Boston University scientists claim to have identified a small set of genetic variants that predicts extreme longevity.

The scientists, Paola Sebastiani and Thomas Perls, examined the DNA of 1,055 centenarians living in New England. They isolated 150 gene variants that were common in this population. They subsequently examined a separate sample of centenarians and found that 77% of them had many of the same genetic variants.

The centenarians in the original cohort had as many disease-associated gene variants as shorter-lived people, so the scientists reasoned that the genes they identified must protect against disease.

This conclusion is at odds with current thinking about extreme longevity which is predicated on the assumption that long life is caused by the absence of disease-causing gene variants, rather than the presence of protective genes.

To find the protective genes, the scientists implemented a genome-wide association study, a technique that has so far failed to meet expectations that it would unlock genetic secrets behind common conditions like diabetes and Alzheimer’s disease.

Some scientists questioned the findings of the BU group. Kari Stefansson, a geneticist who works for Decode Gentics told the New York Times for example, that he was “amazed at how many loci of genome-wide significance have been found in a modest sample size.”

Stefansson’s company has also studied extreme longevity. Apparently, none of the BU group’s 150 genetic variants showed up in the population studied by Decode Genetics.

There are roughly 80,000 centenarians in the US right now. Roughly 15 % of the general population has some or many of the 150 genetic variants found in the BU study. Most of them fail to reach a ripe old age because of accidents or an unhealthy lifestyle.

Their report appears in Thursday’s issue of Science.

Boston University scientists claim to have identified a small set of genetic variants that accurately predicts extreme longevity in humans.

The scientists, Paola Sebastiani and Thomas Perls, examined the DNA of 1,055 centenarians living in New England. They isolated 150 gene variants that were common in this population. They subsequently examined a separate sample of centenarians and found that 77% of them had many of the same genetic variants.

The centenarians in the original cohort had as many disease-associated gene variants as shorter-lived people, so the scientists reasoned that the genes they had identified must protect against disease.

This conclusion is at odds with current thinking about extreme longevity which is predicated on the assumption that long life is caused by the absence of disease-causing gene variants, rather than the presence of protective genes.

To find the protective genes, the scientists implemented a genome-wide association study, a technique that had previously failed to meet expectations that it could unlock genetic secrets behind common conditions like diabetes and Alzheimer’s disease.

Some scientists questioned the findings of the BU group. Kari Stefansson, a geneticist who works for Decode Gentics, told the New York Times for example that he was “amazed at how many loci of genome-wide significance have been found in a modest sample size.”

Stefansson’s company has also studied extreme longevity. Apparently, none of the BU group’s 150 genetic variants showed up in the population studied by Decode Genetics.

There are roughly 80,000 centenarians in the US right now. Roughly 15 % of the general population has some or many of the 150 genetic variants found in the BU study. Most of them fail to reach extreme old age because of accidents or an unhealthy lifestyle.

The report appears in Science.

The NIH has rejected a request to approve several dozen colonies of human embryonic stem cells for use by federally funded researchers. The lines were created by Reproductive Genetics Institute, a private infertility clinic based in Chicago. They contain mutations thought to be linked to several diseases including cystic fibrosis, muscular dystrophy and Huntington’s disease.

Many scientists believe that studies using these lines will reveal new information about the diseases, and perhaps lead to new treatments, but NIH Director Francis Collins nixed the proposal on grounds that the acquisition of the new lines violated his organization’s strict ethical guidelines.

The new stem cell lines were obtained from embryos donated by couples that were receiving treatment for infertility. The company decided against using them after tests revealed the genetic defects.

An NIH advisory panel tasked by Collins to evaluate the situation found however, that the consent forms used by RGI to secure the lines included unacceptably broad language and required couples to give up their right to sue the clinic for any cause.

Collins’ decision will limit research on the valuable cell lines to scientists who have secured private funding. The new NIH director did approve 8 other new stem cell lines, meaning that federally funded scientists have 75 different lines they can use for research.

