From Microbes to Biofuel

During my career as a clinical pharmacist, bacteria and I were NEVER friends. More often than not my patients were infected with some potentially lethal bacterium, and it was my job to provide the magic elixir to eradicate those nasty organisms from their bodies.

So you can imagine my surprise, and interest, to discover that the particularly vicious bacterium Escherichia coli (E. coli for short) is being used to make diesel fuel. My first thought was that it was about time for those malicious, hardy bugs to have a higher purpose.

A recent article in Scientific American explained that scientists have discovered a way to induce E. coli (which normally reside deep in our intestines and aid in food digestion) to produce hydrocarbons that become fuel for big trucks and other powerful machines.

By intricately attaching bits of various microbes and specific parts of the camphor tree into the genetic code of E. coli, the bug changes its primary job of breaking down what we eat to making and replicating hydrocarbon molecules into diesel fuel.

The experiments have been so successful that the diesel fuel products produced could be used directly in existing engines and completely replace fossil fuels. Scientists state that the next step is to develop the bacterium into a more efficient “work horse” that could be deployed industrially.

The E. coli bacterium already is a hardy entity and scientists are working to harness its high tolerance for harsh working conditions (such as the high acidity and warmth of the human digestive tract). That hardiness has already helped the bacterium survive its own production of fuel, an environment that would prove toxic to other microbes.

Currently, the industrial strength E. coli are fed a mixture of sugar and yeast extract, a diet too expensive to make the process financially equitable to the diesel fuel refined from crude oil. But scientists believe that they may be able to fine-tune the genetic engineering of E. coli to use organic wastes from agriculture, and possibly even sewage, as a nutrient. At that point, the process would be feasible and the resulting product would be a suitable replacement for fossil fuels, possibly even replacing jet fuel and gasoline as the process becomes further refined.

Encouraging work at the University of California, Berkeley, to alter E. coli genetics has allowed scientists to produce bacteria that digest the inedible parts of plants (the cellulose parts) and turn them into microbial diesel.

Currently, E. coli is used to make specialty oils for expensive cosmetics. The cosmetic company Amyris makes squalane, a popular moisturizing oil, from bacterium grown in vats in Brazil. The biochemists at Amyris have also produced a special variety of yeast to manufacture an antimalarial drug called artemisinin.

But precious cosmetic oils and specialty drugs are not sold as cheaply as biofuel and that is the challenge in engineering microbes to become industrial work horses to produce economical products that compete with what’s already on the market.

Biotechnology makes monumental advances almost daily, but sometimes it’s still not fast enough to satisfy the possibilities.

Thoughts? Comments? I’d love to hear them!

When Soft Drinks Were Not So Soft

Medical experts argue about the health benefits of soft drinks. Sodas have been linked to our country’s growing obesity problem as well as to a lengthening list of other diseases. But a review of the history of two popular soft drinks indicates that the argument is not a new one.

Seven-Up®, created by Charles Griggs in 1929, was originally named “Bib-Label Lithiated Lemon-Lime Soda” and was used as “a pick me up” drink. It contained seven ingredients and that long mouthful of a name was eventually shortened to 7-UP® as the product became more popular.

Seven-Up® was originally marketed as an over the counter remedy to cure hangovers. Early advertising stated that “7-Up takes the ouch out of the grouch!” It was the ultimate mood elevator. That’s because until 1948, the product contained lithium citrate, a mood-stabilizing drug.

Lithium citrate, a popular patent medicine in the late 19^th and early 20^th centuries, “evened out” a person’s psyche and brightened the outlook of depressed patients. In later years, lithium became an early treatment for bipolar disease. It was particularly beneficial in softening the manic phase of manic-depression.

By the 1950’s, 7-Up (stripped of its lithium citrate additive) became a popular mixer in alcoholic beverages—again being used to soften one’s mood.

Another popular remedy was Coca-Cola®. Conceived in 1886 and first bottled in 1899 and originally called “Pemberton’s French Wine Cocoa”, the product was initially a version of the European French Wine Cocoa. It was formulated at the Eagle Drug and Chemical Company, a drug store in Columbus, GA owned by pharmacist John Pemberton.

