Stephan Becker is tired of waiting. Virologist at the University of Marburg in Germany is part of a consortium of scientists that is willing to do a trial of a vaccine candidates for Ebola security. But the doses, it is supposed to test on 20 German volunteers are still in Canada. Negotiations with the US company that owns the license for marketing the vaccine that contains a gene for sewn Ebola surface protein in a pathogen known animal viruses such as vesicular stomatitis virus (VSV) have unnecessarily delayed the start of the trial, Becker and several other scientists say science . "It drives me crazy that we're sitting here and could do something, but things do move forward," said Becker.
Today and tomorrow, Ebola scientists and business representatives and regulators are meeting in its headquarters in Geneva, Switzerland, World health Organization (wHO) to discuss how to accelerate the clinical development of vaccines, a process that normally takes years. more specialists and more public health believe that vaccines will have an important role to play in stopping the catastrophic epidemic in West Africa, which has so far caused at least 6553 cases and over 3,000 deaths in Guinea, Sierra Leone and Liberia (These are the reported figures, the real toll is known to be much higher.).
given the emergency, it is inexplicable that one vaccine candidates developed at the public health Agency of Canada (PHAC) Winnipeg, has yet to go into the arms of the first volunteer, said virologist Heinz Feldmann, who helped develop the any vaccine to PHAC. "It's a farce, these doses are lying around there while people are dying in Africa," said Feldmann, who now works in the laboratories of the Rocky Mountains of the US National Institute of Allergy and Infectious Diseases (NIAID) in Hamilton Montana
in the center of the controversy is NewLink Genetics, a small business in Ames, Iowa, who purchased a license to market the Government of Canada's vaccine in 2010 and is suddenly caught in what WHO calls "the most acute severe public health emergency seen in modern times." Becker and others say that the company is dragging its feet the last 2 months because it is worried about losing control of vaccine development . But Brian Wiley, vice president of business development at NewLink Genetics, says the company is doing all it can. "Our program has grown at an unprecedented rate," he said. Although it took another few months, "we would still break a record in terms of getting this into patients." Wiley explains the holdup is the "administrative process": agreement on a protocol, get employees to sign good contracts, provide insurance in case something goes wrong
Marie-Paule Kieny, specialist vaccines and wHO Director-General, disputes NewLink is dragging its feet. . "So far, we have been able to solve problems along the way, to move as quickly as possible," she said.
Phase I trials for another vaccine candidate, which has pitted Ebola genes into a chimpanzee adenovirus, began in early September in the US and UK. "We have human safety data in approximately 20 people and everything looks good so far," said Ripley Ballou, who is in charge of the Ebola vaccine program (GSK) GlaxoSmithKline in Rixensart, Belgium. Further tests are planned for Switzerland, Mali and Uganda; Ballou said altogether 150 volunteers will receive single-dose vaccine.
A Canadian vaccine developed stock VSV is stored to PHAC in Winnipeg. The Canadian government had 1500 doses 8-1000 which he donated to WHO; the rest is held by NewLink Genetics.
Scientists say WHO bottles have already been sent to research centers who plan to phase trials. Such a trial is scheduled to Walter Reed Army Institute of Research in Silver Spring, Maryland; Other studies by a consortium that includes WHO and Becker are on the drawing boards in Hamburg, Germany, in Geneva, and at sites in Kenya and Gabon. PHAC is ready to ship doses "on a moment's notice," said a representative.
But for a clinical trial to begin, regulators need information on how the vaccine was made, and who resides with NewLink Genetics, which has been slow to release, people familiar with the negotiations say. Wiley said he "knows that the logistics are" not on the manufacturing information. he adds that NewLink wants to be in charge of all security tests. "I do not know think it's unreasonable that we want to be in control of the test and get things done," says Wiley.
