(In honour of a new science scout badge)

The “I’m a marine biologist and, to be honest, I kind of hate dolphins” badge.
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So you want to be a marine biologist? Well sonny, or sonnette, as the case may be, why don’t you just sit down and let a real marine biologist give you some damn good advice. And wipe that smirk off your face, sit up straight and for goodness sakes stop fidgeting! You’d think you had lice the way you are carrying on. You do? Oh well, never mind.

First of all there are three really, really bad reasons to want to be a marine biologist. If you have even an inkling that these are yours, please run away as fast as possible, ‘cause neither you nor we will be happy.

Three Really, Really Bad Reasons to Want to Be a Marine Biologist

Reason Number One: “I want to be a marine biologist so that I can talk to dolphins.”

Believing this is simply the Kiss of Death. This is the verbal equivalent of reaching down your throat, pulling out your own intestines, wrapping them around your neck and choking yourself. When we hear this our impulse is to thwack you a good one on your keester with the frozen haddock we keep within arm’s reach just for this occasion.

And why is that? It is because, and please listen carefully, while you may want to talk to dolphins, dolphins do not want to talk to you. That’s right. Mostly, dolphins want to eat fishes and have sex with other dolphins. And that pretty much cuts you out of the loop, doesn’t it? Oh, I know that there are the occasional dolphins that hang around beaches, swim with humans and seem to be chummy, but these are the exceptions. You don’t judge the whole human race by the people who attend monster car rallies, do you?

Just be honest with yourself. If you want to talk to dolphins you don’t want to be a biologist. What you really want to do is explore your past lives, get in touch with the Cosmic Oneness and conduct similar-minded individuals on tours to Central America looking for evidence that We Are Not Alone. Our experience is that people who feel this way last about 6.5 minutes in any biology program.

Reason Number Two: “I want to be a marine biologist because I really like Jacques Cousteau.”

That’s nice. We really like Jacques Cousteau, too. But, drinking thousands of gallons of red wine while scuba diving around the world does not make you a marine biologist. It makes you a wonderful and effective spokesperson for the sea, and gives you a liver with the consistency of a chocolate necco wafer, but it does not make you a marine biologist.

Reason Number Three: “I want to be a marine biologist because I want to make big bucks.”

Okay, here’s the bottom line. By Federal law, marine biologists have to take a vow of poverty and chastity. Poverty, because you are not going to make squat-j-doodly in this job. Just how squat is the doodly we are talking about? Well, five years after finishing my PhD I was making slightly less than a beginning manager at McDonalds. Ooh, a 36 year old guy with 13 years of college and 5 years of post-doctoral experience making just about as much as a semi-literate 19 year old with pimples the size of Bolivia, who can speak perhaps 3 words at a time before the term “you know” enters the conversation.

And chastity because, well, who’s going to date a marine biologist? The smell alone tends to dissuade a large proportion of the opposite sex.

Two Really, Really Good Reasons to Want to Be a Marine Biologist

Reason Number One: “You can dress and act almost any way you want.”

This is true. Marine biologists are almost entirely free of any of those silly restrictions that blight the professional landscape of our fellow proletarians. This is because no one really cares about what we do or what we say. You want to come to work dressed in scabrous khaki shorts and a torn black Sandman shirt? Fine. You want to grow a scruffy beard, get a tattoo of a gooseneck barnacle on your arm or burp at inopportune moments? No problem, just do good work.

Reason Number Two: “If you like it, just do it.”

Look, the reality is that you only go around once in life and if, by chance, you do come back, knowing how you have behaved in this life, you will undoubtedly come back as a slime mold. And most slime molds cannot be marine biologists. So just go out there and do what you enjoy. Marine biology is a wonderful profession. You want to find cancer cures by grinding up sponges? How about figuring out why hammerhead sharks always come back to the same seamount? Or where is the missing carbon dioxide that industries are producing; could the ocean be soaking it up? All neat projects. But pay attention here. None of this involves drinking copious quantities of fermented grape juice, while intoning “The ocean, she is strange and wondrous, filled with animals that disturb even a Frenchman.”

The ocean is an exciting, never-dull place that is perfect for piddling away your existence. And just think, you actually get paid to think cool thoughts and do cool things.

And so what if you will never have sex again?

(Thanks to James Wood for the badge suggestion)

Inspired by space travel and Joyce Kilmer’s “Trees”

I think that I shall never see
A thing as lovely as a pea

A pea whose shell is green and bright
Having withstood the years of flight

A pea without flavor dried away
Despite sitting in the cargo bay

A pea that’s sturdy, firm and round
In which some vit’mins are still found

Piled en masse on my plate
Having cleared the take-off weight

Such dreams from only fools like me
Why can’t NASA make a pea?

“Ay, thou art for the grave; thy glances shine
Too brightly to shine long; another Spring
Shall deck her for men’s eyes—but not for thine—
Sealed in a sleep which knows no wakening.
The fields for thee have no medicinal leaf,
And the vexed ore no mineral of power;
And they who love thee wait in anxious grief
Till the slow plague shall bring the final hour…”

From Consumption by William Cullen Bryant
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Tuberculosis (TB) is a disease of global concern, and one of the oldest enemies of the human race: the records of its presence date back as far as 2400 years BC[1]. The deadly plague has claimed many lives throughout the ages, and it is still claiming more. In 1993, the World Health Organization (WHO) declared TB a “global emergency”[2]. It is estimated that one third of the world population is currently infected with TB, and the numbers are increasing by approximately 8 million annually[2, 3]. TB is the second leading cause of death worldwide and the leading cause of infectious disease mortality, contributing to more than 3 million deaths annually [3, 4, 5]. Co-infection with HIV greatly complicates matters, as it weakens the immune system and increases the susceptibility to TB infection[3]. Of those who are encounter TB each year, 0.9 million are also infected with HIV[3,6]. This co-infection is associated with an increase in the quantity and severity of TB symptoms and a faster progression to death[3]. In addition to the problem of HIV co-infection, the ongoing generation of multidrug-resistant strains of M. tuberculosis (the bacterium causing TB) which are resistant to most conventional therapies is adding to the problem. Simultaneous infection with an MDR TB strain and HIV has a very poor prognosis with an average life expectancy of only two months[3]. It is believed that TB will kill approximately 90 million people over the next three decades, and the depletion of the human resources that is a direct result of this in turn poses major economic threats to those countries with a TB epidemic[3, 5]. This calls for immediate action to develop more effective prevention strategies and therapies.

What TB does to the human body

Figure 1. Electron Micrograph of M. tuberculosis
(Image courtesy of the Institut Pasteur Image Library)

Tuberculosis is caused by Mycobacterium tuberculosis (or M. tuberculosis, see Figure 1), a slow growing bacillus which is an obligate human pathogen (i.e. it cannot survive outside the human body)[7, 8, 9]. Infection with M. tuberculosis causes latent disease in the majority of cases, which may develop into active pulmonary TB[10]. The body’s reaction against M. tuberculosis infection typically consists of strong cell-mediated immunity (involving T lymphocytes) [10, 11]. One class of T lymphocytes known as Th1 cells or CD4⁺ T cells release cytokines (cellular hormones) such as interleukin-12 or interferon g, which in turn enable the infected cells to engulf mycobacteria and prevent their proliferation[12, 13]. Another line of defence is provided by cytotoxic T cells (a.k.a. CD8+ T cells), which could directly target the infected cells and kill them by creating a pore in the cell wall and secreting toxic molecules into the cell[10, 13]. In addition, mechanisms exist to prevent an excessive immune response[13]. Once these mechanisms of host defense against M. tuberculosis are weakened (which could be due to a variety of environmental factors), the latent infection transforms into active disease[14]. The clinical symptoms of active pulmonary TB could be non-specific, such as fever, wasting, ill appearance, headache, and back and abdominal pain[15]. Active TB could also lead to lung abnormalities, such as cavitation, necrosis (cell death within the lungs), fibrosis and scarring, which could eventually lead to death[4]. TB can spread through the aerosol, vascular, and lymphatic routes, and therapy generally requires six to twelve months of antibiotic treatment[4, 15].

