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A Closer Look at the Human Gene Editing Lab – Futurism

In BriefAs the scientific community takes in the work of the team whoedited the DNA of the human embryos this month, different opinionsabout the safety, efficacy, and potential of the technique abound. The Gene Editing Process

In a lab at Oregon Health & Science University, biologist Shoukhrat Mitalipov and a team of experts have been exploring and learning how to edit the DNA in human embryos efficiently and safely. This month, they announced their successful edit and correction of a mutation which causes a heart condition that can be fatal hopefully the first landmark step of many on the road to preventing thousands of genetic diseases with editing.

To edit an embryo, a researcher will begin by taking a human egg and monitoring it on a computer screen. They will then inject, with a pipette, donor sperm and CRISPR, microscopic chemical sequences that act as a gene-editing tool, that is designed to make the precise desired edit. CRISPR then goes to work, slicing the target defect from the DNA. After this editing process, the scientists place the embryos created using the process in an incubator and monitor them.

Mitalipov and the team believe that the editing process finally started to work when they began to inject the sperm and CRISPR into the egg simultaneously. Waiting until the embryos were already created produced results that were less accurate and more likely to be plagued by dangerous mutations. And, while the team isnt totally certain on how the process works, they believe that the slice CRISPR makes as it targets defects triggers the repair process in the embryo.

Thus far, the results from this study appear to be promising. However, many questions in the scientific community about the technique itself and the underlying ethics of the process remain. For example, the technique has not yet been reproduced by other teams, and some scientists believe that the data doesnt support the conclusions Mitalipov and the team are claiming.

Others are more concerned that this kind of technology has not been proven safe. worried that less careful scientists might rush ahead too quickly and attempt to make babies before the technique has been proven to work and be safe. Any change to the genome, or germline editing, could be passed along for generations, perpetuating mistakes and even potentially leading to the development of new diseases. Harvard Medical School Dean George Daley told NPR, I think it would be professionally irresponsible for any clinician to use this technology to make a baby. Its just simply too early. It would be premature.

Still, others are critical of the technique from an ethical standpoint, arguing that scientists editing embryos are playing God, and pushing the field toward selling the ability to create designer babies to parents who can afford the technology. I think its extraordinarily disturbing, Marcy Darnovsky, head of the watchdog group the Center for Genetics and Society, told NPR. Well see fertility clinics advertising gene editing for enhancement purposes. Well see children being born who are said to biologically superior.

Mitalipov and the team acknowledge these criticisms and agree, specifically, that the technique requires reproduction and further testing and should be used for medical purposes only. However, they point out the amazing potential that the technology has to improve our world and the quality of human life. Mitalipov thinks the process may eventually be able to wipe out many genetic diseases:

[There are] about 10,000 different mutations causing so many different conditions and diseases, he said to NPR. Were talking about millions of people affected. So I think the implications are huge.

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A Closer Look at the Human Gene Editing Lab – Futurism

Life Lessons: Next generation testing – WFMZ Allentown

VIDEO Life Lessons: Next generation…

When Audrey Lapidus 10-month old son, Calvin, didnt reach normal milestones like rolling over or crawling, she knew something was wrong.

He was certainly different from our first child, said Lapidus, of Los Angeles. He had a lot of gastrointestinal issues and we were taking him to the doctor quite a bit.

Four specialists saw Calvin and batteries of tests proved inconclusive. Still, Lapidus persisted.

I was pushing for even more testing, and our geneticist at UCLA said, If you can wait one more month, were going to be launching a brand new test called exome sequencing, she said. We were lucky to be in the right place at the right time and get the information we did.

In 2012, Calvin Lapidus became the first patient to undergo exome sequencing at UCLA. He was subsequently diagnosed with a rare genetic condition known as Pitt-Hopkins Syndrome, which is most commonly characterized by developmental delays, possible breathing problems, seizures and gastrointestinal problems.

Though there is no cure for Pitt-Hopkins, finally having a diagnosis allowed Calvin to begin therapy.

The diagnosis gave us a point to move forward from, rather than just existing in that scary no-mans land where we knew nothing, Lapidus said.

Unfortunately, there are a lot of people living in that no-mans land, desperate for any type of answers to their medical conditions, said Dr. Stanley Nelson, professor of human genetics and pathology and laboratory medicine at the David Geffen School of Medicine at UCLA. Many families suffer for years without so much as a name for their condition.

What exome sequencing allows doctors to do is to analyze more than 20,000 genes at once, with one simple blood test.

In the past, genetic testing was done one gene at a time, which is time-consuming and expensive.

Rather than testing one sequential gene after another, exome sequencing saves time, money and effort, said Dr. Julian Martinez-Agosto, a pediatrician and researcher at the Resnick Neuropsychiatric Hospital at UCLA.

The exome consists of all the genomes exons, which are the coding portion of genes. Clinical exome sequencing is a test for identifying disease-causing DNA variants within the 1 percent of the genome which codes for proteins, the exons, or flanks the regions which code for proteins, called splice junctions.

To date, mutations in the protein-coding parts of genes accounts for nearly 85 percent of all mutations known to cause genetic diseases, so surveying just this portion of the genome is an efficient and powerful diagnostic tool. Exome sequencing can help detect rare disorders like spinocerebellar ataxia, which progressively diminishes a persons movements, and suggest the likelihood of more common conditions like autism spectrum disorder and epilepsy.

More than 4,000 adults and children have undergone exome testing at UCLA since 2012. Of difficult to solve cases, more than 30 percent are solved through this process, which is a dramatic improvement over prior technologies. Thus, Nelson and his team support wider use of genome-sequencing techniques and better insurance coverage, which would further benefit patients and resolve diagnostically difficult cases at much younger ages.

Since her sons diagnosis, Lapidus helped found the Pitt-Hopkins Syndrome Research Foundation. Having Calvins diagnosis gave us a roadmap of where to start, where to go and whats realistic as far as therapies and treatments, she said. None of that would have been possible without that test.

Next, experts at UCLA are testing the relative merits of broader whole genome sequencing to analyze all 6 billion bases that make up a persons genome. The team is exploring integration of this DNA sequencing with state-of-the-art RNA or gene expression analysis to improve the diagnostic rate.

The entire human genome was first sequenced in 1990 at a cost of $2.7 billion. Today, doctors can perform the same test at a tiny fraction of that cost, and believe that sequencing whole genomes of individuals could vastly improve disease diagnoses and medical care.

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Life Lessons: Next generation testing – WFMZ Allentown

Genetics | The Smithsonian Institution’s Human Origins Program

DNA

Through news accounts and crime stories, were all familiar with the fact that the DNA in our cells reflects each individuals unique identity and how closely related we are to one another. The same is true for the relationships among organisms. DNA, or deoxyribonucleic acid, is the molecule that makes up an organisms genome in the nucleus of every cell. It consists of genes, which are the molecular codes for proteins the building blocks of our tissues and their functions. It also consists of the molecular codes that regulate the output of genes that is, the timing and degree of protein-making. DNA shapes how an organism grows up and the physiology of its blood, bone, and brains.

DNA is thus especially important in the study of evolution. The amount of difference in DNA is a test of the difference between one species and another and thus how closely or distantly related they are.

