Phenomenon, and other brain phenomena
The question I would like to pose to you this week is, can a neurologic disease enhance the function of the nervous system? I came across this idea while re-watching the 1996 film, Phenomenon, starring John Travolta, Kyra Sedgwick, Forest Whitaker and Robert Duvall. The movie was about a simple guy in small town USA, who is transformed by…this phenomenon. Overnight, he becomes hyperintelligent, learning conversational Portuguese during a 25-minute car ride, developing new solar technology, inventing a fertilizer-based fuel product, and just for funsies, cracking US military codes. He develops extrasensory perceptions such as the ability to feel ultralow frequency tremors in the earth that predict an earthquake is coming, he could sense where an extremely sick boy was hiding in an orchard, he even develops telekinesis. At the end of the movie, the viewer learns that all of Travolta’s talents and abilities are the consequence of a malignant brain tumor called an astrocytoma. But is Travolta’s medical condition based in science, or is it more science fiction?
As a medical student, I came across this book, Survival of the Sickest, by Sharon Moalem. Anyway, this book is about genetic mutations and infectious organisms that have survived over generations and generations because they provide us with some sort of survival advantage. In some unanticipated way, they enhance the function of an organ system, or of the organism’s body. And this isn’t just true of humans, it’s also observed in a number of other species.
Let’s take a certain breed of wood frogs for example. In the winter, these small guys are at risk of freezing to death. But scientists have observed that hyperglycemia in these frogs is actually a protective mechanism. First, hyperglycemia is associated with dehydration. As you have seen in patients with diabetes, they urinate a lot. The high serum glucose eventually enters their urine, creating an osmotic gradient that draws out more water, which dehydrates the body. This means less available water in tissues relative to the concentration of other solutes, such as glucose. Some experts believe the same process explains why diabetes has also evolved in humans. It facilitates survival in colder climates. And sure, after 20 or 30 years of untreated diabetes, you get kidney problems, heart problems, and you’re at risk of strokes, but when the average life expectancy of early humanoids was just a few decades, this long-term risk was vastly outweighed by the early survival advantage of hyperglycemia in colder climates.
Let’s move on to a more human-specific example. Many of you probably know why sickle cell anemia has persisted throughout human generations as a fairly common disease, especially among many African peoples. It’s because sickle cell anemia reduces your risk of acquiring malaria—an extremely common mosquito-born parasite endemic to many African countries. This is a classic teaching example of survival advantage in medical textbooks. But what you may not know is why would a disorder like hereditary hemochromatosis, a disorder characterized by abnormal iron metabolism, thrives among Northern European peoples. An autosomal recessive condition with a high expressivity, hereditary hemochromatosis increases your risk of developing liver failure, liver cancer, diabetes, heart failure, and other complications that begin to manifest in early adulthood. So how have we not selected out patients with this disease who may be symptomatic by the time they reach a reproductive age? Well, as it turns out, hemochromatosis not only increases organ deposition of iron, but it sequesters iron from certain cells—notably macrophages. In certain populations, like those of Northern Europe where tuberculosis is common, TB is more of a threat to life than genetic disorders which may kill you over a matter of decades. In patients who have the gene mutation for hemochromatosis, whose macrophages are starved of iron, mycobacterial species grow much more slowly and proliferate less rapidly. This at least partially explains why the prevalence of hereditary hemochromatosis is greater among Europeans, because it likely has contributed to increased survival in a population at high risk of acquiring TB.
But neither of these are neurologically-enhancing conditions. Is there a disease out there which fits that description? Turns out, this is a really tough question to answer, and it’s more difficult than you’d think to just brainstorm diseases. So I approached the question in a couple of ways.
First. I tried to imagine something that at its biological basis would be helpful to the person. Like being able to see at a far distance, so you can spot that lion in the savanna. But hyperopia and related neuro-ophthalmic conditions aren’t great examples for how a condition may improve the physiologic function of the brain. What about an enhanced fight or flight response, something where you have a hypervigilant sympathetic nervous system that keeps you at constant attention? A pheochromocytoma may possibly explain this, but it’s also not the best example since people also experience a lot of fatigue, rather than a continued state of alertness. After a few more examples, I really couldn’t find a good solution where a disease enhances a normal, favorable physiologic response.
