StemCell Therapy

Sam Erickson followed his love of science to outer space one summer during an internship at NASA. He came away fascinated by seeing into deep space by interpreting interaction between matter and infrared radiation.

Now a full-fledged researcher at the University of Minnesotas College of Biological Sciences, the 25-year-old Alaska native is immersed in something far more earthly: killing carp. His fast-moving genetic engineering project is drawing attention from around the country as a potential tool to stop the spread of invasive carp.

I want to make a special fish, Erickson said in a recent interview at Gortner Laboratory in Falcon Heights.

In short, he plans to produce batches of male carp that would destroy the eggs of female carp during spawning season. The modified male fish would spray the eggs as if fertilizing them. But the seminal fluid thanks to DNA editing would instead cause the embryonic eggs to biologically self-destruct in a form of birth control that wouldnt affect other species nor create mutant carp in the wild.

His goal is to achieve the result in a controlled setting using common carp. From there, it will be up to federal regulators and fisheries biologists to decide whether to translate the technology to constrain reproduction of invasive carp in public waters.

What were developing is a tool, Erickson said. If we could make this work, it would be a total game-changer.

Supervised by University of Minnesota assistant professor Michael Smanski, Erickson recently received approval to accelerate his project by hiring a handful of undergraduate assistants. He also traveled last month to Springfield, Ill., to present his research plan to the 2020 Midwest Fish and Wildlife Conference.

Were pretty excited about where his project is at, said Nick Phelps, director of the Minnesota Aquatic Invasive Species Research Center at the U. Things are sure moving fast. Theres excitement and caution.

Ericksons research has received funding from Minnesotas Environment and Natural Resources Trust Fund. No breeding populations of invasive carp have been detected in Minnesota, but the Department of Natural Resources has confirmed several individual fish captures and the agency has worked to keep the voracious eaters from migrating upstream from the lower Mississippi River. Silver carp, bighead carp and other Asian carps pose a threat to rivers and lakes in the state because they would compete with native species for food and habitat.

Erickson views his birth control project as one possible piece in the universitys integrated Asian carp research approach to keep invasive carp out of state waters. Already the DNR has supported electric barriers and underwater sound and bubble deterrents at key migration points. Another Asian carp-control milestone was closing the Mississippi River lock at Upper St. Anthony Falls in Minneapolis in 2015.

Shooting star

Growing up in Anchorage, Erickson had never heard of Macalester College in St. Paul. But he visited the campus at the urging of a friend and felt like he fit in. He majored in chemistry and worked for a year at 3M in battery technology. But his interests tilted toward the natural world and how to better live in cooperation with nature, he said. Erickson met with Smanski about research opportunities at the university and was hired on the spot.

Smanski, one of the universitys top biological engineers, said carp is not an easy organism to work with and Erickson lacked experience in the field. But he hired the young researcher and assigned him to the carp birth control project because he seemed to have a rare blend of determination and intelligence.

I could tell right away when I was talking to him that he was like a shooting star, Smanski said. If you set a problem in front of him, he wont stop until he solves it Hes taken this farther than anyone else.

In two short years, Smanksi said, Erickson has mastered genetic engineering to the point that his research is starting to bear fruit.

With his new complement of research assistants, Erickson aims to clear his projects first major hurdle sometime this year. The challenge is to model his experiment in minnow-sized freshwater zebrafish. The full genetic code of zebrafish like common carp is already known.

Ericksons task is to make a small change to the DNA sequence of male zebrafish, kind of like inserting a DNA cassette into the fish, he said. During reproduction, the alteration will create lethal overexpression of genes in the embryonic eggs laid by females.

By analogy, Erickson said, the normal mating process is like a symphony with a single conductor turning on genes inside each embryo, Erickson said. But the DNA modification sends in a mess of conductors and the mixed signals destroy each embryo within 24 hours.

In the lab we have to make sure were causing the disruption with no off-target effects, he said. If we can do this in zebrafish, we hope to translate it. They are genetically similar to carp.

Ericksons upcoming experimentation with tank-dwelling live carp could be painfully slow because the fish only mate once a year. But hes working his way around that problem by altering lighting conditions and changing other stimuli in his lab to stagger when batches of fish are ready to reproduce.

The birth control process projected to be affordable for fisheries managers if it receives approval is already proven to work in yeast and insects. And Erickson said the same principles of molecular genetics have been used to create an altered, fast-growing version of Atlantic salmon approved for human consumption in the U.S.

Were not building a new carp from the bottom up but its kind of a whole new paradigm, so we have to get it done right, he said.

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Solution for a scourge? University of Minnesota scientist is progressing with carp-killer tool - Minneapolis Star Tribune

The quick sequencing of the SARS-CoV-2 genome and distribution of the data early on in the COVID-19 outbreak has enabled the development of a variety of assays to diagnose patients based on snippets of the viruss genetic code. But as the number of potential cases increases, and concerns rise about the possibility of a global pandemic, the pressure is on to enable even faster, more-accessible testing.

Current testing methods are considered accurate, but governments have restricted testing to central health agencies or a few accredited laboratories, limiting the ability to rapidly diagnose new cases, says epidemiologist and immunologist Michael Mina, the director of the pathology laboratory and molecular diagnostics at Brigham and Womens Hospital in Boston. These circumstances are driving a commercial race to develop new COVID-19 tests that can be deployed within hospitals and clinics to provide diagnostic answers in short order.

Globally, nearly 89,000 cases have now been reportedmore than 80,000 of these in Chinaalong with more than 3,000 deaths. The virus has been found in 64 countries, six of those in just the past day.

The full genome of the novel coronavirus was published on January 10 of this year, just weeks after the disease was first identified in Wuhan, China. A week later, a group of researchers led by German scientists released the first diagnostic protocol for COVID-19 using swabbed samples from a patients nose and throat; this PCR-based protocol has since been selected by the World Health Organization (WHO).

Not all countries have adopted the WHOs recommended diagnostic, including the US.

The assay was initially developed from genetic similarities between SARS-CoV-2 and its close relative SARS, and later refined using the SARS-CoV-2 genome data to target viral genes unique to the newly discovered virus. In particular, the test detects the presence of SARS-CoV-2s E gene, which codes for the envelope that surrounds the viral shell, and the gene for the enzyme RNA-dependent RNA polymerase.

Yvonne Doyle, the medical director and the director of health protection for Public Health England, tells The Scientist in an email that once a sample is received by a laboratory, it takes 2448 hours to get a result. Commenting on the tests accuracy, she says all the positive results to date in the United Kingdom, a total of 36 so far, have been confirmed with whole genome sequencing of the virus isolated from patient samples, and the analytical sensitivity of the tests in use is very high.

This approach also underpins COVID-19 laboratory testing in Australia, where 27 cases have so far been diagnosed, says medical virologist Dominic Dwyer, the director of public health pathology for NSW Health Pathology at Westmead Hospital in Sydney. We decided in the end to have a screening approach using the WHO primers that target the so-called E gene of the coronavirus, he says. If a screening test is positive, we then do some confirmatory testing which selects other targets of the virus genome.

The laboratory at Westmead Hospital also does a complete sequencing of every virus sample to look for possible new strains of SARS-CoV-2 and has shared some of those sequences in the international Global Initiative on Sharing All Influenza Data (GISAID) database for other researchers to study. The staff also cultures the virus and images it using electron microscopy. Thats not really a diagnostic test, but gives you some confirmation of what youre seeing in the laboratory, Dwyer says.

He adds that, so far, theres no suggestion of false positive findings, because every positive test has been confirmed with whole genome sequencing, viral culture, or electron microscopy. As for false negatives, he adds, it would be hard to know if any infected patients were mistakenly given the all-clear.

Not all countries have adopted the WHOs recommended diagnostic. The US Centers for Disease Control and Prevention (CDC), for instance, has developed its own assay that looks for three sequences in the N gene, which codes for the nucleocapsid phosphoprotein found in the viruss shell, also known as the capsid. The assay also contains primers for the RNA-dependent RNA polymerase gene. Dwyer says that the principles of testing are the same; its just the genetic targets that vary.

Mina says its not clear why the CDC chose to develop a different assay to that selected by the WHO and taken up by other countries. Was this actually based on superior knowledge that the CDC had, or was this more of an effort to just go our own route and have our own thing and feel good about developing our own test in the US versus the rest of the world? says Mina, who is also assistant professor of epidemiology at the Harvard School of Public Health. The CDC declined to respond to questions from The Scientist.

In the UK, testing for COVID-19 is being done by a range of accredited laboratories across the country. In the US, all laboratory testing for COVID-19 has until recently been done exclusively by the CDC. The turnaround time for a result has been 2472 hours. Mina argues that enabling hospitals to conduct their own on-site diagnostics could speed up the process. For instance, hospitals can generate flu results within an hour, Mina says, most commonly using assays that detect viral antigens. We spend a lot of money getting rapid turnaround tests in the hospital for flu, for example, because we have to know how to triage people.

The day or two or three that it takes to get COVID-19 results has had logistical ramifications for hospitals, Mina says. If we have a patient who we only suspect is positive, even if they are not positive, just the suspicion alone will lead us to have to find an isolation bed for them, he says.

There has been a move by the CDC to send out RT-PCR test kits to state health laboratories, says Molly Fleece, an infectious diseases physician at the University of Alabama at Birmingham. Hopefully, more laboratories around the country will be able to have access to these testing kits and be able to test specimens instead of having to send all the specimens to the CDC for testing, she says.

However, that plan hit a snag recently when one of the CDC kits reagents was found to be faulty. The agency has announced that the reagent is now being remanufactured.

There are now numerous companies working on commercial test kits in response to the rising diagnostic demands of the epidemic. Most are applying the same real-time PCR methods already in use, but others are taking a different approach. For instance, Mina and colleagues are trialling a diagnostic in partnership with Sherlock Biosciences, based in Cambridge, Massachusetts. The researchers are using CRISPR technology to tag the target SARS-CoV-2 sequences with a fluorescent probe.

Were not at that stage yet of rolling out the serology or antibody tests.

Dominic Dwyer,NSW Health Pathology at Westmead Hospital

In many ways its similar to real-time PCR but its just more sensitive and much more rapid, Mina says. Another CRISPR-based diagnostic protocol developed by researchers at the McGovern Institute at MIT uses paper strips to detect the presence of a target virus, and claims to take around one hour to deliver the result. It has not yet been tested on COVID-19 patient samples, and the institute has stressed the test still needs to be developed and validated for clinical use, for COVID-19 or any other viral disease. Meanwhile, Anglo-French biotech company Novacyte has announced the release of its real-time PCR diagnostic kit for COVID-19, which it says will deliver results in two hours.

A different diagnostics approach would be to devise blood tests for antibodies against the SARS-CoV-2 virus, a development that Mina says will be an important next step for monitoring the spread of the virus. Could we just start taking blood samples from people around the world and see how many people who had no symptoms or very minimal symptoms may have actually been exposed to this? Mina asks.

Dwyer says such approaches could help detect any false negatives that slip through the PCR-based protocols, but were not at that stage yet of rolling out the serology or antibody tests. Numerous groups are trying to isolate antibodies, some with more success than others. Researchers at Duke-NUS Medical School in Singapore have used antibody testing to demonstrate a link between two separate clusters of infections, and in patients who had cleared their symptoms at the time they were given the antibody test. Meanwhile, researchers in Taiwan are also working to identify a SARS-CoV-2 antibody that could be used for diagnostic testing, and they say such a test could deliver a result in a matter of minutes rather than hours.

Bianca Nogrady is a freelance science writer based in Sydney, Australia.

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How SARS-CoV-2 Tests Work and Whats Next in COVID-19 Diagnostics - The Scientist

When immunologist Dr. Wei Cao joined Baylor College of Medicine three-and-a-half years ago, her first project was to investigate how inflammation contributes to Alzheimers disease.

Alzheimers is the most common cause of dementia among older adults. The current understanding is that, in addition to having beta-amyloid plaques and tau protein tangles, the brains of patients with this condition have a marked inflammatory response, and that this inflammation might be more of a problem than protein aggregation itself, said Cao, associate professor of molecular and human genetics and the Huffington Center on Aging at Baylor.

Inflammation in Alzheimers disease involves the activation of two types of cells in the brain: the resident immune cells called microglia, and astrocytes, star-shaped cells that support neuronal functions. In addition, there are elevated levels of cytokines, molecules that are produced by immune cells to promote inflammation. But the question remained, how does chronic inflammation in brains with Alzheimers disease lead to neuronal dysfunction and the consequent neurodegeneration and dementia?

Amyloid plaques in the brains of people with Alzheimers disease have a heterogeneous composition; for instance, some may also contain sugars, lipids or nucleic acids. Previously, Cao and her colleagues found that amyloid fibrils with nucleic acids, but not those without them, triggered immune cells in the blood to produce type 1 interferon (IFN). IFN is a potent cytokine produced when immune cells sense nuclei acids, such as those that come from viral particles, in their environment. IFN triggers a beneficial inflammatory response that is the first line of defense against viral infections.

While it is best known for its ability to induce an antiviral state in cells, IFN is also involved in immune modulation and tissue damage associated with infectious, autoimmune and other conditions. But, until now, IFN has not been explicitly implicated in Alzheimers disease, Cao said.

In this project, we focused on what was going on in brains with Alzheimers disease, said Dr. Ethan R. Roy, a graduate student in the Graduate Program in Translational Biology and Molecular Medicine at Baylor while he was working on this project. We began by investigating whether microglia from the brain were able to respond to the amyloid/nucleic acid combination by producing IFN.

Roy looked at multiple Alzheimers mouse models in the lab of Dr. Hui Zheng, professor of molecular and human genetics and director of the Huffington Center on Aging, who also is co-principal investigator of the study. Roy found that almost all the animals brains in these models had plaques containing nucleic acids. The composition of these plaques had not been well characterized before, Roy said.

