Chemistry, Evolution, and Christian Worldview

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Arsenic Life?

a puzzling biochemical press conference // the natural laboratory at Mono Lake // a global scientific test // phosphorus builds, arsenic kills // how to mop up arsenic // magnesium’s fitting relationship // a less wonderful life is more predictable

GE OL OGY SH A PE S CH E M IST RY AT MONO L A K E

In December 2, 2010, at 11:16 a.m., I received the first of three emails from students in my biochemistry class, all asking if I had heard the news. A press conference at 11 a.m. had announced that scientists had discovered a bacterium that uses arsenic instead of phosphorus in its DNA. Soon there was a hashtag for this: #arseniclife. We were excited and a little puzzled. I had just lectured about how phosphorus was uniquely useful to DNA. I shrugged and mumbled something about how textbooks can be rewritten.

Today, the dust has settled— and the textbook reads the same as ever. DNA is made of phosphorus, never arsenic. That December press conference was followed by two full years of multiple experiments in labs around the world. It confirmed what the textbook said all along, yet the story was well worth it. The “arsenic life” story was never just about microbiology. It’s about science itself, how we know things, and the nature of natural history.

Everyone should know this story. It will temper expectations when the next press- conference- induced hashtag makes its way halfway around the world while science is still lacing up its boots. More than that, it shows something deep about what kind of world we live in, something underreported because it is so intricate and comes from so many different places. There is a hidden order that makes some sense of biology and even sociology, and that hidden order is chemistry.

All life, from a lakewater bacterium to the neurons firing in your brain as you read this, is hemmed in. It is free to randomly adapt to its surroundings with nearly infi- nite creativity, but its overall path is as constrained as if it were walking on the deck of a ship crossing the ocean. The ultimate movement, on the scale of billions of years, is shaped by chemical rules.

One of these rules is that phosphorus makes good DNA, while arsenic does not. To reach this conclusion, we have to start where the arsenic life story started. The home of the purported arsenic- using bacteria that caused all this trouble is in a remote spot of California called Mono Lake.

McFarland, Ben. A World from Dust : How the Periodic Table Shaped Life, Oxford University Press, Incorporated, 2016. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/gcu/detail.action?docID=4413924. Created from gcu on 2021-03-26 08:27:58.

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Mono Lake sits at the bottom of a basin just east of Yosemite, at the foot of Mount Conness. It is one of the oldest lakes in North America, peaceful and uniquely beauti- ful, with towers of rugged tufa that look like they belong on an alien moon. It is also poisonous. Its arsenic- laced waters put the surrounding ecosystem under constant chemical threat.

Mono Lake is an unusual place, hosting unusual life, which even uses unusual atoms. Its unusual chemistry comes from its unusual geology. From above, Mono Lake is an asymmetric shape, its west shore squarish and angular, its east a round arc. This sharp western edge is cracked by a geological fault, traced by Highway 395. West of this fault, the Sierra Nevada mountains are pushed up by deep geological forces, while to the east, the lake is pulled down. The mountains to the west catch the moisture so that Mono Lake itself is arid and rain- shadowed. This is where the Nevada desert begins.

Highway 395’s fault still bubbles with potential volcanoes. The pressure from underneath raises the entire Sierra Nevada range by about a millimeter a year, tilting it up and away from the Mono Lake basin. Sometimes the pressure is released explo- sively. A volcano 250 years ago suddenly formed a new island in the middle of lake.

The water in Mono Lake is a concentrated, liquid form of the Sierra Nevadas. Like the Dead Sea, Mono Lake sits at the bottom of a bowl of rock, with many streams running in but no streams running out. Once an atom arrives at Mono Lake, it can- not leave unless it is light enough to evaporate up, liquid enough to seep down, or lucky enough to be eaten by an animal that can walk or fly away. Water carries heavy rock atoms down from the surrounding hills and they are trapped.

At Mono Lake, the water is as much mountain as it is lake. The dissolved rock, especially the calcium, makes Mono Lake’s water very “hard.” It is so hard that when it evaporates, towers of tufa rock are left behind (Figure 1.1). The classic album cover to Pink Floyd’s Wish You Were Here was taken at Mono Lake. It shows a diver’s legs projecting out of blue water with wrinkled towers of sand- colored rock all around, as if his splash was turned to stone. Sometimes the water in lakes like this can get so “hard” that a bird sitting on the water too long will calcify. The rock creeps up and coats the bird’s feathers, eventually overtaking and ossifying the entire bird, like something from the works of Edgar Allan Poe.

Tufa towers are built from chemistry, and the work is done by time. You can make your own by mixing baking soda, table salt, Epsom salts, and Borax in a gallon of water, then adding calcium chloride. Your bucket will include six elements important to rocks (and to life): sodium, chlorine, magnesium, sulfur, calcium, and carbon. Only the boron (added as Borax) does not play a major role in this book. After mix- ing, all you need is the patience to wait for the water to evaporate. Over months, inexorably, the calcium will link together with carbonate from the baking soda to make limestone tufa.

As the calcium turns into tufa, the other chemicals stay dissolved in the lake water. The first two, sodium and chlorine, come from table salt and dissolve well in water. Too heavy to evaporate, sodium and chlorine remain trapped in Mono Lake and make it twice as salty as the ocean. Most of the remaining rocky atoms are

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3 Arsenic Life?

surrounded by shells of oxygen atoms in water— carbon as carbonate (that was the baking soda), sulfur as sulfate (Epsom salts), boron as borate (Borax), even arsenic as arsenate (not included here because I presume you don’t want poison in your bucket).