So I reasoned it out a second way, kind of opposite to the first. Instead of thinking about a condition that enhances a normal, favorable biological function, what conditions are associated with an impairment in normal but unfavorable biological function? Take pain for example. Sure, it’s evolutionarily helpful because it informs us to steer clear of sharp objects and avoid being bitten by rattlesnakes. But even a moron knows to keep away from these things. So why have pain if you can just develop common sense? A congenital insensitivity to pain may be an elegant solution to this, and people who have this condition often have a mutation in a particular gene of sodium channels expressed in the dorsal root ganglia—particularly in pain-sensing neurons—called the SCN9A gene. The most common variant of this class of diseases is HSAN 1, or hereditary sensory and autonomic neuropathy, which is an autosomal dominant condition. This is different from the ludicrous example of the James Bond villain from The World is Not Enough who cannot feel pain because a bullet is lodged in his thalamus. Patients with SCN9A mutations really cannot feel pain, with less impairment in the ability to perceive pressure, vibration, and position—but still, these nerves are not perfectly functional. And often patients with this class of disorders present early with recurrent painless bone fractures, ulcerations of the skin at the extremities, and severe joint injuries that only worsen over time. It turns out, we do really need our ability to sense pain.
So that approach didn’t work out to well. Next, I tried to imagine what conditions out there exist where a person would have an exceptional talent? What kind of patient has a unique ability? Thinking about this was a little easier, and two examples immediately came to mind: The savant syndrome and hyperthymesia.
The savant syndrome is a neurologic condition characterized by overall mental disability with what is described as an “island of genius.” Think of Dustin Hoffman in Rain Man. In that 1988 film, Dustin Hoffman’s character, Raymond Babbitt, has an encyclopedic knowledge of all things music, literature, sports, zip codes, calendar dates, and so on. While this is a fictional example, it is based in part on prior reports of genius children who suffer from autism. It’s thought that savants are quite common, with an incidence of 1 in 10 to 1 in 100 patients with autism. Almost always, these people have an incomparable expertise in mathematics or memory, but their social skills and capacity for functioning independently are often sorely lacking. While having a powerful cognitive ability may make somebody more useful in a group environment, there does not seem to be an obvious evolutionary advantage given the discounted skills in other critical domains responsible for survival.
Hyperthymesia is the second example I’m thinking of. The other term for hyperthymesia is highly superior autobiographical memory, or HSAM. These patients remember everything that has happened to them. They can recall names, dates, events, and word-for-word conversations they’ve had, from years and years ago. There have only been a few dozen of these cases documented in the literature. But such a mental capacity is not without consequence. These patients are constantly remembering sequences of events, they are exhausted by the tirelessness of their memory recall, and it significantly interferes with their attention in the present moment. This biological blessing is also extremely limited. Patients with hyperthymesia appear to have selective memories. If asked to remember a specific fact, like how many rugs Paul Manafort has been hoarding, they might have trouble recalling that number. But they may remember the exact patterns of the rugs, or what your hair looked like when you told them that fact. Using a real world example from when humans were just learning to stand upright, hyperthymetics—if they existed back then—may have remembered how many fish you caught 7 winters ago when food was scarce, but they may have difficulty remembering where that fresh water stream was or how to get back to it. And these patients may have other psychological comorbidities. One theory as to how these people develop such an impressive memory recall is that they are constantly retrieving this information, and thereby living in the past. All the horrible events they’ve ever experienced—arguments, breakups, broken bones, car accidents, horror movies, family deaths—they continue to re-experience them over and over. This formed the basis for the lack of forgiveness felt by one of House’s patients back in season 7. In that show, the patient, a waitress at a small time restaurant, holds such a grudge for her sister that it actually makes her physically sicker. You can imagine, it’s hard to forgive and forget if you cannot forget.
Bottom line. There’s not really a great example where a neurologic condition actually improves the nervous system. Hyperthymesia is probably the closest we can get. There are definitely no reported cases of brain tumors or inflammatory diseases or strokes that enhance brain function. Caffeine and neurostimulants, as we discussed before, can enhance the physiologic function of the brain and improve performance, but only mildly. Pathophysiologic equivalents, like a pheochromocytoma which is a very poor comparison, are not great examples of any condition that may benefit the nervous system. Genetic mutations such as those affecting SCN9A, which cause congenital insensitivity to pain would be nice, did they not result in such profound bodily injury. And then there are some multifactorial and still unexplained conditions like the Savant Syndrome and hyperthymesia where mental skills may be quite profound, but only at the cost of other cognitive domains. In all, some conditions may come close to John Travolta’s condition in Phenomenon, but maybe there is more fiction to that story than science.
BrainWaves’ podcasts and online content are intended for medical education and entertainment only.
- Costanzo JP, Lee RE, Jr. and Lortz PH. Glucose concentration regulates freeze tolerance in the wood frog Rana sylvatica. J Exp Biol. 1993;181:245-55.
- Moalem S, Weinberg ED and Percy ME. Hemochromatosis and the enigma of misplaced iron: implications for infectious disease and survival. Biometals. 2004;17:135-9.
- Nagasako EM, Oaklander AL and Dworkin RH. Congenital insensitivity to pain: an update. Pain. 2003;101:213-9.
- Saloviita T, Ruusila L and Ruusila U. Incidence of Savant Syndrome in Finland. Percept Mot Skills. 2000;91:120-2.