Life, According to Mary Shelley

Weather can have profound effects upon history.  In 1815, the largest volcanic eruption ever recorded occurred on the island of Sumbawa in Indonesia.  It wiped away all life on the island and sent enormous plumes of sulfur into the atmosphere.  The clouds spread to Europe over the next year, causing the snow to turn brown, along with heavy amounts of rainfall, lower temperatures, and poor harvests.  The dreary weather would give the year 1816 the unflattering nickname of “The Year Without a Summer.”

Mary Shelley
Mary Shelley.
(Image: Public domain)

It was during this cold and wet year that a small group of companions met at  Lake Geneva in Switzerland for a summer vacation.  Members of the party included the poet Lord Byron, his physician John Polidori, and Byron’s mistress Claire Claiborne, who was carrying Byron’s child.  Also at the lake was the poet Percy Shelley, who had just abandoned his pregnant wife to elope with Claire’s stepsister, the 18-year-old Mary Godwin.  Percy was a philanderer, but Mary had fallen deeply in love with him, and her liberal upbringing argued in favor of a less traditional relationship.  She had already given birth to Percy’s daughter a year before, but the birth was premature, and the young child perished a week after she was born.  Mary and Percy had been devastated, and Mary had been plagued by nightmares of the deceased child.  But her spirits were high when she arrived at Lake Geneva because she had just given birth to their second child, William, and throughout the summer the unmarried Mary Godwin would brazenly call herself “Mary Shelley.”

The companions would go boating on the lake whenever they could, but for most of the time the weather was horrible.  On one particularly stormy night, after reading a book of ghost stories, Lord Byron suggested that everyone create their own spooky tales and share them with the rest of the group.  John Polidori wrote a short story called “The Vampyre,” which was the first incorporation of vampirism into a literary genre, and it set the stage for all future vampire stories such as Dracula and, yes, even the Twilight series.  Mary, on the other hand, could not come up with a story as quickly as the others.  She agonized for days, listening to everyone’s conversations during the day and to the rain pelting on the roof of the chalet at night, and eventually the amalgamation of these external stimuli awakened something in her mind.  She sat down to begin writing her first novel, Frankenstein.

I first read Mary Shelley’s Frankenstein when I was in high school, and I remember being surprised by the nature of the monster in the book, who was an intelligent, agile being tormented by loneliness – not the slow, clumsy, barely self-aware creature that we see in movies.  A few years ago, I found a cheap paperback version of the novel with a preface that was written by Mary in 1831, thirteen years after the book was originally published.  In the preface, she described how the group was stuck indoors during the bad weather, and she mentions the conversations that gave her the idea for her novel.  There were
discussions about galvanism, which is the movement of muscle when electricity is applied to it, and the possibility of using it to reanimate dead tissue.  But Mary went on to describe the conversation further, and she wrote one particular passage that fascinated me.  It was the bit that first got her thinking about the idea of putting life into a completely lifeless material:

They talked of the experiments of Dr. Darwin… who preserved a piece of vermicelli in a glass case, till by some extraordinary means it began to move with voluntary motion.

It conjures a funny image: a piece of pasta (vermicelli) displayed in a glass case and brought to life by a scientist.  But the understanding of life in 1816 was different than it is today; it was common at the time to believe that living animals can emerge spontaneously from nonliving material – an idea known as “spontaneous generation.”  Crocodiles would come from rotting logs at the bottom of lakes, flies would bud from putrid material, and pieces of driftwood would give rise to geese.  Scientists in the 17th and 18th century would perform experiments in attempts to test this idea.  Many would prove it to be false, but some, like the Flemish physiologist Jan Baptist van Helmont, claimed that trees arose from water, mice from soiled cloth and wheat, and – my favorite – scorpions from a piece of basil placed between two bricks.

But Mary’s passage still puzzled me – a piece of pasta in a glass case under Darwin’s watchful eye.  After doing some research, I found that the “Dr. Darwin” who Mary mentioned was Erasmus Darwin, grandfather of Charles Darwin (who was only a child at the time).  Erasmus was a physician, a naturalist, and a friend of Mary’s family.  He was also a poet, and he had recently composed an epic called The Temple of Nature– a long poem that describes his view on the evolution of animals from microscopic creatures to human beings (his grandson would later famously propose the mechanism of how this occurs).  Erasmus was part of a growing community that did not believe in the spontaneous generation of large animals, but he did believe that microscopic animals – the miniscule one-celled creatures you see in pond water – could undergo spontaneous generation and arise from inanimate substances like water and flour.  Erasmus wrote about one of these creatures: the tiny vorticella, a tulip-shaped animal that seemed to appear – and move around with voluntary motion – wherever there is water.  Desmond King-Hele, a biographer of Erasmus Darwin, believes that Mary Shelley – or someone else in the Lake Geneva gathering – confused vorticella with vermicelli, which would explain Mary’s strange passage about the moving pasta in the glass case.

