Pesticides and food: It’s not a black and white issue

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FIRST ARTICLE: Has pesticide use decreased over the last 40 years?

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Why 2018 might not be a banner year for CRISPR gene editing in humans

Ever since scientists first used CRISPR-Cas9 to edit living human cells in 2013, they’ve been saying that the possibilities for using it to treat disease are virtually endless….

The hope is that CRISPR could be used in a one-time procedure to cure some of the most devastating inherited disorders and cancers, some of which have no or few current treatment options…

That might be the dream, but the reality is far different. Already, investigators have delayed the start dates of clinical trials. And the studies slated to start in the next year or two will treat a small number of patients with a few rare diseases. It will probably be years before the technology can be used for more common diseases in more patients.

In the U.S. and Europe, 2018 might not be the banner year that CRISPR devotees had been hoping for, but Alexey Bersenev, director of the Advanced Cell Therapy Lab at Yale-New Haven Hospital, says 2019 could see a dozen or so submissions for clinical trials.

“The field is currently over-optimistic about possible results of clinical trials,” says Bersenev, who is also cofounder of the database celltrials.org, which tracks cell therapy trials. “Every new and hot biomedical technology usually undergoes an inflated expectations phase.” He says he wouldn’t be surprised if investigators further delay their anticipated clinical trials.

Read full, original post: CRISPR in 2018: Coming to a Human Near You

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Will new wave of gene-edited crops ease public fear of GMO food?

To many scientists, the potential of gene editing seems nearly limitless, offering a new way to rapidly create plants that are drought-resistant, immune to disease, or improved in flavor. A supermarket tomato that tastes good? That could happen if scientists restore the flavor-making genes that make heirloom varieties delicious. What about a corn plant with twice as many kernels? If nature allows it, scientists believe, gene editing could let them build it.

There is another reason gene editing is causing excitement in industry. The U.S. Department of Agriculture has concluded that the new plants are not “regulated articles.” The reason is a legal loophole: its regulations apply only to GMOs constructed using plant pathogens like bacteria, or their DNA.

To the critics, any attempt to reclassify engineered plants as natural is a dangerous fiction. “If they don’t have to go through the regulatory requirements, then it is game on again for genetic modification in agriculture,” says Jim Thomas, head of a nonprofit called the ETC Group that lobbies on environmental issues. “That is the prize. They are constructing a definition of a GMO so that gene editing falls outside it.”

Read full, original post: These Are Not Your Father’s GMOs

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Navigating the ‘promise and peril’ of bioengineering

We’re standing on the threshold of extraordinary capability in synthetic biology. CRISPR-Cas9, the genome editing technique discovered in 2014, is at the forefront of this newfound potential for innovation. These advancements provide an opportunity to solve problems in food supply, disease, genetics, and—the most tantalizing and forbidden of prospects—modifying the human genome….

However, many experts warn of the dangers of these new capabilities. A vast torrent of money is flowing towards biotech startups, and the race to be first can encourage cutting corners…

How can we realistically assess the potential risks and rewards? Now, a new study combining researchers from the US and the UK, published recently in eLifeSciences, gives an expert perspective on 20 emerging issues in bioengineering.

The researchers sorted the 20 developments into different time horizons: the next five years, the next decade, and more than a decade away.

Yet as it becomes accessible by more and more people, there are other risks…Genetic information will become the new currency; just as an algorithm today can be worth millions or wreak havoc, soon the same security measures will need to apply to genetics. We can only hope that these security efforts are well-funded and carried out with the utmost care. The consequences of a computer virus can be damaging; the consequences of ‘malware’ for humans could be far worse.

Read full, original post: The Enormous Promise and Peril of Bioengineering’s Pandora’s Box

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Personalized piglets could offer insights into disease progression in children

To better understand [incurable inherited disease neurofibromatosis type 1, Charles] Konsitzke learned, you need a species that’s closer in both size and biology to a person, and yet is still relatively easy to raise and study. That is, you need pigs. “Pigs closely represent humans,” says Neha Patel, who directs the UW neurofibromatosis clinic. “People with NF-1 have varied cognitive deficits, from severe learning issues to subtle problems. If you imagine studying those in a rat, you’d only get a crude picture of how that translates to humans. But pigs are intellectual animals.”

..

Konsitzke and [researcher Dhanu] Shanmuganayagam aren’t just planning to develop pigs that can model the symptoms of NF-1. They want to use the revolutionary gene-editing technique known as CRISPR to create pigs that have the specific mutations of a particular individual. Each child with NF-1 would get their own personalized piglet, whose version of the NF1 gene matched their own. The piggy proxy could be monitored to see how the kid’s condition might progress, especially since they mature faster than humans do.

The team delivered their first edited animal in November 2016, which carried a set of NF-1 mutations that had been reported in an earlier published study. They have since engineered three more animals, each with a different cluster of mutations.

