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What makes you you? Ask your genome.

• Text adapted from NewScientist.com news service, Dan Jones, 19 August 2006

CRAIG VENTER can make a unique claim. "To my knowledge I am the only person on
the planet to have their genome decoded," he says with a hint of satisfaction. He is the
driving force behind the commercial effort to sequence the human genome, so it is
perhaps not surprising he was the first to attain this level of self-knowledge.

He hopes he will not be alone for long. The J. Craig Venter Science Foundation is
sponsoring a $10 million prize for anyone who can get the cost of sequencing an
individual's genome down to $1000. Venter predicts it will be scooped within a decade.
At this price, plenty of people will be able to unravel their personal genetic story. "That's
when we're going to see a massive shift in the study of human genetic variation and our
own personal genetic make-up," he says.

Venter believes that once geneticists can compare thousands or even millions of
individual genomes, they will get a better handle on why, as individuals, we turn out the
way we do. Already we can link certain genes with diseases, personality traits, cognitive
styles, aptitudes and the like. And although Venter does not believe in genetic
determinism - the view that our fundamental nature is written in our genes - he still
champions the importance of genes. "We're clearly not born blank slates, but I think the
genetic effects on these traits are a lot stronger than most people are willing to deal with."
Venter thinks that the analysis of entire personal genomes, together with information
about how people actually live their lives, will provide a whole new window onto the
complex interplay between your nature and your nurture. This avalanche of genomic
knowledge could render the Freudian revolution a footnote of intellectual history. And
unlike psychoanalysis, it might even give you the information you need to ensure your
kids reach their full potential.

Some readers will find this prospect tremendously exciting, others quite terrifying. The
fact is, though, that if Venter's dream is ever to become reality, a lot of people need to get
their DNA sequenced. To get the ball rolling, Venter plans to unveil his genomic portrait
on GenBank, the US National Institutes of Health genetic sequence database, making it
freely available to anyone. Perhaps you are tempted to join him. If so, before you shell
out the cash, you will probably want to know what you will be getting for your money.
Put plainly, will you attain a level of self-knowledge previously unknown to humankind,
or will your genome tell you little you didn't already know?
Do you really want to know?

The most obvious benefit of genomic knowledge is in predicting if and when you are
likely to succumb to illnesses such as heart disease, stroke, Parkinson's and diabetes.
Armed with this information, you could decide to take preventive medicines, or make
lifestyle changes to delay or stave off the development of a condition. In a decade, we
will undoubtedly know far more about how certain versions of various genes are linked to
particular conditions. Venter, unsurprisingly, is ahead of the game. A look through his
genome has prompted him to start taking cholesterol-lowering drugs called statins to
delay or prevent heart disease.

Such insight sounds attractive, but it also raises the thorny issue of how to deal with
information about your chances of future health, particularly as medical professionals
might not be on hand to provide their interpretive and counseling skills. In a few cases
the implications of finding a certain mutation will be certain. People with a particular
duplicated region of chromosome 4, for example, always develop Huntington's disease.
More often, though, the link between a sequence of DNA and any disease it might
contribute to is much less clear-cut, often depending on the combined effects of many
genes and environmental factors.

This goes to the heart of the main problem with personal genomic. Gone are the days
when people talked about "the gene for X". Rare cases like Huntington's aside, at best all
we can say about most sequences of DNA is that they confer on carriers a certain
likelihood of developing a particular condition or trait. For example, a genetic variant
could have a harmful effect in 70 per cent of people, but no detectable effect in the
remaining 30 per cent. "Understanding this whole field will come down to probability
statistics, which are very hard to interpret," admits Venter. In essence, the vagaries of
genetic prediction mean that some people might benefit greatly, and others not at all.

The problem of probabilities is even greater when trying to understand the genetic basis
of aspects of personality, temperament and intelligence than for many health-related
traits. The details of human behaviors are not spelled out in the genome; social and
cultural factors profoundly influence how we think and act. That doesn't render genes
irrelevant. Genes are crucial to the development of the mind, personality and behavior,
just as they are for building limbs, lungs and livers. "Genes help wire up brains and guide
individual neurons to their destination," says Gary Marcus, a developmental psychologist
at New York University. "So genes play a pretty big role in building some of our
cognitive processes, like the kinds of memory and fundamental reasoning skills we
have."

In the absence of any other clues about a person's aptitudes, genetic analysis, though
imperfect, might be better than nothing. "Good teachers try to tailor their teaching to an
individual's strengths and weaknesses," says Marcus. "The genome could be one more
tool to guess what these are." Genetic forecasting about talents or deficits that are hard to
assess early on in life could also prove useful. "Such predictions might be useful if they
are made in childhood. Parents can make extra efforts, for example, to encourage the
musical development of a child with 'musicality' genes," says Judith Rich Harris, an
independent psychologist based in New Jersey.

