Helix Takes Clinical Genetic Testing Straight to Consumers

During a recent Uber ride, Madhuri Hegde’s driver asked her what she did for a living. The chief scientific officer for laboratory services at PerkinElmer, she prepared to bore him with a description of the tests her company had developed—most recently to flag serious genetic disorders. Instead, he was intrigued. “Where can I get one of those?” he asked.

For years, PerkinElmer has only offered that clinical test to doctors. It screens for all 59 genes that researchers are sure play a role in one of 34 conditions you can treat if you catch it early enough. Genes like PKP2, mutations in which can increase the risk of arrhythmogenic right ventricular cardiomyopathy, a leading cause of sudden heart failure in young people. Or ATP7B, which can point to Wilson disease, where copper accumulates dangerously in the liver. Usually physicians only prescribe the test when they think their patients might be at risk for one of those conditions. But soon, anyone curious about their health—Hegde’s Uber driver included—will be able to request it.

PerkinElmer announced Tuesday it will start selling its test this summer through the consumer genomics marketplace Helix, a spin-out of sequencing giant Illumina. Helix launched its platform last July, with 18 products meant to inspire customers to embark on a journey of discovery through DNA. Some boasted dubious science; some were just silly. Only one of them had a hardcore health bent—a test to see if hopeful parents carried any disruptive genes they could pass on to their kids.

Since then, though, Helix has built a number of partnerships to offer more medically relevant insights, PerkinElmer being one. Helix says it's just responding to demand; patients are into democratizing access to clinical tests. But as more people turn to their DNA to make decisions about their health, medical professionals who help make those decisions wisely worry about their ability to keep up.

“You may think DNA is DNA regardless of what you’re looking for, but context really matters here,” says Ana Morales, a certified genetic counselor at the Ohio State University Medical Center and president-elect of the American Board of Genetic Counseling. Normally, a doctor would order a test like PerkinElmer’s when a patient starts presenting symptoms, like an abnormal heart rhythm. Maybe they even have a brother or sister with similar complaints. Algorithms and experts would then comb through the patient’s DNA looking for places in their genome where specific mutations—called variants—might appear. All mutations aren’t created equal; they’re only looking for ones that geneticists have validated as playing a role in certain diseases. How big a role changes from variant to variant, and from patient to patient. Without symptoms, matching becomes a guessing game.

“We’re now moving away from interpreting a variant in someone who has a disease to someone who doesn’t,” says Morales. “That is possible, but the level of expertise required to do that is limited to within a few experts in the genetic community. There’s only a very select group of people in the US right now who would feel comfortable doing that on a routine basis.”

That’s one reason a doctor might not tell all their patients about the availability of tests like this one. The other is cost. Sequencing plus analysis can run into the thousands of dollars, which insurers won’t reimburse if the test-taker is healthy. Right now insurance companies are only required to cover such screens under certain criteria—like if a woman has a family history of breast cancer. Responsible physicians are reluctant to put their patients or their institutions on the hook for that bill.

Hegde says Helix’s infrastructure will allow them to offer the test at a greatly reduced rate when it actually launches on the platform a few months from now, though she couldn’t give an exact price tag. That includes whole exome sequencing on their Illumina machines (that’s the portion of the genome that codes for proteins), and the physician network that Helix has already built out to accommodate any products that might require a doctor’s signature. That’s right, to buy this test you’ll still need to talk to a doctor—just maybe not the one you’re used to seeing for your annual check-up.

Customers who want to buy PerkinElmer’s test have to fill out a brief questionnaire—some basic family history and reasons why you might want to take the test—which gets routed to a hire-a-doc third party. If there’s a chance they’re already presenting symptoms or have a family history suggesting a condition that would be covered by insurance, they’ll suggest that user go the traditional testing route through their primary physician. If they appear healthy, they get the all-clear to order the test.

Then Helix sequences all 22,000 coding regions of the customer’s genome and sends the file over to PerkinElmer for analysis, which takes about a week. If they find anything that requires further attention they’ll bring in some real humans to compare what they know about the customer with what they know about the variant—how it’s inherited, how it changes pathways in the body. It could take another week to spit out that report, which goes back to the physician network, which then contacts the customer with any variants that could require follow-up. Genetic counseling services also bundled through Helix’s platform will be available upon request.

“We’re really trying to focus on the 99 percent of people that have never had access to this kind of testing, but of course we want it to be responsible access,” says Helix co-founder James Lu. “It’s for people who are ostensibly healthy and want to stay that way for as long as possible.”

Access to those kinds of proactive customers are what drew Hegde to Helix. “Not a lot of people know about this kind of testing,” she says. “But for every one of the 59 genes on this list there are interventions, and earlier intervention translates to saving health care costs as well as lives.”

It’s true that on an individual level, knowing you have a bad BRCA mutation might lead you to more regular check-ups and an earlier diagnosis of breast or ovarian cancer. But on the question of whether or not widespread genetic testing will actually lead to better outcomes and cut costs? Researchers still aren’t so sure. And with only about 4,000 certified genetic counselors total in the US—or one for every 80,000 Americans—it’s hard for most medical professionals to justify widespread testing. But hey, if your doc won’t order up a test you want, we’re betting Helix can find you one who will.

More Consumer Genetics

Read more: https://www.wired.com/story/helix-takes-clinical-genetic-testing-straight-to-consumers/

Women May Have an Alternative to Freezing Their Eggs

Here’s how it could go: Some day in the future, it’s routine for every young woman of a certain age—for argument’s sake, let’s say 21—to undergo a procedure to snip off a piece of tissue from one of her ovaries. Her doctor slices up the tissue into a half-dozen or so microthin sections; these are frozen, to be used whenever she’s ready for a baby. Her ovaries function normally, and she keeps menstruating and ovulating just as she has since puberty. But she doesn’t worry about rushing into baby-making. The timetable of how her life unfolds need not adhere to a pesky biological clock.