Prevention strategies

Currently, the only available preventative measure against TB is vaccination with an attenuated form of Mycobacterium bovis (a relative of M. tuberculosis which affects cattle)[6]. This vaccine was developed by Calmette and Guerin during the first two decades of the twentieth century, and having yielded positive results in animal studies, it was given to humans in the early 1920s [12]. The bacillus Calmette Guerin, as it came to be called (or BCG in short) remains one of the most widely prescribed vaccines in the world[3]. It is recommended by the World Health Organization for all infants under 1 year of age, and every year 100 million newborns are vaccinated[6]. More than 3 billion people are estimated to be vaccinated with BCG so far, giving BCG the status of the vaccine with the highest global coverage (80%) [6]. Despite its widespread application for over 80 years, BCG remains the most controversial vaccine in current use[3]. The amount of protection offered by BCG against pulmonary TB has varied greatly in different studies, ranging from zero to 80% [3, 6]. Despite this variation in different populations, there is general consensus that BCG offers good protection against childhood TB, and also against leprosy (another disease caused by a mycobacterial species) [3, 6, 12]. However, the protective efficacy of BCG wanes over a period of 10-12 years, which is illustrated by an increase in active TB cases in adolescents previously vaccinated with BCG [6]. Another disadvantage of BCG is that the vaccination leads to the development of a delayed type hypersensitivity response which cannot be distinguished from infection with M. tuberculosis, creating difficulty in the diagnosis of TB[3]. Furthermore, since BCG is a live vaccine, it is capable of causing disease in immuno-suppressed individuals, such as those infected with HIV[3].

WHY have we failed?

The great variation in the efficacy of BCG may be due to several factors. It is important to note that not all BCG vaccines are identical in their composition. There are several strain variations between the vaccines developed in different laboratories and environments and the storage and treatment of BCG may also vary in the different local laboratories[6, 12]. Furthermore, there are genetic and nutritional differences in the populations that were studied in various experiments, which could affect the vaccination outcome[6]. The role of environmental factors which contribute to vaccine efficacy should also be taken into account. For example, exposure to other environmental mycobacteria (which are more abundant in tropical climates) prior to vaccination with BCG may reduce the efficacy of the BCG vaccine[6]. A recent study has also found that chronic infection with some other parasites (such as roundworms) changes the immune response in such a way that Th1 cytokines are not produced, lowering the protection offered by BCG [6]. Moreover, factors such as the route of administration and optimal vaccine delivery must be considered when evaluating the failures of BCG [6].

In addition to these general “experimental variations”, BCG itself has several shortcomings which may lead to its low efficacy. For instance, during the process of attenuation which leads to the production of BCG, M. bovis is robbed of many of its important antigens[6, 12]. Antigens are a cell’s surface molecules which are recognized by the host’s body as potential pathogens and elicit an immune response. Several of these antigens (such as ESAT-6 and MPT64) which have been shown to elicit a strong host immune reaction are missing in BCG [6, 12]. In one experiment, a recombinant BCG vaccine was created which expressed the immunodominant antigen of M. tuberculosis, known as Ag85B. This modified BCG was found to yield greater protection against TB than conventional BCG [12]. Another problem associated with this vaccine is the type of immune response it elicits in the host organism. BCG’s ability to induce a response in CD8+ T cells has been questioned. In comparison, M. tuberculosis has been found to gain access to the cytoplasmic compartment of infected cells and thus facilitate a response in CD8+ T cells [12]. Finally, while BCG does not immunize the vaccinated individual for life, repeated BCG vaccination also fails to “boost” the protection offered by the primary vaccination[6]. It is clear that these limitations need to be overcome in any new vaccine candidate against TB.

And DNA walks in …

Thus the novel approaches for developing a TB vaccine have been targeted at eliminating the shortcomings of BCG. One method known as DNA vaccination utilizes plasmid DNA (which is a circular, double-stranded DNA often isolated from bacteria) to encode the protein of interest (which is usually a potent antigen from M. tuberculosis or a related species) to elicit an immune response in the host organism[13]. Of the 200 candidate vaccines which have been studied over the past two decades, DNA vaccines are of special interest for a variety of reasons. First, they are safe and do not have the problem of inherent pathogenicity associated with live vaccines such as BCG [3]. That means that they could probably be used on immuno-suppressed individuals without making them sick. Second, the stability of the DNA molecule may eliminate the problem of transportation associated with BCG and the necessity to develop the vaccines at local hospitals and laboratories[13]. Third, DNA vaccines have been shown to generate long-lasting immunity in several animal models[3, 13]. One of the remarkable and rather rare abilities of DNA vaccines is their strong activation of CD8+ T cells, which serves to eliminate the pathogens by directly killing the infected cells[6, 12]. Finally, plasmid DNA can be used to deliver multiple antigens by cloning different genes in the plasmid vector[3]. Studies have shown that the DNA vaccines encoding multiple antigens have a greater protective efficacy than those encoding a single protein[16]. Thus, mixing various vaccine components, which may be difficult in other vaccination techniques, appears to be feasible using DNA vaccines[16]. One strategy which has led to a longer-lasting immune response in some animal models is the use of DNA vaccines to prime the immune system, and then boosting the vaccine efficacy by using another vaccination technique[6, 12]. This “prime-boost” method has been found to offer greater protection compared to the use of repeated administration of a DNA vaccine alone[6, 12].

Towards a brighter future

Despite the recent advances in biotechnology and the successful results of DNA vaccination in animal models, the above findings must be taken with a note of caution. BCG itself has in fact been quite efficient in animal models, whereas this efficiency was not replicated in human trials[12]. Thus our first step must be to evaluate the efficacy of these different types of vaccine in a model in which BCG fails[12]. Furthermore, no single DNA vaccine has been found to offer great protection against TB. However, as we enhance the available DNA vaccines, there are many reasons for optimism. Some ways in which the potency of DNA vaccines could be increased are to modify the DNA vector to allow a greater expression of the desired antigen or more specific targeting of the antigen, to use adjuvants (i.e. molecules that elicit a strong immune response in the host) for boosting the immunogenicity of DNA vaccines, and to facilitate plasmid DNA uptake by the cells[16]. Many potent M. tuberculosis antigens have already been shown to be compatible with the DNA vaccine technology, and although the single DNA vaccine has not been shown to be much more effective than BCG, evidence suggests that multiple DNA vaccinations or delivery of multiple antigens by a single vaccine could be useful alternatives [6, 12, 16]. Since the recent biotechnological advances seem capable of implementing the necessary modifications, the strengths of the DNA vaccine may provide a reasonable hope for its successful human testing in the future[3, 16]. And maybe, maybe one day, William Bryant’s poem could be changed to something like this:

“ ’Though the fields for thee have no medicinal leaf,
The double helix comes forth with mighty power;
And they who love thee watch in disbelief
The plague’s dismal doom in its final hour.”

References

1. Brewer, T.F., and Heymann, S.J. Arch Med Res. 2005; 36(6): 617-621.

2. Kremer, L., and Besra, G.S. Expert Opin Investig Drugs. 2002; 11(2): 153-7.

3. Mustafa, A.S. Curr Pharm Biotechnol. 2001; 2(2): 157-173.

4. Dheda, K., Booth, H., Huggett, J.F., Johnson, M.A., Zumla, A., and Rook, G.A.W. The J Infect Dis. 2005; 192:1201-1210.

5. Sacksteder, K.A. and Nacy, C.A. Expert Opin Biol Ther. 2002; 2(7): 741-9.

6. Haile, M. and Kallenius, G. Curr Opin Infect Dis. 2005; 18(3): 211-215.

7. http://www.sanger.ac.uk/Projects/M_tuberculosis/gfx/mtb_medium.gif

8. Murry, J.P., and Rubin E.J. Trends Microbiol. 2005; 13(8): 366-372.

9. Vaerewijck, M.J.M., Huys, G., Palomino, J.C., Swings, J. and Portaels, F. FEMS Microbiology Rev. 2005; 29(5): 911-934

10. Aliberti, J., and Bafica, A. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(3-4): 283-288.

11. McKenzie, B.S., Corbett, A.J., Brady, J.L., Dyer, C.M., Strugnell, R.A., Kent, S.J., Kramer, D.R., Boyle, J.S., and Lew, A.M. Immunol Res. 2001; 24(3): 225-44.

12. Agger, E.M., and Andersen, P. Vaccine. 2002; 21: 7-14.

13. Sbai, H., Mehta, A., and DeGroot, A.S. Curr Drug Targets Infect Disord. 2001;1: 303-313.

14. Frothingham, R. Stout, J.E., Hamilton, C.D. Int J Infect Dis. 2005; 9(6): 297-311

15. Potter, B., Rindfleisch, K., and Kraus, C.K. Am Fam Physician. 2005; 72(11): 2225-32.

16. Ulmer, J.B. Scand J Infect Dis. 2001; 33: 246-248.

The ID debate is getting pretty trite. The only thing keeping it interesting to me is the incredible lengths that both sides will go to get their points across. Whether it’s sending free, lavish copies of an anti-evolution book to every evolutionary scientist in the western world (Harun Yahya) or inventing a the label of “bright” for you and your enlightened, like-minded friends (Richard Dawkins), the intensity of the fighting seems to be escalating. The media, our supposed source for clear thought, is acting more like a bookie at a boxing match: whoever wins, the real winner is the house. And don’t get me started on the internet! This whole thing should have been called a draw a hundred years ago.