This is already possible to some extent. "There are other ways of finding out that one has
untapped talents," Harris points out. As a child she disliked and avoided maths, but in
college she did surprisingly well on a maths aptitude test, and even enjoyed taking some
maths classes. Later, when bedridden through illness, she worked out a mathematical
theory of human information processing that has since been published. "Doing well on
that test at the age of 20 made me realize that my earlier avoidance of math had been a
mistake," Harris says.

Venter's biography offers a similar example. After enlisting in the US navy, he, like all
new recruits, went through a series of examinations, including an IQ test. When the
results came back, Venter found himself top out of 35,000 test scores. This served as a
wake-up call, making him reconsider his academic potential, and setting him on the path
to his present position.

Clearly, life offers us many chances to test our aptitudes, and information from a personal
genome could be a useful complement. It might even provide a basis for making ballpark
predictions about how children will turn out. As adults, though, we don't just want to
know about our strengths and weaknesses; we also want to understand how we have
become what we are. Where some people now look to psychotherapists for such answers,
in the future others may be tempted to consult their DNA. Could the information packed
into our genomes really change our view of ourselves as individuals?
The answer might seem to be a resounding "yes". After all, geneticists already compare
the composite human and chimp genomes to get insights into the genetic basis of chimp
and human natures. So shouldn't a comparison of genomic portraits from two individuals
reveal the genetic basis of why they differ?

What genes won't tell you

This is tricky terrain. The first misstep is to unreasonably elevate the power of genes. "We
measure the genetic effects because we can," Venter says. "We don't know how to
measure all the environmental effects that impact on our lives, or we would. The danger
lies in attributing too much significance to something just because you can measure it."

A second and bigger stumbling block is that when thinking about individuals, probability
complicates matters enormously. "Probabilities are perfectly reasonable as summaries of
tendencies of multiple events or individuals in a large sample," says Steven Pinker, a
cognitive psychologist at Harvard University, "but they are puzzling, perhaps even
meaningless, when applied to a single event or individual." The relevance of probabilities
after the event is even more questionable. It is a moot point, for example, whether gene
analysis could be used objectively to determine the likelihood that a given pianist would
have become a pianist.

All this is an attempt to explain retrospectively why you are the way you are. Though you
can assign probabilities to candidate causes - to this gene or that environmental effect -
either, or both, could have played a part in shaping you, with plenty of other factors and
some random noise thrown in for good measure.

Your long-lost twin

Nevertheless, there is a way of thinking about your genomic portrait that might go some
way towards helping you come to terms with who you are. "Having one's genome
decoded is like finding out that you have an identical twin who was reared somewhere
else," says Harris. "It lets you see the possibilities your genes provided you with, the
selves you might have become, but didn't."

The "genomic twin" idea gives a visceral edge to thinking about the cold, abstract strings
of DNA code that spell out our genomes. Harris tells a true story of twins separated at
birth and raised apart. One became a concert pianist, the other was offered music lessons
in childhood but declined. "I wonder what that twin thought when she met her concert-
pianist sister," she says. "Did she realise that she, too, might have been an excellent
musician if she had only accepted the offer to take lessons?" These are ultimately
unanswerable speculations, but that doesn't diminish their intrigue for such curious
animals as humans.

Now imagine that you have had your genome decoded, and the sequence has been sent to
you on a CD. You pop it in your computer, run a scan and find out that you have
"musicality" genes (imagining for the moment they exist and have been identified). How
would you react? Well, such a discovery should prompt the same kinds of reflections
suggested by Harris, with the same caveat. In both cases, we cannot unravel the specific
genetic, environmental and random effects that made us the way we are - the probabilities
make the picture so fuzzy you can't make out details. In this case, the best you can do is
to try your hand at piano and see how it goes. Maybe you'll pick it up, maybe you won't.

In many cases, knowing that you have gene variants associated with certain strengths or
weaknesses, tastes or temperaments will probably add little to your self-knowledge. "If I
know that I'm impulsive, that should affect how I evaluate an appealing temptation in
front of me now. If I know I have genes that probabilistically predispose me to
impulsiveness, that is far less relevant to my situation," Pinker argues. "It's the
impulsiveness that matters - whether it was ultimately due to genes, environment, chance
events in zigzagging neurons is far less important, indeed, perhaps irrelevant."

