Category Archives: Human Genetics

In his paper, Dr Smith argues that genetically modifying embryos to prevent the transmission of serious genetic diseases is indeed ethical and, from a utilitarian standpoint, the only conceivable way to deal with disease-associated genes in an embryo.

Dr Smith wrote that genetic modification would allow doctors to help prevent cardiovascular disease, cancer and dementia, as well as other illnesses, in future humans. It would also stand to reason that that lifespans could be substantially extended, Smith said.

While there is still a stigma on genetic modification in society, Dr Smith believes that we are perhaps only less than two years away from ethically making genetically-modified babies.

Other bioethicists and scientists dont quite agree with Dr Smith, noting that the risks of gene editing have not all been confirmed and are still being studied.

According to CNN, Joyce Harper of the University College London (UCL) Institute for Womens Healthtold the Science Media Centre (SMC) in London that she does not believe that there are adequate experiments that will prove that this technology is safe.

While Harper acknowledges that genome editing has huge potential, she wants public debate and legislation to ensure we have carefully thought this through.

Others have also criticised Dr Smiths work. Sarah Norcross, director of the Progress Educational Trust (PET), an organisation whose aim is to improve the publics understanding and view of genetics, said that Smiths analysis is flawed.

In terms of what people think on the subject, Norcross noted that more work and research need to be done in order to better understand the risks of the technology.

Referencing the work of Chinese scientist He, Norcross told the SMC that lessons should be learned from his mistakes. If this technology is to be put to similar use in future, then far higher scientific and ethical standards need to be met, said Norcross. /TISG

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Genetically-modified babies are 'ethically justifiable' and could be a possibility in two years: Expert - The Independent

A DNA test can reveal surprising facts about us certain genes make us more inclined to have dry earwax, for example, and others make us more likely to sneeze when we see a bright light. Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA.

Innocuous facts like these were what DNA kits were used for finding out when they first became commercially available. However, as the tests have become more sophisticated, the companies behind them have shifted their marketing focus. Users of at-home DNA tests have been known to uncover deep-rooted facts about themselves, from discovering long-lost relatives to learning of their ancestors origins and their susceptibility to genetic diseases.

Finding out that you have a pre-existing health condition might not seem like the best idea for a Christmas present, but that hasnt stopped the test kits from enjoying a surge in popularity. MIT Technology Review estimates that by the start of 2019, more than 26 million people had taken an at-home ancestry test. The market is expected to be worth $45bn by 2024.

Nevertheless, despite the emerging industrys rampant growth, there have been mounting concerns that its practices could infringe on consumers rights. Whenever people fork out $100 to $200 for a DNA test, the hidden cost of that transaction is their personal data which, from then on, is held in the databases of a private company. Once these companies obtain genetic information, its very difficult for users to get it back.

By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair

Ignorance is blissLong before people were able to take DNA tests from the comfort of their own home, psychologists worried about their possible impact on peoples mental health. Ever since the Human Genome Project was started in 1990, many scholars have maintained that DNA tests should be used with caution, on the grounds that understanding ones own health risks could lead to anxiety or depression.

Conversely, a study by the Hastings Centre found that discovering an increased risk of developing Alzheimers disease did not make people more depressed or anxious. And in the event that people discover a particularly urgent health risk like a mutation of the BRCA1 or BRCA2 genes, which puts individuals at a high risk of developing cancer at a young age any adverse psychological effects are presumably worth it to obtain this life-saving information.

However, at-home DNA tests could still pose a risk to mental health, in part because they remove medical professionals from the equation. Adrian Mark Thorogood, Academic Associate at the Centre of Genomics and Policy, warned that this is far from best practice for receiving a DNA test result. Results should be communicated through a medical professional who can interpret the result in the individuals specific context, and offer a clear description of the tests limits, he told The New Economy.

Without a professionals assistance, users could be left alone to battle with a troubling revelation about their health. There is also a danger that without guidance, some people could misinterpret their test result, placing undue stress on their mental health.

There is another unpleasant discovery that people can make through a DNA test one they may be even less prepared for. By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair. Others have discovered they were conceived by rape and that their mother decided to never tell them. What began as a seemingly harmless urge to find out more about their heritage ends in psychological trauma and family breakdown.

Brianne Kirkpatrick, a genetics counsellor, is part of a growing sector of therapy specifically tailored towards helping people come to terms with receiving unexpected DNA results. One cant help but wonder whether her patients end up wishing theyd never taken the test at all.

I dont recall anyone saying they wish they could go back and not learn the truth, Kirkpatrick said. But I have had a number of people say to me they wish they had found out their shocking information from a person, rather than a computer.

While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications

The fact that virtually anyone can now find out their real parentage through a simple DNA test has wide-reaching repercussions for the accountability of paternity. Historically, men have always had a much greater ability to conceal their status as a parent, as they dont have to bear the child. The world of direct-to-consumer DNA testing blows this capacity for anonymity out of the water.

This is particularly problematic when it comes to sperm donation. Anonymity is a key selling point for many potential donors, but now all their future biological offspring has to do is swab the inside of their cheek to completely compromise that anonymity. Research suggests that we could see a drop in donor rates as a result. A 2016 study in the Journal of Law and the Biosciences found that 29 percent of potential donors would actually refuse to donate if their name was put on a registry.

The wave of parental discoveries made through direct-to-consumer DNA tests raises questions about where the responsibility of the seller sits in all this. Most health professionals recommend that individuals seek out genetics counselling once they receive DNA results. Some, like Invitae, offer counselling services but arent direct-to-consumer companies. Many of those that are including 23andMe do not offer such a service. It could be argued that this shows a certain disregard for the consequences of using their product. Unfortunately, irresponsible decisions like this have tended to characterise the industrys path to success.

Genetic Wild WestIn September 2019, 17 former employees from the Boston-based genetic testing company Orig3n accused the firm of giving consumers inaccurate results. Allegedly, if a customer took the same test twice, their results could be extremely different each time. A former lab technician produced a leaked report to Bloomberg Businessweek that revealed 407 errors like this hadoccurred over a period of three months.

Part of Orig3ns USP was that it offered advice supposedly calculated based on a consumers genetic profile. Former employees have cast doubt over the companys modus operandi by claiming that the advice they gave was in fact routinely lifted from the internet. The advice given ranged from the technically correct but uninspired to the broadly unhelpful such as telling people to eat more kale and the utterly bogus, like advising clients to eat more sugar to eliminate stretch marks.

Although Orig3n is a relatively small player in the sector, news of this scam nonetheless illustrates how little protection consumers have in this nascent market. Analysts say we are currently witnessing a Wild West period in the consumer genetics space thanks to a lack of regulation, raising concerns over whether we can trust these companies with our genetic data. While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications.

In the United States, if my social security number is stolen, that is difficult, but not impossible, to get frozen, changed, etc, said Natalie Ram, an associate professor at the University of Maryland Francis King Carey School of Law and a specialist in bioethics and criminal justice. But theres literally no way to change your genetic code.

Genetics platforms like 23andMe, AncestryDNA and FamilyTreeDNA are now sitting on a goldmine of very personal data. In 2013, a 23andMe board member told Fast Company that it wanted to become the Google of personalised healthcare. If this statement makes anything clear, its that the company wasnt planning on making its millions simply by selling DNA test kits: its mission was always to amass significant amounts of data on its users, which it could then monetise.

There is a wide range of reasons why companies might want to buy genetic data. Perhaps the most benign is medical research, which genetics platforms allow users to opt in or out of. But other companies might use your genetic data to better sell you products or, conversely, deny them to you for instance, one sector that would see a clear monetary value in obtaining genetic data is insurance. In the US, the Genetic Information Nondiscrimination Act of 2008 prevents employers and health insurers from using a persons genetic information when making decisions about hiring, firing or raising rates. However, this does not include life insurance or short or long-term disability insurance.

At first glance, it seems as if theres a simple solution: if users are concerned about these risks, they should just choose for their data to be kept anonymous. However, choosing this option is not as foolproof as it once was. As long ago as 2009, researchers demonstrated that they could correctly identify between 40 and 60 percent of all participants in supposedly anonymous DNA databases by comparing large sets of that data with public datasets from censuses or voter lists. Since that experiment, DNA databases have grown massively.