Or should it have? Can some real intellectual advance come from all this madness? As someone who has picked a side but sees no point in picking fights, there is one thing I have noticed, a phenomenon that most people entrenched in the fighting are missing. This phenomenon is even eerily reminiscent of a well known evolutionary principle, and it is this: the ID movement coupled with evolutionary science is as effective at producing a better theory of evolution as an evolutionary arms race is at producing more complex organisms. That’s right, there is an invisible hand moving amongst the chaos. Allow me to explain.

ID is very often maligned for being an entirely unscientific enterprise because it makes no testable hypotheses. This is not exactly true. It makes one, a hypothesis popularized by Michael Behe as the irreducible complexity hypothesis. The idea, however, is not new and was even made explicit by Darwin at the very beginning. He said, “If it could be demonstrated that any complex organ existed which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down.” To someone who has a vested interest in Darwin’s theory breaking down, this sounds like a tantalizing challenge. As the field of evolution has expanded and engulfed newer and more complex fields like biochemistry and development, the processes that constitute life seem more bafflingly complex than ever. Instead of the eye, nowadays one would more likely hear about the cilia or the blood-clotting pathway as the ultimate example of an answer to Darwin’s challenge. For many in both camps, Richard Dawkins’ flippant answer of “we’re working on it,” just doesn’t cut it. Looking at the Dynein and Kinesin proteins that tightrope walk along 30 nanometer microtubules with their special deliveries between two organelles in a cell, even the most secure evolutionist wipes sweat from his or her brow and thinks I sure hope the Discovery Institute hasn’t seen this.

And this is just the point. What feels better for an evolutionist than figuring out that some animals with fully functional clotting are missing major elements of what we know as the blood-clotting pathway? Figuring it out and presenting it in the spotlight of the Dover trial, shutting down the ID defense, and the having the judge write a cutting 100+ page report documenting your opposition’s defeat, that’s what. Rest assured, however, that the IDers will not go home and toss out their holy books in favor of the Origin of Species. The defeat will only inspire them to look ever more deeply, scrutinizing every little detail of evolutionary theory, probing the foundations until another weak spot is hit. Can you see now how absolutely perfect this relationship is? If TH Huxley was Darwin’s bulldog, then ID is Dawkins’ basset hound, an organization whose goal is to sniff out weak points in evolutionary theory, almost like a third-party auditor making sure your books are in order. Evolutionists retaliate, showing that Darwin’s challenge has not been met, and the cycle continues, producing as a side effect an even more coherent evolutionary theory.

The ID debate is simply not a scientific or a logical one. It is a metaphysical one, in which two basic assumptions about the world are pitted against one another. Unless one side can get the other to radically alter their entire world-view, bits of evidence either way will be trivial battles won and lost with little long-term effect. Until then, the war rages on. Considering that the more we know in biology, the more it makes our heads spin, it will likely keep raging for years to come. The good news is that until the Lion lies down with the Lamb, the real benefit of all this conflict is to the theory of evolution itself.

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Abstract

In this series, twenty one dialogs that reference genetics from the six seasons of the HBO television series The Sopranos are cited and discussed, in chronological order, from the perspective of a fan who is a geneticist. The context of each citation with respect to the plot and characters will be the main focus of discussion.

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Dialog Three (Season I, Episode 7: Down Neck).

Tony is discussing Anthony Jr.’s behavior and evaluation for A.D.D. with his psychiatrist, Dr. Melfi.

“You Are What You Are”

Tony: “My son is doomed, right?”

Dr. Melfi: “Why do you say that?”

Tony: “Come on- this is the part where I’m supposed to tell you how terrible my father was and the terrible things he did to me. And how he ruined my life. I’ll tell you something, I was proud to be Johnny Soprano’s kid. When he beat the shit out of that guy, I went to the class, I told them how tough my father was.”

Dr. Melfi: “Do you think that’s how your son feels about you?”

Tony: “Yeah, probably. And I’m glad. I’m glad if he’s proud of me. But that’s the bind I’m in. Cause I don’t want him to be like me. He can be anything he wants to be. He can be like this guy I knew in high school. His grandfather invented these
little ties that go on the end of salamis, made millions of dollars sitting on his ass.”

Dr. Melfi: “Have you communicated any of this to your son? “

Tony: “Not in so many words. Probably not at all. What difference would it make, you said so yourself. It’s in the blood. It’s hereditary.”

Dr. Melfi: “Genetic predispositions are only that, predispositions. It’s not a destiny, written in stone. People have choices.”

Tony: “She finally offers an opinion!”

Dr. Melfi: “Well they do. You think that everything that happens is pre-ordained? You don’t think human beings possess free will?”

Tony: “How come I’m not making fuckin’ pots in Peru? You’re born to this shit. You are what you are.”

Dr. Melfi: “Within that, there’s a range of choices. This is America.”

Tony: “Right. America.”

This is the third direct mention of genetics on the show, and it serves to draw attention to the idea that the pathological behavior in the Soprano family is a function of both nature and nurture, but in the context of a number of other ambivalent and complex forces making Tony’s life, and the plot of the show, richly complicated. Anthony Jr. has been evaluated for Attention Deficit Disorder by the school psychologist, who has determined that Anthony Jr. is a borderline case. Tony resents the idea that what seems like normal behavior to him for a 12-year old is treated as a disease.

Tony is also worried that Anthony’s disruptive behavior at school might be a sign that he is destined to follow Tony into a life of crime, which isn’t what it used to be, and which Tony doesn’t want for his son. We see the similarities and differences between Tony’s experience with his father and Anthony’s current situation. Although Tony and Carmela are much less dysfunctional than Tony’s own parents were, Tony recalls how he was proud of his father in spite of his realization that he was a criminal capable of violent behavior. Tony realizes that Anthony Jr. may feel the same way about him once he figures out what he does for a living, but Tony knows that there’s no future in the mafia any more and he doesn’t want Anthony’s difficulties in school and his lack of conventional ambition to lead him, by default, to an interest in Tony’s business.

One would think that Tony’s childhood in the Italian section of Newark where the mafia was endemic to the culture would explain his career choice, while Anthony’s experience as a kid growing up in an affluent New Jersey suburb would guarantee his passage into legitimate society. Tony has, however, generalized an assumption that attention deficit disorder is hereditary to the possibility that Anthony Jr. is “doomed” to gravitate toward the same life of crime because heredity is working against him in spite of his more favorable environment. Besides parental influences, social and cultural influences, the decline of the mafia from its golden era of Tony’s childhood, the possibility of genetic predisposition to criminality emerges as a crack in the image of America as a land of freedom and opportunity where even the children of second generation immigrant mafia dons can aspire to follow the conventional American dream.

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Dialog Four (Season Two, Episode Fourteen: Guy Walks Into A Psychiatrist’s Office).

“Even With Our Genes”

Tony and his sister Janice are sharing a cigarette by the pool just after Janice has returned to New Jersey after many years away from home.

Tony: “You look sensational Janice- not a line.”

Janis: “Two beautiful kids- you must be proud.

Tony: “Yeah, yeah- how about that, huh? Even with our genes.

This fourth reference to genetics on the show continues to develop the “nature-nurture” theme with respect to the pathological behavior of the Soprano family as a function of both nature and nurture. Tony’s therapy sessions with Doctor Melfi have focused largely on stresses related to his work and his relationship with his mother Livia, but his panic attacks imply something physiologically defective as well. The return of Tony’s sister Janice, and her subsequent prominence in the plot and in Tony’s personal life turns the focus of the show even more toward Tony’s family dynamics amidst the plot lines revolving around organized crime.

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Dialog Five (Season Two, Episode Fifteen: Do Not Resuscitate).

“A Report on DNA”

Tony, his wife Carmela, his daughter Meadow and his son AJ are sitting down to a dinner of macaroni and cheese.

Carmela: ” …did everybody take a vow of silence or something- nobody’s got anything to report”?

AJ: “I gotta write a report on DNA for biology.”

