

The energy-reducing strategy employed by the molecules that form cell membranes is nothing short of magical. Millions of individual amphiphilic molecules quickly clump together, forming a smooth, flexible double layer of lipids—a lipid bilayer. The resilient lipid bilayer provides a simple and elegant solution to the phospholipid’s ambivalence toward water. All of the hydrophobic chains of atoms point toward the middle of the structure, well away from water, while the hydrophilic phosphate ends all wound up on the outside of the cell facing the wet environment or on the inside facing the water-based contents of the cell. This arrangement accomplishes the vital functions of holding the cell together while separating its inside from the outside.

Life has perfected this task of separating the inside from the outside, but could such an emergent, self-organizing process have arisen naturally in the lifeless prebiotic soup? The answer, once again, is to be found in the laboratory. Some amazing experiments have been performed by the Swiss biochemist Pier Luigi Luisi, who has spent decades studying lipid self-organization.

Not only can Luisi and co-workers form vesicles with ease, but they also demonstrate that these structures can grow, gradually incorporating new lipid molecules from solution. They’ve also shown that vesicles are autocatalytic—that is, they can act as templates that trigger the formation of more vesicles. And, under the proper circumstances, vesicles can even divide—a kind of self-replication.

These intriguing emergent behaviors have led Luisi to propose the “Lipid World” scenario for life’s origin. In this conceptually simple model, prebiotic lipids formed abundantly on Earth and in space. Once in solution, these lipids self-organized into cell-like vesicles that captured a primitive genetic molecule, some early, simpler version of DNA or RNA. Now the Swiss team has set its sights on incorporating self-

Cell membranes are formed from amphiphiles, which are elongated molecules that have both water-attracting and water-repellent ends (A). When placed in water, these molecules self-organize into a bilayer (B), which can form a spherical vesicle (C).

replicating pieces of RNA into self-replicating vesicles, perhaps even to make the first synthetic life-form. It hasn’t happened yet, but the chemical pieces are close to falling into place.

In the relatively brief history of origins research, a mere handful of experiments may be counted as classics. Louis Pasteur’s refutation of

spontaneous generation and Stanley Miller’s electric-spark synthesis experiments have achieved that status, as has the novel vacuum-chamber research of Lou Allamandola and his colleagues at NASA Ames. Their results changed the way we think about life’s origins. The same high regard is accorded David Deamer’s remarkable discoveries of lipid self-organization in spaceborne molecules.

For almost three decades, Dave Deamer has been a popular professor of biochemistry in the University of California system. Lean, bright-eyed, with a neat graying beard and dark-rimmed glasses, he delivers lectures in a gentle and reassuring voice, like a scientific Mister Rogers. Listening to his low-key delivery, you might not guess that he is one of the world’s most respected experts on the origin of life. [Plate 6]

Deamer caught the origins bug in 1975, when he took a sabbatical from the Davis campus of the University of California and went to study lipids with Alec Bangham at Cambridge. Their work revealed that the size and resilience of vesicles depends on the size and shape of the dissolved lipid molecules. In the course of these investigations, they realized that vesicles might have provided the first sheltering environment for life. If lipids existed in the early oceans, then prebiotic vesicles may have been abundant.

Deamer returned to Davis and continued this line of research, which led to his most famous experiment. That work, completed in 1988, focused on carbon-based molecules extracted from the Murchison meteorite. Ever since it landed in the Melbourne cow field in 1969, origins scientists all around the world had been bargaining and pleading for a piece of the prize. Deamer’s precious 90-gram Murchison fragment, about the size of a walnut, arrived from the Field Museum in Chicago. Dave and his collaborator, chemist Richard Pashley of the Australian National University, went straight to work. Their focus was the lipids, essential biomolecules but ones that did not seem to be produced in sufficient abundance by Miller’s spark process. Perhaps, they thought, carbonaceous chondrites provided those necessary raw materials for life’s membranes.

Deamer and Pashley ran their sample through a series of chemical steps to break apart the dense black meteoric mass into chemically distinct fractions—steps that in some ways mimicked millennia of chemical weathering processes on the primitive Earth. Whatever molecules they found were thus likely to have occurred on the prebiotic Earth, as well. First they pulverized a portion of the meteorite into fine

black powder. Their straightforward procedure involved grinding the rock while it was submerged in a liquid mixture of water, alcohol, and chloroform. These solvents don’t affect the crystalline minerals that form the bulk of the Murchison, but they do dissolve different suites of interesting organic molecules. After several minutes of grinding, Deamer and Pashley poured their fine-grained slurry into a test tube, placed it into a centrifuge, and let it spin.