Later, maybe much later, maybe not for another 20 years, this woman wants to start a family. She remembers those strips of ovarian tissue in deep freeze. Each strip contains thousands of follicles, the proto-eggs of the ovary, preserved at their peak. The follicles in her body have been getting progressively less robust, but in the lab freezer her proto-­eggs have been in suspended animation, protected from the degradation of age.

So she goes back to the doctor, who defrosts one of the strips and implants it in her ovary. It becomes established there, starts pumping out hormones at the level of a younger woman, and transforms one follicle each month into a mature egg. Each menstrual cycle, the hardy egg of a 21-year-old is deposited into the fallopian tube, where it can be fertilized. Ideally, one of those youthful eggs turns into an embryo that embeds itself in the uterus and grows into a healthy baby. Ideally, that one strip of ovarian tissue keeps producing hormones and releasing eggs for years, long enough for the woman—who might be 45 or even older by the time it’s all done—to have a couple of children.

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If the first implant doesn’t work, or if it stops working before the woman’s family is complete, doctors can defrost and implant another strip. And if she doesn’t need the strips for childbearing—maybe she decides not to have children at all, or she gets pregnant naturally without needing to take any strips out of deep freeze—she can use them for a different purpose: postponing menopause. As she enters her fifties, this woman thaws a strip and has it implanted in her forearm, where it releases estrogen and other sex hormones in a way that mimics the feedback loop of a younger woman, in theory with fewer side effects than with artificial hormones. She still menstruates, which is the downside, but she also remains at lower risk of chronic conditions, like heart disease and osteoporosis, that usually get worse after menopause, at least in part because of the drop in estrogen. In this future, the one-two punch of nature’s timetable—first making it harder to have healthy babies after about age 35, then making it harder to stay healthy yourself after about age 50—is something women have finally transcended.

Here’s the reality of where things stand: At the Center for Human Reproduction in New York, there’s a room with a boxy machine that slow-freezes slices of ovarian tissue before they are transferred to a stubby deep-freeze tank that bears an uncanny resemblance to R2-D2. But of the 14 tanks in the room, most contain frozen embryos or frozen eggs or sperm, not ovarian tissue. That’s because right now, removing ovarian tissue involves an expensive surgery requiring a hospital stay. (Infertile men can have a bit of testicular tissue removed via a comparatively simple probe-and-snip procedure; the hope is that a similar procedure can be developed for women.) Transplanting the tissue later requires another operation.

Which is all to say, we already do live in a world where bits of ovarian tissue can be harvested, frozen, and then reimplanted later to make a woman fertile, but it’s harrowing. The process was developed for young women or girls with cancer, who face oncological treatments that are certain to make them sterile; since 2004, about 100 babies have been born to these women using the technique. In the view of most researchers and the American Society of Reproductive Medicine, ovarian tissue extraction is still too experimental to recommend for healthy women.

As she enters her fifties, the woman thaws a strip and has it implanted in her forearm, where it releases estrogen and other sex hormones in a way that mimics the feedback loop of a younger woman.

But soon, say experts like Sherman Silber, director of the Infertility Center of St. Louis, freezing ovarian tissue could become the next big form of what’s known as “social freezing” (or, as it’s called in some waggish circles, “AGE freezing,” short for “anticipated gamete exhaustion”)—whereby women try to prolong their fertility not for a medical reason but just to give themselves the option of delayed childbearing. For now, the only way to pause the biological clock this way is to freeze one’s eggs, a route taken by some 6,200 women in the US in 2015. But egg freezing is expensive (up to $18,000 per cycle) and uncertain. Experts calculate that each egg frozen before age 38 has just a 2 to 12 percent chance of turning into a baby one day. Egg freezing also requires women to inject themselves with hormones powerful enough to produce more than 10 times the normal number of mature eggs at a time. These hormones can lead to mood swings, nausea, and abdominal pain; a slight chance of the serious condition known as ovarian hyperstimulation syndrome; and an unknown risk of ovarian or breast cancer down the road.

So as women wait longer and longer to have kids—more than 26,000 women 40 or older became first-time mothers in 2016, an increase of nearly 30 percent over 2001—there’s plenty of incentive for the fertility industry to figure out how to make ovarian tissue extraction a better bet than egg freezing. For one thing, it would do away with the need for multiple rounds of in vitro fertilization. If all goes well, Silber says, the thawed and transplanted tissue will latch on to the rest of the ovary, become functional within about four-and-a-half months, and lead to pregnancy the old-fashioned way.

Roger Gosden, who helped develop the ovarian tissue-freezing procedure in sheep in the 1990s, worries that the social freezing of ovarian tissue will be fraught with the same hazards and anxieties as egg freezing: “A lot of commercial pressure and social pressure” will promote a procedure that most women end up not even needing—all “at great cost, great inconvenience, and a little bit of risk.” It’s also possible that the whole cold-storage approach to infertility could eventually be replaced by a better one: turning stem cells into egg cells, say, whenever a woman is ready to conceive.

But the biggest benefits of socking away young ovarian tissue may come at the other end of a woman’s reproductive life cycle. “One of the really big health challenges of the future is that we’re getting too old,” says Claus Yding Andersen, a professor at the Laboratory of Reproductive Biology at the University Hospital of Copenhagen. “The longer you’re in menopause, the greater your risk of osteoporosis and cardiovascular disease. The very best thing you can do to reduce those risks is to have your own menstrual cycles.” However they go about managing their fertility, women of the future who wait until their forties to start having children will probably want to put off the indignities of an aging body as long as possible. They will know they’ll need a spring in their step—not to mention sturdy hearts and flexible knees—if they’re going to keep up with those long-awaited kids.

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Robin Marantz Henig (@robinhenig) is a science writer and the author of nine books, including Pandora’s Baby.

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Read more: https://www.wired.com/story/reboot-reproduction-modern-fertility/

Does testosterone make you mean?

The risk-taking male hormone is blamed for everything from sexual violence to the financial crisis, but some researchers are starting to question the supposed links

Charles Ryan has a clinic in San Francisco at which he regularly relieves men of their testosterone. This chemical castration, as it is sometimes known, is not a punishment, but a common treatment for prostate cancer. Testosterone doesnt cause the disease (currently the third most deadly cancer in the UK), but it fuels it, so oncologists use drugs to reduce the amount produced by the testicles.