Read full, original post: Turning Piglet Into Personalized Avatars for Sick Kids

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Milk without cows: Commercialization of synthetic dairy products in the works

Berkeley-based Perfect Day – which is creating ‘vegan’ dairy proteins without cows – is in talks with food industry partners about scaling up production in order to introduce dairy ingredients that vegans, vegetarians and dairy lovers alike can enjoy in products “in every aisle of the grocery store.”

Perfect Day is one of a new breed of companies in the ‘cellular agriculture’ business – using genetically engineered yeasts that have been ‘programmed’ to produce proteins or other ingredients found in plants or animals – on an industrial scale, without raising animals, and with less impact on the environment.

So how are the proteins produced?

In a nutshell, Perfect Day takes food grade yeast, and adds DNA sequences (which can be 3D printed using DNA synthetic biology techniques) which effectively instruct that yeast to produce the proteins found in milk – predominantly casein, but also lactoglobulin and lactoalbumin, the two proteins that form the bulk of whey protein in milk. It then throws them into big fermentation tanks with corn sugar and other nutrients to feed on and sits back while they get to work.

When the microbes have done their work at the bio-refnery, Perfect Day’s dairy proteins – which have the same organoleptic properties as their animal-based counterparts – are harvested via a mechanical process and can be used in everything from ice cream to branded fluid milk, protein powders and shakes, yogurt, pizza and any other product containing dairy proteins….

Read full, original post: Perfect Day in talks with food industry partners to commercialize animal-free dairy ingredients

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5 things you should know before buying a consumer DNA test kit

Genetic testing kits you can do at home seem to be on many holiday wish lists this year; one even landed on Oprah’s list of favorite things. The affordable kits, like those from 23andMe and ancestry.com, can scan your genes from a spit sample. But it’s important to know what they can and cannot do when it comes to teaching you about your medical well-being. Here are five things to know—before you ship off your saliva—if you get a genetic testing kit for the holidays.

You won’t find out everything about your genes

Most genetic testing companies don’t actually sequence all three billion base pairs of your entire DNA. They generally focus on certain sections where there is stronger information about what genetic changes mean.

You’ll learn more about where you came from

Much of the appeal of getting your DNA sequenced is learning about how much of your genome you share with people from all over the world. It is possible to discover a surprise Scottish heritage, for example, or even that you’re related to George Washington.

Genetic sequencing is particularly good at this, since it can find common DNA denominators among people of different racial and ethnic origins. Some people have even used genetic ancestry testing to find biological parents or lost relatives.

[Editor’s note: Click the link below to see the full list]

Read full, original post: DNA Testing Kits Are on Everyone’s Holiday List. 5 Things to Know If You Get One

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Video: MIT scientists create plants that glow in the dark

Imagine that instead of switching on a lamp when it gets dark, you could read by the light of a glowing plant on your desk.

MIT engineers have taken a critical first step toward making that vision a reality. By embedding specialized nanoparticles into the leaves of a watercress plant, they induced the plants to give off dim light for nearly four hours. They believe that, with further optimization, such plants will one day be bright enough to illuminate a workspace.

This technology could also be used to provide low-intensity indoor lighting, or to transform trees into self-powered streetlights, the researchers say.

To create their glowing plants, the MIT team turned to luciferase, the enzyme that gives fireflies their glow. Luciferase acts on a molecule called luciferin, causing it to emit light. Another molecule called co-enzyme A helps the process along by removing a reaction byproduct that can inhibit luciferase activity.

The MIT team packaged each of these three components into a different type of nanoparticle carrier.

The researchers’ early efforts at the start of the project yielded plants that could glow for about 45 minutes, which they have since improved to 3.5 hours.

[Editor’s note: Read the full study (behind paywall)]

Read full, original post: Engineers create plants that glow

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Biotech advocates hope Trump tackles regulatory overreach on GMO crops

The agricultural biotech sector is cheering President Donald Trump’s assault on regulatory overreach, seeing its best shot in years to streamline 30-year-old rules governing approval of genetically engineered crops.

Agritech companies want Trump’s USDA to revamp rules that they say block innovation and are hopelessly antiquated. Doing so, they say, would enable farmers to produce more healthful and sustainable crops — everything from more flavorful tomatoes to heat-resistant lettuce and gluten-free wheat.

Currently, genetically engineered crop developers must go through an onerous and often yearslong regulatory process, even for changes that might have happened in nature and pose no known risks to consumer health or other crops. It takes 11 years on average and about $136 million to get government signoff for a GE plant, according to a 2011 CropLife International study — far too expensive for any but the biggest players.

But updating the regulations is likely to be difficult. Many consumers and environmental groups are still leery of genetically modified foods. Some seek strict regulation of even the smallest changes to protect organic crops from potential contamination, and to ensure that Americans know what they are eating — an argument that convinced Congress to impose a federal standard for disclosing GMO ingredients in food last year.

Read full, original post: Trump’s opportunity to change America’s fruits and vegetables (behind paywall)

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How tricking mosquitos into thinking they’ve already mated could fight disease

If you thought the sex lives of humans were complicated, consider the case of the female Aedes aegypti mosquito, bringer of Zika, dengue, and yellow fever: She mates but once, in seconds and on the wing, with one lucky male; spurns all further advances from other potential suitors; and stores enough sperm from that single encounter to lay more than 500 eggs, which she nourishes with the blood of human hosts.