Interestingly, Cao, Roy and their colleagues found that the same mouse brains that had amyloid plaques with nucleic acids also showed a molecular signature mimicking an antiviral IFN response. Further experiments revealed that nucleic acids in the plaques activated brain microglia, which produced IFN that in turn triggered a cascade of inflammatory reactions that led to the loss of synapses, the junctions between neurons through which they communicate. Synapse loss is a key part of neurodegeneration and can lead to memory loss and eventually dementia.

It is well known that synapse loss is directly mediated by the complement system, which is part of the immune system. It comprises a group of proteins that work together to clear microbes and damaged cells, but it also is involved in inflammation.

Although we knew that complement activation triggered synapse loss, what we discovered was the chain of events that led to this outcome. The chain of events points to IFN-mediated pathways controlling complement activation, Cao said.

We were very excited to find that blocking the IFN-triggered cascade of reactions significantly dampened microglia activation and reduced synapse loss in our mouse models, further supporting the leading role of IFN in this process, Roy said.

This study provides a major advance in the understanding of a process that leads to neuronal damage, by connecting IFN, complement and synapse loss: IFN controls the expression of multiple components of the complement cascade and mediates synapse elimination in a complement-dependent manner.

The researchers looked into human brains with Alzheimers disease to see if they presented with characteristics that were similar to those they had observed in mouse models of the condition.

We found that human brains with Alzheimers disease have profound activation of the IFN pathway, suggesting that mechanisms similar to the one we found in mice may be involved in neuronal destruction in people with the disease, Roy said. Further studies need to be conducted to evaluate this hypothesis.

This is important because it would lead to a better understanding of how the disease occurs and suggest novel therapies for this incurable disease.

The accumulation of amyloid plaques in human brains is known to poorly correlate with the severity or duration of dementia. There are people without signs of dementia who harbor significant amounts of both amyloid plaques and tau tangles in their brains, but remarkably lack the robust microglial activation and inflammatory response that is associated with loss of synapses and neurons. On the other hand, the brains of people with dementia linked to Alzheimers disease present with amyloid plaques, tau tangles and inflammation that is involved in neurodegeneration.

Our findings in mouse models suggest that it is plausible that plaques that accumulate in Alzheimers disease patients and those in non-demented individuals differ in their content of nucleic acids. It is thus of great interest to examine more closely the molecular constituents of amyloid plaques in the brains of cognitively resilient individuals and compared them to those of Alzheimers disease cases, Cao said.

This work also may provide new insights into the aging brain. Other work has shown that IFN also seems to participate in the normal aging process of the brain. Cao, Roy and their colleagues think it is also worthwhile to further explore the possibility of modulating IFN activity in aging populations.

Interested in all the details of this study? Find them in the Journal of Clinical Investigation.

Other contributors to this work include Baiping Wang, Ying-wooi Wan, Gabriel Chiu, Allysa Cole, Zhuoran Yin, Nicholas E. Propson, Yin Xu, Joanna L. Jankowsky, Zhandong Liu, Virginia M.-Y. Lee, John Q. Trojanowski, Stephen D. Ginsberg, Oleg Butovsky and Hui Zheng. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine; Harvard Medical School; University of Pennsylvania School of Medicine; Nathan Kline Institute, N.Y., and New York University Langone Medical Center.

The study was funded by NIH grants AG05758, AG032051, AG020670, AG054111, NS092515, AG051812 and AG054672. Further support was provided by the Robert A. and Rene E. Belfer Family Foundation, BrightFocus ADR A20183775, Cure Alzheimers Fund and TBMM T32 training grant (ST32GM088129).

By Ana Mara Rodrguez, Ph.D.

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Connecting interferon, neuroinflammation and synapse loss in Alzheimer's disease - Baylor College of Medicine News

Ever since the earliest reports of a pneumonia-like illness spreading within Hubei province in China, the resemblance to the SARS outbreak of 2002-2003 has been uncanny: probable origins in the wild-animal markets of China; an illness that in some people resembles the common cold or a flu, but in others leads to pneumonia-like symptoms that can cause respiratory failure; community transmission that often occurs undetected; super-spreader events; and reported vertical transmission in high-rises or other living spaces where the waste systems are improperly engineered or drain catch-basins are dry, allowing aerosolized particles to pass from one floor of a building to another (see The SARS Scare for an in-depth description of the epidemiology and virology of the SARS outbreak of 2002-2003 and the four independent zoonotic transmissions of 2003-2004).

UPDATED 3-04-2020 at 12:57p.m. See below.

At first, this latest outbreak was referred to as a novel coronavirus, then in the media as COVID-19 (formally, the name for the disease in an infected person who has become sick, a distinction analogous to that between a person who is HIV positive and one who has developed AIDS). Now that the virus has been characterized and its relationship to SARS firmly established, its designation is SARS-CoV-2severe acute respiratory syndrome coronavirus 2.

Will public-health measures be sufficient to contain its spread? How infectious is it? What is the incubation period? Is this a pandemic? What role does the immune-system response play in the progression of the disease? Which populations are most at risk? Can scientists develop a vaccine, and how quickly? These are some of the questions that scientists worldwide are asking, and that a collaboration among Harvard University and Chinese researchers will address as part of a $115-million research initiative funded by China Evergrande Group, which has previously supported Universitygreen-buildings research at the Graduate School of Design, research onimmunologic diseases, and work inmathematics. (See below for the University press release describing the initiative.)

Harvard Magazinespoke with some of the researchers involved in fighting the first SARS outbreak, and those who will be collaborating with Chinese colleagues, in what is already a worldwide effort to control SARS-CoV-2.

Michael Farzan 82, Ph.D. 97, who in 2002 was an assistant professor of microbiology and molecular genetics at Harvard Medical School (HMS) studying the mechanism that viruses use to enter cells, was the first person to identify the receptor that SARS used to bind and infect human cells. SARS-CoV-2 is a close cousin to SARS, and uses the same human receptor, ACE2, reports Farzan, who is now co-chair of the department of immunology and microbiology at Scripps Research. The ACE2 receptor is expressed almost exclusively in the lungs, gastrointestinal tract, and the kidneys, which explains why the disease is so effectively transmitted via both the respiratory and fecal-oral routes.

But there are subtle differences in the new virus behind the current outbreak, he explained in an interview. The viruss receptor binding domainthe part that attaches to the human receptorhas undergone a lot of what we call positive selection, meaning there has been a good deal of evolutionary pressure on that region from natural antibodies, probably in bats or some other animal host that is a reservoir for this disease. So while the virus retains its ability to bind ACE2, Farzan explains, it no longer binds the same antibodies. That is unfortunate, because as the first SARS epidemic wound down, HMS professor of medicine Wayne Marasco had identified a single antibodyfrom what was then a 27-billion antibody librarythat blocked the virus from entering human cells. (Marasco is actively testing new antibodies, hoping to find one that will have the same effect on SARS-CoV-2. For more on Marascos work, see below.) Still, we are not starting from square one, says Farzan.

In animal studies,Remdesivir [a new and experimental antiviral drug] has seemed to work against SARS-like viruses, he says. Its effectiveness will probably hinge on getting it early enough, in the same way that the antiviral drug Tamifluis most effective against the seasonal flu when given to patients early in the course of infection.

And there is a reasonable hope that a vaccine canbe developed, Farzan adds, because the part of the virus that binds the human receptor is exposed and accessible, making it vulnerable to the immune systems antibodies. In addition, the viral genome is relatively stable. That means SARS CoV-2 wont evolve much over the course of an epidemic, so a vaccine that is relatively protective at the beginning of an epidemic will remain effective until its end.

Another reason for optimismdespite the long road to deploying any vaccine in humansis that the science that allows researchers to understand the viruss structure, life cycle, and vulnerabilities is progressing far more rapidly today than during the first SARS outbreak 17 years ago. So, too, is the understanding of the human immune response to the virus, and of the most effective public-health strategies based on the epidemiology of the disease.

When epidemiologists assess the severity of an epidemic, they want to know how effectively the disease can propagate in a population. The first measure they attempt to calculate is the reproductive number (R0)the number of people that an infected individual will in turn infect in an unexposed population, in the absence of interventions. When the reproductive number is greater than 1 (meaning each infected person in turn infects more than one other person), more and more people become infected, and an epidemic begins. Public-health interventions are therefore designed to lower the rate of transmission below 1, which eventually causes the epidemic to wind down. The second number epidemiologists focus on is the serial intervalhow long it takes one infected person at a particular stage of the disease to infect another person to the point of the same stage of the disease. The serial interval thus suggests how rapidly the disease can spread, which in turn determines whether public-health officials can identify and quarantine all known contacts of an infected individual to prevent their retransmitting the disease to others.

Epidemiologist Marc Lipsitch will be one of several Harvard scientists collaborating with Chinese colleagues to fight SARS-CoV-2Photograph by Kent Dayton

Marc Lipsitch, a professor of epidemiology at the Harvard Chan School of Public Health (HSPH), and director of the schoolsCenter for Communicable Disease Dynamics, helped lead one of the two teams that first calculated the reproductive number of SARS in the 2002-2003 outbreak. SARS had an R0 of 3, he recalls: each case led to three others. In that outbreak, about 10 percent of those who became sick died. The good news is that SARS CoV-2 appears to have a much lower R0 than SARS, ranging from the high ones to low twos, and only 1 percent to 2 percent of those who become sick have died. On the other hand, the serial intervalstill being worked outappears to be shorter, meaning the new virus has the potential to spread faster.

In the current epidemic, Lipsitch notes a further concern: the fact that the incubation-period distribution and the serial-interval distribution are almost identical. Thats a mathematical way of saying that people can start transmitting the virus even when they are pre-symptomatic, or just beginning to exhibit symptoms. That makes tracing and quarantining contacts of infected individualsa classic, frontline public-health measurenearly impossible.

Tracing, quarantining, and other public-health interventions, such as distancing measures (closing workplaces or asking employees to work from home, for example) proved sufficient to defeat SARS in the early 2000s. But with SARS-CoV-2, public-health measures alone may prove inadequate. Controlling this version of SARS may require antivirals, stopgap antibody therapies, and ultimately, vaccines, deployedtogetherwith robust public-health containment strategies.

Unfortunately, SARS-CoV-2 is almost certainly already a pandemic, Lipsitch continues: demonstrating sustained transmission in multiple locations that will eventually reach most, if not all places on the globe. The disease appears to be transmitting pretty effectively, probably in Korea, probably in Japan, and probably in Iran. He now estimates that 20 to 60 percent [figures updated 03-04-2020 at 12:57 p.m.]of the adult global population will eventually become infected.

That said, Infected is different from sick, he is careful to point out. Only some of those people who become infected will become sick. As noted above, only about 1 percent to 2 percent of those who have becomesickthus far have died, he says. But the number of people who areinfectedmay be far greater than the number of those who are sick. In a way, he says, thats really good news. Because if every person who had the disease was also sick, then that would imply gigantic numbers of deaths from the disease.

I'm very gratified, Lipsitch continues, to see that both China and Harvard recognize the complementarity between public health and epidemiology on the one hand, and countermeasure-development on the other hand. We can help target the use of scarce countermeasures [such as antivirals or experimental vaccines] better if we understand the epidemiology; and we will understand the epidemiology better if we have good diagnostics, which is one of the things being developed in this proposal. These approaches are truly complementary.

In the short term, Lipsitchwho has sought to expand the modeling activities of the Center for Communicable Disease Dynamics to better understand the current outbreaks epidemiologysays, It would be great toexpand collaborations with Chinese experts. Longer term, I see a really good opportunity for developing new methods for analyzing data better, as we have in previous epidemics. After the first SARS outbreak, for example, epidemiologists developed software for calculating the reproductive number of novel diseases; that software now runs on the desktop computers of epidemiologists around the world. And in 2009, during an outbreak of swine flu in Mexico, Lipsitch and others developed a method for using the incidence of the disease among awell-documented cohort of travelerswho had left Mexico, to estimate the extent of the disease among amuch larger and less well surveyedpopulation of Mexican residents.

What they found then was that the estimated number of cases in Mexican residents likely exceeded the number of confirmed cases by two to three orders of magnitude. The same method is being used to assess the extent of SARS-CoV-2 in China right nowso far without any hiccups. In the Mexican case, Lipsitchreports, the estimates suggested that severe cases of the disease were uncommon, since thetotal numberof cases was likely much larger than the number ofconfirmedcases. So I think we have learned from each epidemic how to do more things. And in between them, you solidify that less visible, less high-profile research that builds the foundation for doing better the next time. His group, for example, has been developing ways to make vaccine trials faster and better once a vaccine candidate exists.

A vaccine is the best long-term hope for controlling a disease like SARS-CoV-2. Higgins professor of microbiology and molecular genetics David Knipe, who like Lipsitch will participate in the newly announced collaboration, works on vaccine delivery from a molecular perspective. Knipe has developed methods to use the herpes simplex virus (HSV) as a vaccine vector and has even made HSV recombinants that express the SARS spike proteinthe part of the virus that binds the human ACE2 receptor. He now seeks to make HSV recombinants that express the new coronavirus spike protein as a potential vaccine vector.

But Knipe also studies the initial host-cell response to virus infection, which is sometimes called the innate immune response. And he has used HSV vectors that expressed the first SARS spike protein to study how it activates innate immune signaling. That is important because inSARS 1, initial symptoms lasted about a week, but it was the second phasecharacterized by a massive immune-system response that began to damage lung tissuethat led to low levels of oxygen saturation in the blood, and even death.The inflammation in the lungs is basically a cytokine storm, an overwhelming and destructive immune response thats the result of innate signaling, Knipe explains. So were going to look at that with the new coronavirus spike protein, as well. This could help to determine the actual mechanism of inflammation, and then we can screen for inhibitors of that that might be able to alleviate the disease symptoms.

