On the beautiful mind
The mind can be thought of as the subjective experience of our stream of consciousness. What happens when our mind tells us that we can see and hear things that aren’t there? What happens when we start to lose touch with reality? This is psychosis and one of the most debilitating psychotic disorders is schizophrenia. The film “A Beautiful Mind” offers us a glimpse of the devastating effects of schizophrenia and how a remarkable man rose to overcome it, eventually triumphant as he accepts a Nobel Prize.
It is the late 1940s, and John Forbes Nash, Jr (played by Russell Crowe), having won the prestigious Carnegie Prize for Mathematics, had just arrived at Princeton University as a graduate student. From the start, it appears that the introverted Nash is not a people person and is excruciatingly awkward with the opposite sex. Nevertheless, he confides in his newfound roommate Charles Herman.
Nash is not content with the mundane part of university life – classes, preferring to devote his time and energy into the completion of his thesis, which he hopes will be a masterpiece. He then finds the inspiration for his novel idea in a bar – as his friends fight over how to tackle a particular blonde. He calls his idea “governing dynamics” and it is now known as the Nash Equillibrium in his honour. Wikipedia summarizes this theory in a succinct manner:
Stated simply, Amy and Bill are in Nash equilibrium if Amy is making the best decision she can, taking into account Bill’s decision, and Bill is making the best decision he can, taking into account Amy’s decision.
With his graduate studies complete, Nash accepts a job at the Massachusetts Institute of Technology. However, he is preoccupied with cracking numbers that he sees in newspapers and magazines in his office, causing him to neglect his teaching responsibilities. Despite this, he was able to fall in love with and eventually marry his student Alicia Larde (played by Jennifer Connelly).
He then believes that he was recruited by the Department of Defense in the Pentagon to decipher Soviet communication codes which are placed in the mass media. There, he encounters a shady man in a top hat, William Parcher who is later revealed to be a Pentagon official. Nash accepts his covert assignment and receives an implant in his forearm from the Department of Defense which allegedly functions as a listening device. Nash becomes increasingly fearful, especially after he believes he was chased by Russian operatives. His paranoid behaviour (turning off the lights, suspicion of people outside his house) alarms his wife. On his return to Princeton, he sees Charles Herman and his niece Marcee who is a young girl. As Nash is about to deliver a lecture, he is brought involuntarily into a psychiatric hospital.
It is then revealed that Nash had been living alone all the while at Princeton. His roommate Charles, his niece and even William Parcher were all hallucinations. Nash even tries to dig out the implant in his forearm with his bare hands, but fails as no such device was planted in the first place. His covert assignment about thwarting Soviet communications was only an elaborate delusion.
Nash is then subjected to a series of insulin shock therapies (which are no longer used today) and started on antipsychotics. His symptoms seem to subside and he is subsequently discharged, but nevertheless, problems soon arise at home. As a result of his antipsychotics, Nash feels his mind has become slow and he struggles with his calculations. He also loses his libido which strains his relationship with his wife. Nash decides to stop taking his pills, hoarding them in a desk drawer instead. Predictably, his paranoid symptoms and hallucinations return.
Nash’s relapse is finally realized by his wife when she noticed he had almost drowned their infant son. He then sees and hears William Parcher instructing him to kill her. She calls for his psychiatrist, but ultimately decides to live with his condition. Nash begins to gain insight that his hallucinations, especially the young Marcee, “never seem to get old”. He then starts to ignore his hallucinations even though they continued to haunt him.
In his later years, it appears that Nash is taking the “newer antipsychotics”. He accepts a teaching position back in Princeton, and in 1994 wins the Nobel Prize in Economics for his in “governing dynamics”, also known as game theory.