“The NIH guidelines for reviewing stem cell lines for federal funding were set up to adhere rigorously to the well-established norms for informed consent,” Collins said in a statement. “It was painful for my advisory committee to recommend against approval of additional lines from RGI because of a consent problem, but rigorous guidelines are only meaningful if they are rigorously applied.”

In a truly remarkable scientific breakthrough, researchers at Synthetic Genomics, Inc. have created a living organism that is wholly controlled by man-made genetic instructions.

“We call it the first synthetic cell,” Craig Venter, the company founder who oversaw the project told the Wall Street Journal. “These are very much real cells.”

The unicellular organism can reproduce but has no living ancestors.

The laboratory methods used to create it, which are patented by Synthetic Genomics, appear to be applicable to other bacterial strains with commercial potential. In fact at least 3 companies are using similar methods to create organisms which produce fuels and vaccines and (better late than never) gobble up oil spills.

“This is literally a turning point in the relationship between man and nature,” said molecular biologist Richard Ebright of Rutgers University. “For the first time, someone has generated an entire artificial cell with predetermined properties.”

Synthetic Genomics provided $30 million to fund the work. It owns intellectual-property rights to the entire process.

To create the new life form, Venter and bioengineer Daniel Gibson stripped out the DNA of a bacterium known as Mycoplasma capricolum and replaced it with a genome they built which was a variant of a second species known as Mycoplasma mycoides. The minor variations amount to biochemical signatures of the scientists, essentially proving the creation was theirs.

“We make a genome from four bottles of chemicals; we put that synthetic genome into a cell; that synthetic genome takes over the cell,” Gibson told the Journal. “The cell is entirely controlled by that new genome.”

The incredible work is documented in Science.

Soon after the announcement, the House Energy and Commerce Committee said it would hold public hearings on the matter in the near future.

Responding to criticism from scientists and the FDA, Walgreens has postponed plans to market a personal genetic test kit made by Pathway Genomics

“We’ve elected not to move forward with offering the Pathway product to our customers until we have further clarity on this matter,” a Walgreens statement said.

The Pathway Genomics kit uses saliva samples to assess one’s risk of contracting in excess of 70 diseases including lung cancer, hypertension and heart disease.

The kits cost $20. They include a plastic container, handy instructions and a postage-paid envelope to ship the specimen to a San Diego-based laboratory. Testing costs an additional $79 to $249.

The state-of-the-art in genomic science these days is that it’s easy and inexpensive to obtain genetic markers for a host of diseases, but there is insufficient data to give much credence to the findings…at least for diseases like cancer, diabetes and heart disease which are thought to be influenced by hundreds of different genes.

“Many of these markers are not understood, even what genes they are affecting right now,” Kenneth Offit, the chief of clinical genetics at Memorial Sloan-Kettering Cancer Center in New York told CNN. “It’s a very, very early stage in this level of genomic research.”

For its part, the FDA said, “Pathway Genomics has moved outside of the currently sanctioned boundaries for lab-developed tests by marketing (its) product in a retail store. These kits have not been proven safe, effective or accurate. Patients could be making medical decisions based on data from a test that hasn’t been validated by the FDA.”

Of note, Pathway Genomics has sold these kits online for the last 8 months. In fact, more than 30 companies offer personal genetic tests on line.

Rejection of the donor organ is a frequent and sometimes life-threatening complication of heart transplantation. It is best handled if caught early, and since early rejection is typically asymptomatic, physicians had heretofore been required to perform regular biopsies to screen for rejection of the transplanted heart.

The biopsy is expensive and not without risk however, so scientists have long searched for a non-invasive alternative to diagnose rejection.

That search may have yielded results. In a presentation at last month’s meeting of the International Society for Heart & Lung Transplantation, Michael Pham and colleagues from Stanford University showed that a genetic test reduced the need for biopsies in selected patients.