Kieny acknowledged that VSV vaccine is behind the candidate GSK, which she says possibly "due to the fact that the partnership behind [the GSK vaccine] is more experienced," she hopes that the tests provided at Walter Reed will soon begin; .. those of Europe and Africa can expect to start in late October or early November, she said Wiley said contracts can be signed at the meeting that is taking place in Geneva.
part of the problem may be that NewLink is a small company with about 100 employees, which focused on immunotherapy to fight cancer in recent years. Research and development by the Authority of a Biomedical Advanced US government agency responsible for accelerating the development of emergency medicines and vaccines recently sent two employees to Ames to help Newlink file documents to the States US Food and Drug Administration, a representative of the US government says. "Our foreign aid commitment has nothing to do with our skill, but with urgency around this issue," said Wiley.
The number of Ebola cases is now almost double every 3 weeks. From the start, the experts of Public Health emphasized that the world knows how to contain the Ebola outbreak: find patients early and treat them using very strict hygiene, track and monitor their contacts, and bury dead quickly and safely. But given the magnitude of this epidemic, which has become almost impossible, said Gary Kobinger PHAC. "You would need an army of epidemiologists for it." This has made rapid development of essential vaccines.
"At first we thought that the epidemic would be by the time we prepared a vaccine," said Anthony Fauci, director of NIAID in Bethesda, Maryland. "But the epidemic continued and got dramatically out of control, it has become clear that we need this vaccine to actually contain the epidemic." This does not mean conventional containment strategies should not be used aggressively, and they need larger scale drastically, said Michael Osterholm, director of the Center for Research and Policy at the University Minnesota, Twin Cities infectious diseases.
at the WHO meeting today and tomorrow, experts discuss the many thorny issues that will occur if one or both vaccines successfully pass their Phase I trials. From there, they should be widely available in the affected countries, said Jeremy Farrar, an epidemiologist and head of the Wellcome Trust research charity in London. "I think the big question now is how do we do it while gathering data on safety and efficacy sufficient to be sure that we are doing well," says Farrar.
Fauci believes that, a randomized controlled trial, in which people receive either the vaccine or a real Ebola unrelated shooting such that the vaccine against hepatitis B, will be needed. "If you deploy a vaccine widely in a country, you better be sure it is effective, "he said. But others do not see the use of placebos as an option. "You create a group of people who are not vaccinated and they do not know it," said Kobinger. "If I was a volunteer, I would not be comfortable with this person."
Farrar accepts, moreover, a placebo-controlled study is simply impossible, he said "We are talking about a system totally destroyed healthcare across Liberia and, to some extent, Sierra Leone," said. Farrar. "We just have to be practical." This does not mean scientists will be unable to tell if the vaccine works, he said. Urban areas like Monrovia will inevitably receive the vaccine before reaching other parts, most rural of the country; scientists can compare the impact of the Ebola virus in both areas, in a so-called wedge step study plan. "If you have an effective vaccine to 0%, you immediately."
The offer is likely to be a problem. GSK has promised to produce about 10,000 doses by the end of the year, paid by the Wellcome Trust and others. the company is already working on how to increase production, however, if the first volunteers of the data show that the vaccine has no adverse effects and their immune systems have similar responses that protect monkeys in experiments that attempted to infect them with Ebola. the first signs of what could be available in less than a month, said Ballou. "We would not begin to produce large numbers unless we had evidence that the vaccine has the potential to work," he said.
vaccine production against VSV is already ramping up. The more than 800 bottles now stored in Winnipeg could give a few thousand doses Kobinger said, according to the exact amount needed per dose. "We are making additional power as we speak," Wiley said. "And we expect to have the ability to manufacture tens of thousands of doses by the end of the year." Two other vaccines, another on the basis of VSV and using a modified poxvirus are a few months behind in development.
at the meeting this week, experts will again discuss who gets the vaccine first. most participants in an ethical meeting earlier agents health should be given priority, as they are essential in the fight against Ebola, while presenting a high risk of contracting. in addition, the protection of a vaccine could help convince doctors and nurses to work in affected countries. the vaccine will also be given to other people involved in the outbreak, such as cleaners, ambulance drivers, teams or funeral, Farrar said. But offer the vaccine to patients' families could increase the likelihood they come forward, which would contribute to the detection and control.
The panel participants earlier agreed that children and pregnant women are especially vulnerable and should also be a priority.
