Mar. 27, 2013 ? Scientists at Harvard may have new hope for anyone who's tried to fight the battle of the bulge.
New research, conducted in collaboration with researchers at Massachusetts General Hospital, has found that the gut microbes of mice undergo drastic changes following gastric bypass surgery. Transfer of these microbes into sterile mice resulted in rapid weight loss. The study is described in a March 27 paper in Science Translational Medicine.
"Simply by colonizing mice with the altered microbial community, the mice were able to maintain a lower body fat, and lose weight -- about 20% as much as they would if they underwent surgery," said Peter Turnbaugh, a Bauer Fellow at Harvard's Faculty of Arts and Sciences (FAS) Center for Systems Biology, and one of two senior authors of the paper.
But as striking as those results were, they weren't as dramatic as they might have been.
"In some ways we were biasing the results against weight loss," Turnbaugh said, explaining that the mice used in the study hadn't been given a high-fat, high-sugar diet to increase their weight beforehand. "The question is whether we might have seen a stronger effect if they were on a different diet."
"Our study suggests that the specific effects of gastric bypass on the microbiota contribute to its ability to cause weight loss and that finding ways to manipulate microbial populations to mimic those effects could become a valuable new tool to address obesity," said Lee Kaplan, director of the Obesity, Metabolism and Nutrition Institute at MGH and the other senior author of the paper.
"We need to learn a good deal more about the mechanisms by which a microbial population changed by gastric bypass exert its effects, and then we need to learn if we can produce these effects -- either the microbial changes or the associated metabolic changes -- without surgery," Kaplan, an associate professor of Medicine at Harvard Medical School, added. "The ability to achieve even some of these effects without surgery would give us an entirely new way to treat the critical problem of obesity, one that could help patients unable or unwilling to have surgery."
While the results were exciting, Turnbaugh warned that it may be years before they could be replicated in humans, and that such microbial changes shouldn't be viewed as a way to lose those stubborn last 10 pounds without going to the gym. Rather, the technique may one day offer hope to dangerously obese people who want to lose weight without going through the trauma of surgery.
"It may not be that we will have a magic pill that will work for everyone who's slightly overweight," he said. "But if we can, at a minimum, provide some alternative to gastric bypass surgery that produces similar effects, it would be a major advance."
While there had been hints that the microbes in the gut might change after bypass surgery, the speed and extent of the change came as a surprise to the research team.
In earlier experiments, researchers had shown that the guts of both lean and obese mice are populated by varying amounts of two types of bacteria, Firmicutes and Bacteroidetes. When mice undergo gastric bypass surgery, however, it "resets the whole picture," Turnbaugh said.
"The post-bypass community was dominated by Proteobacteria and Proteobacteria, and had relatively low levels of Firmicutes," he said. What's more, Turnbaugh said, those changes occurred within a week of the surgery, and weren't short-lived -- the altered gut microbial community remained stable for months afterward.
While the results may hold out the hope for weight loss without surgery, both Turnbaugh and Kaplan warned that future studies are needed to understand exactly what is behind the weight loss seen in mice.
"A major gap in our knowledge is the underlying mechanism linking microbes to weight loss," Turnbaugh said. "There were certain microbes that we found at higher abundance after surgery, so we think those are good targets for beginning to understand what's taking place."
In fact, Turnbaugh said, the answer may not be the specific types of microbes, but a by-product they excrete.
In addition to changes in the microbes found in the gut, researchers found changes in the concentration of certain short-chain fatty acids. Other studies, Turnbaugh said, have suggested that those molecules may be critical in signaling to the host to speed up metabolism, or not to store excess calories as fat.
Going forward, Turnbaugh and Kaplan hope to continue to explore those questions.
"We think such studies will allow us to understand how host/microbial interactions in general can influence the outcome of a given diet," Kaplan said. "To some degree, what we're learning is a comfort for people who have an issue with their weight, because more and more we're learning that the story is more complicated than just how much you exercise and how much you eat."