With access to four to five million DNA profiles, upwards of 90 percent of Americans of European descent will be identifiable, said Ram. Its verging on a comprehensive DNA database that no US state or jurisdiction has suggested would be appropriate.

Shaping the lawWith comforting statements like your privacy is very important to us (ancestry.co.uk) and we wont share your DNA (familytreedna.com) emblazoned on their websites, some genetics platforms seem to be making privacy their number one priority. In the US, 23andMe and Ancestry are part of the Coalition for Genetic Data Protection, which lobbies for privacy protection in the DNA space. However, while the coalition advocates genetic data privacy in a specific context, it argues for a one-size-fits-all policy concerning all data. By comparison, the EUs General Data Protection Regulation regards genetic information as personal data, which makes DNA unique from other kinds of data.

There is a fundamental legal problem with boxing genetic data in with all other varieties, including the data that social media websites collect about us. In most cases, what a person does on the internet implicates them alone genetic data is different. We share our DNA with members of our family, which means that sharing it without their consent can be problematic.

Even if I can consent to using my DNA to identify me, that should not extend to my ability to consent to using my DNA to identify my relatives, said Ram. The reason I think thats a really critical distinction is because genetic relatedness is almost always involuntarily foisted upon us. So we dont choose our parents, we dont choose how many siblings we have. Its a product of biology, not a product of choice.

The legal issues surrounding genetic relatedness were put to the test in 2018 when police discovered the true identity of the Golden State Killer, who terrorised California in the 1970s and 1980s in a homicidal spree. Law enforcement officials were able to convict him only because they had succeeded in connecting the DNA of the suspect with that of a family relative on GEDmatch, a genetic database in the public domain. Across the US and around the world, people celebrated the arrest of a notorious criminal. The only problem was that the means of capturing him was not necessarily legal.

Prior to the case, GEDmatchs site policy made no explicit reference to the potential use of consumers data by law enforcement. However, the company defended itself by saying that users should have assumed it could be put to that use.

While the database was created for genealogical research, it is important that GEDmatch participants understand the possible uses of their DNA, including identification of relatives that have committed crimes or were victims of crimes, said GEDmatch operator Curtis Rogers in a statement.

Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA

However, privacy advocates like Ram argue that users consent for law enforcement to look at their data should not have been assumed. At least from a constitutional perspective in the United States, individuals ought to be recognised to have whats called an expectation of privacy in their genetic data, even if they use one of these services, she told The New Economy.

After the case, genetics platforms updated their policies to clarify their position on law enforcements use of peoples data. Interestingly, they took very different stances. While 23andMe and Ancestry said they would not allow law enforcement to search through their genetic genealogy databases, FamilyTreeDNA updated its policy to say it would give up data to officials, but only in the investigation of violent crimes. Users didnt know it at the time, but FamilyTreeDNAs policy update was already too little too late: in January 2019, it was revealed that the company had been secretly working with the FBI for nearly a year to solve serious crimes, without informing its users.

The Golden State Killer case exposed how little protection consumers really had in the direct-to-consumer genetics market. It showed that genetics platforms were capable of suddenly changing or contradicting their own policies and even, in the case of FamilyTreeDNA, betraying the trust of consumers.

Some might argue that this infringement on genetic privacy is simply the price we must pay to catch dangerous criminals. Of course, without the use of a genealogy database, the Golden State Killer may never have been caught. But the fact that genetic data can be harnessed to solve very serious crimes should not justify law enforcements unbridled access to such databases. Abuses of power do happen and, in the context of direct-to-consumer DNA tests, they already have: in 2018, for example, Canadian immigration officials compelled a man to take a DNA test and upload his results to FamilyTreeDNAs website. They then used the website to find and contact some of his relatives in the UK to gather more evidence in order to deport him.

Todays consumers are continually adjusting to shrinking levels of privacy. From the introduction of video surveillance and the mapping of residential areas on Google Earth to the revelation that Facebook harvests vast amounts of user data, we have seen the public react in the same way again and again: there is an initial public outcry, and then consumers simply adjust to the new level of diminished privacy. Our response to the rise of genetics platforms risks the issue being consigned to the same fate.

It is up to regulators to protect individuals right to privacy. While our genetic data may be something of a genie out of the bottle, that should not give the companies that collect it free rein over who sees it and what they choose to do with it.

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Collection of genetic data leads to privacy concerns - The New Economy

A biological clock governs aging in dogs just as in humans.

By Virginia MorellNov. 15, 2019 , 3:42 PM

Our Scotch collie, Buckaroo, is just shy of 14 years old. Following the long-debunked but still popular idea that one dog year equals seven human years, hes almost a centenarian. (This formula may be based on average life spans of 10 and 70 years for dogs and people, respectively.) Now, researchers say they have a new formula (see calculator below)to convert dog years to human yearsone with some actual science behind it.

The work is based on a relatively new concept in aging research: that chemical modifications to a persons DNA over a lifetime create what is known as an epigenetic clock. Scientists have built a case that one such modification, the addition of methyl groups to specific DNA sequences, tracks human biological agethat is, the toll that disease, poor lifestyle, and genetics take on our bodies. As a result, some groups have converted a persons DNA methylation status to an age estimateor even a prediction of life expectancy (worrying ethicists, who say the data could be misused by forensic investigators and insurance companies).

Other species also undergo DNA methylation as they age. Mice, chimpanzees, wolves, and dogs, for example, all seem to have epigenetic clocks. To find out how those clocks differ from the human version, geneticist Trey Ideker of the University of California, San Diego, and colleagues started with dogs. Even though mans best friends diverged from humans early in mammalian evolution, theyre a good group for comparison because they live in the same environments and many receive similar healthcare and hospital treatments.

All dogsno matter the breedfollow a similar developmental trajectory, reaching puberty around 10 months and dying before age 20. But to increase their chances of finding genetic factors associated with aging, Idekers team focused on a single breed: Labrador retrievers.

They scanned DNA methylation patterns in the genomes of 104 dogs, ranging from 4 weeks to 16 years of age. Their analysis revealed that dogs (at least Labrador retrievers) and humans do have similar age-related methylation of certain genomic regions with high mutation rates; those similarities were most apparent when the scientists looked at young dogs and young humans or old dogs and old humans. Most importantly, they found that certain groups of genes involved in development are similarly methylated during aging in both species. That suggests at least some aspects of aging are a continuation of development rather than a distinct processand that at least some of these changes are evolutionarily conserved in mammals, Ideker and colleagues report in a preprint posted online at bioRxiv.

We already knew that dogs get the same diseases and functional declines of aging that humans do, and this work provides evidence that similar molecular changes are also occurring during aging, says Matt Kaeberlein, a biogerontologist at the University of Washington in Seattle, who was not involved with this research. Its a beautiful demonstration of the conserved features of the epigenetic age clocks shared by dogs and humans.

The research team also used the rate of the methylation changes in dogs to match it to the human epigenetic clock, although the resulting dog age conversion is a bit more complex than multiply by seven. The new formula says a canines human age = 16 ln(dog age) + 31. (Thats the natural logarithm of the dogs real age, multiplied by 16, with 31 added to the total.)

Calculate

(*Enter numbers whose value is 1 or greater)

If your dog were a human, it would be:

Using that formula, dogs and humans life stages seem to match up. For example, a 7-week-old puppy would be equivalent to a 9-month-old human baby, both of whom are just starting to sprout teeth. The formula also nicely matches up the average life span of Labrador retrievers (12 years) with the worldwide lifetime expectancy of humans (70 years).

Theyve shown that theres a gradual increase in DNA methylation in both species with age, says Steve Austad, an evolutionary biologist and aging expert at the University of Alabama in Birmingham. He doesnt find that especially surprising, but he thinks the technique could reveal far more interesting results if applied to issues like the different life spans among different dog breeds.

Thats one goal of Kaeberlein, whose groups new Dog Aging Project (open to all breeds) will include epigenetic profiles of its canine subjects. He hopes to find out why some dogs develop disease at younger ages or die earlier than normal, whereas others live long, disease-free lives.

So, how does our Buckaroo fare? Happily, the epigenetic clock calculation goes in his favor. Hes now only 73 in human yearsand a spry 73 at that.

