Hør professor Jan Madsen fra DTU Compute forklare, hvordan deres lab on a chip fungerer, når det analyserer væsker. https://universe.ida.dk/techtopia/episoder/techtopia-74-humle-biochips-og-toiletter-paa-high-tech-summit/
Wired fylder 25. Samtidig er det også 25 år siden, at jeg mødtes med Hanne Møller, Anders Kjærulff, Peter Hesseldahl og Poul Erik Heilbuth for at lave konceptet til Harddisken, der desværre døde som 23-årig. Hvad Wired angår, så skrev jeg kortvarigt og i beskedent omfang for deres britiske udgave i 2011.
Jeg skrev også en lang feature om Lone Frank, som Wired så ikke ville have alligevel – her er den:
What her beautiful genome was hiding
By Henrik Fohns
Who am I? The universal question. Thousands of people continue to ask themselves this question, when they look in the mirror in the morning, and see a body decaying day by day, moving ever closer to the grave.
When Lone Frank looks at herself in the mirror she sees not only her own reflection but also the memory of her loving and beloved late father, who suffered from alcohol abuse and depression. And she sees her mother, who died from breast cancer in her early forties. Lone Frank knows that the slender 44 year old body in the mirror stores information about all of this. While others might just brush their teeth and get on with their working day, Lone wants to unlock the secrets of her body. The good news is that she knows how to do it. She has become her own test person.
On her desk in the living room she keeps a small metallic grey hard drive. It arrived in a bubble wrap envelope from China. It does not look like much, but it contains Lone Frank’s genetic information. Her full genome. Sequenced by BGI – Beijing Genomics Institute. She is one of a select few across the world, who have had their full genome sequenced. Something which is still pretty expensive, but the price is coming down at a rate faster than Moore’s law.
The most common form of DNA sequencing is through the tests, which you can buy via websites like 23andMe and DecodeMe, called consumer genetics. You have the DNA contained in your saliva or a scrape of your inner cheek sequenced at a lab, where they search for certain SNPs – single-nucleotide polymorphism – to ascertain whether or not you are disposed for a number of diseases and traits.
The 44-year old Ph.D in neuroscience, author and science writer at the prestigious Danish weekly Weekendavisen – Lone Frank – has been through all that. Now she has arrived at the gate of the final mystery of the “who-am-I” quest. Her full genome in a box. 21GB of information on a hard drive from China.
“I wasn’t a part of the internet revolution or the early Commodore 64 movement, but I will be a part of the open genetics movement,” she says firmly.
It is no coincidence that she makes this comparison. The genetics movement can easily adopt the old internet catch phrase “information wants to be free”. The genome is nothing but information. Three billion base pairs of genetic information.
“Whether you are a flu virus, a slime mould, a manatree, or a manager, your genetic code contains the same components. Life is not based on chemical substances or molecules but on information, pure and simple,” says Lone Frank quoting her new book “My Beautiful Genome”.
Genetic information is like software programs and data which are expressed in binary code and can be read in the same way by different computers, be it a network of servers, a sleek Mac Book Air or a smartphone. The genetic code’s message is the same. Similarly, a brain cell in a human being reads and translates “gene language” in much the same way as a yeast cell.
When Lone Frank stands in front of the mirror, she does not only see her pronounced nose from her great-grandfather, the thin, bony frame of his wife and her thin lips inherited from her paternal grandmother. She also sees the non-visible heritage of cancer and depression.
Partly due to professional interest – partly because of personal interest fuelled by her father’s recent passing, Lone Frank started a search for her true self. She had already taken the gene test offered by deCODEme, because she was approaching her early forties, the same age at which her mother had died from breast cancer. The test deemed her out of immediate danger. But during a follow up interview with the CEO and founder of deCODEme – Dr. Kári Stefánsson – she learned that she was nowhere near certainty about her condition. It was only risk assessment.
Further medical examinations did not reveal any more, but her family history still pointed at a higher risk, simply because SNPs which are still unknown could code for cancer.
From her father she has inherited a higher risk of peripheral arterial disease (PAD), which is not surprising, because it was exactly what he died from. It means no smoking and minimizing the intake of cholesterol.
And then there is the part about depression.