The European version contained both cocaine and alcohol. I should mention that when cocaine and alcohol are ingested together, they form a chemical called cocaethylene. Cocaethylene works like cocaine in the body, only it produces more euphoria than cocaine alone. Needless to say, the product was very popular in Europe.

The American version contained no alcohol because the Georgia county where Pemberton had his drug store passed prohibition legislation in 1886, making the original French formula illegal. But Pemberton’s product did contain cocaine.

It was recommended as an aid to cure many diseases, including headaches, hysteria and melancholy, and morphine addition. Pemberton himself was a morphine addict because of chronic pain that resulted from a Civil War injury. Pemberton eventually increased the popularly of his product by adding sugar syrup to the formula and calling it “Coca-Cola: The Temperance Drink.”

Coca-Cola® quickly became a popular cocktail among wealthy society people as an “intellectual beverage” and was marketed as a valuable “brain tonic” and “nerve stimulant”. Early advertising stated that the product was a delicious, exhilarating, refreshing and invigorating beverage.

Until 1905, Coca-Cola® still contained cocaine, but it took until 1929 to perfect the extraction process and to finally remove trace amounts of coca’s psychoactive elements from the Coca-Cola product that was marketed at the time. The Coca-Cola Company finally trademarked the name “Coke” in 1944.

The Coca-Cola® that’s sold today still contains coca, but the psychotropic alkaloid is completely removed from it. A New Jersey chemical processing facility has that unique job. It’s been reported that the chemical company imports almost 200,000 kilograms of coca each year for Coca-Cola®, or enough to make more than $200 million worth of cocaine.

So, in view of the fact that, until the early 20^th century, two of our most popular soft drinks were actually carefully disguised psychotropic street drugs, the current argument against consumption of these products because of potential obesity and deteriorating health doesn’t seem so immediate as it once did. At least now you can swear off sodas without having to go to rehab.

Thoughts? Comments? I’d love to hear them!

The Deadliest Drugs in the United States

I often blog about drugs used as poisons, and I guess that’s why someone asked me the other day, “Which drugs are the deadliest in America?”

The question required clarification before answering it. Did he mean the fastest killers, or the most painful drug poisons, or did he want to know something else?

I realized that this person wanted to know hard facts. I could speculate that the answer was illegal street drugs, but I needed to research the subject before making any statements that could not be backed up with published data. What I discovered surprised even me.

Statistics indicate that overdose deaths from prescription painkillers are far greater than any other category of drug deaths—so much so that the statistics for deaths from prescription painkillers exceed those of heroin, cocaine and methamphetamine combined.

A recent report from the Centers for Disease Control and Prevention (the CDC) found that nearly 40 Americans die each day (almost 15,000/yr) from overdoses of prescription painkillers (drugs such as Vicodin and OxyContin).

Dr. Thomas Frieden, director of the CDC stated, “We are in the midst of an epidemic of prescription narcotic overdoses.” And it seems that the problem has gotten worse over the years. There has been a three-fold increase in deaths from narcotic painkillers over the past decade alone.

In April of this year, Popular Science published an article on that very subject. Accompanying it was an interesting graph depicting the number of deaths per 100,000 people from various drugs (including prescription drugs, street drugs and alcohol). The top two spots for the highest number of deaths per 100,000 were narcotic painkillers and psycho-pharmaceuticals, with heroin and cocaine being farther down the list.

Interestingly, marijuana was not even on the list.  The US Drug Abuse Warning Network (DAWN) indicates that there have been no credible deaths reported from cannabis alone, although we can speculate that there are a number of auto collision deaths that might result from cannabis abuse.

Similarly, the chart represents all deaths in the CDC database under the categories accidental poisoning, intentional self-poisoning, assault by drugs and poisoning with undetermined intent, but does not account for deaths related to drug interactions involving combinations of drugs—often deadly combinations, such as the Houston Cocktail of Vicodin, Flexeril and Xanax. I’ll save that discussion of killer drug combinations for another blog.

What the analysis does show is a doubling of deaths from narcotic overdoses between 1999 and 2010, and approximately 70% of those deaths are listed as “unintentional”—translate that as “accidental overdoses”.

Solutions to this growing problem are not simple. A greater reliance on medication use in modern society has given the average person a complacent attitude regarding prescription drugs, and the “immediate fix” of the modern psyche allows for greater use of prescription pain relievers as alternatives to more time-consuming or more costly measures (such as physical therapy, exercise and invasive medical procedures).