Carmela: “Isn’t that interesting! I just saw, on Inside Edition, how there will be no more unknown soldiers because of DNA now. They will be able to identify every single casualty of combat.”

This fifth mention of genetics, by explicitly referencing “DNA”, albeit through AJ’s dim grasp of the subject, injects state of the art genetic science directly into the dialog. This adds a modern touch to the more traditional sense of heredity through familial resemblance, by referring to the molecular level of mechanism underlying the inheritance of biological characteristics that operates in parallel with non-genetic familial inheritance through culture. This explicit reference to DNA puts the old “nature/nurture” dichotomy into a modern context. Tony’s earlier somewhat facetious remark to his sister (“even with our genes”) could be taken to mean simple familial resemblance that doesn’t clearly separate genetics from culture and other environmental factors, since the context and use is somewhat colloquial, and Tony is adept at picking up new language and working it into his conversation in new contexts whether he knows what it means or not. This explicit mention of DNA, however, in a conversation among members of a nuclear family around the dinner table, clearly identifies a hereditary mechanism that is causally independent of all social, cultural and other environmental factors but is also at the core of our individuality, family and humanity.

Carmela’s animated response to AJ’s contribution to the dinnertime conversation, in which she elaborates on the Inside Edition show featuring the use of DNA to ID “unknown soldiers” unwittingly describes a forensic genetic technology that is a real and immediate threat to Tony in his line of work and which applies to Tony and his “soldiers” just as well as the unknown soldiers Carmela is talking about. Whether or not this introduction of forensic genetic technology into the dialog foreshadows future problems for Tony and his crew remains to be seen.

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Dialog Six (Season Two, Episode Fifteen: Do Not Resuscitate).

“A Hundred Million Nucleotides”

The family is sitting down to dinner again.

Carmela: “Tony we’re sitting down!”

AJ: “Ma, DNA- it’s invisible right? But guess how many nucleotides are on each strand?”

Meadow: “Tell her!”

AJ: “A hundred million!”

Carmela: “Wow, that’s amazing.”

This dialog picks up where the previous one left off. Here, AJ almost gives a little “mini-lecture” on genetics. Carmela’s response, however, is more lukewarm this time. We know that AJ doesn’t really understand what he’s talking about. Carmela’s “Wow, that’s amazing” comment after Meadow’s impatient “Tell her!” lacks enthusiasm, and Tony is oblivious to the whole conversation. What’s the point of introducing these two relatively technical pieces of information (DNA is colorless, and each strand has “a hundred million” nucleotides)? One is to reinforce the notion that the previous mention of DNA was not just an ephemeral event in the plot line- here we’re being hit over the head with it.

A second observation is that nobody is very interested in it, except AJ, who is the least capable of understanding its significance. Carmela may have unconsciously recognized that her connection, in the previous conversation, to the use of genetics to ID unknown soldiers is a dangerous threat to Tony and she may not be so eager to encourage further conversation about it, especially given the mood that Tony’s in. Tony is depressed and has more important and immediate problems on his mind. Meadow is annoyed.

As viewers, we’ve been alerted to an additional level of complexity to add to the mix of plot lines, character development, dramatic elements, and possibilities for future directions that may, or may not be followed up or played out, and that make the show so much like “real life”. This may be the point of the additional information presented here. The reference to DNA being “invisible” is interesting because, as far as we’re aware, it is as invisible, but potentially as important as our “mind” or “soul” as an explanation for our behavior. Our DNA does its job shaping our nature and development without any conscious effort on our part.

Whether we think of our genetic heritage in the traditional sense of “family” resemblance, or in the more modern sense of our own personal DNA sequence, we know that much of our individuality and humanity is derived from our hereditary biological makeup. We don’t have to be aware of the billions of nucleotides in each of our cells, or of genes switching on and off as we think, act and react from moment to moment in our lives. We can’t really separate out the role that our genes play, on an individual level, from culture, our individual histories and the moment at hand, and all the other causal factors that define our existence and blend into our unitary sense of self.

This is part of the drama that exists in our own lives that is captured so well by The Sopranos – the complexity of our multiple identities as an individual. We understand Tony through his identity as a mafia don, as a father, a spouse, a psychiatric patient, a friend, as an Italian-American, and on and on and on, and now we can view Tony through his DNA as well.

The relative indifference of the rest of the family to AJ’s enthusiastic update on his technical understanding of DNA may also reflect the fact that unless we’re talking about a cure for cancer, a way to slow down aging or a way to enhance socially desirable qualities in ourselves or our children, most non-scientists aren’t particularly interested in the technical aspects of genetics. They are, however, often fascinated with the mythology of genetics on a personal level, and eager to use “genetics” in the service of rationalization, justification, or personal historical revisionism as an integral part of the “story” that all of us have the privilege of constructing, after the fact, to explain and justify our existence and our behavior. Our current understanding of genetics is sophisticated enough to know that genes are a real and integral part of what we are as a species and as an individual, but it is still incomplete enough so that we can’t explain exactly what we can attribute to our genes versus everything else that defines us as human and as individuals. This is very convenient because we can, like Tony does, pick and choose what we want to take credit for ourselves in our individual lives, versus what we want to blame on our genes or on myriad non-genetic factors whether real or imaginary. Our DNA does not, by itself, determine anything about us with that much precision other than the amino acid composition of the proteins in our bodies.

Why does AJ note, specifically, that there are “a hundred million” nucleotides on each strand of DNA? I suspect that one reason is to convey a sense of the immense complexity and density of genetic information so as to telegraph to the viewer that in spite of the amazing precision and objectivity that DNA fingerprinting may permit when it is used for forensic identification, adding psychiatric behavioral genetic elements to the plot will only make Tony’s character that much more complex and multivariate.

This is very rich material for Tony (and all of us) to work with in the show and in our own lives, respectively, and raises legitimate questions about how much control we really have over our lives and circumstances.

- – -

Dialog Seven (Season Two, Episode Fifteen: Do Not Resuscitate).

“DNA Doesn’t Prevent Comas”

AJ is visiting his grandmother, Livia, in the hospital after overhearing a conversation at home where Janice is trying to talk Tony into authorizing a “Do Not Resuscitate” order for Livia.

AJ: “Gramma- what’s DNR?”

Livia: “Who?”

AJ: “DNR- it’s initials, like, I do this report on DNA, but I heard Dad and Aunt Parvoti talking about your DNR- so is that, like, similar?”

Livia: “Huh? You mean Janice- Janice- they were talking about me?”

AJ: “About your DNR. Cuz that’s what’s confusing- like DNA, everybody’s got that.”

Livia: “She thinks I should have a DNR?”

AJ: “Or that Dad should give it to you or something. Because what if you went into a coma or something? But DNA doesn’t prevent comas, does it? I don’t know- I gotta do this report by Monday.”

AJ’s innocent conversation with Livia about DNA triggers Livia’s realization that Janice wants a DNR (do not resuscitate) order on her medical chart. Livia wastes no time in accusing Janice of plotting against her, talks about Janice’s teenage drug use with her nurse in front of Janice, and even goes so far as to call Carmela as if to begin giving her instructions on what to do “if something should happen” to her. Livia appears to be on the verge of giving Carmela information about money she wants to leave to the children, but Carmela, who is unaware of what’s going on between Janice and Livia, hangs up on her. This juicy plot development is set up nicely by the two earlier dinnertime conversations with AJ about DNA.

A more distant plot connection, that may just be a coincidence, is suggested by AJ’s confused non-sequitur from “DNA” and “DNR” to DNA and comas:

“Because what if you went into a coma or something? Because DNA doesn’t prevent comas, does it”?

Besides moving the plot along nicely with respect to the dynamics between Tony, Livia and Janice, does this reference also foreshadow Tony spending part of Season VI in a coma? Uncle Junior finally succeeds in doing in Season VI what he failed to do in Season II by shooting Tony and putting him in a coma. AJ’s question about DNA and comas could be taken two ways: on the one hand, shared DNA doesn’t prevent Tony’s own relatives from trying to kill him. On the other hand, once Uncle Junior succeeds, through his dementia, in nearly killing Tony, it’s the voices of Tony’s own children that are foremost in Tony’s consciousness when he awakes from his near death experience.

Tony’s emergence from the coma also occurs right after an imaginary conversation in which he tells a hotel bartender that he’s recently been diagnosed with Alzheimer’s and that his uncle also has memory loss and it may be hereditary (see dialog 12 below). These juxtapositions suggest that the relatively few but conspicuous mentions of DNA in connection with Tony, Livia, Uncle Junior and death, dementia and comas are meant to reinforce the core dramatic elements that constitute the “DNA” of the entire series.

