Our cells generate most of the energy they need in tiny structures inside them called mitochondria, which can be thought of as the cells' powerhouses. Mitochondria have their own DNA, independent of the cell's nuclear genome, which is compelling similar to the DNA of bacterial genomes. What this suggests is that many thousands of years ago, mitochondria were not just components of our cells, but were in fact unicellular organisms in their own right. According to this hypothesis – the endosymbiotic theory – mitochondria (and possibly some other organelles) originated as free-living bacteria which later became incorporated inside other cells in a symbiotic relationship.
Like man-made powerhouses, mitochondria produce hazardous by-products as well as useful energy. They are the main source of free radicals in the body – hugely reactive particles which cause damage to all cellular components through oxidative stress. They attack the first thing they come across, which is usually the mitochondrion itself. This hazardous environment has put the genes located in the mitochondrion at risk of mutational damage, and over many years of evolutionary pressure the mitochondrial DNA has gradually moved into the cell's nucleus, where it is comparatively well-protected from the deleterious effects of free-radicals alongside all of the cell's other DNA. This is called allotopic expression, and it has moved all but thirteen of the mitochondrion's full complement of at least one thousand genetic instructions for proteins into the 'bomb-shelter' of the nucleus.
However, the remaining thirteen genes in the mitochondrion itself are subject to the ravages of free-radicals, and are likely to mutate. Mutated mitochondria, as Aubrey de Grey has identified, may indirectly accelerate many aspects of ageing, not least when their mutation causes them to no longer produce the required energy for the cell, in turn impairing the cell's functionality. In order to combat the down-stream ageing damage as a consequence of mitochondrial mutation, de Grey believes that the mitochondrial DNA damage itself needs to be repaired or rendered harmless.
His characteristically bold solution to this problem is to put the mutations themselves beyond use by creating backup copies of the remaining mitochondrial genetic material and storing them in the safety of the cell's nucleus. Allotopically expressed here, like the rest of the mitochondrial DNA, any deletions in the mitochondrial DNA can be safely overwritten by the backup master copy, which is much less likely to mutate hidden away from the constant bombardment of free radicals. There are several difficulties to this solution, not least the fact that the remaining proteins are extremely hydrophobic and so don't 'want' to be moved at all, and additionally the code disparity between the language of the mitochondrial DNA and the nuclear DNA which makes a simple transplantation without translation impossible.
Even if this engineered solution to the problem proves impracticable, at the very least the theory is sound. If we can devise a way systematically defend our mitochondria from their own waste products, we will drastically reduce the number of harmful free radicals exported throughout our bodies, thereby reducing preventing a lot of the damage that distinguishes the young from the old, extending and improving the quality of our lives as a result.
Dr Aubrey de Grey, a gerontologist from Cambridge, believes that ageing is a disease that can be cured. Like man-made machines, de Grey sees the human body as a system which ages as the result of the accumulation of various types of damage. And like machines, de Grey argues that this damage can be periodically repaired, potentially leading to an indefinite extension of the system's functional life. De Grey believes that just as a mechanic doesn't need to understand precisely how the corrosive processes of iron oxidation degrades an exhaust manifold beyond utility in order to successfully repair the damage, so we can design therapies that combat human ageing without understanding the processes that interact to contribute to our ageing. All we have to do is understand the damage itself.
De Grey is confident that he has identified future technologies that can comprehensively remove the molecular and cellular lesions that degrade our health over time, technologies which will one day overcome ageing once and for all. In order to pursue the active development and systematic testing of these technologies, de Grey has made it part of his mission to break the 'pro-ageing trance' that he sees as a widespread barrier to raising the funding and stimulating the research necessary to successfully combat ageing. De Grey defines this trance as a psychological strategy that people use to cope with ageing, fuelled from the incorrect belief that ageing is forever unavoidable. This trance is coupled with the general wisdom that anti-ageing therapies can only stretch out the years of debilitation and disease which accompany the end of most lifetimes. De Grey contends that by repairing the pathologies of ageing we will in fact be able to eliminate this period completely, postponing it with new treatments for indefinitely longer time periods so that no-one ever catches up with the damage caused by their ageing.
To get over our collective 'trance' it is worth realising that this meme has made perfect psychological sense until very recently. Given the traditional assumption that ageing cannot be countered, delayed or reversed, it has paid to make peace with such a seemingly immutable fact, rather than wasting one's life preoccupied with worrying about it. If we follow de Grey's rationale that the body is a machine that can be repaired and restored, we have to accept that there are potential technologies that can effectively combat ageing, and thus the trance can no longer be rationally maintained.
