Friday, August 11, 2017

The effects of sex drive and paraphilic interests on paraphilic behaviours in a nonclinical sample of men and women

The effects of sex drive and paraphilic interests on paraphilic behaviours in a nonclinical sample of men and women. Katrina N. Bouchard, Samantha J. Dawson and Martin L. Lalumière.  The Canadian Journal of Human Sexuality, http://www.utpjournals.press/doi/abs/10.3138/cjhs.262-a8

Abstract: Research on samples of men and women from the general population suggests that paraphilic interests and behaviours are more common in men than in women, but the reasons for this sex difference are unclear. In addition, there is little research on how paraphilic interests lead to engagement in paraphilic behaviours. In this study, we assessed the frequency of engagement in a broad range of paraphilic behaviours in a nonclinical sample of men and women. We expected that men would report engaging in paraphilic behaviours more frequently than women. We also examined whether sex drive explained the sex difference in the frequency of engagement in paraphilic behaviours, as well as whether the relationship between paraphilic interests and frequency of engagement in paraphilic behaviours was stronger at high levels of sex drive. A sample of 305 men and 710 women completed an online survey assessing paraphilic interests and behaviours as well as three measures of sex drive. As expected, sex differences were found, with men reporting more frequent engagement in most paraphilic behaviours. After controlling for socially desirable responding, sex drive fully accounted for the male-biased sex differences. One measure of sex drive–the Sexual Behaviour and Desire Questionnaire–moderated the relationship between paraphilic interests and frequency of engagement in paraphilic behaviours, such that paraphilic interests were most strongly associated with paraphilic behaviours at high levels of sex drive. Taken together, these findings provide further support for the importance of sex drive in understanding the paraphilias.

KEY WORDS: Nonclinical sample, paraphilic behaviours, paraphilic interests, sex differences, sex drive


CEO Turnover and Political Repositioning

CEO Turnover and Political Repositioning. Yosef Bonaparte. University of Colorado Working Paper, June 2017, https://ssrn.com/abstract=2991032

Abstract: This paper examines the relation between political regime change, a new president from a new party, and propensity for CEO turnover. Our key conjecture is that some companies, especially those that are politically sensitive, will politically reposition to adapt to the new political regime, and this political repositioning will be reflected in increased CEO turnover. We find support for this hypothesis, for CEO turnover is at least 24% more likely to happen following political regime change. The economic significance of this CEO political repositioning varies by company characteristics, with repositioning greater among large cap stocks, stocks held by short term investors, and sectors that are politically sensitive. However, political repositioning decreases stock performance relative to the sector, though this effect is weakly significant. These results suggest that political regime change causes firms to reevaluate the required skills of the CEO. Collectively, we find that political repositioning is an important determinant of CEO turnover.

Keywords: CEO turnover and political repositioning
JEL Classification: G02, G11, G12

An evolutionary perspective on cooperative behavior in gamers

Devilly, G. J., Brown, K., Pickert, I., & O'Donohue, R. (2017). An evolutionary perspective on cooperative behavior in gamers. Psychology of Popular Media Culture, 6(3), 208-221. http://dx.doi.org/10.1037/ppm0000097

Abstract: This research was the first experimental study to investigate the effect of video gaming on measures of cooperative behavior from an evolutionary standpoint. The final sample comprised a total 117 participants (39 male, 78 females), with a mean age of 24 years (SD = 8.93). Participants were randomly assigned to 1 of 4 media conditions (violent book, violent video game, nonviolent video game, and violent TV show) and measured on prosocial behavior before any media exposure and assessed on cooperative behavior after media exposure. Novice and regular gamers did not differ on prosocial behavior before gaming. After media exposure, a self-constructed version of the iterated Prisoner’s Dilemma game was used to measure cooperation. Further analyses were then conducted to measure differences between conditions on cooperative behavior. It was found that ***regular and multiplayer gamers were not significantly higher or lower on measures of cooperative behavior compared to novices or solitary gamers***. Although nonsignificant, effect sizes were consistent with past research which suggests heightened cooperation in regular gamers. Media type exposure did not have a significant effect on cooperative behavior. Findings suggest that cooperative behavior is not less prominent in regular or multiplayer gamers than novices or solitary gamers. These results indicate that, contrary to the predictions one may make from the GAM model of violent gaming (Anderson & Bushman, 2001), violent media exposure does not appear to produce reductions in prosocial or cooperative behavior.