Prescription pain relief comes with its own detrimental cost. As we continue the fight against illegal street drugs, we must also inform the public about the improper use of legal prescription drugs, the additive nature of many pain relievers and the diversion of prescription narcotics for recreational drug use.

Listen to your healthcare professional as he/she prescribes or dispenses these medications and read the accompanying literature provided when the drug is purchased. A little education can go a long way toward keeping you from becoming yet another statistic on a chart.

Thoughts? Comments? I’d love to hear them!

Ricin – Another Weapon of Terror

It’s often said that fact is stranger than fiction, so I pose this seemingly ridiculous question to you– What do a martial arts instructor, an Elvis impersonator and the deadly chemical agent ricin have in common?

The answer has been in the news recently – All three are linked to the attempted murders of a U.S. senator and the President.

Earlier this month, an envelope addressed to Senator Roger Wicker, a Republican from Mississippi, allegedly contained the deadly substance ricin. And just a day later, a similar letter addressed to President Obama was discovered and it also allegedly contained a white granular powder that was later identified as ricin. Fortunately, both letters were opened off-site and they never got close to the intended targets.

As the investigations progressed, it was revealed that an Elvis impersonator was connected to the crime. Further evidence indicated that the accused might have been the target of a frame that resulted from a long-standing feud with a martial arts instructor. It’s now believed that this second person may be the real perpetrator and is being charged with developing and possessing ricin, and then attempting to use it as a deadly weapon. If convicted, this martial arts instructor could face a maximum sentence of life imprisonment and a $250,000 fine.

Ricin is one of the most poisonous chemicals on Earth. It’s a highly lethal poison found naturally in castor beans and there is no known antidote.

The chemical Ricin is a naturally occurring protein from the castor oil plant. It’s extracted from the waste matter (called the “mash”) left over from processing castor beans into castor oil. Ricin can be made in the form of a powder, a mist, a pellet, or it can be dissolved in water.

It’s important to point out that commercial castor oil contains none of the toxic proteins from the mash and is a safe product to use.

The medium lethal oral dose of ricin is a little over 3mg. That means a dose of pure ricin about the size of a few grains of table salt can kill an adult human. If the chemical is injected or inhaled, the dose is even lower, about 1.5mg to kill a 150-lb adult.

As with most chemicals, various factors determine how sick a person will become when exposed, and if it will be fatal. These include how much ricin a person is exposed to, how long the exposure lasts, and what exposure method is used. For instance, inhalation and injection are almost always fatal, but ingestion may only make a person extremely sick, especially if medical support is rapidly provided.

The purity of ricin can also significantly affect how lethal a dose is. When the chemical is purified by special, technically advanced processes, the substance is much more deadly than “back kitchen” processing.

Ricin kills by infecting our cellular structures and blocking their ability to synthesize their own proteins. When a cell cannot make protein, key bodily functions shut down and progressive organ failure usually results in death. Even when a person survives ricin poisoning, permanent organ damage often results.

The progression to death is extremely unpleasant. Usually, humans exposed to a lethal oral dose will experience severe vomiting and diarrhea within six hours of exposure and this results in serious dehydration. Eventually, the kidneys, liver and pancreas fail. Death follows soon after.

Inhalation of ricin, on the other hand, produces different effects since the poison interacts with other body parts. Inhaled ricin causes a vicious, bloody cough and the lungs fill with fluid. Eventually, the lungs become so fluid filled that the victim loses the ability to breathe. In effect, the person drowns in the body’s own fluids.

Lethal doses of ricin that are injected usually result in intense flu-like symptoms, swelling around the injection site, and eventual progressive organ failure as the poison circulates throughout the body.

Death from inhalation or injection occurs in about three to five days after contact, but it could be as rapid as 36 to 72 hours. And the death is an agonizing one.

Unfortunately, various techniques for making this poison are readily available on the Internet, and periodically this method of murder is used in terror plots against government or corporate personnel. Therefore, murder by ricin can be categorized as a murder “ripped from the headlines”, making it an interesting and often used lethal weapon on TV, in the movies and in novels.

Of course, if you’ve been reading my past blogs, there are much more imaginative methods for killing off characters in your novels, and I’ll discuss some of them in future blogs.