What this boils down to is that if you are looking for self-knowledge, genes are often not
the best level of analysis. And that's not the worst of it. "One of the biggest dangers of the
information in the genome is over-interpretation by society," says Venter. Genes at best
provide possibilities, not certainties. A particular suite of genes might tend to be
associated with high intelligence or a love of risks, but they are no guarantee of such
traits. The fact that we can talk about such genes does not mean we should attribute too
much power to them. Another is the spectre of self-fulfilling prophecies. If you know that
you have genes typically associated with being bad at music, you might convince
yourself that you are just born without musicality. "If people expect that they're not good
at something, they tend to become not good at that thing," says Marcus.
Looking into your genome could also dredge up trouble. Imagine that a genome scan
revealed that a law-abiding man had genes that gave him a 50 per cent chance of
becoming a criminal. "Will he feel good that he isn't in fact a criminal, or will the
information itself make it more likely that he will embark upon a new career as a law-
breaker?" asks Harris. "And what about the person with a similar genome who has
already committed a serious crime? Can we blame him and punish him for his crime, if it
was his genes that made him do it?"

With all this in mind, what do the experts conclude about the wisdom of getting our
genomes sequenced as soon as the technology makes it feasible? Venter is optimistic
about the promise of greater knowledge. At the moment we face difficult questions about
the underlying causes for our unique repertoire of character traits. "When we have
millions of genomes in hand we'll begin to be able to answer these questions," says
Venter. "Today we know almost nothing compared with what we'll know in a decade or
so."

Get one for your kids

Others are more circumspect, though there is general agreement that a genomic portrait
would provide useful medical forecasts and other practical insights. Whether it would
help you redefine your self-image is more contentious. "For an adult, I don't think it
would make much difference. Whatever the genome brings us has already been
considerably shaped by the environment, enough so that you can learn a lot more about a
person by studying her directly than by studying her genome," says Marcus. "But new
parents might some day want to purchase them to get an early forecast of their children's
likely aptitudes. After all, even before we start to talk we've got a genome."

As the physicist Niels Bohr famously quipped: "Prediction is very difficult, especially
about the future." One thing is certain, though: the more we study human genetic
variation, the more we will know about the genetic basis of our predispositions,
predilections and potential, so boosting our ability to predict how genes will affect the
way people turn out. Some of this progress will come through comparative studies of the
composite human genome and the genomes of chimps and other primates. More will
result from targeted studies into particular diseases and conditions. And, if enough people
follow Venter into the realm of personal genomics and make their individual DNA
available for study, this will undoubtedly provide an additional and powerful lens through
which to look at nature and nurture, and how they modulate each other.

The genome will never tell you everything, however. Even with a better understanding of
which genes are important and why, our genes will never define our destiny. Venter is
living proof of this. By many measures he is a risk-taker - he is an avid sailor and has
taken big scientific chances in his career - but an analysis of his genome for genes
associated with risk-taking and thrill-seeking failed to turn up the expected variants. That
doesn't make him any less of a risk-taker. It just means that his personality has developed
that way regardless of what his genes say.

To your good health


There has always been a discipline of "me-ology". It is called diagnostic medicine. In the
old days this was practised by waiting until you felt unwell and then going to a doctor.
Nowadays, there are batteries of tests that can tell you things about your health long
before you notice any symptoms.

One is a full-body CT scan, a sophisticated X-ray that can pick up early signs of cancer,
heart disease, aneurysm, osteoporosis, kidney stones, gallstones and more. It might even
turn up a real surprise. Perhaps you are a scientific curiosity - one of the 1 in 8500 people
who have a condition called situs inversus, in which your internal organs are the wrong
way round (heart on the right, liver on the left and so on). The condition is almost entirely
benign, so you might never even know, unless you opt for that scan.

Other tests include DXA (dual energy X-ray absorptiometry), which measures total body
fat and bone density. A slew of blood, urine and breath tests will tell you about such
things as your cholesterol level and organ functions, and pick up various diseases from
diabetes and gout to arthritis and cystitis. Some companies even sell home testing kits
that tell women their "ovarian reserve" - how many good-quality eggs are left in their
ovaries. Then there are genetic tests that will increasingly be able to warn you in advance
about the diseases that are likely to strike you later in life (see main story).

The ultimate in medical crystal ball gazing, however, has to be a scientific prediction of
when you will die. To that end, Tom Perls of Boston University has designed a
questionnaire test based on the latest gerontology (www.livingto100.com). Take it if you
dare!

Graham Lawton

The way I see it

Most of us have more or less the same equipment that allows us to touch, see, smell, taste
and hear. Yet we all experience the world in our own way. Your unique senses come from
a combination of genetic, physiological and psychological factors, many of which can be
measured.

