Egypt islands deal with Saudis pits government against courts – The Times of Israel

CAIRO (AP) The past weeks tempestuous parliament approval of a deal transferring two Red Sea islands to Saudi Arabia is putting Egypts government at odds with the judiciary and providing the countrys battered opposition with a nationalist cause to whip up at a time of growing economic distress.

The surprise 2016 deal to hand over the islands of Tiran and Sanafir aimed to strengthen ties with Saudi Arabia, which has provided distressed Egypt with billions of dollars in grants and soft loans over the past four years. It comes amid fitful efforts to establish an axis of cooperation between two powers vying for leadership of the self-styled moderate Sunni Arab camp countries which oppose Shiite Iran and are willing to weigh closer ties to Israel.

But the opposition has proven a headache for President Abdel-Fattah el-Sissi, whose popularity seems to be slipping in the wake of economic liberalization reforms that deeply hurt Egyptians living standards, even while winning global praise. Sissis government has been gaining greater acceptance by other governments internationally, even while facing criticism over its authoritarian policies defended on security grounds that include jailing opponents and crushing rights groups.

With parliaments approval of the handover, the dispute over the islands now pits the legislative and executive branches of government against the judiciary. Courts issued two rulings over the past year that clearly stated the islands belong to Egypt.

In Egypts sometimes murky power structure, it is not clear where such a battle of wills could go.

The issue takes on added significance and sensitivity because Tiran controls the only shipping lane leading to the ports of Eilat and Aqaba, in Israel and Jordan respectively. The closure of the so called Tiran Strait was a main trigger of the 1967 Middle East war.

Egyptian President Abdel-Fattah el-Sissi, right, talks with Saudi King Salman after the king arrived in Sharm el-Sheikh, Egypt, March 28, 2015. (Provided by Egypts state news agency, MENA via AP,)

Saudi Arabias request for the islands and the absence of any official explanation from Cairo or Riyadh has prompted widespread speculation. One scenario says the islands afford the Saudis a say of some sort in renewed Israeli-Palestinian negotiations along with formal contacts with Israel. Another line of speculation says these contacts would contribute toward formulating a joint strategy against Shiite Iran, a nemesis to the Saudis and Israelis alike.

Heres a look at some of the issues related to the islands and how they are likely to evolve:

The maritime border demarcation agreement under which Egypt would transfer control of the islands to Saudi Arabia was signed and announced when Saudi King Salman was visiting Egypt in April 2016. The announcement came as the Saudis unveiled a multibillion-dollar package of soft loans and investments to Egypt, prompting charges the government was handing over the islands in return for Saudi money.

A court in June 2016 ruled to annul the transfer of the islands. When the government appealed, a higher court upheld the verdict in January and asserted that the islands were Egyptian. The higher court alluded to official documents, some dating back to Ottoman and British colonial times, showing Cairos exercise of full sovereignty over the islands over the years and offered a legal opinion that dismissed the agreement as unconstitutional.

The government, meanwhile, filed a case with the Supreme Constitutional Court, seeking a ruling on whether the two courts had jurisdiction over the case. That court starts hearings next month, but a panel of constitutional experts already filed a report saying the courts did indeed have jurisdiction. If thats the case, serious doubts would be cast on the legality of parliaments ratification of the deal.

That, in turn, would usher in a potentially damaging battle between the legislature and the judiciary. In any case, Sissi has to sign off on parliaments ratification before the agreement can go into effect. He has yet to do so, and there has been no word on whether he will await the Supreme Constitutional Courts ruling. He will have to tread carefully given the courts weight and the erosion of parliaments credibility over its handling of the agreement.

Dozens of lawyers shout slogans during a protest against the accord to hand over control of two strategic Red Sea islands, Tiran and Sanafir, to Saudi Arabia in front of the lawyers syndicate in Cairo, June 13, 2017. (AP/Amr Nabil)

The 596-seat legislature ratified the deal on June 14 after four days of at times vicious arguments. Lawmakers on each side threw around accusations of treason, payments by foreign powers and illegal amassing of wealth.

The disorder reinforced critics charges that parliament is just a tool for the government to carry out its agenda and that many of its members lack the political skills to effectively carry out their duties. The government denies parliament is a rubber stamp, pointing to the rare cases where it has blocked proposals.

Perhaps most egregiously, Speaker Ali Abdel-Al asserted that judicial rulings on the agreement amounted to nil, a position seen as contemptuous of the judiciary. But only a mass resignation by the around 100 lawmakers who oppose the agreement might embarrass the chamber enough to trigger calls for its dissolution. In the meantime, more than 100 lawmakers have urged Sissi not to sign off on parliaments ratification before the Supreme Constitutional Courts verdict, according to local media.

Activists raged over the issue on social media. But online calls for street protests achieved a meager response, likely a sign of how Egyptians have become fatigued by recent years instability, cowed by security crackdowns and consumed with economic privations.

Police arrested more than 100 activists and demonstrators over the weekend, of whom about half remain in custody, according to rights lawyers. There were a handful of small protests in Cairo on Friday, quickly broken up by security forces.

But future street action is possible.

If the government went ahead and handed over the islands to Saudi Arabia, we will consider them occupied and will work toward liberating them by all means available, said one opposition leader, Farid Zahran.

An opinion poll conducted by an Egypt-based pollster, Baseera, found that 47 percent of those questioned believed the islands were Egyptian, with only 11% saying they were Saudi. The poll, conducted June 11-12, asked 1,164 people. The margin of error was below 3%.

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Egypt islands deal with Saudis pits government against courts - The Times of Israel

Portland passes stricter rules for golf carts on Casco Bay islands – Press Herald

The Portland City Council on Monday passed more stringent rules for golf cart operators on Casco Bay Islands and opened additional mainland parking spaces for islanders two measures that generally received support from the handful of Peaks Island residents in attendance.

As Peaks has become more popular for tourists, islanders have raised safety concerns about golf cart traffic on their streets. They shared stories of drunken wedding guests speeding around the island and parents driving with children on their laps. Golf carts have been permitted on the islands for decades, but residents say accidents have resulted in property damage and even injury.

The new rules require all golf cart operators to have drivers licenses and prohibit anyone from standing in a moving golf cart or riding in the lap of a golf cart driver or passenger. While the changes were generally well received and passed unanimously, there was some concern they would be difficult to enforce. One resident suggested a moratorium on golf carts to phase them out of the islands, and another asked the police department to be more proactive in penalizing rule breakers.

With these changes I think comes a responsibility of the police department that they are able to make sure that we are as much as possible in compliance, Peaks Island resident Timmi Sellers said. If these new rules go on the book, take steps to enforce it.

Under the previous ordinance, golf cart operators are required to be over age 21 or have a valid license. The new version does not include an age restriction, but all operators must be licensed. It also stipulates that headlights must shine 200 feet ahead of golf carts in order to operate at night, and the carts must have added reflectors.

All golf carts on Peaks, Cliff and Great Diamond islands are already required to be registered with the city and display a sticker, and records show 255 registered golf carts on all three islands. However, residents say many carts are unregistered. Golf carts also are already required to have horns, safety flags and slow vehicle markings, but many do not.

Two companies now lease golf carts for hourly or long-term rentals on Peaks, and representatives from both businesses spoke at Mondays City Council meeting. Both noted their businesses generally follow the requirements of the updated ordinance already, and they said carts from private properties are more often the sources of the islands problems.

When we rent a golf cart, we spend anywhere from five to 10 minutes explaining how the golf cart works, going through all the safety and making folks understand that they have legal requirements, said Mike Sylvester, owner of Mikes Carts. We chase a lot of folks who arent in our carts off the road because it gives a bad name to all of us.

The speed limit for golf carts will increase from 10 mph to 20 mph to conform with the posted speed limit on island roads. The speed limit near the island school would be 15 mph. Few golf carts have speedometers, however, so it is unclear how operators could follow the speed limit.

Robert OBrien, manager of Peaks Island Golf Carts, said golf carts typically cant drive as fast as 20 mph, and he worried the increase might encourage others on the road to speed.

Everyone out there is thinking, we can go faster now, OBrien said.

Lisa Penalver, chairwoman of the Peaks Island Council, credited the golf cart rental companies for educating their customers on safe practices, but said an update was still needed for all operators.

We need to have guidelines, even if we cant always enforce them, Penalver said.

The City Council also asked the Sustainability and Transportation Committee to study the issue of parking for islanders on the mainland near the ferry. In the meantime, the City Council on Monday opened 30 spots on Fore Street as a short-term solution.

Island residents have said competition is fierce for only 55 designated spaces on the mainland near the Ocean Gateway terminal, and they want more spots to be designated for their use.

We have to be mindful of this need of islanders to get to and from their residences and their appointments and their workplaces, City Councilor Belinda Ray said.

Megan Doyle can be contacted at 791-6327 or at:

[emailprotected]

Twitter: megan_e_doyle

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Portland passes stricter rules for golf carts on Casco Bay islands - Press Herald

Merkel: Brexit-Bound Britain Might Copy EU’s Low Tax Islands – New York Times

HAMBURG, Germany German Chancellor Angela Merkel said on Monday that Britain might end up following the example of other islands in the European Union with low tax rates when it quits the bloc.