So, how accurate is the portrayal of schizophrenia in this film? As far as psychiatry is concerned, the film depicts Nash as having hallucinations (perceiving something through your 5 senses when there is nothing there) that are concurrently auditory and visual. These are actually rare, and the real Nash only heard voices (auditory hallucinations are the most common type of hallucination in schizophrenia). He starts to have persecutory delusions (that the Soviet are out to get him) and delusions of reference (believing that there are special codes in the newspapers that only he can decipher). His behaviour becomes erratic and he withdraws socially. The hallucinations and delusions also affect his work and relationship with his wife.
As mentioned earlier, insulin shock therapy is no longer used today. It was once used to treat schizophrenia, by method of injecting large amounts of insulin to induce coma and seizures. This was phased out by the developlment of antipsychotics and electroconvulsive therapy. Typical antipsychotics such as Haloperidol are effective in treating the hallucinations and delusions of schizophrenia but do cause the cognitive impairment and sexual dysfunction depicted in the film. More commonly, they cause extrapyramidal side effects which are problems with muscle tone and coordination. Newer “atypical” antipsychotics are also used today and they have less extrapyramidal and cognitive side effects but can cause weight gain and lead to metabolic syndrome.
In real life, it appears that Nash never took the supposed “newer antipsychotics”, it was added because the screenwriters were worried that it could send the wrong message to the public on the medication compliance. In the past, schizophrenia was traditionally seen as a chronic deteriorating illness (Emil Kraepelin), but this view is now changing. It is now believed that up to 20% of schizophrenics who suffer from acute episodes recover completely. A further 20% have recurrent acute episodes and 40% have a chronic illness. With the advance of biopsychiatry, the prognosis of schizophrenia has improved. Furthermore, Nash most probably suffered from the paranoid schizophrenia subtype, with its relative absence of catatonic and negative symptoms. This is the subtype of schizophrenia with the best prognosis.
Finally, the impact of schizophrenia on the family is dramatically shown in the character of Alice Larde, Nash’s wife who has to live with the paranoia and abnormal behaviour of a schizophrenic. Although in the film she was portrayed as a supporting wife, the real Alicia Larde divorced Nash, only to remarry him when he won his Nobel Prize in 1994. That’s why supportive psychoeducation on schizophrenia and mental illness is crucial for the recovery of patients. Without good social support, schizophrenics are less likely to be compliant and more likely to relapse.
Mental illness is still seen as stigma in society which paralyzes its sufferers. I think that the film “A Beautiful Mind” is a rare film that is both powerful, inspirational and has great value in educating the public on mental illnesses such as schizophrenia in order to erode this stigma.
Reflections on the 8th Inter-Medical Physiology Quiz 2010
At the end of September, I was fortunate enough to be chosen to participate in the 8th Inter-Medical Physiology Quiz this year at Balai Ungku Aziz, University Malaya. A record 41 teams made the trip this year from a diverse group of countries including Sri Lanka, Japan, China, Australia and Romania. The written quiz was absolutely gruelling – a high level of understanding of physiology concepts was needed. Subsequently we were ranked according to the results from the written test.
Quiz day was a test of wits and nerves. The organizers decided to be autonomically sympathetic by making each participant stand to deliver an answer – much like a spelling bee. No discussion between team members was allowed, and penalties were given for incorrect “steals” by the opposing teams. Aggressive teams risked penalties for a higher reward while defensive teams could progress by watching aggressive teams self-destruct. This year, University Malaya clinched the Prof A. Raman Challenge Trophy, defeating a resurgent team from the University of Colombo, Sri Lanka.
The organizing team did a good job as well – they spent a lot on freebies and our accommodation at the rusty Wisma Belia was surprisingly cozy. I was proud that our team reached the quarterfinals of the competition and we exceeded expectations by topping the group during the first round. I hoped that I managed to improve my grasp of physiology despite the limited amount of time spent on the subject in my pre-clinical years.
Combating Medical Ignorance One Comic Strip At A Time
I’ve been away because I just finished my (gruelling) paediatric posting exams – paediatricians are generally very nice people, the kids are adorable but somehow paediatric exams can be nasty and it can all go downhill before you know it.