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The above story is reprinted from materials provided by Harvard University, via EurekAlert!, a service of AAAS.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
A. P. Liou, M. Paziuk, J.-M. Luevano, S. Machineni, P. J. Turnbaugh, L. M. Kaplan. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Science Translational Medicine, 2013; 5 (178): 178ra41 DOI: 10.1126/scitranslmed.3005687
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Mar. 25, 2013 ? Scientists at the Department of Physics of the University of Oulu have teamed up with scientists in France, Russia and Japan to propose a new experimental method for researching positively charged ions. The study, In the Finnish side carried out by postdoctoral researcher Saana-Maija Huttula and Professor Marko Huttula in Oulu, was published in Physical Review Letters on 12 March 2013. The study involved investigating the electronic structure of the argon ions using synchrotron radiation. The proposed theoretical simulations were done using methods developed by an electron spectroscopy research group based at the University of Oulu.
The study was co-financed by the Academy of Finland.
Studying the electronic properties of positively charged ions is very difficult using traditional methods, due to the very low density available in ionic beams. The alternative method proposed by the international research team is based on the single-photon multi-ionisation of the corresponding neutral atom and on coincidence techniques, which allows for the near-simultaneous detection of all the electrons scattered from a single atom.
According to Saana-Maija Huttula, the principal investigator of the present publication, the method has two advantages: the huge intensity generated and the accurate configuration of the electronic initial states of ions. The scientists expect the method to become a common tool that has the potential to lead to important new discoveries in the field of ion research. Coincidence techniques can also be applied directly in the study of the properties of molecular materials. In fact, researchers at the University of Oulu are already expanding their work to heavy-metal compounds and nanoparticles.
More recently, the research team has been studying, for example, the electronic structure and dynamics of mercury molecules and clusters. Mercury compounds, though environmentally hazardous, are an important raw material for the electronics industry, but they also play an important role in atmospheric chemistry, for instance. The team has focused its efforts on the investigation of metallic nanoparticles. In addition, the scientists are actively engaged in international cooperation at the interface of fundamental free-electron laser research and multinational corporate collaboration. At the national level, the team is an active promoter of using synchrotron radiation for research and analysis purposes.
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The above story is reprinted from materials provided by Suomen Akatemia (Academy of Finland).
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Journal Reference:
S.-M. Huttula, P. Lablanquie, L. Andric, J. Palaudoux, M. Huttula, S. Sheinerman, E. Shigemasa, Y. Hikosaka, K. Ito, F. Penent. Decay of a 2p Inner-Shell Hole in an Ar^{ } Ion. Physical Review Letters, 2013; 110 (11) DOI: 10.1103/PhysRevLett.110.113002
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Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
On Tuesday and Wednesday, the U.S. Supreme Court will hear two cases concerning marriage rights for same-sex couples. In one, United States v. Windsor, the court could determine whether the federal Defense of Marriage Act (DOMA) violates the constitutional rights of same-sex couples. The other, Hollingsworth v. Perry, tackles Proposition 8, California?s ban on gay marriage that voters narrowly passed in 2008.
Yahoo News asked Americans who will be affected by these cases to share their stories and perspectives. Here's a sampling of what they said.
'I can't help but hold on to a thread of hope'
In 2010, Jacob Z. Flores had two weddings. He and his husband got married first in Provincetown, Mass., and three weeks later they had a ceremony in their hometown of Victoria, Texas.
Their marriage was legal in Massachusetts. But, Flores writes, they held the second ceremony ?to demonstrate to our friends and family that we were just like the other married couples they knew, whether it was legal in Texas or not."
?Yet, when both weddings were over, I couldn't help but feel cheated," he continued. "In each other's eyes and in the eyes of our friends, we were husbands, but to the federal government we were not.?
So for Flores, this week?s arguments over same-sex marriage in the nation?s highest court are a reason to be hopeful. He sees the cases on DOMA and Proposition 8 as similar to bans on interracial marriage and notes that the Supreme Court struck down such laws.
?I can't help but hold on to a thread of hope,? Flores writes. ?My marriage might be recognized on a federal level soon.?
'I could not perform a gay wedding'
D.L. Teamor, 39, a pastor in Michigan, says she ?cannot and will not judge another person,? but that she feels gay marriage violates the tenets of her faith.
?I believe that marriage is the union of one man and one woman as illustrated in the Bible, the nucleus of my faith,? Teamor writes. ?The laws and lessons contained therein do not change according to modern times or popular outlooks.?
She adds that performing a gay wedding ?would completely oppose my Christian beliefs."
?Sacrilege?
Another clergy member, Gerald Watt, has the same worries as Teamor. Watt says he supports civil unions but is opposed to same-sex marriage. ?To attempt to join two same sex individuals in the sacrament of marriage would be a sacrilege for me,? Watt writes.