Speaking to Wired she sits on her sofa. In the window behind her is a mood lamp, which is meant to heighten your mood during the long and dark Danish winter, now approaching rapidly after a wet and grey summer. She seems in control, but earlier the same morning she was lying on the sofa, screaming that she just couldn’t handle life anymore. She has had several episode of clinical depression, which required drug treatment . Of course this raises the question; Does recurring depression and a consistently dark outlook on life derive from a few unfortunate genes, handed down from two different families? Her family history is a sad one with relatives suffering from depression and suicidal tendencies.
“Mental illness has no biomarkers. The shrink says: “I believe that you suffer from this or that”. It is like medicine from the 18th. Century. The only difference is that today they have medications, but it remains trial and error,” says Lone Frank, who has been on Prozac several times. Something she wishes to avoid though her psychiatrist thinks it is for the best.
From a psychiatric test Lone Frank has learned that she has a certifiably “disagreeable” personality, but she wants to go beyond questionnaires and into biology.
The consumer genetics tests from 23andMe and deCODEme do not test genes which are related to behaviour or the psyche.
But researching the subject Lone Frank finds out that studies suggest a heritability of depression of around 40 percent.
“Most of it is still a mystery but a few genes have been singled out as having an effect and not surprisingly they play a role in the brain’s chemistry. Certain variants of these genes tweak the brain’s physiology to make it more alert to negative emotional stimuli and less resistant to stress. Effects that clearly reveal themselves in experiments where volunteers of different genotypes are submitted to brain scans,” Lone Frank says.
On learning this she decides to have her genes tested. Armed with 14 tubes of blood samples she goes to the Centre for Integrated Molecular Brain Imaging at Copenhagen University Hospitals (CIMBI) to learn more about how effectively her genes code for proteins that are related to the neurotransmitter serotonin. The research team test twelve different genes in trying to find a relationship between anxiety, depression and genes. Lone Frank also has to answer a couple of hundred questions covering all corners of her psyche.
The test of Lone Frank’s genes confirms her suspicion.
“I have a cocktail of all the worst genetic variants. The ones connected to a low stress tolerance, social sensitivity and depression.”
The COMT gene, where Lone has a double dose of the “worrier” variant, which inclines her brain to handle emotional strain poorly, and her BDNF variants, which turn up her reaction to stress, is a bad combination. On top of that, there are two copies of the less efficient MAOA variant, which disposes a person to aggressive and impulsive behaviour – or depression, in the case of women. Finally, she is saddled with two copies of the short SERT variant, which is a notorious guarantee of psychological abrasion. Or as her boyfriend frames it: “It’s remarkable that you haven’t ended up in a closed ward or on early retirement.”
“It’s a cocktail of all the bad stuff,” she admits with a deep sigh.
The uncanny thing about this knowledge is the fact that you cannot do anything about it. The statistics tell you that these genes seem to be connected to a higher risk of depression, but it does not necessarily mean that it is the case for every carrier.
“Associating genetics with mental health is a provocation to a lot of people, because you can’t do anything about it,” says Lone Frank.
And yet she has gained inside knowledge of herself. Reading about the subject she can compare other research to her own profile and her life in general.
“Now I know it’s not only the world being evil, but I do not have the same high stress tolerance as my colleagues at the paper. My reaction to stress is partly a genetic condition. I can now see my own life through another prism. When you start to look at your genome, you find out that the deck of cards you were dealt with is finite. You have to play these cards the best you can – and the 8 of Clubs is not the Ace of Spades. That is just a fact of life,” she says.
These days Lone Frank tries to make her life less stressful. She tries to distinguish between the actual situation and her ability to cope with it.
“I have become better at looking at the situation from the outside. And there is an upside to the vulnerability coin. Researchers scrutinising the highly sensitive among us are finding that these delicate flowers may be more at risk, but at the same time their sensitive brains are better at noticing nuances and catching details. They may process information slower than more robust types but they also do it more thoroughly.”
Which leads her to further experiments.
The Danish pharmaceutical company Lundbeck is conducting a preliminary study in biomarkers. They try to test the activity of selected genes in order to diagnose conditions such as post-traumatic stress disorder, borderline personality disorder, and, especially, depression, and Lone leaps at the chance to become a research subject one more time.