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Here's a better way to convert dog years to human years, scientists say - Science Magazine

The international group of scientists knew they were setting out to investigate an explosive subject: the hereditary basis of human same-sex behavior. Even so, the members of the prestigious Broad Institute in Cambridge, Massachusetts, may not have anticipated the magnitude of the public furor that erupted when they published their study, which identified several markers in certain genetic loci in the human genome related to same-sex sexual experience. The storm of reactions ranged from those who welcomed something seen as heralding significant progress in the field, to others who maintained that it would have been better if the scientists hadnt published anything.

The research results were published in full in the journal Science, at the end of August. This was the most extensive study of its kind ever conducted (there were about a half a million subjects), in which use was made of the GWAS (genome-wide association studies) method to analyze genetic big data. The researchers discovered five genetic markers (frequent, minor changes in the DNA segments of certain chromosomes) that appeared repeatedly among individuals who reported having had same-sex sexual experiences. Slight and frequent genetic variations were identified in both women and men, two others in men only and one more only in women.

No less important in the study, entitled Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior, is the scientists claim that a large number of genetic markers, perhaps even thousands, might operate simultaneously together although each in and of itself is of minuscule weight and influence ones same-sex orientation. Moreover, their study led the researchers to the conclusion that human genetics can explain up to 32 percent of same-sex sexual behavior.

What is at issue here, however, is not what the study contains but what it does not contain. As Melinda Mills, a sociology professor at Oxford, writes in the same issue of Science, there is no way that the researchers findings can be used as a tool to accurately predict same-sex behavior. Specifically, the fact that genetics can explain up to 32 percent of the fact that someone is gay or lesbian, does not mean that sexual identity is determined primarily by environmental factors not to mention social ones. This story is far more complex and has not yet been fully deciphered. Mills views are shared by Andrea Ganna, one of the chief authors of the new study.

What we basically do is statistical associations between having and not having these genetic markers and having or not having same-sex behavior, Ganna told Haaretz in a phone interview. Because we had this uniquely large study, he continued, which allowed us to have robust conclusions, and because we had the technology to measure the genetic markers of so many individuals, the time was right to confirm something that we expected: There is no one specific gay gene. Instead there are a lot of relatively common genetic markers, genetic mutations, that have a small effect on same-sex behavior.

At the same time, adds Ganna, a geneticist at Harvard Medical School and at Finlands Institute of Molecular Medicine, Not everyone is interpreting the fact that theres no single gay gene in the right way.

Gannas concern is shared by scientists around the world. Theyre worried that the researchers findings will fuel prejudice and discrimination against the LGBTQ community, and even spark calls for genetic engineering and genetic diagnosis among its members. So serious are these apprehensions that some have wondered whether the study would not do more harm than good.

As a queer person and a geneticist, I struggle to understand the motivations behind a genome-wide association study for non-heterosexual behavior, Joseph Vitti, a postdoctoral researcher at the Broad Institute, wrote on its blog, adding, I have yet to see a compelling argument that the potential benefits of this study outweigh its potential harms [T]he results presented not only oversimplify the question of biological causality, but also threaten direct damage by perpetuating the stereotype of LGBTQIA+ people as imprudent, while also likening same-sex attraction to a medical or psychological disorder.

Moreover, a website called The American Conservative posted an article entitled Not Born This Way After All? which wondered, skeptically: If the study proves that homosexuality is related to the environment, above all, and not to heredity why isnt it right and proper, in scientific terms, to allow those who so desire to undergo treatment in order to reduce their same-sex desires, which have now been shown not to be genetic?

That, however, is a simplistic reading of the studys findings. According to Michael Bailey, a professor of psychology at Northwestern University in Illinois, who was not involved in the study but has been conducting research on sexual orientation for 30 years, Its very important to understand that environment does not simply refer to social surroundings, like what your parents teach you and what kids you know, trauma and so on theres also a biological environment that begins right after conception.

Three years ago, Bailey and several colleagues published a survey of all the studies and professional literature in the field. The best studies have shown that genes are probably important but not overwhelmingly important, he tells Haaretz. We estimated in our 2016 review that 30 percent of the variation in sexual orientation is due to genetic variations. It may be this finding that led him to conclude that it is the biological environment that is mostly important. Bailey is convinced that men are born with their sexual orientation and that it is not subsequently acquired at any stage. He notes that there are several cases, I think there are seven throughout the professional literature, in which a baby boy was changed into a girl for medical reasons and was raised as a girl. When you follow these individuals through adulthood, you find that they are attracted to women and not to men.

In Baileys view, the best example of how biological-environmental factors can influence sexual orientation is the fraternal birth order effect. The phenomenon, whose existence is well established, he says, shows that the more older brothers a man has, the more likely he is to be homosexual. In practice, every older biological brother increases the probability that the youngest brother will be gay by about 33 percent. Thus, if the probability that a man with no older brothers will be gay is 2 percent, one older brother will increase the probability to 2.6 percent, and a second, third and fourth brother to 3.5 percent, 4.6 percent and 6 percent, respectively. Whats not yet clear is the reason for this.

In my mind, Bailey suggests, the best hypothesis as to why this happens is that a mothers immune system becomes increasingly active and produces antibodies against male proteins over successive births.

Fingers and hands

Behind this hypothesis is one of the most influential figures in the field, American-Canadian clinical psychologist and sexologist Ray Milton Blanchard. He was also among those who linked the fraternal birth order effect to another phenomenon of interest to scientists: the connection between being left-handed and having a same-sex orientation. The most extensive study in this regard was conducted in 2000, incorporating 20 different studies involving 7,000 gay male and female subjects and 16,000 heterosexual ones. It was found that gay men were 34 percent more likely to be left-handed. The situation was more extreme among lesbians: They were seen to have a 91 percent greater chance than straight women of writing with their left hand.

As a result, six years later, a research team led by Blanchard argued that the fraternal birth-order effect is relevant only among right-handed men. The reason is that, in any case, left-handed men who dont have older brothers already have a greater likelihood of being gay than right-handed men with such siblings.

A persons dominant hand turns out to be significant in another sense as well. An article published two years ago (about a study in which all the subjects had taken part in a gay pride parade in Toronto) found a connection between that hand and the gay persons role in bed: that is, the proportion of left-handed gays who defined their sexual behavior as passive or versatile (i.e., sometimes passive, sometimes not) was significantly higher than among those who described themselves as actives who clearly tended to be right-handed.

In research conducted over the years on the subject of the connection between sexual orientation and other attributes of the body, the hand holds a place of honor. But while Blanchard developed his theory on the basis of the whole hand, sometimes a few fingers are also enough: two, to be exact. In his 1998 study, British biologist John Manning confirmed a relatively old hypothesis, first put forward in Germany almost 150 years ago. Its gist is that the proportion between the length of index and ring fingers is, typically, different in men and women. Manning found that this phenomenon was detectable as early as age 2, which led to the observation that its source lies in the differences in testosterone and estrogen levels that already exist in the womb hereinafter: a biological-environmental factor.

Manning did not emphasize the element of sexual orientation in the two books and over 60 articles he wrote on this subject, but in the two decades that have elapsed since his study, more than 1,400 papers have been written on the ratio between the length of the second and fourth fingers (known as 2D:4D) and the connection between it and the level of risk of contracting certain diseases, as well as personality traits, cognitive and athletic abilities and sexual orientation.

One such study, published in 2010, maintained that straight and lesbian women are differentiated by the ratio between the length of the index and ring fingers, with lesbians tending to show a more masculine ratio i.e., closer to the average difference between the length of the fingers, among men. However, no such differences were found between gay and straight men.

Last year a team of scientists led by a British psychologist measured the fingers of 18 pairs of identical female twins, one lesbian, the other straight. Overall, differences in proportion were documented only in the lesbians and only in their left hand, and were comparable to the situation among men. This fact, the team concluded, could indicate a heightened exposure to testosterone in the womb but their study was based on a very small sample and drew much criticism. The critics charged that the conclusion was based on an overly simple means of measurement: of the way only two variables impacted each other. And, they added to bolster their argument, findings of studies involving those fingers have not been replicated in scientific experiments.