Mistake or not, the reanimation of a piece of vermicelli was Mary’s “Eureka moment.”  The night after she heard the conversation, she dreamt of a scientist kneeling next to his creation: a man he had assembled piece by piece, and who now was beginning to stir with life.  Take days of steady rain and add a misunderstanding about a piece of pasta, and you get Frankenstein’s monster.

Vorticella
A vorticella.
(Image: Simon Andrews/Wikimedia Commons)

Although Frankenstein is an example of the false idea that life can arise from non-life, I find it interesting that Mary Shelley was actually writing the story near the beginning of a scientific revolution that would put this notion to rest.  Within forty years following the novel’s publication, scientists developed “cell theory”: the idea that cells are the basic building blocks of all living things, and that every cell arises from the division of a preexisting cell.  Unfortunately for Erasmus Darwin, this applies even to the humble single-celled vorticella.  The vorticella will form a spore-like cyst when it becomes dry.  Then, when water returns, it will sprout back into its active adult form, giving the illusion that it appeared out of nowhere.  Just like all crocodiles come from other crocodiles, and all flies come from other flies, all vorticella come from other vorticella.

Cell theory had profound effects on our understanding of human development.  It was beginning to be understood that there was no “spark” in nature that gives us life.  We grow because our cells divide, and at one time in our lives, every one of us existed as a single cell.  But even that first cell did not arise on its own: it was the result of the fusion of two other cells (the sperm and the egg), which in turn arose via division from other cells in our parents’ bodies.  Before cell theory, Mary Shelley could imagine an origin for life.  After cell
theory, it seemed as though life had no clear beginning: it always sprung from other living things.

It turned out to be a powerful theory, but it also set some limitations to biology.  While biology can tell us in detail the steps of human development, it cannot tell us when human life begins.  As far as biology is concerned, there is no one Eureka Moment.  The generation of the sperm and the egg, conception, implantation, the first critical cell divisions (where 25% of pregnancies end in miscarriages), birth, and the transformation to adulthood… In the eyes of nature, all of these events are equally important links in the long chain of life.

Mary Shelley was no stranger to the trials and tribulations in the cycle of human life.  She valued highly the relationships she had with Percy and their children, and, in spite of Percy’s aversion to a monogamous relationship, she and Percy eventually married.  But she was an unlucky mother.  A year after she wrote Frankenstein, she gave birth to a baby girl, Clara, who died the next year from dysentery.  Then, William, the little boy who had accompanied her at rainy Lake Geneva, succumbed to malaria at the age of three.  She would give birth to another boy, whom she named Percy after his father, and he would be her only surviving child.

Mary would try one more time to bring a child into the world, but she would suffer a miscarriage that would have taken her own life had it not been for the quick thinking of her husband, who plunged her into an ice bath to stop the bleeding.  Two weeks after her miscarriage, Mary’s husband would drown in a boating accident.  Mary was devastated, and she would never marry again.

Mary Shelley died as a result of an unfettered proliferation of cells – a brain tumor – when she was fifty-three.  On the first anniversary of her death, her son opened a desk-box that she kept by her bed, the contents of which Mary had never revealed to anyone.  Inside were the locks of hair from her deceased children, William and Clara, and the charred remains of her cremated husband’s heart along with a handful of his ashes wrapped in a piece of silk.

We cannot say that Mary Shelley had led a particularly blissful life, but what she and the weather gave us in 1816 – besides the immortal monster – was an important slice of scientific history.  Presently, with our technology advancing faster and faster, we have to at least accept the possibility that we may be able to create some form of life from inanimate matter in the future.  But for now, biology teaches us that life is continuous, and, unlike Frankenstein’s monster, it does not have a clear origin – at least, not a recent one.  The
cycle of life-begets-life has been going on for a long, long time, ever since he first cell arose from the salty, brothy oceans of our young planet.

