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Smarter on Drugs

We recoil at the idea of people taking drugs to enhance their intelligence. But why?

Any child can tell you that some people are smarter than others. But what is the difference between the brain of a Ph.D. student and the brain of the average Joe? If we can figure that out, then a bigger question follows: Is it ethical to turn average Joes into geniuses? Evolutionary theory suggests that if we are smart enough to invent technology that can increase our brain capacity, we should be able to use that advantage. It is the next step in the survival of the fittest. As noted psychologist Corneliu Giurgea stated in the 1970s, Man is not going to wait passively for millions of years before evolution offers him a better brain.

That said, gnawing concerns persist when it comes to artificially enhancing intelligence. Geneticists and neuroscientists have made great strides in understanding which genes, brain structures and neurochemicals might be altered artificially to increase intelligence. The fear this prospect brings is that a nation of achievers will discard hard work and turn to prescriptions to get ahead.

Enhancing intelligence is not science fiction. Many smart drugs are in clinical trials and could be on the market in less than five years. Some medications currently available to patients with memory disorders may also increase intelligence in the healthy population. Likewise, few people would lament the use of such aids to ameliorate the forgetfulness that aging brings. Drugs that counter these deficits would be adopted gratefully by millions of people.


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Drugs designed for psychotherapy can also be used to enhance certain regular mental functions. Just as Ritalin can improve the academic performance of hyperactive children, it can do the same for normal children. It is commonly thought to boost SAT scores by more than 100 points, for both the hyperactive and the normal user. Many healthy young people now use it that way for that purpose, and quite frankly, there is no stopping this abuse.

In a way, with these new compounds, we are reliving the stories associated with better-known illegal psychoactive drugs. Morphine is a terrific help with pain produced by burns and other somatic ills; it is also a mind-altering substance that in some areas of society causes tremendous social and psychological problems. Do we stop developing such painkillers just because they might be misused? Even when the issue is simple memory enhancement, we profess great social concern. Why do we resist changes in our cognitive skills through drugs?

The reason, it seems to me, is that we think cognitive enhancement is cheating. If, somehow, someone gets ahead through hard work, that's okay. But popping a pill and mastering information after having read it only once seems unfair.

This position makes no sense. Among the normal population are men and women with incredible memories, fast learners of language and music, and those with enhanced capabilities of all kinds. Something in their brains allows them to encode new information at lightning speed. We accept the fact that they must have some chemical system that is superior to ours or some neural circuitry that is more efficient. So why should we be upset if the same thing can be achieved with a pill? In some way, we were cheated by Mother Nature if we didn't get the superior neural system, so for us to cheat her back through our own inventiveness seems like a smart thing to do. In my opinion, it is exactly what we should do.

Memory Enhancers

Already available, or making their way through the Federal Drug Administration's approval process, are several cognitive enhancers that reportedly improve memory. These are also being called smart drugs, or nootropes, from the Greek noos, for mind, and tropein, for toward. Whenever a study shows that a certain chemical produces even a moderate increase in memory in an animal population (be it fruit flies, mice or humans), one of two things happens. If the compound is not on the market, a pharmaceutical company quickly jumps in to exploit the finding. If the drug is already on the market but is used to treat a known ailment--for instance, Alzheimer's or attention-deficit hyperactivity disorder--a surge takes place in off-label use, for a purpose other than the intended application. Some regulated smart drugs are currently on the market, as are unregulated herbal medications. Entire stores called smart bars have popped up along the West Coast to sell these items.

Work on memory enhancers may be furthest along. Eric R. Kandel of Columbia University, who won a Nobel Prize for his research on learning and memory in the sea slug Aplysia, is one proponent. He found that learning occurs at the synapse (the junction between two neurons) by several means. The synapse is enhanced when a protein called CREB is activated, and CREB plays a role in memory formation in fruit flies and in mice. With these discoveries came the 1998 birth of Memory Pharmaceuticals, Kandel's Montvale, N.J.based company, which hopes to formulate a drug that will raise the amount of CREB in the human neural system and thus facilitate the formation of long-term memories. One of the most promising chemicals is called MEM 1414. If clinical trials go well, MEM 1414 could be on the market after 2008. At least one other company, Helicon Therapeutics in Farmingdale, N.Y., is also investigating CREB to improve human memory formation.

Alternative drugs are also in the works based on other brain mechanisms. Before a neuron naturally increases CREB, certain channels on its membrane must open to allow positive ions to flow into the cell. The ions then trigger a cascade of events leading to the activation of CREB. One channel of interest is known as NMDA. In 1999 Joseph Z. Tsein, Ya-Ping Tang and their colleagues, then at Princeton University, discovered that increasing the number of NMDA receptors in the mouse hippocampus led to better performance on a spatial-memory task. Now researchers and pharmaceutical companies are pursuing NMDA receptor agonists (they combine with the receptors) as nootropes. At least a dozen new drugs of this kind are making their way toward clinical trials.

