Wednesday, December 30, 2015

One Myrrh-aculous Christmas Gift

Biology concepts – synergism, multidrug resistant cancers

The Commiphora myrrha is the classic source for myrrh
resin. It is a short tree that grows in low moisture and
poor soil areas. Its branches are very thorny; some
propose that the crown of thorns Jesus is said to have
worn was made of myrrh twigs.
The three original Christmas gifts are usually listed as gold, frankincense, and myrrh, but why that order? Some say it is because you give gold to a king, frankincense was used by priests, and myrrh was used to anoint the newly dead.

The order goes along with representations of how he was born (as a king), how he lived (as a preacher), and how he died. But I think that sells myrrh short. True, it was used in consecrating and embalming dead bodies, but it is so much more. As with gold and frankincense, there is “myrrh” here than meets the eye.

Like frankincense, myrrh is a resin from a tree that grows in the Middle East, in this case Yemen, Somalia, Eritrea, and Ethiopia. Frankincense and myrrh trees even come from the same family, the Bursceraceae. Being deciduous trees, both frankincense and myrrh are exceptions to the rule that coniferous trees are more likely to be resin producers.

Myrrh resin is an oleo-gum-resin, since it is has essential oils (oleo) and long polysaccharides (gums), as well as resins. It is more complex than frankincense, containing over 300 individual secondary metabolites and other compounds. Being a more complex substance, it might follow that myrrh would have more uses than frankincense, both in ancient times and now. And here is an instance in biology when the logical answer is the correct answer. In addition to being used as incense in rituals and perfumes, it had other mystical properties. It was so prized that it was often worth more than gold.

Greek soldiers always carried myrrh in their travel kits because it was a potent antibacterial and anti-inflammatory agent. Being soldiers, they were likely to be wounded, and those wounds would get infected and swell. If they died, it's good that they had myrrh, because it was also used as an embalming agent and to consecrate the dead bodies.

In Greek mythology, Myrrha was a young lady who committed an awful 
no-no, and was chased across the desert by her father. The gods took pity on 
her and turned her into a tree so she wouldn’t have to run anymore. 
The myrrh resin that drips from the tree is said to be her tears. But I don’t get 
the part where she gives birth to Adonis while she is still a
 tree – family trees aren’t supposed to be literal.
In fact, the Egyptians were some of the first to use myrrh in this way. Combined with natron, a form of salt from the desert, they would stuff the bodies of the dead to pull out the water. This was a big part of the mummification process. The myrrh was there to prevent rotting and to help with the smell.

Myrrh smells good, but tastes horrible. In fact, the name myrrh originally came from the Aramaic word for bitter. To this day, the bitter taste of myrrh oil or powdered myrrh has limited it use in medicines. A recent study fiddled with making emulsions of myrrh in water in order to cover the taste, or adding fat-soluble compounds and using it as a suppository (there is usually good uptake of drugs from the south end of the gastrointestinal tract).

But the ancients still consumed myrrh despite the taste. It is said that someone gave Jesus myrrh dissolved in wine as a painkiller while he was on the cross. Others mixed it with red raspberry leaves to soothe a sore throat. Pliny the Elder wrote of using myrrh to kill bugs in wine and wine bottles before bottling the drink for transport and sale.

Though myrrh has been used for centuries, we have just now started to explain how myrrh functions in these capacities. For example, it is now known that compounds in myrrh called terpenes can interact with opioid receptors in the brain. This is how they act as painkillers.

Myrrh and frankincense components are also being tested in combination as antimicrobial agents. Oils of myrrh alone can kill or slow down some microorganisms; so can oils of frankincense. But adding them together has been shown to be a case of 1+1=3.

This is a demonstration of the concept of synergism. Let’s say that one antimicrobial drug can kill or stop X number of organisms when given at a certain dose. It is often the case that as you increase the dose, you will kill or stop more organisms – up to a point. Almost any drug becomes toxic when you ingest a lot of it. The lowest amount you can give to do the job is the miminal effective dose, and the most you can give is the maximum recommended safe dose.

