Genetic tests that predict a person's risk of disease or suggest which types of treatments may succeed or fail are taking center stage in medicine. However, the lack of consistent government oversight of the testing industry poses enormous concerns for consumers and health professionals, experts said in a letter to Kathleen Sebelius, secretary of the U.S. Department of Health and Human Services.
The letter, signed by a diverse coalition of groups representing genetic testing laboratories, patient advocates, investors and health policy researchers, called for a new framework to oversee genetic testing that is consistent for all tests.
"Advanced diagnostic testing is becoming the standard of care for many diseases," the letter said.
Right now, various tests are subjected to different levels of regulation. Two types of testing systems are available: test kits approved by the Food and Drug Administration and laboratory-developed tests that are regulated by the Department of Health and Human Services. But this system is inconsistent and fails to protect all consumers, said Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University. Some genetic testing labs, for example, are not subjected to proficiency testing to ensure accuracy and quality, Hudson said today at the annual meeting of the American College of Obstetricians and Gynecologists in Chicago.
"The problem is there is no system that makes the requirement of proficiency testing for every company," she said. "There is no way for the public to distinguish between the good guys and the bad guys."
Studies conducted at the Genetics and Public Policy Center and other organizations have shown a wide range of quality in genetic testing. In one study, researchers sent identical medical and genetic information to a company twice with a different patient's name on each test. The company produced different genetic findings for the two "identical" patients, Hudson said. In another situation, a gene testing company touting a service to identify the gender of a fetus based on a blood test from the mother predicted the gender accurately only half of the time -- the equivalent of guessing.
In the letter to Sebelius, the coalition also called for a registry that would include the name of the laboratory performing a test, the name of the company that developed the test and information to support claims of how valid the test is.
Hudson noted that the call for consistent, rigorous regulation of genetic testing comes from diverse groups representing industry and patient interests. "The level of consensus here truly represents a watershed moment in laying this critical foundation for personalized medicine."
Now, if you come here often, you know that loading up on carbohydrates is going to make you pretty chubby. But you notice your fellow diner -- the mouse -- is pretty slim. How does he do it?
This lucky mouse has had a gene knocked out of his genome by researchers in Hei Sook Sul's lab. The observation that mice without this gene can eat all the carbs they want and stay slim -- while other mice fed a high-carb diet do indeed become fat -- leads Dr. Sul to conclude that her lab has found a gene that plays a critical role in the process of converting carbohydrates to fat. And that discovery points to an important new target for drug developers hoping to find a way to prevent and perhaps even reverse obesity in humans.
The discovery of the gene's role in obesity is published in an article in the March 20 issue of the journal Cell.
The gene involved, known as DNA-PK (short for DNA-dependent protein kinase), is widely studied for its role in repairing breaks in the DNA -- a function that has made it critical to cancer research and treatment. But Sul says it was a surprise to discover that the same gene has a key role in the liver's conversion of excess glucose (all that bread, pasta and sugary soda you've failed to work off) to fatty acids.
Not only were mice whose DNA-PK gene had been knocked out 40% leaner than normal mice when all were fed a high-carb, low-fat diet. They also had better blood-lipid profiles, suggesting they'd be at lower risk of developing heart disease.
In an interview, Sul said no one at this point is thinking about gene therapy as a treatment for obesity -- that would be way down the road. Instead, drug developers might look at how the DNA-PK gene calls out other actors to set in motion the conversion of excess calories to fat and find an agent that might disrupt the process.
And if they're successful, you'll be able to join that mouse at the all-you-can-eat pasta bar and look just as svelte as he does.
Four Turkish families have helped researchers solve a long-standing mystery about the biological basis of puberty.
The distantly related families include seven children who grew into their teens and 20s without ever reaching puberty. (Another child, a 5-year-old girl, isn’t expected to hit puberty either.) The rare condition is called normosmic idiopathic hypogonadotropic hypogonadism, or nIHH.
A team of scientists from Cukurova University in Adana, Turkey, and the University of Cambridge in England looked for single-letter mutations in their DNA. They zeroed in on two key genes that appear to activate the cascade of hormones that allow adolescents to reach sexual maturity.
In three of the families, affected children had two faulty versions of a gene called TACR3. In the fourth family, two affected siblings had normal TACR3 genes but inherited defective versions of a related TAC3 gene from both parents. A normally functioning TAC3 gene contains instructions for making a peptide called neurokinin B, and TACR3 codes for the neurokinin B receptor.