To gauge the strength of your taste response, for example, swab a little blue food dye
onto your tongue. The pink bumps you can see standing out against the blue are your
fungiform papillae, which house your taste buds. Now take one of those small plastic
rings used to reinforce punched holes on paper, place it over the centre of your tongue
and count the bumps inside the hole. Researchers have used just this measure to
investigate our personal taste experiences. The average number of bumps is around 20.
Fifty or more, and you are a "supertaster", experiencing certain tastes up to three times as
intensely as "non-tasters" - people with just five bumps. Add to this your individual
experiences of smell, mouth feel and consistency, and you end up with your own personal
flavour sensation.
Similarly, there is emerging evidence that we all live in our own world of sound. A basic
audiogram test will tell you whether you can hear in the normal volume range: you press
a button in response to a tone that gets progressively quieter. Most people pass this test
with flying colours, but there is still a huge variation in our experience of sound.
Functional MRI tests reveal that different people have very different patterns of brain
activation in response to the same sounds. As yet no one is sure why that is, but
researchers at the UK's Institute of Hearing Research are working on it.

As for sight, it seems that when it comes to the brain, we do have similar experiences. A
region involved in face recognition, for example, lights up in response to a close-up shot,
while the part used for navigation is stimulated by landscapes. Still, there are individual
differences in the way we see the world. To test this try tuning a television to the colours
you think best represent real life, then ask a roomful of people how they think it matches
up. Chances are some will find it too green, others too red and so on. Proof, if it were
needed, that your vision of reality is not the same as mine.

Caroline Williams

What is on your mind?

At around $1000 a pop, a personal brain scan is not the cheapest path to self-knowledge,
but it may give you some insights into hidden aspects of your character and subconscious
attitudes.

Perhaps you want to know how cool you are. Steve Quartz from the California Institute
of Technology in Pasadena reckons he can tell you. He will record your brain's responses
to a barrage of images of products, brands and celebrities to gauge your emotional
reactions to what's hot and what's not. The results, he says, will tell you whether you're a
trendsetter or happy to follow the crowd.

Brain imaging can also reveal something about how the choices you make are influenced
by your emotions, gut instincts and subconscious. For example, neuroeconomist Ernst
Fehr from the University of Zurich in Switzerland looked at fMRI scans of people while
they were engaged in tasks in which they had to cooperate and trust others to make
financial gains to assess how Machiavellian they were, and how much they enjoyed
punishing partners who cheat. Similar studies can reveal how gullible or risk averse you
are. Elizabeth Phelps of New York University has even used brain scans to uncover
subconscious prejudices in people looking at faces of individuals of different races. Other
studies show that your brain's response to a moral dilemma can shed light on your style
of moral reasoning.

Is this really telling you anything new or that you couldn't find out with a personality test
or incisive conversation? Probably not. Yet even if you already know that you are
empathic, sensitive to the suffering of others, impulsive or have a tendency to violence, it
is intriguing to see how your brain's responses in these contexts compare with those of
other people. But beware this line of thinking. In truth, if you pay to have your brain
scanned, the personality trait it is most likely to reveal is egotism.

Helen Phillips

It is in your hands

If you have access to a photocopier, this couldn't be simpler. Take a picture of your right
hand, palm down. Now measure the lengths of your index and ring fingers, starting at the
crease nearest your palm. Then divide the former by the latter to give your very own
"second to fourth digit ratio" or 2D:4D. Not impressed? Well you should be, because this
little number says a lot about you - from your sexuality and personality to athletic
prowess and the diseases you are likely to get.

Your 2D:4D seems to be a measure of the levels of sex hormones you were exposed to
when you were in your mother's womb, explains John Manning, a pioneer in this field
from the University of Central Lancashire, UK. The more testosterone, the longer your
ring finger will be; the more oestrogen, the longer the index finger. Women tend to have a
2D:4D close to 1, while men are usually lower at around 0.96. How much you differ from
the average is an indicator of how feminised or masculinised you are.

Studies show that traditional "male" qualities such as assertiveness and skill at certain
mathematical tasks such as rotations are more likely to be found in both men and women
with a low 2D:4D. Low-ratio men have more sexual partners and more children than
high-ratio men, while the most fertile women are those with high 2D:4D. High-ratio
people of both sexes are most likely to be neurotic. Controversially, gay men seem to
have relatively high 2D:4D and lesbians have a low ratio. Your ratio can even predict
your susceptibility to certain diseases: women with higher ratios seem to be more
susceptible to breast and cervical cancer, while high-ratio men tend towards heart disease.