While the genetic difference between individual humans today is minuscule about 0.1%, on average study of the same aspects of the chimpanzee genome indicates a difference of about 1.2%. The bonobo (Pan paniscus), which is the close cousin of chimpanzees (Pan troglodytes), differs from humans to the same degree. The DNA difference with gorillas, another of the African apes, is about 1.6%. Most importantly, chimpanzees, bonobos, and humans all show this same amount of difference from gorillas. A difference of 3.1% distinguishes us and the African apes from the Asian great ape, the orangutan. How do the monkeys stack up? All of the great apes and humans differ from rhesus monkeys, for example, by about 7% in their DNA.

Geneticists have come up with a variety of ways of calculating the percentages, which give different impressions about how similar chimpanzees and humans are. The 1.2% chimp-human distinction, for example, involves a measurement of only substitutions in the base building blocks of those genes that chimpanzees and humans share. A comparison of the entire genome, however, indicates that segments of DNA have also been deleted, duplicated over and over, or inserted from one part of the genome into another. When these differences are counted, there is an additional 4 to 5% distinction between the human and chimpanzee genomes.

No matter how the calculation is done, the big point still holds: humans, chimpanzees, and bonobos are more closely related to one another than either is to gorillas or any other primate. From the perspective of this powerful test of biological kinship, humans are not only related to the great apes we are one. The DNA evidence leaves us with one of the greatest surprises in biology: the wall between human, on the one hand, and ape or animal, on the other, has been breached. The human evolutionary tree is embedded within the great apes.

The strong similarities between humans and the African great apes led Charles Darwin in 1871 to predict that Africa was the likely place where the human lineage branched off from other animals that is, the place where the common ancestor of chimpanzees, humans, and gorillas once lived. The DNA evidence shows an amazing confirmation of this daring prediction. The African great apes, including humans, have a closer kinship bond with one another than the African apes have with orangutans or other primates. Hardly ever has a scientific prediction so bold, so out there for its time, been upheld as the one made in 1871 that human evolution began in Africa.

The DNA evidence informs this conclusion, and the fossils do, too. Even though Europe and Asia were scoured for early human fossils long before Africa was even thought of, ongoing fossil discoveries confirm that the first 4 million years or so of human evolutionary history took place exclusively on the African continent. It is there that the search continues for fossils at or near the branching point of the chimpanzee and human lineages from our last common ancestor.

Due to billions of years of evolution, humans share genes with all living organisms. The percentage of genes or DNA that organisms share records their similarities. We share more genes with organisms that are more closely related to us.

Humans belong to the biological group known as Primates, and are classified with the great apes, one of the major groups of the primate evolutionary tree. Besides similarities in anatomy and behavior, our close biological kinship with other primate species is indicated by DNA evidence. It confirms that our closest living biological relatives are chimpanzees and bonobos, with whom we share many traits. But we did not evolve directly from any primates living today.

DNA also shows that our species and chimpanzees diverged from a common ancestor species that lived between 8 and 6 million years ago. The last common ancestor of monkeys and apes lived about 25 million years ago.

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Genetics | The Smithsonian Institution’s Human Origins Program

Evolutionary Biologists Probe Long-standing Genetics Mystery – Yale News

August 17, 2017

Photo credit: Dreamstime

What makes humans different from chimpanzees? Evolutionary biologists from Howard University and the Yale School of Public Health have developed a unique genetic analysis technique that may provide important answers.

Michael C. Campbell, Ph.D., the papers first author and assistant professor in the Howard University Department of Biology, and co-author Jeffrey Townsend, Ph.D., the Elihu Associate Professor in Biostatistics at Yale, published their findings in the journal Molecular Biology and Evolution.

Their methodModel Averaged Site Selection via Poisson Random Field (MASS-PRF)looks at protein-coding genes to identify genetic signatures of positive selection. These signatures are actually DNA changes that contribute to the development of beneficial traits, or human adaptations, that emerged during human evolutionary history and that are shared across the human species.

It’s a quantum leap in our statistical power to detect selection in recently diverged species.

Other approaches have examined this question but analyses have focused on whole genes, typically missing focused evolution that often occurs in small regions of genes. The method Campbell and Townsend created identifies selection within genes, pinpointing sets of mutations that have undergone positive selection.

Our method is a new way of looking for beneficial mutations that have become fixed or occur at 100 percent frequency in the human species, Campbell said. What we are concerned with are mutations within genes and traits that are specific to humans compared to closely related species, such as the chimpanzee. Essentially, we want to know is what are the mutations and traits that make us human and that unite us as a biological species.

Townsend said the technique has far-reaching implications. It helped the research team discover several genes whose evolution appears to have been critical to the divergence of humans from their common ancestor with chimpanzees. The genes play roles in neurological processing, immunity, and reproduction, and the method could eventually help scientists identify many more. It’s a quantum leap in our statistical power to detect selection in recently diverged species, Townsend said.

Campbell began the research project with Drs. Zhao and Townsend while they were associate research scientists in the Department of Biostatistics at the Yale School of Public Health, before he arrived at Howard University in 2015. Dr. Zhao, currently a research scientist at The Jackson Laboratory for Genomic Medicine, co-authored the paper.

This article was submitted by Elisabeth Ann Reitman on August 17, 2017.

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Evolutionary Biologists Probe Long-standing Genetics Mystery – Yale News

Exclusive: Inside The Lab Where Scientists Are Editing DNA In Human Embryos – NPR

This sequence of images shows the development of embryos formed after eggs were injected with both CRISPR, a gene-editing tool, and sperm from a donor with a genetic mutation known to cause cardiomyopathy. OHSU hide caption

This sequence of images shows the development of embryos formed after eggs were injected with both CRISPR, a gene-editing tool, and sperm from a donor with a genetic mutation known to cause cardiomyopathy.

From the thirteenth floor of a glass tower at the Oregon Health & Science University, you get a panoramic view of downtown Portland and the majestic mountains in the distance. But it’s what’s happening inside the building that’s brought me here.

“Should we go do this thing?” lab manager Amy Koski asks.

She’s just gotten a call from the fertility clinic three floors down. A woman undergoing in vitro fertilization has had her eggs extracted. One of the eggs is too immature to be used to try to create a baby, so she’s donating it to research.

Koski grabs a small metal box and rushes to the elevator. It’s her portable incubator.

“You want to keep the eggs very happy and warm,” she says. “When you’re jostling them and moving them, they get a little unhappy.”

Human eggs are the key starting point for the groundbreaking experiments underway in this lab. It’s run by Shoukhrat Mitalipov, a biologist who’s been on the cutting edge of embryonic genetic research for decades.

Mitalipov and his international team electrified the world this summer when the group announced it had successfully and seemingly safely figured out how to efficiently edit the DNA in human embryos.

For the first time, they said, they had corrected a mutation that causes a potentially fatal heart condition. The hope is this landmark step could someday help prevent thousands of genetic diseases that have plagued families for generations.

Critics, however, pounced on the news. They fear editing DNA in human embryos is unsafe, unnecessary and could open the door to “designer babies” and possibly someday to genetically enhanced people who are considered superior by society.

As the debate raged last week, I asked Mitalipov if I could visit his lab to see the next round of his experiments. He wants to confirm his initial results and determine whether the method can be used to repair other mutations.

He agreed to a visit, and on Monday, I became the first journalist to see these scientists cross a line that, until recently, had been taboo.

A small room for big science

I’ve followed Mitalipov’s research for years and have visited the labs of other scientists doing related work in Stockholm, London and elsewhere.