Understanding her sexual behavior could help prevent her from transmitting the deadly diseases she carries to millions of people every year. Yet many of the mechanisms governing her mating habits remain a mystery.

Recently, however, researchers … demonstrated that a chemical transferred from the male of the species during sex plays a key role in shaping the female’s sexual proclivities. Their work … could yield new strategies for keeping this pest, and the pestilence it spreads, in check.

[S]cientists now have a much better understanding of what shapes female mating behavior not only within one dangerous mosquito species, but across two of them. And those insights could have far-reaching implications.

For example, scientists might eventually be able to limit the number of disease-carrying mosquitoes by using a substance like HP-I to persuade females to avoid mating in the first place.

[Editor’s note: Read full study (behind paywall)]

Read full, original post: Mosquito sex protein could provide key to controlling disease

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FDA approves first gene therapy for a genetic disease—onetime cure for rare blindness

The first gene therapy to restore sight to individuals who suffer from a rare inherited genetic blindness was approved by the U.S. Food and Drug Administration Tuesday [Dec. 19].

The treatment, developed by Philadelphia drug maker Spark Therapeutics and researchers at Children’s Hospital of Philadelphia, represents the first gene therapy for a genetic disease in the United States.

The approval culminates “decades of research that has resulted in three gene therapy approvals this year for patients with serious and rare diseases,” the FDA said.

The other gene therapies, which bio-engineer immune system T cells to attack certain blood cancers, are Novartis’ Kymriah and Kite Pharmaceuticals’ Yescarta. Kymriah’s technology was developed at Penn and CHOP.

Spark’s treatment, to be known by the brand name Luxturna, is intended to be a onetime treatment.

Analysts expect the cost will be $500,000 per eye, or $1 million per patient.


In October, an FDA advisory committee unanimously recommended approval of Luxturna. At that hearing, Joan O’Brien, chair of the University of Pennsylvania’s department of ophthalmology and director of Scheie Eye Institute, told the FDA panel, “My prediction is this work will ultimately transform the lives of individuals, perhaps millions, who are facing a life of blindness.”

This first approval will propel further research into gene therapy treatments for other inherited retinal problems associated with other genes, O’Brien said.

Read full, original post: FDA approves Spark’s gene therapy for rare blindness pioneered at CHOP

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Canada proposes new limits—but no ban—on neonicotinoid insecticides to protect bees

The [Canadian] federal government has proposed tighter restrictions around two insecticides that are harmful to bees, but stopped short of an all-out ban.

Health Canada announced new mitigation measures [Tuesday, Dec. 19] on the neonicotinoids clothianidin and thiamethoxam, pesticides which are sold as seed treatment or sprays to protect agricultural crops from various insects.

Under proposed changes, the product will be banned from some uses such as orchard trees or strawberry patches.

Restrictions are on the way for other uses such as on berries and legumes.

New measures will also require new labelling for seed treatments, which will still be permitted.

“Scientific evidence shows that with the proposed restrictions applied, the use of clothianidin and thiamethoxam does not present an unacceptable risk to bees,” said Margherita Conti, an official with Health Canada’s pest management regulatory agency.

But environmental groups say the new measures fall short of what’s needed to protect pollinators and ecosystems.

Deborah Conlon, a representative of the Grain Growers of Ontario, said measures already implemented, including labelling changes, have led to a decrease in bee mortality.

She called it “good news” that growers will be able to use the products to protect their crops because an all-out ban could have a big financial impact on farmers.

“Insects cause damage, and that impacts yield,” she said.

Read full, original post: New limits, but no all-out ban on pesticides that harm bee population

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Scientists fight back against call for moratorium on gene-drive research

It sounds like the plot of a science fiction novel: Scientists discover how to eradicate an entire species. Environmentalists want to stop the research. A United Nations committee invites experts to an online forum to consider the facts.

Behind the scenes, the scientists organize to present certain information. The environmentalists find out and get access to the scientists’ personal emails and dump them on the internet.

But it’s not fiction. It all happened — the first skirmish in a battle over what could be one of the most powerful technologies ever developed.

That brings us to the great email dump last week. Scientists around the world were stunned when dozens of their personal emails suddenly appeared in the public domain — released by an environmental activist who obtained the documents through U.S. freedom of Information laws.

The emails reveal a Canadian public relations firm, Emerging Ag Inc., recruiting scientists to participate in an online UN gene-drive forum and notifying them when to jump into the discussions.

The emails do reveal a co-ordinated effort to mobilize scientists to defend their research turf, an effort that is funded by deep philanthropic pockets. The Bill and Melinda Gates Foundation has paid $1.6 million US to Emerging Ag for a three-year program to manage the scientists’ network, including setting up a website and organizing meetings.