To get a bigger bang for your buck, sometimes you can add a second drug to the regimen. Drug 1 inhibits or kills X number of organisms and drug 2 affects Y number of organisms. Often, giving drug 1 and 2 together will then inhibit or kill X+Y organisms. This is an additive effect. Drugs with additive effects often work on different targets; they are like eating a foot-long hotdog from both ends. The hotdog goes away twice as fast because the two mouths aren’t competing for the same part of the hotdog.

The white dots are paper soaked in two different antibiotics.
They are put on a plate of bacteria (the hazy diagonal lines).
As the drugs diffuse out, they kill the bacteria (darker, clear
areas, but their concentrations go down the farther they
travel. But look between them, the area where they both are
low concentrations is a bigger cleared area (between red
lines). This is synergistic action.
Every once in a while, using drug 1 and drug 2 together gives you a bigger effect, greater than X+Y; this shows synergy. Synergistic effects are the exception, they don’t come around often and a researcher is lucky to find them. Synergism in drug activity can mediated by different mechanisms, but it may be caused by the second drug turning off the fall-back pathway a cell may use when the primary pathway is affected by the first drug - there are many redundant pathways in cells.

Synergism and additive effects are examples of pharmacodynamic effects; basically, how the drugs work on cells. We will later see how some drugs have pharmacokinetic effects on each other.

When a group in South Africa tested two myrrh oils in combinations with three frankincense oils, they found that a combination of B. papyrifera and C. myrrha oils were synergistic in controlling both Cryptococcus neoformans, a fungus, and Pseudomonas aeruginosa, a gram negative bacterium.

The anti-inflammatory mechanisms of myrrh are just being worked out as well. Recent studies from South Korea indicate that myrrh stops the inflammatory process by inhibiting the production of molecules that promote inflammation. Their 2011 study indicates that myrrh turns off the enzymes that produce nitric oxide, prostaglandins, and some inflammatory cytokines (messengers that have many effects) when inflammation was stimulated by LPS, a cell wall component of many bacteria called lipopolysaccarhide, also called endotoxin. LPS is responsible for things like septic shock and necrotizing enterocolitis.

Rheumatoid arthritis (arthus = joint, and itis =
inflammation of) is mediated by an autoimmune
process that brings much inflammation. Myrrh
has been used for hundreds of years as an anti-
inflammatory drug, but we are just now figuring
out why it works.
They added work in 2012 that shows that myrrh is very good at controlling inflammation after a rupture of the large bowel (which usually causes peritonitis and is very dangerous). This is probably due to its ability to stop inflammation induced by the LPS of the gut bacteria and its ability to kill the organisms as well. Those wise men were really quite wise – they didn’t know why myrrh worked, but they knew it worked, and that was enough.

But even they did not suspect all the wonders of myrrh. It is with cancer that one myrrh component is turning out to be a gift. There are several species of myrrh trees, and a couple, C. mukul and C. molmol, contain a compound called guggulsterone (I love saying that name out loud – go ahead, it’s fun). Guggulsterone is not necessarily toxic to cancer cells by itself, but it may solve a big problem that currently affects many cancer treatments.

We talked a while ago about how bacteria have pumps to kick antibiotics out of their cell, and thereby prevent their action. Cancer cells also have a pump to do this to many cancer chemotherapeutic drugs. The most common of these drug pumps is a membrane channel protein called P-glycoprotein (P-gp). This protein is present in some normal types of cells, working to pump out toxic compounds, like in liver cells and skin cells. This means that cancer drugs on these types of cancers have a hard time staying in the cells.