Still, I stepped into Mitalipov’s embryology lab unsure of exactly what I was about to see and eager to better understand what allowed these scientists to succeed where others had failed.

“This is our small room, but that’s where usually lots of big science happened,” says Mitalipov, who was born in the former Soviet Union. “We believe this room is really magic in terms of science.”

Shoukhrat Mitalipov points to an image of an edited embryo inside an incubator at the Center for Embryonic Cell and Gene Therapy in Portland, Ore. Rob Stein/NPR hide caption

Shoukhrat Mitalipov points to an image of an edited embryo inside an incubator at the Center for Embryonic Cell and Gene Therapy in Portland, Ore.

He points to a microscope where his colleague, Nuria Marti-Gutierrez, has just positioned a Petri dish. I’m able to watch everything she’s doing on a computer screen.

Mitalipov points to a round silvery blob. It’s the egg. “You can see it moving,” he says.

Suddenly, a bunch of tiny ovals flit across the screen. They are sperm from a donor who has a genetic mutation that causes cardiomyopathy, a potentially fatal heart condition.

Marti-Gutierrez draws the sperm into a thin glass rod called a pipette. She then adds a microscopic gene-editing tool a combination of chemical sequences known as CRISPR that can make very precise changes in DNA.

In this case, CRISPR will zero in on the cardiomyopathy mutation to literally slice the defect in the DNA.

Finally, she pierces the shell of the egg with the pipette and injects the sperm and CRISPR. Almost before I know it’s happening, it’s done. A human embryo has been created and edited before my eyes.

“That’s it?” I ask.

“Yep,” Mitalipov says, chuckling to himself.

It was amazingly fast and seemingly easy you could imagine a future where this sort of thing might become routine.

“This is how we do it,” Mitalipov says matter-of-factly. He refers to the process as “DNA surgery.”

Mitalipov and his team immediately do a second edit and then transfer the embryos to a larger incubator. The scientists will then spend the next few days monitoring live video of the two embryos, along with 17 others they had edited the weekend before, to see how they develop.

What’s at work

Mitalipov thinks his team accomplished this feat by injecting the mutant sperm and the DNA editor into the egg at the same time. Previous attempts to edit DNA in human embryos were far less accurate and produced dangerous mutations elsewhere in the embryos’ DNA.

Mitalipov and his colleagues are not sure exactly how it works. But they think that when CRISPR cuts the defective gene, the slice triggers the embryo to repair itself.

If future experiments confirm the results and show that the technique also works for other mutations, Mitalipov thinks the process could wipe out many diseases that have plagued families for generations, though he cautions that any practical application is still easily a decade or more away.

“[There are] about 10,000 different mutations causing so many different conditions and diseases,” he says, pointing to Huntington’s disease, cystic fibrosis and even possibly inherited forms of Alzheimer’s and breast cancer.

“We’re talking about millions of people affected. So I think the implications are huge,” he says.

“I think this is a significant advance,” says George Church, a Harvard geneticist. “This is important not only for parents who want to have healthy children, but more generally, it opens the door to preventative medicine where we can avoid a lot of painful genetic problems.”

Skepticism, criticism and an ethical debate

While the results seem promising so far, there are still many questions. Some scientists remain skeptical that Mitalipov has really done what he says he’s done.

“Unfortunately, the data do not allow the conclusion of correction for the embryos,” says Dieter Egli, a biologist at Columbia University. “There are a number of other outcomes that are much more likely.”

Mitalipov acknowledges that his work still needs to be reproduced by others, but he is confident his method is working.

Others are worried that less careful scientists might rush ahead too quickly and attempt to make babies before the technique has been proven to work and be safe.

“This is a strong statement that we can do genome editing,” says George Daley, dean of the Harvard Medical School. “The question that remains is, ‘Should we?’ ”

“I think it would be professionally irresponsible for any clinician to use this technology to make a baby,” Daley adds. “It’s just simply too early. It would be premature.”

The idea of changing human DNA in ways that could be passed down for generations has long been considered off-limits. The fear is scientists could make mistakes and create new diseases that would persist for generations.

Some critics go so far as to say that scientists are essentially playing God by taking this step. They fear it will lead to parents picking and choosing the traits of their children. While that is not yet technically possible, critics say scientists are moving quickly toward that possibility.

“I think it’s extraordinarily disturbing,” says Marcy Darnovsky, who heads the Center for Genetics and Society, a watchdog group. “We’ll see fertility clinics advertising gene editing for enhancement purposes. We’ll see children being born who are said to biologically superior.”

Mitalipov and his colleagues acknowledge the fears and agree the technique should be carefully regulated and only used for medical purposes. But, they argue, the fears should not stop the research.

“I don’t think I’m playing God,” Mitalipov says. “We have intelligence to understand diseases, eliminate suffering. And that’s what I think is the right thing to do.”

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Exclusive: Inside The Lab Where Scientists Are Editing DNA In Human Embryos – NPR

Bacteria May Rig Their DNA to Speed Up Evolution – WIRED

In 1944, a Columbia University doctoral student in genetics named Evelyn Witkin made a fortuitous mistake. During her first experiment in a laboratory at Cold Spring Harbor, in New York, she accidentally irradiated millions of E. coli with a lethal dose of ultraviolet light. When she returned the following day to check on the samples, they were all deadexcept for one, in which four bacterial cells had survived and continued to grow. Somehow, those cells were resistant to UV radiation. To Witkin, it seemed like a remarkably lucky coincidence that any cells in the culture had emerged with precisely the mutation they needed to surviveso much so that she questioned whether it was a coincidence at all.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

For the next two decades, Witkin sought to understand how and why these mutants had emerged. Her research led her to what is now known as the SOS response, a DNA repair mechanism that bacteria employ when their genomes are damaged, during which dozens of genes become active and the rate of mutation goes up. Those extra mutations are more often detrimental than beneficial, but they enable adaptations, such as the development of resistance to UV or antibiotics.

The question that has tormented some evolutionary biologists ever since is whether nature favored this arrangement. Is the upsurge in mutations merely a secondary consequence of a repair process inherently prone to error? Or, as some researchers claim, is the increase in the mutation rate itself an evolved adaptation, one that helps bacteria evolve advantageous traits more quickly in stressful environments?

The scientific challenge has not just been to demonstrate convincingly that harsh environments cause nonrandom mutations. It has also been to find a plausible mechanism consistent with the rest of molecular biology that could make lucky mutations more likely. Waves of studies in bacteria and more complex organisms have sought those answers for decades.

The latest and perhaps best answerfor explaining some kinds of mutations, anywayhas emerged from studies of yeast, as reported in June in PLOS Biology . A team led by Jonathan Houseley, a specialist in molecular biology and genetics at the Babraham Institute in Cambridge, proposed a mechanism that drives more mutation specifically in regions of the yeast genome where it could be most adaptive.

Its a totally new way that the environment can have an impact on the genome to allow adaptation in response to need. It is one of the most directed processes weve seen yet, said Philip Hastings, professor of molecular and human genetics at Baylor College of Medicine, who was not involved in the Houseley groups experiments. Other scientists contacted for this story also praised the work, though most cautioned that much about the controversial idea was still speculative and needed more support.

