Fire! I Bid You To Burn!!!

When did fire become a thing? Poor old Prometheus… Probably not his fault at all….

When did fire become a thing? No one knows the answer to that question. Fusion certainly occurred before fire—it happens in suns, along with nuclear fission (radioisotopes exist in the sun)—but this is not fire. It appears flamey. It is hot. It radiates through varying segments of the electromagnetic spectrum. But I am going to limit the definition of “fire” to “combustion,” if you don’t mind.

The simplest combustion reaction occurs when pure hydrogen (H2(g)) and oxygen (O2(g)) gasses are combined in a 2-to-1 ratio and given a little energetic push called activation energy (i.e. hydrogen and oxygen will hang out with each other unless they are provided this energy). Diagrammatically, the activation energy looks like this:

activation_energy-svg
Activation energies Ea(X->Y) or ‘Ea(Y->X)’ need to be supplied to initiate the reactions X-> or Y-X, respectively.

The reactants (hydrogen and oxygen in our example) start on the left side of the hump, an appropriate (or excess) amount of energy is provided, and products result on the right side of the hump. The “ΔH” thing on the right side is beyond the scope here but represents a positive, negative, or neutral amount of energy released in the reaction.

The amount of activation energy varies widely from very small (e.g. some explosives) to “no reaction will ever happen regardless of energy input.” Here is what the most basic combustion reaction looks like in chemical reaction shorthand called “stoichiometry:”

2H2(g) + O2(g) → 2H2O(g)

And now, an entertainment of limited scientific value:

Combustion is generally thought to involve hydrocarbons (e.g. octane in the “gasoline” or “petrol” you use in automobiles) or their oxygenated friends the carbohydrates (e.g. cellulose, a polymeric carbohydrate used in paper and present in wood). The simplest combustion reaction is between methane (CH4(g)) and oxygen (2(g)), again resulting water but also resulting in carbon dioxide (CO2(g)) when the reaction occurs efficiently. When it does not occur efficiently or when it occurs in the presence of other substances (e.g. most of the time) it produces by-products including carbon (elemental symbol “C” aka “soot”). Here is the stoichiometry of that simple reaction:

combustion_reaction_of_methane
Combustion of methane in oxygen(with appropriate activation energy added) results in carbon dioxide and water

Methane is commonly known as natural gas, although natural gas is not pure methane when used as a fuel. What the stoichiometry tells us about this reaction is that each molecule of methane uses two molecules of oxygen and produces one molecule of carbon dioxide and two molecules of water, along with an amount of energy released in the process. The energy is used to heat various processes, including home furnaces and water heaters, and used to drive steam and gas turbines to produce electricity.

When octane is used as the hydrocarbon, the balanced equation is as follows:

2C8H18(g) + 25O2(g) → 16CO2(g) + 18H2O(g)

In common English, this means that each molecule of octane requires 25 molecules of oxygen (and that activation energy thing, typically supplied by spark plugs) and results in 16 molecules of carbon dioxide and 18 molecules of water, along with a good burst of energy that drives the pistons, drive shaft, and wheels; the wheels have tires that turn and exert a force against driveways, roads, dirt, mud, water, etc. and the automobile moves forward—or backward—at various speeds as allowed by the transmission.

transverse_engine_layout
A transverse internal combustion engine with the drivetrain for a manual transmission

Candles (if you were wondering where all this leads) are made from paraffin wax, which is a varying mixture of hydrocarbons typically with between twenty (C20) and forty (C40) carbons in their structures. A C20 hydrocarbon like eicosane can have up to 366,319 isomers (isomers all have the same chemical formula of a chemical compound but differ in physical and some chemical properties), while tetracontane (C40H82) has 62,491,178,805,831 (that’s sixty-two trillion four hundred ninety-one billion one hundred seventy-eight million eight hundred five thousand eight hundred thirty-one) isomers (somehow, it seems like more isomers if you spell the number out). The C(xy) compounds between C20 and C40 have numerous possible isomers as well and they increase logarithmically (see chart below) as the number of carbons increase. Not all of these hydrocarbons are in paraffin but these numbers should give you an idea of how chemically complicated a simple candle may be.

log-carbon-no-vs-isomer-no
This website represents output from one method of addressing the number of isomers per number of carbons but it provided a nice Excel-friendly list for my charting purposes. The reference at the bottom of the referenced web page is in German; additional approaches can be found at the link provided at the “discussion” link provided below.

While this already seems like a brain-damaging subclause to our proceedings, the estimates for number of isomers for each number of carbon is actually more complicated than I am representing here. If you have further interest, you can take a look at this discussion. If not, let’s proceed.

There is a standard equation for calculating how much product results from combustion in oxygen of any hydrocarbon; it is:

where z = x + y/4.

This means that in cases where there are 20 carbons as for eicosane, the carbon dioxide and water molecules result in the following way:

2 C20H42(s) + 61 O2(g) → 40 CO2(g) + 42 H2O(g)

or… for each two molecules of n-eicosane (one of about 366 thousand isomers of eicosane) are consumed by combustion, sixty-one molecules of oxygen are consumed, thus producing 40 molecules of carbon dioxide and forty-two molecules of water.

The thing is that it is rare that anyone burns a candle or anything else in pure oxygen. When hydrocarbons are consumed in air, a messier equation obtains to the problem:

Note that carbon monoxide is produced, along with hydrogen gas and the more familiar carbon dioxide and water. This version of the equation is why it is critical to ensure adequate air supply when using a kerosene (or other hydrocarbon-based) space heater in a closed space; the amount of carbon monoxide goes up as the amount of oxygen available goes down. Carbon monoxide, a colorless and odorless gas, causes humans to fall asleep and die due to a special kind of asphyxiation caused by very strong binding of carbon monoxide to the iron atoms in your hemoglobin and myoglobin. Once that happens, those proteins cannot carry oxygen through your arteries and your body is “starved” of oxygen.

carboxyhemoglobin_from_1aj9
Carboxyhemoglobin is formed when carbon monoxide is present; when this happens no more oxygen can be carried by hemoglobin (or myoglobin, a related protein)

Okay, so hydrocarbons burn in air (n.b. there is also lots of nitrogen in air and that produces problematic by-products as well) and that means carbon monoxide, carbon dioxide, water, and hydrogen are produced, along with a substantial amount of particulate matter (e.g. particulate carbon and other solid carbon by-products), which ends up in our shared atmosphere (n.b. there is no “U.S.A. atmosphere” or “China atmosphere,” there is one planetary atmosphere). The most common liquid fuel currently consumed is octane but that is not consumed as pure octane, so there are other hydrocarbons and “stuff” consumed at the same time… in air… which produces problematic by-products.

Here’s a chart of how much world liquid fuel has been consumed and is projected for consumption PER DAY over the listed time period:

world-liquid-fuels-consumption-and-production-balance
Source: U.S. Energy Information Administration

Yes, the chart does indicate that we consume between 94 and 96 million barrels of liquid fuel per day. One barrel of liquid fuel is equivalent to 0.1172 metric tons and a metric ton is 2,200 pounds (for the non-metricized readers). One barrel is 257.4 pounds of liquid fuel. If we are consuming (let’s be modest) 94 million barrels of liquid fuel per day (and let’s be factual) there are 365 days in a year, we are consuming 8,846,490,400,000 pounds of fuel per year. If we were to pretend that all of this were octane (which it isn’t) and all of that octane followed the simplest hydrocarbon-to-carbon dioxide equation provided above (which it doesn’t), we say that every two units of octane produces sixteen units of carbon dioxide. These don’t have the same mass, of course.