Much of this book is spent thinking about what these chemicals are doing at the atomic level, and there are two major differences when you shrink to this scale. The first is that everything is constantly moving. A river on a still day may look serene, but at the biological level it is filled with animals moving, plants waving, and currents flowing. This motion is magnified at the tiniest levels, where molecules wiggle in place or zip about like bees in a bottle.

Second, when molecules fit together, they only care about two things: shape and charge. Shape is familiar— all atoms are spheres that can stack together like a super- market display of oranges— but charge is unusual. Unless you work with wires or rub your feet across shag carpeting, you don’t normally sense charge imbalances at our macro level. But at the nanometer level, charge moves things around. Each atom is made of heavy protons with a positive charge and light electrons with negative charge. When these charges are symmetric and balanced, the overall charge is neu- tral, but when they fall askew, a chain of domino effects can start, and chemistry can happen.

Fig. 1.1 At Mono Lake, did the unusual chemistry that formed the Tufa towers also reshape the elements in microbial DNA? Also, note how magnesium interacts with DNA’s phosphates.

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Here it’s truer than ever that opposites attract, because positive and negative charges pull together. If the pulling forces put two negative electrons between two positive protons, the negatives tie the positives together with a chemical bond. A group of likewise bonded atoms is a molecule. If opposite charges are on two dif- ferent molecules, the two will pull together. The chemistry of Mono Lake— all chem- istry, in fact— is formed from patterns of positive– negative interactions.

Each “- ate” molecule noted earlier is a different element coated with three or four negative oxygen atoms. These are strong negative charges and can pull on neighbor- ing molecules. Sometimes a water molecule comes too close, so that the “- ate” mol- ecule’s negative oxygen attracts the water’s positive hydrogen, and yanks it right off. Take away an H+ from H2O water, and OH

– hydroxide molecule is left behind. So when rock dissolves in water, the rocky “- ate” molecules make enough OH–

hydroxide to change the water chemistry. This change is measured by the pH scale. If almost all of the water is intact, the pH is 7 and the solution is balanced and neutral. If water is pulled apart to make OH– hydroxide, the pH is above 7 and the solution is basic. If instead it’s pulled to make H+ hydrogens, the pH is below 7 and the solution is acidic.

One rule of thumb is that dark granite is acidic, while light limestone is basic. The light- colored spires in Mono Lake indicate basic conditions, and the lake’s pH is around 10. It has as much hydroxide “base” as milk of magnesia and is only a pH step or two away from ammonia. These basic solutions feel slightly slippery, almost thick, as if you could dive in and leave behind a splash of stone.

So Mono Lake is no garden spot, but neither is it dead. Local geology made the lakewater hard and basic, which shapes the local biology. Fish cannot survive in Mono Lake’s high- pH water, but smaller, more nimble organisms can adapt and get everything they need.

In spring, the lake turns green with life as lake algae gorge on the swollen streams’ runoff. The rivulets that feed the lake bring rock molecules such as phosphate for food. Sunlight gives algae power to grow, so they will piece small molecules together into larger molecules that life can use: sugars, fats, and proteins. Brine shrimp eat the algae, and birds eat the brine shrimp— not to mention the black flies that swarm, breed, and thrive on the lakeshore, which from a human perspective may be a little too productive.

But not all rocks are good for life. The high levels of dissolved phosphate in the spring runoff are accompanied by high levels of dissolved arsenic in the oxygenated form of arsenate, which is also concentrated in the lake. Life has learned to live with the arsenic. It was this extreme ecosystem that attracted scientists curious about the biochemistry formed from this poisoned geology.

BAC T E R I A T H AT DE F Y A R SE N IC

This brings us to the December 2010 press conference about arsenic life. Ever since the 1980s, the era of the cold fusion debacle, scientists have learned to be suspicious of science by press conference. Still, this had something that cold fusion didn’t: peer

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5 Arsenic Life?

review and publication in a prominent journal. A group of scientists, including mem- bers of the NASA Astrobiology Institute, published evidence in the journal Science that bacteria from Mono Lake could use arsenic instead of phosphorus.

The question asked in the 2010 Science paper was provocative: Did the extreme environment of Mono Lake force life to build with poisonous elements? In particular, could a bacterium in Mono Lake have performed the biochemical alchemy of living on arsenic, turning a poisonous sword into a productive plowshare?

Felisa Wolfe- Simon is listed in the first, best spot on the 2010 Science paper that claimed that bacteria can pull this off. She grew bacteria in the lab from Mono Lake mud. Day after day, she would reduce the phosphate levels while keeping the arsenic around, in order to prove that the bacteria were not only tolerating the arsenic but actually using it. Day after day, she came into the lab and the bacteria were still defi- antly growing.

Wolfe- Simon removed the phosphate because of a pattern in the periodic table. There, the symbol for arsenic (As) is directly beneath the symbol for phosphorus (P). Each column in the periodic table contains a family of elements that have a simi- lar electron arrangement and therefore often do the same chemistry. Phosphorus is used by all life to build DNA and cell membranes. Once the phosphate was removed, the bacteria would be forced to borrow the next- best thing from the environment instead: arsenate.

