Mysterious new SARS-like coronavirus came from bats

Genetic analysis has confirmed that the cases of SARS-like viral disease that made headlines this fall—first killing a Saudi Arabian man in June and then sickening a Qatari man in September—were the result of a single coronavirus strain that made the leap from bats to humans.

“These two individuals were exposed to the same virus that was harbored in bats in the Saudi Arabian peninsula,” says Ralph Baric, a microbiologist at University of North Carolina–Chapel Hill who was not involved in the work.

A team led by Ron Fouchier, a virologist at the Erasmus Medical Center in the Netherlands, sequenced all 30,000 nucleotides of the new virus’ genome. Reporting today in mBio, the researchers found that the virus is most closely related to two coronaviruses found in bats, one from vesper bats and another from pipstrelle bats. The finding mirrors earlier discoveries that bats often serve as reservoirs and likely sources of coronaviruses for people. It also validates preliminary molecular details reported earlier this month in the New England Journal of Medicine.

In unpublished material disclosed in a press release to accompany the mBio paper, Fouchier and his colleagues additionally found that the isolates from the first two men infected with the virus differed by only 99 nucleotides, indicating that the two viruses are the same species. Genetic data from a third viral isolate taken from another Saudi Arabian man who earlier this month came down with what scientists think is the same coronavirus  are not yet available.

It could be worse

Although it’s still too early to make definitive statements, Baric says that the novel coronavirus—dubbed HCoV EMC/2012—does not appear to be transmissible between people, which distinguishes it from the virus responsible for severe acute respiratory syndrome (SARS) that spread between thousands of people a decade ago, killing around 10% of those infected. “If it were as transmissible as SARS, it would be much more dangerous,” he says.

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Select agent status could slow development of anti-SARS therapies

Saudi Arabian doctors scrambled last month to treat a third person who had fallen ill from a new strain of coronavirus that emerged earlier this year in the Middle East. The man survived with the help of supportive care from his physicians, but one of the other two patients who fell victim to the mysterious virus—a pathogen that resembles the coronavirus responsible for severe acute respiratory syndrome (SARS)—was not so fortunate.

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These recent cases drive home an all too stark reality: a decade on from the SARS outbreak that killed close to 800 people worldwide, scientists still have no proven effective vaccines or drugs that can stop the spread of SARS or SARS-like viruses, let alone mitigate their symptoms. Now, to make matters worse in the face of an emerging threat, a new reclassification of the bioterrorism risk posed by SARS may hamper efforts at novel medical strategies.

“Many labs are going to destroy their [SARS] virus instead of continue to work on it because the burden of regulation is quite high,” says Rachel Roper, a microbiologist at East Carolina University Brody School of Medicine in Greenville, North Carolina.

Roper has worked with SARS since the global pandemic ten years ago. She led the team that sequenced the virus’s genome, and, more recently, she and her colleagues created two experimental vaccines: a whole, killed SARS virus shot and an adenovirus-based vector carrying key SARS structural proteins. Both products elicited some degree of immune response and partially prevented viral replication in mice and ferrets. However, the protection was incomplete.

She had been working to improve both strategies and was already struggling with how she would advance a lead candidate into the clinic in the absence of any natural human SARS challenge against which to test it. Then, on 5 October, the US government announced plans to add SARS to its list of select agents. This reclassification, which goes into effect on 4 December, requires labs to now obtain additional licenses and adhere to stricter levels of biosafety and biosecurity to conduct any experiments with the virus. Although Roper recognizes that the move was made in the interest of protecting public health, for her this was the last straw. She says she no longer plans to work on SARS, opting to destroy her live virus instead of seeking certification for her lab.

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Brigham and Women’s obtains ‘clarity’

It’s got to be quite a competition when the winner can boast solving a family’s medical mystery, but those are the bragging rights the clinical genetics division at Brigham and Women’s Hospital captured when it won Boston Children’s Hospital’s first CLARITY contest (short for Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information).

In January, the Children’s Hospital put out the call for submissions, asking participants to help determine the unknown genetic root cause of illness in three children. The teams could sequence the genomes of the children and their parents, and were tasked with interpreting the information. The ultimate aim of the competition was to shed light on how data from whole genome sequences can be made most useful in a clinical setting (see ‘Genomics contest underscores challenges of personalized medicine‘).