The field of gay science has been on a roll in recent years, but has a far longer history. Its modern phase dates to the early 1990s, when scientists began to publish increasing numbers of studies arguing that sexual orientation has a biological component. A leading scientist in this field is British-American neurobiologist Simon LeVay, who in 1990 performed autopsies on the bodies of 41 people: 19 gay men, 16 straight men and nine women. He discovered that the brain cells known as INAH-3 among the deceased gay men were relatively small, and closer in size to those of women than to heterosexual males.

In 1991, LeVay told Haaretz in a phone conversation, I published a study that got a lot of media attention, related to my observation that there was a region inside the hypothalamus that was different in size between men and women, and also between gay and straight men My additional finding was the difference in size between gay and straight men in this region inside the hypothalamus that is involved in the regulation of sexual behavior.

Adds LeVay, My general feeling is that there are certainly strong biological influences on peoples sexual orientation, but we cant say everything is genetic.

In the spirit of the period, and in light of the AIDS epidemic at the time, LeVay tried to be as cautious as possible about his conclusions. Its important to stress what I didnt find, he said in an interview to Discover magazine, in 1994. I did not prove that homosexuality is genetic, or find a genetic cause for being gay. I didnt show that gay men are born that way, [which is] the most common mistake people make in interpreting my work.

Three decades after publishing his study, he still thinks media coverage is doing an injustice to research even if its not his. Ive seen some headlines saying, basically, that this study [i.e., that of Ganna and his associates] shows its not genetic, or that are no gay genes, or something like that; and, of course, its not what the study shows at all.

Truly gay

In recent decades, scientific research (on men and women alike) in this realm has relied on an additional field: molecular genetics. The pioneer is geneticist Dean Hamer, who in 1993 conducted the first study of its kind.

We noticed that being gay, for males, tended to pass down through the mothers side of the family, he told Haaretz. And that is characteristic in genetics of something on the X chromosome because males get their X chromosomes from their moms That led us to look in families where there were gay brothers, to see if they shared anything on the X chromosome.

And thus, recalls Hamer, he and his team discovered Xq28: a genetic marker that plays a part in determining whether a person will be heterosexual or gay. He emphasizes that this is a factor, its not the factor and actually, overall, its not even the most important factor. He adds, Whats good about genetic studies, is that you know that whatever you find is a causal factor, because of course people are born with their genes, and its not something that changes over time.

LeVay, he explains, is looking directly at the brain, and were looking at what we think is building the brain and genes. Yet, its very difficult to know whether one was born with a brain like that, or whether that brain developed that way because of your behavior the causality is rather unknown.

At the same time, Hamer adds, That doesnt mean there arent specific pathways, because there has to be some sort of a pathway in the brain that controls sexual orientation. We know, for example, that the reason you become a male or a female is very simple: If you have a certain gene on the Y chromosome, you will produce male hormones, and if you have those you make a penis and scrotum and you become male. Accordingly, Theres probably some pathway in the brain that does same thing for sexual orientation, but were not going to discover it from genetics The answer will probably emerge from some sort of very sophisticated brain and developmental studies.

For 35 years, Hamer accumulated experience as a scientist at the National Institutes of Health in Bethesda, Maryland. That period is behind him. He doffed the white coat and now lives in Hawaii, where he makes films. But even if hes no longer occupied with research, it still occupies him.

Hamer: Back in the 1990s, I, along with all the scientists involved, believed that if we did good genetic studies wed find the important genes. For example, well find a gene that is responsible for the production of testosterone, and if its functioning was low, it would be possible to say that this is the cause of homosexuality in a particular person. But it turns out that it doesnt work that way. For every mental trait that has been studied everything you can imagine in the brain, for every single trait, theres a [vast number of] genes not to mention a host of complex societal and environmental factors.

For his part, Hamer has much praise for the Broad Institute study: The new GWAS study is really important, because for the very first time they used a huge sample and they mapped every inch of the genome. And this has never been done before. All the other studies were much smaller, or used many fewer genetic markers. But he also demurs: Whats very important is to look at what they actually analyzed. They didnt analyze people who were gay or lesbian, but anyone who had one single same-sex experience, which is quite different... They were measuring something more like openness to sexual experimentation.

As Hamer sees it, If you look for those five markers, or even just the three strongest markers, they are not necessarily found in people who actually identify as gay or lesbian. If you take people who are gay, like me, and look for those markers theyre not significantly there.

Hamer thinks that the whole field is lagging behind because of insufficient research, owing to the stigmas that plague the subject. I dont think sexuality is any more complicated than many other areas of human personality and individual differences, he observes, noting, We formally established that male sexuality is something that is deeply ingrained in people, its not any sort of choice really. It starts really early in life, and it has a major biological component to it. But, how it works? What the biological component is? Were completely unaware and dont know anything, and we barely know more than we did 25 years ago, or in the 1940s, when Kinsey did his work, to be honest.

Hamer was referring to biologist Alfred Kinsey, who in 1948 stunned the American public with his book, Sexual Behavior in the Human Male, which addressed previously taboo subjects, and challenged the traditional beliefs and existing knowledge about human sexuality. Kinsey had conducted a survey of men, which found that 37 percent of his subjects said they had undergone a homosexual experience of some kind, and 10 percent said they had been exclusively gay for three years of their adult life a statistic which to this day is generally said to represent the proportion of people engaging in same-sex behavior.

At the same time, subsequent studies reveal that the percentage of people who define themselves as exclusively homosexual is far lower, though it fluctuates from one article to the next. For example, a 2011 survey of nine different studies on the subject revealed that approximately 3.5 percent of Americans identify themselves as gays, lesbians or bisexuals. A poll involving 1,000 Jewish Israelis in 2012 found that 11.3 percent of the male respondents and 15.2 percent of the female ones said they felt an attraction to members of the same sex. However, only 8.2 percent of the men categorized themselves as gay or bisexual, while 4.8 percent of the women said they were lesbian or bisexual.

For his part, Ganna, of the Broad Institute, understands some of the criticism of his research. What we studied is not related directly to the biology, but to extended environmental factors related to it. Its not about our sample size once you have a lot of individuals, you can capture very small effects. But are these directly influencing same-sex behavior, or other things related to this topic? As a medical example, think about a study that looks for associations between genetic markers and lung cancer. In that example, what we found are genetic variants regarding how much you smoke, which is related to lung cancer.

One of the lessons, and one of the most interesting points arising from the study has to do, says Ganna, with the mode of measurement that had been in use since 1948, when Kinseys scale ranked individuals as being between 0 (totally heterosexual) and 6 (totally homosexual).

Ganna: Basically, the tendency is to locate individuals on a continuum. You can supposedly be anywhere between 100 percent heterosexual to 100 percent homosexual, which implies that the more youre homosexual, the less youre heterosexual, and vice versa. We show that this assumption actually doesnt hold water: When we look at the genetic data, its not that straightforward, theres no simple continuum of sexuality.

So, actually, you are refuting the Kinsey scale?

Ganna: Thats exactly one of our conclusions. What were now doing is, rather than asking people to put themselves on a scale somewhere between being exclusively heterosexual or exclusively homosexual, we ask them how much theyre attracted to men and women. You could be attracted to either of them, very attracted to both of them or to one more than the other. And that information will be crossmatched with genetic markers.

In the final analysis, he adds, We showed that this is just another natural human variation. Sexual orientation, similar to many other behavioral traits, is complicated and is composed of different factors. The interesting thing is how genetics and environment work together. If you think about how much more prevalent same-sex behavior has become lately, people engage in it more than in the past. And thats clearly not because our genetics are changing. Its because of the environment, because society is becoming more open and laws are changing.

Further research should focus on the relationship between environmental factors and genetics, Ganna says, and on how they interact. Its somewhat misleading to think of nature and nurture as separate aspects; they both contribute. So, it would be wrong to say that you can use only DNA to predict if someone will engage in same-sex behavior, but you also cant say its simply a [matter of] choice.

In summary, he says, I think that the more people who will understand that there are genetic and environmental components to sexual behavior, the better and this is a message that goes beyond just sexuality.

Choice and lifestyle

However, the relationship between science and the environment, and particularly the people living in it, is a complicated one. The subject definitely should be studied, but the social aspect of it is problematic, says LeVay, the neurobiologist. I am gay myself, and I feel strongly that gay people should be valued and accepted into society, regardless of what caused their sexual orientation. I dont think its vital for gay liberation to prove that gay people cant help but be gay there are plenty of other reasons [for accepting them], including basic human rights.

