Synthetic Biology and Making Morphine in the Lab

Prescription pain medicine addiction has become prevalent and widespread with several areas in the U.S. calling it a public health crisis. Opiates include prescription pain medicines, such as Vicodin, OxyContin, or fentanyl. The surge in opiate drug addiction can be traced to changes in the increase in prescriptions for opiate drugs beginning in the 1990s. Now headlines tout the possibility of a “home-brewed heroin.”

If we unpack the headline, it turns out this “home-brewed” heroin is not exactly here yet. Scientists have replicated all of the metabolic processes that opium poppies use to turn glucose into morphine. They have replicated parts of this process in yeast strains in an effort to make less addictive pain medicines as well as other analgesics. This synthesis of cellular processes is called synthetic biology. By way of a quick review, synthetic biology involves creating the digital DNA code to make proteins, the internal machinery of a cell, in the lab. Yeast and e.coli are simple organisms and are often used to insert the DNA in a cell fitted with the necessary equipment to replicate and express the DNA. Craig Venter, in his book on synthetic biology, Life at the Speed of Light, calls DNA the software and yeast provides the hardware. Scientists want to tweak the software to make tailor-made drugs.

Synthetic biology overlaps with genetic engineering, but where it differs is that synthetic biology allows scientists to replicate an entire cellular pathway within an organism, such as yeast, as opposed to inserting or deleting mutations in a DNA strand and then inserting it in a cell.

The metabolic pathway reported in Nature (See the Nature News article) is the first part of the glucose-to-morphine pathway. The second part of the pathway, as well as a reaction that links the two parts, was recently reported by other research groups. All of these parts have been demonstrated separately in various yeast strains. If scientists were to combine these parts in one yeast strain, then theoretically, they would be able to convert glucose to morphine. This has not been done yet, but will likely occur soon.

The process for making morphine from glucose is complex (it’s approximately eighteen steps), and because scientists do not know the whole genome for the opium poppy, they have had difficulty identifying the enzymes that catalyze each step in the reaction pathway. To overcome this hurdle, scientists turned to enzymes in other organisms to that catalyze similar reactions. The most recent research that identifies the first half of the morphine pathway used an enzyme from sugar beets that scientists mutated to ensure that it produced the product they needed without unwanted byproducts.

The question remains, are we at a point where people can brew their own synthetic morphine? The short answer is no, not yet.

First, all of the steps have not been combined into a yeast strain. While this may be the next step in making synthetic morphine in the lab, it will need to be tested, and it may not work at first. Once scientists succeed at creating a yeast strain that can accomplish all of the steps, the process will need to be refined and optimized.

Secondly, in order for someone to brew their own morphine, he would have to acquire the yeast strain containing the synthetic DNA. This would mean acquiring the yeast from someone who not only knows the DNA code, but also has a PCR machine or some way to make synthetic DNA and then incorporate it into yeast.

Lastly, even if someone did acquire the yeast strain, according to Christine Smolke of Stanford University whose lab has made a semi-synthetic opioid using yeast, in an interview with Wired, said that the fermentation process would require specialized equipment and conditions that would be difficult to do outside a laboratory. It would also not produce enough morphine to make it cost effective.

While we are not at the point of worrying about home-brewed liquid morphine, the authors of the study were concerned about future consequences of their research. One of the motivations for designing the synthetic pathway is to tweak it to make less addictive pain medicine or to make medicines for other uses. This same ability to tweak the morphine-producing pathway could also be used for nefarious purposes.

The authors of the study sought ethical guidance from biotechnology-policy specialists Kenneth Oye, of MIT and Tania Bubela, of the University of Alberta. They published an article in Nature with Chappell Lawson, also from MIT, that came out in tandem with the research article. Oye, Bubela, and Chappell delineate the ethical and legal considerations for such research and provide four broad areas that should be considered:

  • Engineering – The yeast strains could be engineered to make them less appealing to criminals and more difficult to cultivate outside of a laboratory setting, similar to biocontainment practices with e. coli.
  • Screening – Since the DNA sequence would need to be ordered from a lab, there could be a screening process in place that flags orders of opiate-producing yeast strains
  • Security – They could employ biosecurity measures, such as watermarking yeast made from certain labs and background checks on people working with the strains.
  • Regulation – Opium is a globally controlled substance. The laws that apply to opium could be extended to cover opiate-producing yeast strains.