In the centrifuge, the pulverized meteorite solution rapidly separated into three fractions. A small pile of dense mineral fragments settled to the bottom of the tube, to be set aside just in case more studies were required. On top was a layer of water–alcohol solution, which dissolved and concentrated amino acids, sugars, and a variety of other water-soluble organic species. This fraction, too, was set aside. In the middle was a layer of chloroform, an effective solvent for any lipids the meteorite might hold. They found that the chloroform fraction had extracted more than a tenth of a percent of the meteorite fragment’s mass—a surprisingly high concentration of tantalizing organic species.

Further separation was performed using chromatography. Following much the same protocols as Stanley Miller had employed decades earlier to separate his amino acids, Deamer and Pashley evaporated a portion of their chloroform sample to reveal a yellowish-brown concentrated solution. They placed a drop of this concentrate on the corner of a 4 × 4-inch glass plate that had been coated with a soft, porous white powder (an effective replacement for the older-style chromatography paper). They used ether, a colorless strong-smelling solvent, for the first chromatographic stage, stretching the dried dot into a streak. Then they rotated the plate 90 degrees and used chloroform to spread the streak into a distinctive two-dimensional array of compounds.

Viewed in daylight, the dried glass plate was unimpressive, with only the original brownish spot and a few faint yellowish areas nearby. But Deamer knew that many otherwise invisible compounds fluoresce brightly under “black light.” When he darkened the room and shone an ultraviolet lamp on the plate, he was delighted to see a rich display of colors sweeping across it in a broad arc.

Deamer and Pashley identified a half-dozen distinct fluorescent regions, each with a different, as yet unknown suite of ancient cosmic organic molecules. They meticulously outlined each area by scratching the soft, powdery white surface; then they scraped off and collected

powder from each of those areas into test tubes. A quick wash in chloroform was all that it took to recover the precious suites of Murchison molecules.

Keen with anticipation, the chemists placed the chemical fractions one-by-one into water and watched to see if anything interesting happened. They began with “spot 1,” with molecules that had concentrated in an elongated area close to the original drop on the chromatography plate. Deamer and Pashley watched transfixed as the invisible molecules, once dispersed throughout the meteorite, spontaneously arranged themselves into tiny spheres no more than a hundredth of an inch across—about the size of many modern microbes. What’s more, they found, these weren’t just little drops of oil or fat floating in water. These structures had an inside and an outside. The molecules had organized themselves into bilayers, just like a cell membrane—an elegant example of emergence.

It was a breakthrough moment for origin researchers. Deamer and Pashley had shown that ancient lipid molecules, synthesized at some distant place in space and delivered intact to Earth, form tiny enclosed structures that are in many ways like the membranes encasing living cells. One of life’s most basic requirements—the isolation of inside from outside—suddenly seemed to have been hard-wired into the fabric of the universe.

Dave Deamer’s Murchison experiments were conceptually simple and beautifully executed. So when new lipid-rich samples came along, he repeated the process.

Lou Allamandola and his NASA Ames team realized that their growing inventory of organic molecules, synthesized under simulated deep-space conditions of ultracold vacuum with ultraviolet radiation, contained a significant fraction of yellowish oily stuff just as the Murchison meteorite did. In particular, when they irradiated an ice made principally of water and alcohol with a bit of ammonia and carbon monoxide thrown in, they produced an intriguing residue of fluorescent material. Much of that material was known to be the familiar multiringed hydrocarbons known as PAHs, but other molecules appeared to have an amphiphilic character. Naturally, they turned to Dave Deamer to check it out.

Samples in hand, it took Deamer less than a day to confirm what the Ames researchers had hoped. Once the correct fraction of fluorescent molecules was concentrated, stunning vesicles appeared spontaneously in water. The press trumpeted the result, and a colorful photograph of the delicate tiny spheres graced the front page of the Washington Post above the headline “IN SPACE; CLUES TO THE SEEDS OF LIFE.” The implications were profound: Even before the formation of planets and moons, in the tenuous vacuum of frigid space, the raw materials for life abound, ready to organize spontaneously into cell-like structures.