At the same time, he adds, this issue is socially relevant, because of traditional notions that see same-sex relations as a choice, a lifestyle or sinful behavior.

In recent years, there have been many studies showing that peoples attitudes toward homosexuality are closely tied to their beliefs about what makes people gay, says LeVay, citing a survey that showed there was a high probability that people who think homosexuality is a choice will object to a gay person being their childrens teacher which in a way might make sense, he adds: If you think being gay is something infectious, socially contagious, and you didnt want your kid to be gay, then you wouldnt want their teacher to be gay ... It follows that demonstrating that biological factors are involved, helps counter those ideas. Still, Im a bit ambivalent about the use of this type of research as some sort of a political weapon in the struggle for gay rights.

The Broad Institute study contains a reminder of the problems and stigmas that still exist with regard to the LGBTQ community. One of the parameters it considers are genetic correlations between genes that are ascribed to homosexuality, and certain psychological problems.

Bailey, the psychologist: One thing that was perceived as controversial, was to look for and find a genetic overlap between homosexual sex genes and genes associated with depression. Its not the same as saying all people who engage in homosexual sex are depressed for genetic reasons, but its also not something that can be easily ignored. There are assumptions that the higher rates of depression among gay men and lesbians is due to the way they are mistreated by society, but the evidence for that is not so overwhelming. There is also the fact, for example, that you have as high a rate of depression among homosexual men in the Netherlands, which is very tolerant, as you have in some less tolerant places, like the United States.

Ganna, for his part, tries to soften that criticism: Even if we see genetic overlap, or correlation, it is not set in stone that weve found a biological mechanism that causes depression and same-sex behavior, he says. There are many explanations for why this one genetic marker is associated with both things. But finding these correlations help us study human traits in general.

In the meantime, there is a price to be paid for conducting research in this realm, which all those involved must be aware of. Reminders of this abound, and are almost routine. In some cases whats at stake is not even a groundbreaking study or one of tremendous scientific importance. In 2017, for example, two researchers from Stanford published an article stating that gay men are predicted to have smaller jaws and chins, slimmer eyebrows, longer noses, and larger foreheads; the opposite should be true for lesbians. In the next stage, they created a facial-recognition program with the aid of more than 14,000 images taken from a singles site of straights and LGBTQs. The program was able to distinguish between gays and lesbians and heterosexuals with an accuracy of 81 percent for men and 71 percent for women, in contrast to an average rate of successful human guesses of 61 percent and 54 percent, respectively. Even though the program achieved relatively impressive results, the study as such drew widespread criticism not unusual for researchers engaged in such studies.

The Stanford gays identification program may be an extreme example, in this respect, but its also a byproduct of the considerable surge in studies in this field, a trend that began in the early 1990s. Together with the scientific community, media interest in the subject of same-sex orientation and its causes has contributed substantially to transmitting messages and shaping public opinion.

In the United States, this can be seen in a series of polls conducted by Gallup, Inc. The first one, conducted in 1977, found that only 13 percent of the respondents believed that homosexuality is an innate tendency, while 56 percent attributed it to environmental factors. This approach remained largely constant until the period between 1989 and 1996, when the rate of those supporting the innate thesis leaped from 19 percent to 31 percent; by 2001, it stood at 40 percent. Almost a decade and a half later, the annual poll produced, for the first time, a larger proportion who agreed with the innate argument. The latest survey, from the end of last year, showed this trend continuing: More than half of the American public believes that gay people are born with their sexual orientation, whereas only 30 percent attribute it to environmental factors (10 percent said both factors play a part, 4 percent cited other factors and 6 percent said they werent sure).

Changes in the perceptions of the origins of sexual orientation are having a pronounced effect on the struggle LGBTQ individuals are waging for equal rights. The latest Gallup poll shows that an absolutely majority (88 percent) of those who believe that homosexuality is an innate trait also support legitimizing same-sex marriages. In contrast, most of those who see this orientation as being environmentally driven (61 percent) are against.

When it comes to public opinion, which is very important, the born this way idea has been really resonant and has had a very positive impact on society, Hamer maintains. Public opinion polls asked people whether they think [gays] were born this way or not, and we know that believing that homosexuality is innate correlates with having positive feelings toward gay rights. Overall, its been important in educating the public about who we are, as gay people.

Such messages are reaching Israel as well. A poll conducted by the Dialog Institute for Haaretz at the end of 2013 found that 70 percent of those questioned favored full rights for same-sex couples, while 64 percent specifically backed their right to surrogacy. However, two polls conducted in the wake of the surrogacy law protest in July 2018 presented slightly lower numbers: About 57 percent of respondents expressed support for the right of same-sex male couples to surrogacy.

These polls did not ask Israelis whether they believe the origin of same-sex orientation is innate or environmental. If you ask Bailey, though, that doesnt really matter.

Ive gone to great lengths to try to persuade people not to base equal rights for gay people on the causal hypothesis, he says. Its a terrible idea to say gay people should have equal rights because they were born that way. Its terrible in part because some criminals might be born that way, and you dont want to them to have the same rights. Being gay doesnt harm anybody, other than people who are close-minded and easily offended. Preventing people from expressing their homosexuality is quite destructive for them. Thats true whether gay people are born that way or not.

See the article here:
Is sexual orientation genetic? Yes and no, an extensive study finds - Haaretz

News

Researcher Tom Cappola tells us about the latest clinical trials and medical breakthroughs to be announced during Scientific Sessions.

Chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania, Tom Cappola.

For the first time in its near 100-year history, the American Heart Association (AHA)will host its annual meeting in Philadelphia. AHAs Scientific Sessions is the largest cardiovascular meeting in the United States. On November 16-18, the meeting will attract nearly 18,000 attendees from more than 100 countries to the Pennsylvania Convention Center, and an additional two million medical professionals who will participate virtually in lectures and discussions about basic, translational, clinical and population science innovations aimed at reducing disability and deaths caused by cardiovascular disease and stroke.

The American Heart Association is excited to be in Philadelphia, said Michelle Kirkwood, director of National Science Media Relations for AHA. It has been on our wish list for some time, especially since the renovations at the Pennsylvania Convention Center and the citys landmark, robust nonsmoking laws that align directly with the American Heart Associations health and wellness goals. We are excited for our thousands of attendees to visit Philadelphia.

More than 610,000 people die of heart disease in the United States every year, according to the CDC. While heart disease is a leading cause of death for both men and women, it claims the lives of over 400,000 American women each year, or one death every 80 seconds. During the three-day meeting, more than 12,000 leading physicians, scientists, cardiologists and healthcare professionals in the global cardiovascular health community will host 850 educational sessions and more than 4,100 original research presentations to unveil the late-breaking science, clinical trials, and novel therapeutics and pathways that are shaping the future of cardiovascular care.

Its very fitting for Scientific Sessions to be here, chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania Tom Cappola said. We have the first medical school in the country and the first teaching hospital in the country. It makes sense that these new innovations would be presented in a place where theres already been so much innovation.

Cappola will be one of several Penn researchers leading the Cardiovascular Expert Theater, Innovations in Cardiovascular Therapies session during the meeting. Here are just a few big trends in heart care that Cappola says we can expect to learn more about during this weekends meeting:

Using artificial intelligence to monitor heart health

Artificial intelligence (AI) is having a big impact on cardiovascular care. Results from two preliminary studies to be presented this weekend will show AI can be used to accurately examine electrocardiogram (ECG) test results to possibly predict irregular heartbeat and risk of death. There will also be a presentation on the Apple Heart Study, which found that the Apple Watch and other wearable remote monitoring devices may be capable of detecting atrial fibrillation (aFib), an irregular and often rapid heartbeat that can lead to blood clots, stroke, heart failure and other complications.

Identifying new risk factors for aFib and stroke

George Mason University researchers will present results from two studies that found young people who smoke marijuana regularly have an increased risk of stroke. According to the study findings, young adults between the ages 18 and 44 who reported frequent use of marijuana, cigarettes and e-cigarettes were three times more likely to suffer stroke than young adults who did not smoke marijuana at all. The study also found that African-American males between the ages of 15 and 24 faced the highest risk of being hospitalized for arrhythmia.

