My Beautiful Genome

by Lone Frank

  “We don’t talk about that sort of thing,” says the chief surgeon, who gets an almost indignant look in her eyes. “This is genetic counseling, and my job is to make sure that the person I’m counseling understands the options and chooses what is right for them. I have no agenda or position on what they should do. All that about having the breasts removed – and the press love to write about that – very few end up choosing that. It’s a big decision and something that people resort to in families in which a slew of young women have died and in which, after conversations here and with breast surgeons and plastic surgeons, a woman figures out that this is what she wants. Then we support the decision.”

  “It is a procedure that takes more than a full year,” adds Gerdes in a steady voice. “First, they remove both breasts and nipples and place a tissue expander under the breast muscle. They pump a little salt water into them at the beginning and, over a few months, they are gradually expanded. Then, you have silicone implants put in and a reconstruction of the nipple done with tattooing.”

  “Yes, it’s a question of whether it’s worth all that trouble at my age,” I say, hoping to get another reassurance that I’m still young. It doesn’t come, but the chief surgeon suddenly broadens the conversation to include a new organ.

  “We also have to remember that there are ovaries to take into consideration. Mutations in BRCA1 especially increase the risk of ovarian cancer significantly and can provide for up to a sixty percent risk.”

  Okay, annual checkups for the ovaries as well.

  “But it’s a fact that the ovaries are not as easy to check as the breasts. And ovarian cancer is much more difficult to treat than breast cancer. The mortality rate is quite high. In fact, they recommend removing both ovaries preventively.”

  I hadn’t thought about that.

  “The extent to which they provide hormone treatment to avoid premature menopause is a slightly ticklish question,” Gerdes says. “Estrogen is one of the things that stimulates the development of breast cancer. On the other hand, studies show that the removal of the ovaries in women with BRCA1 mutations helps protect against breast cancer.”

  Still, I would like the test. When it comes right down to it, I have no children, so at least there won’t be others who will be touched by the result.

  “So, we need to look at your family tree,” says Kjergaard, tracing a finger from my mother to her brother, my uncle, and then from him to his daughters, my two cousins. “If you have inherited a mutation from your mother, there is a fifty percent chance that her brother carries the same mutation. And if that is the case, there is a fifty percent chance that your cousins do as well.”

  “And you have a brother,” her boss adds. “He might also carry a BRCA mutation that we find in you and, in him, it might give rise to an increased risk of prostate cancer that he can pass on to his children.”

  I burble something about contacting my brother if it should become relevant. My cousins, as well.

  “Yes, because that is something we can’t do,” Kjergaard says, getting up. “So I’ll order a blood test,” and it’s as though there is something final embedded in her words. “You can go down and have a blood sample taken. Then, we’ll call you in for consultation when the genetic analysis has been done, which could take a couple of months.”

  She sits down to enter my data into the computer system but then abruptly turns toward me.

  “When you hear from us, you won’t be able to see from the wording of the letter whether there is something wrong or not – we only talk about that face to face.”

  I shake hands with both of them, and everyone smiles, unconcerned. But I think to myself how the little “see you later” that finally slips out sounds kind of strange.

  THE WARD WHERE blood samples are taken on the ground floor runs like a well-oiled machine. You take a number and sit down beside the other patients, with their greyish skin, hospital gowns, and portable stands for intravenous drips. When your number comes up, you are called into a little booth, where a frighteningly efficient lab worker pokes a hole in your vein and drains the necessary blood. It takes at most two minutes, and not a word is exchanged before you’re sent off again.

  Outside in the real world, I forget my bicycle and get almost halfway home before I think of it.

  Later, I run through my conversation with the two doctors and play out the different scenarios. Suddenly, it’s as if the only realistic outcome of the test is that I have BRCA mutations and therefore have to take a position on the available options. In my inner ear, I can very clearly hear Kári Stefánsson say “bilateral mastectomy” without the slightest wobble in his voice.

  But could I voluntarily go through the whole thing, the breast operations and the removal of my ovaries, not to mention the consequences of early menopause? To get cut up crosswise to Sunday and come out at the other end ready for grey hair and liver spots? On the other hand, how would it be to live in the constant fear that the next checkup will reveal the insidious disease?

  At night, I’m seized by some bizarre ideas about the two BRCA genes and the proteins the genes code for, whose job is to carry out ongoing repairs to the genome. In a series of cartoon-like images, I envision how chromosomes sustain harm. When the back of the long DNA molecules is broken, a system is set in motion to put the strands right again; BRCA1 and BRCA2 take on this heavy burden. But if the genes are mutated, the proteins are handicapped. It is like being assisted at the roadside by a blind car mechanic with one arm. Sometimes it goes well, but sometimes the repairs go wrong, and very rarely something so harmful will happen that it destroys some of the control mechanisms that keep the cell from growing wildly. The result is the first uncontrollable cancer cell, which just keeps growing and growing.