Ryan gets to know his patients well over the years, listening to their concerns and observing changes in them as their testosterone levels fall. Because it involves the so-called male hormone, the therapy poses existential challenges to many of those he treats. They know that every day, millions of people from bodybuilders and cheating athletes to menopausal women enhance their natural levels of testosterone with the aim of boosting their libido, muscle mass, confidence and energy. So what happens when production is suppressed? Might they lose their sex drive? Their strength? Their will to win?

The fears are not always groundless. Side-effects can also include fatigue and weight gain. But Ryan has witnessed positives, too. As professor of medicine and urology at the University of California, he has noticed that the medical students who have passed through his clinic in the 18 years that he has been treating prostate cancer invariably comment: Dr Ryan, your patients are so nice. He replies, jokingly: Its because they dont have any testosterone. They cant be mean.

Could there be some truth in that glib reply? Ryan knew his patients hadnt always been so kind. Before being robbed of their testosterone, they might have been personable and adept at small talk, but they werent nearly as interested in other people. He could feel a hypothesis coming on: that as mens testosterone levels lower, their capacity for empathy will rise. In his new book, The Virility Paradox, he argues that the fact that reducing testosterone in these ageing men may lead to increased empathy, more emotional engagement in relationships and a softening of aggression could be something of a silver lining.

Ryan started measuring his patients empathy quotients, using a survey developed for studying autism. Its too early to release detailed results, he says, but we do see increases in the empathy scores in many patients on the treatment.

He also dived into the literature on testosterone, attempting to understand what exactly was happening to them. Try as he might, however, he found little conclusive evidence for many of the claims made about testosterone, such as a link between hormone levels and risk-taking or sexual violence. Theres so much ambiguity in the science, he says. Many of the studies had been carried out on disappointingly small numbers of people.

Ryan is one of several researchers who are questioning the accepted wisdom about testosterone. It is often wheeled out as an excuse for patriarchal society, in arguments along the lines of: women, with their lower testosterone levels, have evolved to nurture and multitask in the domestic sphere, while men are hardwired to take risks, compete and furnish as many women as possible with sperm, thus ensuring the future of the species. But, as Ryan points out, obviously behaviour and cognition are extraordinarily complex and dont pivot on one molecule.

The psychologist Cordelia Fine makes a compelling case that it is our culture rather than our hormones that most influences gendered behaviours. As she writes in Testosterone Rex (winner of the Royal Societys science book prize for 2017) testosterone has been blamed for the financial crash of 2007-08, yet studies show that, although women have lower levels than men, they can have a higher appetite for risk even when it comes to financial decisions. She uncovered similar stories when it came to the evolutionary need for more sexual partners (more babies get made if women sleep around, too) and competition for status.

Fines pluck in challenging the scientific status quo could itself be viewed as classic testosterone-fuelled behaviour. She has cojones, you might say. She asserts that many typically female behaviours, such as deciding to have babies, are riddled with risk, only womens risks dont seem to count when it comes to testosterone mythology.

While Ryan comes at the subject from a different angle, both authors highlight how little research there is into testosterone in women. And yet we know it is vital to them (for example, oral contraception reduces testosterone levels, which can lead to low mood and libido). It can also influence sexual orientation, Ryan writes, with studies showing that self-described lesbians are likely to have [indications of] higher foetal testosterone levels than women who identify as heterosexual.

The lack of research, meanwhile, hasnt prevented a fierce debate about testosterones role in womens sports, with high levels seen as conferring an unfair advantage. The athlete Caster Semenya, who won a gold medal in the womens 800m at the 2016 Olympics, has extremely high natural testosterone levels for a woman. She had to prove her gender, and medically suppress the hormone before competing (although this ruling is currently suspended). Meanwhile, in 2016, the International Olympic Committee ruled that transgender women could compete without having had surgery, on condition that their testosterone levels were no higher than cisgender womens.

Not that testosterone levels are consistent in anyone. They rise and fall all the time, according to season, health, relationship and parental status, age, time of day (higher in the mornings) and emotional responses. When a man hears a woman cry, his testosterone goes down. When a person cares for their child, the bonding or love hormone oxytocin rises, while testosterone falls. If a threat to status or territory is perceived, testosterone rises again. Its the situations, the culture even, that seem to pull the hormones strings. Testosterone, in both men and women, also works in a feed-forward system: when you win at something, you get a spike in testosterone that as well as making you feel dominant and confident, increases your sensitivity to the hormone encouraging further swagger and quests to win.

Another of the hazards when studying testosterone is that there are three significant measures of how strong its force is in you. You can check levels in the bloodstream, but we already know how they fluctuate. The second measure is the number and sensitivity of androgen receptors, which vary significantly from person to person. (Testosterone is one of three hormones known as androgens, and receptors are what allow them to act on the cells in our bodies.) Third is the amount of testosterone to which we were exposed in the womb, most of which is produced by the foetus itself. This exposure is harder to gauge, although the difference between the lengths of the index and ring fingers is often used as a marker. The smaller the difference, the theory goes, the greater that foetal exposure.

This complex web, says Ryan, means that responses to hormonal suppression therapy are highly variable, based on [individuals] intrinsic biology. I have patients whose testosterone I take away and they dont have any [unwanted] side-effects. In fact, they say: I feel better. My brain is less clouded with intrusive thoughts about sex and things like that.

In a sort of mirror-image experiment, the writer Ann Mallen recently told how she accidentally rubbed testosterone cream into her skin every day for a month due to a mixup at the pharmacy. She wrote in the Washington Post that her sexual appetite became a constant distraction, as did her new persistent bouts of irrational anger. She concluded that underneath the high-pitched whine of our sex hormones, we are neither [male nor female].

Because women are more responsive than men to supplemental testosterone, they were used in one of the key studies into how testosterone essentially removes the burden of empathy from moral decision-making. Its known as the trolley car experiment. Picture a runaway tram hurtling down the tracks towards five unsuspecting workers. Theres a lever that would divert the tram to another track, but theres someone working on that track, too. You have to kill somebody to save five others, says Ryan, and you have to act fast.