In one Penn study to be presented this weekend, researchers found women who are diagnosed with peripartum cardiomyopathy (PPCM) during late pregnancy or within a month following delivery are more likely to experience restored cardiac function and improved outcomes compared to those who are diagnosed later in the postpartum period. The findings underscore the need for increased awareness and monitoring of heart failure symptoms, particularly among black women, who, on average, are diagnosed significantly later than white patients, according to study results.

Making advances in genetics and genomics

Another big trend at this years meeting will be the continued advancement in genetics and genomics, and how thats impacting cardiovascular care.

I think that genomic medicine has arrived and its arriving in waves, but it will ultimately affect all aspects of cardiovascular care, Cappola said. We have lots of people getting their 23andMe for sort of recreational purposes and they dont know what to do with it. But were starting to figure out what to do with that genetic information to improve care.

Another Penn Medicine study to be presented during the meeting will show why taller people may have an increased risk of developing atrial aFib. The research found a strong link between the genetic variants associated with height and ones risk for AFib, for the first time demonstrating that height may be a causal not correlated risk factor for the condition. Researchers hope insight from human genetics in large studies like this one will help them better understand causal risk factors for common disease.

It takes expertise to find links like this. Thats why researchers go to the American Heart Association meetings. You get all the experts together, they share their knowledge and this helps us to actually figure out what to do with this genetic information, Cappola said. Thats true across the board, but its particularly important for genomic medicine as it continues to advance.

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The American Heart Association's Annual Conference Comes to Philly This Weekend - Philadelphia magazine

Researchers have found that taller people have an increased risk of developing atrial fibrillation (AFib), an irregular and often rapid heartbeat that can lead to stroke, heart failure and other complications.

The research, which reveals a strong link between the genetic variants associated with height and one's risk for AFib, is the among the first to demonstrate that height may be a causal--not correlated--risk factor for AFib.

Researchers found that the risk for AFib climbed as one's height increased, with every one-inch increase in height translating to about a three percent increase in risk of Afib--independent of other clinical factors--as compared to those at average height (5 feet and 7 inches).

"Our findings suggest it may be beneficial to incorporate height into risk-prediction tools for AFib," said the study's lead author Michael Levin from University of Pennsylvania.

"While current guidelines advise against widespread screening for AFib, our findings show that a certain group of patients--specifically, very tall patients--may benefit from screening," Levin added.

AFib, which affects more than 33 million people worldwide, is a common, abnormal heart rhythm.

There are a number of clinical risk factors for developing AFib, including high blood pressure, heart disease, diabetes, and obesity.

Observational studies, examining population-level data, have found that taller individuals appear to have a higher risk of developing AFib.

To further examine the association between height and Afib, the research team leveraged data from the Genetic Investigation of Anthropometric Trials (GIANT) consortium, which studied more than 700,000 individuals to identify genetic variants associated with height.

They also examined data from the Atrial Fibrillation Genetics (AFGen) consortium, which studied more than 500,000 individuals to identify genetic variants associated with AFib.

The authors employed a statistical method which uses genetics to precisely estimate the relationship between two traits.

Their analysis revealed that genetic variants associated with height were also strongly associated with Afib, suggesting that increased height may be a cause of atrial fibrillation.

This relationship remained strong even after adjusting for traditional AFib risk factors, like heart disease, high blood pressure, and diabetes, among others.

From there, researchers used a similar statistical method to conduct an individual-level analysis of nearly 7,000 individuals enrolled in the Penn Medicine Biobank.

They found that height, and genetic variants associated with height, are strongly associated with an increased risk of AFib, independent from traditional clinical and echocardiographic risk factors.

"These analyses show how we can use human genetics to help us better understand causal risk factors for common disease," said the study's senior author Scott Damrauer.

The study is scheduled to be presented at American Heart Association 2019 Scientific Sessions in Pennsylvania, US.

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Taller People have Increased Risk of Irregular Heartbeat - News18

HURRICANE What would life be like if you knew you would get cancer one day, but could prevent it beforehand? Clinicians in Utah are hoping to accomplish just that through a new study.

One St. George man said he's participating for the health of his posterity.

Durward Wadsworth, 76, grew up on a farm in Southern Utah. He worked alongside his family tending to the fruits trees, horses, and other animals.

"We had to milk cows and bring hay in," he said.

The farm has remained, but things have changed.

"I have a brother that passed away. I have a sister that passed away, Wadsworth said.

They both died from cancer. Wadsworth was also diagnosed with colon cancer and finished chemo only a year ago.

It's not a fun treatment, he said. He went to the Dixie Regional Cancer Center for 12 rounds of chemo.

As a teenager Wadsworth was exposed to radiation during nuclear testing at the Nevada National Security Site.

"As kids, we didn't know any different, so we would go up on the hill and watch when one would explode and you could actually see the mushroom and hear the boom, he said.

Both his family history of cancer and heart disease, and his exposure to radiation, had him concerned.

His son encouraged him to participate in Intermountain Healthcare's HerediGene population study. Clinicians hope this study, in collaboration with deCODE Genetics of Iceland, will help them better understand the human genome.

Dr. Lincoln Nadauld, Chief of Precision Health at Intermountain Healthcare, said the study is unprecedented. He said it looks at the link between genes and human disease.

"This study is the largest of its kind. It's an attempt to map the genomes of 500,000 people over the next five years, Nadauld said. There is no genetic study in health care that has ever been reported or ever attempted that compares in size or scope.

Nadauld said this study will impact generations to come.

(It) will allow us and subsequent generations to better understand health and the origins of disease and health care-related issues, he said. It's going to change the way that we deliver health care for the better.

Nadauld hopes the study will help doctors better predict and prevent disease before someone is ill.

So let's intervene with either a medicine or a lifestyle change so that you never have to experience heart failure or heart attack or a stroke, he explained.

While this type of precision genomics started in oncology, Nadauld said his team has applied it to all of their medical disciplines, including cardiovascular and neurodegenerative disorders, metabolic issues and even mental illness.

This study could uncover the link between mental illness and genes, and could identify new treatments for mental illness, he said.

Even though Wadsworth still has a lot of life to live, he knows he probably won't personally benefit from the study by the time its completed. "But, you know, my posterity will benefit, he said.

That's enough motivation for him. Wadsworth said he doesn't want his five children and 18 grandchildren to suffer through cancer like he did.

"We want the best health care for them, he said. He also hopes they'll carry on the family farm.

Nadauld said the study isn't just for people who have been sick, but will include mostly healthy individuals.

He said it just takes a simple blood draw to participate. Nadauld said by the end of the year there will be 25 different walk-in clinics across the entire state.

Nadauld said he anticipates a very small percentage of the participants will be informed of a health issue, in which doctors and patients need to take action.

We expect that will happen in about 3% of our participants, he said.

See the rest here:
A new study hopes to prevent disease before it starts through genetics - KSL.com

New Registry, cvMOBIUS, Will Assess Lipid Therapies and Five-Year Cardiovascular Outcomes in 8,500 High-Risk Patients With a Recent Atherosclerotic Cardiovascular Disease Event

THOUSAND OAKS, Calif. (Nov. 15, 2019) Amgen in collaboration with the Duke Clinical Research Institute (DCRI) today announced plans to initiate theCardiovascularMulti-dimensionalObservationalInvestigation of theUse of PCSK9 inhibitors (cvMOBIUS) studythe first large-scale real-world study to assess lipid management and the impact of PCSK9 inhibitors on cardiovascular (CV) outcomes in clinical practice. While there is strong evidence demonstrating the efficacy of PCSK9 inhibitors from various randomized clinical trial studies, there is less information on the effectiveness of these medicines on cardiovascular outcomes in real-world practice.

The cvMOBIUS study will be conducted across the U.S. and Canada and will begin patient enrollment this month. A prospective observational registry of 8,500 adults eligible for treatment with a PCSK9 inhibitor will be followed for five years. In parallel, an electronic health record (EHR)-based registry will follow a broader population of adults hospitalized with atherosclerotic cardiovascular disease (ASCVD) at participating sites.

