Chinese Scientists Edit Genes of Human Embryos, Raising Concerns

Georgia O’Keeffe.  The Chestnut Grey, 1924

By GINA KOLATA The New York Times, APRIL 23, 2015

The experiment with human embryos was dreaded, yet widely anticipated. Scientists somewhere, researchers said, were trying to edit genes with a technique that would permanently alter the DNA of every cell so any changes would be passed on from generation to generation.

What is the Human Genome Project?

Begun formally in 1990, the U.S. Human Genome Project was a 13-year effort coordinated by the U.S. Department of Energy and the National Institutes of Health. The project originally was planned to last 15 years, but rapid technological advances accelerated the completion date to 2003.

Ebola and the Vast Viral Universe

 

Advances in microscopy have allowed scientists like Sriram Subramaniam and colleagues at the National Cancer Institute to look at the workings of tiny viruses. In this case, microscopy was used to illustrate the complex process in which human cells infected with HIV-1, green and blue, are linked to uninfected cells.CreditIllustration by Donald Bliss/N.I.H, from The Journal of Virology/American Society for Microbiology

By NATALIE ANGIER, The New York Times, 27.10.2014

Behind the hellish Ebola epidemic ravaging West Africa lies an agent that fittingly embodies the mad contradictions of a nightmare. It is alive yet dead, simple yet complex, mindless yet prophetic, seemingly able to anticipate our every move.

For scientists who study the evolution and behavior of viruses, the Ebola pathogen is performing true to its vast, ancient and staggeringly diverse kind. By all evidence, researchers say, viruses have been parasitizing living cells since the first cells arose on earth nearly four billion years ago.

Some researchers go so far as to suggest that viruses predate their hosts. That they essentially invented cells as a reliable and renewable resource they could then exploit for the sake of making new viral particles.

It was the primordial viral “collective,” said Luis P. Villarreal, former director of the Center for Virus Research at the University of California, Irvine, “that originated the capacity for life to be self-sustaining.”

“Viruses are not just these threatening or annoying parasitic agents,” he added. “They’re the creative front of biology, where things get figured out, and they always have been.”

Researchers are deeply impressed by the depth and breadth of the viral universe, or virome. Viruses have managed to infiltrate the cells of every life form known to science. They infect animals, plants, bacteria, slime mold, even larger viruses. They replicate in their host cells so prodigiously and stream out into their surroundings so continuously that if you collected all the viral flotsam afloat in the world’s oceans, the combined tonnage would outweigh that of all the blue whales.

Not that viruses want to float freely. As so-called obligate parasites entirely dependent on host cells to replicate their tiny genomes and fabricate their protein packages newborn viruses, or virions, must find their way to fresh hosts or they will quickly fall apart, especially when exposed to sun, air or salt.

“Drying out is a death knell for viral particles,” said Lynn W. Enquist, a virologist at Princeton.

How long shed virions can persist if kept moist and unbuffeted — for example, in soil or in body excretions like blood or vomit — is not always clear but may be up to a week or two. That is why the sheets and clothing of Ebola patients must be treated as hazardous waste and surfaces hosed down with bleach.

Viruses are masters at making their way from host to host and cell to cell, using every possible channel. Whenever biologists discover a new way that body cells communicate with one another, sure enough, there’s a virus already tapping into exactly that circuit in its search for new meat.

GRAPHIC

Treating Ebola: The Hunt for a Drug

Although there are currently no drugs or vaccines approved in the United States to treat or prevent Ebola, health officials have used several experimental drugs in the recent epidemic.

OPEN GRAPHIC

Reporting recently in Proceedings of the National Academy of Sciences, Karla Kirkegaard, a professor of microbiology and genetics at Stanford University School of Medicine, and her colleagues described a kind of “unconventional secretion” pathway based on so-called autophagy, or self-eating, in which cells digest small parts of themselves and release the pieces into their surroundings as signaling molecules targeted at other cells — telling them, for example, that it’s time for a new round of tissue growth.

The researchers determined that the poliovirus can exploit the autophagy conduit to cunning effect. Whereas it was long believed that new polioparticles could exit their natal cell only by bursting it open and then seeking new cells to infect, the researchers found that the virions could piggyback to freedom along the autophagy pathway.