P-gp pumps cancer drugs back out of cells with
the help of changing ATP to ADP. This can lead to
drug resistant cancers. We are looking for inhibitors
that might block the action of P-gp by taking away
its ATP or by competing with the drug for the pump,
so less drug is pumped out.
Other cells can up-regulate the production of P-gp once they start to receive the cancer drugs. Either way, it leads to multidrug resistant (MDR) cancers – a serious problem. Many attempts have been made to develop P-gp inhibitors, but most have been either ineffective or toxic.

Enter guggulsterone (let’s call it GGS for short) – new research shows that this compound from myrrh can reverse MDR in several types of cancer. The mechanism is just now being uncovered; GGS can act as a competitive inhibitor of P-gp, meaning that it is pumped out just like the cancer drugs. But the more time P-gp spends pumping out GGS, the less time it is pumping out cancer drug, so it becomes more effective. It does not appear that GGS stops production of P-gp or other actors in this play, it just keeps them busy – but it does it without being toxic. This is a pharmacokinetic effect, one drug (GSS) has an effect on how another drug (cancer drug) is acted on by the cells, in this case by keep the drug in the cancer cell much longer.

In the cases of pancreatic cancer and gall bladder cancer, very new studies show that GGS in combination with the cancer drug gemcitabine, works much better than the drug alone. The combination causes higher levels of apoptosis in these cancers, perhaps through the action of keeping more drug in the cancer cells, but GGS may have other cytotoxic effects as well.

Osteoporosis leads to less dense bones, which can alter posture 
and lead to bone breaks. It looks like the guggulsterone in 
myrrh can prevent bone resorption after menopause. It may 
even increase density and be a treatment for bone breaks.
And this is the most amazing part, even though it may be inducing damage in some cells, a new use for GGS is to prevent damage to heart muscle cells (cardiomyocytes). The cancer drug doxorubicin (DOX) is a very good cancer killer, but its use is limited because it damages the cardiomyocytes. GGS has recently been found to protect cardiomyocytes from DOX damage by preventing the up-regulation of many pro-apoptotic proteins. But GGS helps kill cancer cells by promoting apoptosis – what gives? Become a biologist and find out, it can be your gift to the rest of us.

Next week – the biology of New Years’ exercise resolutions!

Xu, H., Xu, L., Li, L., Fu, J., & Mao, X. (2012). Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines European Journal of Pharmacology, 694 (1-3), 39-44 DOI: 10.1016/j.ejphar.2012.06.046

Wang, W., Uen, Y., Chang, M., Cheah, K., Li, J., Yu, W., Lee, K., Choy, C., & Hu, C. (2012). Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro BMC Complementary and Alternative Medicine, 12 (1) DOI: 10.1186/1472-6882-12-138

de Rapper, S., Van Vuuren, S., Kamatou, G., Viljoen, A., & Dagne, E. (2012). The additive and synergistic antimicrobial effects of select frankincense and myrrh oils - a combination from the pharaonic pharmacopoeia Letters in Applied Microbiology, 54 (4), 352-358 DOI: 10.1111/j.1472-765X.2012.03216.x

For more information or classroom activities, see:

Myrrh –

Additive and synergistic effects in pharmacology –

Multidrug resistance in cancer –

Wednesday, December 23, 2015

The Resin For The Season

Biology concepts – sap, resin, latex, mucilage

Frankincense is a solid material than starts out as a 
liquid that oozes from a tree. In the presence of air, 
the resin turns hard. When burned, many 
fragrant and brain altering compounds are released.
We saw last week that gold doesn't just look good, it has a significant place in biology. This week we take a look at frankincense, a natural tree product prized for its use in sacred rituals. The Catholic Church is the number one purchaser of frankincense, but that may be about to change, especially for medicine. The wise men must have done some heavy thinking before they made their gift choices for Jesus – gift cards are so impersonal.

A 2008 study may have defined just why frankincense is used in religious rituals. Burning the resin releases incensole acetate (IA), one of the resin’s key components, which activates transient receptor potential vanilloid (TRPV3) ion channels in the skin and brain. This ion channel is responsible for mediating a warm feeling in the skin, but TRPV3 channels also mediate brain activity.