Some scientists believe the pieces of the first cell appeared after a sudden thunderous crash from a fertile meteorite, or from a bolt of lightning that brought the right combination of molecules together.  Others believe it happened more slowly, as parts were assembled haphazardly piece-by-piece until the right combination for survival and replication was achieved.  Regardless of how it happened, the earth had successfully given birth to the first cell, the cell that would eventually produce crocodiles and vorticellae and Mary Shelley and her cancer.  It would be the earth’s own Eureka Moment, occurring some four billion years ago on a hitherto desolate planet, like a pivotal moment of inspiration on a dreary, rainy summer day.

Posted in Biology, Essays, History, Origin of life | Tagged , , , | 3 Comments

Of cicadas, mayflies, and naiads

A dog-day cicada. Photo: Bruce Marlin/Wikipedia Commons

A few days ago, I opened the front door to pick up the newspaper and was greeted by a large, bulky insect, a cicada, perched on the threshold and facing the door as if it were waiting for someone to let it in.  I gave it a nudge, and it skittered and tumbled away, half flying, half bumping, rattling loudly.  When I went back outside about an hour later, the cicada was still there, on its back, lifeless.

Such misunderstood creatures, these cicadas.  They appear during the warmest time of the year – in fact, the bug that showed up at my door was from the genus Tibicen, or dog-day cicada.  These insects molt shortly after they appear, leaving eerie-looking empty bug-shaped shells stuck to a tree trunk, a fencepost, or the side of your house.  After they molt, they congregate in trees and rattle away in search of a mate.  And within a week or so, you start seeing their bulky bodies littering the ground.

And then there are the 13-year and the 17-year cicadas, or “periodical” cicadas, so-named for their peculiar life cycle where they emerge en masse every 13th or 17th spring (depending on the species) to the horror of many squeamish humans.  I was living in Nashville, TN, during one such outbreak in 1998.  A lot of native Tennesseans prepared themselves for it (and by “prepared themselves” I mean “left the state”), and others sold T-shirts boasting that they survived the great cicada invasion of 1998.  The “invasion” did not disappoint.  Thousands of periodical cicadas – red-trimmed and smaller than the black dog-day cicadas – were absolutely everywhere for about three weeks.  And then they were on the ground, dead, crunching under your tires and feet.  So I ask you, should we pity the lowly, short-lived cicada, which shows up for a couple of weeks every year, just to mate and die?

Consider an even more extreme example of a creature that has an apparently short lifespan: the mayfly.  Mayflies are notorious for their truncated lives, some apparently living for no more than 30 minutes.  In Germany, the mayfly is known as Eintagsfliege, or one-day fly.  In France, it is called the “ephemere”: the ephemeral, the transient, the fleeting.

I’ve had plenty of first-hand experience with mayflies.  For the past six years I’ve been a member of StreamWatch, a volunteer organization that monitors the health of nearby streams.  We do this by taking samples from underneath the rocks in the stream bed and identifying the invertebrates (insects, snails, crustaceans, etc.) that call the river bottom their home.  The classes of invertebrates we find tell us what kind of state the stream is in.  Mayflies do not tolerate pollution too well, and so they are rare in impaired waters but one of the most common invertebrates we find in healthy streams.  But it’s not the adult form that we see – it’s always the immature or nymph stage that lives under water:

Left: A mayfly naiad, about 3/4" long, resting in a shallow stream (Photo: Rob Tilghman). Right: An adult mayfly (Photo: Richard Bartz/Wikipedia Commons)

Mayfly nymphs, or naiads (named after the beautiful young women of the water in Greek mythology) are autonomous, aquatic creatures, complete with six legs and a full set of gills.  They feed on algae and other plant material, and they can move quickly to escape a predator by swimming in an up-and-down motion like a miniature dolphin.  Mayflies will stay in this naiad state – fully functional except for the ability to mate – for a year or more before they pupate and transform into the adult mayfly that we typically see swarming and then dying within a day.  A year is not a bad life span for an insect – at the very least, it’s a lot better than the single day we usually attribute to mayflies.  What’s more, the adult mayfly is not much more than a flying set of reproductive organs.  It doesn’t even eat – actually, it cannot eat even if it tried, because it has nonfunctional mouthparts and its gut is filled with nothing but air.  On the other hand, as a naiad, it leads a very active life: swimming, crawling, eating.  At the ripe old bug-age of a year or two, it molts, mates, and dies.