Lundbeck is interested in how her organism chooses to interpret her genes. To get this information, they isolate white blood cells and calculate the number of RNA molecules, which are transcribed from a group of selected genes and provide a measure for how much of the corresponding protein can be formed.
This is not traditional genetics, it is epigenetics. Epigenetics is all about the strange and wonderful things that can’t be explained by genetics itself. It is presumably in epigenetics that the encounter between inheritance and environment will be resolved.
“Until relatively recently most scientists believed that epigenetics was not relevant for adults – it was a phenomenon largely restricted to embryos, where the genome was programmed in ways that would govern the rest of the organism’s life,” says Lone Frank.
But epigenetics is interpreted and reinterpreted all the time. How does the body handle genetic information?
Cancer has many epigenetic factors. Some cells are turned on and some are turned off causing cancer or in the case of other genes – depression. What Lundbeck is trying to find, is a way to use an epigenetic test to define what kind of drugs people should take to turn cells on and off and thereby prevent the outbreak of certain diseases.
What Lundbeck and Lone Frank are looking for is a genetic signature. Like many cancers, a mental disorder could leave a signature that shows which genes have been turned on and off. This means that even though Lone Frank does not have a depression currently, you can still read from her pattern of genetic expression that she did have one and what happened.
Based on this pattern Lundbeck hopes to develop drugs which can turn genes on/off and thus treat the mental condition.
“In the future when you have a full genome sequencing you will receive concurring updates on stuff like your intestinal flora and probably also about epigenetics. Have some important genes been turned off or on in certain cells since you were last checked?” says Lone Frank.
At the end of 2010 the list of published, freely accessible genomes stood at two dozen. Research institutions hold unpublished records of almost two hundred people more. The 1000 Genomes Project is sequencing the genomes of over a thousand volunteers for public use, and the even more ambitious Personal Genome Project is endeavouring to collect a hundred thousand genomes. These genome collectors are pursuing all types of variation.
We humans do not just carry small, discrete SNPs, with an A in one and a G in another, ready to be noted and entered on a database. We also carry far more drastic mutations: large pieces of DNA may have fallen out, been duplicated one or more times or simply have moved around and landed in different places in the genome.
When a person is tested for a number of known SNPs a gene chip is used. Inside this ingenious, postage-stamp sized device, small pieces of DNA are placed, which flutter like sea grass on the ocean floor. Current gene chips can typically test between half a million and a million SNPs, drawn from across the landscape of chromosomes. This massive quantity of data is fed directly into a computer, and software is used to find patterns in the chip’s genetic observations.
The question posed by bioinformaticians is basic: Does one or more SNP recur far more frequently in sick persons than in persons, who are well. If it does, the mutation is considered a marker associated with the disease.
This is the kind of information that Lone Frank received on the hard drive from China and she frankly admits that she could not make anything of the information on the small hard drive. It stayed a black box of mystery to her until she handed it over to a friend, who is a bioinformatician.
In Denmark Lone Frank is also known in public for her fierce quarrels with religion. She is commonly featured in debates about abortion rights and ethical questions related to science. She has appeared on stage with the likes of the evolutionary biologist and author Richard Dawkins and the biology professor P. Z. Myers. This has made her a sort of heroine in atheist circles.
The bioinformatician Stinus Lindgreen, who has agreed to unlock the secrets of the Chinese hard drive, is also chairman of the Danish Atheist Society which fights for a separation between state and church in Denmark. Furthermore he runs an atheist brewery called Djævlebryg (the Devil’s Brew) that among other beers produces an imperial stout called Gudeløs (Godless), which is also exported to America. Every time someone buys a bottle of Gudeløs, they donate one Danish krone (12 pence) to the Atheist Society.
Stinus Lindgreen works mostly on sequencing old DNA from 4000 year old inuit or 100 year old aboriginals. The sequencing is done by BGI, so the tall ponytailed atheist is familiar with the type of data he received from Lone Frank.
“It’s a jigsaw of three billion base pairs that I have to assemble to a full genome and find the variants. I do not make the risk assessments, that’s for biologists to do, all I do is assemble the picture,” he says, while sipping coffee from an Atheist Society mug in his small office at Copenhagen University’s department of biology.
On his computer monitor – 42 inches – we learn, what Lone Frank sees in her mirror every morning. On the screen Lone Frank has become only numbers and capital letters arranged in rows, which to an outsider make very little sense. But Stinus Lindgreen can quickly point out the interesting places, where mutations occur.