The idea, he says, is to stop theinflammatoryresponse now killing people in the respiratory phase of the disease by targeting the specific molecular interaction between the virus and the host cell. This, he explains, aligns with one of the principal initial goals of the collaboration, which is to support research both in China and at Harvard to address the acute medical needs of infected individuals during the current crisis.

Another form of frontline defense against the virus is antibody therapy. In an epidemic, this type of therapy is usually administered as a prophylaxis to first responders at high risk of infection, or as treatment to patients who are already sick or to people who might be harmed by a vaccine, such as pregnant women, the elderly, or those with co-morbidities. Wayne Marasco, an HMS professor with a lab at the Dana Farber Cancer Institute, was the first to develop antibody therapies against SARS and MERS, a related coronavirus, in 2014. What he learned in those outbreaks was that using only a single antibody to bind the viruss receptor binding domainthe part of the virus that attaches to the human receptoris not enough to prevent escape through mutations that neutralize the therapy. You have to use combinations of antibodies to block the escape pathways, he explains. But the combinations have to be carefully designed to avoid the risk that the virus will evolve a gain of functionor the virus coming out of the patient is more pathogenic than the virus you started to treat.

During the MERS outbreak, Marasco led the Defense Advanced Research Projects Agencys 7-Day Biodefense program.DARPA would drop an unknown pathogen off at our doorstep, Marasco says, and we had seven days to develop a therapeutic that could be manufactured at scale. A second DARPA-funded project focused on reducing the cost of therapies to less than $10 a dose. The government has made efforts to streamline that process to get the production sped up and the cost decreased, he notes, although the efforts are independent of regulatory approval, which has a life of its own.

Marasco currently collaborates with an international team that can perform studiesincluding some that cant be done at Harvardthanks to ready access to a Biosafety Level 4 laboratory and to non-human primates for testing. The team is working to develop antibody therapies effective against SARS-CoV-2, but Marasco cautions that the situation is pretty worrisome with a disease that has a long latency period when people show no symptoms, and when public-health officials cannot identify source cases (as in Italy and in the single case of apparent community transmission in California reported February 26).

The problem in getting ahead of this now, he continues, is funding. Government resources are generally a redistribution of funds that have previously been granted to projects such as the Ebola outbreak in West Africa, or come as administrative supplements to preexisting grants. But with the pace of this epidemic, a lack of resources is limiting what can get done and how quickly it can be accomplished. Beyond the creation of therapeutics, there are all kinds of epidemiologic considerations that require rapid funding, from investigating modes of transmission to field testing for infection.

In the near term, the way to treat masses of patients, he says, is to take blood plasma from someone who has recovered and administer it to an infected person. The convalescents antibodies then fight the infection. The FDA would never approve it, he notes, but it does work. Ultimately, the treatment of choiceand the most cost-effective approach, he says, will be a vaccine.

In the last days of 2019 and the first days after the New Year, we started hearing about a pneumonia-like illness in China, says Dan Barouch, an HMS professor of medicine and of immunology known for his anti-HIV work, whose lab has developed a platform for rapid vaccine development. (During the Zika virus outbreak of 2016, for example, his group was the first to report, within a month, a vaccine protective in animal models.) When the genome of the virus was released on Friday, January 10, we started reviewing the sequence that same evening, working through the weekend. By Monday morning, we were ready to grow it.

His concern about this latest outbreak was that the rate of spread seemed to be very rapid. In addition, the outbreak had the clinical features of an epidemic. We reasoned that this might make it difficult to control solely by public-health measures, he says, particularly because the virus can be transmitted by asymptomatic individuals. Thus, if the epidemic is still spreading toward the end of this year or early 2021, by which point a vaccine might be available, Barouch explains, such a remedy could prove essential. Historically, when viral epidemics don't self-attenuate, the best method of control is a vaccine.

Although Barouchs Beth Israel Deaconess Medical Center lab is working on DNA and RNA vaccines, a new technology that has the potential to cut vaccine development times in half, large-scale manufacturing using so-called nucleotide vaccines is unproven. That's why I think there needs to be multiple parallel vaccine efforts, he emphasizes. Ultimately, we don't know which one will be the fastest and most protective. At the moment, he reports, there are at least a half dozen scientifically distinct vaccine platforms that are being developed and he believes that vaccine development for this pathogen will probably go faster than for any other vaccine target in human history.

Ever since I graduated from medical school, he points out, there have been new emerging or re-emerging infectious disease outbreaks of global significance with a surprising and disturbing sense of regularity. There is Ebola. There was Zika. There were SARS, MERS; the list keeps growing. With climate change, increasing globalization, increasing travel, and population shifts, the expectation is that epidemics will not go away, and might even become more frequent.

In this global context, Barouch emphasizes the importance of a collaborative response that involves governments, physicians, scientists in academiaandin industry, and public-health officials. It has to be a coordinated approach, he says. No one group can do everything. But I do think that the world has a greater sense of readiness this time to develop knowledge, drugs, and therapeutics very rapidly. The scientific knowledge that will be gained from the vaccine efforts [will] be hugely valuable in the biomedical research field, against future outbreaks, and in the development of a vaccine to terminate this epidemic.

University provost Alan Garber, a physician himself, adds that Global crises of such magnitude demand scientific and humanitarian collaborations across borders. Harvard and other institutions in the Boston area conduct research on diagnostics, virology, vaccine and therapeutics development, immunology, epidemiology, and many other areas.With its tremendous range of expertise and experience, our community can be an important resource for any effort to address a major global infectious disease outbreak. Our scientists and clinicians feel an obligation to be part of a promising collaboration to overcome the worldwide humanitarian crisis posed by this novel virus.

UPDATED 3-03-2020 AT 12:10 p.m.TO INCLUDE A REPORT FROM THE MEETING WITH CHINESE COLLEAGUES

In a closed-door meeting that took place Monday, March 2, 2020, at Harvard Medical School, nearly 80 Boston-area scientists gathered to discuss with colleagues from China participating via video link how to respond to COVID-19 disease and the SARS-CoV-2 virus that causes it. This was the first meeting to take place as a result of the collaboration with scientists at theGuangzhou Institute of Respiratory Health announced on Monday, February 24.In attendance locally were experts from Harvard Medical School (HMS), the Harvard T.H. Chan School of Public Health, the HMS-affiliated hospitals, the Ragon Institute, Boston University, the Broad Institute, MIT, the Wyss Institute, as well as representatives from industry. The workshop, convened by HMS dean George Q. Daley, was a planning session to map out the process for coordinating on collaborative projects, designed to allow the participants to meet, form working groups by research area, and determine next steps.

The collaboration harnesses the strengths of the Boston scientific and biomedical ecosystem, the events organizers said in a statement, with the critical experience of Chinese scientists, who are providing on-the-ground insight into diagnostics and care for patients on the frontlines.

This public health crisis, they continued, is an opportunity to catalyze an unprecedented level of collaboration among various scientific efforts across Boston and Cambridge to address both the acute, most pressing challenges of this particular epidemic but also to establish a framework for future collaborations and create a more nimble rapid-response system for other epidemics.

The meeting was organized according to areas of research interest, need, and opportunity including:

The meeting demonstrated the need to establish a collaborative regional response capacity, not only for this outbreak, but for other future emerging infectious diseases, said the organizers. They are now working to create an organizational structure that will formalize the working groups in each of the above areas, and allow for the optimal deployment of resources including disciplinary and clinical expertise, shared core facilities, and funding.

The official Harvard press release follows:

Harvard University Scientists to Collaborate with Chinese Researcherson Development of Novel Coronavirus Therapies, Improved Diagnostics

At a glance:

Since its identification in December, the novel coronavirus has quickly evolved into a global threat, taking a toll on human health, overwhelming vulnerable health care systems and destabilizing economies worldwide.

To address these challenges, Harvard University scientists will join forces with colleagues from China on a quest to develop therapies that would prevent new infections and design treatments that would alleviate existing ones.

The U.S. efforts will be spearheaded by scientists at Harvard Medical School, led by DeanGeorge Q. Daley, working alongside colleagues from the Harvard T.H. Chan School of Public Health. Harvard Medical School will serve as the hub that brings together the expertise of basic scientists, translational investigators and clinical researchers working throughout the medical school and its affiliated hospitals and institutes, along with other regional institutions and biotech companies.

The Chinese efforts will be led by Guangzhou Institute of Respiratory Health and Zhong Nanshan, a renowned pulmonologist and epidemiologist. Zhong is also head of the Chinese 2019n-CoV Expert Taskforce and a member of the Chinese Academy of Engineering.

Through a five-year collaborative research initiative, Harvard University and Guangzhou Institute for Respiratory Health will share $115 million in research funding provided by China Evergrande Group, aFortuneGlobal 500 company in China.

We are confident that the collaboration of Harvard and Guangzhou Institute of Respiratory Health will contribute valuable discoveries to this worldwide effort, said Harvard University President Lawrence Bacow. We are grateful for Evergrandes leadership and generosity in facilitating this collaboration and for all the scientists and clinicians rising to the call of action in combating this emerging threat to global well-being.

Evergrande is honored to have the opportunity to contribute to the fight against this global public health threat, said Hui Ka Yan, chair of the China Evergrande Group. We thank all the scientists who responded so swiftly and enthusiastically from the Harvard community and are deeply moved by Harvard and Dr. Zhongs teams dedication and commitment to this humanitarian cause. We have the utmost confidence in this global collaborative team to reach impactful discoveries against the outbreak soon.

While formal details of the collaboration are being finalized, the overarching goal of the effort is to elucidate the basic biology of the virus and its behavior and to inform disease detection and therapeutic design. The main areas of investigation will include:

With the extraordinary scale and depth of relevant clinical and scientific capabilities in our community, Harvard Medical School is uniquely positioned to convene experts in virology, infectious disease, structural biology, pathology, vaccine development, epidemiology and public health to confront this rapidly evolving crisis, Daley said. Harnessing our science to tackle global health challenges is at the very heart of our mission as an institution dedicated to improving human health and well-being worldwide.

We are extremely encouraged by the generous gesture from Evergrande to coordinate and supportthe collaboration and by the overwhelmingly positive response from our Harvard colleagues, said Zhong, who in 2003 identified another novel pathogen, the severe acute respiratory syndrome (SARS) coronavirus and described the clinical course of the infection.

We look forward to leveraging each of our respective strengths to address the immediate and longer-term challenges and a fruitful collaboration to advance the global well-being of all people, Zhong added.

Harvard University ProvostAlan M. Garbersaid outbreaks of novel infections can move quickly, with a deadly effect.

This means the response needs to be global, rapid and driven by the best science. We believe that the partnershipwhich includes Harvard and its affiliated institutions, other regional and U.S.-based organizations and Chinese researchers and clinicians at the front linesoffers the hope that we will soon be able to contain the threat of this novel virus, Garber said. The lessons we learn from this outbreak should enable us to respond to infectious disease emergencies more quickly and effectively in the future.

Read the original here:
Harvard and Guangzhou Institute of Respiratory Health Team to Fight SARS-CoV-2 - Harvard Magazine

Close inspection: A neuronal tract that connects the brains hemispheres is absent or thinner in people with TBR1 mutations (bottom) than in controls (top).

People with mutations in a gene called TBR1 have unusual features in several brain regions, along with autism traits and developmental delay, according to a new study1.

TBR1 encodes a protein that is involved in brain development. It controls the expression of several other autism-linked genes that lay out the structure of the cerebral cortex, the brains outer layer and locus of higher cognition.

Studies in mice have suggested that deletion or mutation of TBR1 results in structural abnormalities in the brain2. The layers of the cerebral cortex in these mice may be disorganized, and connections in the amygdala a structure involved in processing emotions may be missing.

However, few studies have examined how TBR1 mutations affect people.

Mutations in the gene have been linked to intellectual disability and autism, but more subtle features have not been well documented, says lead investigator Sophie Nambot, a clinician who specializes in medical genetics at the Centre Hospitalier Universitaire Dijon Bourgogne in France.

Previous research documented about 13 people with TBR1 mutations, but the reports included minimal information about outward characteristics, and few include brain-scan data, Nambot says.

The new study adds 25 previously unreported individuals to the literature, along with detailed descriptions of their physical, neurological and genetic features. The findings were published in January in the European Journal of Human Genetics.

It greatly increases the number of individuals and types of mutations in the TBR1 gene that are associated with developmental disorders, says John Rubenstein, professor of psychiatry at the University of California, San Francisco, who was not involved in the study.

Nambots team identified people with TBR1 mutations by contacting national and international health networks, such as GeneMatcher and DECIPHER. They ultimately recruited 25 people, ranging in age from 2 to 29 years, at 22 sites.

Scientists at the centers gathered information about these individuals development and autism traits, such as communication difficulties, lack of eye contact and restricted interests.

All 25 have intellectual disability or moderate-to-severe developmental delays; 19 show autism traits.

The researchers also scanned the individuals genomes to identify small and large mutations in TBR1. Combining their data with those from previous studies, the team identified 29 different single-nucleotide variants.

Magnetic resonance images from seven of the people revealed previously unidentified structural differences in their brains, Nambot says. These differences are in the cerebral cortex; the anterior commissure, a neuronal tract that connects the two hemispheres of the brain; and the hippocampus, an area involved in learning and memory.

In two of the people, the ridges in the cerebral cortex are unusually broad and thick, and in three people, the hippocampus is malformed.

The hippocampal problems are very likely to affect learning and memory, says Robert Hevner, director of neuropathology at the University of California, San Diego. The findings may explain why people with TBR1 mutations have developmental delays, he says. They also support prior studies suggesting that TBR1 affects a type of cell that helps organize the cortex and the hippocampus during fetal development.

Notably, in all seven people, the anterior commissure is thin or absent.