"contrary to the predictions one may make from the general aggression model of violent gaming, violent media exposure does not appear to produce reductions in prosocial or cooperative behavior. Regular gamers were just as prosocial and cooperative as novice gamers"

Check also: Excessive users of violent video games do not show emotional desensitization: An fMRI study. Gregor Szycik et al. Brain Imaging and Behavior, June 2017, Pages 736–743, https://www.ncbi.nlm.nih.gov/pubmed/27086318

And: Overstated evidence for short-term effects of violent games on affect and behavior: A reanalysis of Anderson et al. (2010). By Hilgard, Joseph; Engelhardt, Christopher R.; Rouder, Jeffrey N. Psychological Bulletin, Vol 143(7), Jul 2017, 757-774. http://dx.doi.org/10.1037/bul0000074

Elections and Divisiveness: Theory and Evidence

Elections and Divisiveness: Theory and Evidence. Elliott Ash, Massimo Morelli and Richard Van Weelden. Journal of Politics, http://www.nber.org/papers/w21422.pdf

Abstract: This article provides a theoretical and empirical analysis of how politicians allocate their time across issues. When voters are uncertain about an incumbent's preferences, there is a pervasive incentive to "posture" by spending too much time on divisive issues (which are more informative about a politician's preferences) at the expense of time spent on common-values issues (which provide greater benefit to voters). Higher transparency over the politicians' choices can exacerbate the distortions. These theoretical results motivate an empirical study of how Members of the US Congress allocate time across issues in their floor speeches. We find that US senators spend more time on divisive issues when they are up for election, consistent with electorally induced posturing. In addition, we find that US house members spend more time on divisive issues in response to higher news transparency.

Biased Policy Professionals -- World Bank interns are shocked, shocked! by confirmation bias.

Biased Policy Professionals. Sheheryar Banuri, Stefan Dercon, and Varun Gauri. World Bank Policy Research Working Paper 8113. https://t.co/Jga1EUEkbF.

A large literature focuses on the biases of individuals and consumers, as well as “nudges” and other policies that can address those biases. Although policy decisions are often more consequential than those of individual consumers, there is a dearth of studies on the biases of policy professionals: those who prepare and implement policy on behalf of elected politicians. Experiments conducted on a novel subject pool of development policy professionals (public servants of the World Bank and the Department for International Development in the United Kingdom) show that policy professionals are indeed subject to decision making traps, including sunk cost bias, the framing of losses and gains, frame-dependent risk-aversion, and, ***most strikingly***, confirmation bias correlated with ideological priors, despite having an explicit mission to promote evidence-informed and impartial decision making. These findings should worry policy professionals and their principals in governments and large organizations, as well as citizens themselves. A further experiment, in which policy professionals engage in discussion, shows that deliberation may be able to mitigate the effects of some of these biases.

My comment: Most strikingly? They are shocked, shocked! that policy professionals show confirmation bias. What they expected? Did they do their homework?

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"If respondents evaluate data objectively and independent of prior beliefs regarding redistribution,
they should have offered equally accurate assessments of the minimum wage study and skin cream
study frames. Alternatively, if respondents are influenced by their ideologies or values, accuracy in
the minimum wage frame should have been lower than in the skin cream frame. In fact, respondents were significantly less accurate in the minimum wage treatments (45% responded with the correct answer) relative to the skin cream treatments (65% responded with the correct answer [...]"

Check also: Dispelling the Myth: Training in Education or Neuroscience Decreases but Does Not Eliminate Beliefs in Neuromyths. Kelly Macdonald et al. Frontiers in Psychology, Aug 10 2017.  http://www.bipartisanalliance.com/2017/08/training-in-education-or-neuroscience.html

And: Wisdom and how to cultivate it: Review of emerging evidence for a constructivist model of wise thinking. Igor Grossmann. European Psychologist, in press. http://www.bipartisanalliance.com/2017/08/wisdom-and-how-to-cultivate-it-review.html

Is Imagination of the Infidelity More Painful than Recalling Actual Infidelity? It is.

Is Imagination of the Infidelity More Painful than Actual Infidelity? Farid Pazhoohi et al. Current Psychology, https://link.springer.com/article/10.1007/s12144-017-9637-1

Abstract: It has previously been reported that men and women are concerned with different aspects of infidelity. However, some researchers question the existence of such a sex difference. This discrepancy might happen because the intensity of emotions differs between those who have experienced infidelity and those who only imagine how they would feel if that happened. Additionally, the emotions that the betrayer experiences have been neglected in previous studies. Moreover, there has been no investigation regarding the differences between imaginative and actual emotions that someone experience regarding ones’ partner's or own’s infidelity. Therefore, the current study aimed to test the emotions that both men and women and both the betrayer and the victim of betrayal experience in the actual and the imaginative infidelities. Results showed that emotions were more intense while participants imagined infidelity than when they recalled an actual infidelity. Also, sex difference was larger in the imaginative infidelity.