I got the chance to work with Dave Deamer following a conversation at one of NASA’s first astrobiology meetings, in April 2000. Dave had been asked to present a keynote lecture on self-organization to the audience of geologists, chemists, biologists, and astronomers, not to mention a smattering of philosophers and ethicists.

Some scientific lecturers try to snow their audiences. Deamer is different; he meets the audience more than halfway, with comfortable metaphors, familiar examples, and elegant demonstrations. At this lecture, he held up two large beakers, both with colorless solutions. When mixed, the resulting liquid immediately became cloudy white; we were looking at the spontaneous self-organization of lipids, he explained.

At Carnegie, my group’s 1996 pyruvate work had been sitting on hold for years. We knew we’d made a lot of interesting organic molecules by heating and squeezing pyruvate, but other than the fact that the reactions occurred rapidly under hydrothermal conditions, the relevance to life’s origin wasn’t clear. Perhaps, we thought, the yellow, oily goo that oozed out of our gold capsules held self-organizing molecules. That might be worth investigating, because we had started with a core metabolic molecule. It would be newsworthy if there were a facile path from primitive metabolism to membranes.

On hearing my story, Dave immediately invited me to his specially equipped lab at UC Santa Cruz (where he had moved in 1994) to try the experiment. The following winter, I prepared some new pyruvate-plus-water capsules and subjected each of them to two hours at 2,000 atmospheres and 250°C. I brought them, unopened, to the beautiful Santa Cruz campus.

In spite of his insanely busy schedule as faculty member in two departments, supervisor of two laboratories, and mentor to several graduate students and postdocs, Dave was a gracious and attentive host. He welcomed me to his biochemistry lab and we set to work immediately.

Once I had opened the capsules (which responded with the now familiar bang! and intense oily foaming), he led me step-by-step through the chloroform extraction, concentration, and preparation of a 10 × 10-inch glass plate for chromatography. I had pored over his 1989 paper several times, so it was a delight to duplicate that work with my own samples under his supervision.

Within a couple of hours, I had decorated a glass plate with a small yellow-brown dot of unknown chloroform-soluble compounds. We gently lowered the plate into a deep glass tank into which I had poured a half-inch layer of pungent ether. (The strong smell triggered a brief, vivid flashback to an early childhood moment—a menacing masked anesthesiologist bending over me, smothering my face prior to a ton-sillectomy. I had to shake away the disturbing image.) As with Deamer’s earlier work, the solvent pulled the glass plate’s single yellow-brown spot into a long streak. Then we rotated the plate and the chloroform smeared the streak into what we hoped would be a distinctive pattern of organic compounds.

I felt more than a little tingle of anticipation as the lights went out and the UV fluorescent lamp flicked on. The results were gorgeous! A brilliant yellow, blue, and purple pattern appeared, blazing across the plate in a diffuse 7-inch-long arc of color. We were delighted to see several distinctly fluorescing areas, strikingly similar in detail to the Murchison sample [Plate 6]. Noting the correspondence, Dave suggested that we first concentrate on a blue fluorescing area most closely matching the position of his original “spot 1.”

Again, we followed the 1988 procedures: Carefully mark the glass plate, scrape off the white powder from the area of interest, wash that powder with chloroform to redissolve the fluorescing molecules, and dry the extract (by this time the lab area smelled strongly of the chloroform–ether mix). Then the big test. Would my concentrated extract perform the self-organization trick?

The test was quick and easy. We applied a bit of the extract to a droplet of water on a glass slide and watched in the microscope, which used a UV light to highlight fluorescent molecules. Sure enough, tiny

green fluorescing spheres appeared, like a fantastic display of Christmas lights. [Plate 7] Beautiful, but were they vesicles that trapped the surrounding liquid, or simply solid spheres? That was key to determine if we had really made cell-like bilayer membranes.

Deamer’s technique was to repeat the microscope observations, but this time starting with a strongly fluorescing red dye in the water. For a second time he applied a bit of the extract to the water and, once again, green fluorescing spheres formed. If we had made hollow vesicles, then they would capture the distinctive red dye. To find out, Dave carefully flushed the slide with new, nonfluorescing water. Lo and behold, the centers of the tiny green vesicles glowed red. We knew we had made bilayer membranes from nothing more than pyruvate and water.