Thoughts? Comments? I’d love to hear them!

THALLIUM – The Poisoner’s Poison!

It’s not often that I come across a method to kill a character in one of my novels with delightful efficiency and flair, but thallium is one of those chemicals. It piqued my interest some time ago and I couldn’t resist sharing it with you.

Thallium is a bluish-white metal that, in pure form, is odorless and tasteless. When combined with chorine, it turns colorless and dissolves well in water. That means it’s not easily detected in food or drink. To me, thallium seemed like a perfect substance to kill a fictional character and, as I researched the subject in greater detail, I was right.

In years past, thallium was used as a rat poison and an ant killer, but since 1975 it’s been banned in the United States and many other countries due to safety concerns. It’s highly toxic and readily absorbed through the pores of skin.

Thallium’s extreme toxicity is due in part to its chemical similarity to potassium. It uses the body’s potassium uptake pathways to be absorbed, although it bypasses the natural self-limiting mechanism that we have for potassium ingestion. Thallium also binds with sulfur, an element essential for nutrient absorption and utilization, and it disrupts necessary cellular processes. That’s primarily why it’s such a good rat poison.

One of its more distinctive side effects is hair loss. In fact, it was once used as a depilatory agent before its toxicity was fully appreciated. Another distinctive sign of thallium poisoning is that it damages peripheral nerves, causing excruciating pain. Victims are said to experience severe stomach cramps, nausea, and sensations similar to walking slowly over hot coals—in short, it’s a dramatic way to kill off a character you no longer need.

Thallium was very popular in the past as a murder weapon. In fact, it was often referred to as “The Poisoner’s Poison” and “The Inheritance Powder”.

Investigations into suspicious deaths have discovered thallium in tea, sodas,soups and various foods. Radioactive thallium poisoning was said to be a favorite of KGB assassins and documentation suggests that Saddam Hussein used it to poison dissidents.

Murders from thallium have fallen out of favor in more recent mystery novels, but the substance has taken center stage in thrillers and stories of international intrigue.

But be warned! There are now diagnostic tools to detect and quantify thallium poisoning in blood and urine to aid medical and legal investigators looking into suspicious deaths. Normal body concentrations are minimal (usually less than 1mcg/L), but a poisoned victim could have a thousand to ten thousand times this normal level (1-10mg/L). But without body fluid analysis, symptoms easily could be attributed to some other illness. It’s reasonable to assume that proper diagnosis might not be made before death occurs.

Depending on the thallium dose and the duration of exposure, a patient might recover with an antidote (Prussian blue, for example) and other life support treatments. More likely, however, the victim will be beyond hope and die a painful death within days of exposure.

Fortunately, thallium is more regulated now than it was in the past. Presently, it’s used mainly in manufacturing electronic devices and semiconductor parts. However, I’m sure a creative villain can find a reliable source when the need arises.

Thoughts? Comments? I’d love to hear them!

Red Wine and Dark Chocolate are the Best Drugs!

Two of my favorite food groups: red wine and dark chocolate – and now I discover that both are among the healthiest foods one can eat. But hold on a minute. There’s a catch.

Scientists have found that it’s not the wine or the chocolate themselves that are beneficial. It’s a chemical within them called resveratrol. That’s the healthy part.

In animal studies, resveratrol has been shown to prevent both disease and aging. It’s been discussed as a fountain of youth. The problem is that you’d have to drink a river of red wine (about 100 bottles per day) or eat a football field of dark chocolate to experience life-changing health benefits.

As a clinical pharmacist, I’ve often said that we can live better through chemistry. And that mantra could be true in this case. Although we can’t drink enough red wine or eat enough dark chocolate to prevent disease or reverse the aging process, we can isolate the chemical, duplicate it in a lab and develop drugs that act like concentrated resveratrol. If scientists accomplish that, we could truly have a pharmaceutical fountain of youth!

The basis for that bold statement is that resveratrol stimulates specific proteins in our bodies. These proteins are called sirtuin proteins (or SIRT1 for short). They break down certain types of damaging proteins and instruct other proteins to repair and regenerate cells.