On a more positive note, anyone with a low 2D:4D is likely to have higher than average
aerobic efficiency, which means you should be good at endurance sports. So, if you are
deciding whether or not to sign up for the next marathon, head for the photocopier.

Kate Douglas

Bright future

"How smart are you?" "What kind of intelligence do you have?" "Test your emotional
intelligence". A quick Google of such phrases will bring up enough intelligence tests to
keep you occupied for weeks. When you get bored, you can even test your dog. Online
tests can be fun, but you shouldn't take the results too seriously. The validity of tests
claiming to measure emotional intelligence is questioned by many psychologists, for
instance, as is the whole notion that there are different kinds of intelligence.
For an accurate measure of your IQ, you will need to do a formal test such as the
Wechsler Adult Intelligence Scale III, which has to be given by a trained tester. This
measures different aspects of intelligence, such as verbal comprehension, processing
speed and working memory, but people's scores in each aspect are closely related, which
is why the test is said to measure general intelligence, or g. Although the use of such tests
is highly controversial, there is no doubt the results are a good predictor of how well
people will perform academically and in their jobs. What's more, as a New Scientist
reader, you can be confident of your result - you are damn smart.

Michael Le Page

Where do I come from?

Ever wondered if your parents brought the wrong baby home from the hospital? Or
perhaps you think you might be descended from Joan of Arc or the Irish King Niall of the
Nine Hostages? A host of companies now offer genetic genealogy tests. These can tell
you whether you share a recent common ancestor with another individual, whether your
family tree is correct, where in the world your ancestors came from and even from which
ancient human lineage you descend.

The results of such tests need to be treated with caution, however. Most look either at the
Y chromosome, which is passed from father to son, or at mitochondrial DNA, inherited
from your mother. Such tests tell you nothing about your father's mother, or your mother's
father, and so on. Go back 14 generations and you have 16,384 ancestors, but only one
provided your Y chromosome (if you have one) and only one donated your mitochondrial
DNA.

What's more, the accuracy of such tests depends on how many distinct variations, or
markers, they look at. An accounting professor in Florida recently hit the headlines when
he was told he was a direct descendant of Genghis Khan. As many as 16 million men
living in a broad swathe across Asia share the same Y chromosome, thought to be that of
the Mongol conqueror. The professor's result was baffling, though, because he is of
European descent. The mystery was solved when a second test looking at more markers
ruled out any relation to marauding Mongols.

Tracing geographical ancestry can also be difficult. It is only possible, for instance, to say
that you are from a specific tribe in west Africa if you have a pattern of markers unique to
that tribe. Yet most mitochondrial DNA patterns are found in all populations across west
Africa, making such tests a disappointment to many African Americans hoping to trace
their roots. A newer method called biogeographical ancestry estimation can provide a
more comprehensive picture. It looks at 200 or so markers on several different
chromosomes. The result might tell you, for instance, that you are 75 per cent western
European and 25 per cent Native American.

One thing is for sure: as sequencing methods improve and databases expand, genetic
testing will get cheaper and better, and reveal ever more about our ancestry.
Michael Le Page

Up close and personal

Few things are more personal than personality, and if you are curious about yours, there
is no shortage of ways to find out. Just don't expect anything too subtle. A questionnnaire
to "reveal" whether you are an introvert or an extrovert, for instance, might ask: "if you
meet a group of new people, do you (a) stick with your friends, or (b) mingle as much as
possible?". Yet tests similar to these are the staple diet of personality research, and they
can reveal a surprising amount about your biological make-up.

The idea that people can be classified into personality types is as old as civilisation itself.
The 2nd-century Greek physician Galen thought that personality was constructed from
four basic elements: melancholia, irritability, optimism and phlegmatism. Modern
theories take a similar approach, but generally break it down into the five "dimensions"
extroversion, neuroticism, agreeableness, conscientiousness and openness to experience.
Your score on each dimension, as measured by a detailed questionnaire, determines your
overall personality.

Over the past decade, personality research has been invaded by geneticists, molecular
biologists and neuroscientists, all searching for the "biological correlates of personality" -
actual physical differences between individuals that can explain the variation in their
personality scores. As a result the field has become much more grounded in hard biology.
Twin studies, for example, suggest that your genes have at least as much influence on
your personality as your upbringing and experiences. The genes themselves are also
coming into focus, with dozens of gene variants now linked with various personality
traits. Meanwhile, neuroscientists have discovered that there are real, consistent
differences in brain activity between people who score high or low on certain personality
traits. Personality testing may once have been dismissed as mere psychobabble, but it is
rapidly becoming an objective science of me.