Merkel, who said it was already hard to organise fair tax competition in Europe, also announced plans for a Franco-German corporation tax reform.

Speaking to non-governmental organisations in Hamburg before she hosts a G20 summit there next month, Merkel said: "I don't want to pillory anyone but the island states of Ireland, Malta and Cyprus say: we have a bad geographical location, we're at such a disadvantage, we can only attract companies by having very low taxes."

She added: "And when, within the context of Brexit, Britain one day decides to step into this tax competition too, then of course that would be a huge challenge for countries."

Germany and France will therefore attempt a joint corporation tax reform via a common tax assessment framework "so that at least two countries can be a role model", she said, adding that this could also be a blueprint for a global tax system.

The G20 summit is due to take place in Hamburg in early July. On July 13 the governments of Germany and France will meet in Paris for the Franco-German Council of Ministers, where they want to make proposals for closer cooperation in areas such as tax.

In a manifesto document ahead of a June 8 election, Britain's Conservatives - who emerged as the largest party but lost their parliamentary majority - said corporation tax would be cut to 17 percent by 2020.

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Merkel: Brexit-Bound Britain Might Copy EU's Low Tax Islands - New York Times

Japanese Visitors’ Flight To Disputed Russian-Held Islands … – RadioFreeEurope/RadioLiberty

A flight scheduled to take former Japanese residents to two Russian-held islands in the Pacific Ocean has been canceled because of heavy fog conditions on one of the islands, Japanese Foreign Ministry officials say.

The ministry press service on June 19 said, "The flight has been canceled due to bad weather. We are now considering the possibility to arrange a new flight."

The visit was set to begin on June 18 to the disputed islands, which Tokyo calls the Northern Territories and Moscow calls the Southern Kuriles.

It would have marked the first time Japanese citizens were allowed to travel by air to the island chain. Previous Japanese visitors were forced to travel by ship under a complicated procedure.

The flight with 70 people aboard by Russian airline Aurora was delayed on June 18 and June 19 because of heavy fog at the Mendeleyevo airport on Kunashir Island in the chain.

The visitors were going to "pay respects" to the graves of family members, officials said.

Although Russian-held, Japan still claims the islands, which the Soviet Union seized in the closing days of World War II.

Lingering tensions over the islands have prevented Japan and Russia from signing a peace treaty to formally end the war.

In April, Russian President Vladimir Putin said he had agreed with Japanese Prime Minister Shinzo Abe to start flights for former Japanese residents to "visit graves of ancestors" on the islands.

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Japanese Visitors' Flight To Disputed Russian-Held Islands ... - RadioFreeEurope/RadioLiberty

New ferry Salish Eagle starts service Wednesday in Gulf Islands – Times Colonist

The Salish Eagle, the second of three new vessels joining the B.C. Ferries fleet this year, begins service Wednesday with a 9:10 a.m. sailing on the Tsawwassen-Southern Gulf Islands route.

The Salish Orca was the first of the trio in service, starting in May on the Powell River-Comox route. The Salish Raven arrived in Victoria on June 7 and is due to start service in the fall, also in the Southern Gulf Islands.

All three ferries are 107 metres long and can carry 145 vehicles and 600 passengers. They were built in Poland at an overall cost of $200 million and are all duel-fuel able to run on natural gas or ultra-low sulphur marine diesel.

B.C. Ferries plans to run all three on natural gas, which it says means a reduction of 9,000 metric tonnes of carbon dioxide emissions annually, compared with running the vessels on marine diesel the same as taking 1,900 passenger vehicles off the road per year.

The new ferries were named to honour the Coast Salish people and each has been adorned with First Nations art.

The arrival of the Salish-class vessels means the Queen of Burnaby and Queen of Nanaimo are being retired, while the Bowen Queen will be taken out of regular service and used as a utility vessel.

Times Colonist

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New ferry Salish Eagle starts service Wednesday in Gulf Islands - Times Colonist

Genetics Might Be Settling The Aryan Migration Debate, But Not How Left-Liberals Believe – Swarajya

Writing in The Hindu, Tony Joseph has claimed that genetics has very sure-footedly resolved the debate about whether there was a migration of Indo-European people (Aryans) into the subcontinent around 2000-1500 BCE apparently, the unambiguous answer is yes. To anyone with a nodding acquaintance with the literature in the area, such an assertion is unfounded. Given the sheer importance of this topic to Indian history, it is necessary to challenge Josephs one-sided presentation of facts. There also seems to be much that is questionable in his very approach, and this deserves scrutiny.

Conclusions decided upon in advance?

Ironically, after saying that the dominant narrative so far that genetics had disproved Aryan immigration had not been nuanced, he abandons nuance himself.

Noting the clear slant in his article, and his quoting of Razib Khan, who was sacked as a columnist by the New York Times apparently for racist views, I got in touch with Dr Gyaneshwer Chaubey, senior scientist at the Estonian Biocentre, Tartu, and a widely-published scholar in the area. Indeed, Chaubey is a co-author with Peter Underhill (whom Joseph quotes) of the 2015 study on the R1a haplogroup that Joseph cites in his article.

To my surprise, it turned out that that Joseph had contacted Chaubey and sought his opinion for his article. Chaubey further told me he was shocked by the drift of the article that appeared eventually, and was extremely disappointed at the spin Joseph had placed on his work, and that his opinions seemed to have been selectively omitted by Joseph a fact he let Joseph know immediately after the article was published, but to no avail.

Having known Chaubeys views for some time now especially that the origin of the R1a is far from settled I was not surprised to hear this. This in itself gives the lie to Josephs claims of the unambiguous conclusions of genetics about the hypothetical Aryan immigration.

Mitochondrial DNA vs Y-chromosomal DNA

Joseph claims that we only had mitochondrial (mt-) DNA (which is inherited from the mother) analysis till recently, which failed to capture the fact that it may have been mostly Aryan males who migrated first to the subcontinent and intermarried with the native women. This, apparently, has been conclusively established by a recent avalanche of Y-chromosomal DNA (which is inherited exclusively by sons from their fathers) data, which shows a Bronze Age gene flow into the subcontinent. This remark seems to suggest an embarrassing lack of familiarity with the literature.

Also, does Joseph seriously imagine geneticists would not have envisaged the possibility of males spearheading a migration all along? The first suggestion that Y-chromosomal DNA analysis may be making a case for Indo-European immigration, and the proposal that the R1a haplogroup (M17) may be a marker for this migration, was made as early as 2001.

This was subsequently contradicted in 2006 in a seminal Y-chromosomal DNA study by a group that included Richard Villems, Toomas Kivisild and Mait Metspalu, also of the Estonian Biocentre, and among the leading authorities in this area (Kivisild has since moved to Cambridge, but Villems and Metspalu are Chaubeys current colleagues at Tartu). Villems and Kivisild were, in fact, co-authors in the 2001 paper I just mentioned, but revised their view about a migration after a fresh analysis of more extensive data.

This paper, concluded, It is not necessary, based on the current evidence, to look beyond South Asia for the origins of the paternal heritage of the majority of Indians at the time of the onset of settled agriculture. The perennial concept of people, language, and agriculture arriving to India together through the northwest corridor does not hold up to close scrutiny. Recent claims for a linkage of haplogroups J2, L, R1a, and R2 with a contemporaneous origin for the majority of the Indian castes paternal lineages from outside the subcontinent are rejected...

The dominant narrative that Joseph talks about actually stems from this study, and Im not sure he is qualified to dismiss it as a bit of a stretch. This study, which has never really been contradicted, is, in fact, published in a much more respected journal than BMC Evolutionary Biology from where Joseph cites Martin Richards paper. This is significant, as good studies in this area have generally found a place in highly-ranked journals, even if they have arrived at diverging conclusions.

Indeed, this itself would suggest there are very eminent geneticists who do not regard it as settled that the R1a may have entered the subcontinent from outside. Chaubey himself is one such, and is not very pleased that Joseph has not accurately presented the divergent views of scholars on the question, choosing, instead to present it as done and dusted.

The R1a haplogroup

There are some inherent issues in regarding the R1a as a marker for any hypothetical Indo-European migration.

Firstly, Iranian populations, who are also speakers of the Indo-Iranian family of languages like most North Indians, have very little R1a. Also, tribal groups like the Chenchus of Andhra Pradesh and the Saharias of Madhya Pradesh show anomalously high proportions of R1a. The Chenchus speak a Dravidian language, and the Saharias an Austro-Asiatic one (though they have recently adopted Indo-European languages).

They are hunter-gatherer peoples who remained stunningly isolated without admixing much with other population groups, and consequently, their lifestyles have remained startlingly unchanged for millennia, as they would have been before the start of settled agriculture.

The best that studies which argued that the R1a could be used as a marker for the hypothetical Indo-European migration could do was to simply ignore these groups as aberrations. But is that very convincing? Note that it is possible no, almost certainly the case there were many tribal communities with high proportions of R1a that, unlike the Chenchus and Saharias, were assimilated into the caste matrix over the millennia. So how correct is it to link the R1a with an Indo-European migration?

Significantly, Richards et al acknowledge Chaubeys critical advice with their manuscript. That seems like a euphemism for saying that Chaubey (and, by extension, the Tartu school) had reservations about their conclusions, which is probably why he is not a co-author. So what should one make of Josephs claim that geneticists have converged on an answer?