Rather than asking very broad questions like are mutations always random? I wanted to take a more mechanistic approach, Houseley said. He and his colleagues directed their attention to a specific kind of mutation called copy number variation. DNA often contains multiple copies of extended sequences of base pairs or even whole genes. The exact number can vary among individuals because, when cells are duplicating their DNA before cell division, certain mistakes can insert or delete copies of gene sequences. In humans, for instance, 5 to 10 percent of the genome shows copy number variation from person to personand some of these variations have been linked to cancer, diabetes, autism and a host of genetic disorders. Houseley suspected that in at least some cases, this variation in the number of gene copies might be a response to stresses or hazards in the environment.

Jonathan Houseley leads a team that studies genome change at the Babraham Institute in Cambridge. Based on their studies of yeast, they recently proposed a mechanism that would increase the odds for adaptive mutations in genes that are actively responding to environmental challenges.

Jon Houseley/QUANTA MAGAZINE

In 2015, Houseley and his colleagues described a mechanism by which yeast cells seemed to be driving extra copy number variation in genes associated with ribosomes, the parts of a cell that synthesize proteins. However, they did not prove that this increase was a purposefully adaptive response to a change or constraint in the cellular environment. Nevertheless, to them it seemed that the yeast was making more copies of the ribosomal genes when nutrients were abundant and the demand for making protein might be higher.

Houseley therefore decided to test whether similar mechanisms might act on genes more directly activated by hazardous changes in the environment. In their 2017 paper, he and his team focused on CUP1 , a gene that helps yeast resist the toxic effects of environmental copper. They found that when yeast was exposed to copper, the variation in the number of copies of CUP1 in the cells increased. On average, most cells had fewer copies of the gene, but the yeast cells that gained more copiesabout 10 percent of the total population became more resistant to copper and flourished. The small number of cells that did the right thing, Houseley said, were at such an advantage that they were able to outcompete everything else.

But that change did not in itself mean much: If the environmental copper was causing mutations, then the change in CUP1 copy number variation might have been no more than a meaningless consequence of the higher mutation rate. To rule out that possibility, the researchers cleverly re-engineered the CUP1 gene so that it would respond to a harmless, nonmutagenic sugar, galactose, instead of copper. When these altered yeast cells were exposed to galactose, the variation in their number of copies of the gene changed, too.

The cells seemed to be directing greater variation to the exact place in their genome where it would be useful. After more work, the researchers identified elements of the biological mechanism behind this phenomenon. It was already known that when cells replicate their DNA, the replication mechanism sometimes stalls. Usually the mechanism can restart and pick up where it left off. When it cant, the cell can go back to the beginning of the replication process, but in doing so, it sometimes accidentally deletes a gene sequence or makes extra copies of it. That is what causes normal copy number variation. But Houseley and his team made the case that a combination of factors makes these copying errors especially likely to hit genes that are actively responding to environmental stresses, which means that they are more likely to show copy number variation.

The key point is that these effects center on genes responding to the environment, and that they could give natural selection extra opportunities to fine-tune which levels of gene expression might be optimal against certain challenges. The results seem to present experimental evidence that a challenging environment could galvanize cells into controlling those genetic changes that would best improve their fitness. They may also seem reminiscent of the outmoded, pre-Darwinian ideas of the French naturalist Jean-Baptiste Lamarck, who believed that organisms evolved by passing their environmentally acquired characteristics along to their offspring. Houseley maintains, however, that this similarity is only superficial.

What we have defined is a mechanism that has arisen entirely through Darwinian selection of random mutations to give a process that stimulates nonrandom mutations at useful sites, Houseley said. It is not Lamarckian adaptation. It just achieves some of the same ends without the problems involved with Lamarckian adaptation.

Ever since 1943, when the microbiologist Salvador Luria and the biophysicist Max Delbrck showed with Nobel prize-winning experiments that mutations in E. coli occur randomly, observations like the bacterial SOS response have made some biologists wonder whether there might be important loopholes to that rule. For example, in a controversial paper published in Nature in 1988, John Cairns of Harvard and his team found that when they placed bacteria that could not digest the milk sugar lactose in an environment where that sugar was the sole food source, the cells soon evolved the ability to convert the lactose into energy. Cairns argued that this result showed that cells had mechanisms to make certain mutations preferentially when they would be beneficial.

Budding yeast (S. cerevisiae) grow as colonies on this agar plate. If certain recent research is correct, a mechanism that helps to repair DNA damage in these cells may also promote more adaptive mutations, which could help the cells to evolve more quickly under harsh circumstances.

Jon Houseley/QUANTA MAGAZINE

Experimental support for that specific idea eventually proved lacking, but some biologists were inspired to become proponents of a broader theory that has come to be known as adaptive mutation. They believe that even if cells cant direct the precise mutation needed in a certain environment, they can adapt by elevating their mutation rate to promote genetic change.

The work of the Houseley team seems to bolster the case for that position. In the yeast mechanism theres not selection for a mechanism that actually says, This is the gene I should mutate to solve the problem, said Patricia Foster, a biologist at Indiana University. It shows that evolution can get speeded up.

Hastings at Baylor agreed, and praised the fact that Houseleys mechanism explains why the extra mutations dont happen throughout the genome. You need to be transcribing a gene for it to happen, he said.

Adaptive mutation theory, however, finds little acceptance among most biologists, and many of them view the original experiments by Cairns and the new ones by Houseley skeptically. They argue that even if higher mutation rates yield adaptations to environmental stress, proving that the higher mutation rates are themselves an adaptation to stress remains difficult to demonstrate convincingly. The interpretation is intuitively attractive, said John Roth, a geneticist and microbiologist at the University of California, Davis, but I dont think its right. I dont believe any of these examples of stress-induced mutagenesis are correct. There may be some other non-obvious explanation for the phenomenon.

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I think [Houseleys work] is beautiful and relevant to the adaptive mutation debate, said Paul Sniegowski, a biologist at the University of Pennsylvania. But in the end, it still represents a hypothesis. To validate it more certainly, he added, theyd have to test it in the way an evolutionary biologist wouldby creating a theoretical model and determining whether this adaptive mutability could evolve within a reasonable period, and then by challenging populations of organisms in the lab to evolve a mechanism like this.

Notwithstanding the doubters, Houseley and his team are persevering with their research to understand its relevance to cancer and other biomedical problems. The emergence of chemotherapy-resistant cancers is commonplace and forms a major barrier to curing the disease, Houseley said. He thinks that chemotherapy drugs and other stresses on tumors may encourage malignant cells to mutate further, including mutations for resistance to the drugs. If that resistance is facilitated by the kind of mechanism he explored in his work on yeast, it could very well present a new drug target. Cancer patients might be treated both with normal courses of chemotherapy and with agents that would inhibit the biochemical modifications that make resistance mutations possible.

We are actively working on that, Houseley said, but its still in the early days.

Original story reprinted with permission from Quanta Magazine , an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

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Bacteria May Rig Their DNA to Speed Up Evolution – WIRED

Will Gene Editing Allow Us to Rid the World of Diseases? – Healthline

Scientists recently used a gene-editing tool to fix a mutation in a human embryo. Around the world, researchers are chasing cures for other genetic diseases.

Now that the gene-editing genie is out of the bottle, what would you wish for first?

Babies with perfect eyes, over-the-top intelligence, and a touch of movie star charisma?

Or a world free of disease not just for your family, but for every family in the world?