Telomeres are repetitive DNA sequences which cap the ends of chromosomes, protecting them from damage and potentially cancerous breakages and fusings. They act as disposable buffers, much as the plastic aglets at the end of shoelaces prevent fraying. Each time a cell divides, the telomores get shorter as DNA sequences are lost from the end. When telomeres reach a certain critical length, the cell is unable to make new copies of itself, and so organs and tissues that depend on continued cell replication begin to senesce. The shortening of telomeres plays a large part in ageing (although not necessarily a causal one), and so advocates of life extension are exploring the possibility of lengthening telomeres in certain cells by searching for ways to selectively activate the enzyme telomerase, which maintains telemore length by the adding newly synthesized DNA code to their ends. If we could induce certain parts of our bodies to express more telomerase, the theory goes, we will be able to live longer, healthier lives, slowing down the decline of ageing.
Every moment we're fighting a losing battle against our telomeric shortening; at conception our telomeres consist of roughly 15,000 DNA base pairs, shrinking to 10,000 at birth when the telomerase gene becomes largely deactivated. Without the maintenance work of the enzyme our telomeres reduce in length at a rate of about 50 base pairs a year. When some telomeres drop below 5,000 base pairs, their cells lose the ability to divide, becoming unable to perform the work they were designed to carry out, and in some cases also releasing chemicals that are harmful to neighbouring cells. Some particularly prominent cell-types that are affected by the replicative shortening of telomeres include the endothelial cells lining blood vessels leading to the heart, and the cells that make the myelin sheath that protects our brain's neurons. Both brain health and heart health are bound to some degree to the fate of cells with a telomeric fuse. The correlation between telomere length and biological ageing has motivated a hope that one day we will be able to prevent and perhaps reverse the effects of replicative senescence by optimally controlling the action of telomerase.
The complexity of synthesizing proteins for specific purposes is so great that predicting the amino acid sequences necessary to generate desired behaviour is a huge challenge. Mutations far away from the protein’s active site can influence its function, and the smallest of changes in the structure of an enzyme can have a large impact on its catalytic efficacy – a key concern for engineers creating proteins for industrial applications. Even for a small protein of only 100 amino acids long there are more possible sequences than there are atoms in the universe.
What this means is that an exhaustive search through the space of all possible proteins for the fittest protein for a particular purpose is essentially unachievable, just as a complete search through all possible chess games to decide the absolutely optimal next move is computationally impractical. This is true both for scientists and for nature. This means that even though evolution has been searching the space of all possible proteins for billions of years for solutions to survival, it has in fact explored only a minute corner of all possible variations. All evolved solutions are likely to be 'good enough' rather than the absolute optimum – it just so happens that the ones already 'discovered' are sufficient to create and maintain the diversity and richness of life on planet earth.
New ways of efficiently searching this vast space of possible sequences will reveal proteins with properties that have never before existed in the natural world, and which will hopefully provide answers to many of our most pressing problems. Directed evolution not only provides a faster way of searching this space than many other methods, but it also leaves a complete 'fossil record' of the evolutionary changes that went into evolving a specific protein, providing data on the intermediate stages which will offer insight after detailed study into the relationship between protein sequence and function. Unlike natural evolution, directed evolution can also explore sequences which aren't directly biologically relevant to a single organism's survival, providing a library of industrially relevant proteins, and perhaps one day creating bacteria capable of answering worldwide problems caused by pollution and fossil fuel shortage.
Neo-evolution is factorially faster than normal evolutionary processes. Our genetically engineered organisms have already neo-evolved – shortcutting traditional evolution to produce desirable results without the costly time-delay of selection over hundreds or thousands of generations. Higher-yielding and insecticide-resistant crops have been engineered through the painstaking modification of individual genes, achieving better results than years of selective breeding in a fraction of the time. Genetic engineering of humans, both embryonic and those already alive, will perhaps one day bring the benefits of this new type of evolution to our bodies.
At the moment, we simply do not understand how DNA sequences encode useful functions, and so genetic engineering remains a tremendously costly and laborious process. It cost $25 million and took 150 person-years to engineer just a dozen genes in yeast to cause it to produce an antimalarial drug, and commercial production has yet to begin. The amount of time and money required to effect a beneficial result through genetic engineering – even if it involves relatively simple changes to only a dozen genes – is so costly that the transformative idea of neo-evolved humans has been kept at a safe distance.