Cardiovascular disease is one of the most significant public health issues facing our country today. Gathering robust, large-scale data from diverse patients will better inform lipid management and help decrease the burden of cardiovascular disease in these high-risk patients, said Ann Marie Navar, M.D., Ph.D., assistant professor of medicine at the Duke University School of Medicine and member of the DCRI. The clinical evidence supporting the efficacy and safety of PCSK9 inhibitors in patients with cardiovascular disease is well established, but we still have a lot to learn about the benefits of these medicines in the real world.

Patients who have experienced a recent ASCVD event, including a myocardial infarction (MI), are at higher risk of experiencing another CV event, especially within the first year after.1,2Lipid lowering is one of the key approaches for reducing a patients risk for secondary events.1Based on large randomized trials, major professional cardiology societies, including the American Heart Association and the American College of Cardiology, acknowledge that lower is better when it comes to low density lipoprotein cholesterol (LDL-C) management in patients who have experienced an MI and other ASCVD events.3

LDL-C is one of the most important modifiable risk factors for cardiovascular disease, so lipid management is an essential element in reducing future CV events and improving clinical outcomes for high-risk patients, said Eric D. Peterson, M.D., MPH, distinguished professor of medicine at the Duke University School of Medicine and member of the DCRI. This large registry will examine how care is being delivered in clinical practice to patientswhether we are using the right medicines, whether we are reaching guideline-based LDL-C targets, and the degree to which achieving these goals impacts outcomes in real-world practice.

The cvMOBIUS study is important because it is one of the few instances that researchers will utilize data pulled directly from hospitals EHR systems for research. This should help set the stage for future big data analyses and pragmatic clinical trials, said Dr. Peterson.

Two large randomized outcomes trials, including the Repatha(evolocumab) cardiovascular outcomes (FOURIER) study, have demonstrated that innovative therapies like PCSK9 inhibitors lower LDL-C levels and can reduce the risk of heart attacks in high-risk patients with established cardiovascular disease. Additionally, the VESALIUS-CV trial, initiated in March 2019, is an ongoing randomized outcomes trial, designed to evaluate the long-term effects of Repatha in high-risk cardiovascular disease (CVD) patients without a prior heart attack or stroke. The study will be the first to investigate long-term outcomes in this population with Repatha for a minimum of four years.

Amgen is committed to building a vast body of evidence for Repathaclinical trial and real-world effectiveness data setsto advance the knowledge and treatment of cardiovascular disease, saidDavid M. Reese, M.D.,executive vice president of Research and Development at Amgen. This study will generate valuable real-world evidence to help us demonstrate that PCSK9 inhibitors, like Repatha, are an important treatment option for very high-risk patients and can help prevent recurrent cardiovascular events in the real world.

Drs. Navar and Peterson are co-primary investigators of the study.

About cvMOBIUS

cvMOBIUS is a multicenter prospective observational registry in the U.S. and Canada. The study will be comprised of two parallel arms: a multicenter, prospective observational arm that will include 8,500 patients who experienced an ASCVD event within 12 months, from 250 sites; and a parallel EHR-based registry of a larger cohort of patients hospitalized with an ASCVD event treated at participating centers. The primary endpoint includes time to death, any non-fatal MI and any non-fatal ischemic stroke (IS).

About the Duke Clinical Research Institute

The DCRI, part of the Duke University School of Medicine, is the largest academic research organization in the world. It delivers on its mission to develop and share knowledge that improves the care of patients through innovative clinical research by conducting groundbreaking multinational clinical trials, managing major national patient registries, and performing landmark outcomes research. DCRI research spans multiple disciplines, from pediatrics to geriatrics, primary care to subspecialty medicine, and genomics to proteomics. The DCRI also is home to the Duke Databank for Cardiovascular Diseases, the largest and oldest institutional cardiovascular database in the world, which continues to inform clinical decision-making 40 years after its founding.

About Repatha(evolocumab)

Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.4

Repatha is approved in more than 70 countries, including the U.S.,Japan,Canadaand in all 28 countries that are members of theEuropean Union. Applications in other countries are pending.

Repatha Cardiovascular Outcomes (FOURIER) Study Design

FOURIER (Further cardiovascularOUtcomesResearch with PCSK9Inhibition in Subjects withElevatedRisk), a multinational Phase 3 randomized, double-blind, placebo-controlled trial, was designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The primary endpoint was the time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint was the time to cardiovascular death, MI or stroke.

Eligible patients with high cholesterol (LDL-C 70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] 100 mg/dL) and clinically evident ASCVD at more than 1,300 study locations around the world were randomized to receive Repatha subcutaneous 140 mg every two weeks or 420 mg monthly plus effective statin dose; or placebo subcutaneous every two weeks or monthly plus effective statin dose. Optimized statin therapy was defined as at least atorvastatin 20 mg or equivalent daily with a recommendation for at least atorvastatin 40 mg or equivalent daily where approved. The study was event-driven and continued until at least 1,630 patients experienced a key secondary endpoint.

Important U.S. Product Information

Repatha is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor antibody indicated:

to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.

as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primaryhyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein cholesterol (LDL-C).

as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.

The safety and effectiveness of Repathahave not been established in pediatric patients with HoFH who are younger than 13 years old or in pediatric patients with primary hyperlipidemia or HeFH.

Important U.S. Safety Information

Contraindication:Repatha is contraindicated in patients with a history of a serious hypersensitivity reaction to Repatha. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha.

Allergic reactions:Hypersensitivity reactions (e.g. angioedema, rash, urticaria) have been reported in patients treated with Repatha, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with Repatha, treat according to the standard of care, and monitor until signs and symptoms resolve.

Adverse reactions:The most common adverse reactions (>5% of patients treated with Repatha and occurring more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.

From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising.

Allergic reactions occurred in 5.1% and 4.7% of Repatha-treated and placebo-treated patients, respectively. The most common allergic reactions were rash (1.0% versus 0.5% for Repatha and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).

The most common adverse reactions in the Cardiovascular Outcomes Trial (>5% of patients treated with Repatha and occurring more frequently than placebo) were: diabetes mellitus (8.8% Repatha, 8.2% placebo), nasopharyngitis (7.8% Repatha, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha, 4.8% placebo).

Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients assigned to Repatha compared with 7.7% in those assigned to placebo.

Homozygous Familial Hypercholesterolemia (HoFH):The adverse reactions that occurred in at least two patients treated with Repatha and more frequently than placebo were: upper respiratory tract infection, influenza, gastroenteritis, and nasopharyngitis.

Immunogenicity:Repathais a human monoclonal antibody. As with all therapeutic proteins, there is a potential for immunogenicity with Repatha.

Please contact Amgen Medinfo at 800-77-AMGEN(800-772-6436) or 844-REPATHA (844-737-2842) regarding Repathaavailability or find more information, including fullPrescribing Information, atwww.amgen.comandwww.Repatha.com.

AboutAmgenin the Cardiovascular Therapeutic Area

Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses,Amgenis dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide.5Amgen'sresearch into cardiovascular disease, and potential treatment options, is part of a growing competency atAmgenthat utilizes human genetics to identify and validate certain drug targets. Through its own research and development efforts, as well as partnerships,Amgenis building a robust cardiovascular portfolio consisting of several approved and investigational molecules in an effort to address a number of today's important unmet patient needs, such as high cholesterol and heart failure.

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve peoples lives. A biotechnology pioneer since 1980, Amgen has grown to be the worlds largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

References

1.Yusuf S, et al. Lancet. 2004;364:937-952. 5. Ference BA, et al. EHJ. 2017;38:2459-2472.

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First Large-Scale Registry to Evaluate Real-World Lipid Management and Effectiveness of PCSK9 Inhibitors Announced - Cath Lab Digest

If the man in your family photo album is a farmer, then theres a meagre half a per cent chance your mum was actually knocked up by a shearer or the postman.

If the man who taught you to tie your shoelaces is economically challenged, poorly educated and has the family in a crowded tenement, then the rate that you were fathered by a bored and equally poor neighbour goes up to about 6 per cent.

In other words, the higher the population density, and the less well-off your situation, the greater the chance that you are a result an extra-pair paternity event (EPP) otherwise known as infidelity.

These are the broad findings of an investigation into biological fatherhood amongpeople living in parts of Western Europe over the past 500 years.