Another question is which country to focus on. If early doses will be sent to Liberia, where the epidemic appears to be growing the fastest, or Guinea, who was about to contain the Ebola virus at least twice? "You could make a good case for either," said Brian Greenwood, an epidemiologist specializing in vaccines at the London School of Hygiene & Tropical Medicine, who chairs a session at the meeting. "These are all very difficult issues, and this is why you need to get a lot of brains all the people who really know it from different aspects and try to come to some sort of consensus."
* Ebola files: given the current Ebola epidemic, unprecedented in terms of the number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection of research and articles on viral disease available for researchers and the general public.
During a monitoring hearing at the US House of Representatives yesterday, lawmakers grilled health officials over the response to the first Canadian case Ebola and asked them to respond to the idea that many Republicans now-promote the prohibition of flights from West Africa. When Tom Frieden, director of the Centers for Disease Control and Prevention, said the restrictions would cause travelers to redirect through other countries, which makes them more difficult to track, representative Henry Waxman (D-CA) came to his defense with a visual aid.
map he presented, illustrating the relative flow of passengers on Ebola-affected countries in West Africa to the rest of the world, came from a article published Sept. 2 in PLOS Currents: outbreaks . One of its authors, the physicist Alessandro Vespignani of Northeastern University in Boston, said he did not know his work was featured in the debate until some colleagues have warned him yesterday. The map shows the complexity of the global travel flows, he said, but in the rest of the document, "we are more quantitative than that." The authors gathered this flight information with equations describing the dynamics of probable transmission in 16 countries high risk of Ebola virus importation to predict the likelihood that each will see a new imported case. According to the most recent forecast of the group, the risk of another infected person arriving in the US on October 31 given the current reductions air traffic is about 25%. the published work simulates how the reduction of travel can reduce the spread of the disease at this time, their estimates assume an overall 80% reduction in travel Vespignani but notes that the reduction of traffic is just "putting off the problem for a finite amount of time." (The 80% decline is equivalent to a delay of 3 to 4 weeks in a probable case, he said.) "This debate is not to divert the discussion from the real issue, which is to win the battle in Africa" .
Ira Longini, a biostatistician at the University of Florida in Gainesville and another author on the paper PLOS , said he thinks "it's fine" for the Congress to use the work an audience, but deplores the fact that "people are notoriously bad on the interpretation of probability." plots show the group how the probability of new imported cases would fall if the flow of travelers has decreased, but did not wade into the complex costs and benefits of a travel ban. "You can point on this plot and argue both ways," says Longini. The group plans to issue a new document next week that looks at the impact of travel restrictions that some airlines and governments have already imposed. "They can point to one side," he said
* Ebola files :. Given the current Ebola epidemic, unprecedented in terms of the number of people killed and the rapid geographic spread, Science and Science Translational Medicine made a collection of research articles and news on the viral disease available for researchers and the general public
< span property =. "Schema: name" content = "invokes debate Ebola Congress PLOS paper" class = "meta-rdf hidden element">There are two months when the clinician Tim Flanigan arrived in Monrovia to help Liberia fight the epidemic Ebola, it took a few days to ambulances responding to calls, people dying were turned back by the processing units designated health workers ran short of personal protective equipment, and the bodies were left in the street. "There was not enough support and there was a feeling that the world did not understand the severity of this outbreak was," says Flanigan, who works at Brown University and former head of the diseases program infectious there. "Now it is radically different in Monrovia, which is wonderful to see."
Bruce Aylward, assistant director-general in charge of the operational response to Ebola World health Organization (WHO) confirmed at a conference today to the press that the number of reported cases has declined in Liberia, the hardest hit country in the Ebola epidemic. "It seems that the trend is real in Liberia and that there may in fact slow down the epidemic there, "said Aylward, who noted that the processing units in several localities have cots available.
