- About the Library
- Harvard Links
- Digital Resources
- Digital Exhibits
'Our premise is that mechanics play a role in almost all biological processes, and with these DNA-based tension probes we're going to uncover, measure and map those forces,' says biomolecular... Adherent cells, the kind that form the architecture of all multi-cellular organisms, are mechanically engineered with precise forces that allow them to move around and stick to things. Proteins called integrin receptors act like little hands and feet to pull these cells across a surface or to anchor them in place. When groups of these cells are put into a petri dish with a variety of substrates they can sense the differences in the surfaces and they will "crawl" toward the stiffest one they can find.
Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). Harvard Stem Cell Institute scientists at Massachusetts General Hospital have devised a new way to use stem cells in the fight against brain cancer. A team led by neuroscientist Khalid Shah, MS, PhD, who recently demonstrated the value of stem cells loaded with cancer-killing herpes viruses, now has a way to genetically engineer stem cells so that they can produce and secrete tumor-killing toxins.
This image shows, from the left: Katherine Jones, Salk professor, and first authors Yupeng Chen and Lirong Zhang. Like a slumbering dragon, HIV can lay dormant in a person's cells for years, evading medical treatments only to wake up and strike at a later time, quickly replicating itself and destroying the immune system.
Nature Newsblog - Fri, 2014-10-24 15:47
Posted on behalf of Declan Butler.
The World Health Organization (WHO) announced plans on 24 October to produce millions of doses of two experimental Ebola vaccines by the end of 2015.
US National Institute of Allergy and Infectious Disease
Hundreds of thousands of doses should be available to help affected countries before the end of June, the WHO said at the conclusion of a meeting in Geneva. Vaccine makers, high-level government representatives, and regulatory and other bodies gathered to discuss the design and timing of planned clinical trials, as well as issues of supply and funding for mass vaccination programmes.
Phase I trials of two vaccine candidates have started, and as many as five additional vaccines could begin testing by 2015, says Marie-Paul Kieny, WHO assistant-director general for health systems and innovation.
As of 19 October, Ebola had infected almost 10,000 people in Sierra Leone, Liberia and Guinea and killed around 5,000 of them, the WHO estimates. The true figures are likely higher, as many cases go unreported. With no end to the epidemic yet in sight, a working vaccine could be a game-changer.First clinical trials underway
The two vaccines whose production will be increased are already in early stage testing in healthy volunteers. One is a chimpanzee adenovirus vaccine containing a surface Ebola protein (ChAd3), developed by the US National Institute of Allergy and Infectious Diseases and drug giant GlaxoSmithKline. It is being tested in the United States, the United Kingdom and Mali.
The other is a recombinant vesicular stomatitis virus (rVSV) vaccine, developed by the Public Health Agency of Canada and licensed to NewLink Genetics in Ames, Iowa. It is being tested in the United States, with plans to start trials soon in Europe and Africa.
These phase 1 trials will assess the vaccines’ safety and whether they elicit levels of immune response that have been shown to confer protection in non-human primates. The trials will also assess the dose needed to generate sufficient immune response, which in turn helps determine how quickly manufacturers can produce doses.
A third candidate is a two-vaccine regimen: one developed by US pharmaceutical company Johnson and Johnson and the US National Institute of Allergy and Infectious Diseases, and another by Bavarian Nordic, a biotechnology company based in Denmark. It will begin phase 1 testing in the United States and Europe in January. Johnson and Johnson announced on 22 October that it would spend up to US$200 million to fast track the vaccine’s development; it plans to produce more than a million doses in 2015, with 250,000 available by May.Advanced testing
The first phase II and III trials, to test efficacy as well as safety, are set to start in Liberia in December and in Sierra Leone in January. The current plan is to test both the GSK and NewLink vaccines simultaneously, but that could change depending on the results of the ongoing phase I trials. Data from the phase II and III tests is expected by April, Kieny says.
The ‘three-arm’ Liberia trial would test and compare the safety and effectiveness of the two vaccines against each other and a placebo. Each vaccine would be tested on 10,000 subjects, with an equal number of subjects given placebo. This allows researchers to obtain quick, reliable data on how well the vaccines work.