The researchers in Israel found that IA activates the cFos transcription factor in the brain, leading to anxiolytic (anxio = anxiety, and lytic = destroying) and anti-depressive feelings. Mice without TRPV3 channels did not show cFos activation or behavior changes when exposed to IA. It appears that burning frankincense makes one feel happier and more in tune with whatever activity is going on at the time, including religious rituals.

The fact that there is a psychoactive agent in frankincense is amazing enough, but there’s more biology to this second gift. Recent evidence indicates that the oils and other compounds in frankincense may save lives– if the trees that produce frankincense don’t disappear in the next 50 years. Unfortunately, their extinction is a distinct possibility – we must save this precious sap, or resin, or whatever it is.

Trees can produce various oozings and liquids. Pancake syrup most often comes from the sap of a maple tree, while your stick of Wrigley’s spearmint uses the latex that exude from many different kinds of plants. Gum drippings may also be used in chewing gum (Chiclets used chicle gum), but gums are now more commonly found in paints and erasers. The aloe vera you use on burns is a type of mucilage, rich in glycoproteins. But many plants, especially coniferous trees, exude resins when they are under attack or are damaged.

Amber is fossilized resin. Scientists learn much from organisms caught 
in it and thus preserved. Recent evidence also shows that amber can 
help us track bug attacks on plants from the days of dinosaurs. 
Gum is semi-solid, and rubbery. The gum shown is chicle, used 
for many years in Chiclets gum. Mucilage is produced by 
many pants, including as a treat and trap for insects in carnivorous
plants like this sundew. Maple sap is clear and dilute when tapped from
a tree. It must be boiled for hours to reduce it to syrup. Latex rubber is 
naturally white. The first car and bicycle tires were all white, not
just white-walled.
Gums can also be used for defense, but are made directly from disintegrating internal plant material. They harden to a certain degree after being exuded from the plant tissue, but are more known for their ability to increase the viscosity of a liquid, due to their long polysaccharide molecules. Bacterial agar plates use a gum from seaweed to grow microorganisms.

Sap is the sugary fluid that travels up and down in the xylem of vascular plants, providing the different structures with carbohydrate to produce ATP at the cellular level. Therefore, sap is a nutritive liquid and all trees produce it – but not all taste good.

Mucilage is similar to sap. It also contains glycoproteins and other carbohydrate-containing molecules, and is important for food and water storage in almost all plants, especially cacti. However, mucilage can be used for other purposes, like luring insects into carnivorous plant traps, such as the flypaper plant.

People used to lick mucilage everyday, but technology has reduced its role in our lives. When mixed with water, mucilage is an adhesive, like on the backs of stamps. You don’t have to lick your computer screen to send an e-mail, so mucilage is less important to us in these modern times.

Resins become definite solids when exposed to air. They are not nutritive, and contain primarily the byproducts and secondary metabolites of other cellular processes. While gums and saps are soluble (will dissolve) in water or fat, resins are stable in water but will dissolve in alcohol.

The reason for resin production is not fully understood. They may play a role in defense or tissue injury, but may instead serve to rid the plant of unneeded or unwanted waste products. Indeed, when trees are cut to harvest frankincense, the first resin produced is discarded, because it contains many toxins and foul smelling chemicals.

The Boswellia sacra tree grows in a harsh
environment. The roots can grip onto stones and
they grow out of the ground as buttresses to keep
the tree stable on the cliff sides.
Resins are produced mostly by coniferous trees (like pine trees). This makes frankincense an exception, since it comes from the Boswellia sacra tree, a deciduous tree (trees that lose their leaves in the winter). Frankincense is different from other resins in another aspect as well, it is technically a gum resin, since it has many compounds that are of the gum variety within its resin. The gum-like essential oils in frankincense are one of the reasons it is sought after as an incense.