But there are other ways to neo-evolve that might make the possibility of too-good-to-miss genetic enhancements in humans a reality before long. Earlier this year, for instance, the National Academy of Engineering awarded its Draper Prize to Francis Arnold and Willem Stemmer for their independent work towards 'directed evolution', a technique which harnesses the power of traditional evolution in a highly optimized environment to accelerate the evolution of desirable proteins with properties not found in nature. Rather than attempt to manually code the strings of individual DNA letters necessary to effect a particular trait, directed evolution and its associated 'evolution machines' take a prototype 'parent' gene, create a library of genetic variants from it and apply selection pressures to screen for the strains that produce the desired trait, iterating this process with the best of each batch until the strongest remain. This was first evidenced in 2009, when geneticist Harris Wang used directed evolution to create new proteins in E. coli bacteria that would produce more of the pigment that makes tomatoes red than was previously possible.
To achieve this genetic modification without manually fine-tuning each gene, Wang synthesized 50,000 DNA strands which contained modified sequences of genes that produce the pigment, and multiplied them in his evolution machine. After repeating the process 35 times with the results of each cycle fed into the next, he produced some 15 billion new strains, each with a different combination of mutations in the target pigment-producing genes. Of these new strains, some produced up to five times as much pigment as the original strain, more than the entire biosynthesis industry had ever achieved. The process took days rather than years.
There are three distinct possibilities for how technological and medical advancement will impact future human evolution. The first contingency is that the human species will undergo no further natural selection, because we may have already advanced to a position of evolutionary equipoise, where our technologies have artificially preserved genes that would otherwise have been removed by natural selection; evolution no longer has a chance to select. As a species we already control our environment to such an extent that traditional evolutionary pressures have been functionally alleviated – we adapt the environment to us rather than the other way around. Indeed, local mobility and international migration allow populations to genetically integrate to such a degree that the isolation necessary for evolution to take place may in fact already no longer possible.
The second possibility is that we will continue to evolve in the traditional way, through inexorable selection pressures exerted by the natural environment. The isolation necessary to allow the impact of any environmental changes to be selected for in the population will now be on the planetary scale, enabled by colonization of distant space.
The third possibility is that we will evolve in an entirely new way, guided not by unconscious natural forces but by our own conscious design decisions. In this neo-evolution we would use genetic engineering to eliminate diseases like diabetes, protect against strokes and reduce the risks of cancer. We would be compressing a natural process which takes hundreds of thousands of years into single generations, making evolutionarily advantageous adjustments ourselves.
From an economic perspective, cheating is a simple cost-benefit analysis, where the probability of being caught and the severity of punishment must be weighed against how much stands to be gained from cheating. Behavioural economist Dan Ariely has conducted experimental studies to test whether there are predictable thresholds for this balance, and how they can be influenced.
In one study, Ariely gave participants twenty maths problems with only five minutes to solve them. At the end of the time period, Ariely paid each participant one dollar for each correctly answered question; on average people solved four questions and so received four dollars. Ariely tempted some members of the study to cheat, by asking them to shred their paper, keep the pieces and tell him how many questions they answered correctly. Now the average number of questions solved went up to seven; and it wasn't because a few people cheated a lot, but rather that everyone cheated a little.
Hypothesizing that we each have a “personal fudge factor”, a point at which we can still feel good about ourselves despite having cheated, Ariely ran another experiment to examine how malleable this standard was. Before tempting participants to cheat, Ariely asked them to recall either ten books they read at school or to recall The Ten Commandments. Those who had tried to recall the Commandments – and nobody in the sample managed to get them all – did not cheat at all when given the opportunity, even those that could hardly remember any of the Commandments. When self-declared atheists were asked to swear on the Bible before being tempted to cheat in the task, they did not cheat at all. Cheating was also completely eradicated by asking students to sign a statement to the effect that they understood that the survey falls under the “MIT Honor Code”, despite MIT having no such code.
In an additional variant of the same experiment, Ariely tried to increase the fudge-factor and to encourage cheating. A third of particpants were told to hand back their results paper to the experimenters, a third were told to shred it and ask for X number of dollars for X completed questions, and a third were told to shred their results and ask for X tokens. For this last group, tokens were handed out, and the participants would walk a few paces to the side and exchange their tokens for dollars. This short disconnect between cash and token encouraged cheating rates to double in this last group.