To make this simple, a gallon of gasoline weighs about 6 pounds. Each gallon of gasoline produces about 18 pounds of carbon dioxide (idealized as stated above). If we divide the number of pounds of liquid fuel consumed annually by 6, we will have an estimate of the number of pounds of carbon dioxide produced. Well, the number is:

(8,846,490,400,000 pounds of fuel per year)/(1 gallon/6 pounds) =
1,474,415,066,666.67 pounds of carbon dioxide/year

To do our numbers-into-language thing, that is one trillion four hundred seventy-four billion four hundred fifteen million sixty-six thousand six hundred sixty-seven (let’s round up, given the decimal figure) pounds of carbon dioxide produced from the aforementioned pounds of liquid fuel. Pretty incredible, right?

The bottom lines are these:

  1. we can’t breathe carbon dioxide (it chokes us)
  2. actual combustion produces lots of other by-products that are also not useful for human respiration and cause various respiratory illnesses (cancer, emphysema, asthma for starters)
  3. these numbers don’t include gaseous fuel like methane, ethane, propane, or butane (starting with pentane and going up to heptadecane (C17), the compounds are liquid at 25°C), which are also used as fuels.
  4. these numbers don’t include non-petroleum fuels such as ethanol, which is an oxygenated hydrocarbon but also produces all the by-products listed for hydrocarbons
  5. Our global economy is heavily dependent on consuming something that
    1. is finite in quantity and
    2. produces harmful by-products
    3. is going to go up in price as the amount available nears complete consumption
  6. We have not solved the equation for producing less carbon dioxide and less harmful by-products while maintaining our current lifestyles.

Okay, end of lesson. Talk amongst yourselves. This all needs to be solved.

Burn a candle while you’re at it. Couldn’t hurt (much).

Featured image: Catano Oil Refinery Fire

Something is Going Well Around Here!

The 1,000 “like” road marker disappearing in the rear view mirror…

The WP auto-post function just told me that I have accumulated 1,000 “likes,” which are all because the imaginary “you” have been appreciating what I’ve been pouring forth since June 22nd. It hasn’t been four months yet and I have so many “likes!” Who knew?!?

I’ve logged 87 posts (one was a repeat, so doesn’t really count and one was a reblog in respect for a new WordPress-induced friend) in 111 days, meaning that I’ve hit about 78% of the days between start and present. Not bad. Could be better. Let’s see if I can pick up the slack.

Thank you, everyone!

MSOC

Border Follies

There are four borders on our planet and we’re not one of them.

There are four borders on our planet:

  1.     The air we can breathe and the air we cannot.

This border is gradual and becomes more real as any of us ascend into our atmosphere. While the troposphere contains ~80% of our air (which is a mix of gases as faithful readers already know), the stratosphere holds a mere 19% or so. As we leave sea level and go up mountains, there is less air, therefore less pressure exerted by the air upon us. By the time we get around to climbing Mount Everest, there is so little oxygen left in the lower pressures of atmosphere experienced at that altitude that climbers must bring their own. On the other hand, it gets much colder as we climb so there are two good reasons to remain close to flat land: (1) decreasing air and (2) decreasing temperature. This is all graphed out in the Pressure scale helpfully included in the following:

atmosphere-structure
The Structure of the Atmosphere

As a little imagination game, imagine that your roommate and/or spouse (depending on years of commitment) has just cracked open a rotten egg in your kitchen. The spreading smell represents earth’s atmosphere and you want to get as far away from that particular atmosphere as possible. The farther you remove yourself, the less the smell and (for purposes of this analogy only) the less atmosphere there is. Although you can’t really smell air, you can experience its absence quite profoundly (caution: side-effects may include a light-headed feeling, confusion, dizziness, shortness of breath, and death).

2.   The air we can breathe and the earth we cannot.

While sea level and much mountain air is pleasant to breathe, inhaling earth of any kind results in clogged oral and nasal passages. If attempts to breathe earth are continued, bronchi and alveoli may become non-functional leading to a lack of air and at least some of the side-effects mentioned above. Do not breathe earth. While it is good for plants to stick their snouts deep within a nice chunk of earth, particularly when it is enriched with supplements, we must insist that you do not attempt to replicate their behavior. While a diagram of the earth coming into contact with air is not very exciting, there are many important processes that happen between the various solid surfaces, natural and human-made, and the air. Here’s a nice diagram of how the stuff we put into the atmosphere comes back for visits:

atmosphere_composition_diagram-en-svg
The structure of earth’s atmosphere and how what we do on the surface has an effect.

3.    The air we can breathe and the water we cannot.

You would think this boundary is as boring as the one between the air and the earth and you would be incorrect. The atmosphere and bodies of water of significant size have a very dynamic interaction. This incredible time-lapse map of global oceanic currents (courtesy the nice people at NASA) shows their beauty, dynamism, local and transglobal effects, their overall complexity:

But these are only the surface manifestations of phenomena that reach into the clouds and oceanic depths as well. The following video, produced by NASA using data from a number of their satellites and narrated by Liam Neeson, starts with an explanation of how the earth is protected and affected from the sun’s energy output by the magnetosphere.

Chances are that you may have missed the thermodynamic heat pump that powers circulation in our oceans. It is called thermohaline (“temperature-salt”) circulation or conveyor belt. As surface water is warmed by the sun at the equator it is swept north and south toward the icy poles. There it is cooled. As cold salt water is denser than the warm variety, it sinks as it approaches the poles and is swept along the ocean’s floor back towards the equator and elsewhere around the globe. Given the complexity of the currents and circulation, it is thought that it may take up to 1,000 years for one unit of water (let’s say a cubic kilometer) to circulate back to its point of origin.

4.    The water we cannot breathe and the earth we cannot breathe.

This is not our realm. We belong walking along the surface of the earth, breathing the atmosphere and drinking the purer forms of water. We must take our atmosphere with us when we move into the water or earth.

Our takeaway lesson? While you can only breathe the air portions of this very real barrier between the air and water or between earth and water, the effects that air, earth, and water have on each other is astonishingly complex and persistently in motion. Without this perpetual motion going on between the three of them, there would be no weather and no recycling of the gaseous and aqueous realms so necessary for us to live.

The fifth border is imaginary—human-made—compared to the four above. Here is one way of picturing it:

political_map_of_the_world_june_2010
For a more legible version

All these countries, all these governments, all these people divided up by imaginary lines cut into the earth and bleeding the blood of its citizens. Why do some people want to go elsewhere? Why are “violations” of these imaginary lines fraught with so much emotion, so much passion, so much need?

Here’s another way of looking at these imaginary lines:

Adjusted Net National Income Per Capita - US$
Courtesy World Bank databases (if you’re curious, it is free to do your own data searches)

At one end of the spectrum of net national incomes, we have Malawi, a country that is full of nice people who through no fault of their own barely scrape through a year on virtually nothing… and that’s the AVERAGE income! At the other end, we have Qatar, Monaco, the Scandinavian countries, some others (the names aren’t as important as the concept here). The average net national income across all countries is around $45,000/year.

The reasons the imaginary boundaries are important is that people who have governments that don’t work in the interests of the families who live there want to leave and find opportunity elsewhere, which makes their destinations nervous—probably for some good reasons. The destinations of choice all seem better from a distance as the people who want to leave their countries are doing fairly poorly. As more people arrive at their destinations, it is likely that the quality of life in that country will be overwhelmed by newly arrived citizens—and the existing citizens who were already doing poorly and will see a deterioration in their quality of life. On the other hand, the people who leave their countries of origin leave behind many family members, the culture and geography they know and appreciate, their way of doing things, which may have been that way for millennia and are much loved.

The solutions are not easy. I propose the following:

  1. The countries that are not doing well by their citizens must determine why there are disparities in quality of life and correct them so that anyone who wishes can make a one-to-one comparison between their lives at home and their imagined lives elsewhere.
  2. This will often mean that the people who are doing the best in those countries must find ways to share their success with more of their citizens. As it is often the case that wealth from natural resources, agriculture, etc., are harvested by the poor and enjoyed by those who are already comfortable, that seems to be an appropriate basis for sharing. Do corporations and governments own the natural resources of any particular country? I would think all citizens of the planet “own” them equally and that the corporations and governments are only there to ensure equitable distribution of them and any profits that arise from manufacturing.
  3. The countries that are doing well must find ways to channel resources to the countries who are not. These resources must find their ways first to the people who need them the most. Once inequities in education, nutrition, safety, health, domicile and baseline income are addressed, more generalized issues (e.g. governmental corruption) must be addressed as well.