But both Aylward and Flanigan immediately warned against premature optimism. "My god, the biggest mistake now would be if people start to think," Do we really need all these new beds? "Aylward said." I'm terrified that information will be misinterpreted and that people will begin to think, "Oh, great, it's under control." This is like saying your pet tiger is under control. This is a very sick, very dangerous. "
Flanigan stressed that the time has come "to redouble our efforts," especially regarding contact tracing and monitoring their health. "This is a huge task and we need to do a much better job," he said.
the apparent drop in cases could mean that families hiding patients and secretly bury the dead, but it is more likely a combination of factors has reduced the spread of the disease, Aylward said. "there was a rapid expansion in safe burial practices during the month of September," he said adding that many people were isolated in Ebola treatment units, the fight against the spread. It was also intensive community education about the disease, including how it spreads, the value of seeking care, and self-protection strategies.
The situation in Guinea and Sierra Leone, two other hard-hit countries, has not changed dramatically.
in a disconnect with the decline in Liberia, Aylward noted that WHO has raised 13,703 cases -a leap of more than 3000 of [chiffrespubliés on 25 October. He said the sharp increase reflects reports a backlog of cases, "With the huge increase in some countries, especially in September and October, people behind on their data," he said. "They were left with huge piles of paper and we knew we were going to see jumps in the case at times that will be associated with more new data coming in that are actually old cases." He said about 2,000 of the latest cases were from old data to Liberia, where case reports continues to be a problem. "The data for Liberia are missing for 19, 20, 21, 26 and 27 October," the WHO's last update note.
The WHO has warned that the models suggested the epidemic would be increase exponentially and the virus was ahead of the answer. Aylward noted progress, but pointedly did not say the answer was now ahead of the virus. "We are seeing a slowdown in the rate of new cases certainly," said Aylward. "The danger is now instead of a downward trend that we descend to zero, we find ourselves with an oscillating pattern where the disease starts to go up and down and start getting re-infected areas. What happens to the heat this thing and it slows down is not necessarily what brings us to zero. "
Flanigan said the challenge now is to obtain better data for counties, not countries, to better understand the contours of the epidemic and how to respond." Each case has need a very aggressive response, "he said
* Ebola files :. given the current Ebola epidemic, unprecedented in terms of the number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection of research articles and news on the viral disease available free researchers and the general public.
Ebola, influenza and cold viruses have given a bad name. But there may be a bright side to these small packages of genetic material. Researchers studying mice have shown that the virus can help to maintain and restore a healthy gut in much the same way that friendly bacteria are.
The work "shows for the first time a virus can functionally substitute for bacteria and provide beneficial effects," says Julie Pfeiffer, a virologist at the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study. "It is shocking."
our bodies are mostly microbes, with each to welcome us trillions of bacteria that our so-called microbiome. These bacteria appear to play a role in all of our weight to our allergies. But the virus also hiding in and around these bacteria and they far exceed the microbes.
as the microbiome, this "virome" may be important to human health. a recent study, for example, found that viruses that are abundant in saliva can eliminate harmful bacteria. Kenneth Cadwell, a virologist at New York University School of Medicine in New York, wanted to know what virus in the intestine could be done. In particular, he was interested in a group called norovirus. Although they are known to cause diarrhea outbreaks on cruise ships and diseases in laboratory mouse colonies, norovirus infect mice without adverse effects.
Indeed, he and his postdoc Elizabeth Kernbauer have now found that certain norovirus have a good side. In the laboratory, the researchers were breeding mice in sterile environments, such as rodents and young people lack the typical portfolio of microbes and viruses than other mice. Germ-free mice are abnormal. They are not quite certain T cells, which are important for immune function, and they are too many other immune cells involved in allergic reactions. They also abnormally thin villi, fingerlike microscopic projections on the intestinal wall that help absorb nutrients. Other researchers have shown that bacteria to mice without giving germs can rebalance the numbers of immune cells and fertilize the villi. Adding a mouse norovirus germ-free has the same beneficial effect, compared Kernbauer, Cadwell and Ding Yi, a pathologist at New York-Presbyterian Hospital in New York online today in Nature . Two other types of norovirus similar help make the healthy gut again, they found.