Belgian geneticists began their project by pondering an awkward evolutionary fact: remaining faithful to ones partner isnt always the most advantageous strategy for producing quality offspring.

Males may benefit from straying by siring extra offspring the idea being the more the merrier, and the greater chance some of them wont be duds. Likewise, females may benefit by mating with superior males men they may not succeed in partnering up with, but who are happy to share themselves episodically.

But in human societies over time, the researchers wondered, how often have extra-pair paternity events really happened?

Of course, extra-pair paternity, especially due to adultery, is a popular topic in gossip, jokes, TV series, and literature, said Dr Maarten Larmuseau, guest professor in the Department of Human Genetics at theKatholieke University Leuven in Belgium.

But scientific knowledge on this phenomenon is still highly limited, especially regarding the past.

To estimate historical EPP rates among married couples, the researchers identified 513 pairs of contemporary adult males living in Belgium and the Netherlands who, based on genealogical evidence, shared a common paternal ancestor and therefore barring a bit on the side should have carried the same Y chromosome.

The evidence showed no significant difference in EPP rates between countries despite key religious differences, the researchers concluded. But they varied widely with socioeconomic status and population density.

The EPP rate was much lower among farmers and more well-to-do craftsmen and merchants (about one per cent) than among lower class labourers and weavers (about four per cent).

Putting the two together, the researchers report that the estimated EPP rates for the families varied from about 0.5 per cent among the middle to high classes and farmers living in the most sparsely populated towns to almost 6 per cent for the low socioeconomic classes living in the most densely populated cities.

The study covered a time period of several centuries during which there were dramatic changes in the human social environment, including the rapid urbanisation that accompanied the Industrial Revolution in 19th century Western Europe.

The researchers say the findings support evolutionary theories suggesting that individual incentives and opportunities for seeking or preventing extra-pair mating should depend on the social context.

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Good news for rural families: The odds are pretty good that your dad is really your dad - The New Daily

Sharing of information is not evolution. Its like sharing library books instead of writing new ones. Biologists are continuing to uncover ways that living things pass around what they know. This is not good for Darwinism, which requires new information to arise by chance.

Science Daily uses the analogy of fishing with rod and reel to illustrate what bacteria do to acquire information they need.

A new study from Indiana University has revealed a previously unknown role a protein plays in helping bacteria reel in DNA in their environment like a fisherman pulling up a catch from the ocean.

The discovery was made possible by a new imaging method invented at IU that let scientists see for the first time how bacteria use their long and mobile appendages called pili to bind to, or harpoon, DNA in the environment. The new study, reported Oct. 18 in the journal PLOS Genetics, focuses on how they reel their catch back in. [Emphasis added.]

Pili (singular, pilus) are tiny extensions from the cell membrane that grow out and then retract. Why should a bacterium invent a way to defeat antibiotics when it can fish for it? The paper indicates two issues for ID vs Darwinism: (1) information is shared, and (2) molecular motors do the work.

Almost all bacterial species use thin surface appendages called pili to interact with their environments. These structures are critical for the virulence of many pathogens and represent one major way that bacteria share DNA with one another, which contributes to the spread of antibiotic resistance. To carry out their function, pili dynamically extend and retract from the bacterial surface. Here, we show that retraction of pili in some systems is determined by the combined activity of two motor ATPase [i.e., ATP-spending] proteins.

This is a far cry from claims by Darwinians decades ago that the rise of antibiotic resistance represents Darwinian evolution in action before our eyes.

The promise of making your own household goods by 3-D printing them hasnt quite arrived, but in theory, you could make a complex object of any shape, like a car part or tool, on your 3-D printer if you had the code for it. A recent paper in PNAS suggests that something similar happens in yeast. In this case, a prokaryote shares information with a eukaryote. Carla and Paula Gonalves found a way that eukaryotic yeasts which lost the code for vitamin B1 can retrieve it from bacteria and make their own again.

Food is the only source of the essential vitamin B1 for humans, but many microorganisms such as yeast and bacteria can synthetize it themselves. Here we report on a group of yeasts that have lost part of the vitamin B1 biosynthetic pathway in the past but have managed to rebuild it by capturing multiple genes from bacteria through horizontal gene transfer (HGT). We show a mosaic pathway composed of yeast and bacterial genes working coordinately to accomplish the synthesis of an essential nutrient. This involved adaptation of the bacterial genes to the very different expression rules in their new environment using several different mechanisms. Our results endorse HGT as an important mechanism for evolutionary adaptation in eukaryotes.

The authors can call it evolutionary adaptation to please the censors, but its really information sharing. Nothing evolved. The yeast didnt re-invent the vitamin B1 synthesis pathway; they lost it (as Behe would say, they devolved), and so they borrowed genetic instructions from bacteria to get back to where they used to be. The authors very few instances of the words evolved and evolution in the paper seem superfluous to any serious consideration of causation or explanation.

Picture information-sharing tunnels at the nanometer scale. These would be way too small to see, so it would require indirect imaging techniques to observe them in action. A team of scientists possibly uncovered a novel mechanism in mammalian inter-cellular cytoplasmic transfer and communication between mammalian cells. Its just a preprint in bioRxiv, so the story will need further verification, but if observations confirm what the scientists think they are seeing, tunneling nanotubes and fine and often branching cell projections pass organellar cargo from cell to cell. In their experiments, healthy cells were found pumping material to malignant cells.

Discrete, rapid and highly localized transfer events, evidenced against a role for shed vesicles. Transfer coincided with rapid retraction of the cell-projections, suggesting a hydrodynamic mechanism. Increased hydrodynamic pressure in retracting cell-projections normally returns cytoplasm to the cell body. We hypothesize cell-projection pumping (CPP), where cytoplasm in retracting cell-projections partially equilibrates into adjacent recipient cells via micro-fusions that form temporary inter-cellular cytoplasmic continuities.

Cells can not only use protrusions to pump but also to poke neighboring malignant cells. In Nature, Kendall Powell discusses the growing realization among microbiologists that cells can evict, kill or cannibalize less-fit rivals. To do that, cells must have methods of sensing who is good and who is bad, and cooperating as a team. The burgeoning field of cell competition uses the Darwinian lingo of fitness and competition, but this really sounds more like a case of what Marcos Eberlin calls Foresight: the ability to foresee problems and have mechanisms in advance to deal with them.

The best-known case of genetic information sharing is, of course, sexual reproduction. Humans are all one species, Homo sapiens, so everyone is genetically compatible. But what about alleged human ancestors with other species names? Can they share genes?

One of the most astonishing developments in paleoanthropology in the last two decades was the discovery of Neanderthal DNA within us. As the myth of Neanderthals being other members of Homo began to crumble, first it was small bits of Neanderthal DNA, then more and larger segments. Next, Denisovan DNA was found mixed in with Neanderthal and living human genomes. Now, New Scientist reports, Long strand of DNA from Neanderthals found in people from Melanesia. Some paleoanthropologists are thinking that all three groups were genetically compatible with Homo erectus and other archaic humans.

Michael Marshall suggests that theres function, not just randomness, in these cases of genetic mixing:

The archaics have contributed to the success of humans that left Africa, says Eichler. Neanderthals and Denisovans lived in Europe and Asia for hundreds of thousands of years before modern humans emerged from Africa, so they would have evolved adaptations to the different climates, foods and diseases. These useful genes were kind of test-run in our precursors, says Eichler. Theyre basically borrowed.

Predictably, Marshall remains Darwinian in his thesis, but its not necessary to assume that the Africans invented their adaptations by chance mutations and natural selection. ID research could approach the same observations with Foresight in mind: humans have always had engineered mechanisms that could adapt to a wide variety of circumstances. If African meets European and they get twinkles in their eyes, why, theres a quick way to share their library books.

So, scientists continue to find ways that organisms share pre-existing genetic information. Old Darwinian paradigms continue to fall as observations reveal useful information passing through tunneling nanotubes, pili, and secretion systems from cell to cell. Organisms wouldnt borrow useless junk. If they are found reeling in DNA or passing it through secret passageways, it must be a good read.

Photo: Library shelves, bySusan YinviaUnsplash.

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More Ways of Information Sharing Found in Living Things - Discovery Institute