He lives in Illinois, which is debating legalizing gay marriage. He notes that the proposed law allows for clergy to be exempt from performing same-sex weddings, but he fears that provision might not last.
?I can see a time when test cases will eventually force the government to withdraw credentials from clergy like me,? he writes. ?I might even be sued for violation of someone's civil rights.?
?Anxiety and anticipation?
Kate Coenen has been engaged since July, but she hasn?t made any solid wedding plans. Her fianc?e is finishing her degree at the University of Michigan, and they don?t know where they?ll live after graduation.
?Because each state has its own approach to same-sex marriage, we may end up in a state that won't recognize our relationship,? Coenen, 26, writes. Regardless of where they wind up, Coenen says she and her fianc?e ?plan on building our lives together whether or not we end up living in a state where we can marry legally.?
To her, the potential for broader recognition of gay marriage is more than just a symbol. She, too, wants to take advantage of ?tangible benefits that many people in straight couples take for granted.?
The end of DOMA ?would give our lives a greater degree of stability and certainty,? she writes.
But no matter how the Supreme Court cases turn out, Coenen, who was a student at the University of Iowa when the state?s Supreme Court legalized gay marriage there in 2009, is optimistic about the prospects for gay marriage.
?I look forward to sharing that future with my wife-to-be,? she writes.
?DOMA is a slap in the face?
A.R. Treadway lives with her partner of seven years in DeLand, Fla., where they are raising her son from, as she puts it, her ?former life.?
She believes ?DOMA is a slap in the face??one with practical implications for her family.
?I want to be able to have the same rights and protections my parents have,? Treadway writes. ?When my father passes away, my mother is eligible to collect his benefits [and] make arrangements for his burial. ... If I died tomorrow, my fianc? couldn't make funeral arrangements for me or claim my son as her son, which would mean a nasty court battle between my family and his birth father.?
She also hopes to one day see gay marriage recognized in all 50 states. But, as she awaits the outcome of the DOMA and Proposition 8 cases, she is seeing some advances for LGBT rights in Florida and is ?enjoying the little victories.?
Worry at church and at work
Matt Bianco, 36, of Southern Pines, N.C., works at a Christian company and is an elder in his church. He fears that broad legalization of gay marriage could force both institutions to violate their conscience.
?In both cases, they have the right, and possibly the duty, to oppose gay marriage, including the funding of health and benefits coverage for the gay spouse,? Bianco writes.
For him, the root of the problem is the government?s involvement in marriage in the first place. He writes that ?the government has usurped authority it does not have? by giving benefits to married couples. And now, with the Supreme Court cases looming, he sees moral conflicts on the horizon over the granting of those benefits.
?This is not simply a matter of gays wanting equal access to marriage; this is a case of the government imposing acceptance of and financial support of gay marriage upon individuals and employers who are morally opposed to gay marriage,? he writes.
Contact: Michael Bishop michael.bishop@iop.org 01-179-301-032 Institute of Physics
Up until now, the invisibility cloaks put forward by scientists have been fairly bulky contraptions an obvious flaw for those interested in Harry Potter-style applications.
However, researchers from the US have now developed a cloak that is just micrometres thick and can hide three-dimensional objects from microwaves in their natural environment, in all directions and from all of the observers' positions.
Presenting their study today, 26 March, in the Institute of Physics and German Physical Society's New Journal of Physics, the researchers, from the University of Texas at Austin, have used a new, ultrathin layer called a "metascreen".
The metascreen cloak was made by attaching strips of 66 m-thick copper tape to a 100 m-thick, flexible polycarbonate film in a fishnet design. It was used to cloak an 18 cm cylindrical rod from microwaves and showed optimal functionality when the microwaves were at a frequency of 3.6 GHz and over a moderately broad bandwidth.
The researchers also predict that due to the inherent conformability of the metascreen and the robustness of the proposed cloaking technique, oddly shaped and asymmetrical objects can be cloaked with the same principles.
Objects are detected when waves whether they are sound, light, x-rays or microwaves rebound off its surface. The reason we see objects is because light rays bounce off their surface towards our eyes and our eyes are able to process the information.
Whilst previous cloaking studies have used metamaterials to divert, or bend, the incoming waves around an object, this new method, which the researchers dub "mantle cloaking", uses an ultrathin metallic metascreen to cancel out the waves as they are scattered off the cloaked object.