Overall, the headlines are a little misleading in that we are not yet on the cusp of people brewing their own morphine. However, the authors should be commended for considering the consequences of publishing their research and seeking ethical guidance. It is a good example of pre-emptively considering the hazards and consequences of technological advancement rather than responding to a crisis.

For more information, see my article in Salvo 31, “Dying to Feel Good: Modern Self-Realization & the Painkiller Addiction Epidemic

Indiana’s HIV crisis

Indiana is dealing with an incredible HIV outbreak, centralized in Scott County. The HIV outbreak has been directly tied to needle use for opiate drug users. The Governor has called it a public health crisis, and while normally an opponent to needle exchanges, he is allowing for a 30-day needle exchange to curb the outbreak of HIV.

To give you a sense of the numbers, typically Scott County will see about five new cases of HIV in a year. They saw 26 new cases between mid-December and the beginning of March, and the count is up to 72 cases as of March 26.

The cause of the cases has been traced to intravenous drug use of a liquid form of Opana, a prescription painkiller. Doctors in the area report that the drug addiction problem, like many other places in the US, has been going on for at least the last ten years, with increasing incidences of other blood-borne diseases from needle sharing and deaths due to overdose.

Scott County is struggling against poverty as well as addiction. However, opiate drug addiction is a problem that is spanning all demographics across the US. My article in Salvo Issue 31 looks at nationwide statistics of opiate drug addiction from both prescription pain medicine and heroin use and the underlying causes.

Typically, people start with prescription pain medicines. It can even be from their own prescription that they obtained legitimately for a hurt back or a tooth extraction or any number of reasons that physicians dole out prescriptions for hydrocodone. One guy, mentioned in my article, got hooked on fentanyl after receiving it as an anesthetic for a colonoscopy. He was already abusing alcohol and other substances in an effort to cope with depression over a break-up. Fentanyl, indeed, served as a pain reliever in more ways than one.

Not everyone becomes addicted to opiate drugs when they take pain medicines, but with chronic use, many people do become addicted. And, unfortunately, it is a very difficult addiction to break. Once you’ve tickled those paths in your brain, the tracks that usually take naturally produced endorphins (named for endogenous morphine), you wear a neurological path that is VERY difficult to undo. Unlike endorphins, which our bodies administer through a sophisticated regulatory process that ensures you are receiving the right amounts, opiate drugs stand in as stronger, more potent endorphin replacements.

On a short-term, temporary basis, opiate drugs, like hydrocodone, are supposed to decrease pain, and many of them, when in pill form, are time-released. When our bodies experience pain, endorphins help to quell the effects; however, the endorphins are not enough for injury or sickness, so people take pain medicine. Sometimes people will experience some physical withdrawal symptoms when they stop taking pain medicine if they have been taking them for a while, but physical withdrawal does not necessarily mean the person is addicted. Even physical tolerance is not the full picture of addiction. Addiction has to do with seeking out a high, and in an effort to do so, the person becomes consumed with overcoming physical tolerance to the point that he or she may grind pills and take them intravenously or turn to heroin which is cheaper and sometimes easier to obtain. Scott County is seeing the effects of people sharing needles for opiate drug use.

My article gets into both the neuroscience as well as the cultural and psychological factors that lead to addiction. Suffice it to say that one of the problems is accessibility to a substance that is too potent and too addictive to be administered for trivial reasons (such as tooth aches or minor aches and pains).

Prior to 1990, opioids were not typically prescribed as painkillers except for cancer patients. But in 1990, that all changed. Doctors wanted a solution to patients’ chronic pain,  patients were desperate for relief, and big pharma was ready to profit from the situation. Fast forward to now. The CDC reports that in 2014, physicians wrote 259 million painkiller prescriptions in a single year, the equivalent of one bottle of pills per American. They have seen a four-fold increase in overdose deaths since 2000.