Scientists have known for years that more commonplace chemicals such as adrenaline, glucose and caffeine increase memory and performance. We all know it, too: procrastinators find clarity of mind in the adrenaline rush to meet a deadline; we try not to work on an empty stomach; and we are willing to pay a premium for a vente latte--all testimony to our appreciation of these legal activities.

Self-medicating with Starbucks is one thing. But consider the following. In July 2002 Jerome Yesavage and his colleagues at Stanford University discovered that donepezil, a drug approved by the FDA to slow the memory loss of Alzheimer's patients, improves the memory of the normal population. The researchers trained pilots in a flight simulator to perform specific maneuvers and to respond to emergencies that developed during their mock flight, after giving half the pilots donepezil and half a placebo. One month later they retested the pilots and found that those who had taken the donepezil remembered their training better, as shown by improved performance. The possibility exists that donepezil could become a Ritalin for college students. I believe nothing can stop this trend, either.

This anecdote reminds us that the unintended use and misuse of drugs is a constant. Trying to manage it, control it and legislate it will bring nothing but failure and duplicity. This fact of life needs to be aired, and our culture needs to reach a consensus about it. Aricept (the commercial name for donepezil) works, caffeine works, Ritalin works. Individuals will use such drugs or not use them, depending on their personal philosophy about enhancement. Some people like to alter their mental states; others do not.

My guess is that, on average, adults will choose not to use memory enhancers or the theoretically more obscure IQ or cognitive enhancers. Why? Because when memory is in the normal range, we adapt to its level and set our personal psychological life in that context. Increasing our memory capacity might send a ripple effect across the landscape of our daily lives. After all, we spend a good part of each evening trying to forget many of the day's memories. Over a lifetime we have built up our personal narrative based on the efficiency of our memory and our capacity to forget. Any significant or even slight change in these capacities will have to be integrated into the backbone of that narrative, changing the mental life of a person.

For a society that spends significant time and money trying to be liberated from past experiences and memories, the arrival of new memory enhancers has a certain irony. Why do people drink, smoke marijuana and engage in other activities that cause them to take leave of their senses? Why are psychiatry offices full of patients with unhappy memories they would like to lose? And why do victims of horrendous emotional events such as trauma, abuse or stressful relationships suffer from their vivid recollections? A pill that enhances memory may lead to a whole new set of disorders. Maybe the haunting memories of a bad experience will become ever present in consciousness after taking an enhancing pill. This problem and dozens of others may well be the outcome.

Of course, many steps precede success in drug development, and some critics doubt we will see these newer memory enhancers in our lifetime. Although studies on animal models find that certain drugs improve memory or performance on specific tasks, it is not clear that they would help humans. Many nootropes that were promising in lab animals have failed miserably in human clinical trials. Is this because millions of years of evolution have led to a human brain whose neurochemical concentrations are at optimal levels? Another hurdle for drugs is their potential to cause deleterious effects. Some accounts of mice with altered smart brains, for instance, show that the mice are not only more receptive to learning but are also more sensitive to pain.

Superintelligence

Enhancing memory is one issue. Making people smarter--more able to contemplate complex ideas with greater ease and facility--somehow seems more problematic. Do we want a nation full of Harvard graduates? On the surface it seems insane. But the basic science suggests that superintelligence is not far-fetched.

Defining what it means to be smart has frustrated psychologists for years. IQ and SAT tests, though long-standing indicators of academic success, are far from perfect indicators of success in the real world. Intelligence tests, especially the IQ test, measure people's analytical skills, verbal comprehension, perceptual organization, working memory and processing speed. This type of intelligence is called psychometric intelligence, and although it is not the only type (some researchers believe in multiple intelligences, even including athletic ability), it is testable and so remains one of our primary gauges.

In 1904 Charles Spearman, an English psychologist, reviewed the literature of the 19th century on intelligence and found that people who performed well on one test of intelligence seemed to perform well on all others. Spearman theorized the existence of a general intelligence, which he termed g, that is used to process many domains and thus makes some people good at nearly all intelligence challenges. Many investigations since 1904 have supported Spearman's idea, and the current consensus among scientists and psychologists is that a g factor accounts for a great deal of the variance in intelligence test scores.

Recently geneticists have discovered that even such abstract qualities as personality and intelligence are coded for in our genetic blueprint. Studies of the genetic basis of g are just beginning, and because g most likely arises from the influence of many genes, the hunt will be a long one. Yet one study has already found that a gene on chromosome 6 is linked to intelligence.