He has taken the information from BGI and compared it to, what he calls “a reference genome”, which is the data from the human genome project available for free on the web. He is now looking for places in Lone’s genome which are different from the reference genome. He is also doing a quality check of the data.
The DNA sequencing is organized in eight lanes on a plate of glass. One lane is reserved for quality testing; the seven remaining lanes are filled with DNA from the test person. When Stinus Lindgreen is putting the puzzle together, he is searching for what looks like a variation from the reference genome, but in some case it might just be a sequence of poor quality.
“I expect that for every thousandth position in a genome, I will find a difference. If the sample is of a high quality, I know for certain that this really is a mutation,” Stinus Lindgreen explains.
The one in a thousand variations are what researchers are looking for, when they try to unlock even more secrets of our bodies. When consumer genetics companies produce their results and you browse your genetic data in a Facebook-like interface at their website, they only tell you about the very small number of genetic variations, which so far have been proved to play a part in the occurrence of diseases and traits. They look for variations known to have certain effects.
What Lone Frank hopes to do with her full genome sequencing is to use it for future checks. Whenever new variations are discovered, Lone Frank’s genome will be ready to be referenced. If new research about cancer or depression turn up, she is ready, due to the content of the small Chinese hard drive.
Recently Danish and Chinese researchers have found more than 50.000 new DNA changes (mutations) in the genome. Between two and five percent of the 200 Danes who was surveyed in the test have these mutations. The researchers looked for the inherited elements in the development of a number of diseases, including blood clots in heart and brain, obesity and type 2 diabetes.
When new research like this is published, Lone Frank does not have to wait for the consumer genetics companies to offer tests that include the new SNPs. Stinus Lindgreen can run a reference test on Lone’s genome right away to find out, whether she is also a carrier of the newly discovered mutations. That is why she finds it so important to have a full genome sequencing.
To most people this is futurism. What about the rest of us, who have not gone this far? How will the new world of genetics affect us in the shorter run?
For Lone Frank there is little doubt.
“Right now the FDA (US Food and Drug Administration) recommends for 70 different named drugs that you have a SNP test before you start using them. But surveys show that only one percent of American doctors use DNA testing before writing a prescription. This is important, because one in every five patient dies due to wrong dosage.”
If you do a SNP test of certain genes, you can determine, how your body will translate certain drugs.
“Society needs to educate doctors. There is a lot of debate about regulating the market for consumer genetics, but there are already many test possibilities, which can be used for treatment and prevention. It is still an emerging technology, but it also took quite a while for computers to be recognized,” Lone Frank says and continues:
“The genome is not a straight jacket but a soft pliable sweater. The more we know about our deepest nature, the better we can shape, form and transcend it.”
She sees herself as a modern day astronaut. But space is no longer the place. Her own body is her final destination.
“My Beautiful Genome: Exposing Our Genetic Future, One Quirk at a Time” by Lone Frank is published by Oneworld
Henrik Fohns is host and editor at the radio show Harddisken at the Danish Broadcast Corporation in Copenhagen
DØDSFALD: John Perry Barlow døde i sidste uge 70 år gammel. Manden som skrev manifestet om det frie, uafhængige internet “A Declaration of the Independence of Cyberspace” i 1996.
“Regeringer i den industrielle verden, I trætte giganter af kød og stål, jeg kommer fra Cyberspace, Sindets nye hjem. På vegne af fremtiden, beder jeg jer fra fortiden om at lade os være i fred … I har ingen rettigheder her, hvor vi samles.”
Han skrev manifestet en nat på World Economic Forum i Davos som et svar på verdensledernes arrogance og digitale uvidenhed og som en protest mod daværende præsident Bill Clintons Communications Decency Act, der skulle regulere pornografisk materiale på internettet.
John Perry Barlow var også medstifter af den elektroniske borgerrettighedsbevægelse Electronic Frontier Foundation og dermed konsekvent fortaler for ytringsfrihed på nettet.
Hans projekt handlede i høj grad om, at vi skulle genopfinde os selv i en ny virtuel verden uden regeringskontrol og nationale grænser.
Du kan høre om hans manifest – og mange andre tekonologimanifester – i Techtopia #25.