The fact that elements in a column of the periodic table are chemically similar is incredibly useful in the lab. If you want to tweak a molecule, try switching out some of its elements for others in the same column. They often will bond the same but will have different shapes that change the chemistry just a little. In 2006, chemists built a new superconductor from lanthanum, oxygen, iron, and phosphorus. If phosphorus worked, the researchers reasoned, why not try its chemical cousin one box down, arsenic? They did, and it worked, if anything, even better.

In superconductors the two can substitute, so why not in DNA? Before finding the Mono Lake bacteria, Wolfe- Simon asked the same question in a 2009 paper titled “Did nature also choose arsenic?” She speculated that a “shadow biosphere” of arsenate- using organisms may have played a part in life’s origins— in other words, an alien biochemistry.

The problem is that for all known organisms, phosphorus is essential for life, while arsenic is only essential for death. In this case, their chemical family resemblance explains why arsenic is such a dangerous poison (and useful operatic plot device). Today both molecules are found surrounded with oxygens, as the “- ate” molecules phosphate and arsenate. As the periodic table would allow us to predict, their shapes are the same, and their sizes are also practically the same: if phosphate is a handball, then arsenate is a racquetball. If you can mistake one for the other when rummaging around inside a gym bag, then the cell likewise can grab an arsenate when it intends to use a phosphate.

Phosphate and arsenate may look the same, but they do not act the same. If you ingest too much arsenic, you will experience headache, confusion, and sleepiness. Your body tries to expel it out of, ahem, one end or the other. Many different parts

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of your body break down at once. Your stomach and muscles ache and convulse, and your kidneys malfunction. Everything that grows will misfire, whether it’s your hair falling out in clumps or your fingernails turning white. Enough arsenic causes coma and death.

The difference between life- giving phosphate and life- stealing arsenate is all in the timing. Phosphate latches onto other molecules and stays bound for days, but arsenate binds and then drops off in a matter of seconds. Phosphate is the studious engineer that builds bonds to last, while arsenate is much more easily distracted. Arsenate’s bigger size makes for longer bonds allowing just enough room for water. Water, pressing in from all directions, squeezes into arsenate and breaks its bonds. In a test tube, arsenate chemicals break down in seconds. Arsenic simply does not cohere with the body’s proteins and metabolites— it sticks but does not stick around.

Arsenic is toxic when it is used by the body in the place of phosphate. It is like an old post- it that falls off too fast. Phosphate sends essential messages for muscle contraction and growth throughout the body, which arsenate disconnects. When the phosphate messages die, so does the cell. Rapidly living cells (hair and kidneys) are the first to feel the pinch, but all cells use phosphorus, so all cells are in danger. Heart cells without energy shut down and die.

Arsenate also carries a second kind of danger. Because it is bigger than phos- phorus, arsenic has more room to carry extra electrons. In a cell, arsenate absorbs electrons like an electronic sponge, and this sabotages the cell’s electron balance. Arsenate sheds its electrons randomly, and these extra electrons react powerfully with molecules, especially oxygen. Random reactions shred the cell like interior shrapnel. In an experiment in which yeast cells were fed arsenic, when the electronic balance was disrupted, the DNA fragmented like a dropped egg. Arsenic also pushes proteins out of shape by interfering with their sulfur atoms.

From this perspective, it seems like folly to grow cells in arsenic- rich, phosphate- poor broth, but the proof is in the experiment. Wolfe- Simon’s logic was also based on the periodic table, and in the fact that microbes thrive in Mono Lake, tolerating chemical conditions that destroy plants and animals in hours. A single- celled organ- ism without complex systems may be able to heave a microbial sigh and turn in the absence of phosphate to the next- best thing, even if the next- best thing is normally poisonous. Could a microbe turn an element of death into one of life?

Wolfe- Simon’s experiments showed that the microbes could live in high levels of arsenic and very low levels of phosphate. This was an exciting result, but still, just the beginning. Survival in arsenate does not mean the cell is made of arsenate. Atoms are too small to see with a microscope, so Wolfe- Simon and company looked at the cells themselves, and observed bacteria that looked inflated and shot through with huge holes filled with arsenate. Bacteria usually do this when faced with a toxin— they shove the toxin inside a bubble like they’re cleaning house by shoving all the extra stuff in a closet. Just don’t open the closet.

Wolfe- Simon and colleagues still had to show that the arsenate replaced phosphate in essential molecules. Inside the cell, phosphate sticks to proteins, coats cell membranes, and f loats around as small energy- bearing molecules like

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7 Arsenic Life?

adenosine triphosphate (“ATP,” in which “TP” means tri- phosphate). Perhaps most important, phosphate forms the backbone of DNA, the molecule that tells the cell how to make all the other molecules. If Wolfe- Simon could find arsenate not just lightly stuck to, but permanently fixed in the backbone of DNA, that would close the case.

But the smoking gun wasn’t found. The rest of Wolfe- Simon’s paper contains several surprisingly weak experiments. Isolated DNA showed a faint shimmer of arsenate in a large DNA molecule, but the shimmer was so faint it could have been background noise. X- rays shot through the cells produced a complex shape of data. This did not look like plain old arsenate, so it might have been bound to something, but then again, it didn’t clearly look like anything else either. The data were faint and the error bars shown bracketing the data were too large for many scientists’ comfort, including my own. Instead of a firm conclusion, we had a mystery.