In a follow-up experiment, the researchers treated normal laboratory mice with antibiotics for 2 weeks, then gave them a norovirus. Antibiotics have upset the balance of immune cells and damage the intestinal mucosa, narrowing of the villi, but as with germ-free mice, the guts of the mice recovered with the help of norovirus. Kernbauer and colleagues then conducted the same experiment, but instead of adding the virus they replaced stunned various bacteria by antibiotics. Each bacterium has helped restore some aspect of the health of the gut, but not the same full range of the virus.
In a final experiment, the team infected mice treated with antibiotics with a pathogen that causes weight loss, diarrhea, and damage to the intestinal wall. Treatment with attenuated these effects. The virus has also helped protect mice against tissue damage from a toxic chemical.
Cadwell, Kernbauer and Ding began to track how the virus gives a hand. They found that stimulates an immune response which comprises a signaling molecule called interferon. "We interferon as a starting point, and now we want to know how interferon is conferred these benefits," said Cadwell
. "The idea that this virus can be beneficial in some way will be very controversial, "since most people think of general virus and norovirus in particular as harmful, says Juris Grasis, an immunologist at the State University of San Diego in California who was not involved in the work. Nevertheless, the study "could give us clues about human health as to what might be important in the immune system to fight or use norovirus."
the work has implications beyond norovirus, Pfeiffer added. investigations of human virome are many viruses that do not cause the disease. "Maybe in some situations, they may be beneficial."
The author and her two children in. She asked for genetic testing, as many do, in part to protect their own health as they grow
PHOTO :. © April SAUL
Rarely could I be described in a title in The New York Times , which is why I stayed on a earlier this fall. "Study of Jewish Women Shows a link to cancer without family history," said history September 5 Uncomfortable, I read on. "Women of Ashkenazi Jewish descent who tested positive for genetic mutations that cause cancer in random screenings have high rates of cancer ovarian and breast cancer, even when they have no family history of the disease, researchers reported on Thursday. "
Hmmm.
science has been my professional home for the past 13 years and in that time, I have written and spoken about genetic testing with dozens of experts from the edge of field cut. I chronicle the scientific advances, ethical dilemmas, life saving tests, the anguish he ignites. I've never turned the lens on my own DNA.
Suddenly there was no escaping it. My parents are both of Ashkenazi origin. To my knowledge, nobody on either side of my family has ever had breast or ovarian cancer. But suddenly I saw how a mutation in the genes described in this article BRCA1 and BRCA2 , had slipped unnoticed through a small family of my father, heavy on chromosome Y therethrough; his older brother; my three cousins, two of whom are men. I remembered that my paternal grandfather had suffered from prostate cancer, which eventually spread to her bones and killed him. My uncle had the disease, too. In addition to their storied role in breast and ovarian cancer, BRCA mutations are associated with prostate cancer in men. I had long known that Ashkenazi Jews are more likely to carry mutations in these genes. But that was as far as my knowledge went.
When I probed the numbers, they were not particularly reassuring. A quick Google search, why had I never done this before? -revealed That one in 40 Ashkenazi wear BRCA mutations, compared with as little as 800 in the general population. Like almost all cancer-related genes, BRCA1 and BRCA2 were discovered in families riddled with disease. But the September study, led by Ephrat Levy-Lahad, a medical geneticist at Shaare Zedek Medical Center in Jerusalem, argued that other families shared a high risk if they had the same mutations.
The newspaper article that has everything triggered, published in early September.
PHOTO: © April SAUL
Several authors, including Mary-Claire King of the University of Washington, Seattle, BRCA1 's discoverer, say all women, regardless of family history should know if they have dangerous mutations in BRCA1 and BRCA2 . Other experts are not yet convinced. Perhaps even more controversial is that to track tens of risk genes discovered in the last decade, some tenuous linked to cancer. I could have written a nuanced story Science on both sides of the debate. But when it came to my own health, 486 Israeli women with BRCA mutations, half without a family history, but all very vulnerable to cancer, was all it took.
Time seemed gasoline. I am 38 years old; ovary removal in BRCA carriers recommended by 40. I called the hospital in suburban Philadelphia where my children, now 2 and 5 years, were born and spoke with a genetic counselor. She has a family history and agreed that yes, testing BRCA was worth it, and yes, the insurance would probably cover it in my case.