At the end of the Washington Post article reporting on Scott County’s crisis, Dr. William Cooke points out that this issue is not unique to Scott County, Indiana. They are the canary in the coal mine.

Where Do Babies Come From? Induced Pluripotent Stem Cells…Sort of

Recent headlines tout that it may be possible for same-sex couples to have biological children thanks to stem cell technology. Using skin stem cells, scientists from the University of Cambridge and the Weismann Institute found that it is possible to make primordial germ cells, the cells that eventually form into egg and sperm (gametes), from induced pluripotent stem cells created from a donor’s skin.

The opportunity for same-sex couples to have biological children may take over the headlines, but it is not the only, or necessarily the primary reason, scientists are interested in this research. One thing scientists hope to do is to use this technique to study age-related diseases. As we go through our lives, we accumulate epigenetic messages that tell genes when to turn on or off, when to make more cells, or when to stop making cells. Recent research shows that certain cancers and age-related diseases are likely due to these epigenetic factors going awry. These epigenetic factors are “reset” in germ cells, meaning scientists can start over and see how these factors develop at the cellular level. There is still much research that needs to be done in this area, including questions as to which epigenetic factors are passed on and which ones are actually reset in germ cells (See Nature’s recent issue on the results of the NIH’s Roadmap Epigenetics Project here).

While the epigenetic research is interesting, the headlines emphasize the reproductive possibilities. This technique could be another option for infertile couples who want to have biological children, including same-sex couples who want children that are biologically related to both of them. However, what is not touted as loudly is that, for now, the technology only works for male same-sex couples.

The why this technique can be used for two men but not two women has to do with how the cells are made. Primordial germ cells are made from skin cells are taken from each person to be converted into induced pluripotent stem cells. Those stem cells are then converted into primordial germ cells by turning on or off certain genetic factors involved in converting pluripotent stem cells to particular cell types.

Female cells have XX chromosomes and male cells have XY chromosomes, but in order to make primordial germ cells that are precursors to sperm, researchers need a Y chromosome. Lead researcher, Dr. Hannah pointed out, that it is easier to take away a chromosome than to insert one. Women don’t have any Y chromosomes to contribute, meaning that making primordial germ cells from women “is a long way off.”

Finally, one of the more troubling factors in this research is that little has been said about the health and well-being of the children that would be produced from this technique. A key point in the original research article in Cell is that SOX17 is a key factor in the process of making primordial germ cells and likely plays an important role in gene regulation. This was surprising to scientists because SOX17 does not play a key role in mouse development. This means that even though mice have been used in prior studies on creating primordial germ cells, they may not be a good model system for creating the subsequent sperm and egg cells. Often before a procedure or a drug makes it to human trials, it is first tested in mice and then in primates. When it comes to human development, though, things do not translate from animal models to human models as easily.

Once scientists are able to take the primordial cells and advance them to egg and sperm cells, they will be able to create an embryo. However, because the mouse models are different, this is a case in which we have no way of knowing whether these embryos or the children will be healthy until the experiment is actually done.

It is unclear from the interviews or the article if the assumption is that “unhealthy” embryos will die off before they implant in the uterus or how exactly researchers are expecting to test whether this technique work as another reproductive technology. If unhealthy embryos die, this poses an ethical problem for those that assume embryos should be granted dignity in their own right. But even if one does not accept that embryos are accorded a certain level of dignity, what about babies and children? What do scientists plan to do if the children born from this procedure are unhealthy or deformed?

Finally, it is worth mentioning that this technique would provide a source of eggs, which are needed for various other reproductive techniques and research endeavors. For example, The UK just passed legislation permitting what has been dubbed “three-parent IVF” in which scientists transfer the nucleus from one woman’s egg to another woman’s enucleated egg that will then be used in IVF. The hope is to prevent mitochondrial disease which is genetically passed down to offspring from the mother. Obtaining skin cells from a donor is much less invasive and poses less of a risk to the donor than obtaining her eggs after inducing hyperovulation.