The adult dog-day cicada, like the mayfly, spends most of its life in its nymph stage, except the cicada nymph lives underground, contentedly nibbling on roots for three years.  The periodical cicadas live even longer underground: 13 or 17 years.  When an adult cicada emerges, like the mayfly, it does not have much in terms of defense, which is quite unfortunate for a rather large, bulky, relatively slow-moving bug.  And there are plenty of animals like birds, lizards, small mammals, and even other insects that would love to take advantage of a cicada for an easy meal.  And then there’s the predator that mother cicadas would warn their children about if they could: the dreaded “cicada killer”, a large wasp that will paralyze a cicada, lay eggs in it, and drag it to the wasp’s nest where it will be food for the growing wasp larvae.  But many cicadas do survive, because – like the mayflies – their sheer numbers are just too much for the predators to completely consume.

And what about that lonely Tibicen that showed up at my door, just in time to die?  In spite of that tinge of sorrow I felt when I first saw it on its back, I shouldn’t feel unhappy for it because I know it was at the end of its natural 3-year-long insect life.  I think we have a tendency to misunderstand these creatures because we (and the animals we most closely relate to) spend most of our lives as fully-developed adults, and, for the most part, any stage prior to this is considered to be juvenile, dependent, and relatively brief.  I was thinking about this a couple of days ago as I was walking through a cemetery at St. Luke’s church (ca. 1632) in Smithfield, VA.

A robber fly consuming its prey, a dog-day cicada. Photo: Rob Tilghman. (Many thanks to Professor Charles Holliday of Lafayette College for identifying the robber fly.)

I saw a cicada being consumed by a large robber fly (see picture) on the gravestone of Hilder Owen Winall, who died in 1922 when she was 28 – a full-fledged adult, although definitely still too young, in human terms, to depart this earth.  There were also plenty of graves for people who lived to ripe old ages, like James P. Owen (probably Hilder’s father), who was almost 94 years old when he died in 1953.  But it’s the graves of young children (very commonplace in old cemeteries, unfortunately) that always break my heart, like that of “Little Daisy”, who died in 1901 at the age of 11.  Poor young Daisy.  We can mourn for such a flower who wilted before she finished blooming, a naiad who never was able to experience the trials and tribulations of adulthood.  But we cannot feel sorry for the cicada that fades away in the grasp of the robber fly, because it has lived a long life.  In fact, to say that the cicada is alive only when it is an adult would be like saying a daisy is only alive when it is in bloom.

Photo: Rob Tilghman

 

 

 

[Edit: Shortly after I published this post, Prof. Holliday (who identified the robber fly in the picture above) sent me a picture of another young child’s gravestone in Massachusetts.  I think fits well with the theme of this essay: What we may see as a brief existence may in fact be just one stage in a lifetime.]

Another sad gravestone of someone who died too young. Photo by Prof. Chuck Holliday.

Posted in Biology, Essays | Tagged , , , | 2 Comments

The whites of our eyes

The CGI special effects in the new Planet of the Apes movie are impressive, especially all the work that was done to make “Caesar” – the leader of the rebellious apes – look so real.  I recently read a blog post by science writer Faye Flam for the Philadelphia Inquirer, where she pointed to the reason why Caesar looks so “human” to us: the CGI guys gave Caesar whites in his eyes.

Real chimps don’t have whites in their eyes, which makes it hard for us, and for other chimps, to tell which way they’re looking.  But here’s the coolest part: humans are the only primates that do have whites in their eyes.  According to this story in The New York Times, human eyes probably evolved in a way to help us cooperate with each other – after all, humans have the most complex social networks of all creatures on the earth, and our eyes let us communicate non-verbally with each other.  In fact, a person will instinctively follow your eyes if you shift them, even if you don’t move your head.  A chimp, however, will be much more likely to follow your glance only if you move your whole head.

I’m probably not the first person to do this, but here’s a picture of the original Caesar from the movie, and the same picture with the whites of the eyes darkened like a real chimp using Photoshop.  I think it makes a huge difference.

Caesar from the movie (left), and Caesar with no whites in his eyes (right). Notice that his pupils haven't changed, but it's a lot harder to see which way he's looking. Original image from Twentieth Century Fox/allmovies.com

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Virchow’s family tree

Rudolf Virchow in 1861, two years after he published Cellular Pathology.  Image from Wikipedia Commons.

Rudolf Virchow in 1861, two years after he published Cellular Pathology. Image from Wikipedia Commons.

With their technology so severely limited (as compared with today’s world), I’m always amazed at how often the 19thcentury scientists got things right.  Maybe it’s because we only hear about the scientists whose theories have survived the test of time: Charles Darwin, Louis Pasteur, Paul Ehrlich.  Still, it is no small feat to develop such a theory, and it’s often amusing and informative to go back to its roots in history.