Research in mice demonstrates a similar phenomenon, says Yi-Ping Hsueh, distinguished research fellow in neuroscience at the Institute of Molecular Biology in Taiwan, who was not involved in the new study. In 2014, Hsuehs team found the anterior commissure to be partially missing in mice lacking one copy of TBR1, resulting in social and cognitive problems2.

Unlike mouse studies, however, the new study does not quantify volume differences in brain structures, which makes it difficult to gauge what should be considered atypical, Hsueh says.

The researchers caution that their sample is small, especially given the range of TBR1 mutations present. Still, they say, their findings may help scientists classify genetic subtypes of autism.

Continue reading here:
Mutations in top autism gene linked to changes in brain structure - Spectrum

What is Genomics?

Genomics is the study of all the genes within an organism, including humans, and how all of those genes are interrelated and influence the organism. Genetics is primarily focused on single genes. Genomics involves sequencing and analysis of genomes through the use of DNA sequencing and bioinformatics.1

How are Genomics Being Used in Toxic Tort Litigation?

The use of genomics to defend toxic tort claims is emerging. For example, defendants in recent cases involving asbestos, benzene, low-dose radiation and other substances have used genomics successfully. These successes tend to occur after an early and careful look at the facts of a case.

For example, defendants recently and successfully used a genomic causation defense in two mesothelioma cases involving males, who developed peritoneal mesothelioma in their 30s, with little or no known exposure to asbestos fibers. The early age of cancer onset was a material fact suggesting a genetically caused cancer. Another fact suggesting that genomics should be considered is the presence of a family history of cancer, especially early onset cancers or multiple cancers in particular family members. Contrary to what one might assume, the family history does not need to involve the same cancer or the same organ. That is because adverse germline mutations (ones that are inherited) can cause cancers located on different organs.

What can Genomics Revealabout Cancers?

As explained by members of ToxicoGenomica, a multidisciplinary group of scientists and lawyers that provide services for using genomic and systems biology data in civil litigation, the application of Next Generation Sequencing (NGS) technologies in toxic tort cases can reveal the presence or absence of evidence of toxicant exposure and damage that is locked within the genetic blueprint of an individual, and in appropriate cases, can assess alternative causation.

In other words, the process can reveal objective evidence showing that adverse gene mutations were sufficient to cause a cancer without regard to exposure to a particular substance (such as asbestos fibers).

How is the Genomic Information Obtained?

The initial steps in the gene sequencing process are not complex. The first step is to obtain a source from which laboratory technicians can obtain DNA that meets standard criteria. Typically, DNA is either extracted from small samples of fresh blood (about two teaspoons) or from tumor biopsy tissue samples that include some non-cancerous tissue.

In some situations, old biopsy material may serve as a source of DNA, even if the biopsy sample was taken for reasons not involving cancer.

Reasons Why Using Genomic Evidence is a Good Idea.

1) To break up purported class actions. By exposing the material physical differences between plaintiffs, class claims can be defeated.

2) To force plaintiffs to back down. In toxic tort litigation, some of the most financially successful plaintiffs firms use templates for their cases. This allows them to recycle the same theories and defenses with only a modest investigation of the individualized facts. Firms using such a model are disinclined to invest the time and money needed to understand genomics and the genomics of a particular plaintiff. Instead, they may dismiss claims or settle for a relatively small amount.

According to a lawyer affiliated with ToxicoGenomica, we are seeing an increase in cases settling quickly after disclosure of a high quality expert report that proves up the existence of combinations of adverse germline mutations inherited by a person with cancer and a family history of cancer.

3) To dispute exposure. Some forms of genomic analysis can be used to generate data to show whether a plaintiff has or has not been exposed to a particular toxicant. For example, increasing numbers of studies evaluate the presence or absence of exposures based on patterns involving small or large segments of RNA. Studies of this sort are increasingly used to assess genomic changes related to use of tobacco.2

4) To combat the scope of general causation. Genomic evidence can provide previously unknown, but objective evidence, to dispute general long-held beliefs about general causation. For example, for years, juries were unpersuaded by the argument that mesothelioma could be idiopathic, meaning cause unknown. Todays jurors, raised on TV shows such as CSI, expect and want to see objective scientific data. Recently, researchers used new scientific tools (e.g., CRISPR) to create genetically engineered mice that developed mesotheliomas without asbestos exposure when given mutations that promoted general cancer development, supporting the argument that mesotheliomas can be idiopathic or at least not related to asbestos exposure.3 These new genomic and molecular tools, such as CRISPR, are of paramount importance for litigation. It allows researchers to perform studies and experiments that were previously not possible to determine the impact of various substances on humans and even a given individual. Risk managers, lawyers and others do not need to know the nuances of how to use these tools, but they should know of their existence. To read more on this subject, see my three-part Article Using Genetic Evidence to Defend Against Toxic Tort Claims, co-authored with Dr. Whitney Christian and initially printed in the Intellectual Property & Technology Law Journal (2017). https://www.bclplaw.com/images/content/9/9/v2/99117/IP-Reprint-Article-complete.pdf

5) To demonstrate alternative causation. Genomics can provide objective evidence of the presence or absence of adverse germline mutations known to play a causative role in the hundreds of known familial cancer syndromes. Persons who inherit these adverse germline mutations are genetically predisposed to develop cancers and/or other conditions attributable to inherited mutations.4

6) To demonstrate a plaintiffs susceptibility to or resistance to a particular toxicant.

The presence of a protective mutation (an allele) may make it less likely that the substance in question actually caused the disease. For example, in a benzene case, the plaintiffs expert claimed that the plaintiff likely had a genome that made him more susceptible to a disease when benzene was metabolized. The scientists at ToxicoGenomica assessed his relevant genes and found the opposite, that he had a favorable genome that helped his body resist possible adverse effects. After receiving the data generated by ToxicoGenomica, the plaintiffs expert changed his mind and agreed that: 1) the plaintiff was not susceptible and 2) had a robust genome with respect to metabolism of benzene.

7) To contest specific causation. Genomics increasingly can identify somatic signature mutations patterns or non-inherited mutations in tumors. These patterns of somatic mutations increasingly can be used to provide objective evidence showing that a particular toxicant caused the tumor. Extensive somatic mutation pattern analysis of lung cancers in smokers has produced large amounts of data objectively showing that particular lung cancers arose from tobacco smoking instead of something else. In other instances, the pattern may suggest that the tumor arose because of an inherited mutation in a gene such as KRAS.5

8) To tackle specific causation. In some cases, gene expression profiling can be used to determine with more precision whether a persons disease was or was not caused by a specific toxicant. Exposure to certain substances leaves behind genetic fingerprints. If those fingerprints are missing, then it is reasonable to conclude that the toxicant did not cause the disease.

This technique was used successfully in a case involving naturally occurring radioactive materials. The defendants were able to show that the footprints were missing and that the plaintiffs gene expression instead supported that view that she had developed cancer from inherited mutations. 6

Caution for the Defense Attorney. While genomic evidence can help defendants, it can certainly be used to support a plaintiffs claim and provide evidence of both exposure and causation. As a result, it would be wise for counsel to assess carefully whether genomics is appropriate in a given case.

An example of genomics aiding plaintiffs lies in a federal multi-district litigation involving a diabetes drug known as Actos, which was alleged to cause bladder cancers in some people. The MDL court held an extensive Daubert hearing, which included expert opinions on how genomics could provide a logical explanation for why cancers developed in an unusually short time period (less than 1 year). The court decided to admit the genomic evidence, which made plaintiffs claims much more plausible. After that ruling, and after some other trial losses, defendants subsequently agreed to pay over $2 billion in settlements.

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Why Companies Should Consider Genomic Evidence In Defending Toxic Torts - Lexology

The United States government is a massive employer, and is always looking for qualified candidates to fill a wide variety of open employment positions in locations across the country. Below youll find a Qualification Summary for an active, open job listing from the Department of the Army. The opening is for a Supervisory Clinical Laboratory Scientist in Fort Leonard Wood, Missouri Feel free to browse this and any other job listings and reach out to us with any questions!

Supervisory Clinical Laboratory Scientist Fort Leonard Wood, MissouriU.S. Army Medical Command, Department of the ArmyJob ID: 222868Start Date: 03/03/2020End Date: 03/16/2020

Qualification SummaryWho May Apply: US Citizens In order to qualify, you must meet the education and experience requirements described below. Experience refers to paid and unpaid experience, including volunteer work done through National Service programs (e.g., Peace Corps, AmeriCorps) and other organizations (e.g., professional; philanthropic; religious; spiritual; community; student; social). You will receive credit for all qualifying experience, including volunteer experience. Your resume must clearly describe your relevant experience; if qualifying based on education, your transcripts will be required as part of your application. Additional information about transcripts is in this document. Basic Requirement for Supervisory Clinical Laboratory Scientist: A. A Bachelors or graduate/higher level degree from a regionally accredited college/university including courses in biological science, chemistry and mathematics, AND successful completion of a Medical Laboratory Scientist/Clinical Laboratory Scientist program accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) or an accrediting body recognized by the U.S. Department of Education at the time the degree was obtained. OR B. At least a full 4-year course of study that included 12 months in a college or hospital-based medical technology program or medical technology school approved by a recognized accrediting organization. The professional medical technology curriculum may have consisted of a 1-year post- bachelors certificate program or the last 1 or 2 years of a 4-year program of study culminating in a bachelors in medical technology. OR C. A bachelors or graduate/higher level degree from an accredited college/university that included 16 semester hours (24 quarter hours) of biological science (with one semester in microbiology), 16 semester hours (24 quarter hours) of chemistry (with one semester in organic or biochemistry), one semester (one quarter) of mathematics, AND five years of full time acceptable clinical laboratory experience in Blood Banking, Chemistry, Hematology, microbiology, Immunology and Urinalysis/Body Fluids. This combination of education and experience must have provided knowledge of the theories, principles, and practices of medical technology equivalent to that provided by the full 4-year course of study described in A or B above. All science and mathematics courses must have been acceptable for credit toward meeting the requirements for a science major at an accredited college or university. Acceptable experience is responsible professional or technician experience in a hospital laboratory, health agency, industrial medical laboratory, or pharmaceutical house; or teaching, test development, or medical research program experience that provided an understanding of the methods and techniques applied in performing professional clinical laboratory work. Certification/licensure as a medical technologist (generalist) obtained through written examination by a nationally recognized credentialing agency or State licensing body is a good indication that the quality of experience is acceptable. Evaluation of Education and Experience: The four major areas of clinical laboratory science are microbiology, clinical chemistry, hematology, and immunohematology (blood banking). Qualifying course work in these areas includes bacteriology, mycology, mycobacteriology, tissue culture, virology, parasitology, endocrinology, enzymology, toxicology, urinalysis, coagulation, hemostasis, cell morphology, immunology, serology, immunoserology, immuno-deficiency, hemolysis, histocompatibility, cyto-genetics, and similar disciplines or areas of laboratory practice. Related fields include physiology, anatomy, molecular biology, cell biology, embryology, pathology, genetics, pharmacology, histology, cytology, nuclear medicine, epidemiology, biostatistics, infection control, physics, statistics, and similar areas of science where the work is directly related to the position to be filled. Exemption: You are exempt from the basic requirements above if you are a current federal employee occupying a position in the 0644 occupational series and have been continuously employed in this occupational series since September 27, 2017 or before. Note: You will be required to provide appropriate documentation to the respective Human Resources Office to validate your status. In addition to meeting the basic requirement above, to qualify for this position you must also meet the qualification requirements listed below: Experience required: To qualify based on your work experience, your resume must describe one year of specialized experience which includes providing various verification duties in a laboratory. This definition of specialized experience is typical of work performed at the next lower grade/level position in the federal service (GS-09). OR Education: I have at least two and a half years (45 semester hours) of progressively higher level graduate education leading towards a Ph.D. or equivalent doctoral degree from an accredited college or university that is directly related to the work of the position. OR Combination of Education and Experience: A combination of education and experience may be used to qualify for this position as long as the computed percentage of the requirements is at least 100%. To compute the percentage of the requirements, divide your total months of experience by 12. Then divide the total number of completed graduate semester hours (or equivalent) beyond the first year (total graduate semester hours minus 18) by 18. Add the two percentages. Experience or graduate education must have been in (1) the general field of medical technology; (2) one of the disciplines or specialized areas of medical technology; or (3) a field directly related and applicable to medical technology or the position to be filled. AND Certification: Certification from the American Society for Clinical Pathology (ASCP), American Medical Technologist (AMT) or other board or registry deemed comparable by the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) or their designee as a Medical Technologist (MT) or Medical Lab Scientist (MLS) is required.

If youd like to submit a resume or apply for this position, please contact Premier Veterans at abjobs@premierveterans.com. All are free to apply!

Apply

Post a job on LemonWire. Email jobs@lemonwire.com.Want to advertise on listings like this? Email ads@lemonwire.com.

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Supervisory Clinical Laboratory Scientist Job in Fort Leonard Wood, Missouri - Department of the Army - LemonWire

When Emma Hodcroft read that, seemingly out of nowhere, a rash of cases of the novel coronavirus had popped up in Britain in late January, she started collecting media reports on them, searching the articles for clues as to how it had moved to the island nation. Early reports suggested that a lone traveler from Singapore, who was unaware he was infected with virus, had visited a French chalet for a few days and had spread the virus to others at the ski resort. This intrigued Hodcroft, who is half British and a postdoctoral researcher in evolutionary biologist Richard Nehers lab at the University of Basel in Switzerland, where she uses genetics to study and track diseases. She took notes on the cases that were associated with the infected traveler. At first, there wasnt that much information and the story was simple, she tells The Scientist. But more and more cases kept appearing, and she found it hard to keep track of who had traveled to which country and when they were diagnosed.