I booked an appointment. I was about to discover my own tape of the new world of genetic testing for cancer, which would take me beyond BRCA and a more uncertain ground.
THE AUTOMATIC DOORS SWISH soundlessly open as I step into the hospital's cancer center. A genetic counselor with brown, curly hair and glasses approach me, smiling, clipboard in hand. In her office, she released a pedigree of my family sketched in pencil square for men, for women circles, slashes through those who died in the cause of death scribbled next to them. I thought I just loan-after all, I am here only to BRCA tests, and only because of my ancestry, but it turns out I did not. Hysterectomy my grandmother included the removal of her ovaries? (I hazard a guess and members of the family request after the fact, we do not know if I got it right.) Is my grandmother die of stomach or colon cancer? "She was in her 0s," I said. I still carry a vague memory of his visit to the hospital, in 3 years, shortly before his death. "Does it matter when someone's that old ? "
The advisor pulls a sheet of paper and places it on the table. There is a list of 21 genes associated with breast and ovarian cancer. Eleven are in pink and gray labeled "high risk"; three are in the purple category "moderate risk"; and seven are turquoise and described obliquely as "new genes." This is Breast / Ovarian Cancer Panel of GeneDx company in Gaithersburg, Maryland, but as is often the case in oncology, many genes contribute to of other cancers, too. it confers a risk of stomach cancer 40% to 83%. removing the stomach is recommended if the test is positive. another, TP53 , confers a risk cancer in women and a chance of 73% for men of almost 100% TP53 cancers include brain cancers and sarcomas
regarding two genes. on the panel BRCA1 and BRCA2 , there is little doubt that in families predisposed to cancer, screening saves lives: in-depth study of BRCA carriers found that those who have their ovaries removed were 80% less likely to die from ovarian cancer and 50% less likely to die of breast cancer. Prophylactic mastectomy appears to reduce the risk of breast cancer by at least 95%.
But many other genes for which the test was discouraged some years because their impact on health was uncertain are "now regularly offered," said Kenneth Offit, chief of clinical genetics at Memorial Sloan Kettering cancer Center in New York City. "This is the paradox that we fell in." Just as risk genes more cancer were discovered, the cost of their deep sequencing. the result is a proliferation of panels designed to decipher DNA.
how each of these genes increases the risk in individuals, and at what age, is often blurred. "clinical work came out ahead of us," says Fergus Couch, an authority on BRCA and other breast cancer genes at the Mayo Clinic in Rochester, Minnesota. "The [sequencing] The technology changed so fast" that "we did not have time" to develop answers to questions from patients and physicians now asking.
In the summer of 2013, GeneDx launched its breast / ovarian cancer-Panel stimulated in part by the decision of the Supreme Court against the patent claims of Myriad Genetics on BRCA genes. Other companies, including himself and Ambry Myriad Genetics and academic medical centers, jumped with panels of several dozen genes linked to a range of cancers. "We are really looking at things that will provide the physician the possibility of a treatment plan," for example, adding increased surveillance, said Sherri Bale, Director General of GeneDx. The genes on company boards are " a moving target, "she said, with the added culprits and sometimes deleted based on the available scientific evidence. Bale believes that the panels, which cost in the neighborhood of two or three thousand dollars, are suitable for high-risk families, but not for the general population.
THE LIST OF GENES 21 sitting between us, and I consider everything I could learn by simply saying yes. The counselor does not advocate that I sign for the full panel. But it draws my attention to a gene in the purple group to moderate risk CHEK2 . The list of cancers beside him is long: "Breast Female, Male Breast, Colon, prostate, thyroid, kidney, endometrium (serous), ovary." I am vaguely familiar with CHEK2 as a breast cancer gene from my own statement. "Is CHEK2 more common in Ashkenazi?" I ask, still stuck on the heritage that my cancer driver and why I'm in this room to begin.
"No," the adviser responds. But in addition to the prostate, my paternal grandfather had colon cancer. "He was in his 70s!" I protest. Nevertheless, CHEK2 test for me worth considering, the counselor says. A CHEK2 mutation could approximately double the risk of cancer breast, at least 20%. MRI and annual breast mammograms would probably recommended.
