The Best Australian Science Writing 2015 (11 page)

Despite the obvious utility of such information, there is a serious debate in the medical and genetics communities about whether people should be allowed to access their own healthrelated genetic data. In 2013 the FDA suspended the health service offered by 23andMe, one of the main consumer genetic companies in the US. After many months of discussion, the regulatory body permitted 23andMe to offer one of their original battery of tests to the public. It is unclear when, or if, the full service will be restored. At issue is the accuracy of the information being offered and the belief that genetic information should have special safeguards placed upon it. This is quite clearly true for Mendelian diseases. What if consumers discovered terrifying news about themselves or family members? The risk is not to be taken lightly. But modern genomics has also shown us that the majority of risk information to be gained from the genome is not Mendelian but relies on many factors.

Robert Green, a physician-scientist at Brigham and Women's Hospital and Harvard Medical School, told me that much of the fearful attitude toward genetic information was formed in the cauldron of genetic counselling. ‘Huntington's disease has been the paradigm for genetic testing for a long time. It's really not a very good paradigm, because there's a certainty to it, and most other genetic, even Mendelian genetic, variations are not fully penetrant.'

As with almost every aspect of the practical use of genetics, there is currently more opinion than research into many basic questions. Is the discovery of a significant genetic risk by an
individual outside the medical establishment as potentially harmful as many people fear? Preliminary studies have shown that what researchers suspect will be devastating news for people may not necessarily be so. Green used to work with the design and implementation of drug-testing clinical trials, so he decided to test the notion of treating information as if it were a drug: will the information cause benefit or harm or both? The particular information shared in his study was whether subjects had a common variant of the APOE gene, which is connected to a high risk of Alzheimer's. ‘We designed the study carefully with many safety features and we initially did the study with the minimum number of people necessary to answer the question. The results of this study and several others which eventually evaluated over 1000 subjects was that among volunteers, disclosure of genetic risk information, even for a disease as frightening and untreatable as Alzheimer's disease, was quite safe,' he said.

As far as direct-to-consumer testing results are concerned, there are relatively simple ways to filter information. 23andMe graded its results according to how confident it was of the science, and it shared those confidence levels with its customers. If the genetic risk factors for a serious condition were analysed, customers had to specifically choose to ‘unlock' their results, so it was not possible to simply stumble upon them. (23andMe did not test for Huntington's disease.)

When I asked Jeff Carroll what he thought of direct-to-consumer genetic testing, his main concern was the unregulated testing of children. With Huntington's, if there is no question of early onset, it is considered profoundly unethical to test children, as a positive result would severely impact the way that child was treated and how he would feel about himself. Only a child himself, once he reaches the age of 18, is legally allowed to initiate such a test.

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Even if people aren't harmed by learning about their personal genetic risks, critics wonder if they will use the information to improve their lives, to support the health of their families, and to reduce the enormous costs of health care in the developed world. Indeed, small studies have shown that there is not a lot of proactive response when people are informed about their genetic risks. In one study subjects were found to have a higher than normal risk for type 2 diabetes. It is well known that onset of the disease is affected by lifestyle, yet even when the at-risk subjects were given information about their susceptibility, many did not adjust their fat intake or increase exercise or consult medical specialists to minimise their risk.

The irony here is that this finding supports the argument that most genetic information is not exceptional and should not be treated as such by regulators. It's well known that any kind of health information – whether it is heart related, weight related, or aging related – often has little impact when it comes to getting people off the couch. Yet no one is suggesting that the medical establishment should stop trying to communicate information about exercise and food to the public, only that it needs to find better ways to share it.

One researcher surveyed members of a poor community and asked what their response might be to information about their genetic risks. Many were extremely fearful and superstitious, and one man told the researcher that he didn't want to know his results for fear that simply learning about them would somehow cause the condition to occur. Clearly, education is necessary to help many people understand that genes are almost never by themselves fate. One of the most direct ways to do this is to help people become acquainted with their own genome.

So far there has been little penetration of genomic data into
the medical community. Customers of 23andMe and other direct-to-consumer companies describe taking their reports in to doctors who will often not even glance at the data. ‘How do clinicians cope with a genomic report? How should a report be designed for them? How will they cope with the targeted findings, and how will they cope with incidental findings?' asked Robert Green. All of these questions lag behind the rapid production of massive amounts of genomic data. ‘Why should genomic information be different than any other sensitive medical information a physician handles, like medical history, psychiatric history, substance abuse, HIV positivity, sexual orientation? Physicians are privy to all sorts of sensitive information and have responsibility for privacy and translation to their patient,' Green observed. ‘Unless medicine is foolish and abdicates its responsibilities, it's really incumbent upon conventional medicine to sensibly integrate this into the practice of medicine.' The most important requirement for direct-to-consumer testing is that the information it provides about genetic risk be reliable. In a number of studies agencies of the US government and scientists have compared the results of genetic reports from different testing companies, and in all cases there was divergence in how the companies analysed the results. Some differences will be inevitable, but for certain disorders the same genome, depending on the company, was reported to be high-risk, low-risk, and no-risk. For critics that finding was damning enough to advise against any genetic testing.