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Abstract

In this series, twenty one dialogs that reference genetics from the six seasons of the HBO television series The Sopranos are cited and discussed, in chronological order, from the perspective of a fan who is a geneticist. The context of each citation with respect to the plot and characters will be the main focus of discussion.

- – -

Dialog Three (Season I, Episode 7: Down Neck).

Tony is discussing Anthony Jr.’s behavior and evaluation for A.D.D. with his psychiatrist, Dr. Melfi.

“You Are What You Are”

Tony: “My son is doomed, right?”

Dr. Melfi: “Why do you say that?”

Tony: “Come on- this is the part where I’m supposed to tell you how terrible my father was and the terrible things he did to me. And how he ruined my life. I’ll tell you something, I was proud to be Johnny Soprano’s kid. When he beat the shit out of that guy, I went to the class, I told them how tough my father was.”

Dr. Melfi: “Do you think that’s how your son feels about you?”

Tony: “Yeah, probably. And I’m glad. I’m glad if he’s proud of me. But that’s the bind I’m in. Cause I don’t want him to be like me. He can be anything he wants to be. He can be like this guy I knew in high school. His grandfather invented these
little ties that go on the end of salamis, made millions of dollars sitting on his ass.”

Dr. Melfi: “Have you communicated any of this to your son? “

Tony: “Not in so many words. Probably not at all. What difference would it make, you said so yourself. It’s in the blood. It’s hereditary.”

Dr. Melfi: “Genetic predispositions are only that, predispositions. It’s not a destiny, written in stone. People have choices.”

Tony: “She finally offers an opinion!”

Dr. Melfi: “Well they do. You think that everything that happens is pre-ordained? You don’t think human beings possess free will?”

Tony: “How come I’m not making fuckin’ pots in Peru? You’re born to this shit. You are what you are.”

Dr. Melfi: “Within that, there’s a range of choices. This is America.”

Tony: “Right. America.”

This is the third direct mention of genetics on the show, and it serves to draw attention to the idea that the pathological behavior in the Soprano family is a function of both nature and nurture, but in the context of a number of other ambivalent and complex forces making Tony’s life, and the plot of the show, richly complicated. Anthony Jr. has been evaluated for Attention Deficit Disorder by the school psychologist, who has determined that Anthony Jr. is a borderline case. Tony resents the idea that what seems like normal behavior to him for a 12-year old is treated as a disease.

Tony is also worried that Anthony’s disruptive behavior at school might be a sign that he is destined to follow Tony into a life of crime, which isn’t what it used to be, and which Tony doesn’t want for his son. We see the similarities and differences between Tony’s experience with his father and Anthony’s current situation. Although Tony and Carmela are much less dysfunctional than Tony’s own parents were, Tony recalls how he was proud of his father in spite of his realization that he was a criminal capable of violent behavior. Tony realizes that Anthony Jr. may feel the same way about him once he figures out what he does for a living, but Tony knows that there’s no future in the mafia any more and he doesn’t want Anthony’s difficulties in school and his lack of conventional ambition to lead him, by default, to an interest in Tony’s business.

One would think that Tony’s childhood in the Italian section of Newark where the mafia was endemic to the culture would explain his career choice, while Anthony’s experience as a kid growing up in an affluent New Jersey suburb would guarantee his passage into legitimate society. Tony has, however, generalized an assumption that attention deficit disorder is hereditary to the possibility that Anthony Jr. is “doomed” to gravitate toward the same life of crime because heredity is working against him in spite of his more favorable environment. Besides parental influences, social and cultural influences, the decline of the mafia from its golden era of Tony’s childhood, the possibility of genetic predisposition to criminality emerges as a crack in the image of America as a land of freedom and opportunity where even the children of second generation immigrant mafia dons can aspire to follow the conventional American dream.

- – -

Dialog Four (Season Two, Episode Fourteen: Guy Walks Into A Psychiatrist’s Office).

“Even With Our Genes”

Tony and his sister Janice are sharing a cigarette by the pool just after Janice has returned to New Jersey after many years away from home.

Tony: “You look sensational Janice- not a line.”

Janis: “Two beautiful kids- you must be proud.

Tony: “Yeah, yeah- how about that, huh? Even with our genes.

This fourth reference to genetics on the show continues to develop the “nature-nurture” theme with respect to the pathological behavior of the Soprano family as a function of both nature and nurture. Tony’s therapy sessions with Doctor Melfi have focused largely on stresses related to his work and his relationship with his mother Livia, but his panic attacks imply something physiologically defective as well. The return of Tony’s sister Janice, and her subsequent prominence in the plot and in Tony’s personal life turns the focus of the show even more toward Tony’s family dynamics amidst the plot lines revolving around organized crime.

- – -

Dialog Five (Season Two, Episode Fifteen: Do Not Resuscitate).

“A Report on DNA”

Tony, his wife Carmela, his daughter Meadow and his son AJ are sitting down to a dinner of macaroni and cheese.

Carmela: ” …did everybody take a vow of silence or something- nobody’s got anything to report”?

AJ: “I gotta write a report on DNA for biology.”

Carmela: “Isn’t that interesting! I just saw, on Inside Edition, how there will be no more unknown soldiers because of DNA now. They will be able to identify every single casualty of combat.”

This fifth mention of genetics, by explicitly referencing “DNA”, albeit through AJ’s dim grasp of the subject, injects state of the art genetic science directly into the dialog. This adds a modern touch to the more traditional sense of heredity through familial resemblance, by referring to the molecular level of mechanism underlying the inheritance of biological characteristics that operates in parallel with non-genetic familial inheritance through culture. This explicit reference to DNA puts the old “nature/nurture” dichotomy into a modern context. Tony’s earlier somewhat facetious remark to his sister (“even with our genes”) could be taken to mean simple familial resemblance that doesn’t clearly separate genetics from culture and other environmental factors, since the context and use is somewhat colloquial, and Tony is adept at picking up new language and working it into his conversation in new contexts whether he knows what it means or not. This explicit mention of DNA, however, in a conversation among members of a nuclear family around the dinner table, clearly identifies a hereditary mechanism that is causally independent of all social, cultural and other environmental factors but is also at the core of our individuality, family and humanity.

Carmela’s animated response to AJ’s contribution to the dinnertime conversation, in which she elaborates on the Inside Edition show featuring the use of DNA to ID “unknown soldiers” unwittingly describes a forensic genetic technology that is a real and immediate threat to Tony in his line of work and which applies to Tony and his “soldiers” just as well as the unknown soldiers Carmela is talking about. Whether or not this introduction of forensic genetic technology into the dialog foreshadows future problems for Tony and his crew remains to be seen.

- – -

Dialog Six (Season Two, Episode Fifteen: Do Not Resuscitate).

“A Hundred Million Nucleotides”

The family is sitting down to dinner again.

Carmela: “Tony we’re sitting down!”

AJ: “Ma, DNA- it’s invisible right? But guess how many nucleotides are on each strand?”

Meadow: “Tell her!”

AJ: “A hundred million!”

Carmela: “Wow, that’s amazing.”

This dialog picks up where the previous one left off. Here, AJ almost gives a little “mini-lecture” on genetics. Carmela’s response, however, is more lukewarm this time. We know that AJ doesn’t really understand what he’s talking about. Carmela’s “Wow, that’s amazing” comment after Meadow’s impatient “Tell her!” lacks enthusiasm, and Tony is oblivious to the whole conversation. What’s the point of introducing these two relatively technical pieces of information (DNA is colorless, and each strand has “a hundred million” nucleotides)? One is to reinforce the notion that the previous mention of DNA was not just an ephemeral event in the plot line- here we’re being hit over the head with it.

A second observation is that nobody is very interested in it, except AJ, who is the least capable of understanding its significance. Carmela may have unconsciously recognized that her connection, in the previous conversation, to the use of genetics to ID unknown soldiers is a dangerous threat to Tony and she may not be so eager to encourage further conversation about it, especially given the mood that Tony’s in. Tony is depressed and has more important and immediate problems on his mind. Meadow is annoyed.

As viewers, we’ve been alerted to an additional level of complexity to add to the mix of plot lines, character development, dramatic elements, and possibilities for future directions that may, or may not be followed up or played out, and that make the show so much like “real life”. This may be the point of the additional information presented here. The reference to DNA being “invisible” is interesting because, as far as we’re aware, it is as invisible, but potentially as important as our “mind” or “soul” as an explanation for our behavior. Our DNA does its job shaping our nature and development without any conscious effort on our part.