  When these ideas start metastasizing, I repeat a saying that, in some way, always seems comforting.

  Death must have a cause.

  It was a slogan repeated time and again in my family. We were not afraid of dying, because the consensus was that, in the end, it was not death but life that was a vale of tears. As my father used to say with a wry smile:“I’ve got no problem with death, I just hope there’s no reincarnation.”

  Thus cheered, I remind myself that none of us are free of mutations and genetic weaknesses – the flawless genome does not exist. This is a truth that will become blindingly clear as more advances mount in the world of personal genetics. The more genomes are mapped, the more people there will be who purchase tests and gene profiles, and the more accepted the idea of the imperfect will become.

  Of course, you might be able to turn angst and eternal worry upside down. You could ask whether we might use our familiarity with our personal dispositions to illness to reconcile ourselves with the idea that we will one day depart from this life. I think about this quite a lot.

  Sometimes the waiting seems infinite and unreasonable. Because I know that sequencing the two BRCA genes takes no longer than a week with today’s technology, the system’s two-month waiting period seems especially outrageous. Finally, I call Kjergaard to ask whether something might happen soon. She passes the question on and reports back that the answer will come next week. She probably also senses a certain anxiety, because she offers to save time by notifying me about the appointment for our final conversation by e-mail instead of by letter. I thank her.

  The e-mail arrives three days later.

  “Your results are ready. You may come by my office on Monday at 3 p.m. We recommend that you bring a relative to the consultation.”

  It’s Friday. All weekend I’m plagued by diarrhoea.

  “YOU LOOK A little stressed,” says the chief surgeon, placing a piece of paper with two signatures in front of me. “But, fortunately, I have good news for you.”

  Response to mutational analysis for hereditary mamma (ovary) cancer (BRCA), it reads on top in large letters. Below the conclusion is written in small letters: No pathogenic mutation in BRCA1 or BRCA2 has been detected.

  I’ve grown accus
tomed to the tight feeling in my gut, but now it dissolves and makes room for a sort of bubble. The office seems warm and inviting, and even Kjergaard smiles broadly and persistently. I breathe out demonstratively.

  Fantastic! I’ve avoided the statistics and my family curse, I say foolhardily. No BRCA mutations but, to the contrary, an analysis from deCODEme that points to a smaller risk than the average – I’m in seventh heaven.

  “No, no. You can’t look at it that way,” Kjergaard emphasizes at once. “We can’t know what the situation was in your mother and grandmother. It could easily have been a flaw in genes we know nothing about yet, and which has been passed on to you.”

  She stresses that the medical system’s recommendations are still on the table: regular checkups with the breast surgeons. That’s fine – nothing she says takes away my feeling of being twice acquitted. With the mention of deCODEme, however, I have reminded Kjergaard of a development she does not care for and which she now begins to discuss. She meets regularly with people who have heard about some chromosome flaw or mutation and go onto the Internet to read up on it and become very frightened.

  “They simply do not understand the information,” she says irately. “And what happens to the healthcare system when we have to advise a stream of people about various tests they have purchased from some private company and can’t interpret themselves? Where are we headed?”

  Offhand, I can’t answer her, but I can easily see the reason for her objections. Right now, the prospects are foggy, but you can still sense that something has to happen in the healthcare system, because a new reality is going to flood it.

  Personal genetics is still in an embryonic state, and people can easily criticize the existing tests and gene profiles for providing too little usable knowledge. But we are also only dealing with the tip of the iceberg. Research – public research – is aimed at developing personal medicine, that is, prevention and treatment adapted to the individual’s physiology, which, once again, has to do with the individual’s genes. In the long term, there will be a general consumption of information and services based on genetics with respect to both diagnosis and treatment. But this is a consumption that, for a great many of the public, will take place directly – at the consumer’s initiative and away from doctors and hospitals. The market is private, prices are dropping rapidly, and the supply will only become more extensive. If you put this together with what’s happening on the Internet, you get a potent mixture.

  It’s not just that everyone will eventually be informed of any possible infirmity and its treatment on the great, omniscient Web, but there will be services such as Microsoft Health Vault and Google Health, where you will be able to sign up for an account and use it to keep your own running medical record. If you get sick, there will be organizations such as PatientsLikeMe, where thousands of patients with particular chronic diseases have congregated into a close social network. And they don’t chat their time away. They monitor their symptoms and the course of their illness in a professional way; they contact researchers, experiment with treatments, and advise each other. In some cases, they even put together research projects completely outside the healthcare system.

  Patients aren’t what they used to be, and the doctor’s role is also being transformed. As opposed to the good old days, when doctors were everyday gods, all-knowing experts who charted the course of your health unchallenged, the physicians of the future will be service technicians. Middlemen in white gowns who have the necessary authorization to provide the services the healthcare system offers but who, in many instances, know no more than the patients do. Perhaps even less. Right now, in the United States there is a violent debate about what should be done to reduce doctors’ ignorance about genetics. Studies show that most “ordinary” doctors do not know enough about genetics to be able to advise their patients on the content and significance of various consumer genetics tests, and specially trained genetic counselors are few. On the other hand, this profession is one of the fastest growing in the world. While it should be applauded that people are taking responsibility for their own health, it must also be acknowledged that the development of personal genetics pushes this responsibility further and further into each person’s own hands.