I saw thwart. Adding another gene for the test had never occurred to me. and yet, if the test is positive, the share price seems relatively benign and potentially save lives.
"Let's do it," I say. We talked for about 40 minutes.
the counselor fate . a consent form "There is one more thing," she explains a text block is titled It reads, in part. "variant of uncertain significance (SUV)." "I can learn a SUV was identified by this test. this means that a genetic change (variation) has been identified, but it is unclear whether the variant can cause cancer. "A particular cancer gene may have thousands of variations, some showing in a handful of families around the world. Some variants are a major contributor to the disease, while others are benign changes in DNA that, in practice, mean nothing.
again, my years of medical journalism were able to prepare. "How common are these in BRCA and CHEK2 ? "I ask. for BRCA1 and BRCA2 , the counselor explains, about 2% of people have an SUV. (I learn later that VUs rates fluctuate according to the company offering the test.) She does not know about CHEK2 , but is happy to discover. it also stresses that looking for an SUV does not affect medical advice and that the hospital contact me if an SUV is then reclassified as either harmless or pathogens.
I push aside my hesitation, sign the forms, and am off to the lab for a blood test.
Driving home, my intolerance of uncertainty rears its head. Do I really want to know if I am an SUV? What's the point? This afternoon, I send the advisor by email. I told him I'm worried that learning VUSs "cause me anxiety and there will be no benefit in having this information. I wonder if it is possible not to receive information on any SUV which can be found in the tests. ... is that an option? "
How a BRCA1 mutation raises the risk of breast cancer of a woman depends on her age, family history and other variables, such as the examples below illustrate.
She wrote back quickly and pleasantly. She checked with GeneDx and learned that, for regulatory reasons, they are obliged to share information if an SUV is found. It will ask its medical director if the hospital can keep an SUV find me. But she also wondered if "you feel anxious not know whether or not you can be contacted in the future about a reclassified SUV. ... There are chances that you not have an SUV and you may feel a relief to know that you do not have it. "
She later wrote to say that his medical director is retained a comfortable SUV if no pathogenic variants turn up And there's more good news. She learned that the rate of SUV for CHEK2 , by GeneDx, is only 1.6%, much lower than it thought that the well-origin estimates vary depending on who you ask. I SHELVE my inner dialogue where the information I want.
Two days later while GeneDx is the analysis of my DNA, I'm on the phone with Susan Domchek, an oncologist the study of the breast cancer genes at the University of Pennsylvania. We discuss cancer risk genes in people with no family history of disease. Spontaneously, Domchek raises CHEK2 testing . "We do not know how to integrate it into patient care, "she complained, referring to HIV-positive women and their families. "What percentage of the time it really add anything to the situation?" I do not speak my own CHEK2 test is in progress. Instead, I learn about the frequency of CHEK2 mutations in the general population. Domchek the response that people only about one in 0 in the United States is a carrier helps me breathe.
Domchek is one of many researchers trying to clarify the interaction between genes and cancer diseases. With Offit, Couch, and others, has developed an online registry called PROMPT which opened earlier this fall. It aims to save thousands of people who have had the test panel offered by a host of companies, including GeneDx, Ambry, Myriad, Quest Diagnostics, and Pathway Genomics. Their goal is a database that will help them examine how specific gene variations affect health.
"We need to experience the world with all these panels," said Couch. It also highlights an irony: Despite some concern, scientists need him as panel testing to continue, because it is their best shot to collect sufficient data to address research questions. At the same time, "You do not want to do science ... at the expense of the patient," he said. Couch is part of an international consortium called ENIGMA working to sequence the breast cancer genes from 40,000 cancer patients and healthy people. the project nailing the risk conferred by different mutations and study the impact of VUSs about the disease.
multigene panels for the risk of cancer are increasing and change, including that of 21 genes associated with breast, ovarian and other cancers, shared with the author before his own test
DATA :. GENEDX ONCOLOGY PROGRAM
outside the United States, signs of cancer genes are largely limited to research settings, and investigators often do not share information about the changes that have a small or unknown risk. There is much debate about what to say volunteers. "We struggle with it," said Hans Ehrencrona, a clinical geneticist at the Lund University Hospital in Sweden. "Where do you draw the line, no one knows for sure."