Hodcroft decided to generate an infographic showing the connections between the traveler from Singapore and the other coronavirus cases emerging in Europe. I thought, Ill make an image and see if anyone else finds this useful, she says. She posted the image on Twitter, and somewhat unexpectedly, it got a lot of attention, she says. People were definitely really, really interested in this. So I kept that image updated over the next week or so. As she updated it, the graphic showed that at least 21 people were exposed to the virus at the ski resort the traveler from Singapore visited; 13 of those people ended up developing COVID-19, the disease caused by the virus. After shed finished the preliminary work, a colleague of Hodcroft saw it and suggested she write it up for publication. She posted the paper on February 26; the next day it appeared in Swiss Medical Weekly.

Hodcroft talked with The Scientist about the work, how its conclusions have been supported by genetic testing of viral strains from patients, and what it tells us about the spread of the virus, SARS-CoV-2, in other countries.

Emma Hodcroft: Firstly, that it seems like so many people [at least 13] could be infected by a single person. It seems like they were infected by the man who traveled from Singapore. So thats quite a lot of forward transmission on his part in a fairly short time period; he was only in France for about four days. Of course, this could be some unusual event that doesnt normally happen, but it lets us put an outer bound on what is possible even if it is not common.

The other thing thats surprising is that, according to the patient statement that he released, the focal patient never had any symptoms. In his own words, he never felt sick. So he did all of this transmission without ever having any indication that he was unwell or that he should be taking any precautions to modify his behavior. It tells us that some infections might be from people who never even know that theyre sick.

Text continues below infographic

Contact tracing showing the spread of SARS-CoV-2 in a particular cluster of patients in Europe.

EH: As far as we can tell, no one from this cluster had severe symptoms. It seems like some people did have some symptoms, but they were never serious. And thats also interesting because it shows that if we didn't know about this outbreak, its pretty likely that these people would have kind of written this off as a bad cold or the flu. None of them would have ended up going to hospital or significantly changing their behavior. And again, this indicates that it might be quite hard, and it is becoming quite hard, to contain this virus because some people don't feel very unwell, such that they would change their behavior or go for testing.

EH: In the US, from the information available, it still doesnt seem like the US has really ramped up testing. We dont know the number of tests that have been performed because its come down off of the CDC website, which is a little concerning. But at least the last reports that were given to us show the US was really lagging behind most countries in the number of tests that it had done.

A few days ago, the research group called the Seattle Flu Study, which is designed to take community samples from random people who have any kind of cough, runny nose, or cold-like symptoms and look for the fluthey pivoted and started testing some of the samples for coronavirus. They found a case in the Seattle area and sequenced the viral genome of the infected person [posted on NextStrain] and showed it links very closely with another case in the Seattle area thats from mid-January. And so this strongly suggests (though we dont yet know for certain) that there has been ongoing undetected transmission in Seattle since mid-January and wasnt picked up because we werent looking for it. This has become clearer in the last few days, as more cases and even deaths have been reported in Washington State. That tells us the virus hasnt just appeared in the last few days in the area.

Text continues below graphic

The viral genome of the first case in Washington (USA/WA1/2020) is identical to Fujian/8/2020. The genome of the virus from a second case in Washington (USA/WA2/2020) is identical to the first Washington case, except it has three additional mutations. This suggests WA1 was a traveler from China bringing the virus to Snohomish County, Washington in mid-January, where the virus circulated undetected for about five weeks, a timespan that explains why WA2 is so similar genetically, with a few mutations. The graphic shows the connection to the other cases with viral sequences now available.

EH: This virus causes respiratory illness, which can make you feel unwell for a few days and then you get better or it can progress. If the illness progresses it can cause lung damage that makes the person more susceptible to other illnesses, such as bacterial infection. This can be treated too and for many people that treatment turns the course of the infection, but some dont and the effort can essentially delay their death. So the infection may have occurred weeks [before a person dies]. This is not something intrinsic to this virus, however. With respiratory illness, its usually something that takes a substantial amount of infection and lung damage before you succumb to it.

EH: Sequencing can tell us a lot about what is happening with the virus right now. The Washington samples are a perfect example. . . . Without having these genomes, we never would have seen this signal of ongoing transmission, which we saw just before the case explosion in Washington. And on the flip side we can tell when cases are coming in from other countries. We have another genome from Washington State thats grouping with genomes that we know have a travel history to Italyso it seems like this could be a case where [an infected person] came back from Italy.

When you have a very small number of cases of a disease, you can do this just through epidemiological contact tracing: you can go to everyone and ask questions and find out the connections between the cases. As the case numbers scale up, this becomes very hard to do. With genetic sequencing, we can do this without having to go and try and figure out where everyone was at the time of infection. Weve had an influx of sequences from Brazil, Switzerland, Mexico, Scotland, Germany. These have clustered with sequences from Italy and have a travel history from Italy and so from that we can show that Italy really is now exporting cases around the world to multiple countries.

EH:Theres been a lot of modeling, not only with genetics but epidemiologically in the last few weeks, and we had pretty strong indications that circulation was wider than publicly thought. At the time, we did try to some extent to get this message out to government health agencies and the public in general. I do think that in the future, incorporating a little bit more of that scientific expertise perhaps into the public dialogue and government decision-making could make a big difference. The earlier that you can act in an epidemic, you have more effect you can have, because one person goes on to infect a few more people who go on to infect a few more people. Its much harder once that has gone up to 10 [infected] people, than if you can stop with person one.

One thing I would note is that studies have shown that limiting transportation really doesnt make much of an impact for outbreaks. Quarantining particular cities, if they seem to be epicenters, can work as a preventive measure, but as the epidemic scales up, you move past being able to contain it in this sense, [and] what you end up doing is just disrupting supply routes, interrupting business, making all of these things much harder.

Editors note: This interview has been edited for brevity.

Ashley Yeager is an associate editor atThe Scientist. Email her at ayeager@the-scientist.com. Follow her on Twitter @AshleyJYeager.

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Coronaviruss Genetics Hint at its Cryptic Spread in Communities - The Scientist

Trevor Bedford, a researcher at Seattles Fred Hutchinson Cancer Research Center, discusses how genome sequencing is being used to track the spread of the COVID-19 coronavirus at the American Association for the Advancement of Sciences annual meeting. (Fred Hutch News Service Photo / Natalie Myers)

An evolutionary analysis based on the genome sequences of COVID-19 coronavirus samples taken from patients in the Seattle area suggests that the number of infections doubles roughly every six days, which translates into hundreds of infections over the course of the past six weeks.

So far, 18 cases have been confirmed in Western Washington, including 14 in King County and four in Snohomish County, north of Seattle. As of today, five patients have died four in King County and one in Snohomish County.

But the analysis laid out in a series of tweets from Trevor Bedford, a researcher at Seattles Fred Hutchinson Cancer Research Center who specializes in the study of viral dynamics, concludes that many more people are likely to be part of a chain of infections leading from the first patient in the U.S. to be diagnosed with the virus. Some probably passed along the virus even though they didnt know they were infected a phenomenon known as cryptic transmission.

Depending on how the computer modeling is tweaked, as many as 1,500 people may have picked up the virus through the transmission chain that began with the patient known as WA1, who traveled from the Chinese city of Wuhan to Snohomish County in mid-January.

There will be more in the whole state, Bedford wrote. He said he suspected that the Seattle areas current coronavirus situation is similar to what the situation was in Wuhan around Jan. 1, when the spread of the infection was beginning to pick up steam. Three weeks later, Wuhan had thousands of infections and was put in large-scale lockdown, Bedford wrote today in a blog post that supplemented his tweets.

Bedfords conclusions are based on a close comparison of viral genome sequences from WA1 and another Snohomish County patient known as WA2, leading to an assessment of where they fit on the broader evolutionary tree for the virus.

The two sequences are similar, but patterns of variation in the genetic code can indicate how much that code has changed in the course of transmission.

The virus from WA1 was sampled on Jan. 19, and the virus from WA2 was sampled on Feb. 28, The viruses genetic codes were sequenced by the research team behind the Seattle Flu Study and shared publicly to the worldwide GISAID database for pathogenic viruses. That allowed Bedford to reconstruct how the coronavirus evolutionary tree spread out over the course of those six weeks.

In todays tweetstorm, Bedford said WA1s case appears to have been the start of a transmission chain leading to WA2. This suggests that the case WA1 infected someone who was missed by surveillance due to mild symptoms, and a transmission chain was initiated at this point in mid-January, he wrote.

The transmission chain that went through WA2 wasnt picked up, probably due to the fact that until last week, the testing effort was focused on sick people who were traveling directly from China or who were in direct contact with a known case.

This lack of testing was a critical error, and allowed an outbreak in Snohomish County and surroundings to grow to a sizable problem before it was even detected, Bedford wrote in todays blog post.

Bedford emphasized that his analysis, conducted in partnership with epidemiologist Mike Famulare of the Institute for Disease Modeling, was still preliminary. Weve reached out to Fred Hutch for more information about the analysis.

The preliminary conclusions emphasize the importance of taking steps to reduce the spread of the virus: washing hands often, making an effort to avoid touching your face, staying home if youre sick, and avoiding close contact with sick people.

Heres todays full series of tweets from Bedford:

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Genetic analysis suggests coronavirus infections double every six days, spreading to hundreds - GeekWire

It is a truth universally acknowledged that cancer prevention and early cancer detection saves lives.

As scientists and physicians at the major cancer centers work together to unravel the link betweengenetic alterations and cancer risk, genetic testing is rapidly becoming an impactful tool for matching patients to individualized cancer screening programs.

Often called the Angelina Jolie effect based on the actor'slaudable effort to enhance understanding of increased cancer risk for patients with alterations in the BRCA1 or BRCA2 genes the general public has become appropriately more aware of the importance that genetics can play in cancer risk.

Put most simply, genetic testing utilizes DNA usually obtained from small amounts of saliva or blood to identify a genetic mutation, or change, in your DNA that may increase your risk of developing certain cancers. This is determined by sequencing the DNA, which reads the specific DNA code for a subset of genes known to be important for affecting cancer development.

Individuals with a strong family history of cancer or those of a certain ancestry, such as Ashkenazi Jewish ancestry, might be more likely to carry these genetic mutations, but lack of a family cancer history does not mean that someone wont be a carrier. In many cases, genetic risk of cancer arises spontaneously through DNA errors that occur in developing embryos. In other words, genetic risk can result from a spot of ill-timed bad luck, on or before your journey began at the single cell stage.

Being aware that you have a genetic mutation that might increase your risk of developing cancer can help you and your doctor work together and create a personalized plan to help increase your chance of prevention or early detection.

For a man carrying specific alterations in the BRCA2 gene, there may be concern for increased risk of prostate or pancreatic cancer development. The team approach is then taken. After meeting with a genetic counselor, a personalized plan for that patient may entail earlier or more frequent prostate cancer screening, and support for helping the patient change behaviors that may further enhance pancreatic cancer risk, like smoking.

At the Sidney Kimmel Cancer Center at Jefferson, the Mens Genetic Risk centralizes these plans, and coordinates with the patients care team to tailor the individual health plan. Further discussions are also had with regard to cascade testing, or testing family members who may also be at risk. As such, genetic testing can impact not just the patient themselves, but family members as well.

Genetic testing might be recommended to someone if they have a strong family history of cancer, which may include several first-degree relatives parents, siblings and children with cancer; many relatives with the same type of cancer; relatives who were diagnosed at a younger-than-normal age; or a relative diagnosed with a rare cancer, such as a male with breast cancer.

Someone who has already been diagnosed with cancer may benefit from genetic testing as well, especially if they were diagnosed at a young age or have a family history of cancer. Cancers with a known hereditary component include breast, ovarian, uterine, prostate, colorectal, melanoma, pancreatic and stomach cancers.

Having a family history of cancer is not limited to a having a family history of thesamecancer. For example, and related to our case above, a man whose mother or sister had breast cancer might be at risk himself for prostate cancer.

It is also important to note that the presence of a gene mutation is also relevant when treating existing cancer. Certain genetic mutations are also associated with a greater risk of having an aggressive cancer and resistance to certain therapies, which can help your doctor manage specific tumor types.

Your results may help your doctor decide on the best treatment regimen, because researchers have found that some treatments are more effective in people with certain gene mutations. In fact, the FDA has recently approved cancer therapies that are only for patients whose tumors have specific gene alterations and it is expected that many more such targeted therapies will be approved and ready for use in treating cancer.

So what if you have been tested and you do not have an identified genetic risk? It is important to note that not having a family history of cancer or genetic risk of cancer does not guarantee that you will never develop cancer. With regard to family history, the National Cancer Institute notes that only 5-10% of cancers are due to inherited gene mutations.

Additionally, having a family history of cancer does not mean that you are certain to be diagnosed with cancer one day yourself. Genetic testing can help inform you of your genetic risk for certain diseases, but it does not inform you of your overall risk. Other factors that contribute to an increased risk for cancer include environmental factors and lifestyle choices, many of which are modifiable.

If you are considering genetic testing or have questions about whether you or your family should undergo testing, talk to your doctor or other health care providers. Talking to a health professional or genetic counselor can help you decide whether you would benefit from testing. They will collect your family and personal health history, explain what kind of information the test can provide you, and help you decide whether the test is right for you.

After undergoing genetic testing, it is important that you talk to your health care provider about what the results mean for you, whether positive or negative. The results can be confusing, and they can help you interpret your results, allay any fears, discuss potential implications for your family, and help you make an informed decision about how to proceed based on the results. Discussion with a specialist is important for future care decisions.

If appropriate, your doctor may discuss cancer risk-reduction strategies with you, like preventive surgery, medications that help reduce risk or lifestyle changes. They also may recommend alternative screening options to help detect the cancer early, such as beginning mammograms before age 40 or having a colonoscopy at 45 rather than 50.