"When the scattered fields from the cloak and the object interfere, they cancel each other out and the overall effect is transparency and invisibility at all angles of observation," said co-author of the study Professor Andrea Alu.
"The advantages of the mantle cloaking over existing techniques are its conformability, ease of manufacturing and improved bandwidth. We have shown that you don't need a bulk metamaterial to cancel the scattering from an object a simple patterned surface that is conformal to the object may be sufficient and, in many regards, even better than a bulk metamaterial."
Last year, the same group of researchers were the first to successfully cloak a 3D object in another paper published in New Journal of Physics, using a method called "plasmonic cloaking", which used more bulky materials to cancel out the scattering of waves.
Moving forward, one of the key challenges for the researchers will be to use "mantle cloaking" to hide an object from visible light.
"In principle this technique could also be used to cloak light," continued Professor Alu.
"In fact, metascreens are easier to realize at visible frequencies than bulk metamaterials and this concept could put us closer to a practical realization. However, the size of the objects that can be efficiently cloaked with this method scales with the wavelength of operation, so when applied to optical frequencies we may be able to efficiently stop the scattering of micrometer-sized objects.
"Still, we have envisioned other exciting applications using the mantle cloak and visible light, such as realizing optical nanotags and nanoswitches, and noninvasive sensing devices, which may provide several benefits for biomedical and optical instrumentation."
###
From Tuesday 26 March, this paper can be downloaded from http://iopscience.iop.org/1367-2630/15/3/033037/article.
Notes to Editors
Contact
1. For further information, a full draft of the journal paper or contact with one of the researchers, contact IOP Publishing Press Officer, Michael Bishop:
Tel: 0117 930 1032
E-mail: Michael.Bishop@iop.org
IOP Publishing Journalist Area
2. The IOP Publishing Journalist Area (http://journalists.iop.org/journalistLogin) gives journalists access to embargoed press releases, advanced copies of papers, supplementary images and videos. In addition to this, a weekly news digest is uploaded into the Journalist Area every Friday, highlighting a selection of newsworthy papers set to be published in the following week.
Login details will also give free access to IOPscience, IOP Publishing's journal platform.
To apply for a free subscription to this service, please email Michael Bishop, IOP Press Officer, michael.bishop@iop.org, with your name, organisation, address and a preferred username.
Demonstration of an ultra-low profile cloak for scattering suppression of a finite-length rod in free space
3. The published version of the paper "Demonstration of an ultra-low profile cloak for scattering suppression of a finite-length rod in free space" (J C Soric et al 2013 New J. Phys. 15 033037) will be freely available online from Tuesday 26 March. It will be available at http://iopscience.iop.org/1367-2630/15/3/033037/article.
New Journal of Physics
4. New Journal of Physics publishes across the whole of physics, encompassing pure, applied, theoretical and experimental research, as well as interdisciplinary topics where physics forms the central theme. All content is permanently free to read and the journal is funded by an article publication charge.
IOP Publishing
5. IOP Publishing provides publications through which leading-edge scientific research is distributed worldwide. IOP Publishing is central to the Institute of Physics (IOP), a not-for-profit society. Any financial surplus earned by IOP Publishing goes to support science through the activities of IOP. Beyond our traditional journals programme, we make high-value scientific information easily accessible through an ever-evolving portfolio of community websites, magazines, conference proceedings and a multitude of electronic services. Focused on making the most of new technologies, we're continually improving our electronic interfaces to make it easier for researchers to find exactly what they need, when they need it, in the format that suits them best. Go to http://ioppublishing.org/
The Institute of Physics
6. The Institute of Physics is a leading scientific society promoting physics and bringing physicists together for the benefit of all.
It has a worldwide membership of around 40 000 comprising physicists from all sectors, as well as those with an interest in physics. It works to advance physics research, application and education; and engages with policy makers and the public to develop awareness and understanding of physics. Its publishing company, IOP Publishing, is a world leader in professional scientific communications. Go to http://www.iop.org
The German Physical Society
7. The German Physical Society (DPG) with a tradition extending back to 1845 is the largest physical society in the world with more than 59,000 members. The DPG sees itself as the forum and mouthpiece for physics and is a non-profit organisation that does not pursue financial interests. It supports the sharing of ideas and thoughts within the scientific community, fosters physics teaching and would also like to open a window to physics for all those with a healthy curiosity.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Contact: Michael Bishop michael.bishop@iop.org 01-179-301-032 Institute of Physics
Up until now, the invisibility cloaks put forward by scientists have been fairly bulky contraptions an obvious flaw for those interested in Harry Potter-style applications.