Whether we think of our genetic heritage in the traditional sense of “family” resemblance, or in the more modern sense of our own personal DNA sequence, we know that much of our individuality and humanity is derived from our hereditary biological makeup. We don’t have to be aware of the billions of nucleotides in each of our cells, or of genes switching on and off as we think, act and react from moment to moment in our lives. We can’t really separate out the role that our genes play, on an individual level, from culture, our individual histories and the moment at hand, and all the other causal factors that define our existence and blend into our unitary sense of self.

This is part of the drama that exists in our own lives that is captured so well by The Sopranos – the complexity of our multiple identities as an individual. We understand Tony through his identity as a mafia don, as a father, a spouse, a psychiatric patient, a friend, as an Italian-American, and on and on and on, and now we can view Tony through his DNA as well.

The relative indifference of the rest of the family to AJ’s enthusiastic update on his technical understanding of DNA may also reflect the fact that unless we’re talking about a cure for cancer, a way to slow down aging or a way to enhance socially desirable qualities in ourselves or our children, most non-scientists aren’t particularly interested in the technical aspects of genetics. They are, however, often fascinated with the mythology of genetics on a personal level, and eager to use “genetics” in the service of rationalization, justification, or personal historical revisionism as an integral part of the “story” that all of us have the privilege of constructing, after the fact, to explain and justify our existence and our behavior. Our current understanding of genetics is sophisticated enough to know that genes are a real and integral part of what we are as a species and as an individual, but it is still incomplete enough so that we can’t explain exactly what we can attribute to our genes versus everything else that defines us as human and as individuals. This is very convenient because we can, like Tony does, pick and choose what we want to take credit for ourselves in our individual lives, versus what we want to blame on our genes or on myriad non-genetic factors whether real or imaginary. Our DNA does not, by itself, determine anything about us with that much precision other than the amino acid composition of the proteins in our bodies.

Why does AJ note, specifically, that there are “a hundred million” nucleotides on each strand of DNA? I suspect that one reason is to convey a sense of the immense complexity and density of genetic information so as to telegraph to the viewer that in spite of the amazing precision and objectivity that DNA fingerprinting may permit when it is used for forensic identification, adding psychiatric behavioral genetic elements to the plot will only make Tony’s character that much more complex and multivariate.

This is very rich material for Tony (and all of us) to work with in the show and in our own lives, respectively, and raises legitimate questions about how much control we really have over our lives and circumstances.

- – -

Dialog Seven (Season Two, Episode Fifteen: Do Not Resuscitate).

“DNA Doesn’t Prevent Comas”

AJ is visiting his grandmother, Livia, in the hospital after overhearing a conversation at home where Janice is trying to talk Tony into authorizing a “Do Not Resuscitate” order for Livia.

AJ: “Gramma- what’s DNR?”

Livia: “Who?”

AJ: “DNR- it’s initials, like, I do this report on DNA, but I heard Dad and Aunt Parvoti talking about your DNR- so is that, like, similar?”

Livia: “Huh? You mean Janice- Janice- they were talking about me?”

AJ: “About your DNR. Cuz that’s what’s confusing- like DNA, everybody’s got that.”

Livia: “She thinks I should have a DNR?”

AJ: “Or that Dad should give it to you or something. Because what if you went into a coma or something? But DNA doesn’t prevent comas, does it? I don’t know- I gotta do this report by Monday.”

AJ’s innocent conversation with Livia about DNA triggers Livia’s realization that Janice wants a DNR (do not resuscitate) order on her medical chart. Livia wastes no time in accusing Janice of plotting against her, talks about Janice’s teenage drug use with her nurse in front of Janice, and even goes so far as to call Carmela as if to begin giving her instructions on what to do “if something should happen” to her. Livia appears to be on the verge of giving Carmela information about money she wants to leave to the children, but Carmela, who is unaware of what’s going on between Janice and Livia, hangs up on her. This juicy plot development is set up nicely by the two earlier dinnertime conversations with AJ about DNA.

A more distant plot connection, that may just be a coincidence, is suggested by AJ’s confused non-sequitur from “DNA” and “DNR” to DNA and comas:

“Because what if you went into a coma or something? Because DNA doesn’t prevent comas, does it”?

Besides moving the plot along nicely with respect to the dynamics between Tony, Livia and Janice, does this reference also foreshadow Tony spending part of Season VI in a coma? Uncle Junior finally succeeds in doing in Season VI what he failed to do in Season II by shooting Tony and putting him in a coma. AJ’s question about DNA and comas could be taken two ways: on the one hand, shared DNA doesn’t prevent Tony’s own relatives from trying to kill him. On the other hand, once Uncle Junior succeeds, through his dementia, in nearly killing Tony, it’s the voices of Tony’s own children that are foremost in Tony’s consciousness when he awakes from his near death experience.

Tony’s emergence from the coma also occurs right after an imaginary conversation in which he tells a hotel bartender that he’s recently been diagnosed with Alzheimer’s and that his uncle also has memory loss and it may be hereditary (see dialog 12 below). These juxtapositions suggest that the relatively few but conspicuous mentions of DNA in connection with Tony, Livia, Uncle Junior and death, dementia and comas are meant to reinforce the core dramatic elements that constitute the “DNA” of the entire series.

World’s favourite drug

Well known for its effects on reducing tiredness and improving alertness, caffeine has emerged in the 21st century as the most popular psychoactive drug in the world. In this day and age, caffeine can be found in a variety of food products including coffee, tea, soft drinks, energy drinks, chocolates and others. Furthermore, since the isolation of caffeine from coffee beans in 1820, the therapeutic use of caffeine both as an additive to other drugs or as a stand alone tablet has gained attractiveness in various pharmacological applications. In North America, the most common source of caffeine comes from drinking coffee beverages. In fact, more than 75% of the population reported drinking coffee on a regular basis and about 50% reported drinking at least 1 cup of coffee a day. Many consumers drink coffee for its invigorating flavour, many others drink coffee for its social benefits; however, most coffee drinkers rely on the caffeine in coffee to wake up in the morning, to get through a tough day at work or to stay awake enough to finish an assignment. The attractiveness of caffeine comes from its strong psychostimulating properties with minimal side effects. As such, caffeine is often regarded as the miracle drug that allows individuals to function beyond their normal physiological and psychological limits. With such a growing popularity, many urban myths regarding caffeine’s beneficial as well as toxic effects arise. This report will discuss the current understanding on the effects of caffeine in the human body.

Staying awake

Natural sleep and wake cycles in humans depend largely on the activation of cell membrane adenosine receptors in the striatum of the brain. Adenosine receptors are ubiquitously distributed in the human body with a variety of functions. The natural ligand for these receptors, adenosine, is a metabolic end product of most cells. Throughout the day, adenosine builds up in the circulation. The build up of adenosine in the brain binds and activates the adenosine receptors, which then causes decreased activity of the neurotransmitter dopamine. Dopamine in the brain has a stimulating effect causing improved cognition, motivation, increased movement and awareness. Therefore, by decreasing dopamine activity, the body falls into a state of fatigue indicating the need to sleep. During sleep, circulating adenosine is metabolised and cleared thereby restoring dopamine activity causing the brain to wake up.

Within 45 minutes following caffeine consumption, it is completely absorbed and distributed throughout the body. Circulating caffeine can readily cross the blood-brain barrier. Due to its structural similarity with adenosine, caffeine in the brain can act as an antagonist such that it binds adenosine receptors but do not activate them. Therefore, binding of caffeine reduces adenosine activity. This increases dopamine activity, which is responsible for most of caffeine’s psychostimulating effects. The clearance of caffeine varies among individuals depending on age, health conditions and current medications. In healthy adults the half-life of caffeine is approximately 3-4 hours. The half-life is much longer in patients with liver diseases, in young children and in women who are pregnant or taking oral contraceptives. Since caffeine blocks the binding of adenosine to its receptors but do not induce adenosine clearance, once the circulating caffeine level drops, the individual will feel fatigue and tired again. In other words, caffeine does not eliminate the need to sleep, but simply temporarily mask the sensation of sleepiness. Furthermore, while functioning on caffeine, the adenosine builds up even more in the brain such that when the caffeine effect wears off, the fatigue felt is much stronger than before caffeine consumption. Basically, caffeine can allow the individual to stay focused for a few hours, but the recovery sleep required is often more than just a few hours.