B. sacra grows only in the middle eastern countries of Yemen and Oman, and possibly in Somalia. The tree is only 2-7 meters (6-23 ft.) when fully grown, and starts producing resin at a fairly young age of 8-10 years. Its small stature may be due in part to the arid climate that it lives in; there is so little water to be had that B. sacra survives only on the moisture it absorbs from fog.

However uninviting its environment might seem, B. sacra is well adapted to this area and is very finicky in growing anywhere else. In fact, a recent study indicates that they are more finicky than even previously believed. Though living in two different areas (Oman/Yemen vs. Somalia), it had been accepted that these plants were the same species. But based on chemical evaluation of the essential oils of the resins from trees in these two regions, the Oman/Yemen trees of B. sacra are truly different than the B. carterii trees of Somalia.

Initial gas chromatography-mass spectrum analysis did not show significant differences in the kinds of volatile molecules present, but there were large differences in the amounts of the individual compounds in the resin from each species of tree. Later experiments also showed chemical differences in the same compounds from each species.

Yemen and Oman are side by side and Somalia is
just across the Gulf of Aden. But recent studies show
that the frankincense trees that grow in Yemen and
Oman are distinctly different from those in Somalia.
This speciation difference shows that B. sacra REALLY likes to stay close to home. There’s nothing wrong with that, except that the small area that it grows in happens to be one of the most unstable parts of the world. The trees have been over harvested for resin, and this affects the rate at which the trees reproduce. Heavily tapped trees have seeds that germinate only 8-16% of the time, while trees that have not been tapped for resin germinate seeds at a rate of over 80%.

Add goats grazing on the existing trees, global warming, fires, and low genetic diversity in individual stands of trees to the low rate of propagation and this spells trouble for the B. sacra species. Estimates are as dire as a 50% decrease in frankincense production in the next 15 years, to a 90% loss of trees in the next 50 years – but there is hope.

A recent DNA study shows that trees from different parts of the Dhofar region are genetically distinct, and that there is a low level of heterozygosity in the trees of a single area. This low level of genetic diversity results in trees less able to survive changes in environment or biology (genetic diversity is key to natural selection). But some stands show more genetic diversity and arguments are now being made to initiate conservation efforts for the diverse stands, while increasing cross-pollination of the least genetically diverse trees. It is hoped that these efforts, as well as attempts to grow B. sacra in the Sonora Desert of North America, could stave off extinction of B. sacra.
The hippocampus is important in your sense of well-
being. Studies have shown that in people with
depression, the hippocampus is smaller, perhaps from
poor neurogenesis or from increased cell death. Why
the seahorse? In Greek, hippocampus means, “horse sea
monster.” I can see the resemblance.
Why is it important that we save the frankincense trees? Because it is becoming evident that the resinous compounds in frankincense could have great medical benefits to humans – and unhappy mice.

We mentioned above that IA (incensole acetate) of frankincense acts on the brain to increase feelings of well-being. Mice bred to be submissive and to give up (quit) earlier in a test of depressive activity show a much stronger will to live and more positive behaviors when given IA. Recent research in Israel shows that IA influences brain molecular biology, especially in the hippocampus, altering depressive behaviors as much as other chemical interventions. It is hoped that IA may be a viable anti-depressant drug in the future.

This same group showed in 2008 that IA was a significant anti-inflammatory agent, through its inhibitor action on an important transcription factor (called NF-kB) that stimulates expression of inflammatory proteins. In mice with traumatic brain injuries, IA administration resulted in reduced inflammation and pressure on the brain, reduced neuron degeneration, and prevented loss of cognitive function. Their more recent study also indicates that IA is protective in stroke and in the damage that can come after strokes by reintroducing oxygen into the damage part of the brain (when blood flow resumes).