However, researchers from the US have now developed a cloak that is just micrometres thick and can hide three-dimensional objects from microwaves in their natural environment, in all directions and from all of the observers' positions.
Presenting their study today, 26 March, in the Institute of Physics and German Physical Society's New Journal of Physics, the researchers, from the University of Texas at Austin, have used a new, ultrathin layer called a "metascreen".
The metascreen cloak was made by attaching strips of 66 m-thick copper tape to a 100 m-thick, flexible polycarbonate film in a fishnet design. It was used to cloak an 18 cm cylindrical rod from microwaves and showed optimal functionality when the microwaves were at a frequency of 3.6 GHz and over a moderately broad bandwidth.
The researchers also predict that due to the inherent conformability of the metascreen and the robustness of the proposed cloaking technique, oddly shaped and asymmetrical objects can be cloaked with the same principles.
Objects are detected when waves whether they are sound, light, x-rays or microwaves rebound off its surface. The reason we see objects is because light rays bounce off their surface towards our eyes and our eyes are able to process the information.
Whilst previous cloaking studies have used metamaterials to divert, or bend, the incoming waves around an object, this new method, which the researchers dub "mantle cloaking", uses an ultrathin metallic metascreen to cancel out the waves as they are scattered off the cloaked object.
"When the scattered fields from the cloak and the object interfere, they cancel each other out and the overall effect is transparency and invisibility at all angles of observation," said co-author of the study Professor Andrea Alu.
"The advantages of the mantle cloaking over existing techniques are its conformability, ease of manufacturing and improved bandwidth. We have shown that you don't need a bulk metamaterial to cancel the scattering from an object a simple patterned surface that is conformal to the object may be sufficient and, in many regards, even better than a bulk metamaterial."
Last year, the same group of researchers were the first to successfully cloak a 3D object in another paper published in New Journal of Physics, using a method called "plasmonic cloaking", which used more bulky materials to cancel out the scattering of waves.
Moving forward, one of the key challenges for the researchers will be to use "mantle cloaking" to hide an object from visible light.
"In principle this technique could also be used to cloak light," continued Professor Alu.
"In fact, metascreens are easier to realize at visible frequencies than bulk metamaterials and this concept could put us closer to a practical realization. However, the size of the objects that can be efficiently cloaked with this method scales with the wavelength of operation, so when applied to optical frequencies we may be able to efficiently stop the scattering of micrometer-sized objects.
"Still, we have envisioned other exciting applications using the mantle cloak and visible light, such as realizing optical nanotags and nanoswitches, and noninvasive sensing devices, which may provide several benefits for biomedical and optical instrumentation."
###
From Tuesday 26 March, this paper can be downloaded from http://iopscience.iop.org/1367-2630/15/3/033037/article.
Notes to Editors
Contact
1. For further information, a full draft of the journal paper or contact with one of the researchers, contact IOP Publishing Press Officer, Michael Bishop:
Tel: 0117 930 1032
E-mail: Michael.Bishop@iop.org
IOP Publishing Journalist Area
2. The IOP Publishing Journalist Area (http://journalists.iop.org/journalistLogin) gives journalists access to embargoed press releases, advanced copies of papers, supplementary images and videos. In addition to this, a weekly news digest is uploaded into the Journalist Area every Friday, highlighting a selection of newsworthy papers set to be published in the following week.
Login details will also give free access to IOPscience, IOP Publishing's journal platform.
To apply for a free subscription to this service, please email Michael Bishop, IOP Press Officer, michael.bishop@iop.org, with your name, organisation, address and a preferred username.
Demonstration of an ultra-low profile cloak for scattering suppression of a finite-length rod in free space
3. The published version of the paper "Demonstration of an ultra-low profile cloak for scattering suppression of a finite-length rod in free space" (J C Soric et al 2013 New J. Phys. 15 033037) will be freely available online from Tuesday 26 March. It will be available at http://iopscience.iop.org/1367-2630/15/3/033037/article.
New Journal of Physics
4. New Journal of Physics publishes across the whole of physics, encompassing pure, applied, theoretical and experimental research, as well as interdisciplinary topics where physics forms the central theme. All content is permanently free to read and the journal is funded by an article publication charge.