If Underhill expressly stated to Joseph that he has now reversed his published position that there has been no significant genetic influx to Asia from Europe, indeed specifically that he is now convinced the R1a entered the subcontinent from outside, Joseph bafflingly does not reproduce this statement in his article.

The statement Joseph actually quotes merely points out that we have better data now, but that is not the same thing. Joseph also cites his 2015 paper, in which Chaubey is a co-author, but this paper actually underscores the limits of current technology, and says their data is too preliminary to jump to conclusions about migrations and culture shifts.

The genetic data at present resolution shows that the R1a branch present in India is a cousin clade of branches present in Europe, Central Asia, Middle East and the Caucasus; it had a common ancestry with these regions which is more than 6000 years old, but to argue that the Indian R1a branch has resulted from a migration from Central Asia, it should be derived from the Central Asian branch, which is not the case, as Chaubey pointed out.

In other words, contrary to what Joseph claims, as the Y-chromosomal DNA data stands today, there is no support for a recent migration into the subcontinent.

Ancestral North Indians (ANI) and Ancestral South Indians (ASI)

Joseph continues to tilt at windmills when talking about the ANI / ASI construct of David Reich et al., who used analysis autosomal DNA, which is different from mt- and Y-chromosomal DNA.

Joseph writes, ...this theoretical structure was stretched beyond reason and was used to argue that these two groups came to India tens of thousands of years ago, long before the migration of Indo-European language speakers that is supposed to have happened only about 4,000 to 3,500 years ago.

One doesnt know what to make of this. It was geneticists including Lalji Singh and K Thangaraj who were Reichs co-authors in the paper which proposed the ANI/ASI construct who argued that the ANI and ASI are considerably more than 12,500 years old, and not the result of any recent migration.

He then goes on to quote David Reich arguing in favour of a migration from the Steppe around 2500 BCE. Once again, Joseph presents this view as the last word on the subject, although not all geneticists agree.

For instance, Partha Majumdar and co-workers have very recently come up with quite different conclusions in the journal, Human Genetics: In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages (emphasis mine).

The Evidence From Archaeology

Since Joseph believed he was shocking those who believed genetic analysis had disproved Aryan immigration theories, I shall return the favour.

Hypotheses of migrations of Bronze Age populations into the subcontinent fall afoul of archaeological evidence. Paradoxically, as I have described earlier, bronze itself goes missing from the archaeological record for several centuries that are supposed to correspond to the settling of the Bronze Age Indo-Europeans into the subcontinent. As one of the foremost authorities in the archaeology of the Indus Valley Civilisation, Professor Jonathan Mark Kenoyer of the University of Wisconsin points out, this actually reflects a prolonged lack of contact of the subcontinent with the regions the Aryans are supposed to have entered from.

Also, geological evidence shows that the Ghaggar-Hakra river, along whose channels numerous Harappan sites have been discovered, was the River Saraswati described in the Vedas and other ancient literature; indeed, the team of geologists led by Peter D Clift which carried out the geological studies asserted that the descriptions of the Saraswati in those texts was remarkably accurate, as I wrote in an earlier article.

Such findings negate the Aryan immigration model, establish the overlap (if not identity) of the Indus Valley and Vedic cultures, and push back the dates for the composition of the Vedic and other literature considerably.

Agriculture In Subcontinent Indigenous, Autochthonous

There is clear evidence of continuous inhabitation of the Gangetic plain from the Pleistocene. It is also abundantly clear that agriculture was developed indigenously, autochthonously, based on exploiting local resources, at multiple centres on the subcontinent the Saraswati-Indus region, the Gangetic plain, Eastern, Central and Peninsular India in a natural progression from a hunting-gathering lifestyle to a sedentary one, with no external stimulus, but with strong interaction between various regions of the subcontinent themselves right from the earliest Neolithic.

The myth that the founding of agriculture, whether in the Indus Valley or elsewhere in the subcontinent, is owed to migrations from West Asia (the so-called Fertile Crescent) is not supported by archaeological evidence.

Based on current evidence, whether genetic or archaeological, Josephs conclusion that, ...we are a multi-source civilization, not a single-source one, drawing its cultural impulses, its tradition and practices from a variety of lineages and migration histories, is quite simply totally wrong.

One cannot impressed by Josephs quoting of a blogger with a very questionable history like Razib Khan, while selectively omitting the comments of a known scholar in the area like Dr Gyaneshwer Chaubey after having sought them himself.

Can one be sure he has not interviewed other scholars, but left out their views from his article as they didnt suit his pre-determined agenda or just didnt interview scholars he felt held such views?

Joseph and others like him are welcome to write on any topic they please, and are even free to take sides in line with their prejudices. Indeed, all he has done is to paint a very recent paper in a not particularly highly-ranked journal as the final word in the debate, while coolly ignoring well-regarded studies which arrive at differing conclusions in significantly higher-ranked journals.

All one asks is, when writing on a much-debated topic like this one, they should at least show the intellectual sincerity to mention divergent points of view, and not try to create a false impression for the lay reader that they have been conclusively addressed. That is neither very honest nor commendable.

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Genetics Might Be Settling The Aryan Migration Debate, But Not How Left-Liberals Believe - Swarajya

CRISPR/Cas9 gene editing reverses Huntington’s in mouse model – Medical Xpress

June 19, 2017 Mutant huntingtin protein aggregates, seen as darkened nuclei, disappear after gene editing vectors are injected into mouse brain. Credit: Journal of Clinical Investigation

Disrupting a problematic gene in brain cells can reverse Huntington's disease pathology and motor symptoms in a mouse model of the inherited neurological disorder, scientists report.

The researchers used CRISPR/Cas9 gene editing, delivered by a viral vector, to snip part of a gene producing toxic protein aggregates in the brains of 9-month old mice. Weeks later, where the vector was applied, aggregated proteins had almost disappeared. In addition, the motor abilities of the mice had improved, although not to the level of control mice.

The results are scheduled for publication on June 18, 2017 in Journal of Clinical Investigation.

The findings open up an avenue for treating Huntington's as well as other inherited neurodegenerative diseases, although more testing of safety and long-term effects are needed, says senior author Xiao-Jiang Li, MD, PhD, distinguished professor of human genetics at Emory University School of Medicine.

Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin or mHTT) that causes brain cells to die. Symptoms commonly appear in mid-life and include uncontrolled movements, balance problems, mood swings and cognitive decline.

Touted widely for its potential, CRISPR/Cas9 gene editing has not been used to treat any neurodegenerative disease in humans. Several concerns need to be addressed before its use, such as effective delivery and the safety of tinkering with DNA in brain cells. A similar gene editing approach in mice, but using a different technology (zinc finger nucleases), was reported for Huntington's disease in 2012.

The mice used in this study have a human mutant huntingtin gene replacing one of the mouse huntingtin genes. In these mice, motor problems and aggregated mutant huntingtin can be observed around the age of 9 months.

When planning gene editing, the scientists selected guide sequences that targeted both the normal copy and the disease-driving copy of the huntingtin gene. This "non-allele specific" approach would not need to be customized to the patient's genome, unlike other gene editing proposals for Huntington's disease.

The Emory researchers have previously shown that mice older than four months do not need the huntingtin gene to stay healthy, suggesting that treatment strategies that aim to shut off both copies of the gene in adult humans could be safe.

Clinical studies have begun of such treatments, which probably will require continuous administration of the gene-silencing drug. In contrast, a gene editing treatment could be more durable, if it hits enough cells.

To get CRISPR/Cas9-guided enzymes into brain cells, the researchers harnessed a widely used gene therapy vehicle based on AAV (adeno-associated virus). The scientists injected viral vectors carrying CRISPR/Cas9 into the striatum region of the brains of Huntington's disease model mice at the age of 9 months. The striatum is a region of the brain that controls body movement and motor function.

This led to a "dramatic decrease" in aggregated mutant huntingtin in the striatum three weeks later. The study reveals the capacity of brain cells to heal themselves if the genetic source of the toxic proteins is removed, the scientists say.

In comparison with control Huntington's mice, CRISPR/Cas9-injected mice showed significant improvements on tests of motor control, balance and grip strength, although they did not recover to the point where they performed as well as control mice.

Addressing genetic safety concerns, the researchers showed that in brain cells, frameshift mutations triggered by CRISPR/Cas9 occurred predominantly within the huntingtin gene and not in other potential off-target genes.

However, the long-term effects and safety of injecting AAV in the brain to express CRISPR/Cas9 remain to be rigorously tested before applying this approach to patients, Li says.

The co-first authors of the paper are postdoctoral fellows Su Yang, PhD at Emory University and Renbao Chang, PhD at Institute of Genetics and Developmental Biology, Chinese Academy of Sciences.

Emory co-authors include Zhaohui Qin, PhD, associate professor of biostatistics, Peng Jin, PhD, professor of human genetics, and Shihua Li. MD, professor of human genetics. Xiao-Jiang Li also is affiliated with the Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University.

The research was supported by the National Institute of Neurological Disorders and Stroke (NS036232, NS101701, NS095279) and the National Natural Science Foundation of China (grant 91332206).