Read full, original post: Scientists mobilize for a fight over powerful gene-editing technology

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EPA reaffirms global scientific consensus that glyphosate herbicide does not cause cancer

The federal Environmental Protection Agency on Monday [Dec. 19] said glyphosate, the primary ingredient in the weed killer Roundup and one of the most widely used herbicides in agriculture, likely does not cause cancer.

The assessment contradicts the conclusion of a European scientific panel as well as California regulators, who have included the chemical on the Proposition 65 list of probable carcinogens.

Environmentalists worldwide have fought to encourage governments to ban the pesticide.

The European Union in November voted to extend the license of the chemical for five years. EPA will be considering a similar extension of the product’s registration for use in 2019, and Monday’s draft assessment is a foundational document in that process.

The controversy over the chemical is tied to opposition to genetically modified crops — Monsanto (which is merging with agrochemical giant Bayer) has patented versions of several major commodity crops that have been altered to resist its patented Roundup weed killer.

Read full, original post: EPA says herbicide in Roundup weed killer doesn’t cause cancer, contradicting California regulators

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TRAPPIST-1 mini-planetary system and what it means for the spread of life between worlds

There is a mini Solar System in our midst with really good prospects for harboring life. Last month, NASA announced the discovery of four small planets orbiting TRAPPIST-1—a red dwarf star 39 light-years away that already had been known to have three planets in the Earth-Venus size range. Seven Earth-sized planets around a star is an unprecedented find; despite the discovery and confirmation of more than 3,000 extrasolar planets over the past three decades, most such worlds are gas giants, like our own Jupiter and Saturn.

Astronomers have confirmed the presence of only a few dozen worlds as small as the rocky worlds of our inner Solar System and orbiting within the “Goldilocks zone” of their stars –not to close in, not too far out, allowing for liquid water at a planetary surface. For the Sun, that zone is thought to run from the orbit of Venus to the orbit of Mars –or somewhat further, according to new research. Astrobiologists think that surface water makes the presence of life –at least life that we could detect across space– much more likely on any given world. Initially three of the seven planets of TRAPPIST-1 –planets e, f, and g– were said to be in its Goldilocks zone.

Just days after the NASA announcement, however, came another study that added planet h, the outermost world of the seven. Based at the Carl Sagan Center at Cornell, the newer study expands the Goldilocks zone around any star by 30-60 percent, so it has implications far beyond TRAPPIST-1.

Being a much smaller, dimmer, cooler star compared with the Sun, TRAPPIST-1 makes for a system in which things are scaled down. The Goldilocks zone is located very close to the star, closer than Mercury orbits the Sun. This means that all seven planets orbit the star very quickly. Whereas Mercury takes 88 Earth days to orbit the Sun, even the furthest out TRAPPIST-1 world, planet h, orbits in just under 19 days. Of course, days are different there. The planets, especially the inner ones, are probably locked by gravity into a situation where a day and year are the same thing. The same side of the planet faces the star, the way that our Moon keeps face toward Earth all the time.

trappist 12 8 17-2This situation would not necessarily be a problem for life forms, and the scaled down size of the system offers a certain advantage in that the planets are very close together. Rather than being points of light as we see Venus and Mars, somebody on a TRAPPIST-1 planet would see a neighboring world as a circles, gibbous, or crescent, as we see the Moon. The distance between neighboring planets is just a few times the distance between Earth and the Moon. Needless to say, a civilization with our level of technology in such a scaled down system would have a much easier time sending astronauts than we’re having sending astronauts to Mars or Venus.

The sheer number of Earth-sized planets around TRAPPIST-1 is a good thing for the prospects of life throughout the Cosmos. It makes the multiple origins of life of life from non-living chemistry more likely if more worlds are available to serve locations for such an origin, but the TRAPPIST-1 find adds to another dimension of the equation. The close distance between the planets means that if life exists on one world, it will probably exist on all of them. This, in turn, improves the prospects of life surviving planet-wide disasters, like Earth’s Permian-Triassic extinction, which wiped out more than 90 percent of life 250 million years ago.

Caveats on the Goldilocks zone

Although the capability for liquid water is the main factor for habitability, the Goldilocks zone applies to habitability primarily in terms of what could be detected across space. As we move further out from a star, it is possible to have life deep down, for instance in an ocean that exists beneath thick layers of ice, due to heating on the inside of a world. Jupiter’s moon Europa and Saturn’s moon Enceladus are in this category. They are top targets for future space probes looking for extraterrestrial life, even though their surfaces are too cold for liquid water. Life forms in an ocean deep under the surface of an icy moon of another star system would not be detectable remotely by any technology we know, so we define such frigid regions of a star system as being outside the Goldilocks zone.

On the other hand, life on the surface and in the atmosphere of a world produces chemical signatures that will be detectable with instruments that are on the verge of launching into space. Related to this, the new study from Cornell has demonstrated planets in the size range of Earth can warm up through greenhouse heating from hydrogen gas released through volcanic activity. This means extra-strong greenhouse heating and it’s possible if a planet is extremely volcanically active, much more so than Earth ever was. The scaled-up greenhouse effect would make liquid water possible at the surface, where there such a volcanic world orbiting the Sun at a distance intermediate between than of Mars and Jupiter, but hydrogen in a planet’s air also would make any chemical signatures of life easier to detect across space.