This kind of change is needed. The earth—on its own—figures it all out in spite of the various environmental disasters we keep visiting upon it. Now, we the people must figure out how to stop killing each other—or passively allowing each other to be killed—and work through the inequities that we allow to exist between us.

It is easy to come up with arguments that refute these positions: political, religious, racial, gender, class, family history, income, etc. It is better to stop arguing and get to solutions. We are all one thing and that thing is the human species. Let’s solve our problems so we can all stop with the stupidity.

Featured image

The Tree of Genes

I think that I shall never see/a tree as complex as a tree (with apologies to Joyce Kilmer)

By this time in your life (however old you are), you have heard the letters DNA and RNA countless times… or at least once each. You have been told about genomes, genes, and chromosomes, although you may have what is which and vice versa somewhat muddled. You may have a sense that someone somewhere has mapped out the complete human genome and that it is a large bowl of alphabet soup… with a very short alphabet of four letters—A, C, T, and G. You may have even seen references to other genomes from other creatures going through the process of “sequencing” while this sequencing business may remain a mystery.

This is the thing… all of this genetic data has an implication for how biologists—and lay people—have thought about the tree of life since we started grouping similar-looking creatures together into domain, kingdom, phylum, class, order, family, genus, and species. This “tree” metaphor started taking root (yuk-yuk) in the middle ages and became more complicated as more creatures were discovered (this being the usual term that we use when we find creatures that knew they were there all along without being “discovered”). The way we all look is how our genetic makeup is expressed. The genetic makeup has a much more complicated message about how we are all (by all I mean all living entities on this planet) related.

haeckel_arbol_bn
Attribution

First, all living entities contain some type of polymeric nucleotide, whether it is single-stranded DNA or RNA or double-stranded DNA or RNA. But let’s back up. What is life? The generally accepted biological definition is that life must exhibit seven characteristics:  organisms maintain homeostasis, are composed of cells, undergo metabolism, can grow, adapt to their environment, respond to stimuli, and reproduce. This definition covers most of what we perceive as living with the exception of viruses (there is more on those critters at What is life?). A lot of that definition is dependent on polymeric nucleotides in one way or another. There are other definitions of life but this is sufficient for our purposes.

The number of base pairs determined in the human genome is about 3,079,843,747 (3.1 billion). A base pair is either adenine paired through hydrogen bonding to thymine OR guanine paired through hydrogen bonding to cytosine (fun fact: guanine got its name from the biological source from which it was isolated – seabird “guano,” more commonly referred to as poop):

dna_chemical_structure-svg
Attribution

In RNA, thymine is replaced by uracil, another nucleoside (nucleosides do not have the phosphate “backbone” that links the ribose or deoxyribose sugars together to form RNA or DNA chains, respectively).

Within this 3.1 billion base pair code of life, there are currently estimated to be about 21,000 genes, each of which is a message for creating a protein of one type or another, some of which are structural proteins (i.e. make up parts of our bodies) and some of which have a wide variety of functions (e.g. digesting carbohydrates, initiating certain activities in a cell, etc.). The 3.1 billion base pairs are distributed across the twenty-three chromosomes that are packages of DNA with between 50 and 2,000 genes in each chromosome (fun fact: the chromosome with only 50 genes is the Y chromosome that must be present for a male to be “expressed;” the genes in the Y chromosome contain about 59,000,000 base pairs). These twenty-three are paired with identical chromosomes so that most cells contain forty-six chromosomes, useful during cell division, reproduction, and all that crucial life business. The following illustration may help with the geography of DNA, genes, and chromosomes and how they are related:

chromatin_structures
The major structures in DNA compaction: DNA, the nucleosome, the 10-nanometer “beads-on-a-string” fiber, the 30-nanometer fiber, and the metaphase chromosome.
(Attribution)

An odd factor is that there are long segments within these genes that do not seem to have any function, do not seem to be translated onto RNA and coded into any kind of protein or function determined to date. They are like sets of blank pages interspersed in groups within a novel, which is entirely readable without the blank pages. Some geneticists hypothesize that these unused segments are bits of genetics that may have been used by some previous version of ourselves or may be conserved from other creatures in our long evolutionary history but have gone silent for so long that they are like scaffolds left standing outside (or inside) a completely finished building; they aren’t needed but there they are!

An odd factor is that there are long segments within these genes that do not seem to have any function, do not seem to be translated onto RNA and coded into any kind of protein or function determined to date. They are like sets of blank pages interspersed in groups within a novel, which is entirely readable without the blank pages. Some geneticists hypothesize that these unused segments are bits of genetics that may have been used by some previous version of ourselves or may be conserved from other creatures in our long evolutionary history but have gone silent for so long that they are like scaffolds left standing outside (or inside) a completely finished building; they aren’t needed but there they are!

So here’s another interesting fact. Although we think quite highly of ourselves, we are by no means the creature on this planet with the greatest number of chromosomes. With 46 chromosomes per cell, we sit snugly between the rabbit (44) and the chimpanzee, gorilla, and hare (48), or if you prefer, between the Syrian hamster and cultivated tobacco. The kingfisher has 132 bite-sized nuggets of genetic material, while the adder’s tongue fern contains about 1,200 chromosomes.

ophioglossum_closeup
Ophioglossum vulgatum contains roughly 1,200 chromosomes compared to our measly 46

Does this mean we’re less or more than any other life form? No. The genes on these varying number of chromosomes occur in different zones of their distinct strands of DNA and are translated in different ways and while there are expressed similarities between humans and rabbits (e.g. we both have ears that stick out from our heads, erm, we’re both mammals who carry our young internally) and between humans and gorillas (e.g. 96% of base pair sequences are identical; if the gene sequences are compared, the comparison moves up to 98% of the base pair sequences are identical), the genes code for different traits in the final results (i.e. there are similarities but we’re obviously not “the same”).

The implication of genetics is that the “tree of life” model isn’t as much about external or anatomical similarities and differences but is about how genes on chromosomes are expressed. This has resulted in various reconsiderations of how the “tree” concept can be replaced by more genetically-based models. The bottom line is how are sequences of base pairs (DNA) interpreted by RNA and various resulting proteins to produce the life forms all around us? As usual, the models are more complicated.

The following is a “tree of life” based on genomic sequences. How do you read this (aside from the fact that it is impossibly rich in detail and the print is illegible)? At the center of the diagram are a couple of lines radiating out from a short line. These two lines branch out and become two more and those branch into two and this goes on until you end up with various genus and species names arrayed around the edge of the circle. The genii and species that came before the displayed names are not listed; if this diagram is complicated, imagine what a mess it would be if all life forms were listed!

tree_of_life_svg-svg
For a higher resolution version of this file, please go here.

This does not resemble the classical Haeckel tree of life anymore… except, perhaps, if one imagined looking down on a tree from directly above and saw all the branches radiating out from the trunk.

There’s a fascinating website called Open Tree of Life taking shape as more and more genomic data rolls in from laboratories around the world. This model really gets into the details of how these various branches articulate outwards and become the huge variety of life, some of which we have seen but most of which we will never see as we are typically only vaguely familiar with the life forms that make up our immediate environment. To interact with Open Tree of Life (OTL), click on any round node in the model and a new page will open with all the critters mapped to date that fall under that category. To date, the OTL project only has about 50,000 creatures in this database; there are estimated to be 2.6 million separate life forms known, so there is quite a bit of work to do to complete the project. Nonetheless, this is a far more accurate and dynamic view of life on earth than the featured image ever could have hoped to illustrate.