Adenosine build up in the brain also acts on the blood vessels to induce vasodilatation and increase blood flow, which are necessary for deep sleep stages. Needless to say, caffeine will antagonize these effects too preventing deep sleep stages from occurring. This explains why it is difficult to fall asleep or feel refreshed after sleeping while under the influence of caffeine.

Sobering up

Alcohol, like caffeine, is easily absorbed into the circulation and can pass through the blood-brain barrier with ease. Once in the brain, alcohol acts by increasing the turnover of dopamine thereby acting as a depressant and induces fatigue. Since caffeine is so effective at temporarily restoring alertness and keeping the individual awake, many people believe that drinking coffee after consuming large amounts of alcohol will speed up the sobering process. This is, however, false. Caffeine consumption, as described earlier, can increase dopamine activity. This will counter the alcohol effect and increase the individual’s alertness and awareness. However, alcohol also acts on various other parts of the brain including the cerebellum, which is important in muscle coordination for movement and balance. Caffeine cannot fully restore these detrimental effects. Therefore, drinking coffee after large amounts of alcohol consumption is actually more dangerous because it will give the individual a false sense of soberness. The individual would feel more awake and alert but his/her motor and coordination skills are still impaired.

The hangover experienced the morning after heavy alcohol consumption is due to vasodilatation of blood vessels in the brain as a result of dehydration. Caffeine can help reduce the symptoms of hangovers by again antagonizing adenosine receptors causing vasoconstriction. For this reason, caffeine is often included in many prescriptions and off the counter drugs for treatments of headaches.

Weight watchers

Many commercially available diet pills have caffeine as an active ingredient. Surely caffeine can help increase motivation and activeness, but does caffeine have any direct effect on weight loss? Body weight depends on two factors: food intake and energy expenditure. Behavioural studies have shown reduced food intake after caffeine consumption but the exact mechanism remains unclear. However, contradicting argument exist stating that caffeine stimulates release of the stress hormone cortisol, which is associated with increased appetite. Therefore, the effect of caffeine on appetite remains highly controversial.

Circulating caffeine can stimulate activity in the adrenal gland increasing production and release of epinephrine (adrenalin) and norepinephrine (noradrenalin). These two hormones are the main activators of the sympathetic nervous system to induce a “fight-or-flight” response. On top of increasing heart rate and blood pressure, they also induce breakdown of stored energy into blood glucose. In this manner, caffeine can act to reduce body fat stores to feed the increased energy expenditure. However, these effects only last in the few hours before circulating caffeine is cleared. Repeated use of caffeine would build up tolerance to its effects and has not been shown to be feasible in causing long term weight loss when used alone.

Spermacide

Starting in the mid 1990’s, rumours arise stating that certain soft drinks would cause decrease in sperm count in men as well as other genital defects. These were attributed to the introduction of soft drinks that had caffeine contents higher than the existing brands at the time. Some even believed that caffeine is a spermacide and can act as a contraceptive. Studies have found no correlation between caffeine consumption and these claims. However, a recent study published in 2007 showed that men with substantial daily caffeine consumption (> 3 cups of coffee a day) have significantly increased sperm DNA damage associated with double-stranded DNA breaks. Following successful fertilization, these defective sperm DNA can be converted to chromosomal aberrations and genetic mutations. These will greatly increase the risk for developmental defects in the offspring. Ironically, caffeine has been shown to increase sex drive in female mice. The aphrodisiac effects of caffeine on humans still remain unclear though many believe it to be true. The mechanisms of this action are still being studied.

Miracle tonic or devil’s drink

Caffeine has also been shown in some preliminary studies to reduce risk and alleviate symptoms of Parkinson’s disease and heart diseases. It has been shown to improve short-term memory formation and thereby improve learning. But contradictory results exist as well. Very high doses of caffeine, equivalent of 60 cups a day, have been shown to prevent damage on hair follicles. This prompted cosmetic corporations to develop caffeine-rich ointments for topical application to bolding heads. Caffeine has also documented ergogenic properties to increase muscle work capacity to improve strength, speed and endurance. This has become a valuable marketing tool for caffeinated sports and energy drinks. With all these positive advertisements of caffeine consumptions, it almost seems like caffeine really is a miracle drug with little side effects. However, one must be careful when digesting these types of information. Many of these studies conclude based on preliminary results extrapolated from animal studies and their exact effects on humans are not well documented. Furthermore, in often cases the studies were done with much higher doses of caffeine than a cup of drip coffee. It is true that when taken in moderation, caffeine is relatively harmless with no long-term side effects. However, overuse of caffeine can have many detrimental effects ranging from muscle twitching to peptic ulcers. Extreme high doses of caffeine from ingestion of high quantity caffeine tablets can actually result in instant fatality due to overworking of the body.

Many who drink coffee or consume caffeine tablets are still chasing urban myths hoping to lose a few pounds, improve their memory, build up muscle or grow a head full of hair. Until these effects have been confirmed with more scientific studies, one must not expect coffee drinking to perform such miracles. If anything, love coffee for its flavour, drink it for its social benefits, use it for momentary focus for that is all it can do.

Measures: Earthquake magnitude. This is a logarithmic scale, plotting greatest displacement from 0 on seismometer after event occurs.

Range: 0 to 10+

Reference measurements:

0 – 3.4
This is normal. The first step in assessing earthquake severity is determining whether other people are noticing the Earth move as well. If only you seem to be experiencing the Earth moving, you are likely drunk or having an orgasm or both.

3.5
Not usually felt, but will be recorded. Earthquakes of this magnitude are often the result of office horseplay occurring too close to the seismometer (“Dude – careful!”).

3.6 – 4.5
Caused by yo’ mamma walkin’ by (zing!). You can feel these.

4.6 – 6.0
Here is where we start to get into some real earthshaking stuff – like when Britney Spears shaved her head or that time you saw a squirrel do a back-flip. (Corollary: afterwards, when the lights are still swinging and half the people around you are pale with fear, some luminary will inevitably ask “Did you feel that?”)

6.1-6.9
This level could have serious consequences, depending on when and where it hit. That 50 pound weather vane your Dad put up at his summer cottage will likely topple as will your crappy apartment building. But you’ll be studying down in some dank library somewhere, which means you’ll likely be booked to death when the stacks fall onto you.

7.0 – 7.9
Catastrophic. You should, if possible, consider being somewhere else. City swallowing cracks in the Earth’s crust are likely to appear. This is where people like Anne Coulter come from.

>8.0
Repent sins, commit big sin you’ve been putting off, or both (time permitting). Concrete will be like J-E-L-L-O. Try force-feeding your shoe to anyone yelling about “the Rapture” before everything goes black.

History:

Developed in 1935 by Charles Richter (no relation to former New York Rangers goaltender Mike) and Beno Gutenberg (no relation to “star” of Police Academy films Steve). The Richter scale represents yet another log scale that will inevitably bewilder the public (“Logarithmic? Isn’t that where someone uses a stump as a bass drum?”). Note: earthquakes only occurs in regions where people have angered God (unconfirmed).

Related quote:

“AAAAAAAHHHH!” (Richter, the guy in Total Recall who had his arms ripped off.)

Use of “Richter” in a sentence:

“Richter? Damn near killed her!”

all was good in my baton rouge apartment. my backback had been loaded with all of the necessary books required for a night full of studying molecular cell biology. a feeling of virtue coarsed through my blackened veins. as i slung my bag ’round my shoulders and locked up the apt, i felt a severe burning sensation on my forearm. i looked at it and saw nothing, gave it the ole scratch n go, and went to my car. as i was driving, the sensation became a white hot shot of pain…i looked at it again, and it had ballooned into a full-fledged allergic reaction. i of course began to freak, knowing that i had not noticed anything i came into direct contact with–and thought that i would most definitely be the next victim of the flesh eating bacteria. then i saw him…clad in his finest armor…a big, heinous caterpillar on my backpack….this was war. the whole ride to my friend’s place, i contemplated how i would end his pathetic life. i mean, how dare he fuck with me…does he know who i am? i can beat any third grader in the nation in a spelling contest—you dont just cheap shot someone like that. i arrived to my destination and his fate was nearing…but in a sudden flash of compassion, i just flicked him onto the grass…now here is the moral of the story….if the end of the world comes down to man versus caterpillar, i believe we will be the less barbaric of the two, for they are a cruel race, and i don the scars from their senseless brutality.

In reference to this

For once and for all, the argument is NOT about the toilet “seat” being left up or down, it’s the “lid” of the toilet that the argument is all about!!!!