Explore further: Huntington's disease gene dispensable in adult mice

More information: Su Yang et al, CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington?s disease, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI92087

Disrupting a problematic gene in brain cells can reverse Huntington's disease pathology and motor symptoms in a mouse model of the inherited neurological disorder, scientists report.

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Democrats Tie Up The Senate To Protest GOP Health Care Push – NPR

Senate Minority Leader Chuck Schumer of N.Y. speaks to reporters on Capitol Hill. J. Scott Applewhite/AP hide caption

Senate Minority Leader Chuck Schumer of N.Y. speaks to reporters on Capitol Hill.

The Republican effort to overhaul the Affordable Care Act, or Obamacare, has led to a standoff in the Senate.

Senate Democrats on Monday night began using parliamentary maneuvers to slow Senate business as part of a coordinated protest against the GOP push to pass an Obamacare replacement bill. A small group of Republican senators has been working in private for weeks, shielding from public view the bill and the negotiations surrounding it.

In a show of frustration with what they deem the GOP's "shameful" and "secret" legislative process, Democrats on Monday also held the Senate floor with a series of back-to-back speeches.

"If Republicans are not going to allow debate on their bill on the floor or in committee, Democrats will make opportunities to debate," said Senate Minority Leader Chuck Schumer, speaking Monday on the Senate floor. "And these are merely the first steps we're prepared to take in order to shine a light on the shameful Trumpcare bill and reveal to the public the GOP's backroom deal-making."

Liberal activists cheered on social media as Schumer forced McConnell to object to a motion to hold public hearings on the health care bill, and then pressed the Republican leader to commit to 10 hours of open debate.

Senate Democrats, in taking action Monday, are inserting themselves into a process that has excluded them by design. Democratic lawmakers are also responding to growing pressure from progressive activists who have been calling for more aggressive opposition. Members of the Democratic base have expressed concern that Republicans are moving forward with their health care bill while attention has been focused elsewhere namely on the Russia investigations.

Some Republicans are also out of the loop

It's not just Democrats who have been left out of the health care deliberations. Many Republican senators have seen little more than an outline and a Power Point summary of the Senate health care legislation that is being drafted.

"It's not unusual, especially for a big bill like this. It's okay that the drafting is happening behind closed doors," Tommy Binion, a congressional liaison at the conservative Heritage Foundation, told NPR's Morning Edition.

While GOP senators aren't objecting to the process as vehemently as Democrats, a number of Republicans, including Sen. Marco Rubio, R-Fla., say the health care legislation should eventually be subject to open debate.

"If it's an effort to rush it from a small group of people straight to the floor on an up or down vote, it'll be a problem," Rubio said Sunday on CNN's State of the Union.

McConnell: "Nobody is hiding the ball here"

The Republican health care bill could be voted on as early as next week ahead of the July 4th recess without any committee hearings or public input. For his part, Senate Majority Leader Mitch McConnell is defending the closed health care talks.

"Nobody is hiding the ball here," McConnell, R-Ky., told reporters last week. "There have been gazillions of hearings on this subject when [Democrats] were in the majority, when we were in the majority. We understand the issue very well and we are now coming up with a solution."

Republicans contend the secret Senate negotiations give them time and space free from scrutiny to hash out the significant and serious differences among themselves over contentious issues, such as phasing out Medicaid expansion and determining the plan's coverage requirements.

Democrats say the closed talks are a tacit acknowledgment by Republicans that their efforts are unpopular.

"There's only one reason why Republicans are doing this: They're ashamed of their bill," said Schumer on Monday. "The Republicans are writing their health care bill under the cover of darkness because they're ashamed of it, plain and simple."

While the Senate is crafting its own legislation, the House-passed American Health Care Act is viewed unfavorably by a majority of Americans 55 percent compared with 31 percent who viewed it favorably, according to a Kaiser Family Foundation poll released in May.

What's more, the Congressional Budget Office estimated that the House health care bill would result in 23 million fewer people with insurance in a decade, and it would leave many sicker and older Americans with much higher costs.

Republicans eager to move on from health care

Still, Senate Republicans badly want to take up other priorities such as overhauling the country's tax code.

"We've been debating Obamacare's failures and what to do about them for so many years now," McConnell said Monday on the Senate floor. "Members are very, very familiar with this issue. Thankfully, at the end of this process, the Senate will finally have a chance to turn the page on this failed law."

Any legislation the Senate passes would head back to the House for consideration before President Trump can sign it into law.

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Democrats Tie Up The Senate To Protest GOP Health Care Push - NPR

How Did Health Care Get to Be Such a Mess? – New York Times

This contrasts with current examples of such financing arrangements. Where physicians earn a preset salary for example, in Kaiser Permanente plans or in the British National Health Service patients frequently complain about rationed or delayed care. When physicians are paid on a fee-for-service basis, for every service or procedure they provide as they are under the insurance company model then care is oversupplied. In these systems, costs escalate quickly.

Unfortunately, the leaders of the American Medical Association saw early health care models union welfare funds, prepaid physician groups as a threat. A.M.A. members sat on state licensing boards, so they could revoke the licenses of physicians who joined these alternative plans. A.M.A. officials likewise saw to it that recalcitrant physicians had their hospital admitting privileges rescinded.

The A.M.A. was also busy working to prevent government intervention in the medical field. Persistent federal efforts to reform health care began during the 1930s. After World War II, President Harry Truman proposed a universal health care system, and archival evidence suggests that policy makers hoped to build the program around prepaid physician groups.

A.M.A. officials decided that the best way to keep the government out of their industry was to design a private sector model: the insurance company model.

In this system, insurance companies would pay physicians using fee-for-service compensation. Insurers would pay for services even though they lacked the ability to control their supply. Moreover, the A.M.A. forbade insurers from supervising physician work and from financing multispecialty practices, which they feared might develop into medical corporations.

With the insurance company model, the A.M.A. could fight off Trumans plan for universal care and, over the next decade, oppose more moderate reforms offered during the Eisenhower years.

Through each legislative battle, physicians and their new allies, insurers, argued that federal health care funding was unnecessary because they were expanding insurance coverage. Indeed, because of the perceived threat of reform, insurers weathered rapidly rising medical costs and unfavorable financial conditions to expand coverage from about a quarter of the population in 1945 to about 80 percent in 1965.

But private interests failed to cover a sufficient number of the elderly. Consequently, Congress stepped in to create Medicare in 1965. The private health care sector had far more capacity to manage a large, complex program than did the government, so Medicare was designed around the insurance company model. Insurers, moreover, were tasked with helping administer the program, acting as intermediaries between the government and service providers.

With Medicare, the demand for health services increased and medical costs became a national crisis. To constrain rising prices, insurers gradually introduced cost containment procedures and incrementally claimed supervisory authority over doctors. Soon they were reviewing their medical work, standardizing treatment blueprints tied to reimbursements and shaping the practice of medicine.

Its easy to see the challenge of real reform: To actually bring down costs, legislators must roll back regulations to allow market innovation outside the insurance company model.

In some places, doctors are already trying their hand at practices similar to prepaid physician groups, as in concierge medicine experiments like the Atlas MD plan, a physician cooperative in Wichita, Kan. These plans must be able to skirt state insurance regulations and other laws, such as those prohibiting physicians from owning their own diagnostic facilities.

Both Democrats and Republicans could learn from this lost history of health care innovation.

Christy Ford Chapin is an associate professor of history at the University of Maryland, Baltimore County, a visiting scholar at Johns Hopkins University and the author of Ensuring Americas Health: The Public Creation of the Corporate Health Care System.

Follow The New York Times Opinion section on Facebook and Twitter (@NYTopinion), and sign up for the Opinion Today newsletter.

A version of this op-ed appears in print on June 19, 2017, on Page A19 of the New York edition with the headline: How Health Care Went Wrong.

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How Did Health Care Get to Be Such a Mess? - New York Times

Karen Handel doesn’t want to talk about health care – ThinkProgress

Republican candidate Karen Handel talks to supporters in Marietta, Georgia. CREDIT: KiraLerner

MARIETTA, GEORGIAWith one day until the much anticipated special election in Georgias sixth district, the Republican Party is secretly working on its landmark health care bill that will reshape the future of health insurance in the United States. But Republican candidate Karen Handel would prefer not to talk about it.

In an interview with Breitbart News on Monday, Handel claimed that voters in the Atlanta suburbs do not care about health insurance.

It hasnt been that much of an issue on the ground, she said. For voters in the sixth district, the biggest issue is that Jon Ossoff is from outside the district.

A recent Atlanta Journal Constitution poll found that more than 80 percent of likely voters in Georgias sixth district said health care is an extremely important or very important issue, and just one in four said they approve of the plan Republicans rammed through the House last month.

Handel has said she would have voted for that plan, but she and other GOP leaders are not eager to discuss their support. At a campaign stop in Johns Creek, Georgia Monday morning, Handel avoided talking to reporters altogether. Meanwhile, House Majority Leader Kevin McCarthy (R-CA), who was campaigning for the former Georgia secretary of state, quickly rushed away from the event and into his car when ThinkProgress tried to ask him about the massively unpopular Affordable Health Care Act.

McCarthy said he would discuss the bill at Handels next event, but he did not attend.

