Diagram of the CRISPR prokaryotic viral defense mechanismWIKIMEDIA, JAMES ATMOS

Precision gene editing

Clustered regularly interspersed short palindromic repeat (CRISPR) became a household word this year as a growing number of media outlets covered applications of CRISPR/Cas gene-editing—in particular, the manipulation of the human germline. While use of the CRISPR/Cas system is far from new (The Scientist first reported on it in 2009, and chose the gene-editing technique as one of the 2013’s biggest advances), there’s no question that this was the year it attained buzzworthy status.

After researchers at China’s Sun Yat-sen University in April reported using the CRISPR/Cas9 system to edit a gene in human tripronuclear zygotes, US National Institutes of Health Director Francis Collins said his agency would “not fund any use of gene-editing technologies in human embryos.” At an international symposium held earlier this month in Washington, DC, experts...

CRISPR, of course, is the crux of an ongoing patent battle. And while three scientists are often credited with the key discoveries related to the system’s application, several scientists contributed to the discovery of the naturally occuring bacterial immune defense system.

Selected stories

March 1: Red Hot
CRISPR/Cas is all the rage—and getting more precise and efficient.

April 1: Enzyme Improves CRISPR
A smaller Cas9 protein enables in vivo genome engineering via viral vectors.

April 3: Who Owns CRISPR?
With one US patent awarded and many other applications under consideration for the popular genome-editing technology, companies are adopting multiple strategies to navigate the complex intellectual property landscape.

April 6: CRISPR–Enabled Epigenome Editing
Researchers apply the genome-editing technology to alter histones at distant gene enhancers, controlling gene expression.

April 23: Researchers Edit Early Embryos
Investigators in China observed extensive off-target effects when applying CRISPR-mediated gene editing in human zygotes.

April 30: NIH Opposes Editing Human Embryos
Following the publication of a study in which scientists used CRISPR to edit nonviable human embryos, the National Institutes of Health states it will not fund such research.

October 23: More CRISPR Proteins Discovered
Researchers identify three new proteins that may serve as alternatives to Cas9.

September 28: CRISPR 2.0?
A pioneer of the gene-editing technique discovers a protein that could improve its accuracy.

November 13: Cas9 Proofreads Gene Edits
The gene-editing CRISPR/Cas9 system has three checkpoints to ensure it alters the right section of DNA.

November 30: Fiddling with Human Genes
A look at the technologies now helping researchers edit human genes and discussions of the controversy that has ensued.

December 2: A More-Precise CRISPR/Cas9
Researchers have refined amino acids in the Cas9 protein to reduce the occurrence of off-target gene edits.

December 3: Let’s Talk Human Engineering
Experts continue to discuss the logistics and ethical considerations of editing human genomes at a historic meeting in Washington, DC.

December 8: CRISPR Therapy in a Dish
Redirecting the gene-editing tool to modulate gene expression, researchers restore protein function in cells from a child with Duchenne muscular dystrophy.

Spotlight on lymphatic system

© LISA CLARKScientists at the University of Virginia turned heads in June when they reported evidence to suggest that the mouse brain contains lymphatic vessels similar to those found elsewhere in the body. “For many years, we said ‘There’s no lymphatic drainage from the brain,’” Jon Laman of the Erasmus University Medical Center who was not involved in the work told The Scientist at the time. “[This] is a breakthrough study because it shows the presence and functionality of a lymphatic vessel in the dura mater.”

Selected stories

June 1: Brain Drain
The brain contains lymphatic vessels similar to those found elsewhere in the body, a mouse study shows.

August 1: Rethinking Lymphatic Development
Four studies identify alternative origins for cells of the developing lymphatic system, challenging the long-standing view that they all come from veins.

Synthetic opioid from engineered yeast

Yeast growing in a fermenterSTEPHANIE GALANIEHaving worked toward the feat for several years, a team led by investigators at Stanford University this year achieved the complete synthesis of the opioid thebaine from a sugar in engineered Saccharomyces cerevisiae. “It’s the first time an entire pathway from sugar to morphinans has been stitched together,” Ian Graham of the University of York in the U.K. who was not involved in the research told The Scientist in August.

Selected stories

May 19: Yeast-Made Opioid Progresses
Scientists are one step closer to coaxing engineered yeast to produce morphine from a simple sugar.

June 29: Morphine’s Missing Link Found
Researchers identified the last poppy gene product needed to produce morphine in yeast.

August 13: Yeast-Based Opioid Production Completed
Researchers fully engineer a biochemical pathway that turns a sugar into an opioid in Saccharomyces cerevisiae.

Big-time biopharma deals

The year in biopharmaceutical mergers and acquisitions is perhaps best depicted in this TS Live video, published in August:

The deals mentioned in the above video represent only a fraction of the year's biggest buys in the biopharma arena—many more, including some listed below, were announced after this compilation was produced.

Selected stories

May 8: Endo to Pay $8 Billion for Par
The deal would create one of the five biggest generic drugmakers in the U.S.

July 27: Teva Buys Allergan Generics for $40.5 Billion
Meanwhile, Allergan acquires drug developer Naurex in a $560 million deal.

November 23: Pfizer and Allergan to Merge
The two drugmakers will join forces in a $160 billion deal—if it’s given the regulatory green light.

Discoveries of Loki and Homo naledi

H. naledi skull specimensJOHN HAWKSNear hydrothermal vents deep in the ocean and within a nearly inaccessible terrestrial cave, scientists this year discovered what they say are new species. A sea-dwelling microbe, dubbed Lokiarchaea, could shed light on the origins of a common ancestor for archaea and eukaryotes, while the discovery of skull and other bone fragments from age-unknown Homo naledi specimens could lead to insights about ancient humans. 

Selected stories

May 6: Prokaryotic Microbes with Eukaryote-like Genes Found
Deep-sea microbes possess hallmarks of eukaryotic cells, hinting at a common ancestor for archaea and eukaryotes.

September 10: New Homo Species Found
Researchers describe H. naledi, an ancient human ancestor of unknown age that may have buried its dead.

October 6: Homo naledis Hands and Feet
Two new analyses of fossil remains from the recently discovered human relative suggest the species may have been uniquely adapted to both terrestrial and arboreal locomotion.

Genetically engineered foods

Genetically engineered apples (right) resist browning.OKANAGAN SPECIALTY FRUITSIt was a big year for genetically engineered, or genetically modified (GM), foods, with the US Food and Drug Administration’s landmark approval of the first GM animal intended for food and the US Department of Agriculture’s OK for the planting of a GM apple. As The Scientist reported last month, regulators in the U.S. are struggling to keep pace with the newest crop of genetically edited food products.

Selected stories

February 16: USDA Approves Genetically Engineered Apples
Apples genetically modified to resist browning can be commercially planted in the U.S., the government ruled last week.

March 23: FDA Deems GM Apples, Potatoes Safe
Genetically modified, non-browning apples and bruise-resistant potatoes are safe, the US Food and Drug Administration says.

November 19: FDA OKs GM Salmon
AquaBounty Technologies’s fast-growing fish is the first genetically modified animal approved by the US Food and Drug Administration.

November 25: The Unregulation of Biotech Crops
Genetic engineering—once a trigger for federal oversight—is now ushering some modified crops around scrutiny.

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