Crunching the numbers

Earlier this month, researchers Manasvi Lingam and Abraham Loeb of Harvard University posted a new analysis on Cornell University Library’s open access system with calculations showing that it would be extremely easy for microbes to travel between worlds of the TRAPPIST-1 system. Life moving between planets is not a new idea. The concept goes back to Anaxagorus, a Greek philosopher who lived 2,500 years ago. It was revived in 1908 by Swedish chemist Svante Arrhenius, and a century later by several astrobiologists, including in a Scientific American story, by this writer together with Benjamin Weiss of MIT.

trappist 12 8 17-3The 21st century popularization was fueled growing evidence that impacts from comets and meteoroids regularly catapult rock materials into space from the crusts of all inner Solar System planets, and evidence that tons of rocks from Mars arrive on Earth, after spending variable amounts of time in space. One such rock, a meteorite called ALH84001, way hypothesized by the late David S. McKay of NASA and colleagues to contain fossil evidence of Martian microorganisms in a 1996 paper in the journal Science.

The McKay hypothesis survives

The idea met criticism, and sometimes ridicule, leading to a dismissal of the McKay hypothesis in general media based on rationales like this one from the Daily Kos 2016:

So there the matter rests. The data do not conclusively rule out the possibility of Martian life in ALH84001, but each bit of evidence can also be equally well-explained by non-biological mechanisms. Under the scientific principle of “Ockham’s Razor”, in which no new explanatory mechanism can be invoked unless it is necessary to explain the observed evidence, there is no need to postulate the existence of Martian life to explain any of the data. So the scientific consensus is that those who claim the existence of Martian life in ALH84001 do so because they WANT it to be true, not because there is any data or evidence which makes it necessarily true.

The problem is that, in fact, there is a substantial need to postulate a biological source of one of four features that McKay and his team identified in the meteorite: crystals of magnetite. Critics have cited non-biological mechanisms to explain all of the features, including the crystals, but their assumption has always been that non-biological must imply simplicity compared with biological causes. McKay and colleagues, including some researchers from outside of his team, spent many a paper and conference, countering this reasoning.

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Mars

To sum up the case for life, the magnetite crystals have five of six features in common with magnetite crystals that are made on Earth by magnetotactic bacteria. These microorganisms use the crystals to sense Earth’s magnetic field in order to navigate, so there’s an evolutionary reason why biology should also produce such a mineral Mars. On the other hand, the non-biological mechanisms proposed to have created the crystals on Mars require very specific pressure and temperature conditions in a certain geophysical context that has never been observed on Earth, nor on Mars, nor anywhere in nature, and they’re fairy difficult to produce in the lab.

Does this make Martian life the more complex explanation? Before deciding, consider that in the early 2000s, Weiss and colleagues found evidence of an ancient magnetic field on Mars in the same meteorite containing McKay’s proposed fossils. Considering everything, it’s extremely unlikely that all five features observed in the magnetite crystals of the ALH84001 magnetite came together, unless natural selection were involved. A biological origin is a simpler explanation, and so, by Okham’s Razor, the McKay hypothesis remains strong.

Movement of life between planets

The status of ALH84001 notwithstanding, there is no uncertainty about the movement of planetary materials, especially between Mars and Earth. Study of meteorites and testing involving rapid acceleration of rocks suggest that microorganisms could survive heating and shock forces associated from catapulting, due to impact events, plus even small rocks heat only on the surface when entering Earth’s atmosphere, so life forms in the interior could survive the arrival process. Evidence from various experiments conducted in space since the 1960s suggest that small life forms can survive long periods in space, and The Planetary Society is preparing more experiments to test the idea further.

Whereas Anaxagoras, Arrhenius, and others called the scenario panspermia, this term means “seeds everywhere”, so it really refers to the movement of life throughout the Cosmos, meaning between star systems and even galaxies. But to be more conservative, Planetary Society researchers have been using the term transpermia to specify movement of life merely between nearby planets.

All of this is in the context of distances on the scale of our own Solar System, but with the TRAPPIST-1 system, we’re talking about transpermia through Earth-Moon-like distances, so the new calculations make good sense. It should be very easy for life forms to survive within rocks transferred between nearby planets, so easy that it’s almost a sure thing that transpermia occurs at some level. As suggested earlier, this would provide a kind of extinction insurance, and that means that TRAPPIST-1 is a really good place to focus new instruments engaged in the search for extraterrestrial life.

David Warmflash is an astrobiologist, physician and science writer. BIO. Follow him on Twitter @CosmicEvolution.

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US funding for cancer agency threatened over handling of controversial glyphosate report

Three US House Science, Space, and Technology Committee leaders are threatening to cut funding for the International Agency for Research on Cancer over concerns about the agency’s scientific integrity and conflicts of interest.