This research is rife with ethical concerns, most notably the fact that it amounts to human experimentation on people who did not have the opportunity to choose to be the product of experimentation, but must live with the consequences, if they live at all.

Is Being Productive the Highest Good?

Peter from Office Space (Picture from Rotten Tomatoes)

What happens when all we live to work. Let’s take a look at two shows that poke fun at the white-collar office worker. In the movie, Office Space, the main character, Peter, is disillusioned with the “rat race” of office life. His work is repetitive and unimportant, and therefore, he feels that his life is also repetitive and unimportant. His life is centered on his job. He lives to work, and because he does not have the right job, he is unhappy. The “happy ending” of the movie is not that Peter eventually learns that there is more to life than work and his identity is not wrapped up in his job. The happy ending is that he eventually finds a job that has the things he likes, being outdoors and working with his hands.

Jim

Jim from The Office (Picture from http://theoffice.wikia.com/wiki/Jim_Halpert)

In the television show, The Office (U.S. version), one of the characters, Jim, is apathetic about his job at a paper company, Dunder Mifflin. Jim has hobbies, like cycling and playing guitar, but we get the impression that he generally considers his job boring and one of those necessary evils of life (his views change as the series progresses). Dwight, on the other hand, approaches his job at Dunder Mifflin with enthusiasm, showing up early, leaving late, and always trying to be a team player. He also happens to live and work on beet farm, of which he is equally enthusiastic.

Both Office Space and The Office are written so that we relate to Peter and Jim. They represent the angst that most white-collar workers feel, even if we cannot put our finger on exactly what that angst is. Peter wants to be outside. Jim plays music. But are cubicles and paper-pushing really the problem?

Perhaps the problem has to do with how we prioritize our lives. Our Western culture has bought into the idea that productivity is the highest good, and therefore work should be an end in itself. Productivity is certainly one of many signs of a good employee or a well-run business, but it is not an end in itself. Being productive should not be the end-all-be-all of life. To live for productivity is hollow and dehumanizing. Machines are fine-tuned to be optimally productive. People strive for something more, and productivity helps us get there.

What is leisure?

In pre-modern times, people whose lives were centered on work were called slaves or laborers. They put in twelve or fourteen-hour days and spent their non-working time resting and recuperating so that they can work the next day. Their value is in their productivity. This is contrasted to the aristocracy. They engaged in leisure activities, but these activities are not what we think of when we think of “leisure” today. The aristocracy considered leisure activities important for cultural enrichment. Those that used their freedom to engage in diversions or hedonism were considered slothful.

Leisure, in the classical sense of the term, is different from restful activities to help recuperate from a long day or mindless activities to cope with the mental tedium of repetitive, labor-intensive work. Leisure activities consisted of the higher pursuits, like education, art, music, and sport. It is no accident that the word we use for “school” comes from the Latin translation of the Greek word for leisure. Leisure activities often consisted of difficult things that required hard work to master, but these activities were personally enriching and culturally significant. They often involved creating or writing things that have aesthetic appeal and are good in and of themselves.

The Industrial Revolution

This two class system was turned on its head with the advance of the Industrial Revolution. Industrialization, over the course of one hundred years, took menial, repetitive, undignified work and automated it. It also meant that people did not have to work as many hours, allowing all people to have a life that consisted of rest (including sleeping, eating, and bodily care), non-work, and work time. The non-work time was to be a time for leisure pursuits so that all men may cultivate a virtuous character and engage in culture-making.  This resulted in more people getting an education and engage in the arts and sciences.

But something happened that caused people to lose track of those priorities. Mortimer Adler, an early-twentieth century scholar, points out that while the Industrial Revolution did much to dignify work and rid of us a labor/aristocracy class system, it also skewed our understanding of work, leisure, and recreation.