The researchers at Utrecht University gave some of the subjects a shot of testosterone the night before presenting them with the dilemma. The number of respondents who were willing to kill in order to save people, and their confidence in carrying out the act were enhanced, says Ryan. And the equivocation they demonstrated was significantly reduced.

This isnt to say that empathetic people cant make tough decisions. Hormones are a bit-part in a complex cognitive picture. Aaron, a high-flying lawyer treated by Ryan, was adept at suppressing his empathy in order to win a case. But as his testosterone dissipated, he grew more caring and started asking Ryan about his family. At one appointment he asked whether getting emotional was a side-effect of his treatment, after he had wept at the end of a long-distance visit to his elderly mother. Like many patients, writes Ryan, Aaron regards these developments with a measure of surprise. Hormonal therapy hasnt been as bad as he expected, and he admits he has actually come to appreciate some of the effects it has had on him.

However, this outcome posed one worry for Ryan. A major case is heading to trial and Aaron is the lead attorney. Will having a testosterone level at 10% of normal affect his performance? he writes. The answer, it turns out, is no: Aaron had not lost his killer instinct in the courtroom.

You get the sense that Ryan sees toning down testosterone as a force for social good. Take his patient Marcus, an octogenarian who is still a keen runner. When his cancer risk was sufficiently low, he came off hormone suppression therapy and started taking supplemental testosterone to counter its effects. He would come in and talk about his half-marathon, weightlifting, his younger girlfriend, says Ryan. He never talked about anybody but himself. Eventually, he had to quit the supplements because his markers for cancer rose again. He disappears for more than a year, and comes back and is now taking care of his daughter, picking up his grandkids and being a nice grandpa. I think it is misguided for ageing men to think they should necessarily want to have high testosterone levels, because they may pay a price for that in terms of their relationships. They may be more self-centred, lack empathy.

But again, its complicated and depends on the individual. Many men, as they age, feel sluggish and lose muscle mass, lose their self-esteem, so I dont say we shouldnt ever use supplemental testosterone.

Its estimated that one in 10 men aged over 40 in the UK have low testosterone levels, which is in a large part related to obesity. Fat tissues will produce an excess of oestrogen, says Ryan, which leads to reductions in testosterone. Artificially boosting the latter could help them lose the weight, but any other benefits, Ryan warns, could be transient. A study published in the New England Journal of Medicine found that while [their participants on supplemental testosterone] felt good at first and their libidos went up, there werent long-term beneficial effects.

And, of course, they may end up impairing their capacity for empathetic relationships. But there are non-medical ways to boost empathy. In Testosterone Rex, Fine cites a 10-year US study targeting boys at high risk of behaving antisocially later in their lives. Some of them were given coaching to improve their emotional resilience, relationships and educational performance, while their parents were trained to manage their childrens behaviour. The goal was to enable the boys to respond more calmly and less vociferously to provocation. Years later, when the participants had reached their mid-20s, about 70 were deliberately provoked by someone stealing points from them in a game. Not only were the group who had been given coaching as boys less likely to retaliate; their testosterone levels rose less.

Another way, according to Ryan, is to do more childcare. Testosterone levels are 33% lower in fathers of newborns than in non-fathers, making way for a good 25% more oxytocin. This hormone, says Ryan, induces men to spend more time with their children and respond more quickly to their needs. It enables fathers to play more closely with their children, and get less rattled if they cry. (One of Ryans patients started getting down on the floor to play with his grandkids for the first time during hormone suppression therapy.) Romantic love, friendship and pet ownership open the floodgates to oxytocin, too (even a dogs oxytocin rises when it stares into its humans eyes). Less testosterone, more oxytocin, more bonding, says Ryan. Thats another, perhaps more fulfilling, feed-forward system.

Read more: https://www.theguardian.com/science/2018/mar/20/testosterone-myth-male-hormone-behaviour-risk-taking

I have prostate cancer. But I am happy | George Monbiot

The three principles that define a good life will protect me from despair, says Guardian columnist George Monbiot

It came, as these things often do, like a gunshot on a quiet street: shocking and disorienting. In early December, my urine turned brown. The following day I felt feverish and found it hard to pee. I soon realised I had a urinary tract infection. It was unpleasant, but seemed to be no big deal. Now I know that it might havesavedmy life.

The doctor told me this infection was unusual in a man of my age, and hinted at an underlying condition. So I had a blood test, which revealed that my prostate-specific antigen (PSA) levels were off the scale. An MRI scan and a mortifying biopsy confirmed my suspicions. Prostate cancer: all the smart young men have itthisseason.

On Monday, I go into surgery. The prostate gland is buried deep in the body, so removing it is a major operation: there are six entry points and it takes four hours. The procedure will hack at the roots of my manhood. Because of the damage that will be caused to the surrounding nerves, theres a high risk of permanent erectile dysfunction. Because the urethra needs to be cut and reattached to the bladder, I will almost certainly suffer urinary incontinence for a few months, and possibly permanently. Because the removal of part of the urethra retracts the penis, it appears to shrink, at least until it can be stretched back into shape.

I was offered a choice: radical surgery or brachytherapy. This means implanting radioactive seeds in the parts of the prostate affected by cancer. Brachytherapy has fewer side effects, and recovery is much faster. But theres a catch. If it fails to eliminate the cancer, theres nothing more that can be done. This treatment sticks the prostate gland to the bowel and bladder, making surgery extremely difficult. Once youve had one dose of radiation, they wont give you another. I was told that the chances of brachytherapy working in my case were between 70 and 80%. The odds were worse, in other words, than playing Russian roulette (which, with one bullet in a six-chambered revolver, gives you 83%). Though I have a tendency to embrace risk, this was not an attractive option.

It would be easy to curse my luck and start to ask, Why me? I have never smoked and hardly drink; I have a ridiculously healthy diet and follow a severe fitness regime. Im 20 or 30 years younger than most of the men I see in the waiting rooms. In other words, I would have had a lower risk of prostate cancer only if I had been female. And yet I am happy. In fact, Im happier than I was before my diagnosis. How can this be?