Benefits of income: Associations with life satisfaction among earners and homemakers

Benefits of income: Associations with life satisfaction among earners and homemakers. JudithGere and Ulrich Schimmack. Personality and Individual Differences, Volume 119, 1 December 2017, Pages 92-95. https://doi.org/10.1016/j.paid.2017.07.004

Highlights
•    The study tested whether money increases happiness or happy workers earn more money.
•    Results indicated support only for the money-increases-happiness model.
•    Household income predicted life satisfaction regardless of people's earning status.
•    The moderating effect of earning status did not differ across nations.

Abstract: The question of how money and happiness are associated is still debated. This study tested two hypotheses that aim to explain this association: (1) money increases happiness, and (2) happy people make more money. Using data from the World Values Survey (N = 64,923, k = 81 nations), we tested whether earning status (primary vs. non-primary earner) moderates the association between income and happiness. The two theories make different predictions regarding this moderation effect: if money increases happiness, household income should predict happiness equally, regardless of earning status. If happy people earn more money, household income should predict the well-being of primary earners more strongly. Multilevel models indicated that data were consistent with the money-increases-happiness hypothesis: income predicted happiness equally for primary earners, secondary earners, and homemakers who do not contribute to household income directly.

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"gender also predicted life satisfaction such that primary-earner wives were more satisfied than homemaker husbands, an effect that did not differ across nations."

Measuring the Impact of an Unanticipated Suspension of Ride-Sourcing with Uber, Lyft

Measuring the Impact of an Unanticipated Suspension of Ride-Sourcing in Austin, Texas. Robert C Hampshire et al. https://ssrn.com/abstract=2977969

Abstract: On May 7, 2016 residents of Austin, TX voted against Proposition 1, which would have allowed transportation networking companies (TNCs) to continue using their own background check systems. The defeat of the proposition prompted Uber and Lyft to suspend services in Austin indefinitely. The suspension provided for a natural experiment to measure the impact of the suspension on travel behavior. In examining the impact, we conducted an online survey that combines stated and revealed preference questions (N=1,840) of former Uber and/or Lyft users in Austin to explore the effect of the suspension on travel behavior.

Regression analyses, modeled to capture both the before and after travel behavioral pattern of the suspension, were used to test our hypothesis of the impact of the service suspension on travel behavior along three dimensions — mode choice, trip frequency, and vehicle ownership. Our analysis finds that 42 percent of respondents who had used Uber or Lyft to make a trip prior to the suspension reported transitioning to another TNC as the means by which similar trips were most often made after the suspension. A near equal proportion (41 percent) reported transitioning to a personal vehicle, while 3 percent transitioned to public transit. The analysis also suggests that, when looking at trips made for the same purpose pre and post suspension, individuals that transitioned from Uber or Lyft to a personal vehicle were more likely (23 percent more likely) to make more trips than individuals transitioning from Uber or Lyft to another TNC. Additionally, ***approximately 9 percent reported purchasing an additional vehicle in response to the service suspension***. The vehicle acquisition trend was driven primarily by respondents who were inconvenienced by the service suspension — the odds of acquiring a car for an inconvenienced respondent was more than five times that of an individual who was not. These results suggest that TNCs may contribute to reduced car ownership and trip making.

Keywords: On-demand transportation, ride-sourcing, ride-hailing, transportation network companies, service suspension, travel behavior, vehicle ownership, mode shift

My comment: Are we going to stop buying cars?

