Our Beautiful Genomes
A book I'm re-reading lately is My Beautiful Genome by Lone Frank. Essentially, I recommend it, and here's why.
My Beautiful Genome is an account of Lone Frank's journey into finding out what our genomes can say about what, who, and why we are. Or it could be more accurate to say, what scientists thus far understand about the what, who, and why. It's just over 10 years on since the Human Genome Project and Celexa laid out the human genome in its confusing glory- 23 chromosomes, 30,000 genes, 30 billion base pairs- and thanks to techniques, technology and t'internet, times have changed a lot since. The original human genome took 3 billion dollars and 13 years to complete. Nowadays a human genome can be sequenced for almost 1000 dollars in a few hours. So all right, supposing I have a spare 1000 dollars and connections to a world-class lab. Should I get a proof of my own molecular recipe?
Lone, a Danish science writer, sets out to see what can be seen. The easy narrative of the book follows her physical journey to various labs and doctors, countries and universities. It's low on jargon and enjoyable to read, a science travelogue imbued with Lone's own descriptions and inner thoughts, which add a hint of narrative drama to the interview scenes. James Watson gazes at her from thickly bespectacled "golf ball eyes" that are nonetheless "clear without a hint of the common confusions of old age". Lone admits her own faults, such as a blunt personality she feels proud of, while a friend disagrees- "It's cruel!". She describes her fear as she waits to find out if she has BRCA mutations that would show a susceptibility to breast cancer. She reflects openly on mental illnesses in her family and her own experiences in it. She is a likeable, cynical investigator.
The short answer from this book is that genetics still can't reveal much about the average person. However, there are plenty of hints. I daresay that still holds true. This book was published in 2010 so in scientific terms it's a little out of date, especially with a field as fast-moving as molecular biology. Still, I found plenty about the business and politics of genetics that I hadn't been aware of. And Lone's journey contains many interesting tidbits from various research areas that summarise how complicated genomes are. For instance, is human intelligence inheritable? Sure, studies indicate that 80% of a person's intelligence is down to genes. Which genes? Don't know! 20 years of study failed to find any 'IQ genes'. Best case scenario? In another few years, the researchers might whittle it down to a few hundred genes that explain 3-5% of a person's intelligence.
Another surprising fact is that where some genes are concerned, such as a gene that affects how likely you are to get diabetes, it matters who you inherited them from, your father or your mother. You could be more likely to get diabetes if you inherit this gene variant from your father. But you are less likely to get diabetes if you inherit this gene from your mother.
Lone explores the services of a few different companies and research schemes. The Genographic Project can tell you about your ancestry as well as answering bigger, older questions about where early humans lived and moved to. Then there is the big, attractive question of genes and health. Can your genes predict what diseases you might be prone to?
Lone receives a few interpretations of her genes. She has variants that increase her risk of lung and skin cancer, worry and depression, a small hippocampus and obesity. She also has variants giving her higher resistance to malaria and TB.
Lone admits to a few depressive episodes. On the other hand, Lone has always been slim, has a normal-sized hippocampus, and has never had skin cancer. Genomic medicine is still in its infancy, a mix of ambiguity and intrigue. This book cannot be used by a reader as a manual of certified gene variants, but it is scattered with interesting insights from the modern scientists who are wading through the legacy of the Human Genome Project.
Should people get their genomes assessed for probability of diseases? The research continues. Governments such as the UK are funding genomic medicine centres. There's also a scramble of entrepreneurship and commercial ventures. Companies like 23andMe are hoping to be the new Microsoft of personal genetics, offering direct-to-consumer genomic testing. Another genomics motion, deCODE is cataloguing the genomes of most of Iceland. But to me, it seems most of these companies do not provide value for money or time of thought. Studies such as by Erasmus University have shown vastly different results in the answers of your genome analysis, depending on which company you use. Processing errors have happened, resulting in some alarming results and alarming scenes at the consumer's homes. A ruling by the FDA has put a halt on health screening by 23andMe in the USA, but the company is branching out in the UK and Canada.
How long should it be before genomes screening for health is carried out, to prevent misinterpretation and misunderstandings? "It is inevitable that we will come to use it. It would be criminal to decide that people must not use this knowledge before we know how it will affect them biologically, psychologically, and socially," Kari Stefansson, founder of deCODE, argues to Lone. He believes the best way to treat disease is to prevent it, and all would agree. How far back can we prevent disease? Armand Leroi, a geneticist at Imperial College London, has judged the risk of finding disease by screening embryos for known mutations to be around 1 in 256. Lone points out that this level of risk is sufficient to justify cervical and breast cancer screening. Is the stage being set for large-scale embryonic screening?
Then there's the popular topic of how genes influence our behaviour. It's the classic nature vs nurture debate, a popular topic among biologists, psychologists, anthropologists, sociologists, parents, teachers, politicians, everyone... This debate is continually updated with increasingly detailed genetic data, and occasionally thrown to the public forefront by popular books like Richard Dawkins's seminal book, The Selfish Gene. His book launched a thousand debates about whether we were all fleshy vehicles steered by a control-box of self-replicating genes.
"As soon as people hear the word 'heredity' or 'genetic', it immediately gets transformed into 'unchangeable' somewhere in their mind, and that is not the message at all," warns Gitte Moos Knudsen, research director at Center for Integrated Molecular Brain Imaging at Copenhagen University. Lone has gone to see her to see how a personality questionnaire, brain scans, and her genes may be linked up. You'll have to read the book to find out what she discovers. But there's an intriguing mention of a study indicating a genetic basis for differences in behaviour between two major cultures. Gitte also points out that even ostensibly negative genes- like a variant linked to 'oversensitive' behaviour- must give the owner some advantage. Else why would so many people still have this gene?