Putting these results in a social context, Ariely ran yet another variant of the experiment, to see how people would react when they saw examples of other people cheating in their group. Subjects were given envelopes filled with money, and at the end of the experiment they were told to pay back money for the questions that they did not complete. An actor was planted in the group, without the knowledge of the other participants. After thirty seconds the actor stood up and announced that he had finished all of the questions. He was told that the experiment was completed for him, and that he could go home (i.e. keeping the contents of the envelope). Depending on whether he was wearing a shirt identifying him as from the same university as the rest of the students in the test or not, cheating went either up or down respectively. Carnegie Mellon students would cheat more if he was identified as a Carnegie Mellon student, whilst cheating would decrease if he was identified by a University of Pittsburgh shirt.
Ariely's results show that the probability of getting caught doesn't influence the rate of cheating so much as the norms for cheating influence behaviour: if people in your own group cheat, you are more likely to cheat as well. If a person from outside of your group cheats, the personal fudge factor increases, and the likelihood of cheating drops, just as it did with the Ten Commandments experiment, reminding people of their own morality.
The stock market combines a worrying cocktail of features from these experiments. It deals with 'tokens', stocks and derivatives and not 'real' money. Stocks are many steps removed from real money, and for long portions of time. This encourages cheating. Any enclaves of cheating will be reinforced by people mirroring the behaviours of those around them, and this is precisely what happened in the Enron scandal.
Here is a syllogism that is deeply embedded in Western society. Welfare is maximized by maximizing individual freedom. Individual freedom is maximized by maximizing choice. Welfare increases with more choice.
Supermarkets are an embodiment of this belief. They are symbols of affluence and empowerment conferred through their superabundance of choice. The range of products they offer is dizzying. So disorientingly so, in fact, that too many options have paralyzing effects, making it very difficult to choose at all – a fact that completely undermines the belief that maximizing choice has unqualified beneficial effects.
If we finally do manage to make a decision and overcome this paralytic effect, too much choice diminishes the satisfaction that can be gained compared with choices made between fewer options. This is because if the choice you make leaves you feeling dissatisfied in any way it is easy to simulate the myriad of other choices that could have been better. These imagined alternatives, conjured from the myriad real alternatives, can induce regret which dilutes the satisfaction from your choice, even if it was a good one. The wider the range of options, the easier it becomes to regret even the smallest disappointment in your decision.
A wider range of choice also makes it easier to imagine the attractive features of the alternatives that have been rejected, once more diminishing the sense of satisfaction with the chosen alternative. This phenomenon is known as the opportunity cost, the sacrificial loss of other opportunities when a choice is made: choosing to do one thing is choosing not to do many other things. Many of these other choices will have attractive features which will make whatever you have chosen less attractive, no matter how good it really is.
The maximization of choice leads to an escalation of expectations, where the best that can ever be hoped for is that a decision meets expectations. In a world of extremely limited choice, pleasant surprises are possible. In a world of unlimited choice, perfection becomes the expectation: you could always have made a better choice. When there is only one choice on offer, the responsibility for the outcome of that 'choice' is outside of your control, and so any disappointment resulting from that decision can safely be blamed on external factors. But when you have to choose between hundreds of options it becomes much easier to blame oneself if anything is less than perfect. It is perhaps no coincidence that as choice has proliferated and standards have risen in the past few generations, so has the incidence of clinical depression and suicide.
What this means is that there is a critical level of choice. Some societies have too much, others patently too little. At the point at which there is too much choice in a critical proportion of our lives, our welfare is no longer improved. Too much choice is paralytic and dissatisfying, and too little is impoverishing. We don't want perfect freedom and nor do we want the absence of it; somewhere there is an optimal threshold, and affluent, materialist societies have probably already passed it.
Our uniquely large pre-frontal cortex enables us to simulate experiences, allowing us to compare potential futures and make judgements based on these simulations. The difficulty in deciding which of several simulations we prefer arises because we are surprisingly poor at analyzing what makes us happy. Seemingly obvious questions such as 'would you prefer to become paraplegic or win the lottery?' are obscured by the extraordinary fact that one year after each event, both groups report being equally happy with their lives. A preference for one alternative over another can be measured in its ability to confer happiness, and, contrary to all of our impulses, there can be no rational preference in this example when considered over a sufficiently long time-period, as there is no reported qualitative difference between the two levels of happiness after a single year.