When Handel finally addressed health care at a lunchtime campaign stop in Marietta, Georgia, she said she is confident the Senate GOP will provide the American people with transparency before they push for a vote on their Obamacare replacement.

What I know is that the Senate will have transparency as they go forward, she told ThinkProgress.

Senate Republicans have said they will try to hold a vote on the bill before the July 4 recess, leaving little time to read the bill, much less for meaningful discussion or debate.

The CBO issued a report last month on the Houses version of the bill, finding that it would leave roughly 23 million people without health insurance. In the weeks since, popular opinion about the legislation has plummeted, making it the most unpopular major law in recent decades.

Senate Republicans have been attempting to hide from both the press and the public to avoid discussing their proposal. One Senate Republican aide said last week that the decision to release their version of the bill at the last minute is an intentional move to avoid scrutiny.

On Monday, Handel seemed to adopt the same strategy. Speaking to reporters briefly about the issue, she acknowledged that the House bill is not perfect, but still said she would have supported it if she were in Congress.

Ive been very clear from the start that the House bill was not perfect, but in order for us to move forward, we needed to have a bill on the table to begin to work with, she told ThinkProgress.

She continued by citing the common Republican talking point that Obamacare is failing and that the GOP needs to do whatever it takes to push through their own bill.

I know people talk about, what if the exchanges collapse, she said. Well folks, Obamacare is collapsing. I know because my husband and I get our insurance off of the exchanges and our premiums have gone from about $350 a month to $1200 a month. So the status quo was unacceptable.

Handel also talked specifically about reductions to Medicaidthe House version of the AHCA would cut $834 billion from Medicaid over the next decade.

What I support is moving Medicaid to block grants so that the states can drive that process, she said. I have much greater faith in the governor and the state legislature to craft a Medicaid system that is going to be the best fit for the people of Georgia, rather than someone in Washington dictating it.

A number of Democrats in the sixth district told ThinkProgress this week that its unacceptable that the Senate GOP is working in secret to draft such an important bill. But Handel supporters said Monday they are not concerned.

Jamshaid Bhatti, a 28-year-old Marietta resident, said he trusts Republicans and Trump to come up with a solution to decrease health care costs. He said he thinks working in secrecy will help the GOP accomplish its goals.

Thats a pretty good move because we want them to be surprised, he said about Senate Democrats. I do trust my representation.

And Carrie Almond, the president of the National Federation of Republican Women who came to the sixth district from Alexandria, Virginia to support Handel, said GOP leaders know what theyre doing.

I dont really think its a secret process when you have a task force that you put together, she said. They need time to put things together and Im sure when theyre ready, theyll let us all know what theyve put together.

Theyve spent a lot of time working on it in the past and I think theyre going to reveal it at the right time, she added. There will be appropriate due diligence.

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Karen Handel doesn't want to talk about health care - ThinkProgress

How worried are you about losing health care? – Sacramento Bee


Sacramento Bee
How worried are you about losing health care?
Sacramento Bee
Californians have a message for Republican-controlled Washington as the U.S. Senate continues work to overhaul the health care system: We like what we've got. A new statewide poll found that Golden State supporters of the Affordable Care Act, also ...
New study says House GOP healthcare bill would lead to the loss of almost 1 million jobs in 10 yearsBusiness Insider
Our senators must think before voting on health careSavannah Morning News
Where Health-Care Legislation StandsWall Street Journal (subscription)
Vox -Southern Poverty Law Center
all 78 news articles »

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How worried are you about losing health care? - Sacramento Bee

MacArthur’s health-care role fires up challenger – Cherry Hill Courier Post

Michael Catalini, Associated Press 2:04 p.m. ET June 19, 2017

Congressman Tom MacArthur (R-NJ) fields questions from angry voters for nearly five hours during a town hall meeting Wednesday, May 10, 2017 in Willingboro. MacArthur played a major role in reviving the new GOP healthcare bill. Produced by Joe Lamberti

Congressman Tom MacArthur (R-NJ) addresses constituents and concerned citizens of New Jersey in a town hall meeting Wednesday, May 10, 2017 in Willingboro.(Photo: Joe Lamberti/Courier-Post)Buy Photo

TRENTON

A former Obama administration national security aide is challenging the New Jersey Republican congressman who helped revive President Donald Trumps health care overhaul.

Andy Kim, 34, of Marlton, told The Associated Press on Monday that he is launching a 2018 bid for New Jerseys 3rd District House seat against incumbent Rep. Tom MacArthur.

Kim said he is running because of MacArthurs push for an amendment that would allow states to get federal waivers from the requirement that insurers charge healthy and sick customers the same premiums. The change would be for people who let their coverage lapse, but MacArthur says those people would be covered by high-risk pools.

More: MacArthur quits post in GOP group over health care bill

More: MacArthur hauls in big cash at Trump fundraiser

Im running because Im concerned about the direction of our country, Kim said. That legislation is something that is going to endanger tens of thousands in the Jersey 3rd and millions of people in the country.

The Congressional Budget Office estimated the House bill would leave 23 million fewer people with insurance by 2026.

The House passed the measure aimed at replacing the Affordable Health Care Act in May, and Trump celebrated with an event at the White House. The Senate is working on a related measure.

Kims entrance into the race comes after Trump hosted a fundraiser for MacArthur at his Bedminster golf club that raised about $800,000, according to MacArthurs campaign.

It also comes as Democrats across the country are eager to challenge Trumps agenda and deliver him a political blow by picking up seats in contested districts.

MacArthur campaign spokesman Chris Russell defended the congressmans efforts to replace the Affordable Care Act and said hes determined to confront and solve serious problems.

He also jabbed at Kims health care credentials.

As for Andy Kim running on the health care issue, if he is as much of an expert on health care as he was when advising President Obama on ISIS in Iraq, voters in Burlington and Ocean Counties would be wise to keep him on the JV Team, Russell said.

Kim served from 2013 until 2015 as the Iraq director for the Obama administrations National Security Council and before that he was the Iraq director at the Pentagon within the defense secretarys office. He also previously served generals David Petraeus and John Allen in Afghanistan.

He graduated from the University of Chicago in 2004 with a degree in political science and obtained a doctorate in international relations from Oxford University as part of the Rhodes Scholar program.

Southern New Jerseys 3rd District hugs the Delaware River and the Philadelphia suburbs to the west, but also spans the conservative-leaning Pine Barrens and Ocean County to the east. Trump won the district in 2016, but Democrat Barack Obama carried it twice.

Republican Jon Runyan, a former Philadelphia Eagles player, represented the district for two terms before retiring in 2015. Runyan defeated one-term Democrat John Adler in 2010.

Read or Share this story: http://www.courierpostonline.com/story/news/local/south-jersey/2017/06/19/tom-macarthur-trump-healthcare-reform-challenger-reelection/409186001/

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MacArthur's health-care role fires up challenger - Cherry Hill Courier Post

A Couple’s Quest To Stop A Rare Disease Before It Takes One Of Them – NPR

Sonia Vallabh lost her mother to a rare brain disease in 2010, and then learned she had inherited the same genetic mutation. She and her husband, Eric Minikel, went back to school to study the family of illnesses prion diseases in the hope of finding a cure for Sonia. Kayana Szymczak for NPR hide caption

Sonia Vallabh lost her mother to a rare brain disease in 2010, and then learned she had inherited the same genetic mutation. She and her husband, Eric Minikel, went back to school to study the family of illnesses prion diseases in the hope of finding a cure for Sonia.

In 2010, Sonia Vallabh watched her mom, Kamni Vallabh, die in a really horrible way.

First, her mom's memory started to go, then she lost the ability to reason. Sonia says it was like watching someone get unplugged from the world. By the end, it was as if she was stuck between being awake and asleep. She was confused and uncomfortable all the time.

"Even when awake, was she fully or was she really? And when asleep, was she really asleep?" says Sonia.

The smart, warm, artistic Kamni just 51 years old was disappearing into profound dementia.

"I think until you've seen it, it's hard to actually imagine what it is for a person to be alive and their body is moving around, but their brain is not there anymore," says Eric Minikel, Sonia's husband.

In less than a year, Sonia's mom died.

An autopsy showed Kamni had died from something rare a prion disease. Specifically, one called fatal familial insomnia because in some patients it steals the ability to fall asleep.

Basically, certain molecules had started clumping together in Kamni's brain, killing her brain cells. It was all because of one tiny error in her DNA an "A" where there was supposed to be a "G," a single typo in a manuscript of 6 billion letters.

Sonia sent a sample of her own blood to a lab, where a test confirmed she inherited the same mutation. The finding threw the family into grief all over again.

"But that grieving period sort of started to resolve within about a week or so," she says. "And we weren't in crisis anymore. We were finding our way toward a new normal, where this was something that we were going to have to live with and deal with and learn more about."

Today, Sonia and her husband live and work in Cambridge, Mass., where they are both doctoral students in the lab of Stuart Schreiber, a Harvard professor of chemistry and chemical biology. Over the past several years, the couple has completely redirected their careers and their lives toward this single goal: to prevent prion disease from ever making Sonia sick.