A few years ago I bought a 1940 edition of Rudolf Virchow’s Cellular Pathology, originally published in 1859.  Virchow was a German physician with an aggressive personality and a tendency to be confrontational, but he also had a strong sense of empathy and was adept at forming collaborations with other scientists.  Spending a good deal of time treating the lower class, Virchow was an early champion of social medicine, and he even tried to push the future German chancellor Otto van Bismarck to spend fewer resources on an army and more towards public health, to a point where Bismarck challenged him to a duel (Virchow declined).  But Virchow is most famously known for his “cellular theory”.  He challenged the popular idea at the time that cells were more or less passive bystanders during the disease process.  In contrast, Virchow believed that diseases result from changes in cells, as opposed to just overall changes in tissues or organs.  (In modern times, we’ve reduced this even further to identify changes in molecules). 

But the most famous part of Virchow’s cellular theory is his argument against the then-accepted notion that cells could spontaneously arise from a thick organic fluid called the “cytoblastema”.  The idea of spontaneous generation (the origin of living organisms from nonliving material) had been dying a long death at the hands of other scientists for the last two hundred years, and it was slowly becoming accepted that even microbes cannot spontaneously arise on their own (which had seemed to be the case in rotting meat).  Virchow applied this idea to cells in the human body, saying that every cell must come from another living cell, as he clearly stated in Cellular Pathology:

Where a cell arises, there a cell must have previously existed (omnis cellula e cellula), just as an animal can spring only from an animal, a plant only from a plant… No developed tissues can be traced back either to any large or simple element, unless it be unto a cell.

“Omnis cellula e cellula” – all cells from cells.  A fitting rallying call for such an important theory.  Although it was such a game-changer, I have no doubt that had he not proposed it, someone else would have suggested it within a few years, especially since Louis Pasteur finally put the idea of spontaneous generation to rest the same year Cellular Pathology was published.  (Actually, there is controversy as to whether Virchow stole the “all cells from cells” theory from the Polish scientist Robert Remak, who first proposed a similar idea some years before.  No great idea is formulated in isolation – all ideas from ideas – but if Virchow did use Remak’s theory, we must fault him for not attributing the proper credit.)

The general principle that tissues, and therefore organs, and therefore organisms, ultimately originate from a single cell is the idea behind stem cell theory of modern times.  We all start off as one cell, a zygote.  The zygote divides, then divides again, and again, and again, and again… until the mass of cells eventually becomes a human being.  Along the way, some cells start to change – “differentiate” – into more specialized forms – liver cells, nerve cells (neurons), muscle cells, and skin cells – until you have a fully-functioning human being.  The amazing part of his process is that whenever a cell divides, it makes an exact replica of its DNA, so all of the different types of cells in our bodies have the same genes.  So how can cells be so different, yet have the same set of blueprints?

The answer is that cells control which genes are going to be active, and they do this by turning genes on or off, or cranking them up or tuning them down.  Therefore, a liver cell and a skin cell, even though they both have gene X, it may only be active in the liver cell and turned off in the skin cell.  It’s as if each cell is an extremely complicated machine containing thousands of switches and knobs, and the degree and sequence of switch-flipping and knob-turning will determine what the machine does.  What’s more, because all the cells in our body ultimately came from one cell, a sort of “family tree” can be drawn.  The two most common cell types in the small intestine – enterocytes and goblet cells – are virtually “cousins” because their common ancestor is only two or three cells back on the family tree.  However, an intestinal cell and a neuron are much more distantly related, even though they share the same DNA and are ultimately derived from the same cell.

Until recently, it was believed that you can only move in one direction on the cellular family tree: from zygote to differentiated cell.  This is why embryonic stem cells are of great interest, because, according to stem cell theory, these cells can be persuaded to convert to any cell type, although this is no easy task.  But lately there have been breakthroughs in reverting differentiated cells back to their ancestral cells (so-called “induced pluripotent cells”), which may be more useful (and less controversial) because these ancestral cells are much further along in the family tree than embryonic stem cells (think “grandparents” as opposed to “great-great-great-great-great-great-grandparents”).  Scientists have applied this theory in attempts to develop cures for diseases where certain cells are missing or being destroyed, such as diabetes and neurodegenerative diseases.  In the case of diabetes, type 1 diabetics suffer from a loss of the insulin-producing beta cells in the pancreas.  One type of treatment, scientists are hoping, would be to remove some of these precious cells from the patient, coax them into multiplying in the lab to increase their numbers, and then put them back in the patient.  The problem has been that the beta cells don’t seem to grow well, neither in the body nor in the lab, and the ones that do grow in the lab seem to undergo changes and don’t produce much insulin.  So to get around this, researchers at The Hebrew University and Tel-Aviv University in Israel have applied stem cell theory.  They isolated beta cells from the pancreas, and then they used a virus to induce the expression of certain genes which make the beta cells revert back to a state similar to their ancestral cells, which can divide in the lab.  But the cells can still “remember” that they were once beta cells, so, once they have undergone sufficient divisions, they can be easily induced to undergo re-differentiation back into insulin-producing beta cells.