The media gleefully reports behaviour-gene associations that make the best stories. A discovery of an 'infidelity gene', for example. But there is still no consensus on how to divvy up their own behaviour between nature and nurture, and I suspect there never can be. I think we do have free will. We also have brains housing that free will. Brains are made from both genes and general living. There will just be new and interesting ways to look at our brains from a genetic standpoint.
"People cannot stand the complexity of a nuanced problem. There is a huge desire to lean back and say, 'It's my genes, it's not my fault,'" sighs Kenneth Kendler, a psychiatric epidemiologist at Virginia Commonwealth University, during a discussion on genes, growing up, and psychology. He and Lone discuss the difficulty of linking a person's psychology to their genes. There is no single gene variant responsible for causing Alzheimer's, for instance. Most diseases will involve multiple genes acting in ways scientists still don't understand. The same issue will apply for behavioural traits, or psychiatric conditions like depression.
But studying behaviour from a genetic standpoint will help build up the overall understanding. Kenneth mentions the serotonin hypothesis as an example. The major theory is that depression is caused by low levels serotonin, a molecular messenger, in the patient's brain. Drugs that alleviate the symptoms of depression affect serotonin levels. But scientifically speaking, it's not known why this works. There is no 'normal' level for serotonin throughout the brain. Lone reveals a rather striking quote from David Healy, a psychiatrist specialising in antidepressive remedies. "The theory that serotonin levels are the cause of depression is as well founded as the theory of masturbation causing insanity." This doesn't mean we should toss out our antidepressants or stop the self-love, though. It means that the picture is complex and genes are part of the complexity.
Studying genes in detail could also provide a new way to monitor psychiatric therapy. "Psychiatrists used to ask people endless questions about their mothers, as if we could make good predictions on that basis. At least, genes are objective," said Daniel Weinberger, neuroscientist at NIH. And it does not have to stop at what genes each person has from birth. Epigenetics adds another layer of complexity. Studies have shown that life experiences can alter how your genes behave. In a nutshell, this is caused by life adding molecular labels onto your genes. Moshe Szyf, epigenetics expert at McGill University points out benefits of tracking the labels. "If we know the epigenetic signatures and markers - for abused children, for example - we can design behaviour therapies, talking therapies, and study whether they work. Determine whether they remove the markers in question." This hints that future psychiatry could be a synergy of epigenetics, genetics, behaviour and therapy.
There's also a scramble of entrepreneurship to make money out of genes and love. GenePartner claims it can help you find your ideal social and biological partner. To fall in love may lead to having children, and children are the combination of you and your partner's genes. Do genes secretly steer our choices? Can knowing our genes help us choose the best partners? The enterprise is based on a few scraps of intriguing science. Immune system is coded for by genes, and everyone (save clones and twins) has a unique set of immune genes, known as HLA genes. Zoologist Claus Wedekind noticed that many animal species sniff out mating partners who have the biggest differences in HLA genes from their own. The suggested reason is that such pairs produce offspring who have particularly varied immune systems, and are more likely to resist local germs. This tendency has also been noted in humans, in a handful of studies, starting with Wedekind's own study in 1995. Statistically speaking, women prefer the smell of men with the most different HLA genes, marriage choices in some communities appear based on this effect. It's an exciting thing when pieces of scientific evidence can be tied together with evolutionary reasoning. Once I explained to a new boyfriend that given our respective ethnic backgrounds, our HLA genes were likely very different, ergo another reason why our relationship was destined to succeed. I can't understand why he found this so amusing.
On the other hand, Craig Roberts, behavioural ecologist at University of Liverpool warns, "It's a scam. We're not at the stage where we can say HLA genes make a practical difference." There are other factors to consider here than the immune system, and a few other studies go against the varied HLA connection. Again, statistically speaking, studies show that people tend to prefer faces of others who have similar HLA genes. And has anyone studied if human children from varied HLA matches are actually better off?
Many people are afraid of genetic discrimination in the future. This book goes a long way to explaining why this is unlikely to happen by describing the existing science and viewpoints. Of course it remains a risk, which is why people need a gene lexicon containing terms like 'risk' and 'potential', rather than terms like 'good' and 'bad'. Towards the end of the book, Lone discusses how it is thought both biology and sociology- a new 'biosociality'- needs to be a large part of the consciousness of the future. Understanding of genetic difference may show where lifestyle changes could have the greatest impact. Those with predispositions to stress from poorer backgrounds may benefit more from mentoring, or those at greater risks of certain illnesses will need more assistance avoid these things. It will require a sensitivity of thought by any politicians passing legislation, and a malleability of 'nature vs. nurture' thinking on everyone's part. Lone's view is that in understanding more about genomes, we will also come to understand and appreciate diversity.
So at the end of another enjoyable read, would I want my genome sequenced? I certainly would not be afraid to have it done. Will I have it done? I'm in no hurry. I don't think the science is well understood enough yet from an academic perspective to get any useful results. I'm not yet inclined to approach a company to interpret my genes. But it's getting closer, and I suppose, then, so am I. One day, I'll learn more about myself. It's nice to have such things to look forward to.
My Beautiful Genome - a TED talk by Lone Frank
Not quite a blog, but things that I have written. Please note - these writings are unedited, for the purposes of flexing my fingers, and no doubt contain grammatical errors and carelessness of expression I wouldn't allow in professional writing.