Since its invention approximately 60 years ago, the Journal Impact Factor (JIF) has been used to assess the quality of academic literature and the influence of scientific papers on the scientific community. The JIF was proposed by Eugene Garfield in the early 1950s and originally published by his Institute for Scientific Information (ISI) as a subscription buying tool for academic and medical librarians. The JIF assigns a score to scientific journals based on the average number of citations received in a year per paper published in the journal during the two preceding years. It has since become the authority on which journals are considered top tier publications are therefore premiere space for scientists wishing to best publicize their work and gain notoriety.

Unfortunately, the JIF has also become a tool used to ascertain a scientist’s worth and can often be a determining factor in the levels of funding they are to receive. This is an unfortunate turn of events since the JIF contains many deficiencies such as glossing over differences between fields, and lumping primary research articles in with much more easily cited review articles. As such, researchers that publish quality work in lower ranked journals are often at a disadvantage compared to those publishing secondary research in higher ranking journals.

In order to “protest” and counter this phenomenon, a group of publishers from both high impact and low impact journals have formed the Declaration on Research Assessment (DORA) which aims to lower the influence of the JIF on assessing scientific merit.

Dora has released 18 principles which are geared towards accomplishing these goals. Some of the recommendations that stand out the most include:

• JIF should not be used to measure quality of individual articles or to asses an individual scientist’s contributions, or in hiring, promotion or funding decisions
• Funding agencies should place more weight on the scientific content of a paper than its JIF
• Scientific content of a paper should be considered a more important hiring decision than the JIF
• A call for organizations to be open and transparent by providing data and methods used to calculate all metrics
• Researchers should challenge research assessment practices that rely inappropriately on JIF

To download the full list of recommendations visit http://am.ascb.org/dora/files/SFDeclarationFINAL.pdf.

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Ray Cinti
Convent of the Sacred
Heart High School

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After an egg has been fertilized, it divides repeatedly to give rise to every cell in the human body—from the patrolling immune cell to the pulsing neuron. Each functionally distinct generation of cells subsequently differentiates itself from its predecessors in the developing embryo by expressing only a selection of its full complement of genes, while actively suppressing others. “By applying large-scale genomics technologies,” explains Bing Ren, PhD, Ludwig Institute member and a professor in the Department of Cellular and Molecular Medicine at the UC San Diego School of Medicine, “we could explore how genes across the genome are turned on and off as embryonic cells and their descendant lineages choose their fates, determining which parts of the body they would generate.”

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Conventional methods use a centrifuge to spin and separate DNA molecules or strain them from a fluid sample with a micro-filter, but these processes take 20 to 30 minutes to complete and can require excessive toxic chemicals.

UW engineers designed microscopic probes that dip into a fluid sample – saliva, sputum or blood – and apply an electric field within the liquid. That draws particles to concentrate around the surface of the tiny probe. Larger particles hit the tip and swerve away, but DNA-sized molecules stick to the probe and are trapped on the surface. It takes two or three minutes to separate and purify DNA using this technology.

Read the full story on the UW website.

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“This new method is a game changer,” says Jaenisch, who is also a professor of biology at MIT. “We can now make a mouse with five mutations in just three to four weeks, whereas the conventional way would take three to four years. And it’s rather straightforward, probably even easier than the conventional way.”

Scientists create models in mice by altering specific genes that have been associated with a given disease. The models allow for the study of the development and course of the disease and the effects of various interventions, including genetic and chemical. For the past 20 years, the creation of such models has remained relatively unchanged: scientists insert a piece of DNA into a mouse embryonic stem (ES) cell, inject the modified cell into a very early-stage embryo, called a blastocyst, then implant this developing ball of cells into a foster female mouse. The whole process can take years and tens of thousands of dollars to establish a mouse strain with, for example, a single copy of a gene “knocked out”. Such knockouts can only be created in very few species, including mice and rats, whose ES cells can be grown and modified reliably.

The new approach used by scientists in Jaenisch’s lab bypasses ES cells to quickly and efficiently produce mice with mutations in both copies of multiple genes. In next week’s issue of the journal Cell, Haoyi Wang, Hui Yang, and Chikdu Shivalila describe their technique, which is based on a system that certain bacteria use to fend off viral attacks.

This is the first time that the system, known as CRISPR (for “clustered regularly interspaced short palindromic repeat”)/Cas (for “CRISPR-associated”), has been used to alter multiple genes in a single multicellular organism. Shivalila says the process is so accessible that he expects other labs to adopt it quickly.

“For any institution or university with a core facility, we think this will be the way they will start making mice carrying specific mutations because it’s a lot faster and so efficient,” says Shivalila, one of Jaenisch’s graduate students. “We were surprised that we could get two genes ‘knocked out’ at four loci very, very efficiently, about 80% efficiency. If we used TALENs, a more recent and complicated development in genetic engineering, we got 30% efficiency for just one gene.”

Because the CRISPR/Cas technique can generate mutant mice even without using ES cells, a limitation of the conventional method for making models, genetic research may no longer be confined to a limited list of model organisms—those for which ES cells exist.

“This breaks down the definition of model organism,” says Wang, a postdoctoral researcher in Jaenisch’s lab. “So now, even with limited resources, any animal with established embryo manipulation procedures could be the subject of genome engineering. With many of the animals’ genomes that have been sequenced, we could use this technology to establish efficient genetic manipulations in more species, to study the unique biology of each, and to learn more about evolution.”

Thus, Wang, Yang, and Shivalila have used CRISPR/Cas to create mouse models only, but the team is excited broaden its application to other animals.

“We also need to see if the CRISPR/Cas system has any unexpected, undesired off-target effects, changes to the genome that we don’t want,” says Yang, a postdoctoral researcher in the Jaenisch lab. “So we need study this further to establish the fidelity of the system. But I think this will be the way to go.”

Thanks to Whitehead Institute for Biomedical Research for this story.

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