Of course, this is more of a proof-of-principal experiment and far from an actual therapy.  Any treatment that involves a virus is going to undergo serious scrutiny, and a lot of work will need to be done to see what effects this manipulation has on the long-term safety and functionality of the beta cells.  But it is an important step because theoretically it could be applied to many different cells in all types of tissues. 

I think Rudolf Virchow would be proud.  So much possibility from such an elegantly simple theory: all plants from plants, all animals from animals, all cells from cells.

 

Sources:

Virchow, Rudolf.  Cellular Pathology.  John Churchill London, 1859.

Simmons, John. Doctors and Discoveries: Lives that Created Today’s Medicine. Houghton Mifflin Harcourt, 2002.

Bar-Nur, O, et al. “Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells”. Cell Stem Cell, 2011.

Posted in Biology, Essays, History, Medicine | Tagged , , , , | Leave a comment

The Alien from Mono Lake

Mono Lake
Mono Lake (image from Wikipedia Commons)

One of my favorite science fiction movies is Contact, the Robert Zemeckis vehicle that spent some twenty years in developmental hell before finally being released in 1997.  Based on an idea from Carl Sagan (who wrote a book from the story only after the production of the movie got delayed), Contact tells the story of Ellie Arroway, a passionate astronomer who is determined to find proof of existence of extraterrestrial life by tirelessly combing the night sky with satellite receivers.  Not only does she succeed in finding and translating an alien signal, but she also gets chosen to be the one that meets the creature at the source.  The film got panned by a lot of science fiction fans who watched the entire two-and-a-half hours to catch a glimpse of the alien, only to find that it appears to Ellie in the form of – spoiler alert – her deceased father.  I have to admit that I too was a bit disappointed, but, nevertheless, I still really like this movie for two reasons.  First, because it explores the potential conflicts that arise if we ever do make contact with intelligent life from another planet.  Would they be friendly, or would they see us as a disposable obstacle in the quest for natural resources (an attitude that is, unfortunately, not foreign to our own species)?  And how would it affect the way we see ourselves, especially since we are so used to living on the most special planet in the universe?

The other reason I like Contact is because it takes the point of view that there are countless numbers of extraterrestrial civilizations that we just haven’t discovered yet, and that thought tickles the scientist in me.  Ask biologists or biochemists if they believe in the possibility of life beyond our planet, and they will probably say yes because they know that life here on earth is ultimately made of components that follow the basic rules of chemistry, and there is no reason to believe that life wouldn’t arise under similar conditions on other planets.  And considering that there are billions of planets in our galaxy alone (and hundreds of billions of galaxies in the universe), it is almost a given that life is out there. 

Just last fall, NASA announced that they had found the very first earth-like planet nestled in the constellation of Libra about 20 light years away from earth.   According to one astronomer, the planet, Gliese 581 g, has a 100% probability of harboring some kind of life.  It’s about 7 times closer to its sun than the earth is to our sun, but Gliese 581 g’s sun is a relatively weak red dwarf about a third the mass of our sun, and puts Gliese 581 g in the optimal zone to support life.  The discovery caused a lot of excitement.  Imaginations soared.  A couple of people even laid claim to the planet and began selling plots of alien land on eBay.  And then, only two months later, NASA made the announcement that many sci-fi fans had eagerly anticipated: NASA scientists had made a breakthrough in the search for extraterrestrial life.  Here’s what they said:

NASA will hold a news conference at 2 p.m. EST on Thursday, Dec. 2, to discuss an astrobiology finding that will impact the search for evidence of extraterrestrial life. Astrobiology is the study of the origin, evolution, distribution and future of life in the universe.