T H E 2 011– 2 012 MONO L A K E BAC T E R I A TOU R

Six months later, Science magazine took a step I had never seen before. It published eight separate critiques, each short and argumentative, all written by scientists ques- tioning Wolfe- Simon’s paper. Chemists cited arsenate’s fragile bonding chemistry; biologists questioned the techniques; everyone asked why more detailed experi- ments weren’t done. (Now, this is the kind of comment that can always be leveled at a paper— it is much easier to propose an experiment than to carry one out.)

The real hope of changing minds was not in print but in the lab. Wolfe- Simon and others sent bacteria around the world, and other scientists set to work. One researcher in Canada even blogged her experiments daily. In summer 2012, a year and a half after Science first published Wolfe- Simon’s results, two papers appeared in Science, followed by two more in other journals, constituting a parade of evidence:

1. A lab from Switzerland found the Mono Lake bacteria grew at “very low” con- centrations of phosphate but not at “very, very low” concentrations. Some trace phos- phorus could have contaminated Wolfe- Simon’s original media. This Swiss lab also used a technique called mass spectrometry that could essentially weigh individual molecules to look for heavy arsenic atoms. Arsenic levels in DNA were too low to be measured, meaning that the DNA was at least 99.99% phosphate.

2. Rosie Redfield and her lab were the live- blogging Canadian scientists. They also found that the Mono Lake bacteria would not grow in “very, very low” concen- trations of phosphate, and their mass spectrometry results also came up empty. The bacteria acted the same in Vancouver as they did in Switzerland. Finally, Redfield stored the DNA in water for two months, and, anticlimactically, nothing happened. Every arsenate- linked molecule known to chemists reacts with water, but this DNA was as sturdy as normal phosphate- linked DNA, mostly likely because it was phosphate- linked DNA.

This is enough evidence to provide the verdict that the Mono Lake bacteria are not arsenate utilizing but are merely arsenate resistant. This showed that they are not

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arsenic eaters, but it didn’t show what they are. How are they so good at discrimi- nating phosphate handballs from arsenate racquetballs? Two more papers answered these questions:

3. Researchers from Israel used a complex and slow technique with X- rays that can see individual atoms. They examined phosphate- binding proteins outside the cell that find phosphate and let it into the cell. In an arsenate- rich environment, these phosphate- binding proteins would be challenged with thousands of arsenate imposters for every phosphate. This lab looked closely at the Mono Lake bacteria’s phosphate- binding protein, to find out why it was especially good at accepting phos- phate and binding arsenic.

Their pictures showed that the Mono Lake protein has a phosphate- binding hole. This hole is like a lock, and phosphate fits inside like a key. Phosphate’s four oxy- gens are spread out from each other and stick out evenly from the central phospho- rus. This tetrahedral structure is like a camera tripod with the top camera- holding arms extended fully up: the phosphorus is at the middle where the four arms come together and at the tip of each arm is an oxygen atom. The phosphate- binding site on the protein is a “lock” that mirrors phosphate’s four negative oxygens with a slightly larger tetrahedral hole of four positively charged hydrogen atoms (Figure 1.2). The unbalanced charges in both the protein and the phosphate become balanced as oppo- site charges attract and tiny magnets snap the phosphate into place.

Fig. 1.2 Phosphate and arsenate molecules both adopt similar geometries, but a protein can distinguish between them by the O- H angle shown at the top of each molecule.

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The Mono Lake protein has one twist, but it’s a good one. On each tetrahedron, one of the oxygens has pulled an extra hydrogen from water. The angle for this hydrogen is 95 degrees for phosphate and it is 109 degrees for arsenate. This struc- tural difference can discriminate between toxin and nutrient. The Mono Lake pro- tein puts a negative oxygen atom that fits with a 95- degree angle for hydrogen but not a 109- degree angle. This one feature holds phosphate in place while arsenate slips out.

4. The last piece of evidence was making the numbers add up. Wolfe- Simon’s very low phosphate level was not enough for a cell to live on, so how did they make up the difference? A lab from Miami found out a somewhat grisly secret: these bacteria scraped up phosphate by cannibalizing the ribosome, the most important molecule in the cell.

Ribosomes are protein- making molecules made from RNA (a molecule that looks just like DNA except for one oxygen- hydrogen pair). Every protein in a cell is assem- bled by a ribosome. A full quarter of the dry weight of a bacterium is in the ribosomes alone. About one- quarter of the mass of RNA is phosphate, making it a tempting tar- get for a phosphate- starved bacterium. The Miami lab saw the Mono Lake bacterium breaking down its ribosomes for their phosphate backbones. Needless to say, this is not a sustainable strategy in the long term. The cell is chopping up its furniture to feed its furnace.

All four studies converged on a single conclusion: the Mono Lake bacterium resists using arsenate as much as possible. Life as we know it will accept no substitutes, and does not incorporate arsenate but finds new ways to reject it. This was not what Wolfe- Simon was looking for, which makes it even more convincing. The biology changes constantly, but it is molded around a solid, incontrovertible fact of chem- istry: arsenate is not suitable for building DNA. Even in Mono Lake, arsenate DNA would be a house of cards thousands high, falling apart within seconds.