In a December letter to outgoing IARC Director Christopher Wild, Chairman Lamar Smith, Vice Chairman Frank Lucas, and Environment Subcommittee Chairman Andy Biggs reiterated the committee’s request for witnesses to testify at a hearing regarding “data deletion, manipulation and potential conflicts of interest” in IARC’s designation of glyphosate as a probable carcinogen. Wild, who is leaving his post in January 2019, dismissed an earlier request.

A committee aide said the letter targets withholding funds for IARC’s monograph program and not IARC in general. The US provided about $925,000 in 2017 for the program. US contributions to the program totaled $22 million since 1985. Funding from the US makes up about 7.4 percent of IARC’s budget from participating nations, which makes up about two-thirds of its total budget. The remaining third comes from grants, private and international partner donations.

Part of the committee’s concern is that Christopher Portier had input into the glyphosate monograph despite apparent conflicts of interest. Portier worked for the Environmental Defense Fund, an environmental NGO that has periodically campaigned against pesticide use. Media reports indicate Portier also received at least $160,000 as a consultant for attorneys suing Monsanto on behalf of cancer clients. Portier reportedly signed contracts with the law firms days after IARC issued its controversial monograph proclaiming glyphosate to be a probably carcinogen.

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IARC Director Christopher Wild

The congressmen disputed Wild’s assertions that IARC’s monographs are “free from vested interests” and that Christopher Portier had no part in drafting or interpreting IARC evaluations on glyphosate.

“The Committee finds it difficult to view Portier’s view with EDF and his role on the glyphosate monograph as anything but a conflict of interest,” the committee said in the letter.

Changed assessment

In October, Reuters’ Kate Kelland reported that IARC removed “multiple scientists’ conclusions that their studies had found no link between glyphosate and cancer in laboratory animals” and inserted another statistical analysis that reversed the study’s original finding. Kelland reported the substitution reversed the monograph’s conclusion.

Wild defended the monograph process, writing:

…changes made to draft documents are the result of deliberation between Working Group members and for this reason are not attributable to any particular scientist. For all Monograph evaluations, drafts prepared over the months prior to a meeting form the basis of an open and detailed scientific debate during the eight-day meeting in Lyon and are modified by the working group as a result. The final Monograph evaluation represents the scientific consensus of the whole Working Group and does not have individually authored sections.

The US lawmakers also questioned Wild’s argument that Portier was not involved in the changes.

Emails demonstrate that Portier was involved with Working Group authors discussing the drafting of the glyphosate monograph. Additionally, Portier was active in developing responses to the European Food Safety Authority’s (EFSA) assessment on glyphosate, thus influencing the interpretation.

Committee members also contend that Portier “was the mastermind behind a letter” lobbying to reject the EFSA’s glyphosate findings. The letter was signed by scientists who worked on the glyphosate monograph.

“They’re exploiting outmoded, outdated science for a political agenda. People like (French President Emmanuel) Macron use politicized science to appease their left-wing supporters, said food policy writer Julie Kelly, who follows this issue closely.

Macron has vowed to ban glyphosate use in France within three years.

Last summer, California’s Office of Environmental Health Hazard Assessment added glyphosate to its list of carcinogenic agents based solely on IARC’s assessment.

‘Follow the money’

Tim Pastoor who is a consultant for the agricultural biotech and seed industry and a toxicologist retired from Syngenta, recently co-authored a paper that claimed that IARC’s methods for determining whether a substance is carcinogenic are hopelessly outdated, relying on systems developed in the 1960s and 1970s while ignoring decades of cancer research since that time.

“IARC has gone the way of the rotary phone,” Pastoor said. He said rather than consider the importance of dosage and exposure in determining whether a substance is carcinogenic, IARC labels them as either carcinogenic or not carcinogenic, leading to the agency placing eating red meat in the same category as smoking tobacco.Why would the agency cling to such an outmoded system?

“Follow the money. There’s a ton of money riding on plaintiff’s cases that are made more credible by IARC’s findings.”

Last spring, CNN reported that more than 800 cancer patients sued Monsanto, claiming glyphosate gave them cancer.

“If there’s no glyphosate monograph, there are no lawsuits,” said Kelly, the National Review contributor.

She suggested the committee’s next step could be to subpoena US citizens involved in the IARC’s glyphosate assessment, including Portier.

Although the congressional committee doesn’t have direct control over the budget, it could make a recommendation to the House Budget Committee to withhold funding for 2018.

Pastoor said he supports cutting funds to IARC. “My view is that $22 million is a lot of money to be going overseas if it’s going to outmoded, outdated methods of science evaluation.

He also suggested that science groups should get more involved:

It’s high time for scientists who care about how these changes are being made to step forward and speak their mind about how these decisions are being made. Small groups of very vocal people like Chris Portier are stealing the show and taking advantage of their positions to hijack the cancer evaluation process.