The researchers surmised that neurokinin B plays the crucial role of instructing the brain to produce gonadotropin-releasing hormone. That, in turn, prompts the release of other hormones that ultimately stimulate the testes to secrete androgens and testosterone or the ovaries to make estrogen and progesterone.
Writing this week in the journal Nature Genetics, the researchers said the discovery helps answer “an enduring enigma of human biology.” The findings could not only help treat nIHH but aid development of new drugs to treat infertility and diseases related to sex steroids, including breast and prostate cancer.
If you wonder why Gramps' hearing has gone to the dogs and Grandma's hearing has not -- well, there could be a plethora of reasons. Such as lifetime exposure to loud noises, certain meds, certain medical conditions and more. Add genes to the mix. In a study reported in the journal Human Molecular Genetics, researchers at the local House Ear Institute, in collaboration with scientists at several other institutions (see list below), found several genes involved in hearing loss risk, most notably one called GRM7.
GRM7 carries instructions for a protein that is made in cells of the inner ear and is involved in receiving signals from nerves. A nerve-signaling chemical called glutamate attaches to this protein receptor -- and too much glutamate stimulation can damage the fragile hair cells key to hearing. Certain people, it appears, have a gene that directs formation of a receptor that's more sensitive to such damage.
Scientists have actually known for some time that there's a significant genetic contribution to the decay of hearing loss that comes with age -- but it's one thing to know that genes exist, quite another to have tracked any of them down. These days, what with the whole human genome sequenced and high-tech "chips" available for the scanning of tiny variations that exist between one individual and the next, such genes are easier than ever to find.
The study was conducted by Rick Friedman of the House Ear Institute as well as others from House, the Translation Genomics Research Institute in Phoenix, Affymetrix in Santa Clara and the University of Antwerp, Belgium. It involved genetic scans of more than 800 Europeans with age-related hearing loss and a similar number of people without it, for comparison.
By the way, hair cells are very pretty. You can learn more, and see a cool image, here (and also learn about the hope that one day hair cells could be regenerated).
Hair cells do their sound-transmitting job by moving in response to sound. Here's a bizarre movie one Brit scientist made of a hair cell dancing to "Rock Around the Clock." (Make sure you listen to the soundtrack.)
These days, courtesy of whole-genome scanning services, you, me or anyone could cough up a thou' or two and find out our genetic predisposition to Alzheimer's disease, colon cancer, heart disease, more. But what would we do with the info? Quit smoking, eat virtuously and go jogging every day at dawn? Slide into depression? Shrug "what the hey" and party, party, party?
"We have all that potential information to offer people, but it's unknown as to whether it's of benefit," said Dr. Eric Topol, director of Scripps Translational Science Institute in San Diego during a phone call. Now the institute is planning to find out with the help of 10,000 employees, family members and friends of Scripps Health, a nonprofit healthcare delivery network in the San Diego area. Participants get a discounted scan of their genome from Navigenics, one of several companies offering this service. They send off a sample of their saliva and in return, they're tracked for 20 years to see what the news they received did to their lives and their behavior.
As new data roll in on other genetic links to diseases, those will be added to the database -- so people will learn more and more about their disease risks and resilience over time.
Topol already had his DNA scan results and said he was a little bit surprised at the news. Colon cancer runs in his family, but his scan showed he didn't have variants of certain genes that enhance risk for the cancer. "On the other hand, I've spent 25 years on treatment and prevention of heart attacks, and that's where I have a risk."
Ideally, to figure out if the tests had positive or negative effects on people's behaviors, you'd be able to compare them with a group of people who never got the info but would have liked to. Instead, participants will in a sense serve as their own controls: They'll be assessed for their mood, habits and the medical care they seek both before and after they get the scan information.
An interesting fact: Adopted people have been especially keen to enroll in the study, Topol says: "This is the first time they've been able to get any family history about their life, because they don't know their parents at all -- don't know anything about their maternal and paternal blood lines."
You can read more about whole-genome scans in an April Health section article by freelance writer Anna Gosline, who discovered through getting hers that she had a significantly higher lifetime risk for Alzheimer's disease.
With direct-to-consumer genetic testing now widely available, many health professionals have wondered how families with children will deal with the results of genetic testing. Will parents worry excessively if test results suggest a high risk of disease in a child?