IOP Publishing
5. IOP Publishing provides publications through which leading-edge scientific research is distributed worldwide. IOP Publishing is central to the Institute of Physics (IOP), a not-for-profit society. Any financial surplus earned by IOP Publishing goes to support science through the activities of IOP. Beyond our traditional journals programme, we make high-value scientific information easily accessible through an ever-evolving portfolio of community websites, magazines, conference proceedings and a multitude of electronic services. Focused on making the most of new technologies, we're continually improving our electronic interfaces to make it easier for researchers to find exactly what they need, when they need it, in the format that suits them best. Go to http://ioppublishing.org/
The Institute of Physics
6. The Institute of Physics is a leading scientific society promoting physics and bringing physicists together for the benefit of all.
It has a worldwide membership of around 40 000 comprising physicists from all sectors, as well as those with an interest in physics. It works to advance physics research, application and education; and engages with policy makers and the public to develop awareness and understanding of physics. Its publishing company, IOP Publishing, is a world leader in professional scientific communications. Go to http://www.iop.org
The German Physical Society
7. The German Physical Society (DPG) with a tradition extending back to 1845 is the largest physical society in the world with more than 59,000 members. The DPG sees itself as the forum and mouthpiece for physics and is a non-profit organisation that does not pursue financial interests. It supports the sharing of ideas and thoughts within the scientific community, fosters physics teaching and would also like to open a window to physics for all those with a healthy curiosity.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Mar. 25, 2013 ? The first multi-gene DNA sequencing test that can help predict cancer patients' responses to treatment has been launched in the National Health Service (NHS), thanks to a partnership between scientists at the University of Oxford and Oxford University Hospitals NHS Trust.
The test uses the latest DNA sequencing techniques to detect mutations across 46 genes that may be driving cancer growth in patients with solid tumours. The presence of a mutation in a gene can potentially determine which treatment a patient should receive.
The researchers say the number of genes tested marks a step change in introducing next-generation DNA sequencing technology into the NHS, and heralds the arrival of genomic medicine with whole genome sequencing of patients just around the corner.
The many-gene sequencing test has been launched through the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), a collaboration between Oxford University Hospitals NHS Trust and Oxford University to accelerate healthcare innovation, and which has part-funded this initiative.
The BRC Molecular Diagnostics Centre carries out the test. The lab, based at Oxford University Hospitals, covers all cancer patients in the Thames Valley area. But the scientists are looking to scale this up into a truly national NHS service through the course of this year.
The new ?300 test could save significantly more in drug costs by getting patients on to the right treatments straightaway, reducing harm from side effects as well as the time lost before arriving at an effective treatment.
'We are the first to introduce a multi-gene diagnostic test for tumour profiling on the NHS using the latest DNA sequencing technology,' says Dr Jenny Taylor of the Wellcome Trust Centre for Human Genetics at Oxford University, who is programme director for Genomic Medicine at the NIHR Oxford BRC and was involved in the work. 'It's a significant step change in the way we do things. This new 46 gene test moves us away from conventional methods for sequencing of single genes, and marks a huge step towards more comprehensive genome sequencing in both infrastructure and in handling the data produced.'
Dr Anna Schuh, who heads the BRC Molecular Diagnostics Centre and is a consultant haematologist at Oxford University Hospitals, adds: 'Patients like the idea of a test that can predict and say up front whether they will respond to an otherwise toxic treatment. What the patient sees is no different from present. A biopsy is taken from the patient's tumour for genetic testing with a consultant talking through the results a few days later. It is part of the normal diagnostic process.'
Cancer is often described as a genetic disease, since the transition a cell goes through in becoming cancerous tends to be driven by changes to the cell's DNA. And increasingly, new cancer drugs depend on knowing whether a mutation in a single gene is present in a patient's cancer cells.
For example, a lung cancer patient may have a biopsy taken to check for changes in the EGFR gene. If there is a mutation, the patient may then be treated with a drug that works as an EGFR inhibitor. If there is no mutation, such drugs won't work and the patient would get a different drug that would be more effective for them. Knowing the presence or absence of mutations in a certain gene can choose the treatment path for that patient.
The NHS can currently test for mutations in 2 or 3 genes -- genes called BRAF, EGFR or KRAS -- using older sequencing technology that has been around for decades. Efforts are being made to look at increasing the number of cancer genes sequenced to nine as standard.