Based on recent events, many scientists are working toward the latter.

Earlier this month, scientists from the Oregon Health & Science University used a gene editing tool to correct a disease-causing mutation in an embryo.

The technique, known as CRISPR-Cas9, fixed the mutation in the embryos nuclear DNA that causes hypertrophic cardiomyopathy, a common heart condition that can lead to heart failure or cardiac death.

This is the first time that this gene-editing tool has been tested on clinical-quality human eggs.

Had one of these embryos been implanted into a womans uterus and allowed to fully develop, the baby would have been free of the disease-causing variation of the gene.

This type of beneficial change would also have been passed down to future generations.

None of the embryos in this study were implanted or allowed to develop. But the success of the experiment offers a glimpse at the potential of CRISPR-Cas9.

Still, will we ever be able to gene-edit our world free of disease?

According to the Genetic Disease Foundation, there are more than 6,000 human genetic disorders.

Scientists could theoretically use CRISPR-Cas9 to correct any of these diseases in an embryo.

To do this, they would need an appropriate piece of RNA to target corresponding stretches of genetic material.

The Cas9 enzyme cuts DNA at that spot, which allows scientists to delete, repair, or replace a specific gene.

Some genetic diseases, though, may be easier to treat with this method than others.

Most people are focusing, at least initially, on diseases where there really is only one gene involved or a limited number of genes and theyre really well understood, Megan Hochstrasser, PhD, science communications manager at the Innovative Genomics Institute in California, told Healthline.

Diseases caused by a mutation in a single gene include sickle cell disease, cystic fibrosis, and Tay-Sachs disease. These affect millions of people worldwide.

These types of diseases, though, are far outnumbered by diseases like cardiovascular disease, diabetes, and cancer, which kill millions of people across the globe each year.

Genetics along with environmental factors also contribute to obesity, mental illness, and Alzheimers disease, although scientists are still working on understanding exactly how.

Right now, most CRISPR-Cas9 research focuses on simpler diseases.

There are a lot of things that have to be worked out with the technology for it to get to the place where we could ever apply it to one of those polygenic diseases, where multiple genes contribute or one gene has multiple effects, said Hochstrasser.

Although designer babies gain a lot of media attention, much CRISPR-Cas9 research is focused elsewhere.

Most people who are working on this are not working in human embryos, said Hochstrasser. Theyre trying to figure out how we can develop treatments for people that already have diseases.

These types of treatments would benefit children and adults who are already living with a genetic disease, as well as people who develop cancer.

This approach may also help the 25 million to 30 million Americans who have one of the more than 6,800 rare diseases.

Gene editing is a really powerful option for people with rare disease, said Hochstrasser. You could theoretically do a phase I clinical trial with all the people in the world that have a certain [rare] condition and cure them all if it worked.

Rare diseases affect fewer than 200,000 people in the United States at any given time, which means there is less incentive for pharmaceutical companies to develop treatments.

These less-common diseases include cystic fibrosis, Huntingtons disease, muscular dystrophies, and certain types of cancer.

Last year researchers at the University of California Berkeley made progress in developing an ex vivo therapy where you take cells out of a person, modify them, and put them back into the body.

This treatment was for sickle cell disease. In this condition, a genetic mutation causes hemoglobin molecules to stick together, which deforms red blood cells. This can lead to blockages in the blood vessels, anemia, pain, and organ failure.

Researchers used CRISPR-Cas9 to genetically engineer stem cells to fix the sickle cell disease mutation. They then injected these cells into mice.

The stem cells migrated to the bone marrow and developed into healthy red blood cells. Four months later, these cells could still be found in the mices blood.

This is not a cure for the disease, because the body would continue to make red blood cells that have the sickle cell disease mutation.

But researchers think that if enough healthy stem cells take root in the bone marrow, it could reduce the severity of disease symptoms.

More work is needed before researchers can test this treatment in people.

A group of Chinese researchers used a similar technique last year to treat people with an aggressive form of lung cancer the first clinical trial of its kind.

In this trial, researchers modified patients immune cells to disable a gene that is involved in stopping the cells immune response.

Researchers hope that, once injected into the body, the genetically edited immune cells will mount a stronger attack against the cancer cells.

These types of therapies might also work for other blood diseases, cancers, or immune problems.

But certain diseases will be more challenging to treat this way.

If you have a disorder of the brain, for example, you cant remove someones brain, do gene editing and then put it back in, said Hochstrasser. So we have to figure out how to get these reagents to the places they need to be in the body.

Not every human disease is caused by mutations in our genome.

Vector-borne diseases like malaria, yellow fever, dengue fever, and sleeping sickness kill more than 1 million people worldwide each year.

Many of these diseases are transmitted by mosquitoes, but also by ticks, flies, fleas, and freshwater snails.

Scientists are working on ways to use gene editing to reduce the toll of these diseases on the health of people around the world.

We could potentially get rid of malaria by engineering mosquitoes that cant transmit the parasite that causes malaria, said Hochstrasser. We could do this using the CRISPR-Cas9 technique to push this trait through the entire mosquito population very quickly.

Researchers are also using CRISPR-Cas9 to create designer foods.

DuPont recently used gene editing to produce a new variety of waxy corn that contains higher amounts of starch, which has uses in food and industry.

Modified crops may also help reduce deaths due to malnutrition, which is responsible for nearly half of all deaths worldwide in children under 5.

Scientists could potentially use CRISPR-Cas9 to create new varieties of food that are pest-resistant, drought-resistant, or contain more micronutrients.

One benefit of CRISPR-Cas9, compared to traditional plant breeding methods, is that it allows scientists to insert a single gene from a related wild plant into a domesticated variety, without other unwanted traits.

Gene editing in agriculture may also move more quickly than research in people because there is no need for years of lab, animal, and human clinical trials.

Even though plants grow pretty slowly, said Hochstrasser, it really is quicker to get [genetically engineered plants] out into the world than doing a clinical trial in people.

Safety and ethical concerns

CRISPR-Cas9 is a powerful tool, but it also raises several concerns.

Theres a lot of discussion right now about how best to detect so-called off-target effects, said Hochstrasser. This is what happens when the [Cas9] protein cuts somewhere similar to where you want it to cut.

Off-target cuts could lead to unexpected genetic problems that cause an embryo to die. An edit in the wrong gene could also create an entirely new genetic disease that would be passed onto future generations.

Even using CRISPR-Cas9 to modify mosquitoes and other insects raises safety concerns like what happens when you make large-scale changes to an ecosystem or a trait in a population that gets out of control.

There are also many ethical issues that come with modifying human embryos.

So will CRISPR-Cas9 help rid the world of disease?

Theres no doubt that it will make a sizeable dent in many diseases, but its unlikely to cure all of them any time soon.

We already have tools for avoiding genetic diseases like early genetic screening of fetuses and embryos but these are not universally used.

We still dont avoid tons of genetic diseases, because a lot of people dont know that they harbor mutations that can be inherited, said Hochstrasser.

Some genetic mutations also happen spontaneously. This is the case with many cancers that result from environmental factors such as UV rays, tobacco smoke, and certain chemicals.

People also make choices that increase their risk of heart disease, stroke, obesity, and diabetes.

So unless scientists can use CRISPR-Cas9 to find treatments for these lifestyle diseases or genetically engineer people to stop smoking and start biking to work these diseases will linger in human society.