A ‘stepped-wedge’ randomized trial in Sierra Leone would give subjects vaccine sequentially, with no group given a placebo. This is useful for testing products that are expected to benefit patients, and products that are in short supply.
No trial design has yet been fixed for Guinea, where a lack of infrastructure has precluded early testing. If the Liberia and Sierra Leone trials show that the vaccines works and is safe, subsequent trials in Guinea would be used to answer follow-up questions.Ethical and practical considerations
The Sierra Leone trial will enrol at least 8,000 healthcare workers, and other frontline responders, such as ambulance drivers and burial workers. The Liberia trial might included healthcare workers, but these would not be the primary study population, Kieny says.
Any decision to give a placebo to healthcare and other frontline workers will be controversial; many consider it to be unethical, given these individuals’ work caring for Ebola patients, and the risks that they face in doing so.
Mass vaccinations are usually only carried out after years of trials to accumulate full safety and efficacy data. The proposed timeline for Ebola vaccine development is therefore unprecedented.
If existing public-health interventions used to control Ebola outbreaks begin to slow the epidemic, the need for mass vaccination will lessen, Kieny says. But if the epidemic continues to expand, the WHO could consider expanding vaccination programmes.
In the meantime, the WHO and its partners are considering how best to engage with communities to prepare for vaccination programmes. Another issue is simply determining how to keep vaccine cool enough — -80 degrees Celsius — to maintain its efficacy. This will require specialised fridges and the establishment of cold supply chains to affected areas.
Also to be determined : who will pay for mass vaccination. Kieny says simply that “money will not be an issue”. Aid groups and governments have begun to pledge support for such efforts. Médecins Sans Frontières (MSF) has said that it will create a fund for Ebola vaccination, while the European Union has committed €200 million. The GAVI vaccine alliance, the main sponsor of routine vaccinations in low-income countries, is also looking at how it could bring its vast resources and experience to the table. It will put a plan to its board in December as to what role it could play in any Ebola mass vaccination.
Nature Newsblog - Fri, 2014-10-24 13:32
United States regulators are standing by their decision that parents were not properly informed of the risks of a clinical trial in which premature babies received different levels of oxygen supplementation.
From 2005-2009, the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) trial randomly assigned 1,316 premature babies to receive one of two levels of oxygen supplementation in an effort to test which level was best. Though the lower level was associated with increased risk of brain damage and possibly death, and the higher level with blindness, the study leaders said that they did not disclose these risks to parents because all ranges of oxygen used in the trial were considered to be within the medically appropriate range at the time.
The study was supported by the US National Institutes of Health (NIH). On 7 March, 2013, the US Office of Human Research Protections (OHRP) issued a letter determining that the trial investigators had not adequately informed parents about the risks to their babies in the SUPPORT trial. The NIH and many researchers disputed the decision, arguing that it would impede “comparative effectiveness research” studies that are designed to test the best use of approved interventions. Parents of children in the trial, however, and others supported the OHRP’s determination that parents hadn’t received adequate information. The two sides clashed at a meeting convened by NIH and OHRP in August 2013.
Today, 24 October 2014, the OHRP has issued guidance reiterating and clarifying its position on what types of risks must be disclosed to study subjects in comparative effectiveness research studies such as SUPPORT. The agency has determined that risks of the intervention must be disclosed to study participants even if the risks are considered acceptable according to current medical guidelines, if the study intends to evaluate these risks and if the patients’ risks will change when they enroll in the study.
The OHRP said that even though both the low and high levels of oxygen supplementation were considered within the acceptable range, “the key issue is that the treatment and possible risks infants were exposed to in the research were different from the treatment and possible risks they would have been exposed to if they had not been in the trial.”
“[F]or the great majority of infants in the trial, it is likely that their participation altered the level of oxygen they received compared to what they would have received had they not participated,” the OHRP added.
The agency said further that if a trial is designed to compare the risks of potential side effects of a treatment already in use, then the risks are “reasonably foreseeable” and that prospective study participants should be made aware of it.