PHOSPHORUS: T H E L A ST E L E M E N T STA N DI NG

All this re- emphasizes something biologists have known for a long time, that phos- phorus has an unavoidable association with life. In Mono Lake it makes algae bloom in the spring. This extends back in time. Old rocks, after glaciers pass through, have suspiciously high amounts of phosphate. It looks like advancing glaciers scraped phosphate out from rocks and fed it to the sea, seeding a spring- like burst of plant and microbe activity. More phosphorus made more life, as geology led to biology through chemistry. This has implications for all of biochemistry, because other ele- ments that go well with phosphorus also go well with life.

In terms of the periodic table, phosphorus has biological advantages over arsenate below it, over nitrate above it, over sulfate to its right, and over silicate to its left. In fact, it has advantages over every other element on the periodic table in forming a medium- strength bond to negative charge. This makes it the best choice on the table for energy and information chemistry.

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To understand the chemical advantage of phosphorus, let’s shrink to the scale where we can watch atoms move, bond, and fly apart. Instead of an atmosphere, a microbe is surrounded by a blizzard of flowing water molecules. Everything skitters around like a butterfly unless it is tied down. Movement is mediated by the constant random jostling and flow of molecules. It’s like trying to move through the crowd at a big outdoor festival. In this turmoil, the best shapes will fit together like three- dimensional puzzle pieces, propelled by random motion and guided by electric fields of charge. Stable arrangements of atoms that fit together with shape and charge will hold together better (like phosphate in the Mono Lake phosphate- binding protein).

In this context, a molecule needs three characteristics to be useful for building life’s structures:

1. It must be available in water. 2. It must have a fitting shape and charge for its purpose. 3. Its bonds should last as long as they need to (and no longer).

Both arsenate and phosphate are available in Mono Lake, and have similar use- ful shapes and charges, but the third point distinguishes the two: phosphate bonds for a long time, while arsenate does not. Even in a lakeful of arsenate, life chooses phosphate.

To understand phosphate’s unique qualities, start where a chemist starts: its tet- rahedral (that is, four- sided) shape, as shown in Figure 1.2. When dissolved in water, the molecule tumbles freely, and the four oxygens whirl around the phosphorus cen- ter. From a distance, these atoms blur together into a tiny ball of negative charge, joining with the opposite charges on water molecules in an intricate dance.

No other element is used for this purpose by life because no other element has chemical properties like phosphorus. All of the possible chemical options are shown on the periodic table. Take a moment to find the periodic table (Figure 0.1) at the beginning of this book and consider all those boxes, each representing a different element. (As we go through this book, refer back to that table like a map. It works like the map of Middle Earth in Tolkien’s Lord of the Rings.) At first, it seems like the 90 naturally occurring elements give lots of options to make something else like phos- phate. But the options quickly narrow.

First we have to cross off the elements in the first two rows of the periodic table (from #1 hydrogen through #10 neon). These elements are all too small to fit the four bonds to oxygen needed for our tetrahedral arrangement, so they don’t fit rule #2. Then we have to cross off the elements in the third row and below (after #37 rubid- ium). These are big enough, but too rare or too insoluble in their oxygen- bound “- ate” form, so they don’t fit rule #1.

Then consider the columns. The number of electrons exposed in the outermost level of each atom increases from left to right in the table. The farthest left column has one electron and the next column has two (as does the block of elements run- ning from #21 scandium to #30 zinc in general); #5 boron’s column has three avail- able electrons, #6 carbon’s has four, on out to the rightmost row, which has eight

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11 Arsenic Life?

electrons. About one electron in the outer shell is needed for each bond to oxygen. So we have to cross off everything left of #5 boron, which has too few electrons to bind four oxygens, and also cross off the rightmost row, which has too many electrons. This rightmost row, in fact, is entirely composed of gases that don’t react with any- thing else, snobbishly refusing to form bonds (and somewhat spitefully named the “noble gases”).

When you sit back and look at our once- promising collection of candidates, every- thing is crossed off except for aluminum, silicon, phosphorus, sulfur, and chloride. (We skipped over a few exceptions, but even those are crossed off with a little more investigation.) Just by asking how life can form a tetrahedron in water, we have reduced the possibilities from 90 naturally occurring elements to five.

But four of these five don’t work as well as phosphorus. The oxygen- covered forms of aluminum and silicon are rocks, not metaphorically, but literally. They form strong bonds to each other and like to share their oxygens in long, amorphous linked chains. Sand and glass are sharp- edged silicate materials. These are too solid to allow for the flow a living organism needs to change and respond to its environment. They are as frozen in place as a victim of Medusa and would slice through the flowing structures of life.

On the right end is chlorine, which surrounded by four oxygens is perchlorate. Perchlorate reacts so readily that it is used in rocket fuel. Perchlorate is related to the molecules in chlorine bleach. Like arsenate, it is poison, not food. Some fascinating microbes eat chlorate molecules, but they do not appear to build with them.

That leaves phosphate and sulfate. Like phosphate, sulfate can bond biological molecules and is found doing so outside the cell for chemical reasons described later. But phosphate can perform the chemical trick of linking itself when sulfate cannot. If a cell chains two sulfates together in water, half of them will be gone in minutes, while two chained phosphates will last a thousand days. As a chaining molecule, phosphate is eminently transferable. One oxygen can be its left hand and another its right hand. Phosphate can be passed between all sorts of different groups by switch- ing what it’s holding with its left hand, and then its right.