Things like that are always going to need to be treated, said Hochstrasser. I dont think its realistic to think we would ever prevent every disease from happening in a human.

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Will Gene Editing Allow Us to Rid the World of Diseases? – Healthline

White nationalists see a new enemy in pursuit of ‘racial purity’: Science – CNN

In a recent study, researchers found white nationalists sometimes skew their view of science for their own benefit when a genetic test challenges their personal identity. The study, which is currently under review for publication, was led by Aaron Panofsky, an associate professor at UCLA’s Institute for Society and Genetics, and sociologist Joan Donovan.

“White nationalists tend to follow this ideological rule that they have,” and when they get scientific results that don’t align with that rule, they “find some way to get around it,” Panofsky said.

To conduct their study, Panofsky and Donovan analyzed 153 posts where users displayed results of their genetic tests on the white nationalist online forum Stormfront. The posts spanned more than a decade.

Out of the 153 posts, Panofsky said about a third of them were users celebrating “good news,” or results that showed they were as “pure” as they thought they were or more “pure” than they thought.

The other two-thirds were either users analyzing “bad news” from their genetic tests, or results that showed they were less “pure” than they thought, or users who posted their results without context.

Stormfront users employed a variety of services to get their genetic results, from Ancestry.com and 23andMe to DNA Solutions. Companies such as Ancestry.com allow customers to request an at-home test for $99 and up, and then send in their DNA, which scientists use to compare with reference panels. Results can be mailed back in up to six weeks.

In a statement, Ancestry.com spokesman Brandon Borrman said the company does not condone people using its services to justify what they see as racial purity.

“We are against any use of our product in an attempt to promote divisiveness or justify twisted ideologies. People looking to use our services to prove they are ethnically ‘pure’ are going to be deeply disappointed. We encourage them to take their business elsewhere,” his statement said.

Most Stormfront users were motivated to do these tests because they are “invested in remaining white,” Donovan said. “White nationalists are not acting out of ignorance; they’re trying to actively construct a version of an ideological whiteness that depends on science.”

Panofsky said users who were given “bad” results either used the genetic tests to rethink the boundaries of whiteness or looked for an explanation as to why the tests were faulty. Sometimes users would repeat tests multiple times to try and get a “more desired” result.

Some users excused the test results by claiming the genetics companies were run by Jewish people, who purportedly skewed results in an attempt to create a multicultural nation, Panofsky said. Others saw the results as a way to expand the boundaries of whiteness and ask what percentage of nonwhite is “acceptable.”

“The scientific criticisms were often very sophisticated. You get people who say this is bad news here for our nation, but we need to deal with this and change our definition of white nationalism to take account of this,” Panofsky said.

Some users found they were from multiple European cultures, which they used to claim an ideology of multiculturalism without having to accept people of color.

From a white nationalist’s point of view, Panofsky said, such results look like diversity within the European population, while they see all nonwhite people as basically the same.

“It’s not necessarily changing their minds (about getting away from white nationalism), but they’re grappling with it,” he added. “You can’t rely on people learning more about the truth of human relatedness and genetics to change their minds.”

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White nationalists see a new enemy in pursuit of ‘racial purity’: Science – CNN

Cancer Genetics Expert Katherine L. Nathanson, MD, Named Deputy Director of Abramson Cancer Center – Newswise (press release)

Newswise PHILADELPHIA Katherine L. Nathanson, MD, an internationally recognized expert in the field of cancer genetics, has been named deputy director of the Abramson Cancer Center of the University of Pennsylvania. Nathanson is a professor of Translational Medicine and Human Genetics in the Perelman School of Medicine, and the associate director for Population Sciences in the Abramson Cancer Center, co-leader of the Cancer Control Program, and Chief Oncogenomics Physician. She also serves as director of Genetics for the Basser Center for BRCA. She will begin her new role as deputy director immediately.

Dr. Nathanson is a distinguished physician-scientist and has long been a valued colleague and member of the cancer center, said Robert Vonderheide, MD, DPhil, the director of the ACC. Her clinical and research portfolio incorporates an impressive array of diseases. She has played a critical role in many of the ACCs most recent advancements and is well known as an international expert in somatic and germline cancer genetics. I am delighted she has accepted this new leadership role.

As Deputy Director, Nathanson will oversee multiple aspects of the cancer centers scientific and clinical missions, including strategic planning, program development and evaluation, faculty recruitment, leadership appointments, and resource allocation.

Im honored to take on this new leadership role to advance the mission of the Abramson Cancer Center: to reduce the burden of cancer throughout the region, the nation, and the world by extending our integrated program of laboratory, clinical and population-based research, Nathanson said.

Nathanson received her bachelors degree from Haverford College and her MD from the University of Pennsylvania. She completed residencies in Internal Medicine at Beth Israel Hospital in Boston, as well as in Clinical genetics at the Childrens Hospital of Philadelphia and at Penn. She joined the Penn faculty in 2001, and since then, she has published more than 250 peer-reviewed articles in top journals, such as Nature, JAMA, Cancer Cell, and The New England Journal of Medicine. She has an extensive record of national service for multiple organizations including the American College of Medical Genetics and Genomics, where she serves as the Cancer Genetics editor for Genetics in Medicine, and the American Association for Cancer Research. Nathanson is also the chair of the Cancer Genetics study section for the National Institutes of Health and is an elected member of the American Society of Clinical Investigation and the American Association of Physicians.

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Penn Medicineis one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and theUniversity of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according toU.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals byU.S. News & World Report– Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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Cancer Genetics Expert Katherine L. Nathanson, MD, Named Deputy Director of Abramson Cancer Center – Newswise (press release)

Idaho dairy industry elevates worker safety, training – Capital Press

Idahos dairy industry is taking a unique and proactive approach to improving worker safety with a statewide on-farm training program.

Carol Ryan Dumas/Capital Press

David Douphrate, assistant professor of epidemiology, human genetics and environmental sciences at the University of Texas, answers questions during a panel on a new worker training program for Idahos dairy industry during the Idaho Milk Processors Association annual conference, while Robert Hagevoort, extension dairy specialist at New Mexico State University, looks on.

SUN VALLEY, Idaho Training a largely inexperienced, non-English-speaking workforce on Idahos dairies for the ultimate goal of worker safety has become a priority for both dairymen and the processors they supply.

Unfortunately, it took a fatality on a dairy to bring it to the table, Rick Naerebout, director of operations for the Idaho Dairymens Association, said during the Idaho Milk Processors Association annual conference last week.

That tragedy occurred in February 2016, when worker Ruperto Vazquez-Carrera, 37, drowned in a waste pond after mistakenly driving a feed truck into the pond in pre-dawn hours under flooded conditions.

IDFA quickly responded to prevent future tragedies by engaging with experts in worker safety and training to figure out how to get our arms around the issue of comprehensive training, Naerabout said.

We realized we have an opportunity to do more than check a box on safety and be proactive instead of reactive, he said.

The worker training and safety program has been in development for more than a year, and IDFA has hired a full-time worker training and safety specialist to lead it. The program rolled out this week, starting at dairies owned by IDA board members.

Processors are collaborating in the program and sharing in the cost, said Daragh Maccabee, senior vice president of procurement and dairy economics for Glanbia Nutritionals.

Processors met with IDA in April 2016 to discuss a path forward, wanting to participate in a meaningful way, he said.