You can only imagine the buzz this new announcement generated over the Internet. Had life been found on Gliese 581 g?   A rogue radio signal, a cluster of streetlights, a cloud of swamp gas – any hint of life would forever change the way we look at the sky at night.

So you can also imagine the disappointment when, at the promised time, NASA made its announcement: A bacterium that can live off of arsenic had been discovered at the bottom of a California lake. 

No signs of extraterrestrial life, no whispers from a distant world.  Libra’s red dwarf, for now, remains a silent speck in the sky.  It was the biggest let-down for sci-fi fans since the end of Contact.  Why should NASA care if a bacterium lives on arsenic?  Or why should any of us care, for that matter? 

Well, here’s the answer: because it would raise the possibility that life could exist on planets unlike our own. 

All life as we know it is made of six “essential” elements: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur.  All of the essential elements are made up of atoms that are relatively small compared to atoms of other elements, which is why they are clustered together in the top three rows of the periodic table, with the rest of the lighter elements:

Periodic table

The periodic table, with "essential" elements colored orange. Phosphorus (P) and arsenic (As) are outlined in red.

Elements in the same group (column) of the periodic table have similar properties, so it is theoretically possible that an element may be able to substitute for another from the same group, particularly if it is only one element away (up or down).  Some good examples of this are found in some species of microscopic diatoms which use silicon instead of carbon to make their exoskeletons.  Carbon (C) is in group 14 of the periodic table, and silicon (Si) is one element down, in the same group. 

Cells use phosphorus (P) to make DNA and fats, to store and transfer energy, and to modify sugars and proteins.  Arsenic (As), that old poison-of-choice for Victorian murderers, is in the same group (and only one element down) from phosphorus, so it has been hypothesized that arsenic could functionally substitute for phosphorus when arsenic is more abundant in the environment.  What’s more, the biologically active form of phosphorus is phosphate, which is phosphorus bound to four oxygen atoms, and arsenic can react with oxygen in same way to form arsenate:

Phosphate and arsenate

Phosphate (left) and the larger arsenate (right)

(Nitrogen, also in the same group as phosphorus, can also react with oxygen to yield nitrate, but it can only stably do so with three oxygen atoms due to the small size of the nitrogen atom).

So how would you find examples of life on earth that can survive on arsenic instead of phosphorus?  Phosphorus is more abundant than arsenic on this planet – in fact, wherever you find arsenic, you’ll probably find a lot more phosphorus – so any form of life that could use arsenic would probably preferentially use phosphorus anyway.  So the best you can do is to look where there is a high level of arsenic, find something living there (most likely bacteria), and take away its phosphorus supply while still providing it with arsenic.  If something grows, it is likely using arsenate instead of phosphate to make DNA.

This is exactly what Felisa Wolfe-Simon did.  Wolfe-Simon, a microbial geobiologist and a research fellow for NASA and the US Geologic Survey in the San Francisco Bay area, has a keen interest in the interplay between ancient forms of life and the chemical elements in their environment, and how the exposure (and uptake) of certain elements affected biological evolution, particularly in life’s early stages.  She goes by the nickname “Iron Lisa” – a somewhat clever derivative of her first name (Fe [Iron] + Lisa).  Like many successful scientists, she has a definite creative side that serves to balance and fuel her scientific mind (she graduated from college with dual degrees in biology and oboe performance).  She pondered the arsenic question for years, summarizing the hypothesis in a 2009 article in the International Journal of Astrobiology, where she suggests that our planet may have once been home to alternate forms of life that utilize non-typical elements such as arsenic, and that some of these ancient organisms may still exist:

We hypothesize that ancient biochemical systems, analogous to but distinct from those known today, could have utilized arsenate in the equivalent biological role as phosphate.  Organisms utilizing such “weird life” biochemical pathways may have supported a “shadow biosphere” at the time of the origin and early evolution of life on Earth or on other planets.  Such organisms may even persist on Earth today, undetected, in unusual niches.