Boswellic acid is also of use in myeloid leukemia, a type
of cancer of the white blood cells. It seems that BA can
induce the cancer cells to commit suicide, and die after a
period of time like most cells do. BA trigger apoptosis by
stimulating the release of important compounds from the
mitochondria, suggesting to the cell that its energy making
organelles are irreparably damaged.
Another compound in frankincense is showing promise as an anti-cancer drug. An essential oil molecule called Boswellic Acid (BA) has been shown to slow the rate of cancer cell growth. A recent study has delineated at least part of the mechanism of BA-mediated inhibition of colorectal tumor growth.

Cancer is the result of mutations in genes that code for the production of proteins that keep cells living, growing, and dividing forever. BA stops the synthesis of some of these proteins. It turns out that BA stimulates production of a micro RNA (miRNA, a short RNA molecule of about 22 nucleotides) that can bind to the messages transcribed from DNA that would be translated into pro-cancer proteins and stop the proteins from being made. Do you think the three kings had any idea that they were giving a gift that can stop inflammation, depression, and cancer – or they did they just think it smelled nice?

Next week – The third of the original gifts, myrrh. There's a biologic reason frankincense and myrrh were given together as gifts, but science didn't figure it out until just a couple of years ago.

Takahashi, M., Sung, B., Shen, Y., Hur, K., Link, A., Boland, C., Aggarwal, B., & Goel, A. (2012). Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family Carcinogenesis, 33 (12), 2441-2449 DOI: 10.1093/carcin/bgs286

Moussaieff, A., Gross, M., Nesher, E., Tikhonov, T., Yadid, G., & Pinhasov, A. (2012). Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals Journal of Psychopharmacology, 26 (12), 1584-1593 DOI: 10.1177/0269881112458729

Coppi, A., Cecchi, L., Selvi, F., & Raffaelli, M. (2010). The Frankincense tree (Boswellia sacra, Burseraceae) from Oman: ITS and ISSR analyses of genetic diversity and implications for conservation Genetic Resources and Crop Evolution, 57 (7), 1041-1052 DOI: 10.1007/s10722-010-9546-8
For more information, see:

Resin –

Sap –

Gum –

Latex –

Mucilage –

Boswellia sacra –

Wednesday, December 16, 2015

A Gift Worth Its Weight In Gold

Biology concepts – toxicity, trace elements

Say hello to the Holterman nugget of New South
Wales, Australia, supposedly the largest gold
nugget ever found. Strictly speaking, it isn’t a nugget,
but rather a huge vein of gold in a piece of quartz.
And Bernhardt didn’t find by himself, but he was a
shameless media hound and built himself a legend.
In 2nd century Rome, practitioners of Mithraism, a popular pagan religion of the time, had a feast on December 25 to celebrate the god Mithras, the “Invincible Sun.” This also coincided with other feasts for Saturn and the winter solstice. People gave gifts to one another during these holiday celebrations. This practice of gift giving was adopted by Christians when the pagan and Christian traditions were merged, as they often were.

Today, Christmas presents are most often associated with the gifts of the three kings who came to see the baby wrapped in swaddling clothes (although by the time they arrived, Jesus was already a toddler – camels will never be confused with jet planes). Their gifts were gold – a gift for a king, frankincense – a gift for a priest, and myrrh – a gift for one who was to die (used in burial rights).

These three gifts are not exempt from our search for biologic exceptions and amazement. In terms of biology, they are indeed gifts.  This week we will talk about gold, with the others to follow on successive posts, like the ghosts of Christmas past, present, and future.

At December 2012 prices, a 150 lb (69 kg) person has about 37 cents worth of gold in his/her body, excluding any dental work. Hardly worth trying to harvest, but nice to know you’re worth more than you thought. How did the gold get there and is it doing anything?

Living organisms rely on small amounts of some metals and other elements in order to carry out their metabolic reactions. As such, these elements that are needed in small amounts are called trace elements. Examples of important trace elements include selenium, iron, copper, iodine, and zinc. Zinc is probably the king of the trace elements, as it is used in over 200 different reactions in mammalian physiology.