The gene test is known as Allomap. It is marketed by XDx and has been used on 7,000 transplant recipients so far. It costs about $3,000, or 25-40% less than the biopsy.

The study by Pham’s team included 602 transplant recipients. It showed that Allomap was as effective as routine biopsies in preventing serious episodes of transplant rejection like heart failure, the need for a re-transplant or death.

The study was limited to patients who were at low risk for rejection and had undergone the procedure at least 6 months prior to enrollment. Nineteen months after randomization, 14.5% of patients that were followed with the genetic test and 15.3% of those followed with routine biopsies suffered a major complication.

“You’re not going to harm patients by reducing the number of biopsies,” Pham told the Wall Street Journal.

Pham noted that his team’s findings could not be extrapolated to patients that had received a transplant within the last 6 months or to those at high risk for rejection.

The study appears in the New England Journal of Medicine.

Last week, a federal judge threw out patents on BRCA1 and BRCA2, genes whose mutations are linked to breast and ovarian cancer. The decision casts doubt on patents covering thousands of human genes.

In his decision, US District Court Judge Robert Sweet  ruled the patents were “improperly granted” since they involved a “law of nature.” He rejected the notion that isolating a gene made it patentable, calling that “a ‘lawyer’s trick’” which circumvents the “prohibition on the direct patenting of the DNA in our bodies but which, in practice, reaches the same result.”

The case had been brought by patients and medical organizations last May. They argued that genes, as products of nature, are discoverable and hence fall outside of the universe of things that can be patented. They also argued that patents drive up testing costs and stifle biomedical innovation.

Myriad Genetics is the company that held the BRCA patents. It markets a $3,000 test that scans for mutations in the genes which are associated with a high risk of breast and ovarian cancer.

Nearly 20% of all human genes have been patented. Enormous industries have been created around the intellectual property rights granted by these patents.

If the decision withstands a likely appeal, it might become difficult for companies to raise venture capital to support genomics research. “The industry is going to have to get more creative about how to retain exclusivity and attract capital in the face of potentially weaker patent protection,” said Kenneth Chahine, a law professor who filed an amicus brief for Myriad.

In that instance, “the government is going to become the funder for content discovery because it’s going to be hard to justify it outside of academia,” venture capitalist Bryan Roberts told the New York Times.

Everyone knows that people react differently to pain: the initial jab of Novocain at a dentist’s office causes excruciating discomfort for some, while others barely seem to mind. But is that because some people truly feel more pain than others in a given circumstance (such as an injection) or because some people can just suck it up better?

A new study by Frank Reimann and colleagues at Cambridge Institute for Medical Research suggests the former may be true, even though it doesn’t completely rule-out the whimp factor.

Reimann’s group reported in the Proceedings of the National Academy of Sciences that variations in the SCN9A gene were associated with changes in the perception of pain.

To reach this conclusion, they studied kids with a rare condition characterized by an inability to detect pain. These kids can pass knives through their arms and walk across hot coals without a flinch. Reimann’s group found this extremely maladaptive condition was associated with a nonfunctioning SCN9A gene.

The scientists reasoned that polymorphism at the SCN9A locus could cause differing pain thresholds, and tested their hypothesis by examining DNA from 578 people with osteoarthritis. They found that folks having a common variant of the SCN9A gene had lower pain self-assessment scores than those having a rarer form of the gene.

The scientists reproduced their findings in people with back pain, pancreatitis and phantom limb pain.

The SCN9A gene it turns out, codes for a membrane-bound protein on pain sensory nerve cells. The protein is involved with triggering those cells, which then relay a pain message to the brain. Apparently, the version of the protein created by the rare SCN9A decreases firing thresholds in the cells so they are more likely to relay bad news.

The obesity epidemic has become a major public health concern. The phenomenon is typically attributed to changes in diet and lifestyle, and socioeconomic factors like poverty and poor education.

Genetic factors have been known play a role as well, but a recent study by UK-based scientists suggests they play much more prominent role, at least in a subset of people who become morbidly obese at a young age.