Back on topic – despite the fact that patients today are more educated than ever before on their illnesses, medical ignorance has become a serious problem. Parents stop vaccinating their children on unfounded fears of autism. A woman with treatable, early stage breast cancer delays surgery to try out an herbal remedy that her friend had tried. It is peculiar that human beings are so rigid in thought that they “believe what they want to believe” in the face of overwhelming solid evidence. Anecdotal stories from trusted friends are sensationalized by the media, and this steers public opinion away from scientific proof. The effects of medical ignorance can be deadly. Measles and mumps are making a comeback wherever vaccination rates drop, and people who delay treatment of initially treatable diseases inevitably return when it is too late.
I found this incredible series of comic strips by British artist Darryl Cunningham to be most useful in clear public ignorance on scientifically unproven medical myths such as the MMR-Autism debacle. Recently it has been updated with a new comic strip on homeopathy and I have to say I’ve become a fan of his work.
It’s well worth reading the rest of Homeopathy at his website. I’d also like to point you to his first strip on the Vaccine-Autism myth called the Facts In The Case of Dr. Andrew Wakefield. If you’re interested in more, the author also has a graphic novel, Psychiatric Tales, which features his experience in an acute psychiatric ward, mental illness, and ultimately his own struggle with anxiety and depression while training as a psychiatric nurse. Here’s a sample:
Copy Number Variations and Autism
Autism is a life-long neurodevelopmental disability that is characterized by a triad of symptoms;
(i) impairments in social interactions,
(ii) impairments in communication and
(iii) restricted interests and repetitive behaviour.
These symptoms appear before the age of three and it affects boys more than girls (4.3:1). The rapid rise of autism cases being reported over the last decade is as mystifying as the cause of autism itself (claims of a vaccine link have now been firmly debunked).
The impaired social interactions of autistic people stems from an inability to read social cues. Thus they may appear distant, preferring to be left alone or exhibiting social awkwardness in making and maintaining relationships with other people. These social deficits are present from an early age. In autistic toddlers, there is a lack of eye contact. In addition, they smile less and have difficulty with social gestures. Children with autism fail to develop peer relationships that are appropriate with their developmental level.
In autism, there is a delay or total lack of the development of spoken language. Moreover, in those that have adequate verbal ability, they have difficulty beginning or sustaining a conversation with other people. There may also find it hard to understand metaphors and figures of speech, as they tend to interpret language literally. As children, autistic people show a lack of imaginative or make-believe play that is present in their peers. They are less likely to ask for something or share their experiences and are more likely to repeat others’ words (echolalia) and reverse pronouns (referring to themselves as “he”, “she”, “you”)
Besides that, autistic individuals display a variety of repetitive or restrictive behaviour. Characteristic and apparently purposeless movements such as hand flapping, head rolling or body rocking are common. Individuals with autism also have a ritualistic behaviour where they perform daily activities the same way each time. They have difficulty tolerating changes in routines and/or the environment (such as moving furniture). Another diagnostic criterion is an intense preoccupation with a narrow and restricted area of interest, for example in maps, trains or dinosaurs. Often, the autistic individual accumulates a vast amount of information on this particular interest.
It has long been known that autism has a genetic component. But previous studies only accounted for a fraction of the genetic causes of autism. Recently, copy number variations were reported in Nature to be 20% more common in children with autism. What are copy number variations? We are perhaps most familiar with the idea that chromosomes come in pairs, and hence we have 2 copies of a any particular gene, neatly tucked in each chromosome. We are familiar with the idea that mutation happens when a base in the gene itself is not copied correctly, causing an error. However, since the human genome project was completed in 2006, researches have found that there is more to our genetic makeup.