The Oxford scientists are the first to make such multi-gene tests possible in the NHS using the latest DNA sequencing techniques. The NHS service they have launched looks for mutations in 46 genes, and they are now working towards verifying the use of a test involving 150 genes.
Having a diagnostic test or 'panel' that can screen for mutations in multiple genes at once will be important for access to all the new cancer drugs that are coming along.
'It will be very difficult to manage in NHS diagnostic labs without gene panels,' explains Dr Schuh. 'Currently, new cancer drugs tend to get approved alongside a diagnostic test specific to that drug which can determine which patients will benefit. But as more and more drugs like this come along, we can't possibly run all the many different separate tests this could mean. We need one test for a range of drugs.'
Dr Taylor adds: 'We wanted a test that would use the latest DNA sequencing techniques to detect a wide range of mutations in a wide range of genes. A test that would be able to cover more cancers and more treatments, all for a similar cost to conventional methods.'
The test is run on a next generation sequencing platform from Life Technologies Corporation, called the Ion Personal Genome Machine (PGM(TM)). The test and accompanying software have been substantially modified as requested by the Oxford team to fulfil diagnostic standards in their lab.
This work was co-funded by the Technology Strategy Board, the UK's innovation agency, through a grant to the NIHR Oxford BRC, Life Technologies Corporation, AstraZeneca, and Janssen Research & Development, LLC, one of the Janssen Pharmaceutical Companies.
As part of the test development, the Oxford team looked to improve the initial sample preparation in the lab, and to provide the software and infrastructure support to handle and analyse the amount of information involved. Most importantly, the Oxford group has carried out tests and comparisons to verify the robustness of the technique with cancer biopsies direct from patients.
The team compared the new 46 gene test against conventional techniques for 80 consecutive cancer biopsies in the hospital lab's workflow.
The next-generation DNA sequencing method detected all the mutations the conventional method did; it detected new mutations the conventional method didn't; and detected mutations present at much lower levels in the samples. The time taken for the 46 gene test also fitted into the standard turnaround time for samples at the lab.
There is definite benefit in screening some of the 46 genes included in the test; there is probable or likely clinical benefit in screening some of the others; mutations in further genes might be important in some cancers but not others; and the other genes, we don't know as yet. But having this information means researchers can investigate whether a mutation has biological significance.
'We can keep data, bank it and link it with anonymised clinical data on patients' cancers for future research,' explains Dr Schuh.
The test looks for mutations in 'hotspot' regions of each gene -- areas where mutations are more likely to occur. This does mean the test may miss up to 5% of mutations, as they can occur elsewhere, but this is still significantly better than the 'false negative' rate using current methods.
It can also detect mutations present in only 5% of the tumour cells present in a sample. This is much lower than is possible currently, and is important in being able to capture information from cells present in only small numbers in a tumour, but which are still important in driving cancer growth.
Having shown that it is possible to introduce the 46 gene test as an NHS service, the researchers are now moving on to investigate the potential of a test that will sequence 150 genes. The team will use the test first of all with 500 existing samples from patients taking part in cancer clinical trials to be able to compare the results retrospectively with information from the trials. They will then use the test with 1000 new cancer biopsies to better understand how the extra information could be used in guiding treatments for patients and their outcomes.
Dr Schuh says: '"Panel" tests have significant potential while we wait for the cost of sequencing whole patient genomes to come down. Even then, panel tests may be with us for some time. After whole genome sequencing does come into use, it may be that panel tests are used first with patients' biopsies, with only those whose panel test shows no result having their entire DNA sequenced to look for rarer genetic changes.'
Lord Howe, Health Minister, said: 'We want to be among the best countries in the world at treating cancer and know that better tailored care for patients could potentially save lives.
'Health research like this is incredibly important and I'm delighted we could support the work of researchers in Oxford through the National Institute for Health Research Biomedical Research Centre.
'By rapidly translating findings from genetics research into real benefits for patients, their work will make sure that patients get the right treatments straight away, reduce potential side effects and also help us use NHS funds more effectively.'
The 46-gene panel is based on Ion AmpliSeq(TM) chemistry from Life Technologies Corporation. The test requires a very small amount of DNA (5 nanograms), an advantage when working with clinical samples that are typically limited in quantity.
The Ion Personal Genome Machine (PGM(TM) and Ion AmpliSeq(TM) are for Research Use Only, not intended for use in diagnostic procedures. Life Technologies intends to pursue CE-IVD designation for the PGM.
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Public release date: 25-Mar-2013
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