In the study, Sadaf Farooqi of the University of Cambridge and colleagues showed that many such kids are missing a large chunk of DNA, known as SH2B1, from chromosome 16.

The missing genetic code had been known to play a role in regulating weight and blood sugar levels. Kids with the chromosomal abnormality tended to overeat on a massive scale, and gain weight easily. 

To reach these conclusions, the scientists scanned the genomes of 300 morbidly obese kids in search of copy number variants (CNVs), which are lengthy strands of DNA that are either duplicated or missing.
The scientists compared their findings with information from healthy controls.

In their write-up, which appears in Nature, the scientists wrote, “we identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls.”

“Part of chromosome 16 can be deleted in some families. People with this deletion have severe obesity from a young age,” Farooqi told Medical News Today: “One particular gene on chromosome 16 called SH2B1 plays a key role.”

The finding may have broad social implications, since it is common to blame parents or guardians for morbid obesity in kids. The scientists noted for example, that some kids in the study had been handed over to Social Services because their parents were assumed to have been deliberately overfeeding them.

A multinational group of scientists has concluded that about a third of the genetic underpinnings of schizophrenia are caused by the interactions of many thousand common genetic variants. While each variant may be harmless on its own, the combined impact vastly increases the risk of both schizophrenia and bipolar disorder.

The results imply that the genetic basis of the 2 common psychoses  are more complex than had been thought, and that the conditions can develop not just from a rare, devastating genetic variant, but from dozens or hundreds of common ones.

The write-up is in Nature.
 
“This is an enormous first for our field,” co-author Patrick Sullivan told BurrillReport. “We now have the outline of the puzzle, we just need to… see how (the pieces) fit together,” added the professor of psychiatry at the UNC School of Medicine.
 
Although scientists have long recognized that schizophrenia has a genetic basis, it’s only recently that they’ve started pinpointing offending genetic loci.
 
To reach their conclusions, Sullivan and colleagues isolated 30,000 genetic variants that occurred more frequently in 3,000 people having schizophrenia than in a control group without the condition. The team confirmed the differences in 2 other populations of schizophrenic patients and 2 groups with bipolar disorder.

The genetic link between schizophrenia and bipolar disorder had not previously been recognized.
 
“While our study finds a surprising number of genetic effects, we expect that future work will assemble them into meaningful pathways that will teach us about the biology of schizophrenia and bipolar disorder,” senior author Pamela Sklar told Burrill.
 
The scientists also found that a particular HLA haplotype increased the risk for both psychoses. Since HLA proteins are involved in the immune response to infections, they speculated that an infectious agent might be an etiologic factor.

Just 6 years after scientists decoded the human genome, a line of research derived from the breakthrough known as personal genomic medicine is increasingly perceived to be an expensive bear with an uncertain future, according to commentaries in the New England Journal of Medicine.

Since the heralded announcement in 2003, geneticists have undertaken hundreds of genomewide association studies designed to compare the DNA of healthy people with those of patients having specific diseases.

The hope was to pinpoint a handful of culprit genes and by association, biochemical processes that could become targets for disease-modifying drugs, immune therapy or what have you.

But the studies appear capable of explaining just a fraction of the genetic component underlying complex diseases like cancer, schizophrenia and diabetes.

The problem, it seems, has been the assumption that such conditions were promoted by variations in a small number of genes, say 10. Instead, thousands of genes appear to be involved, with multiple variations at each locus exerting myriad effects on other genes and their variants.  

The snafu represents a setback for personal genomics companies that hoped to inform customers about their risk for these diseases.

“With few exceptions, what the genomics companies are doing right now is recreational genomics,” Duke University geneticist David Goldstein told the New York Times. “The information has little or…no clinical relevance.”

In his NEJM piece, Goldstein therefore recommends a strategic shift in genomics research towards decoding the entire DNA of patients with certain diseases.