“If a specific risk has been identified as significant enough that it is important for the Federal government to spend taxpayer money to better understand the extent or nature of that risk, then that risk is one that prospective subjects should be made aware of so that they can decide if they want to be exposed to it,” OHRP said.
The guidance is open to comments until 24 December.
Nature Newsblog - Fri, 2014-10-24 10:47
Government of Western Australia
The state of Western Australia is abandoning a controversial shark-culling programme, but has also gained the right to deploy deadly baited lines for animals that pose an “imminent threat”.
The programme, run by the state government off several Western Australian beaches, had been heavily criticised by scientists when it was announced in 2013. It was due to run until 2017, and had caught at least 170 sharks using hooks suspended from drums moored to the seafloor.
In September the state’s own Environmental Protection Agency halted it. State Premier Colin Barnett then applied to the national government for permission to resume it, but today he announced that his government had ended that effort. “We have withdrawn the application after reaching agreement with the Commonwealth which enables us to take immediate action when there is an imminent threat,” said Barnett.
Under an agreement with the national government, Western Australia will be able to kill sharks in future to deal with a shark that has attacked or with one that it thinks poses a threat. Protocols for how this would happen are now in development.
This apparent concession from the national government has drawn some concern from those celebrating the end of the cull.
“I remain concerned that drum lines could be used in some instances as part of emergency measures and particularly that this could occur without Federal approval,” said Rachel Siewert, the marine spokeswoman for the Australian Greens, in a statement.
The Western Australia cull is also drawing renewed attention to the long-standing cull in Queensland, which continues unabated.
Ernst Mayr Library Blog - Fri, 2014-10-24 10:12
By Gwendolyn Henry, EdM, MSLIS
Archivist and Library Assistant
Ernst Mayr Library, Museum of Comparative Zoology
Processing the Alexander Agassiz’s Expedition and Other Images Collection (1897-1950 (bulk)), which contains 734 gelatin dry plate glass negatives, 268 film negatives and 13 photographic prints requires several key skills: strong attention to detail, the ability to do research, knowledge of descriptive metadata, and most of all a steady hand.
I started this project in April 2012 with little experience in processing glass plate negatives. Before delving into the hands-on technical component of processing, I conducted a bit of research. I asked myself, what is this collection’s provenance?
Using my local resources I gained information from Robert Young, the Ernst Mayr Library’s Special Collections Librarian and records left behind from previous librarians. I learned that the images document the expeditions and work of Alexander Agassiz (1835-1910), a pioneer in oceanographic research, zoological investigation, and mining engineering. Agassiz was best known as a naturalist and for his expeditions, deep-sea investigations, and studies of coral reefs and islands. He devoted four decades to expanding and developing the Harvard University Museum of Comparative Zoology, where he served as curator and director from 1873 to 1910. Included in the collection are many unpublished images from expeditions of the Albatross, Challenger, Croydon, and Yaralla to locations such as Easter Island, Fiji, and Australia, as well as glimpses of Agassiz’s Newport, Rhode Island laboratory and home; also photographs taken by later MCZ director Thomas Barbour and a number of zoological specimen images. The collection, stored in a cabinet in the library’s Room K for decades, was initially processed in the 1970s, when group numbers were assigned and attempts at identification were made.
In order to get myself organized to process this collection I took following steps:
Survey the collection
I began in-depth evaluation of the collection with the sizing and counting of the glass plates. The survey step was necessary to improve control of the images and to order supplies to rehouse them. Maggie Hale from Harvard Library Imaging Services provided a batch-loader spreadsheet and draft work plan template to document the descriptive metadata. Ms. Hale and Brenda Bernier from the Weissman Preservation Center examined the collection and provided technical advice.
Documentation of Descriptive Information
Starting in June 2012, I literally took items from each wooden drawer (see image above), reorganized them by the group numbers and subject areas that were developed by librarians in the 1970’s, measured and documented the length and width of each item, transcribed descriptive information on the original sleeve, and noted the condition and type of each item (broken, chipped, or torn; glass, film or paper photograph) in the batch-loader Google Doc spreadsheet template. After completing the documentation, I grouped the sizes within a group number together. For example for group g3B all the glass plates were put together, and the same method was followed for the film and print photographs. In the screenshot below you will see the digitized glass plate with the descriptive fields listed underneath. The descriptive metadata was gleaned from the batch-loader spreadsheet.