A really great outcome of this project is something called OneZoom. This website starts with a clickable version of the image below (instructions: go to the website and click on any of the bubbles):

top-level-onezoom-map
Snipped from OneZoom

Each click will take you down that particular rabbit hole of life forms. I suggest clicking on the ladybug: (1) you are likely to have some familiarity with these happy-looking little insects (unless you’ve had a swarm of them in your area) and (2) you are probably going to be familiar with other the creatures you encounter down that particular node of life.

One other site you may like to visit and browse (it will take you a while – set aside a few years… or just nibble!) is the Encyclopedia of Life site. The site was the result of a talk by Edward O. Wilson, one of the great biologists (and certainly the greatest myrmecologist) of our current era (and perhaps of all time). He’s no spring chicken, so be patient as he tells you about his love of all of these critters that should be our friends and fellow travelers.

To close out this episode of “It’s More Complicated Than You May Have Not Been Considering in the First Place,” here is a Smithsonian Institution site for a standing exhibit on genomes:

https://unlockinglifescode.org

And here is a website that delves into genetics in more detail:

https://ghr.nlm.nih.gov/primer

And just because genetics should never be considered without attempting to understand the complex nuttiness of life within any individual cell, feast your eyes and ears on this video (prepare to be astonished at all the work you’re doing while you’re attempting to relax):

One final sentence: If you’re young and scientifically inclined, consider learning as much as you can about genetics and its affiliated disciplines (e.g. sequencing technologies); this will be a growth area for decades to come.

Featured image

(As I am not a biologist or a geneticist, I hope I haven’t made egregious, unforgivable errors that might offend The Biology Yak et al.)

When Sounds Became Stories

The bear went over the mountain…

Most of our fellow critters surrendered to geography at some point in their evolution. One rodent species gets broken up into two species when barriers separate them and the factors that supported their initial growth (e.g. predator species or nutrients) are differentiated between the two locations. This is called allopatric speciation but is just a notion to ponder while following the rest of the post.

This didn’t stop humans, though. For whatever reason, when our ancestors encountered barriers they went over the mountains and deserts, crossed the rivers and seas (and oceans!), and kept on going. Why? The most probable reasons are disputes with family members (intra-tribal disputes), the inevitable inter-tribal disputes that arise after familial separations (because we have a hard time letting go), resource limitations (depletion of hunter-gatherer “raw materials), weather fluctuations (e.g. drought), and good old curiosity (“to see what we could see”).

world_map_of_y-dna_haplogroups
This is a complex map more fully explained here. It follows differentiation in Y-chromosome DNA over a few million years. In this map, the earliest known DNA originates in western African, roughly where Cameroon is located. Also interesting is the first migration is southwards towards Namibia, where the Khoi-san people are thought to still speak one of the original human languages (it is sometimes known as the “click” language – and don’t you dare snicker – their people have been communicating far longer than yours).

Why these peregrinations resulted in different languages is a mystery to me but as we wandered I am sure we developed new words. Perhaps our oral word stores (our familiar/tribal/personal lexicons) just changed by dialect creep and then by lexicon differentiation. There was little need for inland valley people to develop a word for seabirds or dolphins. People who fished the oceans didn’t develop a rich thesaurus for describing desert weather.

As this diaspora continued and time passed (we’re talking , those dialects and these needs to discuss various matters must have changed so much that the initial language and the resulting branches just diverged. There were words that remained the same or similar (compare Germanic and Scandinavian words for “day;” numerous examples in other languages abound) and those that were new and unrelated to any previous word.

The stories they all told to each other diverged as well. The Ur-Cameroonians had different origin myths, different sun and moon myths than the Ur-Namibians (n.b. “ur” has the meaning of “proto” or “early” or “primitive” when added as a prefix), and so forth as the people traveled and developed their own stories about how “it” all works. They passed these stories on down to their children as they did for theirs.

Eventually, the Ur-Cameroonians and Ur-Namibians probably didn’t even know what the other was saying anymore. They could learn to understand but their languages had diverged to the point that they  were distinct (or perhaps these two sets of folks could understand each other well but make no sense of what the pygmies said in the Congo rainforest). It is novel in itself that although the languages diverged they could still be learned; the brain could do both things—make new words and learn other (in a way older) words. Pretty neat stuff!

There are two breakthroughs here: the creation of language and (for it would be a long time before it happened as far as we can tell) the creation of written language and the implicit creation of storage media and engraving tools.

As far as we can tell, it is the Sumerians and Egyptians who first engraved their thoughts into clay and stone using the cuneiform and hieroglyphic methods in roughly 3400 to 3200 B.C.E. But cave paintings in various regions predated these folks by tens of millennia, perhaps as much as 40,000 years ago in Sulawesi. Surely, these were a way for the elders to assist themselves in their duty to tell stories. Once the wall was embellished, it was an artifact of the elders. It is likely that their children saw these initial paintings as revered lessons of the ancestors and that the paintings themselves became part of the story.

Today, we download books through the æther and consume them seconds later. This may have all started because the Ur-Cameroonians went walkabout and forgot their initial language. And that their children eventually came up with ways to depict their stories on bark or cave walls or clay tablets and eventually paper. And these letters you see before you, which aren’t before you at all but are on a server that you are mining for information just as I am doing the same.

Astonishing!

apollo-11_stone_slab
A 25.5 to 27.5 thousand-year-old cave painting from a southwestern Namibian cave

Featured image: Khoi-san cave painting from the western cape of South Africa, roughly 3,000 years old. It is more common to see representations of people in African cave paintings than in the European cave paintings (e.g. France, Spain).

“Cures What Ails You!”

Step up! Step up! Are you suffering from an endless variety of maladies? Just take one swig of this and you’ll be free of all worries!

We are all getting older every day. Even the young get old (please don’t repeat this widely; some of your friends will think you’re losing it). As this happens, many of us try to hold on to youth through various means. Increased visits to our physicians, more time doing exercise, watching what and how much we eat all are efforts to maintain health for as long as possible. Many of us, young and old but particularly as the sun gently sets over the horizon, take a variety of health supplements. Whether various of these substances do any good is a hotly debated matter by, on the one hand, the medical research community and on the other, the supplement industry and advocates for less drug-and-surgery-based interventions.

While this is completely understandable from a purely human point of view, there are various important factors that consumers should understand about the way the supplement and pharmaceutical industries are regulated.

In 2013, a market analysis reported that the global market for vitamins, minerals, and nutritional and herbal supplements (VMHS) was around $82 billion annually and was predicted to grow to $107 billion by 2017. Consumers in the U.S. represent about 28% of that market. Of course, the pharmaceutical industry revenues were around $1.2 trillion in 2014 and are expected to grow to $1.6 trillion by 2018-that makes the pharmaceutical industry about 20 times as large in terms of revenue. On the other hand, costs for the pharmaceutical industry are huge. It takes about $2.9 billion to develop a drug through to full approval by regulatory agencies and takes roughly ten years—often more—to develop any successful drug candidate from identification of a molecule with activity to post-marketing study completion. This does not include sales and marketing costs (advertising, pharmaceutical sales) that are often expensive and consistently are under pressure from regulators to behave more ethically. From identification of a possible chemical structure to successfully obtaining marketing permission from a regulatory agency, only about 5 in 5,000 possible drug candidates make it through the entire process; this is only 0.1% of the drug candidates that start out. This percent is likely to go down as (1) more biological drugs are developed for (2) increasingly rare diseases.

As most VMHS products are naturally-occurring substances that are inexpensive to manufacture in bulk quantities,  as no pre-clinical or clinical studies of any kind are required to place them on market, and as little testing is required at any point in the manufacture-to-consumer supply chain, the cost vs. revenue math for supplements is significantly different.