Adler lists four negative consequences of the Industrial Revolution that contribute to our malaise:

  1. The Industrial Revolution eliminated the value of individual craftsmanship. Things that used to be made by artisans and craftsmen, like shoes, clothes, candles, or food, were easily produced in the factory setting, thus trivializing certain kinds of work.
  2. The Industrial Revolution changed our priorities such that producing more and more goods became the purpose of all of our efforts. Adler says that we ought to regard the increase in productivity only as a means and not as an end.
  3. As a result, people now think free time should be used only for recreation (or recuperation) in order to get back to work and produce more. It is no longer a time to engage in those things that are edifying and that often bring people joy. Instead, it is spent engaging in diversions which are not ultimately fulfilling.
  4. Classical, or liberal, education was replaced with training for the job so that a person can become a productive member of society. This perpetuated a kind of empty meaning to education that goes something like this: “Go to school and make good grades, so you can go to a good college, so you can get a good job, so you can be a productive member of society.”

Meaninglessness

By placing an emphasis on productivity, people live to work, and therefore, their free time is spent on things that are not tiring, but also not particularly enriching. This leads to a kind of boredom that philosopher-types like to call hyper-boredom. You get the sense of this hyper-boredom when you watch Peter in Office Space. However, hyper-boredom is more than “being in a funk” or not finding the right job. It is a malaise that is best described as operating as though everything was ultimately meaningless.

Why is a proper view of leisure important? Adler summarizes the classical concept of leisure as “consisting in all those activities by which the individual grows morally, intellectually, and spiritually, through which he attains personal excellence and also performs his moral and political duty.” Essentially, it is the things people love to do and would do whether they were paid or not.

Leisure is not the same has having nothing to do or “killing time” and it is not a diversion to cope with life. Adler points out that, based on the classical concept of leisure, the good life depends on labor, but it consists of leisure.

A couple of caveats are in order, though. First, some people are blessed to be able to do the leisure activities that they love as their full-time job. Adler, a college professor, considered his job both work and leisure. But, as anyone who has ever been a full-time teacher, writer, or artist knows, there is still a labor aspect to their leisure activity. Most people do not consider grading papers, filling out tax forms, or making sales pitches leisure activities. These things tend to be compulsory, making them work rather than leisure.

Second, this is not to say productivity is bad. It is good to be productive as part of pursuing excellence in work. However, orienting your life around productivity is to enslave yourself. Recall that in The Office, Jim was apathetic about work, but Dwight was not. Their characters are meant to be comic foils of each other, but as always, comedy is funny because it contains elements of truth. Dwight had a beet farm, a leisure activity, while Jim had diversions. Jim’s character started to change when he engaged in a meaningful relationship.

We often think that our leisure, or non-work time, is unimportant, but in reality, it is very important. A proper view of leisure helps us orient our lives in a way that acknowledges the reality of having to earn a living to survive but that we crave more than merely survival and consumerism.

NFL and Prescription Drugs

The NFL is being sued by 1,300 former players for the way it distributed prescription pain medicines so players can get back in the game. The former players claim that they were not informed of the side effects of potent pain killers such as Percodan, Percocet, Vicodin, and Toradol. Percodan, Percocet and Vicodin are all opioid painkillers and Toradol is a strong non-steroidal anti-inflammatory (NSAID) drug.

Many of the former NFL players involved in the lawsuit played during the 1980s and 1990s when practices for administering powerful painkillers, both opioids and NSAIDs, were cavalier. Today they are, in theory, more regulated. The players state that the “NFL medical staffs routinely violated federal and state laws in plying them with powerful narcotics to mask injuries on game days.” They also claim that medical staff was negligent by keeping important information on the players’ medical conditions from them, such as markers for kidney disease or broken bones.

At issue are 1) whether doctors and trainers violated the law by illegally administering prescription drugs, and 2) whether players were adequately informed of the side-effects of the drugs as well as informed of any medical issues that doctors found that might affect their decision.

Doctors Behaving Badly?

In an attempt to investigate whether illegal practices were going on, the DEA paid unannounced visits to several professional teams in November (2014) in which they questioned team doctors and trainers after the game. This investigation was to ensure that doctors were prescribing and distributing drugs appropriately, that they were handling controlled substances properly when crossing state lines, and that they had a license to practice in the state. Thus far, the DEA has not found evidence of illegal activities in their investigation.