In addition to the clinical genetic testing, a growing number of companies are making tests available to consumers that can provide insight into ones ancestry, as well as certain health information. There are a few things to keep in mind regarding these direct-to-consumer tests if you decide to go ahead with one.

Ancestry DNA tests are typically not clinical grade, meaning that the information is not of the established quality required to change someones health plan. Even if a cancer gene is suspected on these tests, confirmation would be required using a clinical-grade test that has been deemed valid and reliable for detecting cancer gene alterations.

In addition, many at-home tests are very small in scale, and leave out testing of many genes known to be influential in determining cancer risk. For example, an at-home test might screen for mutations in the BRCA1 and BRCA1 genes, but not for the genes associated with Lynch syndrome, an inherited disorder that increases the risk of several cancer types, including colorectal cancer.

There is a growing concern that negative results from an at-home test can provide consumers with a false sense of security. These tests should not be used as a substitute for the genetic counseling and testing you would receive from your health care provider, who will usually re-order a clinical test to confirm the results, and help you understand the results of the test.

Despite the importance of understanding personal genetic risk of cancer, there are justifiable concerns about privacy. This is an important concept for every person to consider. The Health Insurance Portability and Accountability Act protects your genetic data if you were tested through your health care provider. However, there are fewer protections with the direct-to-consumer DNA testing companies, so be sure to understand the companys privacy policy when signing up for services. Some companies may share your results with third parties, such as medical or pharmaceutical researchers.

A common concern for people considering genetic testing is discrimination based on their genetics. The Genetic Information Nondiscrimination Act is a federal law that protects individuals from genetic discrimination. GINA prohibits health insurers from discrimination based on the genetic information of enrollees, meaning they may not use genetic information to make decisions regarding eligibility, coverage, underwriting or premium-setting. However, GINA does not cover disability, life and long-term care insurance.

GINA also prevents employers who have at least 15 employees from using genetic information in employment decisions such as hiring, firing, promotions, pay and job assignments. Additionally, some states have enacted laws that offer additional protections against genetic discrimination. For more information on GINA and genetic discrimination, click here

In sum, cancer genetics is a rapidly evolving field, and the era is upon us wherein individual wellness plans will be as guided by genetic information as they are by vital signs. It was not long ago when the only genetic testing option was examining the BRCA1 and BRCA2 genes for inherited mutations associated with breast and ovarian cancers.

Fast-forwarding to 2020, we not only understand more about BRCA mutations, but we have discovered that there are many hundreds of other genes related to cancer development and progression. If you had BRCA testing many years ago or were told previously that you were ineligible for genetic testing, talk to your doctor.

As we learn more about genetic mutations and we continue to expand the recommendations for testing to include more people, your doctor might recommend that you undergo genetic testing now or consider additional genetic testing. Understanding your genetic code just might be a life saver!

Karen E. Knudsen, Ph.D., enterprise director at the Sidney Kimmel Cancer Center Jefferson Health, oversees cancer care and cancer research at all SKCC sites in the Greater Philadelphia region. She writes occasionally on topics related to cancer.

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Genetic testing is helping prevent cancer and changing treatment plans - PhillyVoice.com

With new cases and clusters of the Covid-19 illness in the news every day, along with canceled events, closed workplaces, and shortages of hand sanitizer, it can feel like were already losing the fight against this outbreak. But in some ways, scientists are better equipped than ever before to follow and understand the new virus.

Were really at a very exciting time right now, says Emma Hodcroft, a molecular epidemiologist at the University of Basel in Switzerland. Unlike traditional epidemiologists, who monitor when and where sick patients show up, molecular epidemiologists can track disease by monitoring the genes in the virus itself.

Hodcroft is part of the team behind Nextstrain, an open, online platform that detects how diseases are evolving in real time. The team has worked on viruses including influenza, Zika, and Ebola. In recent months, theyve pivoted to studying the new coronavirus that causes Covid-19.

These scientists rely on the fact that viruses, like any living thing, pick up random mutations in their genes sometimes as simple as a change in one letter of the genetic code as they proliferate over generations. The new coronavirus carries its genetic code in RNA rather than DNA as humans and most other organisms do. RNA viruses mutate at an especially high rate, which makes them nimble at evolving and adapting. But that also helps scientific detectives track them.

From a swab of a Covid-19 patients nose, scientists can quickly sequence the entire 30,000-letter genome of the virus infecting that patient, according to Trevor Bedford, a scientist at the Fred Hutchinson Cancer Research Center in Seattle and one of Nexstrains developers. We can use these sequences to reconstruct which infection is connected to which infection, Bedford wrote in a blog post. By building a family tree of viruses, scientists can deduce what the disease has been doing behind the scenes.

For example, the first known Covid-19 patient in this country was a traveler who returned to Washington State from Wuhan, China, in mid-January. Tests for the virus werent widely available then. But at the end of February, scientists with the Seattle Flu Study began looking for the coronavirus in samples from people whod been tested for influenza. They soon found it in a high school student who hadnt been to China.

The genes of the students virus were nearly identical to the genes in the virus of the first Washington patient, with a few new mutations. That suggested the students infection was a direct descendant like a viral grandchild of that first patients. The most likely explanation, Bedford writes, is that the coronavirus had been quietly circulating in the Seattle area for the intervening five weeks and infecting hundreds of people.

Understanding how the disease is moving can help public health officials fight it strategically. For example, the genes of viruses in several other countries match samples from Italy, suggesting travelers to Italy are bringing the virus back home. Hodcroft says thats true of most cases in Switzerland so far. It means the disease might be contained in Switzerland by isolating those people and their close contacts. But in Seattle, if the virus has been spreading in secret, it makes sense for the whole population to take preventive steps like avoiding large gatherings.

Recent technological advances have made this kind of rapid detective work possible. High-quality genetic sequencing has gotten faster, cheaper, and more readily available in recent years. Computing power has increased, too.

The other critical development, Hodcroft says, is not a technological advance but a cultural one. Instead of saving their data for future peer-reviewed publications, scientists are now freely sharing information with each other. Researchers worldwide are posting coronavirus genome sequences to GISAID, an open-access platform created for influenza. On a forum called Virological, scientists are sharing and discussing their own analyses of coronavirus genetic data. Researchers at Johns Hopkins University are pooling up-to-the-minute case numbers at a freely available online dashboard.

Hodcroft says this level of data sharing is like nothing thats happened before. We have never had, in any kind of outbreak, so much information at such a relatively early stage. And that puts us humans in a unique position against our latest viral foe, she says. We really have an unprecedented ability to harness all of this and use it in ways that we couldnt have imagined a few years ago.

Elizabeth Preston is a science writer in the Boston area.

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Some good coronavirus news: genetic detectives are on the case - The Boston Globe

In the unprecedented outbreak of a new coronavirus sweeping the world, the germs genetic material may ultimately tell the story not just of where it came from, but of how it spread and how efforts to contain it failed.

By tracking mutations to the virus as it spreads, scientists are creating a family tree in nearly real time, which they say can help pinpoint how the infection is hopping between countries.

When scientists in Brazil confirmed that countrys first case of coronavirus late in February, they were quick to sequence the germs genetic code and compare it with over 150 sequences already posted online, many from China.

The patient, a 61-year-old from So Paulo, had traveled in Italys northern Lombardy region that month, so Italy was likely where he acquired the infection. But the sequence of his virus suggested a more complex story, linking his illness back to a sick passenger from China and an outbreak in Germany.

As a virus spreads, it mutates, developing random changes in single genetic letters in its genome. By tracking those changes, scientists can trace its evolution and learn which cases are most closely related. The latest maps already show dozens of branching events.

The data is being tracked on a website called Nextstrain, an open-source effort to harness the scientific and public health potential of pathogen genome data. Because scientists are posting data so quickly, this is the first outbreak in which a germs evolution and spread have been tracked in so much detail, and almost in real time.

nextstrain.org

The work of the genome sleuths is helping show where containment measures have failed. It also makes clear that countries have faced multiple introductions of the virus, not just one. Eventually, genetic data could pinpoint the original source of the outbreak.

In Brazil, researchers were able to use gene data to show that its first case, and a second one found later, were not very closely related, says Nuno Faria at the University of Oxford. Samples of the virus from the two patients had enough differences to indicate that they must have been acquired in different locations.

When combined with the patient travel information, this indicates that the two confirmed cases in Brazil are the result of separate introductions to the country, Faria wrote in a discussion of his findings.

Faria Lab

Since there is no vaccine, experts say the best chance of stopping the virus is through aggressive public health measures, like finding and isolating people whove been exposed.

And thats where the viruss evolutionary tree is useful, helping to trace the spread of the germ and detect where containment is and isnt working.

The genetic data shows that the virus entered Europe multiple times. It also now suggests that an outbreak in Munich in January, which researchers believed was caught early, might not have been successfully contained.

Since February 1, about a fourth of new infectionsin Mexico, Finland, Scotland, and Italy as well as the first case in Brazilappeared genetically similar to the Munich cluster, says Trevor Bedford, a researcher at the Fred Hutchinson Cancer Research Center and one of the creators of Nextstrain.

Patient 1 of the Munich branch was a 33-year-old German businessman from Bavaria who became sick with a sore throat and chills on January 24. Investigators say before feeling ill he'd met with a Chinese business partner visiting from Shanghai, who herself later tested positive for the virus.

Within four days, more employees of the company, Webasto, tested positive. Although the company closed its headquarters, it wasnt enough. According to the genetic data, the Munich event could be linked to a decent part of the overall European outbreak, which includes more than 3,000 cases in Italy.

An extremely important take home message here is that just because a cluster has been identified and contained doesnt actually mean this case did not seed a transmission chain that went undetected until it grew to be [a] sizable outbreak, Bedford posted to Twitter.

Thats exactly what viral detectives think may have happened in Washington State in the US, where a first case was discovered nearly six weeks ago. In February, though, when they sequenced the virus from a new case, they found it shared a specific mutation with the first one.

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That meant the two were related and the virus had been silently spreading inside the US all along. Since then, Washington has reported 27 cases and nine deaths, including people who died earlier without being properly diagnosed.

In the wake of the Washington outbreak, critics have blamed the US Centers for Disease Control and Prevention for limiting who could get tested, effectively blinding experts to the course of the outbreak.

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Gene sleuths are tracking the coronavirus outbreak as it happens - MIT Technology Review

It was January of 1980 when 21-year-old Helene Pruszynski was kidnapped, raped and murdered in Douglas County, Colorado. Her body was found in a field, but police never identified a suspect. Pruszynskis murder became a cold case.

We consider a case that does not have any viable leads after one to two years a cold case, cold case detective Shannon Jensen said.

However, Jensen says the case was never forgotten. Detectives continued to re-open it for 40 years. Then, with the help of new DNA technology, the suspect was identified in December of last year as James Curtis Clanton. He will be sentenced on April 10, based on the first-degree murder laws in 1980.

Pruszynskis sister the only immediate family still living finally received the closure she had waited decades for.

She had told us that she thought that this may never be solved, and she had somewhat given up on her hope. And she couldnt believe that after all these years we were able to identify and arrest a suspect in her sisters murder, Detective Jensen said.

One key element to solving the case was DNA from people related to Clanton.

Detective Jensen actively searched a public database called GEDmatch, which is used as a way for people to learn more about their family history. She came across Rob Diehl, who turned out to be Clanton's fourth cousin. When Detective Jensen reached out, he says he went through a wide range of emotions.

However, Diehl says it didnt take long for him to realize he wanted to help, especially when he discovered how serious the crime was. He says because Clanton was such a distant cousin, they never knew each other.

You just think its been cold for decades and so long that if theres no evidence now, this isnt going to be solved for the family or to bring somebody to justice, Diehl said.

So Diehl gave Detective Jensen access to his family tree and his DNA. Those both are critical elements in a newly utilized DNA technology called genetic genealogy.

Traditional genealogy is using public records to document a persons family tree and their ancestors. Genetic genealogy is when youre using DNA to help with that process, Chief Genetic Genealogist CeCe Moore said.

CeCe Moore is the Chief Genetic Genealogist at Parabon Nanolabs. Parabon assisted with Ms. Pruszynskis case, and the tech company has helped law enforcement across the nation identify more than 100 criminals the past two years.

"For us, significant amounts of DNA could be less than one percent, which is really a breakthrough because previously with law enforcement cases, you needed to have an exact match, or a very close family member, Moore said.

In Pruszynskis case, law enforcement in 1980 collected plenty of DNA evidence, and stored it properly making it possible for detectives today to upload a DNA profile to find her killer. In fact, Detective Jensen says shes currently in the process of solving two more cold cases.

This technology has given detectives like myself another tool to add to our toolbox. Its given new life to cases that we once thought might have been unsolvable, Detective Jensen said.

Not only is this technology finding those responsible for crimes, but its also ruling out the innocent.

If genetic genealogy is used earlier in the process, it can really help avoid hundreds or even thousands of innocent people who are looked at as persons of interest in these cases, Moore said.

Moore says 30 million people have uploaded their DNA to genetic websites the past decade. However, in order for law enforcement to gain access to it, you would need to upload your DNA to a public database like GEDmatch, and opt in for law enforcement to see your profile.

If you have done a DNA kit, or youre thinking about doing a DNA kit on ancestry or 23andMe or My Heritage, download that raw DNA data file and upload it to GEDMatch because everyone can be a crime solver, Detective Jensen said.

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40-year-old cold case solved with new genetic genealogy technology - The Denver Channel

By University of Copenhagen The Faculty of Health and Medical SciencesMarch 7, 2020

These are giant squid sucker rings. Credit: The Trustees of the Natural History Museum, London

The giant squid is an elusive giant, but its secrets are about to be revealed. A new study led by the University of Copenhagen has sequenced the creatures entire genome, offering an opportunity to throw some light on its life in the depths of the sea.