A new study sheds some light on the issue and finds, surprisingly, that information from family history and from genetic testing caused equal amounts of concern among parents about their children's risk. The researchers, from the University of Michigan, had hypothesized that parents would place a greater value on genetic tests, and worry more. But when asked about hypothetical situations in which they learned they or their children were at high risk for developing a disease, the 1,342 parents surveyed were not overly concerned about information from a genetic test.
The study, published this week in the Archives of Pediatric & Adolescent Medicine, shows that one's perception of disease risk is not just influenced by numbers but by a variety of cognitive and emotional factors. For example, parents were more likely to be worried about their own health when information came from family history as opposed to a genetic test. "Parents interpreted risk differently for themselves than for their children," said the study's lead author, Dr. Beth A. Tarini, an assistant professor of pediatrics at C.S. Mott Children's Hospital. "For parents, family history -- in effect, one's observed genetic destiny -- trumped disease risk as measured by genetic tests."
As genomic science marches forward, the booming genetic testing industry has spawned a new and improved way for males to avert the agony of male pattern baldness. The folks at HairDX, the company that last January arrived first on the scene with a genetic test for baldness, say that the discovery of several new genetic markers for hair loss -- on Chromosome 20 and in the Androgen Receptor gene --have allowed them to refine (think "new and improved!") their services to men everywhere.
Androgenetic Alopecia, or male pattern baldness, is the most common form of baldness. By the age of 35, two-thirds of men have begun losing hair and by 50, 85% have lost an appreciable portion of their locks. A man's risk of developing what the American Hair Loss Assn. calls "this emotionally devastating disorder" increases with age. And by the time a man notices that he is losing his hair, warn the purveyors of the new genetic test, baldness has already gained a solid foothold, with as much as 50% of one's hair already gone.
Early detection is key, they add.
At a cost of $149, the new-generation HairDX genetic test will let physicians tell men whether they have a genetic variation that gives them a 70% probability of going bald. In the absence of this genetic variant, the news is a bit better: A man can expect, with 70% confidence, that he will not have a shiny head. That is a slightly higher level of prediction than could be had in HairDX's first-generation hair loss genetic test, says a company spokesman.
The news of the Hair Loss 2.0 genetic test was greeted with some derision by certain nabobs of genetic negativism.
"When Congress appropriated the millions of dollars to sequence the human genome and to fund the successor project, their hopes and aspirations clearly were to find a solution to baldness, and Hallelujah, we're only steps away," said Kathy Hudson, director of the Center for Genetics and Public Policy at Johns Hopkins University. "Our work is done."
Hudson did worry aloud about whether those who are at high risk of future comb-over -- or who had been given warning but didn't take action -- could still be subject to employment discrimination. Now, there's a public policy implication worth pondering.
Twenty-six different genes are frequently mutated in the most common form of lung cancer, lung adenocarcinoma, according to a study published in the journal Nature. That more than doubles in one swoop the number of genes known to be implicated in this cancer.
We're not talking about genes that were mutated from birth in individuals -- rather, genetic mistakes that accumulated in lung tissue throughout individuals' lifetimes. To track these genes down, the researchers (who are members of the Tumor Sequencing Project, which is a consortium of scientists from several universities) compared samples of lung cancer tissue to non-cancerous tissue donated by 188 patients with lung adenocarcinoma, screening for genetic mistakes in 623 genes that were already known to be linked to other types of cancers.
Among the 26 genes they found were Retinoblastoma 1, linked to a childhood eye cancer; Neurofibromatosis 1, linked to a rare genetic disorder of uncontrolled nerve tissue; another with a mouthful of a name -- Ataxia Telengiectasia Mutated -- linked to some leukemias and lymphoma as well as a rare neurological childhood disorder.
The findings should be medically useful, researchers say, because the 26 genes are known to be involved in a variety of biological pathways through which cells get their housekeeping done. Sometimes, in cancers, these pathways get turned on when they should be off, or ramped up too high, or too low. If scientists know that a pathway's gone awry in a cancer cell, they can use a drug to interfere with that pathway -- and by so doing, maybe block the growth of a tumor.
The researchers found, for example, that two-thirds of the tumors had an altered "MAPK" pathway -- and there are drugs already known to act against that pathway, called MEK inhibitors. Thus they may prove promising in lung cancer treatment. (MEK inhibitors have been tested with some success in mice with colon cancer, though we all know to be wary about making too much of mouse cures.)