In that way, the virus could expand its infectious empire without destroying perfectly good viral factories en route. The researchers suspect that other so-called naked or nonenveloped viruses (like the cold virus and theenteroviruses that have lately plagued children in this country and Asia) could likewise spread through unconventional secretion pathways.

For their part, viruses like Ebola have figured out how to slip in and out of cells without kicking up a fuss by cloaking themselves in a layer of greasylipids stolen from the host cell membrane, rather as you might foist a pill down a pet’s throat by smearing it in butter.

According to Eric O. Freed, the head of the virus-cell interaction section at the National Cancer Institute, several recent technological breakthroughs have revolutionized the study of viruses.

Advances in electron microscopy and super-resolved fluorescence microscopy — the subject of this year’s Nobel Prize in Chemistry — allow scientists to track the movement of viral particles in and between cells, and to explore the fine atomic structure of a virus embraced by an antibody, or a virus clasped onto the protein lock of a cell.

Through ultrafast gene sequencing and targeted gene silencing techniques, researchers have identified genes critical to viral infection and drug resistance. “We’ve discovered viruses we didn’t even know existed,” Dr. Freed said. And that could prove important to detecting the emergence of a new lethal strain.

Gene sequencing has also allowed researchers to trace the deep background of viruses, which, at an average of a few billionths of an inch across, are far too minuscule to fossilize. In fact, viruses were first identified in the 19th century by size, as infectious agents able to pass through filters that trapped all bacteria.

Through genomic analysis, researchers have identified ancient viral codes embedded in the DNA of virtually every phyletic lineage. The unmistakable mark of a viral code? Instructions for making the capsid, the virus’s protective protein shell, which surrounds its genetic core and lends the viral particle its infectious power.

MORE EBOLA COVERAGE

• 

  Ebola May be Slowing in Liberia, W.H.O. Says

  The World Health Organization’s assistant director general said there had been a decline in burials in the West African nation and no increases in confirmed cases.

• 

  Bellevue Workers, Worn Out From Treating Ebola Patient, Face Stigma Outside Hospital

  Some employees at the New York medical center say they are feeling snubbed, a result of working at the place handling the city’s first Ebola case.

• 

  Unease Lingers in the Bronx Despite a Boy’s Negative Ebola Test

  Doubts and anxiety persist for neighbors in the 5-year-old boy’s building, with some suspicious that the test results are not accurate.

• 

  What You Need to Know About the Ebola Outbreak

  Questions and answers on the scale of the outbreak and the science of the Ebola virus.

“It turns out there are not many ways to make the pieces that will snap together into an effective package,” said Dr. Enquist, of Princeton. “It’s an event that may have occurred only once or twice” in evolutionary history.

Viruses are also notable for what they lack. They have no ribosomes, the cellular components that fabricate the proteins that do all the work of keeping cells alive.

Instead, viruses carry instructions for co-opting the ribosomes of their host, and repurposing them to the job of churning out capsid and other viral proteins. Other host components are enlisted to help copy the instructions for building new viruses, in the form of DNA or RNA, and to install those concise nucleic texts in the newly constructed capsids.

“Viruses are almost miraculously devious,” Dr. Freed said. “They’re just bundles of protein and nucleic acid, and they’re able to get into cells and run the show.”

“On the one hand, they’re quite simple,” Dr. Enquist said. “On the other hand, they may be the most highly evolved form of genetic information on the planet.”

Viruses also work tirelessly to evade the immune system that seeks to destroy them. One of the deadliest features of the Ebola virus is its capacity to cripple the body’s first line of defense against a new pathogen, by blocking the release of interferon.

“That gives the virus a big advantage to grow and spread,” said Christopher F. Basler, a professor of microbiology at Mount Sinai School of Medicine.

At the same time, said Aftab Ansari of Emory University School of Medicine, the virus disables the body’s coagulation system, leading to uncontrolled bleeding. By the time the body can rally its second line of defense, the adaptive immune system, it is often too late.

Yet the real lethality of Ebola, Dr. Ansari said, stems from a case of mistaken location, a zoonotic jump from wild animal to human being. The normal host for Ebola virus is the fruit bat, in which the virus replicates at a moderate pace without killing or noticeably sickening the bat.

“A perfect parasite is able to replicate and not kill its host,” Dr. Ansari said. “The Ebola virus is the perfect parasite for a bat.”