At the end of the day, we all need to make our own decisions about what we are going to do with our personal health. The following material may help you decide whether supplements are appropriate for your desired outcomes.

VMHS market size: https://www.mckinseyonmarketingandsales.com/sites/default/files/pdf/CSI_VMHS_FNL_0.pdf

Pharmaceutical market size: https://www2.deloitte.com/content/dam/Deloitte/global/Documents/Life-Sciences-Health-Care/gx-lshc-2015-life-sciences-report.pdf

Cost of drug development: http://csdd.tufts.edu/news/complete_story/tufts_csdd_rd_cost_study_now_published

Identity:

The chemical formula or herbal source of any pharmaceutical or supplement is the at the core of the issue. If you have Type I diabetes mellitus, you will be prescribed insulin, which is a specific protein with a specific chemical structure and formula depending on its source (e.g. human, bovine, porcine, genetically engineered). While it is injected in an aqueous buffer with some stabilizers, every component of the injection is checked numerous times during the manufacturing process to make sure that nothing but insulin, water, the buffering salts (which hold the water within a specific human pH range), and the stabilizers all have to be present in very specific amounts and nothing else must be in the injection above a certain very low tolerance. If insulin is not present, patients may suffer and may die. If contaminants are present, either carried through from improperly sourced raw materials (e.g. water, salts) or introduced through inadequately cleaned equipment, patients may suffer or die. These outcomes could have an enormous reputational and financial impact on the manufacturing company. Additionally, worldwide regulatory agencies are required to audit manufacturers and determine if they are following best practices for material sourcing, checking material quality, equipment cleaning, and checking the final product, all the way through packaging and storage pre-shipment. It is a complex and meticulous business that requires a large team working together to ensure that patients get the appropriate product.

insulinhexamerSo, the identity of the product—the insulin in the above example—is very important but every component that enters the diabetic’s body is checked almost as much at various stages in the process.

In general, identity in supplements splits into two categories: (1) items that are distinct chemical entities, whether inorganic (calcium, trace metals such as copper, selenium, molybdenum, other minerals) or organic (vitamin C, vitamin B12, riboflavin, vitamin A, niacin, vitamin E, etc.) and (2) herbal supplements (echinacea, ginseng, saw palmetto, St. John’s wort, yohimbine, black cohosh, ginkgo biloba, etc.), which start life as plants, are harvested and preserved in some manner.

I take a multivitamin every morning, in spite of numerous research studies that indicate this is probably not necessary if my diet is relatively healthy (it is but I am a recent convert to a vegetarian diet). My particular multivitamin contains the following chemical items: vitamin A, C, D, E, K, thiamin, riboflavin, niacin, B6, folic acid, b12, biotin, pantothenic acid, calcium, phosphorus, iodine, magnesium, zinc, selenium, copper, manganese, chromium, molybdenum, chloride, potassium, silicon, lycopene, lutein, boron, vanadium, nickel. Each one of these has a weight or international unit (IU; this has to do with the biological activity or potency of the dose provided) associated with it. Along with some of these vitamins, there is a counterion, which makes the mineral (in particular) a salt form. These are not typically considered to have any important supplementary properties (e.g. magnesium oxide; the oxide does not have any claimed importance in the supplement), although in some cases the counterion is specifically used to impart some supplementary material (e.g. calcium phosphate; both ions are used by our physiology). In addition to these vitamins and minerals, there are excipients, which are the materials that help all of the “active” ingredients hang together, remain stable on the shelf for some specific time, and form easily into a pill. In the case of this multivitamin, the excipients include: cellulose gel, starch (corn & tapioca), hypromellose, croscarmellose sodium, silicon dioxide, gelatin (porcine), and polyethylene glycol. These do not have weights or IUs associated with them but the overall formulation of the pill is an exact science called pharmaceutics. Once a formulation is determined, it is best for the manufacturer to hold to the formulation as the quality of the pills will remain within specified ranges. This means that they will not turn to dust in the bottle or spoil early or break too often during shipping, thus leading to return customers.

There is a new category of supplement known as “USP Verified (uspverified.org). The United States Pharmacopeia Convention is a reputable organization that has assisted the U.S. regulatory authority in assuring the identity and purity of pharmaceuticals for decades. They have recently expanded their scope to assist some supplement companies in verifying the identity, purity, and amounts of vitamins and other supplements available on the market. A very limited number of supplement companies have signed up to participate in this service (you can go to the above website to see what products are covered).

While it is not certain that other supplement manufacturers do not follow appropriate controls, the only “good” reason that some don’t is because it is costly and therefore consumes a bit of profit.

In the pharmaceutical arena (which has many detractors, but not for this reason), the company must submit documentation that the medicine they have researched, developed and are selling has the unique chemical structure of that medicine. For instance (and to make this simple), aspirin (acetylsalicylic acid) must have the following structure as proven by several common, validated analytical tests:
aspirin-skeletal-svgAnother way of saying this is that for each compound, it must have the exact number of carbons, hydrogens, oxygens, nitrogens, sulfurs, etc. in the exact interrelated positions as are unique to that chemical compound.

There is some evidence that some supplement products do not include the chemical compounds (vitamins and minerals) listed on their label or that the substances are present but not in the specified weights listed. The consumer is consuming something pill-shaped but what is it? It may be that the consumer is enjoying a pill-shaped item that is mostly substances that have been tested extensively over the years and are “generally regarded as safe” (GRAS) materials. There are many categories of these materials, which are lumped together under the term “excipients.”

There are ongoing studies being performed by the Center for Biodiversity Genomics at the University of Guelph and at other academic centers around the world which attempts to identify the contents of herbal supplements. These supplements should simply be a preserved form of leaf, root, bark, etc. from some plant for which some ancient beneficial property has been observed. Many cultures from around the planet have used these types of materials, usually directly from the plant in question, for centuries, if not millennia. In some cases, benefits have been seen in some patients (the dead ones aren’t around for a discussion). In many cases, an herbal supplement may fit the old “snake oil” profile: “Good for What Ails You!”

Willow bark, for instance, has some pain, inflammation, and fever relief efficacy (it contains the raw material salicin, which is metabolized to become salicylic acid). If we were to purchase a substance called “willow bark” for the purposes described above, we would have a reasonable expectation that the willow bark would (1) be willow bark and (2) contain salicin. A lot of the studies being performed using DNA sequencing have demonstrated that the herbal supplement industry sometimes sells products labeled very specifically to contain a plant substance that does not contain the plant’s DNA (and is, therefore, not the plant) and does not contain the substance known to provide the desired medicinal effects. This is a type of fraud. It will only disappear if consumers demand more from their supplement providers.

Here are some references for further reading:

http://www.theatlantic.com/health/archive/2015/02/how-supplements-work/385119/

http://www.biomedcentral.com/content/pdf/1741-7015-11-222.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216529/pdf/srep00042.pdf

http://www.ncbi.nlm.nih.gov/pubmed/22970567?dopt=Abstract&holding=f1000,f1000m,isrctn

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882080/

https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-016-1086-0

http://www.sciencedirect.com/science/article/pii/S096399691200292X

http://bsh.ahpa.org/SampleHerb1.aspx

http://www.consumerreports.org/cro/2012/05/multivitamins/index.htm

http://apps.who.int/prequal/trainingresources/pq_pres/workshop_China2010/english/22/002-Excipients.pdf

Purity:

For each medicine or excipient, testing has to be performed to ensure that it is reasonably pure. Well, that sounds like an odd thing to say – “reasonably pure.” What does that mean? The FDA has established criteria that require a medicine to be pure from synthesis by-products (solvents, starting materials used in the synthesis, side products that are not the medicine, impurities that may be introduced during the manufacturing process from equipment used). If the drug is dosed at < 2 g/day, the threshold for reporting any impurity is 0.05%. The impurities must be chemically identified if any one of them is above 0.10%. This adds cost to development and is a significant driver for why quality control procedures are in place throughout manufacturing to ensure purity. They must be qualified (i.e. understood for toxicological and/or pharmacological purposes) if they rise above 0.15% or 1.0 mg/day, whichever is LOWER). When it gets to doing toxicological and/or pharmacological tests, the expense goes up really dramatically! If these are the criteria for drugs, shouldn’t they apply to supplements? I believe so. If you take something labelled “vitamin A,” you should have a reasonable expectation that 99.95% or more of that supplement product is vitamin A, as characterized by its chemical structure:
The excipients used should all be pure as well.