  “Where are we headed?” The chief physician’s question rings in my ears. I decide to look for those who might have an educated guess about it: the people who are driving the development. It appears that this embryonic industry and some of its cutting-edge researchers are holding the world’s first conference on consumer genetics. So I’ve bought a plane ticket to Boston to hear what they have to say.

  4

  The research revolutionaries

  The revolution is not an apple that falls when it is ripe.

  You have to make it fall.

  CHE GUEVARA

  I’VE COME TO the sprawling Hynes Convention Center to attend the first international Consumer Genetics Show. The atmosphere is breathless. I’d blame arctic air conditioning, but it’s obvious that everyone here feels they’ve been granted intimate seats at the birth of something magnificent.

  “This is consumer genetics from every conceivable angle,” says the conference’s organizer, the biotech entrepreneur John Boyce. I see many people I know from my circuits around the genomics revolution. Sorenson Genetics is here to talk about Americans’ increasing consumption of genetic paternity tests, which can be purchased by post or at the local pharmacy. DeCODEme, of course, is also in attendance. Its stand, by coincidence, is located next to a couple of competitors that offer to sequence a person’s entire genome, not just a measly million SNPs. Talks cover everything from whether consumer genetics is the business model of the future to how to broadcast your genetic information to the world.

  But there are snakes in paradise. Inside the frigid lecture hall, a panel is discussing the “forces” trying to limit or fence in an otherwise free market. The authorities in Germany, for instance, do not believe it is defensible or desirable to promote advanced genetic tests directly to innocent citizens; since not everyone is capable of understanding genetic information on his or her own, any sort of genetic test must in the future be prescribed by a doctor.

  “The Germans are an interesting people,” a drawling voice announces from the speaker’s podium. It is Kári Stefánsson, and he is apparently in a sarcastic mood. “They are happy to sell you tobacco and alcohol and fast cars, which they know will kill people, but you mustn’t go out and get knowledge about your own risk of disease. That I find a bit strange.”

  “Arrogant shit,” hisses the person next to me, so half the row can hear it. A couple of people nod in agreement, while Stefánsson continues his tirade.

  “Generally speaking, the critique of direct marketing to consumers is interesting. We already know that patients use the Internet and are often better informed than their general practitioner. People are interested in their health and, for me the question is whether we have a responsibility to give them access to the knowledge about genetics that research is producing?”

  Stefánsson decides to use the occasion of the first Consumer Genetics Show to share the news – or assert as fact – that his researchers have discovered some new genetic markers that tell us something about the risk of atrial fibrillation. It appears that variants in the gene ZFHX3, and their location on chromosome 16, significantly increase the risk of atrial fibrillation and, by extension, the risk for the most common type of cerebral hemorrhage. These small hemorrhages may not in themselves be fatal but they can gradually destroy so much brain tissue that it leads to dementia.

  “In the half percent of the population that has the greatest risk for cerebral hemorrhage, we can see that these gene variants provide a whopping seventy-five percent risk. And, at the same time, they provide a far better prediction than the traditional cholesterol measurements. This sort of knowledge can be used to get people into preventative treatment. Yet, still, many doctors and geneticists maintain their resistance – why?”

 
I’m sitting in the fifth row and I’m a little shaken. Not to hear about doctors’ resistance to consumer genetics, or the new German law for that matter; both were predictable. But this stuff about ZFHX3 is totally new to me. Stefánsson’s team published the discovery after I had visited him in Iceland just a couple of months ago. The researchers were moving quite quickly, and quite tangibly. People had a reason to be breathless.

  Since Stefánsson’s ZFHX3 markers hit the scientific literature, they have been entered into the gene profiles from deCODEme, and I’ll now be able to check my situation. And that’s how the process will work from now on. Every time a research group somewhere in the world discovers a new connection between a SNP and a biological characteristic, I, along with every other owner of a gene profile, will be able to log in and pull out my raw data to check my status. One day, we might be alerted to new data for the risk of depression; the next, susceptibility to athlete’s foot. When you think about it, it’s a fascinating way to be connected directly to the forefront of genetic research.

  “Stop!”

  I am pulled out of my musing by a young man, two rows in front of me, who stands and asks whether Stefánsson really thinks he and his colleagues are sufficiently skilled at explaining to people that the knowledge about risks changes swiftly and sometimes drastically.

  “The people who buy your gene profiles this year may find that they have a low risk for something or other. But it may prove they have a high risk next year, because research has advanced and may have revealed that the interim genetic studies didn’t hold water. Your results are very uncertain, but I don’t think the average consumer realizes that.”