Every woman in Sweden who receives BRCA test is now offered the chance to enroll in a study in which it tested for 63 other cancer genes. The results of only seven of them are shared with participants. Many moderate risk genes are not on the list, said Ehrencrona, who is helping lead the effort. As an example, he points out, " CHEK2 is quite common in Sweden. We will not return. "
ONE TUESDAY MORNING IN OCTOBER minutes after a work conference after the call, my phone rings." I have your results, "the adviser announces. For 19 days I met her. "What do you want to know?"
Well, pathogenic mutations, of course, I say
There is good news, she said :. No pathogenic mutations were detected in one of the three genes.
relief rushed through me. "Do you know about any SUV?" Application does. I think CHEK2 , and the SUV of 1.6%, it cited. What are the odds? "Of course, "I said.
" There was no meaning unknown variants detected in BRCA but unknown significance variant was detected in CHEK2 , "she told me. reading the report GeneDx, she explained that my SUV is a deletion of 15 nucleotides of DNA. the variant was found in two men with prostate cancer, and in vitro analysis suggests that causes partial loss of function of the gene.
I expect distress, ringing in my ears, fear coiling in the pit of my stomach. instead, I almost laughed. I think, "that's it? that's what's shared with patients today?" Two men with prostate cancer cells in a petri dish, a loss of function that may or may not result pathogenicity. This does not deserve my mental energy
"People need to become more comfortable with uncertainty," Sharon Plon, a clinical geneticist at Baylor College of Medicine in Houston, Texas, told me a few days later. But she stressed that the recognition of uncertainty "does not mean that we do not know anything." For many families suffering from cancer, large panels provide constructive advice.
I am writing to my cousin in San Francisco to share my test results; she is the only woman close relative of my father's side, where the cluster of cases of cancer and she is more familiar than most signs: His mother. nonbiological my aunt, is the fight against ovarian cancer and signed for a panel of 41 genes offered by the University of Washington, Seattle. She tested negative for all.
My cousin asked me examine the same panel, which has now expanded to 48 genes. in the end, I explained in my message to her, it was not something I wanted. "I know the signs are often discouraged , "she wrote back. There is a view that it does not share. Even without a clear-cut action plan, she wants to know some message from his DNA carries its future. The only reason she avoided testing for itself is because insurance is unlikely to pay for it. "Knowledge is power," she wrote. "I do not mind at all."
The US government lifted a temporary ban on research to develop an animal model for the (Middle East Respiratory Syndrome) MERS virus, a coronavirus lethal spread of camels to the people of the Middle East.
October 17, in an unusual move, the US government stopped federal funding for studies on risk SEAS, SARS or influenza tweak these viruses to make them more pathogenic or transmitted by breathing in the mammals. Among the 18 arrested were at least five projects to work on adapting the MERS virus into mice to generate a strain that sickened animals. This could facilitate studies aimed at understanding the virus and developing vaccines and medicines.
The financial break came as a shock to MERS researchers. At various meetings, including one at the National Academy of Sciences this week, they argued that the development of an animal model for MERS is crucial to tackle the virus, which has infected at least 938 people and killed a third of them. They asked for an exemption set out in the moratorium policy, which allows to continue work "urgently necessary to protect public health."
This exemption has now been approved for at least some of these projects. "We are very happy," said Matthew Frieman of the University of Maryland School of Medicine in Baltimore, who received a call from her program officer at the National Institute of Allergy and Infectious Diseases (NIAID) yesterday. NIAID researcher intramural Kanta Subbarao said its project to develop a rabbit model for MERS was also exempted, and the National Institutes of Health has not responded to a request on other projects at the time of release
* update, December 18, 3:20 p.m. :. NIH confirmed today that the five projects working on a mouse model for MERS were . exempted from the break Two influenza studies have also been granted an exception; no application for exemption were rejected
.