Joe Scott is a freelance agricultural writer. He was an editor with Patch.com and wrote for St. Louis Suburban Journals for 10 years, where he was, for a time, editor of the Warrenton Journal, where he wrote on agricultural among other topics. Twitter: @joescott44

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Free access to CRISPR gene editing? This startup wants to make it possible

CRISPR gene editing is widely regarded as one of the most significant advances in the life sciences in decades. The technology, which allows scientists to slice and dice bits of genetic code with the help of special CRISPR enzymes, has implications in everything from curing devastating diseases to making pigs less fatty to creating bigger, tastier, genetically modified tomatoes.

But existing CRISPR technologies are so red-hot that they’ve prompted an epic intellectual property showdown between the Broad Institute of MIT and Harvard University’s Feng Zhang and U.C. Berkeley’s Jennifer Doudna and her academic partner Emmanuelle Charpentier (and the warring factions’ various affiliated biotechs). Well, Inscripta, a startup backed by Venrock, wants to take the IP considerations out of the equation by providing a new kind of CRISPR enzyme to (most) scientists at no cost.

“We want to liberate the research. We want to make it unencumbered, free,” Inscripta CEO Kevin Ness tells Fortune. Inscripta has a different CRISPR enzyme from the Cas9 and Cpf1 varieties most commonly being experimented with today. Called “MAD7,” the enzyme is available for free to scientists innovating in the space.

Ness sees the democratic approach as key to further unlocking CRISPR’s potential. “You can’t build a house without a hammer,” he says.

Read full, original post: This Startup Wants to Democratize CRISPR Gene Editing By Making It Free

marsili family pain

Italian family’s inability to feel pain spurs research on relief for chronic sufferers

Chronic pain affects millions of people, who not only suffer but also risk becoming addicted to the opioid drugs used to treat it. A new report on six members of a three-generation Italian family who barely notice burns, bone breaks, and even red hot chili pepper extract rubbed into pricked skin, may pave the way to new painkillers — following clues from a single mutant gene.

The new report, published in the journal Brain, is from James Cox, PhD, senior lecturer in the Molecular Nociception Group at University College London (UCL) and colleagues. The featured family experiences very limited pain, unlike the famous case of a 10-year-old boy from Pakistan that I’ve included in every textbook edition I’ve written.

Cox and co-workers introduced the boy in a 2006 paper in Nature, “… a ten-year-old child, well known to the medical service after regularly performing ‘street theatre.’ He placed knives through his arms and walked on burning coals, but experienced no pain. He died before being seen on his fourteenth birthday, after jumping off a house roof.”

The title of that paper, “An SCN9A channelopathy causes congenital inability to experience pain,” tells the tale. The “disease of an ion channel” arises from abnormality of one of several types of proteins that form a channel in cell membranes that admits sodium ions. In the boy’s family, the mutant gene is SCN9A, and the encoded small protein, Nav1.7.

Sodium channel proteins control pain

At least ten genes encode sodium channel proteins, and mutations in them affect the sensation of pain. Mutations that hamper the functioning of the channels diminish pain, like in the Pakistani boy, whose body made too many endogenous opioids.pain 12 17 17 4

Mutations that rev up sodium channels do the opposite, causing “burning man syndrome” (erythermalgia) that makes putting on socks unbearable and “paroxysmal extreme pain disorder,” in which sodium channels stay open too long, causing excruciating pain in the rectum, jaw, and eyes.

The pain-free Pakistani boy and the almost-pain-free Italian family members have mutations in different protein parts of the sodium channels. Researchers from the University of Siena introduced the Italian Marsili family in 2008 in the journal Molecular Pain, which focused more on gene expression in white blood cells than on street performers like the Pakistani boy.

Cox picks up the story: “Around 2010, professor John Wood from UCL visited the Siena Pain School and met Letizia, a member of the family and also an associate professor at the university (and co-author of the 2008 paper) and learned more about her symptoms and those of the extended family. We took blood samples and began analyzing their DNA.” They sequenced exomes, the protein-encoding part of the genome.

The Marsilis barely noticed their oddity, just thinking something wasn’t quite right. A broken limb bone would cause a momentary startle, perhaps fleeting faintness, and then no pain. They could eat lots of red hot chili peppers with nary a flush. They didn’t notice burns until they looked at their skin. Yet their sense of smell was hyperacute, sometimes leading to vomiting in response to strong odors. And they didn’t sweat. Three other families are known to have what’s now called Marsili syndrome, and some of them have unwittingly bitten off fingers and lips.

The Marsili family consisted of a 78-year-old mother and two daughters — a 52-year-old with a 16-year-old daughter and a 50-year-old with 24- and 21-year-old sons. The mom, both daughters, and three grandchildren all experienced the dampened pain response. “Fortunately they haven’t suffered any serious injuries, apart from multiple bone fractures. This may be because they are not completely pain insensitive (unlike the SCN9A patients),” Cox said.