While there are already good practices in place, the event which drew the attention of OSHA, the United Farm Workers of American and the media highlighted a need for more structure. The primary objective of the program is to provide a safe work environment, he said.

People safety is our No.1 priority, and Glanbia wants to support the producer community in a real way, he said.

As an industry, we need to be able to show to the world we are responsible, he said.

IDFA contracted worker safety and training experts David Douphrate, assistant professor of epidemiology, human genetics and environmental sciences at the University of Texas, and Robert Hagevoort, extension dairy specialist with New Mexico State University to develop a program.

Hagevoort said the U.S. dairy industry is experiencing growing pains, with the number of operations decreasing and herd size increasing, driven by economies of scale. It is also moving to automation, with a need for high-skilled workers.

Employment on dairies is not based on skill but on willingness, resulting in a lot of foreign workers unfamiliar with large animals. And its a population challenged by reading comprehension and retention, he said.

Training has to be consistent, repetitive and comprehensive and include both classroom and live training with animals. In addition to the what, the why of safety issues and animal handling must be explained, he said.

Idahos consortium can be beneficial in developing and evaluating training materials and training the trainer to train employees, he said.

Douphrate agreed, saying the focus needs to be on safety leadership and management.

You cant be everywhere on the farm, you have to delegate and need to equip supervisors, he said.

They need to be able to effectively train workers and evaluate whether that training is being retained and workers are applying what they learned, he said.

We want a proactive approach to address injuries and fatalities before they happen, he said.

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Idaho dairy industry elevates worker safety, training – Capital Press

Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

Ever wonder why your friend, co-worker, or partner doesnt get as sick as you, even though they caught the same bug you did? Maybe they made some Faustian bargain that affords them greater protection to infections, or perhaps they are part of some top-secret government experiment that injects them with an array of antigens isolated from an alien race living in Area 51. While both theories are potential explanations, it seems likely that differences in response to infection lie in something a bit more scientificlike genetics. Now, a collaborative team of investigators from the University of Bonn, Germany, and the New York Genome Center has just published findings that map several genetic variants that affect how much gene expression changes in response to an immune stimulus.

Results from the new studypublished in Nature Communications in an article entitled Genetic Regulatory Effects Modified by Immune Activation Contribute to Autoimmune Disease Associationsoffer novel insights into the genetic contribution to varying immune responses among individuals and its consequences on immune-mediated diseases.

Our defense mechanisms against microbial pathogens rely on white blood cells that are specialized to detect infection,” explained co-senior study investigator Veit Hornung, Ph.D., chair of immunobiochemistry at the Ludwig-Maxmilians-Universitt in Munich. Upon encounter of microbes, these cells trigger cellular defense programs via activating and repressing the expression of hundreds of genes.

We wanted to understand how genetic differences between individuals affect this cellular response to infection,” added co-senior study investigator Johannes Schumacher, Ph.D., a research scientist at the Institute of Human Genetics within the University of Bonn.

The human immune system plays a central role in autoimmune and inflammatory diseases, cancer, metabolism, and aging. The researchers discovered hundreds of genes where the response to immune stimulus depended on the genetic variants carried by the individual.

“These genes include many of the well-known genes of the human immune system, demonstrating that genetic variation has an important role in how the human immune system works,” noted lead study investigator Sarah Kim-Hellmuth, Ph.D., a postdoctoral researcher at the New York Genome Center. “While earlier studies have mapped some of these effects, this study is particularly comprehensive, with three stimuli and two-time points analyzed.”

In the current study, the research team captured genetic variants whose effects on gene regulation were different depending on the different infectious state of the cells. These included four associations to diseases such as cholesterol level and celiac disease. Moreover, the researchers discovered a trend of genetic risk for autoimmune diseases such as lupus and celiac disease to be enriched for gene regulatory effects modified by the immune state.

“Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5-ppp-dsRNA) [lipopolysaccharide, muramyl dipeptide, and 5′ triphosphate double-stranded RNA], and profile the transcriptomes at three-time points, the authors wrote. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS [genome-wide association study] loci and showed a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases.

Co-senior author Tuuli Lappalainen, Ph.D., assistant professor at Columbia University and core member of the New York Genome Center added that this data supports a paradigm where genetic disease risk is sometimes driven not by genetic variants causing constant cellular dysregulation, but by causing a failure to respond properly to environmental conditions such as infection.”

Using the collected monocyte samples, the researchers treated the cells with three components that mimic infection with bacteria or a virus. They then analyzed how cells from different individuals respond to infection by measuring gene expression both during the early and late immune response. Integrating the gene expression profiles with genome-wide genetic data of each individual, they were able to map how genetic variants affect gene expression, and how this genetic effect changes with the immune stimulus.

Findings from this new study provide a highly robust and comprehensive dataset of innate immune responses and show wide variation among individuals exposed to diverse pathogens over multiple time points. The investigators identified population differences in immune response and demonstrated that immune response modifies genetic associations to disease. The research sheds light on the genomic elements underlying response to environmental stimuli and the dynamics and evolution of immune response.

“It’s been known for a long time that most diseases have both genetic and environmental risk factors, concluded Dr. Lappalainen. But it’s actually more complicated than that because genes and environment interact. As demonstrated in our study, a genetic risk factor may manifest only in certain environments. We are still in early stages of understanding the interplay of genetics and environment, but our results indicate that this is a key component of human biology and disease. The molecular approach that we took in our study can be a particularly powerful way for researchers to delve deeper into this question.”

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Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

Genetic disorder gets name change, but patient’s father still not happy – Retraction Watch (blog)

Credit: Online Mendelian Inheritance in Man

The leading genetic disease database has chosen a new name for a genetic condition, following complaints from a man whose son has the condition.

On Aug. 11, 2017, two days after our coverage of the situation, the Online Mendelian Inheritance in Man (OMIM) database changed the primary name of the phenotype associated with mutations in the RPS23 gene. The new name describes a set of features: Brachycephaly, Trichomegaly, and Developmental Delay, or BTDD.

Brachycephaly describes a condition where the back of the head is abnormally flat and trichomegaly refers to extra length, curling, pigmentation, or thickness of the eyelashes.

Marc Pieterse, of the Netherlands, has a son with the rare RPS23 mutation, one of two known patients in the world. The mutation affects ribosomes, cell components involved in protein production. On Aug. 9, we reported on Pieterses crusade against OMIMs original name for the condition, which dubbed it a syndrome. He has feared that calling it a syndrome would stigmatize his sons condition and tried to get the paper underpinning the OMIM entry retracted. The American Journal of Human Genetics has said it will not retract the paper.

Pieterse told us hes only partially pleased the name has been changed hes still unhappy that the original title, MacInnes Syndrome, remains listed as an alternate one.

Initially, OMIM had named the phenotype associated with RPS23 mutations after Alyson MacInnes, a researcher at the University of Amsterdams Academic Medical Center. The name had been selected by OMIM, following a standard procedure of using the last name of the last author of the scientific paper that described the link between the mutation and the set of features.

Pieterse told Retraction Watch that he doesnt think BTDD is a great name, but he likes it much better than the previous one:

I think in the long term, its not describing well what is going on. As an intermediate solution for this naming game, I can live with it. If they want to describe it in this way, I wont be upset about it.

However, OMIM lists MacInnes Syndrome as an alternative title, which Pieterse says he will not endure:

Take out the alternative name. You dont need an alternative name anymore now

I dont think its a big deal for OMIM to leave it out.