This is a result of the impact bias, the tendency of our emotional simulator to overestimate the intensity of future emotional states, making you believe that the difference in two outcomes is greater than it really is. In short, things that we would unthinkingly consider important, like getting a promotion or not, passing an exam, or not or gaining or losing a romantic partner, frequently have far less impact, of a much lower intensity and a much lower duration than we expect them to have. Indeed, in an astonishing study published in 1996, it was found that even major life traumas had no effect on subjective well-being (with very few exceptions) if they had not occurred in the past three months 1.
The reason for this remarkable ability is that our views of the world change to make us feel better about whatever environment we find ourselves in over a period of time. Everything is relative, and we make happiness where we would otherwise believe there to be none. To truncate a well-known quotation from Milton, “The mind is its own place, and in itself can make a heaven of hell”. Daniel Gilbert, Professor of Psychology at Harvard, calls this 'synthesizing happiness'.
Synthetic happiness differs from 'natural' happiness in that natural happiness is what we feel when we get what we wanted, and synthetic happiness is what we (eventually) feel when we don't get what we wanted. The mistake we make is believing that synthetic happiness is inferior to natural happiness. This mistake is perpetuated by a society driven by an economic system which relies on people believing that getting what you want makes you happier than not getting what you want ever could. We can resist this falsehood by remembering that we possess within ourselves the ability to synthesize the commodity that we always pursue, and that we consistently overrate the emotional differences between two choices.
- 1. Suh, Eunkook, Ed Diener, and Frank Fujita. "Events and Subjective Well-being: Only Recent Events Matter." Journal of Personality and Social Psychology 70.5 (1996): 1091-102. Print.
Optical illusions are a visual proof of a built-in irrationality in the way we reason. In some illusions we can be shown two lines of equal lengths and yet perceive one to be longer than the other. Even when we see visual proof that the lines are in fact of equal length, it's impossible to overcome the sense that the lines are different – it's as if we cannot learn to override our intuitions. In the case of optical illusions, our intuition is fooled in a repeatable, predictable fashion, and there is not much we can do about it without modifying the illusion itself, either by measuring it or by obscuring some part of it.
Dan Ariely, a behavioural psychologist currently teaching at Duke University, reminds us that optical illusions are a big deal. Vision is one of the best things that we do – we are evolutionarily designed to be good at it, and a large part of our brain is dedicated to being good at it, larger than is dedicated to anything else. The fact that we make such consistent mistakes, and are repeatedly fooled by optical illusions should be troubling. If we make mistakes in vision, what kind of mistakes will we make in those things that we have no evolutionary reason to be any good at? In new and elaborate environments like financial markets, we don't have a specialized part of the brain to help us, and we don't have a convenient visual illustration with which to easily demonstrate the mistakes we make. Is our sense of our decision making abilities ever consistently compromised?
Ariely suggests that we are victims of decision making illusions in much the same way we are victims of optical illusions. When answering a survey, for instance, we feel like we are making our own decisions, but many of those decisions in fact lie with the person who designed the form. This is strikingly shown by the disparity in the percentage of people in different European countries who indicated that they would be interested in donating their organs after death, as illustrated by a 2004 paper by Eric Johnson and Daniel Goldstein. Consent rates in France, Belgium, Hungary, Poland, Portugal, France and Austria were over 99%, whilst the UK, Germany and Denmark all had rates of below 20%. This huge difference didn't arise due to strong cultural differences, but through a simple difference in the way the question on the form was presented. In countries with a low consent rate, the question was as an opt-in choice, as in 'Check the box if you wish to participate in the organ donor programme'. People didn't check the box, leaving the form in its 'default' state. Those presented with the inverse question, an explicit opt-out rather than explicit opt-in, also left the box unchecked. Both groups tended to accept whatever the form tacitly suggested the default position was. The two types of forms created strongly separated groups of consenting donors and non-consenting donors across the countries, separated by nearly 60% as a direct result of how the question was phrased.
This is just one example of how we can reliably be led into making a choice that isn't a choice at all, suggesting that our awareness of our own cognitive abilities isn't quite as complete as perhaps we would like. Recognizing this in-built limitation like Laurie Santos, Ariely stresses that the more we understand these cognitive limitations, the better we will be able to design and ameliorate our world.