Sailors yarns about the Kraken, a giant sea-monster lurking in the abyss, may have an element of truth.

Our initial genetic analysis generated more questions than it answered. Professor Tom Gilbert

In 1857, the Danish naturalist Japetus Steenstrup linked the tell tales of ships being dragged to the ocean floor to the existence of the giant squid: A ten-armed invertebrate, that is credibly believed to grow up to 13 meters and weigh over 900 kg.

Now, more than 160 years later, an international team of scientists have sequenced and annotated the genome of a giant squid.

These new results may unlock several pending evolutionary questions regarding this mantled species, says the research leader, Associate Professor Rute da Fonseca from the Center for Macroecology, Evolution and Climate (CMEC) at the Globe Institute of the University of Copenhagen.

Throughout the years only relatively few remains of giant squids or, Architeuthis dux have been collected around the world.

Scale of size between human and giant squid. Credit: University of Copenhagen

Using mitochondrial DNA sequences from such samples, researchers at the University of Copenhagen have previously confirmed that all giant squids belong to a single species.

However, our initial genetic analysis generated more questions than it answered, says Professor Tom Gilbert of the GLOBE Institute, who was part of the previous work on the giant creature.

These new results may unlock several pending evolutionary questions regarding this mantled species. Associate Professor Rute da Fonseca

Producing a high-quality genome assembly for the giant squid proved as challenging as spotting one of these animals in their natural environment.

This was, however, an important effort as the genome is the ultimate toolkit available to an organism.

The challenges in the lab started with the fact that available samples originate from decomposing animals, usually preserved in formalin or ethanol at museums around the world.

This means that most of them cannot be used to obtain the high-quality DNA necessary for a good genome assembly.

This project reminds us that there are a lot of species out there that require individually optimized laboratory and bioinformatics procedures. Associate Professor Rute da Fonseca

Furthermore, elevated levels of ammonia and polysaccharides in the tissues were likely the behind repeated failures in producing suitable libraries for nearly all available sequencing technologies.

This project reminds us that there are a lot of species out there that require individually optimized laboratory and bioinformatics procedures. An effort that is sometimes underestimated when designing single-pipeline approaches in large genome-sequencing consortia, says Rute da Fonseca, who started leading the project when working as an Assistant Professor at the Department of Biology in the University of Copenhagen.

Despite the many challenges, the research group managed to get hold of a freshly frozen tissue sample of a giant squid collected by a fishing vessel near New Zealand. An incredible stroke of luck, according to the research leader.

Left: Giant squid specimen kept at the Darwin Center Tank Room at the Natural History Museum, London. Right: The same individual being measured prior to fixation. Credit: The Trustees of the Natural History Museum, London

Using this sample, the researchers were able to produce the currently best available cephalopod genome.

This genomic draft provides for a unique possibility to address many emerging questions of cephalopod genome evolution, the researchers behind the study explain.

By allowing the comparison of the giant squid with the genomes of better-known types of cephalopods, scientists now hope to discover more about the mysterious giant creatures without necessarily having to catch or observe them in the depths of up to 1200 meters that they inhabit.

For example, the new genomic data might allow scientists to explore the genetic underpinnings of the giant squids size, growth rate, and age.

Read Revealed: The Mysterious, Legendary Giant Squids Genome for more on this research.

Reference: A draft genome sequence of the elusive giant squid, Architeuthis dux by Rute R da Fonseca, Alvarina Couto, Andre M Machado, Brona Brejova, Carolin B Albertin, Filipe Silva, Paul Gardner, Tobias Baril, Alex Hayward, Alexandre Campos, ngela M Ribeiro, Inigo Barrio-Hernandez, Henk-Jan Hoving, Ricardo Tafur-Jimenez, Chong Chu, Barbara Frazo, Bent Petersen, Fernando Pealoza, Francesco Musacchia, Graham C Alexander, Jr, Hugo Osrio, Inger Winkelmann, Oleg Simakov, Simon Rasmussen, M Ziaur Rahman, Davide Pisani, Jakob Vinther, Erich Jarvis, Guojie Zhang, Jan M Strugnell, L Filipe C Castro, Olivier Fedrigo, Mateus Patricio, Qiye Li, Sara Rocha, Agostinho Antunes, Yufeng Wu, Bin Ma, Remo Sanges, Tomas Vinar, Blagoy Blagoev, Thomas Sicheritz-Ponten, Rasmus Nielsen and M Thomas P Gilbert, 16 January 2020, GigaScience.DOI: 10.1093/gigascience/giz152

Aside from the University of Copenhagen (Denmark), the collaborating scientists come from several universities around the world.

The Villum Fonden, Marie Curie Actions, and the Portuguese Science Foundation (FCT) have supported the research project, among others.

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A Sea Monsters Genome Full Genetic Sequence of the Elusive Giant Squid - SciTechDaily

Seattle Genetics, Inc. (Nasdaq:SGEN) announced today the cancellation of the Companys presentation and webcast at the Cowen 40th Annual Healthcare Conference on Tuesday, previously scheduled to take place on March 3, 2020 at 9:20 a.m. Eastern Time. Management will no longer be attending the conference as a precautionary measure related to travel amidst the evolving coronavirus situation.

About Seattle Genetics

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the companys industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer and in clinical development for metastatic colorectal cancer. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200302005307/en/

Contacts

Investors:Peggy Pinkston(425) 527-4160ppinkston@seagen.com

Media:Monique Greer(425) 527-4641mgreer@seagen.com

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Seattle Genetics Announces Cancellation of Presentation and Webcast at the Cowen 40th Annual Healthcare Conference - Yahoo Finance

Recent socio-economic migration within the United Kingdom has influenced the geographic distribution of human DNA linked to traits such as education levels and health, according to a new study published in Nature Human Behaviour.

We were interested in looking at the geographic distribution of human DNA. I have studied the geographic distribution of genetic ancestry differences before, but not yet the geographic distribution of the genetic predisposition to heritable traits and diseases, said lead author Abdel Abdellaoui of the University of Amsterdam.

UK Biobank provided a dataset that was large enough to have a look at this, so we did for more than 30 traits and diseases, including physical and mental health, personality, and educational attainment.

Drawing on data from 488,377 people of European descent surveyed for the UK Biobank, the researchers examined about 1.2 million genetic variants to calculate the polygenic scores an estimate of someones genetic predisposition for a certain characteristic for 33 measures related to economic, health and cultural outcomes. These included but were not limited to physical and mental health, religion, addiction, personality, BMI, reproduction, height and educational attainment.

The researchers found that 21 traits showed significant regional clustering on a genetic level after controlling for ancestry. The findings suggest that regional differences in educational attainment genes are the result of more recent selective migration within the country.

When looking at regional differences between genes for a wide range of traits, genes that are associated with educational attainment show the largest regional differences in Great Britain. These differences are increasing over time, as higher educated individuals leave the poorer regions of the country. These poorer regions show worse living circumstances than the rest of the country, which contributes to worse health outcomes in these regions, Abdellaoui told PsyPost.

The researchers noted that people tend to migrate to improve their skills or employment prospects. In the late nineteenth and early twentieth century, for example, many people left small farms to work industrial jobs in urban centers.

This study has scientific as well as societal implications. There are several widely used study designs that assume that genes are randomly distributed across geography, which we show is not the case. Also, we should take better care of the poorer regions of the country, since the poor living conditions there are causing these regions to have worse health outcomes and are driving talented people away, which is increasing genetic differences between poor and rich, Abdellaoui said.

Our research shows that people have polygenic scores that are more similar to their neighbours polygenic scores than to those of people who live far away. While some of this clustering could come from ancestral differences, we find some of it seems to have a more recent origin. And, when we look at how our subjects have moved during their lifetime, we can see that this clustering is increasing, added co-author David Hugh-Jones in a news release.

There are a few caveats, however. The genetic effects on educational attainment are difficult to quantify, because the genetic predisposition for lower education coincides with worse living conditions that also have a detrimental effect on educational outcomes. Within family studies may offer a solution for this, which is something we are currently working on, Abdellaoui explained.

The study, Genetic correlates of social stratification in Great Britain, was authored by Abdel Abdellaoui, David Hugh-Jones, Loic Yengo, Kathryn E. Kemper, Michel G. Nivard, Laura Veul, Yan Holtz, Brendan P. Zietsch, Timothy M. Frayling, Naomi R. Wray, Jian Yang, Karin J. H. Verweij, and Peter M. Visscher.

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Migration is increasing regional differences in genetic factors associated with the ability to learn - PsyPost

What would the implications be if decoding your genes cost less than a pair of designer jeans? We might soon find out after a Chinese company claimed it can sequence the human genome for $100.

The speed at which the price of genetic sequencing has fallen has been astonishing, from $50,000 a decade ago to roughly $600 today. For a long time, the industry saw the $1,000 genome as the inflection point at which we would enter the genomic agewhere getting a read out of your DNA would be within reach for huge swathes of the population.

That milestone has come and gone, but progress hasnt stopped. And now Chinese firm BGI says it has created a system that can sequence a full genome for just $100. If the claims hold up, thats a roughly six times improvement over state-of-the-art technology.

The key to the breakthrough is a significant increase in the size of the chip that is used to analyze genetic data, so twice as many genomes can be processed at once. Their machine also uses a robotic arm to dunk the chip into baths of the chemicals used to carry out the sequencing process, which allows them to be reused multiple times.

The company says the system, which will be made available to customers late this year, is aimed at large-scale genomics projects and could make it possible to decode the DNA of 100,000 people a year.

The breakthrough could spur further price falls as well, by breaking the stranglehold that industry leader Illumina has had on the market. Dennis Grishin, co-founder of startup Nebula Genomics, told MIT Tech Review that he believed the reason the price of genetic sequencing had remained stuck around $1,000 in recent years was due to Illuminas near monopoly.

A $100 genome could significantly broaden the scope of what we can do with genetic data. The growing field of population genetics promises to uncover the genetic quirks that set different groups of people apart, which can prove vital for developing new medicines and understanding the susceptibility of different groups to certain conditions.

While some ambitious projects, such as the UKs biobank project aimed at collating genetic data on 500,000 people, are already underway, the cost of sequencing has so far limited the scope of these projects. A dramatically cheaper system could see these kinds of initiatives become far more commonplace, greatly expanding our understanding of genetic diversity among humans.

By bringing the cost of full genome sequencing within reach of everyday people, the approach could also dramatically expand the scope of personalized medicine. While services like 23andMe have seen a huge expansion in consumer genetic testing, these services only decode a small fraction of the genome that isnt particularly useful for medical purposes.

DNA sequencing is already used to tailor cancer treatment by determining how peoples genetics are likely to influence their response to certain treatments, but it is still far from standard practice. At $100 the practice could become far more common and also be expanded to predict responses to a host of other treatments, ushering in a new era of personalized medicine.

Theres also hope that it would enable new tests that could provide early warning of susceptibility to a host of genetic diseases, or even sequence the DNA of patients microbiomes to detect imbalances in their gut flora that might be responsible for certain conditions or impact their responses to certain treatments.

Rade Drmanac, chief scientific officer of Complete Genomics, a division of BGI, told MIT Tech Review that at $100 it could soon be common to sequence the DNA of every child at birth. This could provide unprecedented early-warning for a host of diseases, but would also open up a Pandoras box of ethical concerns.

The movie Gattaca already explored the potential for discrimination when genetic testing becomes trivially easy, particularly when paired with increasingly powerful genetic engineering that is bringing the potential for designer babies ever closer.

Perhaps more importantly though, our understanding of how our genetics impact our lives is still very hazy. While we have identified some genes that strongly influence propensity for certain diseases, most human characteristics are governed by complex interactions between multiple genes whose activity can vary throughout our lives in response to environmental pressures.

Our ability to read our DNA is far ahead of our ability to understand it, which could lead to all sorts of problemsfrom creating a new class of worried well flagged as at risk of certain conditions that never come to be, to unnecessarily medicalizing or stigmatizing patients in ways that alter the trajectories of their lives.

With a $100 genome now within reach, we will have to tackle these issues with urgency to make sure the genomic age is one to look forward to rather than one to fear.

Image Credit: Pete Linforth from Pixabay

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Scientists have linked a missing gut microbe to ulcerative colitis, opening the door to a possible new treatment.

A team of scientists from Stanford University School of Medicine, California, has identified a gut microbe that is missing in some people. This finding may be key to why some individuals develop ulcerative colitis.

The research appears in the journal Cell Host & Microbe.

The scientists hope that by replacing the function of this missing microbe, it may be possible to develop new and more effective treatments for ulcerative colitis.

The National Institute of Diabetes and Digestive and Kidney Diseases note that ulcerative colitis is a type of inflammatory bowel disease.

It causes inflammation and sores in a persons large intestine, which can result in abdominal pain, weight loss, diarrhea containing pus or blood, and other issues.

The symptoms of ulcerative colitis can range from mild to severe, and there is currently no cure. Instead, treatments focus on keeping the disease in remission for as long as possible.

Treatment usually begins with medications, but if these do not work, surgery may be necessary.

According to the Crohns and Colitis Foundation of America, 2345% of people with ulcerative colitis will eventually need to have surgery.

Surgery involves the complete removal of a persons colon and rectum. The surgeon will then create either a stoma, which acts as an external pouch to collect intestinal contents, or an ileoanal reservoir, which is a J-shaped pouch at the end of the small intestine that does the same job.

Until now, scientists have not been sure why ulcerative colitis affects some people and not others. The new research from the team at Stanford suggests that a key reason may be the lack of particular gut microbes.

Some people who have surgery to create the J-shaped pouch for their ulcerative colitis will then find that inflammation and the associated symptoms return.

Interestingly, people who have the genetic condition familial adenomatous polyposis (FAP), which also requires the creation of a J-shaped pouch, never experience any inflammatory symptoms.