 Wolfe-Simon had the knowledge and the access to the technical expertise of colleagues to test this idea.  All she needed was a source of bacteria, preferably from some place that is naturally high in arsenic (an “unusual niche”).  She chose Mono Lake, a relatively small, shallow body of water just east of Yosemite National Park and practically in her backyard.  Because there is no outlet for the lake’s water, dissolved salts and minerals (including arsenic compounds) accumulate to make the water very alkaline and saline – at least twice as salty as the ocean.  But this lake is not barren.  Single-celled algae live in the warmer waters along its coast, and they form a critical link at the end of a surprisingly active if not typical food chain.  During the summer, the lake boils with trillions of the tiny brine shrimp Artemia monica, a species unique to this particular body of water.  Brine flies scuttle around its beaches and lay eggs in its water, using bubbles of air as mini scuba tanks as they crawl across the lake’s floor.  The fly larvae, once a staple for indigenous people of the area, are an important food source for thousands of species of migratory birds as they journey through the valley.  All this, in and around a lake that contains a human-lethal dose of arsenic in every 10 liters of its water.  If there were organisms that could incorporate arsenic into their biochemistry instead of phosphorus, there would be a decent chance that something could be found in Lake Mono.

So Wolfe Simon and colleagues began the search for this hypothetical creature by collecting sediments from the lake and diluting the samples over and over in a nutrient broth free of phosphorus but with increasing amounts of arsenic.  Most of the living microorganisms died off; what survived was a single strain of bacteria that was still able to multiply in the presence of arsenic and, supposedly, in the absence of phosphorus.  Wolfe-Simon named the strain GFAJ-1 (“Give Felisa A Job”), and set about trying to determine if it was actively substituting arsenic for phosphorus in its DNA.  Her group used mass spectrometry to analyze the bacteria and its DNA after it had been growing in arsenic, and found that As was present in the protein and DNA fractions of the cells.  The group also measured X-ray absorption and concluded that the bonds that As was forming in the bacterial DNA were similar to those formed by P in typical DNA.  They submitted their findings to the high-profile journal Science, which published an online version of the article on December 2, 2010 – hence the proud announcement by NASA the very same day.

But Science did something a bit out of the ordinary for this particular paper: they waited to publish the hard-copy version of the paper until the scientific community had an ample amount of time to review and to respond to its findings.  When Science did eventually print the paper, it was accompanied by eight critiques plus a rebuttal by Wolfe-Simon.  Most of the critiques pointed out specific problems with the techniques used in the paper, such as questionable calculations of As:P ratios in the bacteria, a relatively superficial analysis of the bacterial DNA, incomplete purification of the DNA, and the fact that the bacteria themselves look a bit swollen and “unhealthy”  when cultured in the presence of arsenic:

GFAJ-1

GFAJ-1 grown in phosphorus (left) and arsenic (right). (Images from Wikipedia Commons)

But perhaps the biggest problem that Wolfe-Simon and colleagues must face is that arsenate is much more unstable than phosphate.  Phosphate esters – which are required for the incorporation of P into DNA – have half-lives of millions of years, while the analogous arsenate esters only exist for a millisecond before they fall apart.  So how could the cell use arsenate as a building material?  This is the main reason why many biochemists find the results of this study so hard to swallow, and why the burden of proof lies so heavily on Iron Lisa’s shoulders.  But to her credit, she has made GFAJ-1 freely available to other scientists with the hope that they will repeat and expand upon her own work.  We shall see if this little creature will find its way into microbial history.

While it may yet be possible (however unlikely) that life can arise in the absence of one or more of the essential elements, our own planet of earth serves as a shining model of how life can materialize when those elements are abundant and the weather is right.   So, while the questions surrounding GFAJ-1 remain unresolved, I think the focus for NASA should be more directed towards the other discovery of 2010: Gliese 581 g.  If a planet like Gliese 581 g was so easily found in our own neighborhood, think of how many other earthlike planets there could be in our galaxy alone!  On the other hand, the silence of the universe serves as a solid counter-argument, publicized memorably by physicist Enrico Firme in 1950: “If the universe is teeming with life, where is everybody?”  But perhaps the rare event is not life itself, but rather the emergence from that life a sentient species capable of travelling or communicating billions of miles across that vast, cold, empty vacuum of space.  Nonetheless, even if we were to find extraterrestrial life, and even if it were only a planet crawling with microbes, the discovery would send shockwaves through our culture and rearrange our views of our own little planet.  No longer would earth be an exceptional diamond in a barren universe.  Just like when Galileo announced the sun did not revolve around the earth, or when Darwin wrote that we are a mere twig on the tree of life, or when Newton revealed that an object is not at rest just because we perceive it to be so – science would strike another bittersweet blow, ever forcing us to shift our gaze from our narrow but comforting realm to a wider but much humbler understanding of ourselves.  Yet we will never stop searching – our curiosity is our bane – for those tiny hints that our world is not unique.  And we will keep finding them, whether they be twenty million light years away or on the salt-encrusted shore of a desert lake in California.

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