Copper is used in many biochemical pathways,
and it is showing promise as an anti-inflammatory
agent. But NO! people - you can’t get the anti-
inflammatory effects by wearing the copper
bracelets or copper-impregnated compression
wear! On the other hand, copper impregnated
clothes are antimicrobial.
Zinc works to control what genes are activated to make proteins (zinc finger transcription factors), as well as DNA and RNA production and destruction. It is stored in the brain to control just how active some neurons become when stimulated, and plays an important role in neural plasticity – the reordering of neuron connections after experiences and sleep, you may know it as learning and memory. Make sure you take your zinc before studying for that big test!

Because you need only a “trace” of these substances to maintain growth, development and health, they are also called micronutrients. Their functions can be quite diverse. Iron is the oxygen carrier in hemoglobin, but you only need a trace in your diet because you are so good at preserving what you already have. Selenium is contained in a non-traditional amino acid called selenocysteine, which is important for antioxidant proteins (selenium replaces sulphur in the traditional cysteine).

The biologic rule is that gold is not a trace element! Supposedly, no living organism uses gold in its physiology, but you know there has to be an exception. In 2002, Russian scientists investigating a membrane bound enzyme of the aurophilic (au = gold, and philic = loving) bacteria, Micrococcus luteus, showed that the enzyme contained gold in its active site (the area that binds the molecule to be chemical reacted). The gold was important for converting methane to methanol, giving the bacteria a way to produce energy when traditional food sources were scarce.

But we, and presumably ever other organism don’t have this system, so why is there gold in our body? It turns out that we have many things in our body that we don’t use, they just accumulate, things like lead, mercury, cobalt, arsenic. Some are toxic at low levels and some are useful unless we get too much of them. We have discussed the problems associated with having too much iron, and copper excess can be toxic as well. We said zinc is important for many reactions, but too much zinc can hinder copper absorption and you can end up with a copper deficiency. This is just as dangerous as copper excess.

The liver is the site of much detoxification in the body.
Two systems are at work, one to break down or modify
fat soluble toxins, and the other to prepare them and
water soluble toxins for elimination in the bile or urine.
Toxic heavy metals often just get stored in the liver and
cause damage later.
If the element itself or amount of the element is toxic, then we have to get rid of some; this is the job of the liver. In some cases even gold can be toxic; as we accumulate more and more gold in the liver and kidney, it can disrupt their functions. Poor liver and/or kidney function – you die. The classic form of toxic gold found in nature is called gold chloride or “liquid gold,” which causes organ damage in humans and severe toxic effects in other organisms, but there is an exception.

A microbiologist and a professor of electronic art at Michigan State University have worked with a bacterium that can withstand gold chloride levels that would kill every other known organism. They found that Cupriavidus metallidurans was hundreds of time more resistant to gold chloride than any other organism.

C. metallidurans takes in the gold chloride and processes it to pure 24 karat gold, and then deposits it in a thin layer as part of the community of proteins and insoluble products that the bacteria builds around its colony. These organized layer of proteins, lipids and carbohydrates are called biofilms, and are being recognized as very important in bacteria ecology and pathology. In the case of C. metallidurans, the biofilm is intrinsically valuable to Wall Street.

Other organisms accumulate gold as well – bacteria, fungi, algae, fish, etc., but as does everything else in biology, it starts with the bacteria. It turns out that some bacteria excrete high levels of acidic amino acids – aspartate and glutamate (ate means acid). Yes, amino acids that are used to build proteins are organic acids, hence the name.

To dissolve gold out of powdered and broken rock,
many mines like this one in Brazil spray the ore with
sodium cyanide in water. They collect the runoff and
precipitate out the purer gold. I guess they don’t worry
about all the living things contaminated with the
The bacterium Chromobacterium violaceum actually makes and excretes cyanide. Cyanide binds stably to gold and silver, so it is used in gold mining to bind and concentrate very fine gold particles in rocks. Then the gold can be collected and precipitated. These examples show that if gold is in the immediate environment of these various organisms, it can be dissolved by the organic molecules and taken up by the bacteria when they feed.