In 1975, Charles Gerba published a scientific article describing the phenomenon of bacterial and viral aerosols due to toilet flushing. It states, every time a toilet is flushed, an aerosol plume of contaminated water droplets is ejected into the air and lands on everything in the bathroom, including you, your toilet paper, clean towels & toothbrush! During the study, gauze pads were placed around the experimental bathroom and close-up photos of the germy ejecta taken that looked like “Baghdad at night during an air attack.” The study showed that significant quantities of contaminated bacteria & virus filled microbes of urine and fecal matter floated around the bathroom and for at least “two hours” after each flush.

So guys, pleeeease, just CLOSE THE LID!

Linda

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It’s an interesting paper but I think it clearly disregards the second toilet seat found on the majority of household toilets. I believe that instead of the one toilet seat down norm that for the non-cooperative instance both seats should be left down. I don’t have the math background to provide you with the proper gaming analysis. It seems to me that it provides an equal opportunity for lifting the seats to both parties involved. I think lifting two seats is an easy a task as lifting one. So in every instance of use a seat is lifted. It also gives both parties the opportunity to chastise the other in the case of the seats not being returned to the down position as opposed to just the male party getting chastised.

Bob

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This analysis focuses entirely on the costs of moving the seat from one position to another, and thus is seriously flawed. It leaves out other important costs and risks related to leaving the *lid*, as opposed to the seat up. And of course, if one must raise the lid, the marginal cost of additionally raising the seat also is very small.

Since males, despite all their mothers’ training, seem unable to imagine the risks of leaving the lid up, here are a few:

1) The household five-year-old drops any number of items into the toilet

2) The household five-year-old drops any number of items into the toilet and flushes it

3) The household adults drop an item into the toilet.
- From sad experience, this could be a valuable piece of jewelry
- It could be something large enough to plug up the toilet.
- It could be something small enough to pass through the toilet drain, but block up the small spot where the main sewer line has collapsed but time and distance from the drains has heretofore allowed drainage.

4) Research has shown that the aerosol created by flushing contains a large number of viruses and bacteria. Closing the lid before flushing largely blocks this aerosol. See here and, for a lighter view, see here.

It is entirely possible that the inclusions of these additional costs would show that leaving the seat and lid down increase social welfare, decrease total cost of operation, or both. Unfortunately, these costs depend on probability of occurrence and would require actual data on the risks rather than pure logic.

Lisa

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Another important consideration in whether to keep a toilet seat up or down is whether or not you have pets who might suffer negative consequences if the seat is left up. In my case I have parrots who can fly into the water and drown, and a dog who could drink the water and become ill if there are residual chemicals from cleaning or if the water is of poor quality. For me it’s easy – the toilet seat stays down…..

SB

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I had a male acquaintance who saw no problem in urinating from the standing position while the seat was down. When queried, he expressed no hesitation to sit on a toilet seat he had sprinkled. There’s always some freak to ruin the game.

Sincerely,

Ken

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The article on toilet seat norms and the calculated “cost” on both genders of leaving them in various states (Hammad Siddiqi) was entertaining and very insightful. Being male myself, I particularly appreciated that scolding was taken into account. However, the article makes no mention of the third party of opinion. No, not alternative orientation or gender, but the cross-section of both males and females that simply don’t care one way or the other for such nonsense and don’t understand or perpetuate this quirky social feud. There are two schools of reason within this third demographic.

The first says that it shouldn’t matter what position the fudpucking seat is left in. It’s just a seat. We’re humans, really really smart primates, relatively speaking. We build bridges, blast holes through mountains, alter coastlines, and have yet to find anything that we aren’t willing to invest time and effort to stick our collective noses in. The majority of our entertainment culture consists of ways to waste time and run around, and the industry behind the curtain busts its ass to ensure that we continue just that. Since when are we such pansies that we can’t take the fraction of a second to flip a toilet seat? Also, injury, old age, and odd scenarios aside, who lacks the foresight to get to the bathroom in their own home with sufficient time to prevent accidents? Has a seat flip ever been so critical a time factor that it was the straw that broke fortune’s back for you or anyone you know?

This policy of “who gives a shit” embraces anarchy for its tendency to diminish expectations and assumptions, that is, where those expectations may easily segue to disappointment or frustration. If you’re entering a situation with no worries, that’s what you’ll get. This means: 1, take no offense from any configuration you find; it’s all chance. 2, make no offense by intentionally leaving a configuration other than you normally would, not that it would make any difference anyway because nobody would take it as such (see 1).

Following these, one would approach, reconfigure if needed, perform their function, and leave it in whichever position. This seems to me to be the best way to reduce the number of times the seat itself is changed, for those who care about durability, and is also the easiest on both genders. The most number of steps either would incur is one, “reconfigure if needed”.

The second school is a more sanitary extension of the first, requiring the addition of a step. If it doesn’t matter what position the seat is in before use, then perhaps nobody will mind if a default of “closed” is adopted. When not in active use, close the toilet, both seat and lid. That’s why it has one! That so few seem to use lids as designed is probably the biggest oversight of the whole debate.

The “closed default” policy is utilitarian, with sanitation, safety, and common sense above momentary inconvenience. Either gender has exactly two steps added: Open to use, close when done. Whether you’re lifting the whole seat or just the lid, it’s just one motion, and certainly the most even result. Lids keep things out that should be. Pets and children come to mind. “European” flushers (if it’s yellow, let it mellow) probably don’t like to leave their savings in plain view. If you are one though, and you do, please stop. And the next time you have to fish a set of keys or your contacts out of the bowl, or you slip on wet tile and inadvertently shove your arm into it while trying to break the fall, consider this policy.

Enjoi!

Matt

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There is another cost of keeping the toilet seat down, which has not been well considered by the author. The issue occurs if John is older, with mild benign prostatic disease or other condition that forces him to go to the bathroom for #1 during the night. Experience shows that in this case the light in the bedroom and bathroom is usually off and John is unwilling to open the light and create a situation in which it is more difficult to get back to sleep afterwards. Indeed, he may be performing the whole operation with his eyes closed or at least partially closed. He then gets into the bathroom and knows by experience where the toilet is and can in general locate himself reasonably close, perhaps by the touch of the toilet on his legs, but it is dark, he does not want to put on the light and he has no idea whether the seat is up or down. In fact, by now, he is in urgent need of performing #1, and likely doesn’t care. If the toilet seat is up and his aim is reasonable then no problem. But if the toilet seat is down and his aim is only in the general direction, then there is a strong likelihood that this will result in #1 on the toilet seat. This can create even more yelling by Marsha when she comes to use the toilet and finds the seat down, but with #1 on it. So this adds a complexity to the problem and my totally intuitive analysis is that it is better to keep the toilet seat up and endure moderate yelling than keep the toilet seat down and endure significant yelling.

Morry

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I noted a possibly large omission in the above paper. As a result of leaving the toilet seat in the open position, the protective cover of the toilet cannot be closed. This leaves both parties open to the disastrous possibility of knocking toiletry items into the toilet. One possible outcome is documented in Seinfeld Episode 150, The Pothole. This open hazard creates a dangerous environment in the bathroom, and is the very reason I champion the lowering of all protective covers on the toilet bowl at all possible times.

I expect this would alter your calculation significantly.

See also http://www.stanthecaddy.com/seinfeld-episode-guide/ for more information.

Best,

Jeremy

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Thanks for an interesting economic analysis, but I can only assume the article had no input from women because it misses the most important cost.

That is, from a female user’s perspective, if the toilet seat is unpredictably in the up position, there is a small but real chance that she will not notice and will simply sit, assuming that the seat is down – with catastrophic results including a cold, wet bottom and the need for a shower. Call this chance “F” in honor of the profanities it usually inspires. Chance “F” is likely to be higher if the female user has been habituated to a single use toilet – for, when she is the only one using it, she can assume that the seat is always down, and doesn’t need to pay attention. Chance “F” is also higher in the middle of the night, when the female user is likely to a) be groggy b) not bother to turn the light on. When chance “F” happens in the middle of the night to a groggy female user, the catastrophic results are even more catastrophic.

Therefore, in the example given in the article, it is not accurate to measure Marsha’s costs under strategy J by px1/2xC. There is an additional cost – the catastrophic chance “F” with cost C(F).

Therefore, Marsha’s costs would be: px(1-F)x1/2xC + pxFx1/2xC(F).

Female consensus is that C(F) is so high compared to C as to be almost infinite for practical purposes, therefore the optimal toilet use strategy is obvious from either a utilitarian or a game-theoretic perspective: “Just put the bloody seat down!”

Zoe

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