W6-Why Haven’t We Found a Cure for Ebola in Boston?

In West Africa alone, the World Health Organization reports that the current Ebola outbreak— the most severe on record—has killed more than 6,000 out of the 17,000 people who have contracted it. Here in Boston, you could literally bump into someone working on a cure, but it’s a process often hampered by lack of funding and facilities.

Across the river, the Wyss Institute at Harvard University has developed a device that may be able to remove Ebola (and other pathogens) from the bloodstream. Researchers at the Sabeti Lab at The Broad Institute of MIT and Harvard have attempted to unlock the way the virus works by sequencing and analyzing more than 99 Ebola virus genomes. They also catalogued 395 mutations.

Before this year’s outbreak, many Americans had never heard of Ebola. But the virus isn’t new. It first emerged in 1976, and over the decades, the Ebolavirus genus has mutated into five strains, four of which make humans sick. Though unprecedented in its size and spread in populated areas, the world has seen the 2014 strain, called “Zaire,” before. Researchers say the Zaire strain is more than 90 percent identical to the virus that caused the first known outbreak. It’s slightly more similar to an outbreak that happened in 1995, and it’s even more similar to a 2007 outbreak.Down Huntington Avenue, Northeastern University bio and chemical engineers are using nanotechnology to kill Ebola and stop it from mutating.

It’s been almost 40 years since we first saw Zaire ebolavirus. So why aren’t we further along on a cure? Research on viruses like Ebola in Boston often gets to a certain point, then must take a pause until the timing, funding, and available facilities align to test researchers’ theories. This can add years of delay to an already complicated process.

Facilities

At this point, the only places that can work with the Zaire ebolavirus and its mutations are biosafety level 4 (BSL-4) laboratories with the safety protocols and isolation components required to work with dangerous and rare viruses. But there are approximately 10 labs like this in the United States, at different stages of clearance and construction, which can create a bottleneck for research.

Boston actually has one of those labs. The National Emerging Infectious Disease Laboratory (NEIDL) was built by Boston University on its South End medical school campus in 2008. BSL-2 and BSL-3 research is performed there, but between the political, legal, and regulatory hurdles (not to mention the outcry from the surrounding community), the BSL-4 lab has yet to open (and the BSL-3 only opened in January of this year).

As the Ebola outbreak raged last fall, NEIDL was in the midst of inspections by the Boston Public Health Commission and the Centers for Disease Control and Prevention, to hopefully, finally, clear the last hurdles so researchers can get to work.

At Boston University School of Medicine’s microbiology lab, virologist John Connor is one of the researchers waiting for the lab to open. Connor’s team has been collaborating with other BSL-4 labs in the country for the past five years on building a portable diagnostic test tool ideal for remote areas with limited electricity. Connor has National Institutes of Health (NIH) funding for his diagnostic work, so it’s progressing and continuing to be tested. But he says he wishes it could have all taken place closer to home.

“Having a facility that can operate safely and effectively in close proximity to lots of intelligent people should speed up a lot of the development process, because it’s a lot easier to have conversations and get things started when it’s 15 minutes on the T and on the No. 10 bus, versus going down to the CDC or the NIH,” Connor said. “There’s a ceiling on the amount of work that can be done because of the amount of facilities.”

For the past four years, Connor has also been developing treatments for rare viruses including Ebola, but they might not see light by the time this outbreak is contained.

“What we’re really trying to do is find new ways that people haven’t tried before to find molecules that look and find the Achilles heel in viruses like Ebola,” said Connor. Before the Zaire ebolavirus reemerged in 2014, Connor’s team in March published research identifying a small molecule that inhibits Ebola (and other viruses) from replication. These molecules could lead to the development of an antiviral treatment that stops the virus from growing in a sick person.

“The life cycle of the virus is that it comes into a cell, and then it’s supposed to make copies of itself, and then brings in genetic material and makes copies of that genetic material to make a new virus cell and RNA delivery,” Connor said. “The molecule we developed appears to block that engine.”

Down the hall from Connor, Elke Mühlberger is researching enzymes to train the molecules Connor discovered to block the Ebola virus’s replication. But her work at the NEIDL lab and collaboration with Connor’s team can only go so far without BSL-4 facilities.

The team has managed to prove their Ebola antiviral works in a culture at other BSL-4 labs, but now Connor is waiting to test whether the molecule inhibits the virus in a small animal. Then, they can escalate to a non-human primate, and finally, submit their research for approval with the FDA to test a small group of patients. That’s a five-year timeline—without any delays.

Funding

Unfortunately, Connor’s team lacks the funding from the NIH to take the antiviral research forward, even if the NEIDL resources were fully available. It’s a common story these days.

Connor’s antiviral project has been on hold for over a year and a half. Although the Food and Drug Administration has sped along the development of a few Ebola vaccines, his project is too far behind in the process to be escalated. Even if it wasn’t, Connor says vaccines that protect people and contain Ebola’s spread tend to get preference over therapeutic treatments.

“The likelihood of developing post therapeutic treatments is much less [than a vaccine],” Connor said. “If you use a post exposure therapeutic, you can protect the people that were affected. If you use a vaccine, you can not only protect the people who have been infected but also the people who have not yet been infected and ideally limit the prospects of it happening again.”

The NIH has been working on a vaccine for the Zaire ebolavirus since 2001. After 13 years of work, it has reached animal trials. But when the outbreak began to spread rapidly this summer, the vaccine had not reached a phase 1 clinical trial to be tested on humans. Dr. Francis Collins, the head of the NIH, blamed the cut in research funding for slowing down all research, but especially the development of vaccines for infectious diseases.

“I have to tell you, if we had not gone through this 10-year decline in the support of biomedical research, we would be a year or two ahead of where we are now,” Collins said at House Energy and Commerce Subcommittee on Health in September. “And think about the difference that would make, had we in 2014 been in the position to distribute rapidly tens of thousands of doses, in collaboration with our colleagues at GSK, of this vaccine, how much different would this be and how many lives would have been saved.”

Connor said progress is very difficult when it’s so hard to find research dollars. “We’ve worked for a number of years developing antiviral candidates to target these nasty viruses, and the work we’re doing there is important,” said Connor. “And the NIH agrees with us, but the money just isn’t there.”

And neither is a cure.

Correction: A previous version of this article identified The Broad Institute as part of Harvard. The Broad Institute is an independent organization affiliated with Harvard and MIT. The picture of the researcher is at the Broad Institute, not the Sabeti lab as previously captioned.

From: http://www.boston.com/health/2014/12/08/why-haven-found-cure-for-ebola-boston/MSlcjIbkLmuNCycszqhJGJ/story.html

Vocab. 

literally -從字面上

sequencing - 排序

genomes - 基因組

catalogued - 編目

mutations - 突變

strain - 應變

unprecedented - 史無前例

align - 調整

protocol - 協議

hurdles - 障礙

when-12.08.14 | 6:23 PM

where- Boston, US

why- not enough facilities

what- reserchers have worked on finding cure for Ebolavirus, but delayed due to lack of facility.

how- One team actually have found a cure for Ebola, but now the process of developing the cure is stopped beacuse of the lack of facilities.