There was a “real question of whether these technologies are ready for prime-time clinical applications,” says Isaac Kohane, an endocrinologist at Children’s Hospital. “What these teams have demonstrated is that going from end to end—from a genome sequence to a clinical readable report—can be turned into a routine process.”

Of the 23 teams submitting entries, three were able to identify both mutations in the titin and GJB2 genes that, respectively, explained the muscle weakness and hearing impairment afflicting one of the youngsters, a sixth grader. The Brigham and Women’s team provided the most insight on these points, winning the $15,000 top prize. Meanwhile, a team from University of Iowa in Iowa City was awarded $5,000 as a finalist for their approach to communicating unexpected genetic results, which they based on patient preferences. A German team (with representatives from the gene sequencing companies Genomatix and CeGaT, as well as the Institute of Pathology at the University of Bonn) also received $5,000 as a finalist for flagging all likely genetic mutations in the three cases.

The Children’s Hospital team behind the contest plans to publish a paper comparing and contrasting the various approaches taken by the entrants in the contest, according to Kohane. The hope is that this information from the contest will help inform procedures in the gene sequencing field. They’re also planning a second challenge, focused on cancer genomes, to carry on their efforts of helping understand how to process the large data sets and communicate the information to patients.

Image courtesy of Shutterstock

Insurance challenges may lie ahead for New York labs hit by hurricane

At the end of turbulent week, the extent of the damage caused by Hurricane Sandy on biomedical research in the Northeast remains unclear, particularly at New York University’s Smilow Research Center, which flooded during the storm. The most devastating loss at the labs there may be the death of thousands of genetically modified mice and rats, and these animals represent the culmination of many years of research and thousands of dollars in funding. Although the cages the rodents lived in may be insured, it’s likely impossible to recoup the money and time spent to engineer the animals themselves. Biomedical scientists may not think about the insurance needs for their labs on a daily basis, and as some Nature Medicine spoke with, it’s not always easy to get experiments up and running even when insurance is in place.

The accident in May at the McLean Hospital in Belmont, Massachusetts, may provide a glimpse of the challenges ahead for local labs. Around 50 brains from individuals with autism were ruined when the freezer they were stored in malfunctioned, warming up without setting off any of the in-place indicators. The hospital will likely receive reimbursement for the failing freezer, and compensation for new freezers the hospital has had to rent in the interim, but there will likely be no reimbursement for the brains themselves, says Peter Paskevich, senior vice president of research administration at McLean. Money can’t buy back what they lost, Paskevich adds: “We could get half a million dollars for the autism collection but it doesn’t matter — it’s still going to take 20 years to replace it.” McLean is currently negotiating with a private insurance company that will cover the accident, though the dollar amount has not been decided.

Other universities are primarily self-insured, meaning the university compensate for such disasters with their own funds that they set aside earlier, says George Stancel, executive vice president for academic and research affairs at the University of Texas Health Science Center in Houston. UTHealth experienced flooding and damage after Hurricane Allison in 2008, and relied on primarily on its self-insurance, though its buildings were insured through a separate insurer. The Federal Emergency Management Agency (FEMA) also helped with repairs and rebuilding labs, Stancel says.

Similarly, when the University of Iowa, in Iowa City, experienced severe flooding in 2008, it also relied on help from FEMA as it rebuilt, as it was primarily self-insured, says Mark Arnold, a chemist at the university.

It’s currently unclear what type of insurance policy NYU will rely on as it begins to rebuild; it is busy coping with the damage and has yet to respond to requests for comment from Nature Medicine. But in the meantime researchers at other intuitions who have endured damage from other natural disasters offer the following advice on how to start rebuilding to scientists affected by the storm this week:

  • Take inventory. In sorting through all equipment, take detailed notes of what has been damaged and what may have been damaged. FEMA and most insurance companies require detailed inventory lists for reimbursement, Stancel says, and Arnold warns that even if something seems to be working right now, it may still have suffered damage, so noting its exposure now is critical for reimbursement.
  • Keep track of time. As researchers, graduate students and laboratory assistants are reentering labs and attempting to move precious items to safer locations, keeping track of time may mean that the insurance company could reimburse these hours down the road.
  • Call the program officers who are responsible for labs’ funding to see if there is any option for extending research deadlines or securing supplemental research funding. The NIH extended deadlines for researchers at UTHealth following Hurricane Allison, Stancel says.
  • Help graduate students get on a fast track. Losing research is most devastating for graduate and PhD students who are attempting to complete research in a set period of time. Stancel, who was dean of the graduate school when Hurricane Allison hit, says he immediately asked graduate students to start rethinking their projects. Having them work at and with other laboratories helped alleviate the time crunch, he says.
  • Consider how buildings may be rebuilt and redesigned so this doesn’t happen again. While the desire to get labs rebuilt will be immediate, taking some time to decide what the best path forward for prevention of a reoccurrence of the situation is worthwhile. For example, Stancel moved all of the animal laboratories from the basement to the fifth and sixth floors to prevent animals from drowning in future floods.
  • While most insurance policies don’t have a way to reimburse researchers for their lab animals, which hold so much work, collaborating with other researchers who have done similar work may help to quickly rebuild at least parts of the populations that were lost. Yariv Houvras, who studies zebra fish at Cornell Weill Medical School in New York City says that because he’s distributed lines of his fish to other researchers, he could get similar lines back in the case of a disaster. Researchers at the University of Pennsylvania in Philadelphia, and Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, have already made offers, according to The New York Times.
  • Raise money for research. While funding agency want to help researchers, Arnold says the University of Iowa received limited extra funding after their flood disaster, because research funding is so tight. In the case of Hurricane Sandy, it may be possible to set up a relief fund, as New York and the surrounding area are receiving “national and international attention.”

Got extra tips? Leave them in the comments section, or tweet at us — @NatureMedicine.

Image: NOAA

Lupus antibodies may provide new option for cancer therapies

Radiation and chemotherapy are sometimes not strong enough to conquer aggressive tumors, but a new method promises to help cancer treatment become more effective. The approach uses antibodies produced by the body when a person has lupus, an autoimmune disorder that can affect the skin, joints, and other organs. These lupus antibodies can weaken cancerous cells by penetrating the cells’ nuclei and disrupting their DNA, priming the cells for destruction by radiation or chemotherapy, according to a preliminary study published in Science Translational Medicine on 24 October.

“It’s remarkable that an antibody could have this ability to penetrate a living cell,” says Jim Ford, an oncologist at the Stanford University School of Medicine in California, who authored a commentary piece on the paper. “It’s a totally new therapeutic approach.”

In the study, researchers implanted mice with breast cancer and brain cancer, and then gave the animals a one-time dose of lupus antibody. The scientists had isolated the antibody from cells from another group of mice that had been manipulated to have a rodent version of lupus. They followed the antibody injection with radiation in one experiment, and with chemotherapy in another test. In both experiments, the mice treated with the antibody showed significantly stronger response to the secondary treatment compared to the group receiving only radiation or chemotherapy.

For example, in the radiation experiment, the scientists considered the rate at which the tumors tripled in size. They found tumors treated with the antibody grew more slowly, taking 5.7 days longer (13.7 days total) to triple than tumors not treated with the antibody, which tripled after just 8 days. The treatment was also successful in human cells in a dish, according to study author Peter Glazer, a radiologist at the Yale University School of Medicine in New Haven, Connecticut .

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Mouse stem cells manipulated to create egg-producing ovary

From recent news about uterus transplants to controversy over the possibility of so-called ‘three-parent children’, the lengths to which modern medicine will go to achieve conception are increasingly expanding. Creating an ovary that can itself produce viable eggs might soon be added to that list.

In a study published online today in Science, Japanese researchers report that embryonic stem cells from mice can be manipulated to form an ovary that produces viable eggs, the second known method of creating a viable gamete from stem cells.

The scientists, led by Katsuhiko Hayashi at Kyoto University in Kyoto, Japan, used both stem cells and fibroblasts taken from mouse embryos. They then manipulated the function of specific genes to create cells that were very similar to primordial germ cells, which become eggs. The manipulated cells were divided into two groups, with some being cultured in vitro with gonadal cells, a germ cell native to the ovary, and some not, ultimately creating two different types of “reconstituted ovaries.”

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