The two wear bright colors and laugh easily. When they answer my questions, they look at each other instead of at me. They like complicated board games, urban walks and efficient cooking. They are thinkers and problem solvers, which is why, when Sonia got her genetic test results, it changed everything.

The change

"It didn't happen all at once," Sonia says. "There wasn't a day when we woke up and said, 'OK let's change everything about our lives.'"

At the time, Sonia, who has a Harvard law degree, had just started a new job as a legal consultant. Eric was a transportation analyst.

But they couldn't stop thinking about Sonia's test result. They started researching prion diseases online, and invited over friends who are biologists and chemists, to help them understand the science.

"And around that time," Sonia says, "we both enrolled in night classes as well," in subjects like biology and neuroscience.

They were hungry to learn more as quickly as possible; the night classes weren't enough.

"I was basically fresh out of law school and started walking into classes at MIT during the day because this was kind of all I could think about," says Sonia, who at the time wore sneakers every day so that she could rush between work, classes, and a neuroscience lab at Massachusetts General Hospital. She'd started volunteering there, thanks to a professor from one of her classes, and mentors in the lab who helped her learn everything from how to use a pipette to how to work with human brain cells.

"And from there, this is where things happened surprisingly quickly," Sonia says.

Eric and Sonia prepare materials for an experiment measuring prion protein in spinal fluid. They're both third-year Harvard graduate students doing research at the Broad Institute in Cambridge, Mass. Kayana Szymczak for NPR hide caption

Eric and Sonia prepare materials for an experiment measuring prion protein in spinal fluid. They're both third-year Harvard graduate students doing research at the Broad Institute in Cambridge, Mass.

The couple started a nonprofit, Prion Alliance, in hopes of raising money for research. Sonia left her legal job to work in the Mass General lab full-time as a technician. Then, Eric left his job and joined a genetics lab, applying his skills in coding to analyzing genetic data, rather than transportation data.

"I was getting left behind!" he says. "Sonia was out there doing all this science. It was her day job now and I was still in my old career and, you know, it was a good job and all, it was meaningful, but it wasn't the mission that it was increasingly clear that we were going to be on."

Just months after they'd finished grad school in law and urban planning, the pair went back to graduate school, this time in biomedical sciences to study prion diseases.

"You are talking to two third-year graduate students," says Eric.

Life as scientists

The two now share an office and a lab bench, under Schreiber's supervision, at the Broad Institute of MIT and Harvard.

"There's a date in the future when Sonia will get the first dose of the drug that's going to save her life," Eric says. "What can I do today that brings that date closer to the present?"

A posted printout of an email says: "Let's just blast forward and solve problems as they become real and as they need immediate solutions." It's a note Schreiber sent the pair at one point when they were worrying about bureaucratic hoops they had to jump through.

"I thought it was a good philosophy, so we printed it out and put it on the wall," says Eric.

Sonia and Eric are "the best of humanity" Schreiber tells Shots. "Their story is, of course, remarkable, and they personify the concept of patientscientists. But their deep understanding of science and ability to innovate and execute on one of the hardest challenges in biomedical science are breathtaking."

Schreiber says that his lab, like many others in biomedicine, has long included researchers who are physicians as well as scientists; that dual training and experience brings an important perspective to the research, he says.

"But the last decade has seen the emergence of patientscientists including Sonia and Eric, but also others in my lab," he says. "And this has had an even greater impact on the lab. They remind us of our mission to understand and treat human disease."

Still, it's really hard to cure diseases especially conditions like this one, because the usual way scientists look for a treatment isn't going to work.

Sonia is 33 years old. On average, people with the kind of genetic mutation she has usually start to show symptoms at age 50. But they could surface at any time. Symptoms of fatal familial insomnia have set in as early as age 12 and as late as 84. Once they do, it's a rapid decline like Alzheimer's disease on fast-forward.

"You're healthy, you're healthy, you're healthy and then you're falling off a cliff," says Sonia. "You wait a little bit too long, and that patient is gone. We need to get out ahead of it aggressively."

The challenge

They need to keep Sonia from getting sick in the first place. And they need to do it quickly. But right now, Sonia appears to be just fine, and that's actually one of the first obstacles.

Across medicine, there is an understandable resistance to testing experimental drugs on healthy people. That's why, traditionally, drug trials go something like this: Take a group of people who are sick, give some of them an experimental medicine, and wait to see if it makes them get better, live longer, or decline more slowly than people who didn't get the drug.

But Sonia has to convince the medical establishment that, especially in the age of genetics, some people who seem perfectly healthy should be considered patients.

Sonia measures prion protein in mouse cells. In prion disease, certain proteins in the brain start clumping together, which eventually kills neurons. Kayana Szymczak for NPR hide caption

Sonia measures prion protein in mouse cells. In prion disease, certain proteins in the brain start clumping together, which eventually kills neurons.

"We have to be willing to act upstream of what we would traditionally call 'illness'," she says.

It's a shift in mindset that she had to come to grips with, personally.

"I feel very lucky to be healthy today," she says. "But I hold a sort of dual reality understanding of my own health, which is that I'm healthy today but very seriously at risk for a very serious disease."

Others in the medical field, like Dr. Reisa Sperling, who studies Alzheimer's disease, are making the same mental shift as they think about the best time to intervene.

"Alzheimer's disease is a terrible disease. Many people fear it more than cancer," says Sperling, a neurologist with Brigham and Women's Hospital and Massachusetts General Hospital.

Like Sonia and Eric, she, too, is on a quest to prevent even the first symptoms of a terrible brain disease.

Sperling is now enrolling people whose brain scans show they might be in the very early stages of Alzheimer's in a clinical trial to test an experimental drug treatment. And she's planning another study in people as young as 50 who have no noticeable symptoms, but are at high risk of developing them.

"It really does primarily come down to thinking about disease as beginning years before symptoms," says Sperling. "If we can shift that thinking not just in Alzheimer's disease, but in rarer diseases like prion diseases I think this is the way we win the war."

But before any of that can happen with a prion disease, there's the problem of actually doing the science to find a good candidate drug.

The plan

Researchers don't have one in hand yet, but they have a clear idea of what it should look like, based on studies in mice. Sonia and Eric already are talking to pharmaceutical companies that may be involved in running human trials in the future, and have requested a meeting with the Food and Drug Administration to talk about what a trial should involve.

Other efforts at treating prion disease have focused on preventing the misfolded proteins from killing brain cells, or on preventing them from accumulating. Sonia and Eric have a different approach.

"We're really interested in preventing the misfolding in the first place," says Sonia.

"Sonia's brain is producing this mutant protein," Eric says. "But as far as we know it's not misfolded yet, and the disease process hasn't started. I want her brain to be producing half or less of the amount of that protein as she is [producing] right now, because we know that less is better."

Essentially, they want to muffle the faulty gene in order to reduce the amount of prion protein floating around in Sonia's brain.

But a key question right now is this: Say they make the right drug and give it to Sonia and others with her type of mutation. If the goal is to change nothing about her current health, then how will they know it's actually working?

A traditional clinical trial is out of the question, Eric says.

It would be unethical and untenable he says, to "just treat half of the people with a drug and half with placebo and then wait 30 years to see when they die."

Not only would that kind of experiment condemn some patients to terrible death, it would also be wildly expensive and require thousands of participants. There are only a few hundred people in the U.S. with prion disease mutations.

"Instead, we need a biomarker," Eric says. "We need some laboratory test that we can run on a living human to see if the drug is having its effect."

The answer, Sonia and Eric hope, could be in a very cold refrigerator in the lab where they work. It's full of samples of spinal fluid. In mouse studies, at least, reducing prion protein in the brain seems to delay disease progression.

So, Sonia and Eric are now studying samples of spinal fluid from all sorts of people from people who already have symptoms of prion disease, from others like Sonia (who have mutations for prion disease but no symptoms yet) and from healthy controls. The aim is to establish how the levels of protein in the samples change over time, to figure out if protein levels would be a good enough measure to say, "Yes, this drug works."

"We have strong evidence that 50 percent [reduction] if we could achieve that would be protective," says Sonia, based on preliminary findings in mice.

Others are optimistic, too

Sonia and Eric are organized, hardworking, and efficient. Ultimately, for them, failure is not an option. But on a day-to-day basis, failure is what science is all about.

Ericl and Sonia on their wedding day in 2009. Zamana Photography/Courtesy of Sonia Vallabh hide caption

Ericl and Sonia on their wedding day in 2009.

"In biology, if everything you did one day goes wrong, and then you figure out why it went wrong, that was a good day," says Eric, who chronicles their struggles on a blog.

It's an achingly slow process. But Eric thinks they will do it they'll find a drug.

"I'm an optimist that we'll get there in our lifetime," he says, "but not this year and not next year."

He's not alone in his optimism. Sonia and Eric have some powerful colleagues who believe the couple can pull it off colleagues like Eric Lander, a renowned mathematician, geneticist and molecular biologist. He started the Human Genome Project and founded the Broad Institute where Sonia and Eric now work.

"This is not pie in the sky," says Lander. "I see a path forward for multiple shots on goal. All you have to do is get one through."

Fifteen years ago, he says, solving this puzzle would have seemed impossible. But now he believes the science, the technology, and the knowledge about what certain mutations mean for a person's health have made defeating prion disease possible.