We celebrated that night with a bottle of Napa Valley cabernet and talk of next steps and publications. We both knew that the pyruvate results were at best a footnote to the Murchison and NASA Ames discoveries, but the experiments seemed to underscore the inevitable emergence of self-organizing molecular systems along the path to life.

To be sure, many problems remain to be solved. Recent work by Deamer’s group suggests that lipid self-organization may be sharply limited by the presence of dissolved calcium and magnesium, seawater ingredients that would have been present in significant concentrations in Earth’s early ocean. Perhaps life can begin only in fresh water, or maybe some as yet unidentified varieties of lipid molecules were involved. And, as many biologists have been quick to point out, the vesicles produced in Deamer’s work are a far cry from actual cell membranes, which feature a mind-boggling array of protein receptors that regulate the flow of molecules and chemical energy into and out of the cell.

These details will occupy researchers for decades to come, but the emergence of cell-like vesicles from simple molecules is now one of the best-understood features of life’s origin.

New ideas about the emergence of self-organized molecular systems keep origin-of-life workers on their toes. An especially intriguing recent proposal comes from Oxford chemist Christopher Dobson and his collaborators at the National Oceanic and Atmospheric Adminis-

tration (NOAA) in Boulder, Colorado. In 2000, they published a speculative yet persuasive hypothesis on lipid self-organization in the Proceedings of the National Academy of Sciences. Elaborating on earlier unpublished work by the geophysicist Louis Lerman at Stanford, Dobson’s group focused on the possible roles of atmospheric aerosols in prebiotic synthesis and molecular organization.

Many organic molecules—especially lipid molecules like the ones Deamer isolated from the Murchison meteorite—could have accumulated at the ocean’s surface like an oil slick. As wind kicked up white-caps and waves crashed onto the earliest shores, a continuous fine mist of aerosol particles—tiny droplets, some smaller than a thousandth of an inch across—would have sprayed into the atmosphere from the oily surface. Each water droplet would have contained a significant concentration of organic molecules that almost immediately would have formed a membranous shell around the wet interior. The largest of these droplets would have fallen quickly back into the foam, but smaller aerosol particles are quite robust and could have remained suspended in the atmosphere for months or even years, riding wind currents like microscopic gliders high into the stratosphere.

Dobson and colleagues speculate that lipids in each aerosol particle formed a spherical, single-layer structure with the hydrophobic ends facing the atmospheric exterior and the hydrophilic ends facing the aqueous interior. Many of these aerosol particles would have incorporated reactive, water-soluble organic molecules, which might have undergone further chemical reactions in sunlight. Each particle would have had weeks or months to experience such energetic transformations; each would have been, in effect, a tiny chemical experiment.

For hundreds of millions of years, aerosol particles in numbers beyond imagining drifted into the skies. Upon their return to the ocean, each hydrophobic aerosol particle would have been spontaneously coated by more lipid molecules at the ocean’s surface to form a bilayer structure—the emergence of the familiar membrane structure of cellular life. In the words of Dobson, “Organic aerosols offer more than freedom from the tyranny of the tidal pool or Darwin’s ‘warm little pond’; they offer a possible mechanism for the precursory production and the subsequent evolution of populations of cells.”

In either scenario, whether in the form of wind-blown aerosols or water-bound vesicles, lipid self-organization seems to have been an essential step in isolating the insides from the outsides of cell-like struc-

According to the theory of Christopher Dobson and colleagues, the surface of the ancient ocean was coated with amphiphilic molecules. The action of ancient waves and winds would have formed aerosol particles surrounded by lipid molecules (A). These particles might have remained in Earth’s atmosphere for months (B), but would eventually return to the ocean (C), and form cell-like bilayer structures (D) (after Dobson et al., 2000).

tures. But a membrane, by itself, is not life. Other essential biomolecules, including proteins, carbohydrates, and nucleic acids, had to be assembled from the soup. The trouble is that the building blocks of these macromolecules—amino acids, sugars, bases—are all water soluble. By themselves, they can’t self-assemble in water.

What to do? Call in the rocks.

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