But Peter Kraft and David Hunter of the Harvard School of Public Health, publishing in the same issue, remain optimistic about genomewide association studies.

“There will be more common variants to find,” Hunter told the Times. “It would be unfortunate if we gave up now.”

Plavix-popping patients in posession of a particular gene that prevents its proper metabolism were at twice the risk of sustaining cardiovascular events, and the risk could not be mitigated by high doses of the stuff, according to 2 studies presented at last week’s meetings of the American College of Cardiology.

In the first study, Paul Gurbel and colleagues showed that 21% of patients with the cytochrome P450 2C19*2 polymorphism had a cardiovascular event within a year following coronary artery stenting, even though they received Plavix to prevent such occurrences.

The University of Maryland-based scientists found that only 10% of noncarriers experienced that outcome.

“This common variant encodes a defective enzyme that likely fails to convert Plavix to its active metabolite, leading to lesser inhibition of platelet function and diminished cardiovascular protection,” Gurbel told MedPageToday.

In the second study of 33 patients that had a poor response to the standard 75 mg dose of Plavix, Jean-Philippe Collet and colleagues at INSERM in Paris found that doubling the standard dose improved results in all but 7 patients.

Six of these 7 patients were CYP2C19*2 positive.

The scientists prescribed Effient, an alternative antiplatelet drug to eligible patients in this group, and all responded nicely.

“The day is rapidly approaching” when physicians can determine in advance how patients will respond to antiplatelet therapy and select agents likely to be effective “rather than blindly administering Plavix as we do now,” Gurbel concluded.

Plavix is co-marketed by Sanofi-Aventis and Bristol-Meyers Squibb. It is the world’s second largest selling drug, with $4 plus billion in revenues last year. It enjoys patent protection until November, 2011.

Eli Lilly and Daiichi Sankyo co-developed Effient, which was recently approved in the EU and is edging toward FDA approval.

Scouting video on the Big O confirms he doesn’t just lean left politically.

Interestingly though, 5 of the last 7 presidents have been left-handed including Ford, Reagan, Bush the semi-reasonable, Clinton and Obama. Only Carter and Bush II went right.

That seems odd given that only 10% of humans are lefties, but it’s probably just a statistical fluke.

Even if it wasn’t, no one knows whether or how left-handedness impacts factors that drive electoral success like political skill, smarts, charisma, appearance, insider connections, and wealth. 

And before lefties start popping their collars, they’d be well to remember they’re at increased risk of accidental death not to mention a possibly increased risk for some psychiatric diseases. 

It’s not clear why some people become left-handed, although genes are clearly involved. About one-quarter of the sons of left-handed parents are left-handed, whereas only 10% of boys who have right-handed parents end up as southpaws.

But genes aren’t the whole story since 20% of identical twins have different handedness.

Non genetic effects on handedness can be demonstrated in chickens, in whom brain lateralization is driven by light penetrating the shell during incubation.

In most chick embryos, the right eye is exposed to light. These chickens end up being more adept at identifying food and prey with their right eye, and are better able to detect predators and potential mates with their left eye.

If the eggs are incubated in darkness however, the resulting adults don’t lateralize this way.

A consortium of US scientists has reported that an easy-to-perform analysis of 50 genes can reliably sort breast cancer tissue samples by type and predict which therapies are most likely to work. 
  
Philip Bernard, Joel Parker, Matthew Ellis and many others published the heartening findings in the Journal of Clinical Oncology.

“Unlike a widely used genomic test that applies only to lymph-node negative, estrogen-receptor positive breast cancer, this new genomic test is broadly applicable for all women diagnosed with breast cancer,” Ellis, a breast cancer expert from Washington University told BurrillReport.
 
To develop and validate the 50 gene test, the scientists reviewed more than 1,000 breast cancer tissue specimens. They were able to establish a genetic signature for each major form of breast cancer: luminal A, luminal B, basal-like and HER2-enriched.
 