Copy number variation
Let’s say there’s an imaginary chromosome A and it has a pair, chromosome B. On the long arm of both chromosomes A and B lies a copy of a gene, which we shall call K. Sometimes during cell reproduction, part of the long arm of chromosome A gets accidentally duplicated. The result is that chromosome A contains 2 copies of gene K , and adding this up with the copy of gene K on the matching chromosome B, we get a total of 3 copies. This is called copy number variation – quite simply it is the variability in the number of copies for a gene. To illustrate this point further, the amylase gene is present in European Americans in a range from 2-15 copies. The more copies of the amylase gene, the faster the person can break down starch. Copy number variations account for each individual’s uniqueness and they are actually quite common in the human genome.
According to the Nature article, these copy number variations could be inherited from parents. Strikingly however, these events also happened de novo. This means the mutation are not found in the parents, but arose spontaneously in the child’s DNA. This can happen when errors occur in the formation of the parental gametes, which are then copied into the child’s DNA. The unique genetic disruptions found in the children studied increased their genetic susceptibility to autism. Hundreds of both inherited and de novo copy number variations have been found in the DNA of the autistic children studied. Hence, autism is better thought of as a group of diseases rather than a single entity – which poses more questions rather than answers.
How Endogenous Retroviruses Predict Evolution by Common Descent
I highly recommend the Facts of Evolution Series on Youtube. In this latest installment, the author talks about retroviruses. These are viruses that reverse transcribe RNA into DNA (which is the opposite of what most organisms do). Examples of such retroviruses are the HTLV-1 virus which causes leukemia and the HIV virus which causes AIDS. However, some retroviruses can insert their DNA into host germ cells where they are inherited by descendants of the host. These are called endogenous retroviruses (ERV), and they persist in the genome of the species that becomes infected.
Under the idea of common descent, we can predict the evolutionary relationships of different species by comparing their genomes and identifying ERVs. If the ancestor of humans have acquired ERV1 after the split from other apes, we can expect to find ERV1 in the genome of all humans but not in the genome of any other ape. With the advance of genetics, scientists are comparing ERVs between species and so far everything has added up, thus providing another strong evidence for evolution.
Interestingly, where mammals except monotremes are concerned, ERVs are known for role in allowing pregnancy to occur. During pregnancy, some ERVs are turned on and they cause an immunosuppressive effect to protect the embryo from the maternal immune system. It is thought that at some point a retrovirus infected an early mammalian ancestor, and this enabled the evolution of vivaparity as the fetus became more resistant to the mother’s immune system. They also play a role in the formation of the placental syncytium, via viral fusion proteins. An example of a viral fusion protein in retroviruses we see today is gp41 seen in HIV.
The Fish Tank Ward Round
Today I followed the ward round by the head of the paediatrics department at the hospital I’m currently attached to. The one thing that made my day was the fact that, in transit from one room to another, in the middle of the ward round, we stopped. In front of us stood a mighty fish tank, teeming with several species of fish that were oblivious to there whereabouts (right in the middle of a busy paediatrics ward). The head of the department eagerly inquired about the status of the fish. And a bright houseman, seemingly prepared, gleefully presented that the fish seemed to be in good health.
Minute details were not overlooked, such as the fact that fish pellets that were too small rapidly sank to the bottom of the tank, thus fattening the filter fish (DBKK) , while leaving the mid-tank dwellers malnourished. They even took note of a stray filter feeder that seemed a little too eager to spend it’s time near the air-water boundary of the tank. It’s reassuring to know that at times, doctor’s can just pause and not focus on medicine all the time, despite the constant demands of the profession. In fact, being consumed by medicine is one of my fears as I know I am an intense person by nature. To be able to look beyond the menial tasks, to be able pursue interests outside of the hospital – is paramount for the survival of our individuality.
Should Medical Students Study Evolution?
It was Russian Orthodox Christian and evolutionary biologist Theodosius Dobzhansky who famously said in 1973 that “Nothing in biology makes sense except in the light of evolution”. Today, evolution is undeniably the keystone of almost every biological science. It is therefore shocking to know that one vital field seems to have been left behind. Where in the science of medicine is evolution?