The reason is that Ive sought to apply the three principles which, I believe, sit at the heart of a good life. The first is the most important: imagine how much worse it could be, rather than how much better.

When you are diagnosed with prostate cancer, your condition is ranked on the Gleason Score, which measures its level of aggression. Mine is graded at seven out of 10. But this doesnt tell me where I stand in general. I needed another index to assess the severity of my condition, so I invented one: the Shitstorm Scale. How does my situation compare to those of people I know, who contend with other medical problems or family tragedies? How does it compare to what might have been, had the cancer not been caught while it was still apparently confined to the prostate gland? How does it compare to innumerable other disasters that could have befallen me?

When I completed the exercise, I realised that this bad luck, far from being a cause of woe, is a reminder of how lucky I am. I have the love of my family and friends. I have the support of those with whom I work. I have the NHS. My Shitstorm Score is a mere two out of 10.

The tragedy of our times is that, rather than apply the most useful of English proverbs cheer up, it could be worse we are constantly induced to imagine how much better things could be. The rich lists and power lists with which the newspapers are filled, our wall-to-wall celebrity culture, the invidious billions spent on marketing and advertising, create an infrastructure of comparison that ensures we see ourselves as deprived of what others possess. It is a formula for misery.

The second principle is this: change what you can change, accept what you cant. This is not a formula for passivity Ive spent my working life trying to alter outcomes that might have seemed immovable to other people. The theme of my latest book is that political failure is, at heart, a failure of imagination. But sometimes we simply have to accept an obstacle as insuperable. Fatalism in these circumstances is protective. I accept that my lap is in the lap of the gods.

So I will not rage against the morbidity this surgery might cause. I wont find myself following Groucho Marx who, at the age of 81, magnificently lamented: Im going to Iowa to collect an award. Then Im appearing at Carnegie Hall, its sold out. Then Im sailing to France to pick up an honour from the French government. Id give it all up for one erection. And today theres Viagra.

The third principle is this: do not let fear rule your life. Fear hems us in, stops us from thinking clearly, and prevents us from either challenging oppression or engaging calmly with the impersonal fates. When I was told that this operation had an 80% chance of success, my first thought was thats roughly the same as one of my kayaking trips. And about twice as good as the chance of emerging from those investigations in West Papua and the Amazon.

There are, I believe, three steps to overcoming fear: name it, normalise it, socialise it. For too long, cancer has been locked in the drawer labelled Things We Dont Talk About. When we call it the Big C, it becomes, as the term suggests, not smaller, but larger in our minds. He Who Must Not Be Named is diminished by being identified, and diminished further when he becomes a topic of daily conversation.

The super-volunteer Jeanne Chattoe, whom I interviewed recently for another column, reminded me that, just 25 years ago, breast cancer was a taboo subject. Thanks to the amazing advocacy of its victims, this is almost impossible to imagine today. Now we need to do the same for other cancers. Let there be no moreterriblesecrets.

So I have sought to discuss my prostate cancer as I would discuss any other issue. I make no apologies for subjecting you to the grisly details: the more familiar they become, the less horrifying. In doing so, I socialise my condition. Last month, I discussed the remarkable evidence suggesting that a caring community enhances recovery and reduces mortality. In talking about my cancer with family and friends, I feel the love that I know will get me through this. The old strategy of suffering in silence could not have been more misguided.

I had intended to use this column to urge men to get themselves tested. But since my diagnosis, weve discovered two things. The first is that prostate cancer has overtaken breast cancer to become the third biggest cancer killer in the UK. The second is that the standard assessment (the PSA blood test) is of limited use. As prostate cancer in its early stages is likely to produce no symptoms, its hard to see what men can do to protect themselves. That urinary tract infection was a remarkably lucky break.

Instead, I urge you to support the efforts led by Prostate Cancer UK to develop a better test. Breast cancer has attracted twice as much money and research as prostate cancer, not because (as the Daily Mail suggests) men are the victims of injustice, but because womens advocacy has been so effective. Campaigns such as Men United and the Movember Foundation have sought to bridge this gap, but theres a long way to go. Prostate cancer is discriminatory: for reasons unknown, black men are twice as likely to suffer it as white men. Finding better tests and treatments is a matter of both urgencyand equity.

I will ride this out. I will own this disease, but I wont be defined by it: I will not be prostrated by my prostate. I will be gone for a few weeks but when I return, I do solemnly swear I will still be the argumentative old git with whom you are familiar.

George Monbiot is a Guardian columnist

Prostate Cancer UK can be contacted on 0800 0748383

Read more: https://www.theguardian.com/commentisfree/2018/mar/13/prostate-cancer-happy-diagnosis-operation

Ultra-processed foods may be linked to cancer, says study

Findings suggest increased consumption of ultra-processed foods tied to rise in cancers, but scientists say more research is needed

Ultra-processed foods may be linked to cancer, says study

Findings suggest increased consumption of ultra-processed foods tied to rise in cancers, but scientists say more research is needed

Read more: https://www.theguardian.com/science/2018/feb/14/ultra-processed-foods-may-be-linked-to-cancer-says-study

Spread of breast cancer linked to compound in asparagus and other foods

Using drugs or diet to reduce levels of asparagine may benefit patients, say researchers

Spread of breast cancer linked to compound in asparagus and other foods

Using drugs or diet to reduce levels of asparagine may benefit patients, say researchers

Read more: https://www.theguardian.com/science/2018/feb/07/cutting-asparagus-could-prevent-spread-of-breast-cancer-study-shows

Will Your Baby Like Cilantro? These Genetic Tests Say They Can Tell

You have instant communication, on-demand entertainment, and dial-up transportation—why should you have to wait nine months to see what kind of baby you’re going to have? Now there’s an app for that.