The researchers wanted to work out why this was the case. To do so, they compared two groups of participants, one with FAP and the other with ulcerative colitis, looking for any significant differences between them.

They found that a key difference was the presence of a type of bile acid in the intestines, which was in far greater quantities in those with FAP than in those with ulcerative colitis.

These bile acids are a natural part of a healthy gut and help break down fats.

In the intestines, bacteria convert these bile acids to secondary bile acids.

The scientists were able to identify a specific bacterial family called Ruminococcaceae that was underrepresented in those with ulcerative colitis.

Ruminococcaceae bacteria are the main type of microbe that converts primary bile acids into secondary bile acids.

As Dr. Aida Habtezion, an associate professor and senior author of the study, notes: All healthy people have Ruminococcaceae in their intestines. But in the [ulcerative colitis] pouch patients, members of this family were significantly depleted.

Helping to confirm their findings, the investigators found that stool samples from the participants with FAP turned primary bile acids into secondary bile acids, whereas samples from those with ulcerative colitis did not.

The team then gave acid supplements to mice who had ulcerative colitis to replace any missing secondary bile acids. This reduced inflammation as well as the normal symptoms of colitis in mice.

This study helps us to better understand the disease, says Dr. Habtezion.

We hope it also leads to our being able to treat it with a naturally produced metabolite thats already present in high amounts in a healthy gut.

Dr. Aida Habtezion

To get to this point, the team is now conducting a clinical trial to discover whether an acid supplement can help people with ulcerative colitis.

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Testing for the novel coronavirus in the Seattle area will get a huge boost in the coming weeks as a project funded by Bill Gates and his foundation begins offering home-testing kits that will allow people who fear they may be infected to swab their noses and send the samples back for analysis.

Results, which should be available in one to two days, will be shared with local health officials who will notify those who test positive. Via online forms, infected people can answer questions about their movements and contacts, making it easier for health officials to locate others who may need to be tested or quarantined, as well as to track the virus spread and identify possible hot spots.

Initially, the lab will be able to conduct about 400 tests a day, eventually expanding to thousands of tests a day, said Scott Dowell, leader of coronavirus response at the Bill & Melinda Gates Foundation. The project is ramping up as quickly as possible, but its not clear exactly when it will launch, he added. Among other things, software needs to be upgraded to handle the expected crush of requests, and a detailed questionnaire finalized for people who request tests.

Although theres a lot to be worked out, this has enormous potential to turn the tide of the epidemic, Dowell said.

While Public Health Seattle & King County has confirmed 71 cases and 15 deaths as of Saturday, modeling by Trevor Bedford, a computational biologist at Fred Hutchinson Cancer Research Center, suggests the actual number of infections in the Seattle area is between 500 and 600. Unchecked, that is projected to increase to 30,000 by the end of March underscoring the importance of slowing the spread as quickly as possible, Dowell said.

The new effort aims to leverage the formidable resources and expertise of the Gates Foundation, known for fighting disease and epidemics around the globe, to assist local health agencies struggling to keep up with a fast-moving outbreak. The Seattle area has emerged as an epicenter of the new disease, with far more cases and deaths than any other U.S. city.

One of the most important things from our perspective, having watched and worked on this in other parts of the world, is the identification of people who are positive for the virus, so they can be safely isolated and cared for, and the identification of their contacts, who can then be quarantined, Dowell said.

But testing has been limited until now, leaving many people frustrated and frightened. Last week, a laboratory at UW Medicine got approval to begin processing specimens collected by physicians and other health care providers. The Gates-funded project will reduce the need for sick people to visit a doctors office or clinic, lowering the chance of exposing others.

The initiative grew out of the Seattle Flu Study, a 2-year-old research project based at the University of Washington to track the spread of infectious diseases like influenza. Funded with $20 million from Bill Gates private office, the project recruited thousands of volunteers and sent them self-test kits. The focus has now shifted entirely to the new coronavirus, using similar methods to aid the public-health response.

When the expanded testing system is up and running, people in the Seattle area who think they might be infected with SARS-CoV-2, the scientific name for the new coronavirus, can fill out a questionnaire online. If their symptoms are consistent, they can request a test kit, which will be delivered to their home within two hours. The swabs will be collected and delivered to the UW lab.

The Gates Foundation recently announced its committing $5 million for coronavirus response in the Seattle area, and much of that will go for the expanded testing and analysis. While the initial focus will be on the Seattle area, the plan is to eventually expand statewide, Dowell said.

Outside of King County, one person has died and more than 30 infections have been confirmed as of Saturday.

A major goal of the project is to collect as much information as possible online, which will ease the burden on health officials who are stretched thin and hard-pressed to investigate every new case. Local resources have been focused on Life Care Center, the Kirkland nursing home that accounts for the majority of deaths.

They simply dont have enough epidemiologists to do the shoe-leather epidemiology, the house-to-house case identification, Dowell said.

The Seattle Flu Study already has contributed greatly to the understanding of COVID-19, the respiratory disease caused by the new coronavirus. As the outbreak started in China, the scientific team, co-led by Dr. Helen Chu, an infectious-disease specialist at UW Medicine, quickly developed a genetic test for the virus, similar to one they used for flu.

A physician who knew about the work sent in a sample from a teenage patient suspected of having the disease, and the lab was able to identify what was only the second case in the state at that time.

The flu-project scientists also did the first genetic analyses of new coronavirus cases in Washington, and will continue that work. Bedford, the computational biologist, used those first genomes to analyze changes in the virus over time and concluded that it had probably started circulating in the state earlierthan anyone realized.

The Seattle Flu Study has also already been collecting nasal swabs from volunteers for a research study on the new coronavirus. People can still sign up for that study, but they cannot get their individual results yet.

The Seattle Flu Study is led by the Brotman Baty Institute in collaboration with UW Medicine, Fred Hutch and Seattle Childrens hospital.

The Gates Foundation has also committed $100 million to the global coronavirus response, with an emphasis on vaccine and drug development and improved testing, treatment and control in vulnerable parts of Africa and South Asia.

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U.S. government officials say a million promised tests for diagnosing coronavirus infections will soon be in the mail. But that still leaves many state and local laboratories without the ability to test for the virus, crucial for curbing its spread around the country.

Some states have developed their owntests. Clinical testing companies are now joining the ranks. LabCorpannounced March 5 that physicians or other authorized health careproviders could already order its test. QuestDiagnostics announced the same day that the company will also offercommercial tests as soon as March 9, pending U.S. Food and Drug Administrationreviews. Participation of those two commercial laboratories could greatlyexpand testing capacity in the United States.

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But for now, we still find ourselves asa country with pretty limited capacity to test, says Michael Mina, anepidemiologist at the Harvard T.H. Chan School of Public Health in Boston.

Heres what you need to know aboutcoronavirus testing in the country.

As of March 6, at least 45 states arenow doing testing for SARS-CoV-2, the virus that causes the disease. Wyoming,Oklahoma, Ohio, West Virginia and Maine as well as Guam, Puerto Rico and theVirgin Islands are listed as in progress of having labs certified to dotesting, according to the U.S. Centers for Disease Control and Prevention. Evenstates that have tests may have only a single kit, containing enough materialto test just 700 people, Mina says.

As of March 5, 1,583 people had beentested at CDC. That figure doesnt include tests now going on in many state orcommercial laboratories, which began this week. Contrast that with the UnitedKingdom, where 20,388 people have been tested as of March 6. Only 163 cases ofCOVID-19 have been detected there. Switzerland, which had 181 cases and onedeath as of March 6, has tested more than 3,500 people.

In the United States, more than 250people in at least 23 states had confirmed cases of the coronavirus diseaseknown as COVID-19, and 14 had died, as of March 6. More cases can be expectedas testing ramps up, experts say.

As more cases are found, healthofficials will need to test contacts of people who carry the virus, and otherill people in affected communities may demand tests, all escalating the needfor more tests.

Vice President Mike Pence told reporters March 5, We dont have enough tests today to meet what we anticipate will be the demand going forward, according to CNN. But having companies tests in the mix could help testing ramp up relatively quickly.

To get a more complete picture of howwidespread the virus is in the United States, were going to needmillions and millions and millions of tests, said Anthony Fauci, directorof the National Institute of Allergy and Infectious Diseases in Bethesda, Md.,during a CNN town hall on March 5.

Health professionals will swab apersons nose or throat, collect phlegm coughed up from the lungs, or squirtliquid into the nose, throat or lungs and collect the liquid again for testing.Neither Quest nor LabCorp will collect such specimens, but doctors or otherhealth providers may send samples to the labs for testing.

Then, those samples are analyzed in a laboratory, where technicians must extract and purify the viruss genetic material from the mucus, cell debris and other stuff in the samples.That sample preparation process is usually the biggest bottleneck [in testing], says Brent C. Satterfield, founder and chief scientific officer of Co-Diagnostics, a company based in Salt Lake City and Gujarat, India, that has developed its own coronavirus test. That test can be used clinically in Europe, but has not yet been approved for use in the United States, although other labs can use components of the companys test to build their own diagnostic tests.

All of the coronavirus tests being usedby public health agencies and private labs around the world start with atechnique called polymerase chain reaction, or PCR, which can detect tinyamounts of a viruss genetic material. SARS-CoV-2, the virus that causesCOVID-19, has RNA as its genetic material. That RNA must first be copied intoDNA. Thats a lengthy part of the process, too, says Satterfield, adding 15to 30 minutes to the test.

After that, the PCR can begin. Theprocess makes millions to billions of copies of selected segments of DNA. Inthe case of the coronavirus, the CDCs original test scanned for three of theviruss genes, but now tests for two. The World Health Organizations test,developed by infectious disease researcher Christian Drosten at the Charit UniversittsmedizinBerlin and colleagues, tests for three genes but is a bit different than theCDC tests. The PCR step typically takes 45 minutes to an hour, Satterfieldsays.

Some assays give instant yes or noreadings, but others may also take time to analyze. All together, it may takeabout three hours to complete a test, Satterfield estimates.

PCR tests are not simple enough to do ina doctors office.

In the United States, a doctor is nowallowed to decide if a test is warranted and collect the sample, but then mustship the sample off for other trained professionals to prepare and test.

Testing was initially limited to onlythose people with symptoms and a travel history to an affected area or contactwith a known case. On March 4, the CDCrelaxed some restrictions on who can get tested. People still haveto be sufficiently sick and have failed a flu test in order to qualify forcoronavirus testing, Mina says.

In some states, the positive test results arecalled presumptive positives until the CDC can confirm them. In those cases,the final official result may take days. LabCorp estimates that it will takethree to four days to return results to physicians.

Many doctors offices can do a rapid influenzatest. But those flu tests dont use PCR, Satterfield says. Instead, they detectproteins on the surface of the influenza virus. While the test is quick andcheap, its also not nearly as sensitive as PCR in picking up infections,especially early on before the virus has a chance to replicate, he says. By theCDCs estimates, rapid influenza tests may miss 50 percent to 70 percent ofcases that PCR can detect. The low sensitivity can lead to many false negativetest results.

Flu tests also arent as specific for aparticular virus strain as PCR is. About 5 percent to 10 percent of the time,flu tests may mistake a different virus for the flu, creating a false positiveresult. Specificity is a big deal when youre testing large numbers of peoplewho arent expected to be positive, Satterfield says. If youre going to testin one of the states that doesnt have a coronavirus outbreak right now, with aspecificity of 90 percent, 10 out of every 100 people are going to show uppositive even though the coronavirus isnt there yet.

Accurate diagnosis is a very highimperative for this [coronavirus], Satterfield says.

An additional benefit of a PCR test isthat it may be able to detect viruses earlier in an infection than a flu-style testcan, he says, perhaps not in the first day, but a couple of days into aninfection when the virus is replicating strongly, but the bodys immune systemhasnt yet begun to fight and produce symptoms. In every infectious disease Iknow of, that is the most contagious period for a person; the point in timewhen the virus has multiplied to its maximum capacity and the body has not yetstarted to rein in on it, Satterfield says. Being able to identify people inthat period and isolate them from others could help curb the spread of thedisease.

Delays started with a manufacturing flawin the CDCs original PCR test, which caused components that detect one of the threetargeted viral genes to not work properly, the health agency says.

Those woes sound like user error to Co-DiagnosticsSatterfield. A lot of what they are seeing is probably due to inconsistent usein the field, he says. Tests that work phenomenally well in the lab, whenthey are sent to the field, sometimes just dont work the same, he says.

Co-Diagnostics test also uses PCR buttests for only one gene versus three. Sometimes the more complexity you havein a test, the more things you have that can go wrong, Satterfield says.

Some delays in getting testing off theground came from emergency measures enacted by the FDA, Satterfield says. Normally,big medical testing labs, such as state health labs and companies like LabCorpand Quest Diagnostics, are allowed to develop and validate their own tests. Butwhen the coronavirus was declareda public health emergency on January 31, labs needed emergencyuse authorization before using their tests to diagnose cases. Eventhe CDC had to get permission to use its test. But on February 29, FDAannounced that labs could devise their own tests and use them clinically whilewaiting for the agency to review their applications. FDA does not intend toobject to the use of these tests for clinical testing while the laboratoriesare pursuing an EUA, the agency saidin a statement.

It looks like there were some prettylarge blunders that led to some serious delays, says Mina, the epidemiologistat Harvard. Instead of reducing the amount of testing at the start of anepidemic we should have been expanding it as quickly as possible and callingfor all hands on deck, he says.

Those delays and the initial limitationson who could be tested may have allowed some cases to slip through the cracksand start community outbreaks in Washington and California.

It will vary from place to place. If you have symptoms of COVID-19 fever, dry cough and often fatigue contact your doctor or local or state health department for more information. Do not go to the emergency room for testing, officials say.

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