"Human genetics and molecular medicine are reaching a point of maturity where they're becoming much more powerful," he says. "It's exciting and important and there's nobody who's more motivated than somebody who's going to be affected by the disease themselves."

One small success

In one way, Sonia and Eric have already stopped the disease in its tracks.

Sonia is very pregnant. She's due in July to have a daughter a daughter without a mutation for prion disease. That's something the couple made sure of by screening embryos after in vitro fertilization.

A collection of mementos from Sonia and Eric's wedding in 2009 hangs on a wall in their apartment. Kayana Szymczak for NPR hide caption

A collection of mementos from Sonia and Eric's wedding in 2009 hangs on a wall in their apartment.

So, they've stopped the transmission of prion disease in Sonia's line of the family. And in a way, that's a gift from Sonia's mom, Kamni, the couple says.

"If my mom was still alive, we wouldn't know any of this and we wouldn't have had the opportunity to choose to have a mutation-negative baby," says Sonia. "But, tragically, it also means that they'll never meet."

Sonia and Eric hope that, by the time their daughter is in elementary school, Sonia will be taking an experimental drug that could keep her as healthy as she is today.

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A Couple's Quest To Stop A Rare Disease Before It Takes One Of Them - NPR

Liquid Biopsy Guides New Prostate Cancer Drug Trial – Genetic Engineering & Biotechnology News

Its been no secret that screening methods to detect prostate cancer have been woefully lacking and largely inconsistent with respect to the results they provide. Yet, with the rise in validated biomarkers and advanced diagnostics coupled with next-generation sequencing methods, new liquid biopsy assays are guiding physician treatment options. Now, a group of investigators at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust have developed a three-in-one blood test that could transform the treatment of advanced prostate cancer through the use of precision drugs designed to target mutations in the BRCA genes.

"Blood tests for cancer promise to be truly revolutionary, noted Paul Workman, Ph.D., chief executive of The Institute of Cancer Research, London. They are cheap and simple to use, but most importantly, because they aren't invasive, they can be employed or applied to routinely monitor patients to spot early if treatment is failingoffering patients the best chance of surviving their disease.

The research team was able to isolate cancer DNA in a patients bloodstream and determine which men with advanced prostate cancer were likely to benefit from treatment with a new class of drugs called poly(ADP-ribose) polymerase (PARP) inhibitorsspecifically the drug olaparib. Moreover, the scientists were able to use the test to analyze DNA in the blood after treatment had started, so people who were not responding could be identified and switched to an alternative therapy in as little as four to eight weeks. The third aspect of the new test came when the research team was able to monitor a patient's blood throughout treatment, quickly picking up signs that the cancer was evolving genetically and might be becoming resistant to the drugs.

Findings from the new study were published recently in Cancer Discovery in an article entitled Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.

"Our study identifies, for the first time, genetic changes that allow prostate cancer cells to become resistant to the precision medicine olaparib, explained senior study investigator Johann de Bono, M.D., professor of cancer research at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust. "From these findings, we were able to develop a powerful, three-in-one test that could in future be used to help doctors select treatment, check whether it is working, and monitor the cancer in the longer term. We think it could be used to make clinical decisions about whether a PARP inhibitor is working within as little as four to eight weeks of starting therapy.

The investigators are optimistic that the new test could help to extend or save lives by targeting treatment more effectively, while also reducing the side effects of treatment and ensuring patients don't receive drugs that are unlikely to do them any good. Additionally, the new study is also the first to identify which genetic mutations prostate cancers use to resist treatment with olaparib. The test could potentially be adapted to monitor treatment with PARP inhibitors for other cancers.

"Not only could the test have a major impact on the treatment of prostate cancer, but it could also be adapted to open up the possibility of precision medicine to patients with other types of cancer as well," Dr. de Bono remarked.

In the study, researchers at the ICR and The Royal Marsden collected blood samples from 49 men at The Royal Marsden with advanced prostate cancer enrolled in the TOPARP-A Phase II clinical trial of olaparib. Olaparib is good at killing cancer cells that have errors in genes that have a role in repairing damaged DNA such as BRCA1 or BRCA2. Some patients respond to the drug for years, but in other patients, the treatment either fails early, or the cancer evolves resistance. Evaluating the levels of cancer DNA circulating in the blood, the researchers found that patients who responded to the drug had a median drop in the levels of circulating DNA of 49.6% after only eight weeks of treatment, whereas cancer DNA levels rose by a median of 2.1% in patients who did not respond.

Men whose blood levels of DNA had decreased at eight weeks after treatment survived an average of 17 months, compared with only 10.1 months for men whose cancer DNA levels remained high.

"This is another important example where liquid biopsiesa simple blood test as opposed to an invasive tissue biopsycan be used to direct and improve the treatment of patients with cancer," commented David Cunningham, Ph.D., director of clinical research at The Royal Marsden NHS Foundation Trust.

The researchers also performed a detailed examination of the genetic changes that occurred in cancer DNA from patients who had stopped responding to olaparib. They found that cancer cells had acquired new genetic changes that canceled out the original errors in DNA repairparticularly in the genes BRCA2 and PALB2that had made the cancer susceptible to olaparib in the first place.

"To greatly improve the survival chances of the 47,000 men diagnosed with prostate cancer each year, it's clear that we need to move away from the current one-size-fits-all approach to much more targeted treatment methods, concluded Matthew Hobbs, Ph.D., deputy director of research at Prostate Cancer UK. The results from this study and others like it are crucial as they give an important understanding of the factors that drive certain prostate cancers, or make them vulnerable to specific treatments.

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Liquid Biopsy Guides New Prostate Cancer Drug Trial - Genetic Engineering & Biotechnology News

Developing a Gene Therapy with Transformative Potential for Patients with Recessive Dystrophic Epidermolysis Bullosa – Drug Discovery &…

The term butterfly children sounds pleasant but refers to a harsh reality: children with epidermolysis bullosa, or EB, an inherited, genetic blistering skin disorder, are born withskin as fragile as a butterflys wings.

EB affects all races, ethnicities and both genders, and has no cure. According to the Dystrophic Epidermolysis Bullosa Research Association of America, every year about 200 children are born with EB in the United States.

There are several types of EB. The most common type of severe EB is recessive dystrophic epidermolysis bullosa, or RDEBa progressive, devastatingly painful and debilitating disease that affects up to ~2,500 patients in the U.S. and often leads to death. RDEB causes severe blistering and areas of missing skin in response to any kind of friction, including normal rubbing and scratching.

Cause of RDEB

RDEB is an autosomal recessive, inherited skin disease caused by null mutations within the type VII collagen gene (COL7A1). The mutations cause an absence or reduction of functional collagen VII (COL7), which make up anchoring fibrils that maintain binding of the epidermis to the dermis. The disease is characterized by a mechanical fragility and repeated blister formation in the sub-lamina densa at the level of the structurally defective anchoring fibrils.

Development of a New Gene Therapy

Fibrocell, a gene therapy company, is applying its distinctive autologous fibroblast technology to develop FCX-007, its candidate for the treatment of RDEBand potentially the first investigational therapy to target the underlying cause of the disease.

FCX-007 is being developed in collaboration with Intrexon Corporation, a leader in synthetic biology.

FCX-007 is an autologous dermal fibroblast genetically modified to express functional COL7 that is missing or deficient in RDEB patients. Transduced with a lentiviral vector containing COL7A1, FCX-007 is injected directly into the papillary dermis of blisters and wounds where the COL7 protein could enable formation of anchoring fibrils to hold the layers of skin together. The goal of the therapy is to provide high levels of functional COL7 directly to the affected areas while avoiding systemic distribution. This localized therapeutic approach is compatible with the unique biology of each individual patient.

The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to FCX-007 for the treatment of Dystrophic Epidermolysis Bullosa, which includes RDEB; likewise, the FDA granted both Rare Pediatric Disease and Fast Track Designations to FCX-007 for the treatment of RDEB.

A poster presented at the American Society of Human Genetics Annual Meeting in October 2015 addressed the preclinical development of FCX-007 for the treatment of RDEB. As noted in the poster, in vitro product development data indicates that cGMP scale FCX-007 cells express full-length COL7 exhibiting the proper trimeric structure, size and binding functionality.

Production of the lentiviral vector (LV-COL7) was successful, resulting in an infectious titer of ~9 x 106 IU/mL. The integrated transgene copy number per cell was dependent on the virus dose. FCX-007 was produced by expanding fibroblasts from skin biopsies, transducing with the vector, followed by subsequent expansion, harvest and cryopreservation. The COL7 expression from the FCX-007 cells was confirmed by ELISA and Western Blot as well as qRT-PCR and immunofluorescence staining.

The structure of expressed COL7 was confirmed to be predominantly trimeric by immunoprecipitation/SDS-PAGE/Western blot analysis. The COL7 produced from the FCX-007 cells was demonstrated to be functional by binding to Laminin332 in an in vitro binding assay as well as by correction of the hypermotility phenotype of RDEB cells in an in vitro migration assay.

The presentation also reported in vivo results from a preclinical animal model evaluating FCX-007 in RDEB and normal human skin xenografts implanted onto the dorsum of immunodeficient SCID mice. The grafts consisted of human fibroblasts and keratinocytes in a bilayer. The goals of the study were to confirm persistence, distribution and localization of COL7, and to evaluate any potential for product toxicity or vector biodistribution.