In a modern-day reboot of Lindsay Bluth’s “Mommy What Will I Look Like” business venture, Denver-based startup HumanCode has introduced BabyGlimpse. It’s a $259 test that uses DNA from each member of a couple to predict how their future child might look and act—from skin, hair, and eye color to preferred kinds of snacks. (With a variant of the SLC2A2 gene your kiddo might have more glucose receptors than average, and therefore a sweet tooth, so goes the scientific reasoning.) Fun, right?

“We’ve coined it sunshine science,” HumanCode co-founder Jennifer Lescallet told the Balitmore Sun last month. “You get to look at the fun part of your potential future baby versus some of the scary stuff.” The scary stuff being more traditional carrier screen genetic tests, which tell couples if they have any disease-related genes they could potentially pass on to their offspring. These are either ordered by a doctor based on family history, or are now increasingly available to buy directly, after an online or phone consultation with a physician.

BabyGlimpse is one of the latest examples of a growing direct-to-consumer genetic testing industry aimed at new, expecting, and aspiring parents. Some, like BabyGlimpse, rely on a combination of each partner’s DNA. Others, like Orig3n’s Child Development test, collect spit or cheek swabs from the new kiddos themselves, and then work with labs to sequence, analyze, and interpret that genetic information. The companies behind these tests say they’re mostly for entertainment, and for educating folks about how genetics work. But doctors and public health officials have concerns that they might, in fact, do the opposite.

“At this point in time, in 2018, consumers should approach these tests with caution,” says Muin Khoury, the director of the Office of Public Health Genomics at the Centers for Disease Control and Prevention. His five-person team tries to help people understand how to use genomics appropriately to improve public health. They currently designate direct-to-consumer tests with a “tier 3” classification, meaning that “there is no evidence for clinical validity or utility of such applications in healthy individuals.”

Khoury says personal genomic testing isn’t harming anyone, but it’s also not conferring any real health benefits. “And we still don’t understand very well the unintended consequences of labeling people,” he says. “Once you think you know certain information, it’ll affect how you think about your baby for life.”

Some things, like knowing about lactose intolerance and peanut allergies from an early age, could certainly make for happier and healthier outcomes. But what about traits like math ability, noise pattern and music learning, and bone strength, which Orig3n claims to be able to tell you something about? The fallout could be subtle, but insidious. Maybe you discourage your kid from playing sports because Orig3n told you she was among the 30 percent of the population with weaker than average bones. Or you don’t give them a hard time about their sub-par math scores. Instead of telling them they can be whatever they want to be, you tell them they can be whatever they want to be, within genetic constraints.

HumanCode

The company gives you percentages, which is as much certainty as the science will allow, but the reality of genetics in the wild is more complicated still. Humans are born with two copies of every gene; one from each parent. The two different versions of each gene combine and interact to make a totally unique genome. Some traits, like eye color, are controlled by only a handful of genes. Others, like height, are likely influenced by thousands. HumanCode and Orig3n use machine learning models trained on a mix of publicly available genomes and proprietary data to come up with what’s called polygenic risk scores for each trait. Basically, a predicted likelihood that your kid will be taller than six feet, say, or be bad at math.

But the thing about these kinds of genes is that they’re not deterministic. (Unlike genetic diseases such as cystic fibrosis, which are clearly linked to changes in a single gene.) What you eat, where you live, what kind of an education you get—all of these things have as much, if not more, of an impact than your DNA. That’s not to say there isn’t strong evidence that certain genetic variants are associated with specific traits. But genes alone can’t predict how tall you’ll grow or how good you’ll be at long division.

Non-geneticists tend not to think too hard about these distinctions. “I think consumers are going to have to learn to differentiate between products that are scientifically rigorous and truly health-related and products that are the genetic equivalent of skin cream for wrinkles, and that’s a big lift,” says Robert Green, who studies direct-to-consumer genetic testing at Brigham and Women’s Hospital. “Genetics is novel and poorly understood and we haven’t yet immunized ourselves against these exaggerated claims. These companies are using our respect for the science of genetics to do an end-run around common sense.”

There may be a day in the future where common sense (and science) dictate that every infant get their genes sequenced upon birth. But until then, maybe save your money and get to know your baby the old-fashioned way, with time.

Read more: https://www.wired.com/story/will-your-baby-like-cilantro-these-genetic-tests-say-they-can-tell/

Cancer Diagnosis from a Blood Draw? Liquid Biopsies Are Still a Dream

Nick Papadopoulos tracks down tumors for a living. Not with X-rays or CT scans, but with DNA. The oncologist and director of translational genetics at the Johns Hopkins Kimmel Cancer Center has spent decades uncovering the unique sets of mutations that define cancers—the kind of genetic signals that not only drive tumor formation and metastasis, but distinguish one cancer from another. And now, he’s working to develop a test that could sniff out those signals before a patient starts to get sick.

It’s the kind of test that Papadopoulos thinks could have saved his uncle’s life, had it been around a few years ago. “He had no symptoms until a cough showed up,” he says. But when it didn’t go away he went in for an X-ray, and there on the radiograph were the lesions. Dozens of them, filling his entire chest cavity. The doctors sequenced the tumors, and got him signed up for a clinical trial for a new, targeted drug. It worked for a few of them, shrinking them back to almost nothing. But the rest developed resistance.

“He was supposed to only live two months, and the drugs prolonged his life by a year. But that year wasn’t good.” says Papadopoulos. “I think it’s time to start thinking more about detecting cancers early and less about treating them when they are late.”

On Thursday, Papadopoulos’ research group at Hopkins revealed a novel blood test based on the combined analysis of DNA and proteins that correctly detected eight kinds of the most common cancers with a range of accuracies—from 98 percent for ovarian cancers to less than 40 percent for breast cancers. Published in Science, the test is just one among many so-called “liquid biopsies” in development; noninvasive tests that classify cancers by identifying the tiny bits of DNA that tumors shed into the bloodstream.

Most published studies, including this one, focus on measuring and monitoring advanced tumor stages. A few liquid biopsies have even been approved to help match tumors to targeted drugs. But the dream is to develop a simple blood test to actually diagnose solid tumors in healthy-looking people. The scarcity of circulating cancer biomarkers (both in quality and quantity; tumor DNA makes up less than 0.1 percent of blood) has held those aspirations back for decades. But now, sensitive assays and computational platforms are driving the discovery of biomarkers and better ways to measure them, luring a pack of well-financed startups into the field.