Then, having accurately classified 133 consecutive tissue specimens using their tool, the scientists assessed how the different breast cancer phenotypes responded to chemotherapy.

The test turned out to be highly predictive of chemotherapy response, and superior to currently used tests like estrogen and progesterone receptor status and HER2 gene expression status.
 
For example, patients with luminal A cancers did not respond to chemotherapy, suggesting that they ought to forgo chemotherapy in lieu of hormone-based treatment.

Conversely, basal-like breast cancer, which carries an ominous prognosis, turned out to be “the most sensitive to chemotherapy. By identifying (the cancer types correctly) we can ensure they are treated adequately,” Ellis said.
 
The scientists are now studying how each breast cancer type responds to the 20 or so chemotherapeutic drugs on the market.

When it’s ready, the new genomic test will be marketed by University Genomics, which is owned by Washington University, the University of Utah and the University of North Carolina.

For decades, scientists theorized that aging was caused by oxidative stress, a phenomenon in which cellular damage is caused by free radicals and nasty oxygen-based molecules that build up over time as byproducts of normal biological processes.

According to the theory, the cellular defense against the culprits-which are enzymes known as superoxide dismutases-gets overwhelmed by the accumulating bad guys and the next thing you know, cells are looking like Methuselah.

From the theory sprung an entire industry hawking antioxidant therapies from Vitamin A to Coenzyme Q which supposedly boosted the body’s ability to water-cannon the free radicals.

Alas clinical trials have never shown them to work and now McGill University scientists are raising doubts about the validity of the oxidative stress theory itself.

Siegfried Hekimi and colleagues disabled one-by-one, 5 genes coding for superoxide dismutases in a worm that goes by the unassuming name C. elegans.

The successive gene deletions did not shorten the worms’ lifespan; in fact in one instance, the altered critters outlived the wild-types.

The report is in PloS Genetics.

Come to think of it, the evidence supporting the oxidative stress theory is circumstantial, Hekimi told BurrillReport.

And oxidative stress could be the result of aging rather than its cause.

“It is true that the more an organism appears aged, whether in terms of disease, or appearance or anything you care to measure, the more it seems to be suffering from oxidative stress. (But) people think correlation is causation,” he told BurrillReport.
 
Hekimi’s not saying oxidative stress is actually a good thing. It clearly interferes with normal cellular functioning. But it’s a stretch, he says, to say that oxidative stress causes aging.

Scientists at Dana-Farber Cancer Institute and the CDC have produced monoclonal antibodies that can destroy most strains of flu virus, a new line of attack that promises to overcome the virus’ maddening ability to mutate and thus fool today’s vaccines.

Such antibodies “could provide broad protection against all seasonal and pandemic influenza A viruses,” according to Wayne Marasco of Harvard Medical School and colleagues.

The potion targets the flu virus near its base, a region that turns out to be genetically stable.

The base mediates viral entry into cells, Marasco’s team wrote in Nature Structural & Molecular Biology.

Today’s vaccines stimulate antibody production against the viral head, a region that demonstrates extraordinary genetic polymorphism. That’s why flu vaccines are useless after one year at best and queueing-up for a jab has become an annual ritual for millions.

Coauthor Ruben Donis of the CDC is confident his group has flu by the short hairs, pointing out to MedpageToday that “By mutating (at the base, the flu virus) commits suicide.” 

The monoclonal antibodies appear to work against multiple strains of flu, including H5N1 avian flu and the H1N1 Spanish flu strain that killed 50 million people in 1918.

They also were shown to prevent flu symptoms in animals even when given 24 hours after exposure to flu virus, so long as they’re given in higher but “achievable” doses, according to the scientists.

The next step is to see whether the antibodies work in ferrets, which strangely enough have immunologic responses to flu virus more like humans than any other species.

Clinical trials could begin in 2 years.
 
The Dana-Farber holds patents on the discovery of the static region and the monoclonal antibodies against it.