The composite RDEB skin grafts were injected intradermally with 1 x 106 FCX-007 cells and analyzed by immunofluorescent staining with human COL7 specific antibodies. Localization of COL7 was observed in composite grafts 10 days post-injection. Positive control grafts generated from normal keratinocytes and fibroblasts showed intense COL7 staining and negative control grafts did not show COL7 staining at baseline measurements.

In a follow-up toxicology/biodistribution study, FCX-007 was well tolerated up to six months post-administration.

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Developing a Gene Therapy with Transformative Potential for Patients with Recessive Dystrophic Epidermolysis Bullosa - Drug Discovery &...

Tapping gene therapy potential for inherited retinal diseases – ModernMedicine

Reviewed by Edwin M. Stone, MD, PhD

Though gene therapy technology already exists to treat most inherited retinal disease, the current challenge is to drive down the costs of implementing the technologythus availing more patients with the benefits of treatments and possibly prevent inevitable visual deterioration.

Edwin M. Stone, MD, PhD, recounted the case of a 14-year-old boy with an inherited eye disease who was born deaf and received bilateral cochlear implants during the first years of his life. The boys visual acuity levels were 20/25 and 20/32 in the right and left eyes, respectively. Despite good visual acuity, more recently, he had been having difficulty seeing in dim light.

A Goldmann perimetry evaluation showed normal responses to large, bright stimuli. However, there was some restriction at the 12e and 14e isopters, explained Dr. Stone, director, Stephen A. Wynn Institute for Vision Research, and professor, Department of Ophthalmology and Vision Sciences, University of Iowa, Iowa City.

A fundus examination showed that both discs were normal and the vessels were slightly constricted. Some pigmentation was present in the midperipheral retina.

Based on these findings, deafness at birth, and retinitis pigmentosa at the beginning of the second decade of life, the patient was given a diagnosis of type I Usher syndrome. Molecular testing showed the presence of the two most common mutations in the USH1C gene, i.e., Val72Val (a splice variant) and Thr78insC.

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Tapping gene therapy potential for inherited retinal diseases - ModernMedicine

Further blow in bid to stop demolition of Scarborough Futurist – The Stage

A bid to save Scarborough's Futurist Theatre from demolition has failed after a High Court judge ruled the council's decision to tear it down should not be reviewed.

It is the latest in a string of attempts to prevent the now derelict theatre from being demolished, a move voted for by Scarborough councillors in January.

Campaigners trying to save the building subsequently employed a team of solicitors to help try and overturn the decision, in which councillors voted 22 to 21 in favour of demolition.

They were seeking a judicial review into the council's decision to demolish the building. However a High Court judge has now rejected their bid to bring proceedings against the council, meaning the vote will not be scrutinised.

Following the council's decision earlier this year to spend 4 million knocking down the former theatre which has been derelict since 2014 the campaign attempted to get the building listed in order to stave off demolition. However, the application was rejected.

A message on Save the Futurist Theatre's campaign page on Facebook said the group would be meeting with its legal team this week.

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Further blow in bid to stop demolition of Scarborough Futurist - The Stage

Last Month Was the Second Hottest May in Recorded History – Futurism

In Brief May 2017 was the second hottest May in recorded history. This year seems to be continuing the trend of being among the hottest ever.

Summer is rapidly approaching and bringing along with it the highest temperatures of the year, for most of the world. It already seems that this year will be keeping pace with recent years and offering up some of the warmest months in all of recorded history.

This past May has been recorded as the second hottest in history, being beaten only by May 2016, which was 0.93 degrees C (33.7 degrees F) higher than the mean temperature between 1951-1980. Every month this year has ranked in the top three warmest months in recorded history. According to The Weather ChannelFebruary, March and April 2017 ranked as second warmest, while January 2017 finished in third place.

Global climate change is clearly the culprit as human activity continues to contribute to global temperature rises. The Paris Climate Agreement set to address this issue by capping this temperature rise at 2 degrees Celsius. However, experts assert that not even this is enough to save our planet. Even more, there are threats to the effectiveness of even that agreement as the Trump administration recently announced its intent to remove the United States from it.There is still hope, though. Leaders across the United States have defied that intention with promises to uphold the accords, despite the administration. Solar power is also increasingly becoming more economically palatable and will soon become cheaper than coal, eliminating a major source of pollution.

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Last Month Was the Second Hottest May in Recorded History - Futurism

NASA Just Discovered 10 Earth-Like Alien Planets – Futurism

A Universe of Earths

Planet hunters and science enthusiasts are rejoicing over NASAs latest announcement. Today, a team of astronomers working with data from the K2 mission released a new catalog of potential alien planets. In a press conference held at NASAs Ames Research Center, the team stated that they hadidentified 219 planet candidates, 10 of which are said to be rocky worlds that are in the habitable zones of stars that are similar to the Sunwhich is ayellow dwarf or G dwarf.

In short, it seems that we have 10 new planets that are Earth-like.

In science, Earth-like worlds are loosely defined as terrestrial worlds that have a chemical composition that is similar to our own planet andorbit in a relatively young stars habitable zone (the habitable zone is defined as the orbit around a star where liquid water could theoretically exist on a planets surface).

The team was composed of Kepler research scientists Mario Perez, from the Astrophysics Division of NASAs Science Mission Directorate in Washington, Susan Thompson, from the SETI Institute in California, Benjamin Fulton, from the California Institute of Technology in Pasadena, and Courtney Dressing, a NASA Sagan Fellow at Caltech.

To date, there are already 4,034 exoplanet candidates identified by Kepler and 2,335 of these have been confirmed. The 10 new exoplanets addto the 49 Earth-like exoplanets in habitable zones that were previously detected by Kepler, more than 30 of which have been verified.

Perhaps the most interesting of these new finds is KY 7711, which Thompson said is located near its star in an orbit that is very similar to the path that Earth takes around the Sun, meaning that it receives the same amount of heat, although it is approximately 1.3 times larger than our planet.

Typically, exoplanetsfall in one of two categories: super-Earths, which have a radius that is 1.5 times that of the Earth, rocky surfaces, and oftenlittle to no atmosphere; and those that are like mini-Neptunes, which are about twice the Earths radius with thick atmospheres and no rocky surface. Exoplanets falling in between these two categories (i.e. worlds that are Earth-like) are smaller and, thus, much harder to identify. But as this latest find reveals, they are out there.

The Kepler space observatory was launched 8 years ago, in March 2009. Its singular mission was to search for planets orbiting other stars in the hopes of finding alien worldsthat are similar to Earth. Fulton explained that, looking back, they wouldnt have expected to identify roughly 50 Earth-like exoplanets so soon.

Both the original Kepler mission and K2 have significantly contributed in the mission to search for potentially habitable exoplanets. Although not part of the original mission, Kepler also provided the first images of the TRAPPIST-1 system, arguably the most notable exoplanet system recently discovered.

Now, as the K2 reaches the end of its four-year run, Kepler scientists think that we are closing in on the end of an era in exoplanet research. But it also marks the beginning of a new one, with missions like the Transiting Exoplanet Survey Satellite (TESS) and the James Webb Space Telescope (JWST) expected to launch soon. Both the TESS and the JWST would look into exoplanets in ways Kepler isnt able to, identifying new information about their composition and habitability.

Undeniably, though, it was Kepler that made all of these future missions possible. Whats exciting about today is we have taken our telescope and we have counted up how many planets are similar to the Earth in this part of the sky, Thompson said at the press conference. With the data I have, I can now make that count. From there, were going to determine how common other planets are. Are there places we could live in this galaxy besides what we call home?

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NASA Just Discovered 10 Earth-Like Alien Planets - Futurism

Elon Musk Just Claimed That The LA Mayor is Open to His Controversial Boring Company – Futurism

In Brief It looks like Elon Musk's tunnel project has the support of Los Angeles mayor Eric Garcetti, according to a recent tweet by the Boring Company's CEO and founder. The L.A. mayor looks to Musk's tunnels to improve traffic conditions to LAX.

Often, legislation can either be an express lane or a roadblock (pun intended) for technological innovation that improves transportation. Getting government to support this type of development, such as Elon Musks famous Boring Company, is definitely a step in the right direction.

In a recent tweet, Boring founder and CEO Elon Musk linkedan interview fromABC this past Sunday that featuredLos Angeles mayor Eric Garcetti. In the snippet, Garcetti was talking about potential solutions to improve the abysmal traffic to the citys airport. In particular, he mentioned Musks tunnel solution. Like many other cities have, Id love to see maybe even with the new tunneling technology that people like Elon Musk is looking at, whether we could have a quick and direct route from LAX to Union Station, Garcetti said.

While Musk noted Garcettis comment to be promising, the serial entrepreneur made an additional comment, saying that government permits are often harder to come by than developing technology. In order for a potentially disruptive technology like the Boring Companys earthquake-proof tunnel system which could potentially improve L.A. traffic to become a reality, there must be more effective and efficient policy making.

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Elon Musk Just Claimed That The LA Mayor is Open to His Controversial Boring Company - Futurism