In 2016, for example, the world’s largest sequencing company, San Diego-based Illumina, spun out a new company called Grail. Its mission is described as “detecting cancer early, when it can be cured.” This ambitious aim is supported by $1.2 billion of venture capital Grail raised last year, which it intends to put toward financing massive, population-based clinical studies and optimizing its sensitive sequencing technologies.

Grail has yet to publish any actual data (its website does advertise a commentary published in Cell last year). And neither has its chief rival in the Valley, a machine learning startup called Freenome. That three-year old company snagged a $65 million Series A last March, led by Andreessen Horowitz. Freenome isn’t limiting itself to the genetic breadcrumbs left by tumor cells—it looks to capture other disease signatures in the blood, like how the immune system changes in response to tumor microenvironments.

Of course, Freenome has offered scant details on how exactly that kind of test would work. “You show your cards at the end, not while you’re playing poker,” says Andreessen partner Vijay Pande, who heads the investment firm’s biofunds. “Publications indicate that you’re not interested in building a company.” That said, he does expect Freenome to publish in a peer-reviewed journal ahead of its first foray into the market.

When that could be, though, is anyone’s guess. To evaluate any of these blood screens, thousands of patients will have to get tested—and then researchers will have to wait for some of them to actually get cancer. That’s the only way to determine not only their predictive power, but also whether they lead to improved patient outcomes. The noninvasive screening tests available today—mammography for breast cancer, a protein-measuring test for prostate cancer—are rife with their own issues. Incorrect diagnoses waste time and money on treatments and burden patients with unnecessary anxiety.

Liquid biopsy is likely to be beset by the same kinds of controversy, says Geoff Oxnard, a thoracic oncologist at the Dana-Farber Cancer Institute and a professor at Harvard Medical School. He routinely uses a single-gene liquid biopsy developed at Dana Farber to figure out which drugs represent the best options for his lung cancer patients. But will early detection versions one day be part of routine doctor’s visits? “No. I think these tests will help us better understand the risks for patients who already have a history of cancer in their family or who’ve already had something show up on a scan,” he says. “But I don’t think we have the kind of data we need to support liquid biopsy as a panacea for diagnosing cancer. At the end of the day, it’s still just a shortcut.”

Still, Oxnard pointed out that Papadopoulos’s test represents an important step forward. One, it starts to identify where a tumor might be located. That’s been a big limitation of liquid biopsies; OK, you’ve found cancer, but what do you do next? Where do you look for the tumor? Most mutations don’t tell you anything about location. But by layering in measurements for 31 additional proteins to their machine learning model, the Hopkins team was able, on the first try, to correctly identify the tissue of origin around 80 percent of the time colorectal cancers, pancreatic, and ovarian cancers.

The other advance is cost. Papadopoulos estimates the test could be commercialized for around $500, and cancer-spotting approaches that rely on ultra-deep sequencing could stretch costs for existing screening tests, which only look for a single gene. “This is great for the field and provides promise that these analyses will become a reality in the clinic,” says Victor Velculescu, an oncologist and colleague of Papadopoulos’ at Johns Hopkins, who has also developed liquid biopsy technologies, though he was not involved in the Science study.

The two have developed a sort of friendly turf war as they’ve turned Baltimore into its own little liquid biopsy hub. Both researchers have recently spun off diagnostics companies to further develop their own early detection technology platforms. Earlier this month, Velculescu’s venture, Personal Genome Diagnostics, hauled in a $75 million Series B led by pharma giant Bristol-Myers Squibb. That brings its total financing to $99 million, putting it on par with some of its better-known counterparts in the Valley, adding some bicoastal intrigue to the race to the market. Whatever the outcome, it’s patients who will ultimately be the winners.

“If it can even catch 50 percent of cancers that right now we have no way of screening for, that’s still 50 percent of patients who can now be treated in Stage 1, when they still have a chance,” says Papadopoulos. “It doesn’t have to be perfect to still save a lot of lives.”

Read more: https://www.wired.com/story/cancer-diagnosis-from-a-blood-draw-liquid-biopsies-are-still-a-dream/

NFL concussion: researchers hope blood tests can better detect head trauma

Several firms trying to develop new methods to assess extent of damage to head and brain

In the second quarter of an NFL game on Thursday night, the Baltimore Ravens quarterback Joe Flacco slid to gain a first down. The 233lb Miami Dolphins linebacker Kiko Alonso flew into him, ploughing shoulder-first into his head.

Such was the force of the hit, Flaccos helmet flew off. He walked from the field but he was dazed and bleeding from one ear. There was little doubt he had suffered a concussion.

It was an extreme example of the brutal reality of football. Many head injuries caused by the game, however, are harder to detect, the product of collisions repeated over time. Some researchers think a blood test may soon be one way of detecting such problems.

At this point there are probably as many as 20 to 25 incredibly insightful biomarkers for brain health, said Kevin Hrusovsky, chief executive of Quanterix, a startup that is one of a handful of companies seeking to develop standardized blood tests to detect concussions.

We are hopeful we will be able to transform brain health in the way weve transformed cardiac health and even cancer health.

Researchers at Quanterix and other companies hope blood tests will soon look for evidence of Alzheimers or dementia, much as standard cholesterol tests now help to assess heart problems.

I think about [such tests] every minute of every day, said Robert Stern, a researcher at Boston University who co-authored a landmark study that found the degenerative disease chronic traumatic encephalopathy (CTE) in the brains of 110 of 111 dead NFL players.

Since the 1920s, researchers have known that repeated blows to the head can result in cognitive degeneration. Recent research has shown how severe such damage can be. However, because CTE in particular can only be diagnosed after death, it is almost impossible to know how many people have it.

Theres been tremendous advances over the last two years with regard to fluid biomarkers and Alzheimers disease, said Stern. We can then exploit whats being done in that area for CTE.