Correction: October 28, 2014

An earlier version of this article referred incorrectly to the position Luis P. Villarreal holds at the Center for Virus Research at the University of California, Irvine. He is a professor at the center and its founding director, but he is not the current director. A picture credit with an earlier version of this article mistated part of the name of an organization. It is the American Society for — not of — Microbiology

 

 

 

 

 

 

 

 

GENCODE: The reference human genome annotation for The ENCODE Project

Jennifer Harrow, Adam Frankish, […], and Tim J. Hubbard

 

Abstract

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

 

Richard Dawkins: Το εγωιστικό γονίδιο*

 

Γιατί υπάρχουν άνθρωποι;

Ζωντανοί οργανισμοί υπήρχαν στη Γη εδώ και 3.000.000.000 χρόνια, χωρίς κανείς να ξέρει από που προέκυψαν, ως τη στιγμή που κάποιος ανακάλυψε την αλήθεια. Το όνομά του είναι Κάρολος Δαρβίνος. Για να είμαστε δίκαιοι, υπήρξαν και άλλοι που είχαν υποψιαστεί την αλήθεια. Πρώτος όμως ο Δαρβίνος έδωσε μια λογική και συνεπή εξήγηση του λόγου της ύπαρξής μας.

Tiny, Vast Windows Into Human DNA

 

Genes found on chromosomes of the fruit fly are regulated much like those of humans though they are but distant relatives. CreditEd Reschke/Getty Images

 

By CARL ZIMMER, The New York Times,  SEPT. 1, 2014

In the history of biology, two little animals loom large.

The Path to Reading a Newborn’s DNA Map / A Catalog of Cancer Genes That’s Done, or Just a Start

The Path to Reading a Newborn’s DNA Map

By ANNE EISENBERGFEB. 8, 2014, The New York Times

 

What if laboratories could run comprehensive DNA tests on infants at birth, spotting important variations in their genomes that might indicate future medical problems? Should parents be told of each variation, even if any risk is still unclear? Would they even want to know?

The Continuing Evolution of Genes

 

 

Studies of the fruit fly, Drosophila melanogaster, have found that some species have new genes, suggesting recent evolution. Credit Zach Wise for The New York Times

By CARL ZIMMERAPRIL The New York Times, 28 April 2014

 

Each of us carries just over 20,000 genes that encode everything from the keratin in our hair down to the muscle fibers in our toes. It’s no great mystery where our own genes came from: our parents bequeathed them to us. And our parents, in turn, got their genes from their parents.

A Powerful New Way to Edit DNA

 

By ANDREW POLLACK, The New York Times, MARCH 3, 2014

 

In the late 1980s, scientists at Osaka University in Japan noticed unusual repeated DNA sequences next to a gene they were studying in a common bacterium. They mentioned them in the final paragraph of a paper: “The biological significance of these sequences is not known.”

Now their significance is known, and it has set off a scientific frenzy.

Seeing X Chromosomes in a New Light

Launch media viewer

In a female mouse’s brain, a left-to-right pattern in the silencing of the X chromosome. These patterns may influence how individual brains function. Hao Wu and Jeremy Nathans/Cell Press

By CARL ZIMMERJAN, The New York Times, 20.1.2014

The term “X chromosome” has an air of mystery to it, and rightly so. It got its name in 1891 from a baffled biologist named Hermann Henking. To investigate the nature of chromosomes, Henking examined cells under a simple microscope. All the chromosomes in the cells came in pairs.

All except one.

The Selfish Gene by Richard Dawkins

– book review

Dawkins argues remorselessly that individual lives are merely punctuation points in automaton genes’ quest for eternity

 

• Tim Radford, guardian.co.uk, Friday 31 August 2012 07.50 BST

Both The Selfish Gene and its author continue to annoy the hell out of assorted philosophers, biologists and bishops. Photograph: Reuters

About “junk DNA”…

 

Θεόφιλος (Χατζημιχαήλ) (1873 – 1934), Η Αγία Άννα της Χαλκίδας, 1927

 

Breakthrough study overturns theory of ‘junk DNA’ in genome

 

The international Encode project has found that about a fifth of the human genome regulates the 2% that makes proteins

• Alok Jha, science correspondent

• guardian.co.uk, Wednesday 5 September 2012 20.03 BST

Science correspondent Ian Sample uses a visual aid to explain the implications of the new research. Video: Guardian Link to this video