Ultimately anyone who participates in personal genetic testing, whether it is historical or health related, should understand that these are thrilling, rich, but early days in this particular science. This moment is to the genomic future as the 1970s and early 1980s were to computers. Back then Steve Wozniak, Steve Jobs, and the unsung heroes of the digital age were tinkering in their garages with proto-personal computers. Now most people use not one or even two but many digital devices on a daily basis.
If someone turned off all the computers tomorrow, the world would stop. People who use genetic services need to tolerate a degree of uncertainty, as advancements will be made. Yet there will always be some uncertainty where the genome is concerned.

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The sharp edge of a genetic legacy is a fatal Mendelian disease. But this is just one of the ways that genes affect our lives. There are recessive diseases and complex disorders whose frequency is affected by ancestry. There are traits that shape our appearance, which people react to, which then shapes our reactions, feelings, and behaviour. Being a creature that is formed from the genomes of two other creatures via a lottery of bits has many consequences, none of which can be completely understood without taking into account our DNA.

DNA tells us that we are creatures of chance and fate and that no one has quite the same mix of the two in his or her life. We think of ourselves as essentially whole, but when we look at our genome, we see that we are composed of many fragments stuck together. Many of our bits have different histories, and they each bring different probabilities into our lives. ‘Nobody is going to have a complement of alleles that is totally perfect,' Jeff Carroll observed:

There is a particularly Western tendency to think that we're pristine or untainted … that we can go off and do anything we want if we work hard enough and nothing can stop us except our own efforts. It's a really, really excellent lie for us all to believe in. But we need to know it's a lie … There are those of us that have extreme cases … [but] even with one of these extreme cases you can still be a useful human being and do good work.

We are also creatures of changeless truths and of interesting possibilities. Once you are born, your spot in the tree of humanity is fixed. You will always have emerged out of everything that shaped the tree before you – the biology and the history. The millions of bits that initially made you – all the cultural bits and the genetic bits, each with its risk factors, predispositions and probabilities – are shaped by that past.

As you develop and grow older in whatever world you live in, the calculations change. Your family, the history of your community, your government, and even your food alter them. You alter them. Why not find out what the calculations are? Doing so will not guarantee that you will learn what will happen, but it may help you to consider the possibilities. Your genome is just the first hand that life deals you. How you play it is up to you.

Messages from Mungo

How I rescued my brain

Why aren't we dead yet?

Maths explains how lobsters swim

Clare Pain

Scientists have uncovered how crustaceans coordinate their curious Mexican wave-style swimming movement.

In a paper for
Proceedings of the National Academy of Sciences
, a team of four mathematicians and a biologist from the US have shown that the creatures' technique is highly efficient and hard-wired in a simple neural circuit.

Crayfish, including yabbies, prawns, lobsters and other crustaceans, swim using a Mexican wave-style motion of four or five pairs of small paddle-like limbs called ‘swimmerets', explains lead author and mathematician Professor Timothy Lewis of the University of California, Davis.

The work is one of only a few examples where a neural circuit underlying a particular behaviour has been understood.

Powering forwards by waving backwards

Each paddle does a ‘power stroke', which pushes water backwards, followed by a ‘recovery stroke', in which the paddle is pulled forwards (in a curled position to reduce drag), ready for the cycle to start again.

The paddles can be moved quickly. ‘The frequency can vary from less than one stroke per second to as much as ten strokes per
second,' says Professor Brian Mulloney, the biologist on the team.

Surprisingly, the Mexican-wave starts at the paddles farthest back on the abdomen and travels towards the head of the crayfish. The wave occurs because each pair of paddles starts their ‘power stroke' a quarter of a cycle later than the pair of paddles behind them.

Using computer modelling of fluid flow, the team examined three ways a crayfish might swim: moving its paddles in unison; a Mexican wave travelling from head-to-tail; and a Mexican wave travelling from tail-to-head (as actually occurs).

‘When I first started thinking about it, I thought the head-to-tail one would be the one with most mechanical advantage, but the modelling showed that wasn't true,' says Lewis.

The researchers found the tail-to-head Mexican wave was 30 per cent more efficient than moving the paddles in unison and between 300 per cent and 550 per cent more efficient than a head-to-tail wave.

Hard-wired to wave

Having found that crustaceans swim very efficiently, Mulloney dissected out the crayfish neural circuit that is known to control the swimming movements, and then he and colleagues used mathematics to analyse the circuit.

In the circuit, each paddle is controlled by a pair of nerve cells that mutually inhibit each other, explains Mulloney. One neurone controls the power stroke and the other the return stroke. The result, he says, is a rhythmic pulse, rather like a metronome, which keeps switching the paddle between power and recovery strokes.

Since there are four or five pairs of paddles (depending on the crustacean), you can think of the complete neural circuit ‘as four or five pairs of metronomes,' says Mulloney.

The Mexican wave happens because each pair of metronomes
controlling a pair of paddles is wired to the metronomes of the next paddles along – in a very specific and asymmetrical way.

The mathematics showed that this asymmetrical wiring was ideally suited to stabilising the quarter-cycle delay in the timing of adjacent paddle pairs that makes the Mexican wave.