Kiko Alonso hits Joe Flacco.

Blood tests for concussive injury could help manage neurodegenerative diseases, for example, answering with more certainty questions about how long an athlete should stay out of play; whether a person is predisposed for neurodegenerative disease; or whether disease is advancing. Stern and others hope the technology will eventually help ordinary people too, such as car accident victims.

There is still disagreement on how tests for concussion, and then neurodegeneration, might be applied. Stern sees a blood test as the first in a series of more specific panels, the way a breast cancer patient might first receive a mammogram, then a biopsy. Hrusovsky hopes degenerative diseases will be found in one blood test hopefully, of course, one developed by his company.

Neurologists currently rely on a series of cognitive tests to see whether symptoms of traumatic brain injury are present. Perhaps that is why Quanterixs work has caught the imagination of the public and the attention of the NFL. Through a partnership with General Electric, the league has given Quanterix $800,000 to continue the research, Bloomberg BusinessWeek reported.

I did the math today, said Pete Cronan, a former linebacker with Washington and the Seattle Seahawks, when asked about his concussions. Ive got six I can remember through my life. The first was when he fell out of a bunk bed as a kid.

But those are the ones that I can remember, he said.

Researchers now consider blows that do not concuss but produce altered states to represent a cumulative danger.

There were thousands of those in my life, Cronan said.

According to the Baltimore Sun, Flaccos injury was the first reported concussion of his 10-year, Super Bowl-winning career.

Were 30-plus years into studying these fluid-based biomarkers, and the data definitely supports that they can be used to correlate quite nicely with injury severity, said Joshua Gaston, a researcher at the University of Texas Southwestern medical center who is also a football fan.

The work was now focused, he said, on making tests reproducible, sensitive, specific.

Read more: https://www.theguardian.com/sport/2017/oct/30/nfl-concussion-head-trauma-researchers-blood-tests

More than 25 million people dying in agony without morphine every year

Concern over illicit use and addiction is putting morphine out of reach for millions of patients globally who need it for pain relief

More than 25 million people, including 2.5 million children, die in agony every year around the world, for want of morphine or other palliative care, according to a major investigation.

Poor people cannot get pain relief in many countries of the world because their needs are overlooked or the authorities are so worried about the potential illicit use of addictive opioids that they will not allow their importation.

Staring into this access abyss, one sees the depth of extreme suffering in the cruel face of poverty and inequity, says a special report from a commission set up by the Lancet medical journal.

In Haiti, for instance, says the report, there are no nursing homes or hospices for the dying and most have to suffer without pain relief at home.

Patients in pain from trauma or malignancy are treated with medications like ibuprofen and acetaminophen, says testimony from Antonia P Eyssallenne of the University of Miami School of Medicine. Moreover, nurses are uncomfortable giving high doses of narcotics even if ordered to do so for fear of being responsible for the patients death, even if the patient is terminal.

Death in Haiti is cruel, raw, and devastatingly premature. There is often no explanation, no sympathy, and no peace, especially for the poor.

A doctor in Kerala, India, which has a palliative care service, told of the arrival of a man in agony from lung cancer. We put Mr S on morphine, among other things. A couple of hours later, he surveyed himself with disbelief. He had neither hoped nor conceived of the possibility that this kind of relief was possible, said Dr M R Rajagopal.

But when he returned, morphine stocks were out. Mr S told us with outward calm, I shall come again next Wednesday. I will bring a piece of rope with me. If the tablets are still not here, I am going to hang myself from that tree. He pointed to the window. I believed he meant what he said.

The commissions three-year inquiry found that nearly half of all deaths globally 25.5 million a year involve serious suffering for want of pain relief and palliative care. A further 35.5 million people live with chronic pain and distress. Of the 61 million total, 5.3 million are children. More than 80% of the suffering takes place in low and middle-income countries.

Jim Yong Kim, president of the World Bank, said things had to change. Failure of health systems in poor countries is a major reason that patients need palliative care in the first place. More than 90% of these child deaths are from avoidable causes. We can and will change both these dire situations.

Morphine is hard to obtain in some countries and virtually unobtainable in others. Mexico meets 36% of its need, China meets 16%, India 4% and Nigeria 0.2%. In some of the worlds poorest countries, such as Haiti, Afghanistan and many countries in Africa, oral morphine in palliative care is virtually non-existent.

Oral and injectable morphine is out of patent, but costs vary widely and it is cheaper in affluent countries like the USA than in poor countries. A second issue is opiophobia the fear that allowing the drugs to be used in hospitals will lead to addiction and crime in the community.

The world suffers a deplorable pain crisis: little to no access to morphine for tens of millions of adults and children in poor countries who live and die in horrendous and preventable pain, says Professor Felicia Knaul, co-chair of the commission from the University of Miami, calling it one of the worlds most striking injustices.

Knaul says she only realised that many people suffered without pain relief when she was working to improve access to cancer treatment in low-income countries. I was shocked. I had no idea. When people were showing me the data I thought it cant be in this world, she told the Guardian.

She had also experienced the need for morphine herself after a mastectomy for breast cancer. When I woke up I couldnt breathe because the pain was so bad. If they hadnt arrived with the morphine I dont know how I would have got through it. And as a young girl in Mexico, she had to watch her father suffer as he died without pain relief.

I dont think that we have cared enough about poor people who have pain, she said. It doesnt make them live any longer. It doesnt make them more productive. It is simply the human right of not suffering any more pain and we dont care about that for people who are poor.

The commission recommends that all countries put in place a relatively inexpensive package of effective palliative care for end of life conditions that cause suffering, including HIV, cancers, heart disease, injuries and dementia.

One of their most emphatic recommendations, says Knaul, is that immediate-release, off-patent, morphine that can cost just pennies should be made available in both oral and injectable formulations for any patient with medical need. The disparity and access abyss between the haves and have-nots is a medical, public health and moral injustice that can be effectively addressed by the commissions recommendations.

Read more: https://www.theguardian.com/science/2017/oct/12/more-than-25-million-people-dying-in-agony-without-morphine-every-year