Poking and prodding in the lab

At the University of Siena, the researchers poked and prodded the Marsilis with pressure gauges on the sensitive area beneath the thumb, exposed their hands to superficial hot and cold, plunged their hands into ice water, and splayed sharp-tipped thingies called von Frey hairs across their inner forearms. Even capsaicin dripped into skin pricks didn’t make them shriek in pain, as most people would when so intimately exposed to chili pepper.

Yet the family members did feel pain not stemming from the body’s periphery: headache, backache, and labor pains. And they experienced deep pressure that would normally cause pain as pleasurable, like a massage.

Cox and his team zeroed in on a gene called ZFHX2 (zinc finger homeobox 2) behind the low pain sensitivity. A single DNA base change alters an arginine to a lysine, hampering the function of the sodium channel protein Nav1.9. Skin biopsies showed that the problem isn’t in the peripheral nerves, and gene expression studies led to the dorsal root ganglia (clustered nerve cell bodies) in the spinal cord. The nerve cells themselves are apparently undamaged — but their signaling appears compromised.

A cascade of gene activity

ZFHX2 encodes a giant protein that is a transcription factor – it controls suites of other genes. The mutation increases expression of six genes while decreasing expression of 16 others, several of them part of pain-signaling pathways and the sense of smell. And the fact that the affected part of the gene is exactly the same in DNA base sequence in a spectrum of species — chimps, dogs, cows, mice, rats, and frogs — indicates its importance.

In parallel to probing the pain-resistant people, the investigators bred mice that either lacked ZFHX2 (knockouts) or had two gene copies bearing the mutation sent in on a bacterial artificial chromosome, in addition to the animals’ own two functional copies (transgenics). Results with the knockouts were inconsistent, but the transgenic mice recapitulated some of the symptoms seen in the people the animals were sensitive to light touch, but didn’t seem to notice hits to their tails, withstood heat, and didn’t mind chili peppers. They also didn’t seem to enjoy massages as the people did. Dissecting spinal cords of the mice revealed the telltale altered gene expression in the dorsal root ganglia.

From mutation to drug discovery

The researchers call the study of the Italian family and others “a powerful route to identify novel analgesic drug targets,” perhaps by developing ways to selectively block sodium channels. “With more research to understand exactly how the mutation impacts pain sensitivity, and to see what other genes might be involved, we could identify novel targets for drug development,” said co-author Anna Maria Aloisi, MD, PhD, who was part of the team that initially identified the Marsili family’s condition and is co-author of the new paper.

But the route to a new analgesic isn’t straightforward, as Cox explained:

ZFHX2 encodes a transcription factor with enriched expression in damage-sensing neurons. Our focus is now to understand which are the critical genes that are dysregulated by the mutant transcription factor in relation to the pain insensitive phenotype. Some of the genes have known links to pain pathways, others are completely novel. In an ideal world, a single druggable downstream gene could be targeted as part of a drug development program, such as by a small molecule or gene therapy.”

Usually gene therapy introduces a functional copy of a gene to augment a disabled one, but in taking advantage of the pain-dampening mutation, gene therapy would actually deliver the mutant ZFHX2 gene into the spinal cord, which has already been done in some of the gene therapies I’ve written about. But the best vector, adeno-associated virus (AAV), isn’t big enough to accommodate the gargantuan ZFHX2 gene, a challenge also encountered in gene therapy to deliver the megagene dystrophin to treat muscular dystrophy. “One way around that would be to shorten the gene to see what bits we could lose and still retain function,” Cox told me.

With 10 percent of the world’s population more than 60 million people living with chronic pain, against the backdrop of minimizing prescription of opioids, a new approach to pain management is sorely needed. Perhaps the rare individuals with inherited diminished or absent pain sensations can help the many people suffering from chronic pain.

Ricki Lewis has a PhD in genetics and is a genetics counselor, science writer and author of The Forever Fix: Gene Therapy and the Boy Who Saved It, the only popular book about gene therapy . Follow her at her website or Twitter @rickilewis.

 

hemophilia

Hemophilia A gene therapy trial results: ‘This is huge’

British doctors say they have achieved “mind-blowing” results in an attempt to rid people of haemophilia A. Patients are born with a genetic defect that means they do not produce a protein needed to stop bleeding. Thirteen patients given the gene therapy at Barts Health NHS Trust are now off treatment with 11 producing near-normal levels of the protein. Jake Omer, 29 from Billericay, Essex, was on the trial and says he feels like he has a new body.

The therapy is a genetically engineered virus. It contains the instructions for factor VIII that Jake was born without. The virus is used like a postman to deliver the genetic instructions to the liver, which then starts producing factor VIII. In the first trials, low doses of gene therapy had no effect. Of the 13 patients given higher doses, all are off their haemophilia medication a year on and 11 are producing near-normal levels of factor VIII.

Prof John Pasi, who led the trials at Barts and Queen Mary University of London, said: “This is huge. “It’s ground-breaking because the option to think about normalising levels in patients with severe haemophilia is absolutely mind-blowing.

An analysis of the first nine patients on the trial was published in the New England Journal of Medicine.

Read full, original post: Haemophilia A trial results ‘mind-blowing’