Call numbers and Hollis record (Hollis #014208913) for the collection were developed by Robert Young. Between September and November 2013 I matriculated in the Library Juice Academy course, Describing Photographs for the Online Catalogue, which increased my skills in providing rich descriptive metadata.
The collection was in remarkable good condition except for a few broken glass plates. The conservation steps taken were to remove dust, and debris. To clean the glass plates, while wearing nylon gloves I held the glass plate with one hand and wiped down the ink-free side with ethanol alcohol soaked cotton cloth. Once dry, I placed the glass plates in acid-free enclosures and boxed them in preparation for digitization at Harvard Library Imaging Services. For films and prints I gently removed dust with either a blower or cotton cloth.
Shipping and Rehousing for Permanent Storage:
Items were grouped – glass plates, followed by film and prints – and placed in temporary record center boxes designed for transport with Volara and bubble wrap for inside padding. They were then brought from the Ernst Mayr Library’s Special Collection to the Harvard Library Imaging Services at Widner Library by Robert Young and his wife Eriko in their car. After the items were digitized and returned to the Ernst Mayr Library, I rehoused them in permanent storage boxes.
Digitization of the collection was completed in August 2014, and the descriptive information from the spreadsheet, linked to the images, is now in the Harvard University Library’s Visual Information Access catalog (VIA), and can be accessed here.
List of materials used:
- Record center boxes for temporary storage and transport.
- Suspension boxes for permanent storage
- ethanol alcohol
- cotton pads
- acid-free sleeves
- magnifying glass
My greatest fear while working with this collection was that I would break a glass plate negative. Luckily for me and the collection, this never happened! What did break was my initial assumption that I wouldn’t be able to personally connect with a scientific exploration collection. Although I held each item up to a light and reviewed them with a magnifying glass in order to better describe them, some details became more apparent once digitized. The digitized collection revealed indigenous and local peoples of Fiji, Samoa, Peru, Samba River Valley, Panama, Cuba and Jamaica.
As an Archivist, my academic training and professional experiences provided me with the ability to arrange and describe collections, and yet they also position me to create more intersections between the collections with their corresponding peoples, cultures, places and times. Two years ago when I took on the project, I did not think of the subject areas of Cultural anthropology, Native aesthetics, Colonization, Sociology or Ecology as research uses in addition to scientific exploration, and zoological specimens. I think of the descendants of the indigenous people in these images and their possibility to have more access to their elders that are long gone. I’m glad I was able to personally connect to a rich part of history.
The discovery of Homo floresiensis: Tales of the hobbit
Nature 514, 7523 (2014). http://www.nature.com/doifinder/10.1038/514422a
Author: Ewen Callaway
In 2004, researchers announced the discovery of Homo floresiensis, a small relative of modern humans that lived as recently as 18,000 years ago. The ‘hobbit’ is now considered the most important hominin fossil in a generation. Here, the scientists behind the find tell its story.
Human evolution: Small remains still pose big problems
Nature 514, 7523 (2014). doi:10.1038/514427a
Author: Chris Stringer
Ten years after the publication of a remarkable find, Chris Stringer explains why the discovery of Homo floresiensis is still so challenging.
Emergency planning: Be prepared
Nature 514, 7523 (2014). doi:10.1038/514430a
Authors: Jennifer K. Pullium, Gordon S. Roble & Mark A. Raymond
Scenario-based training for disasters is better than just drawing up a paper plan, say Jennifer K. Pullium and colleagues.
- Molecular beacons shine light on how cells 'crawl'
- Scientists engineer toxin-secreting stem cells to treat brain tumors
- A new dent in HIV-1's armor
- WHO plans for millions of doses of Ebola vaccine by 2015
- US research ethics agency upholds decision on informed consent
- Western Australia abandons shark cull
- Alexander Agassiz’s Expedition and Other Images Collection: An Archivist’s Process
- The discovery of Homo floresiensis: Tales of the hobbit
- Human evolution: Small remains still pose big problems
- Emergency planning: Be prepared