To those uninitiated with evolution, the human body is often regarded as a perfect creation. Why then, do we get sick? Why for example, do we get heart attacks? When I read about a disease in a medical textbook I expect to find the following:
1. The signs and symptoms of the disease
2. The etiology or pathophysiology of the disease
3. Diagnostic criteria
4. Management
Hence, medical science tells us how heart attacks happen and which kinds of people are most at risk. But does medicine tell us why human beings get heart attacks at all? How can it be that this most basic of questions goes not only unanswered by medicine, but largely ignored?
In 1994, “Why We Get Sick”, a groundbreaking book by Randolph Nesse and George C. Williams ushered in public awareness of evolutionary medicine. To put it simply, it is the application of the principles of evolutionary theory to understand health and disease.
We are already familiar with the concept of antibiotic resistance but current medical education seems to downplay the role of evolution by scarcely mentioning it. Humans and pathogens engage in an evolutionary arms race that can be succinctly explained with a quote from Lewis Carrol’s novel “Through the Looking Glass”. In it the Red Queen says:
“It takes all the running you can do, to keep in the same place”
Hence humans and pathogens are waging an arms race, with each side making small improvements via natural selection in order to maintain its biological fitness. This is known as the “Red Queen hypothesis“. The question posed by the book is this : Could human conditions and sickness be explained by evolutionary principles?
Firstly, human beings are susceptible to some kinds of diseases via our genetic makeup. You may ask why would a defective gene that causes a disease such as sickle cell anemia continue to persist? Shouldn’t natural selection have eliminated it? Unfortunately this isn’t the case because genes don’t care about how happy or healthy we are, it has no purpose but to make sure it gets transmitted to the next generation. Anything that increases the chance of a gene being passed on will be present in future generations. Scientists have discovered that although homozygotes with both copies of the defective sickle cell gene develop sickle cell anemia, heterozygotes with one copy of the defective gene have an increased resilience to malaria.
Sometimes a gene that causes disease has no disadvantage in reproductive output, some have hidden advantages while others still are quirks that only present with disease in a novel environment. Why does a deadly neurodegenerative disease such as Huntington’s disease occur? Because it typically has a late onset in life, whether a person has Huntington’s doesn’t affect how many children he or she will have, and the gene that causes Huntington’s will continue to propagate for generations.
It is also important to understand the environment in which humans evolved in the first place – the African savannah. Imagine now the environment we live in today. We sit on our butts most of the day and load ourselves with a diet rich in “nutrients” that use to be much rarer : salt, sugar and fat. Could it be that “modern” diseases such as lower back pain and heart attacks are actually a result of our bodies having not enough time to evolve and adapt to a new and novel environment?
The budding field of Darwinian medicine can have huge consequences on how we understand disease and how patients are treated. Yet evolution is curiously absent from the medical curriculum. What do we do with the evolutionary hypotheses proposed on disease? We need them to be scientifically tested and thus more research needs to be done in a field that could revolutionize medicine as we know it. Only then can we make sense of why we get sick.
I highly recommend Nesse and Williams’ “Why We Get Sick : The New Science of Darwinian Medicine”, although it is a little old.
http://www.amazon.com/Why-We-Get-Sick-Darwinian/dp/0679746749
Web Resources on evolutionary medicine
1. http://www-personal.umich.edu/~nesse/ – Randolph Nesse’s website
2. http://en.wikipedia.org/wiki/Evolutionary_medicine
Auto-appendectomy
“It seems that I have appendicitis. I am keeping quiet about it, even smiling.” – Leonid Rogozov, Russian surgeon
This is an amazing story I found on Digg where a doctor performed an appendectomy on HIMSELF in the Antartic in 1961.
Leokl
The Philosophical Platypus 