Training in Education or Neuroscience Decreases but Does Not Eliminate Beliefs in Neuromyths

Dispelling the Myth: Training in Education or Neuroscience Decreases but Does Not Eliminate Beliefs in Neuromyths. Kelly Macdonald et al. Frontiers in Psychology, Aug 10 2017. https://doi.org/10.3389/fpsyg.2017.01314

Abstract: Neuromyths are misconceptions about brain research and its application to education and learning. Previous research has shown that these myths may be quite pervasive among educators, but less is known about how these rates compare to the general public or to individuals who have more exposure to neuroscience. This study is the first to use a large sample from the United States to compare the prevalence and predictors of neuromyths among educators, the general public, and individuals with high neuroscience exposure. Neuromyth survey responses and demographics were gathered via an online survey hosted at TestMyBrain.org. We compared performance among the three groups of interest: educators (N = 598), high neuroscience exposure (N = 234), and the general public (N = 3,045) and analyzed predictors of individual differences in neuromyths performance. In an exploratory factor analysis, we found that a core group of 7 “classic” neuromyths factored together (items related to learning styles, dyslexia, the Mozart effect, the impact of sugar on attention, right-brain/left-brain learners, and using 10% of the brain). The general public endorsed the greatest number of neuromyths (M = 68%), with significantly fewer endorsed by educators (M = 56%), and still fewer endorsed by the high neuroscience exposure group (M = 46%). The two most commonly endorsed neuromyths across all groups were related to learning styles and dyslexia. More accurate performance on neuromyths was predicted by age (being younger), education (having a graduate degree), exposure to neuroscience courses, and exposure to peer-reviewed science. These findings suggest that training in education and neuroscience can help reduce but does not eliminate belief in neuromyths. We discuss the possible underlying roots of the most prevalent neuromyths and implications for classroom practice. These empirical results can be useful for developing comprehensive training modules for educators that target general misconceptions about the brain and learning.

Thursday, August 10, 2017

China’s Tool for Social Control: A Credit Rating for Everything

China’s New Tool for Social Control: A Credit Rating for Everything. By Josh Chin and Gillian Wong
https://www.wsj.com/articles/chinas-new-tool-for-social-control-a-credit-rating-for-everything-1480351590
Beijing wants to give every citizen a score based on behavior such as spending habits, turnstile violations and filial piety, which can blacklist citizens from loans, jobs, air travel
WSJ, Nov. 28, 2016

HANGZHOU, China—Swiping her son’s half-fare student card through the turnstile here one Monday afternoon, Chen Li earned herself a $6 fine and a reprimand from a subway-station inspector for not paying the adult fare.

A notice on a post nearby suggested more-dire consequences. It warned that infractors could be docked points in the city’s “personal credit information system.” A decline in Ms. Chen’s credit score, according to official pronouncements, could affect her daily life, including securing loans, jobs and her son’s school admission.

“I’m sure if it comes up, I can explain,“ Ms. Chen said, saying she picked up the card accidentally. “It was unintentional.”

Hangzhou’s local government is piloting a “social credit” system the Communist Party has said it wants to roll out nationwide by 2020, a digital reboot of the methods of social control the regime uses to avert threats to its legitimacy.

More than three dozen local governments across China are beginning to compile digital records of social and financial behavior to rate creditworthiness. A person can incur black marks for infractions such as fare cheating, jaywalking and violating family-planning rules. The effort echoes the dang’an, a system of dossiers the Communist party keeps on urban workers’ behavior.

In time, Beijing expects to draw on bigger, combined data pools, including a person’s internet activity, according to interviews with some architects of the system and a review of government documents. Algorithms would use a range of data to calculate a citizen’s rating, which would then be used to determine all manner of activities, such as who gets loans, or faster treatment at government offices or access to luxury hotels.



The endeavor reinforces President Xi Jinping’s campaign to tighten his grip on the country and dictate morality at a time of economic uncertainty that threatens to undermine the party. Mr. Xi in October called for innovation in “social governance” that would “heighten the capacity to forecast and prevent all manner of risks.”

The national social-credit system’s aim, according to a slogan repeated in planning documents, is to “allow the trustworthy to roam everywhere under heaven while making it hard for the discredited to take a single step.”

Thus far, the pilot data-collecting systems aren’t yet tied together into what Beijing envisions as a sweeping system, which would assign each citizen a rating. It isn’t clear that Ms. Chen’s ticket infraction made it into any central system, although the notice warned that fare-dodgers risked being marked down starting Jan. 1; a station agent said only repeat offenders are reported.

Zan Aizong, a Hangzhou human-rights activist, sees the system, once it’s fully operational, as an Orwellian exercise to keep closer tabs on a populace already lacking basic liberties such as freedom of speech. “Tracking everyone that way,” Mr. Zan said, “it’s just like ‘1984.’ ”


Blacklisted

China’s judiciary has already created a blacklisting system that would tie into the national social-credit operation. Zhuang Daohe, a Hangzhou legal scholar, cites the example of a client, part-owner of a travel company, who now can’t buy tickets for planes or high-speed trains because a Hangzhou court put him on a blacklist after he lost a dispute with a landlord.