all-trans-retinol-svg

Obviously, material with lower purity profiles are less costly. If a manufacturer were to purchase bulk CMC to formulate in with the vitamin A, it should be reasonably free from impurities as characterized above. If a manufacturer were to use 95% pure carboxymethylcellulose (CMC), it would probably cost less than 99.5% or 99.95% CMC. In several of my previous jobs, I had to purchase gases for analytical purposes (hydrogen and nitrogen most commonly). If I purchased 99.9% pure nitrogen it would cost a bunch more than 99% pure nitrogen. Same applies to GRAS excipients. Is this testing done? It may or may not be. The supplement manufacturers do not fall within the purview of the FDA, so they do not need to prove their purity during an initial application for approval for marketing, nor do they need to prove this on a batch-by-batch basis during manufacturing.

One very important aspect of good manufacturing practices (cGMP) is something called cleaning validation. For medicines, all equipment that touches a drug or excipient must be cleaned between batches. The manufacturer must test the equipment after a validated cleaning procedure has been completed. The equipment must be tested for residual cleaning products (soaps, bleach), bacteria, fungi/molds, solvents, drug, excipients, etc. Is this done in the supplement arena? I don’t know and they don’t have to prove they do this. Their only limitations are consumer-driven, e.g. do consumer’s health see a negative effect after taking their supplements or not?

For further reading: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073385.pdf

Stability:

Another factor is how long the supplement (or drug) retains its optimal purity after it has been manufactured. All chemical compounds, including the salt forms of minerals (calcium chloride), interact with other materials in the environment, principally water (humidity), oxygen (it’s all around us) and light (various wavelengths of light, particularly ultraviolet light from sun can change the structure of chemicals) through various chemical mechanisms. Drug companies test stability properties of drug substance (the active ingredient) and drug product (the pill or injectable, etc.) for months and years during research and development and create strategies to optimize the drug stability (for instance, store insulin in a refrigerator). Supplement manufacturers are not required to do this testing, although some may. When products degrade over time, they create a different kind of impurity called a degradant. These are chemical substances that are related to the drug, supplement or excipients that no longer have the properties for which the product was purchased. There are limits to how long a product should be used (usually it is months, sometimes years) after purchase. The consumer has significant responsibility here. How often does a household keep a partially used medication or supplement for over a year or more and then use some? While it is “probably” not going to do significant harm, it is no longer the product that the manufacturer has tested and provided as approved by the FDA.

So, if you are in the habit of sometimes using supplements, then not using them and so on, keep an eye on the expiration date. If you have been keeping them in the dark at normal household temperatures (between 20⁰C and 25⁰C), you’re probably okay to keep using them for a couple of months or so after the expiry date as this date is probably set for an average case scenario. This does NOT apply if you are taking a biological like insulin. If you are taking an herbal supplement, it is difficult to know if (1) the marketed herb is in the bottle, (2) any stability testing was done on how long the herb will remain effective, and/or (3) whether what’s in the bottle will have the desired effect in the first place. Figure out what you need to do to increase the probability that the marketed herb is in the bottle and follow the expiration date advice, if it exists.

Amount:

I touched on this in the “Identity” section above, but it may bear repeating. On any medicine or supplement, there are markings that indicate how much of the active material is contained in a dose (ibuprofen=200 mg/tablet; vitamin C=500 mg/tablet; etc.). Drug companies are held to high standards, above and beyond the purity and stability criteria listed above. Do supplements actually contain the amount of substance that is indicated? We do not always know. Some testing indicated above in the references indicate that in some cases, there is little to none of the labelled substance in the product sold.

Batch-to-batch equivalence and product-to-product equivalence:

Once one batch of medicines is completed, it must be tested to ensure that it meets all the manufacturing criteria as listed above, but each additional batch manufactured must also meet those criteria.

Additionally, when a generic drug manufacturer creates their product, they must prove it is equivalent through extensive in vivo testing (testing in “normal healthy volunteers” or clinical trial participants) to the product made by the company that initially patented the drug. Do supplement companies do either of these kinds of testing? Does one supplement manufacturer prove that their vitamin C is identical to all other vitamin C products available? No. The upshot of this is that while all of the products are labelled “vitamin C,” one product may deliver more or significantly more than the labelled amount, while another delivers less or significantly less. There is a bit of a rocky comparison here: the innovator drug company has created a unique chemical product for the first time, while the supplement company is taking a compound that is found in nature and creating a product. The bottom line remains the same though – any supplement user would probably like to know that the product they are taking is delivering something reasonably close to the labelled amount of the substance and that this is true for each bottle of supplement they purchase from the manufacturer, regardless of batch or time of manufacture.

Pharmacological Effect:

When a medicine is developed it must show a target pharmacological effect within a statistically significant range above placebo or in the range of similar medicinal therapies; developing drugs with a statistical response below similar medicinal therapies is increasingly seen as not worthy of the enormous expense and time involved in drug development. The studies are done following a variety of complicated and statistically robust clinical trials in (1) normal healthy volunteers when the drug is considered sufficiently safe to allow this (many cancer drugs have toxicity profiles that do not allow dosing in anyone but patients) and/or (2) patients who have been diagnosed with the target illness so that the efficacy of the therapy can be evaluated. Often, the trials are doubly blinded so that the physician and the subject/patient are unaware whether they are receiving a medication or not until after the trial is completed and the results are unblinded. By the time a medication is approved by a regulatory agency it has been dosed in thousands of subjects and patients. All effects, positive and negative (adverse events) are tabulated and are provided to the public (e.g. the horrifying list of often minor potential effects heard on TV ads). Supplements rarely, if ever, go through this kind of rigorous testing. If they are tested in this manner, it is usually by academic centers that want to determine if there is anything to the efficacy claims often cited on various supplement-promoting websites.

There is a particular kind of correlation that is studied. It is called the dose-response curve. A single dose or multiple dose regimen is followed – the dose amount (milligrams, for instance) is the known portion of the experiment. The peak concentration in blood and other fluids is studied over many subjects and patients. In the case of multiple doses over many days, the steady-state concentration is determined. The follow-up pharmacological and physiological data is studied; what effect has the drug had on desired and undesirable outcomes? Is blood pressure lowered (if that is desired) or elevated (usually undesirable)? Are liver enzymes constant (usually desired) or do they change (usually undesirable)? Is mood altered, in the case of psychiatric medicines, in a manner that is desirable or not? Is a tumor reduced in size, and if so, are any side-effects minimal in comparison to the improved health of the subject?

In the case of supplements, the same relationships are often claimed (e.g. reduces free radicals in the bloodstream and tissue (vitamin C), improves prostate health (saw palmetto), improves energy (whatever that means), etc.). These are measurable “endpoints” or results in some way, so why aren’t they measured? The primary reason is that it is costly to do so with the same rigor as the pharmaceutical companies must demonstrate. The secondary reason is that very few of the supplement companies actually own the substance they are selling (e.g. vitamin C or saw palmetto), so they cannot patent the substance itself (pharmaceutical companies have a 20-year patent from the time they list the patent with that agency – and that is YEARS before it is approved or marketed). One way supplement companies get around this is they come up with combinations that are “unique” to their firm, but even in these cases, the substances in the product are not unique and another company could come up with a copy of that product if they have sufficient information. Or they could make up a similar product; as there is no requirement for the supplement company to prove pharmacological effect, there is no real reason for any company to copy another manufacturer’s blend.