So-called genetic brain mapping could help the search. Scientists are looking at the structural features (size, volume, and so on) of the brains of many individuals, including twins, familial relatives and unrelated individuals. By scanning all these brains in magnetic resonance imaging machines and looking at the differences, researchers have been able to determine which areas of the brain are most under the control of genes. These studies have emerged only in the past three to four years. Geneticists hope that once they know which brain areas are most affected by heredity, they can figure out which genes are responsible for those regions. With this kind of reverse mapping, the experts should be able to learn more about the genetics of intelligence.

Geneticists and neuroscientists seem to be in agreement: the genes that affect intelligence may be coding for the structure and functions of specific brain areas that underlie Spearman's g. When researchers combine brain mapping with IQ tests, they can begin to tease out the correlations between the size, structure, and volume of brains and intelligence. Neuroscientists have determined that overall brain size has a statistically significant correlation with IQ. More detailed investigations show that the amount of gray matter--consisting mainly of the cell bodies of neurons--in the frontal lobes varies significantly with differences in intelligence scores. That suggests the frontal lobe may be the location of g.

Indeed, John Duncan and his colleagues at the Medical Research Council in Cambridge, England, who put smart volunteers through a multitude of mentally demanding tasks, found that the lateral part of the frontal lobe on both the left and right sides may be the resting place of general intelligence. While undergoing positron-emission tomography (PET) scans, Duncan's subjects selectively activated the lateral frontal cortex during several intelligence tests. Some researchers are skeptical of the importance of Duncan's study, saying it is suggestive at best because we do not yet fully understand what the frontal lobes do. But his findings solidify the fact that we have entered a new age in scientific history--an era that allows neuroscientists to investigate individual differences in intelligence, previously a field only for psychology.

Accordingly, a robust literature concerning neural differences in intelligence has arisen. Further support for the frontal lobe's role comes from the observation that people with frontal lobe damage usually score 20 to 60 points lower on IQ tests than others. These people also have deficits in what is called fluid intelligence, which decreases with age and includes abstract reasoning, processing speed, accurate responses during time constraints and use of novel materials.

Smarter or Just Faster?

The future is here. We have isolated one gene involved in intelligence, and others will follow. We know which parts of the brain are influenced by particular genes and which parts correlate with high IQ. We also know some of the neurochemicals involved in learning and memory. With such knowledge, we will gain understanding of what needs to be manipulated to increase intelligence in people who were not blessed with brilliance in their genomes or further increase the intelligence of those who were. Gene therapy could insert, delete, turn on or turn off genes that we find to be associated with intelligence.

My own belief is that none of this threatens our sense of self. The opportunities to enhance one's mental state abound. Smart describes how well one processes information and figures out tasks. Once something has been figured out, much work must then be applied to the solution, and the smartest people in the world rarely say that the task is easy. They have worked hard to achieve insight and solutions. So we may all get faster at figuring out new problems, but it is not clear what it would mean to get smarter. Smarter is frequently just another word for faster.

Whatever happens, we can be sure that cognitive enhancement drugs will be developed and that they will be used and misused. But just as most people do not choose to alter their mood with Prozac and just as we all reorient our lives in the face of unending opportunities to change our sense of normal, our society will absorb new memory drugs according to each individual's underlying philosophy and sense of self. Self-regulation will occur. The few people who desire altered states will find the means, and those who do not want to alter their sense of who they are will ignore the drug potions. The government should stay out of it, letting our own ethical and moral sense guide us through the new enhancement landscape.

(The Author)

MICHAEL S. GAZZANIGA is director of the Center for Cognitive Neuroscience at Dartmouth College and has served on the President's Council on Bioethics. This article is adapted with permission from his new book, The Ethical Brain (Dana Press, April 2005). Copyright 2005 by Dana Press.

(Further Reading)

 

  • Intelligence Reframed: Multiple Intelligences for the 21st Century. Howard Gardner. Basic Books, 2000.

  • Smart Drugs: Do They Work? Are They Ethical? Will They Be Legal? Steven P. R. Rose in Nature Reviews Neuroscience, Vol. 3, No. 12, pages 975979; December 2002.

 

(Further Reading)

  • Intelligence Reframed: Multiple Intelligences for the 21st Century. Howard Gardner. Basic Books, 2000.

  • Smart Drugs: Do They Work? Are They Ethical? Will They Be Legal? Steven P. R. Rose in Nature Reviews Neuroscience, Vol. 3, No. 12, pages 975–979; December 2002.

SA Mind Vol 16 Issue 3This article was originally published with the title “Smarter on Drugs” in SA Mind Vol. 16 No. 3 (), p. 32
doi:10.1038/scientificamericanmind1005-32