Once gold is consumed and stored by the bacteria, it enters the food chain; millions of organisms feed on bacteria, and millions of organisms feed on the feeders, and so on. Eventually, we end up eating a little gold as well. This is similar to how fish that ingest food and swim in water contaminated by mercury runoff can end up increasing the human levels of mercury – the difference is that mercury is much more toxic than gold.

The accumulation of gold in sedentary organisms may provide someone with a gold rush. A 2010 study showed that the saprobic fungi (those that feed on decaying material) around an existing gold mine contain much higher levels of gold than ectomycorrhizal fungi (those that are parasitic) in the same area.  The accumulation of gold in soil bacteria and fungi may be able to provide scientifically astute miner with clues as to where they should dig the next mine!

The blue toadstool  (Entoloma hochstetteri) is an
example of a saprobic fungus. It gains all the
nutrients it needs from the soil and from decaying
organic material. Therefore, it picks up and
accumulates other things in the soil – like gold maybe.

 Bacteria may prove even more important to miners. December 2012 evidence indicates bacteria that dissolve and ingest gold in the rocks and soil purify it to some degree. When they form biofilms, the gold becomes insoluble again, and nuggets or flakes are formed. Veins of gold may be due to bacterial byproducts and corpses flowing into cracks in the rocks. Makes you look at your gold ring differently, doesn’t it.

We might be able to thank gold-loving bacteria for more than our jewelry – gold is finding its way into medical treatments and tests these days.  Because gold was rare, pure, inert, and costly, early physicians thought it just had to be good for you. Many remedies had gold incorporated into them, including a popular cure for alcoholism called the Keely cure.

The cure was so widely accepted (and patented by Dr. Keely) that even Theodore Roosevelt himself sent his brother, Elliott, to Dr Keely’s clinic in Dwight, IL to be cured of his addiction. It didn’t work, Elliott drank to the point of depression, and died from injuries that resulted from his jumping from a window.

More recent uses of gold include as an anti-inflammatory agent rheumatoid arthritis, including a compound called aurothiomalate. Just how this works remains a mystery, but a 2010 study in chondrocytes (the cells that make cartilage and are present in joints) showed that this drug down-regulates a signaling enzyme (MAP kinase phosphatase 1) that is important for expression of several inflammatory proteins, including cyclooxygenase, p38 MAP kinase, matrix metalloproteinase-3 and interleukin-6.

The aquatic or semi-aquatic plant Bacopa caroliniania can
be loaded with gold nanoparticles and made to give off
light.  Depending on the energy of the UV light shone on
it, it can glow from green to gold to red. Someday, maybe
our tree lined streets will have natural streetlights.
Gold is finding a home as a treatment in other conditions as well including in cancer, viral infections, and parasitic diseases. But gold is being used most often as a carrier. Because gold is practically inert, nanoparticles of gold can be used to carry drugs to specific targets or to be used as imaging agents to illuminate very small structures.

Most spectacularly, gold may help light a dark world. Plants can now be grown with gold nanoparticles that are small enough to be taken up into the leaf cells. When exposed to UV light, the gold releases energy at a wavelength that stimulates chlorophyll to bioluminesce. The plants actually give off light like natural street lights.

That’s a lot of biology for a hunk of metal used for wedding rings and retirement watches – a way cool gift for any biologist. Next week, the biology of frankincense.

  Nieminen, R., Korhonen, R., Moilanen, T., Clark, A., & Moilanen, E. (2010). Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugs Arthritis & Rheumatism, 62 (6), 1650-1659 DOI: 10.1002/art.27409

 Levchenko, L., Sadkov, A., Lariontseva, N., Koldasheva, E., Shilova, A., & Shilov, A. (2002). Gold helps bacteria to oxidize methane Journal of Inorganic Biochemistry, 88 (3-4), 251-253 DOI: 10.1016/S0162-0134(01)00385-3