However, an investigation from Vice Sports into how and where NFL doctors acquired such large amounts of prescription drugs, shows that, at least in the past, they were likely obtaining drugs illegitimately. From 2009 to 2010, several NFL teams, as well as other professional and college sports teams, acquired large amounts of opioids and NSAIDs from a company called SportPharm, an illegal drug distributor operating behind the legitimate company, RSF Pharmaceuticals. RSF Pharmaceuticals eventually shut down, and SportPharm was re-branded as a subsidiary of Champion Health Services, which is still in operation. Many teams would fill prescriptions in player’s names without the player knowing so that the actual quantities would fly under the radar.

Informed Consent

The second issue has to do with players’ rights, and whether they were adequately informed of what drugs they were given, their medical options given their current medical situation, and the long-term side effects.

Many of the players received opiate drugs without being told about their addictive nature, and were often told to take them for longer or in higher dosages than what is recommended by the FDA. Furthermore, many players were given prescription pain medicine without a doctor’s evaluation or monitoring. One former player reports that while playing for one team, an assistant trainer would pass out unlabeled manilla envelopes with pain medicine for any player that raised his hand and said he needed them. Another former player said that envelopes with prescription pain medicine would be waiting in the seats on the airplane for the players.

Player testimonies from the class action law suit website show that many players were given powerful pain medicine instead of being told that they needed rest and recovery or that the problem was actually much worse and required surgery. Several players said that NFL doctors knew of existing health issues, but did not inform the players. Two players’ testimonies state that NFL doctors knew that they had indicators of kidney problems but did not tell the players. Both former players now have renal failure.

Another former player, Rex Hadnot, said in a Washington Post interview that he was given Toradol pills and/or injections once-per-week for nine years. He was never told that Toradol should not be administered for more than five days due to risk of kidney damage, heart attack, and stroke.  He said that sometimes he would receive both a shot and a pill on the same day, a much higher dosage than the FDA recommends.

The Mountain Climber Problem

Part of the problem with discerning the ethics of safety for football players is exemplified in what H. Tristam Engelhardt calls “the mountain climber problem.” In general, climbing a mountain is more dangerous than not climbing a mountain, but we do not consider it unethical to allow a mountain climber to scale a mountain if he so desires. Similarly, playing sports is inherently more dangerous than not playing sports. Football players take on additional risks by choosing to play the sport. Therefore, what protections, if any, are football players owed?

There is a tension between restricting someone’s freedom and allowing them to put themselves in harm’s way. Typically, with the mountain climber problem, ethicists will say that it is unethical to allow additional harm to come to the person such that he or she could not accomplish the stated goal of climbing the mountain. For example, while mountain climbing is inherently dangerous, the climber should still use a harness and ropes. In the case of football players, while it is an inherently dangerous sport, one can enforce safety precautions to ensure that players are not injured in such a way that they cannot play the sport. This is the motivation behind stricter rules to prevent concussions, helmet design, and padding.

The difference between the mountain climber and the football player is that collisions are part of the sport. Pain is a given. The former players who are suing the NFL claim that their health was sacrificed in the name of sales. But, other players criticize the lawsuit as nothing more than a money grab on behalf of former players because they knew what they were risking by playing the sport.

Despite whatever motivations are behind the lawsuit or the NFL’s medical decisions, it is unethical to de-humanize athletes, even if they willingly chose to engage in de-humanizing activities. Let’s take a non-football example: If a woman choses to trade sex for money, she is willingly commodifying herself and ultimately engaging in a de-humanizing activity. While this may have been her free choice, it does not mean that if she goes to a doctor, the doctor is no longer ethically obligated to treat her with human dignity. In other words, even if she chooses to engage in activities that are de-humanizing, that does not mean it is okay for medical health professionals to treat her as less-than-human.

In the case of football players, even if they may choose short-term returns at the expense of long-term injury, they need to be given the opportunity to make an informed choice on the matter because, ultimately, they are the ones that have to live with the consequences.

In the latest issue of Salvo Magazine (Winter, 2014) I cover the larger issue of prescription pain medicine addiction, what opiate drugs actually do to the brain, and how one becomes addicted. The former NFL players’ claims about the over-prescribing of prescription painkillers may be part of a larger national problem that saw a peak in opiate drug prescriptions during the years that many of the former players were active in the NFL.