“This has had a huge impact on the business,” said the client’s wife. “He can’t travel with clients anymore.” Added Mr. Zhuang: “What happens when it punishes the wrong person?”

Hangzhou officials didn’t respond to inquiries.

Another government system blacklists badly behaved tourists.

Driving the social-credit system are the State Council—China’s cabinet—and the central national-planning agency. A blueprint the cabinet published in 2014 stated it aimed to “build sincerity” in economic, social and political activity. It stressed the need for fair and clean government and for punishing polluting factories and bribe-takers.

Blacklists will expose offenders and restrict them from certain activities, while well-behaved citizens will earn access to “green lanes” that provide faster government services, the blueprint said. Citizens in jobs deemed sensitive—lawyers, accountants, teachers, journalists—will be subject to enhanced scrutiny, it said.

The State Council and national-planning agency didn’t respond to requests for comment.

China’s government must overcome technological and bureaucratic obstacles to build a system that can monitor 1.4 billion people. Government departments often guard their information, undermining efforts to build a unified database, and their systems often aren’t compatible, said Meng Tianguang, a political scientist at Beijing’s Tsinghua University who advises the government on applying “big data” to governance issues but isn’t directly involved in the social-credit system.

“Whether we can actually pull this off, we’re in a state of uncertainty at the moment,” Mr. Meng said. “Either way, it’s better than the traditional era,” until recently, he said, “when we had no data and policy was based on the judgment of individuals.”

The Shanghai government on an official website has identified scores of violations that can incur credit penalties in its pilot system, including falling behind on bills and breaking traffic rules. State-media reports list penalties for not being filial to one’s parents. (Under Chinese law, parents over 60 may sue children for not visiting regularly or not ensuring they have enough food.)

Penalties for low scorers will include higher barriers to obtaining loans and bans on indulgences such as luxury hotels, according to state-media reports.

The Shanghai system appears to still be in an early phase. Residents can check their social-credit records, but records reviewed by The Wall Street Journal didn’t show any nonfinancial data. Shanghai city officials didn’t respond to inquiries.

Despite official-media warnings and propaganda promoting sincerity, dozens of people interviewed in Shanghai weren’t aware of the social-credit plan. Many agreed more should be done to enforce higher moral standards, bemoaning habits such as spitting, cutting in line and being cold to strangers in need.

Research by Yang Wang, a Syracuse University expert on internet behavior, has shown Chinese internet users, accustomed to the idea of government snooping, are less concerned with online privacy than Americans. The most common word for privacy, yinsi, didn’t appear in popular Chinese dictionaries until the mid-1990s, he notes.


Behavior reports

In the tree-lined Yangjing neighborhood, subdistrict authorities maintain a database that gives a hint as to what elements of a broader social-credit system might look like. The database collects reports on locals’ behavior from residential committees, said Yuan Jianming, the head of the Yangjing Sincerity Construction Office.

Since mid-2015, the office has published a monthly “red list” of exemplary residents. Zhu Shengjun, 28, a high-school teacher, was named on a September red list. He said he didn’t know why. While he supported efforts to encourage better behavior, he hesitated at the idea of linking that with financial consequences, saying “it seems like too much of a stretch.”

The office also maintains a “gray list” of people behaving badly—throwing garbage out of windows, say—but the office hasn’t decided whether to publicize it, Mr. Yuan said.

In an area with a population of roughly 170,000, only around 120 have made Yangjing’s red list. Officials there complained to Chinese media this year that limited data sharing between departments was hampering efforts to rate people.

Businesses, too, get surveillance in pilot cities, where anyone can look up records on registered companies, though the records are sometimes incomplete. One objective: turning around what leaders see as a crippling lack of trust among citizens from decades of corruption and bare-knuckle competition.

So the social-credit system aims not just to collect data on individuals for official use, it seeks data on the behavior of businesses to analyze and show the results to consumers.

One example is food safety, a major issue since anger erupted over melamine-tainted milk powder that killed six infants in 2008. Subsequent scandals, including the sale of waste oil scooped up from gutters for reuse in restaurants, have continued to fuel mistrust.

Yangjing officials offer a solution: touch-screen displays they installed this summer in some restaurants. The screens, part of a local social-credit pilot system, offer an unusual level of transparency for China. Lit up with slogans—“Join heart to hand, be a model of sincerity” reads one—they display information about where ingredients came from and when waste oil was last picked up. Customers can watch videos on a mobile app showing chefs working, and the system displays the eatery’s health-department rating.