Some cell signals are turned “on” by attaching phosphate to the turned- on mol- ecule through one of its oxygen hands. I imagine the phosphate glowing faint green, both because pure phosphorus can glow green, and because it signals that a pathway is “on,” a “green light” to the rest of the cell. As the signal propagates, more proteins are attached to phosphate, and the cell begins to fill with glowing green beacons. Eventually a protein is turned on that tells the cell to move something, to make some- thing from DNA, or to do whatever the cell may require. Phosphate is transferring information from one part of the cell to another. Because phosphate is bound to the protein with a medium- strength bond, that bond can be broken with a flick of an atom, allowing the signal to be turned off as quickly as it was turned on.

Phosphate may be even more useful for energy transfer than it is for signaling. Two or three phosphates linked together are held in tension. The medium- strength bonds that hold the phosphates together also hold 7 to 10 negative oxygens next to each other. These oxygens repel the negative oxygens in water, protecting the bond

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12 A Wor l d f rom Du s t

from being broken by water’s reactivity, but they also repel each other (if opposite charges attract, like charges repel). When the bond is broken, the oxygens repel apart and accelerate the breaking, releasing energy as they go. Even more important, the released phosphate interacts better with water. Overall, because ATP is more stable broken than joined together, breaking its three phosphates apart releases energy.

Four slightly different triple- phosphate (abbreviated “TP”) groups are found in the cell, called ATP, GTP, CTP, or TTP, depending on what molecular “handle” they have attached to them (abbreviated A, G, C, or T). Your energy- transferring processes turn the food you eat into linked phosphate groups, the most important of which is ATP. Your muscles get energy to move by splitting phosphates off ATP. Also, the first thing you do to break down the sugar glucose is put a phosphate on it. Phosphate both sends signals and holds chemical power.

Finally, phosphate’s energy helps build the most important of all biomolecules, the long- term information storage molecule DNA and its sister molecule, the short- term information transfer molecule mRNA. There are four types of “TP” molecules, each of which matches one of the four “letters” in DNA.

The four oxygens that surround phosphorus give it a negative charge in water, even when it is linked on its left and right. This is why both DNA and RNA end with “A” for “acid,” because a negatively charged phosphate is an acid. An acid is something that has shed a positively charged hydrogen in water, leaving a negative charge behind.

Phosphate may be the only way for nature to make abundant charged chains in water. The negative charges repel and spread the long DNA chain out like a ticker- tape, which is more easily read than a tangled mess. The whole point of DNA is to hold information that is read like an open book, and phosphate keeps the book open.

Steven Benner is a chemist who redesigns DNA’s “bases,” which is another name for what I have called the “handle” end of the nucleotide, the A, C, T, and G parts of DNA. Benner has chemically welded together new alternative bases with remarkable success, and he has gone on the books as saying that the naturally occurring base structure “is a stupid design” that he can improve. I take his word for it on that.

But the reason Benner redesigns bases is that he couldn’t redesign the phosphate at the other end of the molecule. No chemist can redesign the periodic table to find another element that links DNA as well as phosphorus. Years ago Benner started his design program by trying molecules other than phosphate in the DNA that had none of phosphate’s negative charge. They would tangle and fold without phos- phate’s charged self- repulsion. Benner’s research bore fruit only when he turned to the other end of the molecule. (Other scientists have introduced positive nitrogen- based charges to the backbone, but nitrogen doesn’t work for phosphate’s other pur- poses, because three nitrates together are no more stable than three sulfates together.)

In a cell, phosphate is so important and abundant that it causes the problems of abundance, particularly when it comes to charge. If all of these phosphates are trans- ferring information and energy inside the cell, wouldn’t that mean that the inside of the cell should have a negative charge overall? Such a huge charge imbalance would crumple the cell, or promote frequent electrical discharges that would undermine the stability needed for life.

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13 Arsenic Life?

The cell needs something else to balance phosphate’s charge. It needs something positive that can stick around well, but not too well. It needs something discreet that gets out of the way when it’s not needed. So another element must stand beside phos- phate, if phosphate’s negative charges are to work inside the cell.

M AGN E SI U M : PHOSPH AT E ’ S I N V ISI BL E PA RT N E R

When we teach about ATP in high school biology, we teach it wrong, because we have to. By editing it down from “adenosine triphosphate” to “ATP” we make it possible to fit into a high schooler’s brain along with the rest of adolescence. Come to think of it, it’s a miracle that we get ATP to stick in there, considering. But our terminology, shrunken to three letters, edits out ATP’s constant chemical partner.

Negatively charged ATP must be balanced with positive charge. In the cell, posi- tively charged magnesium provides this balance. The chemist in me says we should write it as Mg- ATP, but the contingencies of history make that collection of five let- ters pretty much unpronounceable in English (“Em- gat- puh”?). We are stuck with “ATP” just like we are stuck with QWERTY keyboards. Whether our labels recognize it or not, magnesium is essential wherever phosphate functions, from ATP to RNA.

Many elements have two positive charges like magnesium, but magnesium’s size sets it apart. If we need a positive charge, we need a metal on the left side of the peri- odic table, so cross off the whole right side of the table. On the left side, water reacts with each element and takes away its outer electrons, so the leftmost column loses its one outer electron and has one positive charge as a result. One positive charge is too weak to effectively balance the negative phosphates, so cross that column off. Three positive charges are too strong— they’d stick but we’d never we able to pry them off to move phosphate around. This excludes the column under aluminum on the right. Between these two extremes are elements that are mostly +2.