Cases where the supplement companies get in trouble:

Probably the biggest example of this is with the ephedrine (e.g. ma huang or ephedra) situation a decade back.

http://www.mayoclinic.org/drugs-supplements/ephedra–ma-huang/background/hrb-20059270

Another is colloidal silver as a homeopathic therapy.

https://nccih.nih.gov/health/silver

Cases where pharmaceutical companies get in trouble in spite of regulations:

Johnson and Johnson had one of their manufacturing plants sidelined because of inadequate quality control (i.e. testing of the drug substances and products they were manufacturing).

http://www.washingtonpost.com/wp-dyn/content/article/2010/07/22/AR2010072206169.html

Several Indian manufacturing plants that export generic drugs to the U.S. have been sidelined.

http://www.raps.org/Regulatory-Focus/News/2015/11/09/23562/FDA-Form-483s-From-India-A-Deep-Dive-Into-the-Problems/

While not an actual pharmaceutical company, this pharmacy compounding company made a product contaminated with a fungus that caused numerous deaths:

http://www.cdc.gov/hai/outbreaks/meningitis.html

https://www.washingtonpost.com/national/health-science/compounding-pharmacy-linked-to-meningitis-outbreak-knew-of-mold-bacteria-contamination/2012/10/26/6e3344ee-1fa0-11e2-afca-58c2f5789c5d_story.html

Compounding pharmacies are not held to the same manufacturing standards as manufacturers (although these (as above) can do the wrong thing as well). The FDA is trying to establish a uniform set of regulations to ensure that this does not continue to be a problem: http://www.fda.gov/NewsEvents/Testimony/ucm327667.htm

Conclusion

The bottom line is that it is all about money. If a company does all the types of testing I’ve alluded to their  costs are higher than if they do only some or no testing. Supplements aren’t cheap. If you go to your pharmacy or grocery store (or supplement store for that matter), all the products of a particular type cost roughly the same, although the ones in supplement stores are almost always more expensive. Who made these pricing decisions? Are you paying for the same type of testing for all the products or not? Honestly, no one except the companies themselves know. It’s even difficult to tell whether they ask themselves these kinds of questions.

So how, you might ask, does the supplement industry get around being more diligently regulated? They are putatively healthcare-related products, aren’t they? The consumers are going to place them inside their bodies and hope for results, aren’t they? Yes and yes. The answer is that the supplement industry has a very powerful lobby and this lobby makes sure that the U.S. Congress does not pass legislation to regulate it. Congress gets paid, in some clandestine way, to ensure that consumers are not protected in the same way they are with pharmaceuticals. That is just wrong.

http://www.theatlantic.com/entertainment/archive/2014/06/john-oliver-explores-the-real-reason-for-americas-problem-with-magic-supplements/373228/

http://time.com/3741142/gnc-vitamin-shoppe-supplements/

http://www.nytimes.com/2015/02/06/opinion/the-politics-of-fraudulent-dietary-supplements.html?_r=0

http://www.cbsnews.com/news/dietary-supplements-latest-government-uproar-no-match-for-industry-lobbying-money/

As a consumer, should we be more interested in what profit our supplement companies are banking or should we be concerned about what we are putting in our bodies and why. I’ll vote for the second criteria. I wish more people understood the applicable criteria so that they would demand appropriate testing and quality control standards as well.

Here is peer-reviewed articles on the dubious benefits of supplements, although there are important reasons to follow your doctor’s recommendations if (1) your diet is not normal for some reason or (2) you are pregnant.

http://annals.org/article.aspx?articleid=728199

The bottom line?

caveat-emptor

Test

Another Slow Day in Paradise

It was another slow day in paradise.

It was another slow day in paradise. A and B were flitting about the huge meadow with its vast and varied flowers, shrubs, and trees, all of them spaced perfectly so every flower, shrub, and tree got the perfect amount of sunlight, the perfect amount of water sipped from the fertile earth. Every kind of beetle, fly, bee, ant, butterfly, and spider floated about in the gentle breeze, while every kind of bunny, mouse, cat, dog, horse, goat, sheep, pig, lion, giraffe, elephant, and gazelle pranced about, munching on all of the good things there were to eat, which sprang back up as soon as they were nibbled. A stream ran through the center of the meadow but then again there were streams with stepping stones every so often all over the place. Some had waterfalls and some had pools of just the right depth in their centers, causing the stream to widen a bit more than usual, then tighten back up after the pool was behind the coursing waters.

Theit (that’s what it liked to call itself when it came down to check in with A and B; it wasn’t a real name, sort of a joke—”the it”—you see?) had just wafted in from everywhere and coalesced in the form of a fluorescent tapir. Theit had tried subtler appearances but had to spend too much time convincing these two that it was it. Theit did it gently as the last time it at coalesced, A and B had run off screaming and it took precious seconds to find them cowering behind a baobab tree. This time, Theit found form behind a yew bush growing near one of the streams and strolled out to talk to “the experiment,” as it called them in its mind.

“Hi A. Hi B. How’s it going down here?” The fluorescent tapir spoke in a perfect East African accent, which sounded startlingly like many of the sounds A and B heard on a daily basis, except shaped more carefully and regularly into sounds that made sense to their minds.

A and B stared at the tapir and knew what it said. This sort of thing had happened before and while it had been confusing and a little terrifying at first, they had grown accustomed to unexpected creatures sauntering up to them and having a chat. After all, they spent a good deal of any day doing the same thing with squirrels and horses. Walking up, having a chat, the creatures chatting back. Why not this oddly-hued beast with truncated snout?

“Hi Theit!” they said in unison. It was like they shared a brain. Not always in a good way either. “It’s going the same as always. Nothing new to say, just having a nice day speaking to everyone and enjoying the sunshine and streams and fruits. Did you want something in particular?”

“Well, yes. It’s lesson time.” Theit noticed that both of them shuddered. Theit was aware this was not their favorite activity, which was exclusively wandering about bothering their fellow creatures and picking an excessive number of flowers, which it had warned them about on numerous occasions: “They’re for the bees and butterflies, you two. All you’re doing is taking beauty out of the ground, sniffing it, then throwing it down. Just lean over and do your sniffing on the living thing, please!” he had said. They went ahead and picked flowers as if they had no memory at all.

“Do you remember what we talked about yesterday?” Theit had a really confused sense of time as it meant nothing to it at all, while still being this counter-function it had implanted in the world so that stuff might eventually get done.

A and B shook their heads. No surprise. And, to be fair, it may have been more than a day. Theit needed to work out how to be more regular in lesson-giving.

“Well, we worked through addition and subtraction. Remember those? I give you two fruit, then I give you two more. How many fruit do you have?”

“Two” they said in unison.

Theit breathed in slowly and then let the air escape from the tapirs lungs. “No. I first gave you two fruit. At that time you had two fruit. Then I gave you two more. How many fruit did you have?”

“Two” they said in unison. Then B said “Two two.”

“Good, B! And how many is two two? What do we call that number of fruit?”

“Fruit” said A. “Two two” said B.

“And what do we call “two two,” B?”

“Four?” said B. “Fruit” said A.

“Very good, A! I can hear that you remember the word for two two! That is very nice! Please teach that to A so he remembers, okay?”

“Yes” said B.

“Okay, let’s see how you remember subtraction. If you have four fruit and I ask for two fruit back so that I may share them with other creatures. How many fruit do you have?”

“Two” said B.” “Fruit” said A. At this point Theit thought A’s time might be better spent smacking himself in the head with a rock but Theit didn’t make him do that. Although that made sense. That would have been beneath Theit’s mission with this experiment, which was purely about creation, observation, data, and outcomes.

“B, could you help out A with this subtraction concept? There are bigger numbers to add and subtract and even different ideas that are not addition and subtraction and we must talk about them as well.”