One recent Monday at Jujube Tree, a vegetarian restaurant, the food-safety console was partially obscured by poster board. Manager Wang Dacheng said it was because the system had erroneously downgraded the restaurant’s health rating, and local officials couldn’t fix it. “We have a lot of return customers. What if they come in and see that?” Mr. Wang said. He said he supported the system but was wary of its being applied without better controls.

Yangjing officials didn't respond to inquiries.

For initial social-credit efforts, local officials are relying on information collected by government departments, such as court records and loan and tax data. More-extensive logging of everyday habits, such as social-media use and online shopping, lies with China’s internet companies, including e-commerce giant Alibaba Group Holding Ltd.

A credit-scoring service by Alibaba affiliate Ant Financial Services—one of eight companies approved to pilot commercial experiments with social-credit scoring—assigns ratings based on information such as when customers shop online, what they buy and what phone they use. If users opt in, the score can also consider education levels and legal records. Perks in the past for getting high marks have included express security screening at the Beijing airport, part of an Ant agreement with the airport.

“Especially for young people, your online behavior goes towards building up your online credit profile,” said Joe Tsai, Alibaba’s executive vice chairman, “and we want people to be aware of that so they know to behave themselves better.”

Alibaba shares aggregate data about online sales with China’s statistics bureau but doesn’t divulge personal data unless required to by law, for example in criminal investigations, Mr. Tsai said.

In the U.S., private concerns such as credit-reporting agencies and ride-sharing services compile certain ratings based on consumer data or reviews.

The local-government trials aren’t known to be tapping private-sector data, although the social-credit system blueprint designates internet data as a “strategic national resource” and calls for internet companies to contribute data, without getting into specifics.

Whether private and public data systems will be combined is still being hammered out, said Zhu Wei, a China University of Politics and Law scholar who has advised the government on social-credit efforts.

In an October speech screened to 1.5 million officials, Alibaba Chairman Jack Ma urged law-enforcement agencies to use internet data as a tool to identify criminals, according to posts on a Communist Party social-media feed. He didn’t mention sharing Alibaba’s user data. His comments raised eyebrows for broaching the notion that internet companies might share data with government agencies. Alibaba declined to make Mr. Ma available for comment. “We believe the application of machine learning and data analytics for the purpose of crime prevention is consistent with our core values: solving society’s problems,” the company said

In an interview Nov. 1 with state media, a deputy head of China’s central-planning agency, Lian Weiliang, noted that much of the government’s credit-related data were stuck on “isolated islands” and said a central data platform had been established to encourage information sharing. He said the platform had collected 640 million pieces of credit information from 37 central-government departments and various local governments.

The agency said the government has stopped untrustworthy people, identified by the court system, from buying airline tickets 4.9 million times.

Some advisers to the government, such as Mr. Zhu and Mr. Meng, said they were skeptical the system would meet the 2020 deadline because of the immense task of integrating data and keeping information secure.

In Hangzhou, where Ms. Chen used her son’s pass, residents can check their social-credit records at a government-services center. Records the Journal viewed showed only whether people had kept up with health-insurance and social-security payments—a far cry from the central government’s goals.

—Kersten Zhang, Alyssa Abkowitz and Qian Junya contributed to this article.

Appeared in the November 29, 2016, print edition as 'China’s New tool: a Social Credit score.'

Gene Editing Using CRISPR -- Why the Excitement?

JAMA Viewpoint
Gene Editing Using CRISPR -- Why the Excitement? Anthony L. Komaroff, MD
JAMA. Published online August 10, 2017. doi:10.1001/jama.2017.10159
jamanetwork.com/journals/jama/fullarticle/2646800

The gene-editing technique known as CRISPR (clustered regularly interspaced short palindromic repeats) is only 5 years old, yet it has galvanized biomedical research and raised important ethical questions. What is it, how does it work, and how could it change medical practice?
The Evolution of Gene Editing

Biomedical scientists have been “editing” (or, at least, altering) genes for many years. Recombinant DNA technology allowed particular genes to be inserted into a plasmid (a circle of DNA) or into a virus: bacterial and yeast cells now could produce therapeutically useful human proteins, and viral vectors could perform gene therapy in humans. Gene targeting and RNA interference allowed the knockout of particular genes and the insertion of a healthy gene at the site of a defective gene. Zinc finger proteins and transcription activator-like effector nucleases (TALENs) precisely altered specific genes. Then came CRISPR. Compared with these previous technologies, CRISPR is easier, faster, less expensive, and more powerful.