Over a decade ago, MIT biology professor Leonard Guarente conducted animal studies to understand the function of sirtuin proteins. He discovered that when mice were genetically altered to remove SIRT1 from their bodies, the mice developed metabolic diseases—like diabetes—and were more likely to develop inflammatory diseases and become obese. Conversely, when SIRT1 was present and SIRT1 was stimulated, older mice appeared to be much younger and healthier.

Additional studies conducted at MIT have determined that the SIRT1 present in the brain protects against the neurodegeneration that happens with Alzheimer’s, Huntington’s and Parkinson’s diseases.

Since stimulation of sirtiun proteins appear to reduce disease and the effects of aging (both mentally and physically) in mice, researchers are studying ways to produce a drug that acts like concentrated resveratrol. By stimulating sirtuin proteins with a pharmaceutical equivalent of pure resveratrol, scientists potentially could extend life spans by countering the effects of obesity, certain diseases and the onset of aging.

But are we ready to live better through chemistry with a pharmaceutical fountain of youth? Only time will tell as further studies are completed and the results unfold.

Thoughts? Comments? I’d love to hear them!

Pharmacy Recall Epidemic

In November 2012, I wrote a blog about an outbreak of fungal meningitis that resulted from poor quality control procedures at a Massachusetts compounding pharmacy. It was first reported in September of that year, but evolved into national news because of the alleged horrendous breech in the pharmacy’s compounding practices. The news headlines continued for months as a few isolated illnesses exploded into 419 cases and more than 30 deaths.

Recently, more compounding pharmacies have been in the news for poor quality control issues. A Georgia compounding pharmacy recalled all of its sterile products after the Food and Drug Administration (FDA) documented concerns about the safety of the products shipped from there. The alarm focused on sterile eye drops prepared at the facility. Cases of endophthalmitis, a serious eye infection that can lead to blindness, were traced to the eye drops prepared in and shipped from this pharmacy.

That was the second specialty pharmacy in a week to recall products based on public safety concerns. Earlier, a New Jersey compounding pharmacy recalled all of its products after mold was discovered in bags of magnesium sulfate used to make their sterile preparations.

Compounding pharmacies are specialty practices that create drug formulations based on individual patient needs. Such products historically are prepared on a “made-to-order basis”, usually because available commercial products are not appropriate for the patient. A number of reasons could trigger a special patient need from a compounding pharmacy.

A patient may be allergic to a preservative in a commercially available eye drop and therefore the physician might order a compounding pharmacy to prepare a sterile formulation without any preservative. Or a patient might require a dose concentration that isn’t available in a ready-made product (such as, a much lower or higher concentration than available from a drug manufacturer).

Essentially, compounding pharmacies are the modern version of ancient chemists who created medicines from plants leaves and roots. The coal tar compounds of the 19^th century and the primitive sulfa antibiotics of the early 20^th century are examples of such compounding practices.

There are many fine, reputable compounding pharmacies all across the United States. Unfortunately, it only takes a few “bad apples” to spoil the reputation of the entire professional category.

The pharmacies that seem to make the news are those compounding facilities that expand well beyond their traditional roles of preparing individual prescriptions for individual patients. When a compounding pharmacy distributes hundreds and thousands of drug doses to multiple clinics outside of its local geographic community, they begin to function as drug manufacturers—but without the scrutiny of the FDA.

Compounding pharmacies are licensed and regulated by each state’s Board of Pharmacy. The FDA regulates only drug manufacturing facilities, not pharmacies. When a compounding pharmacy prepares drug doses in massive quantities for widespread distribution, that entity is operating outside of the laws of pharmacy practice and begins to function as a drug manufacturer, albeit without FDA approval for drug manufacturing.

A recent article by Liz Szabo in USA Today quoted Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research. Ms. Woodcock stated, “Health care professionals should ensure that any medicines they administer to patients are obtained from appropriate, reliable sources and are properly administered.”

I could not have said it better myself! Physicians and clinics that don’t use local businesses for drug compounding invite potential disaster. Compounding pharmacies are not drug manufacturers. When such pharmacies choose to function as drug manufacturers and operate without proper regulatory approval, they do so at their own peril, as well as the patients they serve.

Compounding pharmacies are a highly valued specialty in pharmacy practice and provide a much needed service. But, when they operate outside of their legal parameters, it’s a Prescription For Murder.

Thoughts? Comments? I’d love to hear them!