Next we consider abundance (rule #1). Since phosphate is abundant in the cell, its balancing agent must also be abundant. Like before, we cross off the bottom half of the table because the bigger elements down there are not abundant enough. Even if the first long row, from scandium to zinc, was abundant enough (which I’m not sure about), all of those elements stick a little too tightly to phosphate as well. They form high- strength phosphate bonds and solid phosphate rocks, not medium- strength phosphate bonds.

We are left with one column: beryllium, magnesium, calcium (the three atoms below them went home during the previous steps). Since atomic size increases as you move down on the periodic table, beryllium is smallest and calcium is largest. All three of these have two positive charges to effectively counterbalance phosphate’s negative charge.

But like Goldilocks with her three porridge bowls, we can reduce this list from three options to one. First we have to account for the fact that we need something that sticks to three phosphates in ATP, not just one. Magnesium fits perfectly between the oxygens on two adjacent phosphates in ATP, but calcium is too big. This makes magnesium the optimal elemental partner for phosphate.

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14 A Wor l d f rom Du s t

What about beryllium? Even though it’s small and appears as easy to make as the other small elements, because of a quirk of nuclear physics, not much beryllium is actually made in stars (see Chapter 3). This is actually very good for us, because beryl- lium is stickier than magnesium, so sticky that it is toxic to life. Beryllium allergy is caused when it sticks to an oxygen- rich pocket on the surface of a cell and provokes an immune response. Because the beryllium never unsticks, it sets off alarms and immune inflammation that wreck the body.

Magnesium’s stickiness to phosphate is used by the bacterium that causes tuber- culosis. It puts magnesium in a protein toxin that uses the magnesium’s positive charge as something like bait. The magnesium attracts the phosphates from your RNA strands and then reacts with them, snapping them into little pieces. Magnesium forms the edge of a knife that tuberculosis uses against RNA.

But the tuberculosis bacterium must be careful with this magnesium knife, because it can cut up the bacteria’s RNA, too. The microbe makes another protein that acts as a sheath for the knife and covers the magnesium. Even though magne- sium is just one atom among thousands in the protein chain, it is at the very center of how this protein knife works. Chemists are already trying to design a small molecule that can stick to magnesium and blunt tuberculosis’s magnesium knife.

Because of the phosphate- magnesium balance, RNA in the cell carried around a positively charged cloud of magnesium ions, a sort of magnesium aura. Magnesium is especially important when RNA must fold up into a compact shape to do some work, like when the ribosome folds up to build new proteins. The ribosome’s negative phosphates are knit together with magnesium, stabilizing it with a web of positive and negative charges. Ribosomes in plants without magnesium fall apart, and the plants turn old before their time because they are missing this one element.

Many smaller chains of RNA form compact structures with specific shapes that help specific reactions along. For a century we’ve known that proteins do this, which we call enzymes. When RNA does an enzyme’s job, it’s called a ribozyme. Scientists who study ribozymes know the value of magnesium. If they forget to add magnesium to their exper- iments, their ribozymes will fall apart. That’s the kind of thing you don’t forget twice.

Experiments have systematically stepped through the periodic table and tested how different metals can tie together the phosphate chain of an RNA ribozyme. This reveals that magnesium is indeed the best element for this job. Magnesium, with its two positive charges, worked so well that we can say, given the choice between one magnesium and a hundred singly charged potassium atoms, this RNA would still choose magnesium. Magnesium also binds on a timescale faster than milliseconds. Magnesium fits quickly as well as tightly into the RNA chain of the ribozyme.

Magnesium helps with DNA, too. For example, it is an essential ingredient when enzymes proofread DNA. On Figure 1.1, where DNA rises from Mono Lake, mag- nesium is found in its favorite place, nestled between the DNA phosphates. Most pictures of DNA don’t include this aspect of its structure because the magnesium moves around so much, but if the magnesium wasn’t there, the negative phosphates would crumple the cell within seconds. Magnesium and phosphate pair as effectively as steak and red wine.

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15 Arsenic Life?

CH E M IC A L RU L E S A N D A WON DE R F U L DISPU T E

The magnesium- phosphate pairing is only the first of many. In a sense, chemistry is the study of pairings. Chemistry studies the bonds between atoms, and every bond is a pairing with two and only two sides. Even the immature form of chemistry known as alchemy had a place for this idea.

On the biochemical timescale, some pairs are permanent, some are fleeting, and some are repulsive and anti- bonding. Some are very picky about direction, and some don’t care which way is up. But all of these bonds come from atoms attracting and repelling through electron imbalances. All are the consequences of the contrast between two physical pieces: miniscule, flighty, negatively charged electrons danc- ing about; and heavy, solid, positively charged atomic nuclei anchoring the electrons through opposites attracting.

The same physical laws that say that positive and negative charges attract add up to say that, in water, magnesium and phosphate pair especially well. One member may be less famous, like magnesium, but general chemical rules tell us that it is still important. When that pairing chemistry is changed even slightly, like if arsenate pairs more fleetingly with its partners, the consequences can be life- threatening.

Life has a vested interest in collecting phosphate and magnesium, and in rejecting arsenate. A set of protein sensors monitors levels of each and keeps them in balance. The phosphate- binding (arsenate- rejecting) protein from Mono Lake bacterium lets phosphate in. At least two proteins open doors into the cell specifically for magne- sium. One particular magnesium transporter opens in response to an ATP- magne- sium “key,” again showing the complementarity of those two molecules.