How Does CRISPR Work?

CRISPR technology depends on the fact that a strand of nucleic acid (DNA or RNA) with a particular sequence of bases binds naturally to another nucleic acid strand with a matching (complementary) sequence. The workhorse of CRISPR technology is a complex of RNA and protein (primarily nucleases). The most widely used complex is called CRISPR-Cas9.

The RNA in a CRISPR-Cas9 complex has 2 functions. One part is programmed to recognize a particular sequence of bases in the target gene, while the other holds the Cas9 proteins close. Cas9 then unwinds or unzips a double helix so that the target nucleic acid sequence is made “visible” to the matching CRISPR RNA sequence, which quickly binds to its target. Then Cas9 cuts both strands of the target DNA precisely at the right spot.

CRISPR can affect the structure of a gene and can correct a single-base mutation. For example, CRISPR can transform the gene for hemoglobin S (sickle cell globin) into the gene for hemoglobin A. It does this by adding into the CRISPR mix a short DNA sequence for the healthy hemoglobin A gene: after Cas9 cuts the globin gene at the point of the sickle mutation, the sequence that codes for hemoglobin A is inserted.

CRISPR also can affect the expression of a gene: it can shut off the production of a protein, or ramp it up. For example, it can edit the messenger RNA made by a gene; alternatively, it can edit the “noncoding” DNA in the genome that controls the expression of specific genes.
Using CRISPR in Living Organisms

The DNA that codes for the CRISPR RNA, and for the CRISPR proteins (such as Cas9), can be introduced into living organisms using viral vectors, lipid nanoparticles, and other means. Typically, the goal is to reach just the pertinent cells—for example, just hematopoietic stem cells if the goal is to generate hemoglobin A instead of hemoglobin S.

The delivery of CRISPR to a target tissue can be hazardous, and the CRISPR payload does not always reach the intended destination. One way of solving that problem is to first edit an organism’s target cells (such as hematopoietic stem cells) in the laboratory, allow the edited cells to multiply, and then reinfuse those edited cells into the organism, where they home to their target tissue (such as the bone marrow).

CRISPR also can generate organisms in which every cell has been altered in a specific way. For instance, editing the genes in a fertilized egg leads to animals that have the edited genes in every cell.


How Was CRISPR Discovered?

Some medical breakthroughs are inventions, others are discoveries, and some, like CRISPR, are both.

The path leading to CRISPR was tortuous and full of surprises. First, scientists discovered unusual structures in bacterial genomes: clustered regularly interspaced short palindromic repeats (CRISPR) followed by genes for various nuclease proteins. These structures were found to somehow aid a bacterium’s ability to prevent infection by viruses (bacteriophages). The mechanism was subsequently discovered: the CRISPR genes edit viral genes, thereby disabling the viruses.1,2

Then came ultimate discovery and the invention. Scientists realized that the CRISPR-Cas9 complex could be modified and simplified to produce a programmable tool by which the nucleic acids of all plant and animal species could be precisely edited.1,2 The technology was optimized for use in mammalian cells and to edit multiple genes simultaneously.3,4 Subsequent variants of CRISPR technology involving different nuclease proteins have been developed to make CRISPR simpler and more precise.
Limitations of CRISPR

CRISPR allows remarkably precise editing, but it is not perfect. Sometimes, unintended nucleic acid sequences get edited—so-called off-target effects. This may occur more frequently than had been thought. Furthermore, some genetic “defects” that increase the risk of one disease decrease the risk of another. For example, people with sickle cell disease are less vulnerable to malaria: fixing hemoglobin S to solve one problem may cause another. Moreover, scientists understand relatively little about the health effects of “fixing” any particular polymorphic variant. In addition, like any powerful technology, CRISPR could be abused. Indeed, the US intelligence community has publicly expressed concern that CRISPR could produce a weapon of mass destruction.5


How Is CRISPR Affecting Biological Research?

CRISPR technology has transformed genetic research with plants and microbes. It has greatly aided research with many animal models, such as fruit flies, worms, and zebrafish, and has revolutionized the process for creating genetically modified mice,6 essential tools for medical research. Also, CRISPR has made possible the editing of primate genomes. Moreover, CRISPR has been used to treat disease in mice: a viral vector carried a CRISPR complex programmed to edit a mutated gene for dystrophin into the skeletal and cardiac muscle of mice with Duchenne-like muscular dystrophy, and a single treatment led to greatly improved muscle function.7


How Might CRISPR Affect Medical Practice?