“Okay” said B. A said “fruit!”

Theit was a little worried. It seemed that B was slowly understanding the information being shared but A was not. And both of them, to be honest, seemed more concerned with playing with the creatures and picking flowers than they were in learning. How was multiplication and division going to go if adding and subtracting up to four was proving this difficult? Theit let a rare shudder ripple through the tapir’s frame, although Theit was the one shuddering. Was this another failed experiment like the bacteria that ate all its own young and didn’t multiply? Or the lizard that popped off its own head when it was caught by a predator? They seemed like good ideas at the time—bacteria that controlled themselves, lizards with an escape mechanism—but those had gone wrong.

Theit didn’t really know how long that thought lasted. Was it brief or was it really long? In any case, Theit looked up and A was chasing a bunny through the meadow grasses and flowers and B was chasing A. Neither A nor B were catching what they chased but they laughed as they ran. You couldn’t really hate that.

“Come here, you two” said the fluorescent tapir. “More studying to do!”

A and B took their time but came over looking a little petulant with the tapir, which was an odd look as tapir’s usually provoke giggles rather than petulance. Theit didn’t care. It was time for lessons.

“Okay, let’s try something. It’s a trick I use all the time and it works on stars, planets, galaxies, and universes. I even used it here to make all these grasses and trees and flowers and bunnies. You like all these things, right?”

A stared and B nodded. A looked at B and noticed the nodding thing, which he had seen before, and nodded as B took the time to stare.

“Now, I’m going to talk about multiplication. It’s a way to make big numbers of things out of small numbers of things. Just listen and see if you get a pattern. We’re going to start with “one.” One multiplied by one is one. You can say this more simply just by saying “times” whenever you would say “multiplied by,” okay?”

“Okay” they said in unison. Theit had no idea if they were mimicking him or understanding, so he went on.

“If one times one is one, guess what one times two is?”

A said “one” and B said “two.” Perhaps there was some hope for B.

“Next. One times three is what, B?”

B said “three.”

“A. Anything?” asked Theit.

“One” said A, looking quite determined. Inside, the fluorescent tapir sighed a little sigh.

“B, what is one times four?”

“Four” replied B. A rubbed his leg and looked at a flower.

“Let’s try it something, B. What is four times one?”

“One” said B. Theit’s brief snout wiggled a little. It was confirmed. This was going to take a long time. Whatever would happen when the discussion turned to algebra? The snout wiggled ferociously at this thought. Theit sent a calming wave of thought through the tapir and got it to settle down. No one liked a condescending teacher, even if the teacher was a loveable tapir in bright colors.


Theit had a thought. There was a lot to do. Although Theit was coalesced in various forms all over this universe and every other universe doing this same kind of stuff, Theit thought that it might be time to pay attention to some of the more curious experiments and leave these two to their own devices. Their meadow too. It was a nice meadow and was perfectly balanced to live without dying and replenish itself without looking too sad. That took a certain amount of stamina from Theit’s other projects, which were infinite in number and completely manageable but still….

paramecium_caudatum

Theit visited A and B, this time as an enormous paramecium with lots of undulating cilia. A and B knew it was Theit because they had never seen this thing before. Although they found it sort of horrible, they also knew that it was okay to approach it as it ciliated its way over to them.

“A. B. How are you?”

“Good” they said in unison.

“Getting enough to eat?”

“Yes.”

“Finding enough playmates among the squirrels and bunnies?” Theit asked about these because it seemed that A and B had a particular fondness for them over the larger animals or the ones who roared, although they all lived well next to each other. As was planned.

They both nodded. That seemed like an advance. Perhaps B had taught A the nod thing.

“Okay. Well. I have good news and bad news. Which would you like to hear first?”

“Good” they said again, although perhaps they meant that they would like to hear the good news first. That’s how Theit interpreted it.

“Well then. The good news is that all of this stuff you like is going to stay here. You can play with it all and eat fruit and drink from the streams and have as much fun as you like. Would you like to hear the bad news now?” Theit asked.

“Good,” which Theit took as a tacit understanding that they would now like to hear the bad news.

“Well. Hmmm. The bad news. Erm. I’m not sure how this is going to work out but I’m going to be away for a while. I’m not going to be able to perform maintenance on this place. Instead, you’re going to have to start doing it yourself. What does this mean? Well, it means that I’m going to give everything the power to multiply and divide but I’m also going to give everything the power to add and subtract. New stuff will come alive and old stuff will die. Bunnies and horses and trees and flowers and bees will all multiply but their cells—the little bits of life inside them that make all of this stuff work—will divide. That probably makes no sense to you at all since you haven’t really graduated from basic addition and subtraction (and I really don’t want to think about algebra or calculus, Theit said internally) but I’m hoping that if you see it happening it will make sense over time. It may take a while.”

A and B stared at Theit and didn’t move. They really had no idea what Theit was talking about. This was often the case and sometimes if they remained really still for a sufficient amount of time, Theit was quiet and loped off into the trees. It didn’t seem like this thing was going to lope but they could hope.

“It’s been nice, A and B. You’re the only ones I’ve made that are as hairless as you are. Really, you’re just a variation on a theme. See the hairy ones over there? The ones chasing after a zebra? Yeah. You’re the hairless—relatively speaking, of course—variety. And you walk on your back legs without using your front legs. I’m pretty sure that’s going to have consequences, by the way, but that’s beside the point. I do like you. Don’t take any of what’s about to happen personally. It’s not. Really. I just have a lot to do.”

With this statement, Theit coalesced a giant chunk of wrapped paper blocks out of the air and opened one to a middle page.

“See these? I’m going to call them “books” because they don’t have a name. They don’t have a name because I’ve been thinking about them and it’s come time to make some, so here they are. If you look at this page (it’s called a page, guys), you’ll see black squiggly marks. That’s called “writing” and this writing is in the first language of your creature-type. It tells you stuff. But I can’t wait around for you to learn what it says. I’m going to call this “homework” and you have to worry about what it says or you’re going to be a little out of luck for a long time. Okay?”

“Okay” said A and B.

“Okay” said Theit. Then he made the paramecium lope off into the woods.

A and B stared at the “books” and then stared at each other and then sat down.

Then they got up and ran after the bunnies and squirrels.


After a while, A and B noticed that the grasses changed colors and were replaced with other grasses and other flowers and that when they picked the flowers, they didn’t grow back. They noticed that when they picked fruit from the trees, the fruit didn’t grow right back. They noticed that the beasts who roared stopped other creatures from moving and tore them apart and that the smaller creatures kept away from the roarers. Some of the larger creatures were none too thrilled with the roarers either, so a lot of creatures moved away from them and lived in trees. A and B moved along with them. After they ate all the low-hanging fruit, they climbed trees to get the other fruit. After they ate those, they started to look at the bunnies and squirrels sort of like they saw the roarers looking at the bunnies and squirrels. They caught a few and tore them apart but then the bunnies and squirrels got smart and stayed away. And then the streams dried up, so A and B had to start walking. Their hips hurt. Their feet hurt. Their lower backs hurt. And they learned to feel pain, which led them to cry. Then they learned to say mean things to each other, which made one or both of them cry more.

Then one day, B got fatter and fatter and eventually a new creature popped out. B took care of the little creature until it grew. A wandered around playing with animals and flowers and leaving B to do all the work of raising the creature, which was as hairless as they were. And they kept walking until they found a place to call “home,” which was not much like their old place and had less fruit and the creatures stayed away. But it was home and they raised their creature and then another.

There was only one thing they had forgotten. They left the books at the place where Theit made them and had no idea how to get back there.

It took a long time for them to figure anything out. They remembered Theit fondly now and made up some stories, almost none of which were true. And they left out the bits about the fluorescent tapir and the enormous paramecium. They had a difficult time believing those themselves. So who would believe them?

Featured image

Paramecium caudatum
Facade