Not all elements are welcome. Another protein patrols the interior of the bac- terium E. coli, looking for arsenate that sneaked inside. When arsenate fits into its arsenate- shaped binding site, the protein changes shape and binds DNA, which acti- vates arsenate- cleaning proteins that block arsenate’s oxygens with carbon- hydrogen groups. The intruder is neutralized.

Similar arsenate- cleaning proteins are found in plants and animals, especially those chronically exposed to arsenic. In some cases, the periodic table can explain mysterious chemical effects. For example, Leishmania parasites are susceptible to treatments with the element antimony (#51 Sb on the table). But in certain areas of India, such treatments don’t work. Some scientists think they know why, with some experiments in mice to back them up: antimony is right below arsenic on the periodic table and the two are therefore chemically similar. In those areas of India, arsenic frequently contaminates drinking water, and the people who live there have upgraded their internal arsenate- cleaning processes. Because antimony is so chemi- cally similar to arsenic, the two are swept up by the same processes, throwing out the antimony that would otherwise destroy Leishmania. The law of unintended conse- quences extends to chemistry and can be understood with a glance at the periodic table’s columns.

A flotilla of proteins in the cell respond to specific elements, whether as sensors deep inside the cell or transporters opening doors in the cell membrane for needed

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16 A Wor l d f rom Du s t

elements. In the E. coli bacterium, at least five different transporters bring iron inside the cell, which is a huge energetic investment and shows that iron must be pretty important to life. There are also five transporter proteins for zinc, although only two let zinc in and the other three push it out. Copper has two doors opening out; nickel, manganese, and molybdenum each have one door opening in; some magne- sium proteins also work for calcium; and one protein ejects both nickel and cobalt. Sodium and potassium also have proteins responsible for them, pushing sodium out and potassium in.

In this way, the proteins in the cell tell us which elements are crucial for life. Why in and not out, or out and not in? Each has its own chemical reason and rule. Many, like phosphate, play irreplaceable and unique roles. Each element has a distinct his- tory, too. Some have been around since the original quickening of life, and some came late to widespread biochemical use. This history was ordered and sequenced by the rules of chemistry. It even has a chemical direction, moving from left to right on certain segments of the periodic table.

All of this says that, whatever life is, it is not entirely random. Neither is it entirely determined. In chemistry, gases are random, solids are set, and liquids are the in- between stage that flows with motion that is random at the atomic level but predict- able at the human level. Life itself is more like a liquid than a solid or a gas. Life is carried by a river made of chemistry that is pulled along, not by gravity, but by the predictable rules of chemical stability.

The great science communicator Stephen Jay Gould disagreed with this. Gould’s book Wonderful Life (1990) describes the evolution of life as a “lottery” with “thou- sands of improbable stages” (pp. 47, 238). Most strikingly, Gould refers to the “tape of life”: “Wind back the tape of life … let it play again from an identical starting point, and the chance becomes vanishingly small that anything like human intelligence would grace the replay” (p. 14). Gould was speaking of an event that we will return to in Chapter 9, but his argument has been so successful that it needs to be addressed from the beginning.

Gould documented well the damage done by wrong scientific stories. This made him skeptical of grand narratives. So this book’s grand narrative must start from the evidence before it is knit together in a narrative. This story is built from three areas of evidence: rocks (geology), genes (biology), and the chemical rules that tie the two together. To represent these other disciplines, I’d like to introduce Gould to the chemist R. J. P. Williams.

R. J. P. Williams cowrote a book titled Evolution’s Destiny: Co- evolving Chemistry of the Environment and Life (2012) about how chemistry guided evolution. I owe Williams for much of this story. In fact, Williams has been writing books like this for decades now, based on chemical laws. Only in the past few years has the biology caught up with Williams’s chemical predictions, and by and large, it tells the story he expected.

Overall, I think Gould is right when it comes to individual species, but I think he is wrong at the broader levels of ecosystems and planetary evolution. Williams gives reasoning, evidence, and tools that tell a grand narrative tied together by chemistry.

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17 Arsenic Life?

From the proper perspective within this narrative, natural history can indeed be pre- dicted. In the past decade, microbiologists have also challenged Gould by actually running the tape of life repeatedly in the lab, and they too have found predictable patterns.

From this, I conclude that the tape of life is likely more predictable than Gould thought— something less like a tape and more like a river, its liquid flow channeled by the solid banks of chemical laws. We’ve already seen why this river would flow with phosphorus and magnesium, and not with arsenic. The remaining chapters will show why for the rest of the elements.

In each case we begin with the living, thriving specimens at hand. The chem- istry they nimbly perform tells of the underlying rules and pairings of chemistry. Chemists can mimic (as through a glass darkly) some aspects of life in the lab. These experiments tell us the chemical rules, and the best summary of these is in the grid of the periodic table. The periodic table is a map that will guide us through the history of chemistry on this planet.

By paying close attention to biochemistry, a story begins to emerge of order in dis- order, of ingenious organisms persevering through ages of time, of poison and food, of sunlight and water, death and life. It is a story written in elements and channeled by chemical rules of energy, flow, and pairing. We enter the story midway along the road of life, and we begin by looking behind us and counting the footprints.

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