CRISPR has greatly reduced the tumor burden of human prostate cancer cells in mouse xenografts.8 It has made possible a test that can be used in resource-limited settings for immediate diagnostics, such as for Zika virus.9 CRISPR also has been used for editing genes in T cells, ex vivo, to program them to attack a patient’s tumor when those cells are reinfused.

Similarly, it may be possible to edit a patient’s hematopoietic stem cells to correct sickle cell anemia and β-thalassemia. Using CRISPR in humans to edit solid-organ cells in vivo, however, as in the mice with muscular dystrophy, is further off.

The role of CRISPR in treating most of the major causes of disability and death in the developed nations is uncertain. These diseases typically are influenced by variants in multiple genes, each of which only slightly increases disease risk. More important, lifestyle modification is likely to have a greater influence on preventing and controlling these diseases than gene editing, no matter how powerful the technology becomes.

Experiments using CRISPR to edit human germ cells are subject to particular scrutiny because such experiments affect all descendants. Gene editing followed by in vitro fertilization could eliminate the risk that a conceptus would inherit (and pass on) a terrible disease—but it also could create an editing error that would harm future generations. The use of CRISPR to edit disease-related genes in germ cells also could generate a demand to protect all offspring against future risks (such as reducing the risk of Alzheimer disease by converting the ε4 variant of APOE to an alternative polymorphism). Moreover, CRISPR could create a demand for “designer babies” with certain desired traits. Society needs to grapple now with the ethical questions raised by such demands, before the technology can satisfy them.
How Might CRISPR Affect Human Health More Broadly?

CRISPR is being used to make plants and animals resistant to disease; to create certain animals (eg, pigs and cows) that become “bioreactors” for making therapeutic human proteins; and to generate pigs that could serve as human organ donors (such as for heart valve tissue), because their organs do not elicit an immune attack following transplantation. Theoretically, CRISPR gene drives could render mosquitoes all over the globe incapable of hosting various human pathogens.

The discovery and invention of CRISPR are already having a profound effect on biomedical research and are beginning to have an impact on medical practice. The scientists who created the CRISPR technology probably cannot imagine all of the ways in which it will be used. Two of those scientists said it best: “Every time we unlock one of nature’s secrets, it signals the end of one experiment—and the beginning of many others.”5

References at the original source.

Dangerous Days: The Impact of Nationalism on Interstate Conflict

Dangerous Days: The Impact of Nationalism on Interstate Conflict. Jamie Gruffydd-Jones. Security Studies, Fall 2017, Pages 698-728, http://www.tandfonline.com/doi/abs/10.1080/09636412.2017.1336393

Abstract: Does an upsurge in nationalism make interstate conflict more likely? This article gives evidence to suggest that spikes in nationalism do have a direct impact on the likelihood of disputes between states. In it, I use national days or anniversaries as occasions that increase the salience of a national identity and its historical wars. I show that in the two months following national days, conflict is markedly higher than would be expected - almost 30 percent more likely than the rest of the year-and particularly likely for states who initiate conflict or who have revisionist intentions. I demonstrate further how nationalist sentiment can increase international tensions with a case study of national anniversaries in China and Japan. Together, this evidence suggests that the increase in nationalism around national days provides both risks and opportunities to regimes and shapes when they choose conflict over cooperation in international relations.

The "Hearts and Minds" Fallacy: Violence, Coercion, and Success in Counterinsurgency Warfare

The "Hearts and Minds" Fallacy: Violence, Coercion, and Success in Counterinsurgency Warfare. Jacqueline Hazelton. International Security, Summer 2017, Pages 80-113, http://www.mitpressjournals.org/doi/abs/10.1162/ISEC_a_00283

Abstract: Debates over how governments can defeat insurgencies ebb and flow with international events, becoming particularly contentious when the United States encounters problems in its efforts to support a counterinsurgent government. Often the United States confronts these problems as a zero-sum game in which the government and the insurgents compete for popular support and cooperation. The U.S. prescription for success has had two main elements: to support liberalizing, democratizing reforms to reduce popular grievances; and to pursue a military strategy that carefully targets insurgents while avoiding harming civilians. An analysis of contemporaneous documents and interviews with participants in three cases held up as models of the governance approach - Malaya, Dhofar, and El Salvador - shows that counterinsurgency success is the result of a violent process of state building in which elites contest for power, popular interests matter little, and the government benefits from uses of force against civilians.

My comment: I am afraid that this is how things are.