What Does Death Have to Do with Having a Happy Holidays?

Two Christmas stories that have stood the test of time are Charles Dickens’ A Christmas Carol and Frank Capra’s It’s a Wonderful Life. Both stories invite the main character to suppose he were dead. In A Christmas Carol, the ghost of Christmas future asks Scrooge to look at how people will talk about him once he has died. In It’s a Wonderful Life, George Bailey is taken to an alternative world in which he sees how things in his town would be different had he never lived.

Additionally, both main characters must look into the face of death, confronting their own mortality, before they are ready to see that their problems originate in their own hearts. In A Christmas Carol, before Scrooge faces his own death, he encounters Marley’s ghost who warns Scrooge that if he continues in this path, he will end up like Marley, chained to his idol.

In It’s a Wonderful Life, George sinks into such deep despair that he ends up standing on the edge of the bridge considering suicide, but instead rescues another jumper from the bridge. Incidentally, the other jumper was Clarence who, similar to Marley, was once alive but now is dead, and whose mission is to help George live a better life. Scrooge and George Bailey are vastly different characters, yet both are miserable because of the same seed of discontent growing within them, and both are cured through similar means.

Interestingly, what is different about George Bailey and Ebenezer Scrooge is telling. Scrooge is the lonely wealthy man who seeks to rob others of joy because he cannot feel it himself. George is the sympathetic family man who begrudges his tender-heartedness because it has left him poor and stagnant. Both the rich man and the poor man struggle with discontent, and both the rich man and the poor man believe that money is the key to their happiness.

Both men are plagued by the same disease, discontent. When a person is discontent in poverty, he does not see the mercies and blessings he has been given, but only his lack. Puritan writer, Thomas Watson, points out that a man who is discontent in this estate will think even bitter things taste sweet. We see this when George Bailey considers compromising his standards and partnering with Mr. Potter, the town tyrant.

When a person is discontent in wealth, he can never accumulate enough to satisfy his true needs. Scrooge hoarded his wealth as a kind of security. Marley warns that rather than a security it is a fetter. The discontented wealthy man can never acquire enough, and we see this in Scrooge’s bitterness. He left his loved ones to pursue wealth, but wealth proved to be a burden rather than a companion.

By the end of the story Scrooge and George Bailey are not in a different place than they were when they faced their supernatural reminders of their mortality. Yes, George got the lost money back, but his town didn’t change, his house still had the broken bannister, and he still had four children to feed.  Scrooge still lived in the same dark house and Bob Cratchit was still his employee. What changed was their state of mind. And that is the lesson. Contentment is a state of mind, not some perfect combination of annual income, a home’s square footage, stock investments, luxury car, or vacation experiences.

George Bailey and Ebenezer Scrooge may not be characters in our time and place, but their lesson applies now as it did then. Ours is a culture that thrives on us never having enough. There are noble things that we should not be content to endure, like children dying from leukemia, or grandparents whose mind has been ravaged by Alzheimer’s, or diseases that destroy the body and injuries that result in loss of function.

However, wanting to rid the world of innocent suffering is not the kind of discontent that haunted George Bailey or Ebenezer Scrooge and it is not the kind of discontent that is endemic in our own time. Ours is a discontent that says “You deserve the best.” It is a discontent that comes from a sense of entitlement and a lack of thankfulness.

Many people blame our cultural sense of discontent on commercials that tell us that you will be happier driving a particular car or technology industries selling newer and better products before the warranty is out on your old one or magazines with air-brushed models sporting impossibly perfect bodies. But George Bailey and Ebenezer Scrooge didn’t have Cadillacs, iPhone 6s, or Photoshop. These industries are not the problem; they just make a profit from it. The problem is as old as human nature. We are dissatisfied with what we have and instead of addressing the root of our dissatisfaction, we would rather strive for more and more like Scrooge, or sink into despair like George Bailey. Their lesson strikes a chord with us because we are like them, and perhaps, like them, our focus on our lack robs us of our joy in what we have.