The researchers also found key differences between cancers in people with significant histories of smoking, and those who hadn't smoked but still got lung cancer. Smokers' cancers contained many more genetic mutations -- as many as 49, compared with just five in the tumors of nonsmokers.
The degree of genetic variation in the sample is no surprise. Cancer, scientists are learning, is not just one disease -- different genetic mutations can turn a cell rogue. That undestanding is fueling the conviction that cancers, ideally, should be treated in a personalized way -- because the drug that works for one group of patients may not work well for another. Check out the article by Shari Roan on that topic in this week's Health section (a special on cancer).
Last week, California health authorities cracked down on 13 companies that offer personal genetic testing to consumers, saying the labs must prove they meet the state's quality and reliability standards. The state wants to make sure labs offering direct-to-consumer testing are certified and meet quality assurance standards. They also want the labs to show that any testing being sold to Californians has been ordered by a doctor.
That is the crux of this controversy: Should a doctor's authorization be required for someone to obtain personal genetic testing? So far, California and New York state authorities say yes. But this debate is just beginning. The controversy is being played out this week on the many genetic medicine blogs. Daniel at Genetic Future writes:
"To a large extent what's going on here is a turf war between proponents of the old-school medical regulation model and upstart advocates of the free information paradigm of the Google generation."
Jason at TechCrunch suggests the lack of professional medical advice accompanying personal gene testing is troublesome, too:
"The problem with this kind of casual DNA testing is that it almost trivializes the importance of genetic information."
Indeed, what is the intent of personal gene testing? One company, DNA Direct, says it believes gene testing is a medical service and requires doctors to authorize tests. On the other side, some labs are promoting services that help people connect with distant, possibly famous, relatives and discover other, seemingly trivial, information. Example: Do you have a gene that makes you adventurous? Health experts are also becoming increasingly uncomfortable with the publicity surrounding the gene testing of the rich and famous. According to the geneticsandhealth blog, Larry King, cosmologist Stephen Hawking and Microsoft co-founder Paul Allen are all having such tests done. Is personal genetic testing a toy for the rich or a practical medical service?
Tami Dennis, who takes the word "skeptic" to previously uncharted territory, is the Times' Health and Science editor. She's adamant that pitches promoting awareness days, weeks or months are, by their nature, non-stories. And, because she's an adult, she refuses to use words like "veggies," "tummy" and "yummy."
Rosie Mestel, deputy Health and Science editor, studied genetics before abandoning flies, fungi and DNA for health/medical writing. Her hero is the biologist Ernst Haeckel, whose jellyfish paintings inspired snazzy chandeliers. Her favorite toast-spread is Marmite, a British delicacy made of yeast extract. Her least-favorite word is "millenniums."
Melissa Healy is a staff writer for the Health section reporting from Washington D.C. Healy's a veteran of The Times' National staff, having covered the Pentagon, Congress, poverty and social welfare, the environment, and the White House before shifting to Health in 2003. She writes frequently about mental health and human behavior, about federal health policy, prescription medication and ethics in medicine. More wonk than wellness freak, Healy chooses to believe in the health benefits of coffee and wine, and considers water a better work-out medium than beverage.
Karen Kaplan covers genetics, stem cells and cloning. She and colleague Thomas H. Maugh II comprise about 25% of the unofficial MIT-Alumni-in-Journalism Club, and she is proud to have taken more math (5) than English (0) courses in college. Her contributions to Booster Shots will, she hopes, appear more frequently than postings to her mommy blog.
Thomas H. Maugh II has been a science and medical writer at the Times for 23 years. Before that, he was on the staff of the journal Science for 13 years.
He has bachelor's degrees in English and chemistry from MIT and a doctorate in chemistry from UC Santa Barbara.
After a brief stint as a sports writer, Shari Roan turned to health journalism and has covered the topic for The Times for 18 years. She is the author of three books and the mother of two daughters, both teenagers who refer to her as a "health freak." She likes to jog, watch baseball and is very happy that dark chocolate contains some health benefit.
Jeannine Stein writes about fitness, sports medicine and obesity for the Health section. She’s a gym rat from way back and never met an elliptical trainer she didn’t like. Well, maybe one or two. She tempers exercise with a steady diet of reality television because she believes it’s all about balance.
With direct-to-consumer genetic testing now widely available, many health professionals have wondered how families with children will deal with the results of genetic testing. Will parents worry excessively if test results suggest a high risk of disease in a child?