OMIM Director Ada Hamosh, a professor at Johns Hopkins University, is on vacation, her assistant told us. When we spoke to Hamosh for our original story, she told us that the names of phenotypes can change, but the database entry is likely to continue displaying past names:

[OMIM] is a complete record of everything that happened.

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Genetic disorder gets name change, but patient’s father still not happy – Retraction Watch (blog)

Beating the Odds for Lucky Mutations – Quanta Magazine

In 1944, a Columbia University doctoral student in genetics named Evelyn Witkin made a fortuitous mistake. During her first experiment in a laboratory at Cold Spring Harbor, in New York, she accidentally irradiated millions of E. coli with a lethal dose of ultraviolet light. When she returned the following day to check on the samples, they were all dead except for one, in which four bacterial cells had survived and continued to grow. Somehow, those cells were resistant to UV radiation. To Witkin, it seemed like a remarkably lucky coincidence that any cells in the culture had emerged with precisely the mutation they needed to survive so much so that she questioned whether it was a coincidence at all.

For the next two decades, Witkin sought to understand how and why these mutants had emerged. Her research led her to what is now known as the SOS response, a DNA repair mechanism that bacteria employ when their genomes are damaged, during which dozens of genes become active and the rate of mutation goes up. Those extra mutations are more often detrimental than beneficial, but they enable adaptations, such as the development of resistance to UV or antibiotics.

The question that has tormented some evolutionary biologists ever since is whether nature favored this arrangement. Is the upsurge in mutations merely a secondary consequence of a repair process inherently prone to error? Or, as some researchers claim, is the increase in the mutation rate itself an evolved adaptation, one that helps bacteria evolve advantageous traits more quickly in stressful environments?

The scientific challenge has not just been to demonstrate convincingly that harsh environments cause nonrandom mutations. It has also been to find a plausible mechanism consistent with the rest of molecular biology that could make lucky mutations more likely. Waves of studies in bacteria and more complex organisms have sought those answers for decades.

The latest and perhaps best answer for explaining some kinds of mutations, anyway has emerged from studies of yeast, as reported in June in PLOS Biology. A team led by Jonathan Houseley, a specialist in molecular biology and genetics at the Babraham Institute in Cambridge, proposed a mechanism that drives more mutation specifically in regions of the yeast genome where it could be most adaptive.

Its a totally new way that the environment can have an impact on the genome to allow adaptation in response to need. It is one of the most directed processes weve seen yet, said Philip Hastings, professor of molecular and human genetics at Baylor College of Medicine, who was not involved in the Houseley groups experiments. Other scientists contacted for this story also praised the work, though most cautioned that much about the controversial idea was still speculative and needed more support.

Rather than asking very broad questions like are mutations always random? I wanted to take a more mechanistic approach, Houseley said. He and his colleagues directed their attention to a specific kind of mutation called copy number variation. DNA often contains multiple copies of extended sequences of base pairs or even whole genes. The exact number can vary among individuals because, when cells are duplicating their DNA before cell division, certain mistakes can insert or delete copies of gene sequences. In humans, for instance, 5 to 10 percent of the genome shows copy number variation from person to person and some of these variations have been linked to cancer, diabetes, autism and a host of genetic disorders. Houseley suspected that in at least some cases, this variation in the number of gene copies might be a response to stresses or hazards in the environment.

In 2015, Houseley and his colleagues described a mechanism by which yeast cells seemed to be driving extra copy number variation in genes associated with ribosomes, the parts of a cell that synthesize proteins. However, they did not prove that this increase was a purposefully adaptive response to a change or constraint in the cellular environment. Nevertheless, to them it seemed that the yeast was making more copies of the ribosomal genes when nutrients were abundant and the demand for making protein might be higher.

Houseley therefore decided to test whether similar mechanisms might act on genes more directly activated by hazardous changes in the environment. In their 2017 paper, he and his team focused on CUP1, a gene that helps yeast resist the toxic effects of environmental copper. They found that when yeast was exposed to copper, the variation in the number of copies of CUP1 in the cells increased. On average, most cells had fewer copies of the gene, but the yeast cells that gained more copies about 10 percent of the total population became more resistant to copper and flourished. The small number of cells that did the right thing, Houseley said, were at such an advantage that they were able to outcompete everything else.

But that change did not in itself mean much: If the environmental copper was causing mutations, then the change in CUP1 copy number variation might have been no more than a meaningless consequence of the higher mutation rate. To rule out that possibility, the researchers cleverly re-engineered the CUP1 gene so that it would respond to a harmless, nonmutagenic sugar, galactose, instead of copper. When these altered yeast cells were exposed to galactose, the variation in their number of copies of the gene changed, too.

The cells seemed to be directing greater variation to the exact place in their genome where it would be useful. After more work, the researchers identified elements of the biological mechanism behind this phenomenon. It was already known that when cells replicatetheir DNA, the replication mechanism sometimes stalls. Usually the mechanism can restart and pick up where it left off. When it cant, the cell can go back to the beginning of the replication process, but in doing so, it sometimes accidentally deletes a gene sequence or makes extra copies of it. That is what causes normal copy number variation. But Houseley and his team made the case that a combination of factors makes these copying errors especially likely to hit genes that are actively responding to environmental stresses, which means that they are more likely to show copy number variation.

The key point is that these effects center on genes responding to the environment, and that they could give natural selection extra opportunities to fine-tune which levels of gene expression might be optimal against certain challenges. The results seem to present experimental evidence that a challenging environment could galvanize cells into controlling those genetic changes that would best improve their fitness. They may also seem reminiscent of the outmoded, pre-Darwinian ideas of the French naturalist Jean-Baptiste Lamarck, who believed that organisms evolved by passing their environmentally acquired characteristics along to their offspring. Houseley maintains, however, that this similarity is only superficial.

What we have defined is a mechanism that has arisen entirely through Darwinian selection of random mutations to give a process that stimulates nonrandom mutations at useful sites, Houseley said. It is not Lamarckian adaptation. It just achieves some of the same ends without the problems involved with Lamarckian adaptation.

Ever since 1943, when the microbiologist Salvador Luria and the biophysicist Max Delbrck showed with Nobel prize-winning experiments that mutations in E. coli occur randomly, observations like the bacterial SOS response have made some biologists wonder whether there might be important loopholes to that rule. For example, in a controversial paper published in Nature in 1988, John Cairns of Harvard and his team found that when they placed bacteria that could not digest the milk sugar lactose in an environment where that sugar was the sole food source, the cells soonevolved the ability to convert the lactose into energy. Cairns argued that this result showed that cells had mechanisms to make certain mutations preferentially when they would be beneficial.

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Beating the Odds for Lucky Mutations – Quanta Magazine

Why we should all embrace gene editing in human embryos – The Hill (blog)

The first report of gene editing in viable human embryos performed in the United States was published. The landmark study demonstrates that gene editing technology can successfully repair faulty genes in the human germline a scientific term that refers to sperm or egg cells, zygotes, and embryos.

Correcting gene mutations in the germline is powerful because any such modifications are inherited by subsequent generations in a fixed, self-perpetuating configuration. To many, this represents the Holy Grail of modern medicine.

The ability to edit genes at the germline level brings immense prospects for human health and welfare. Clinical applications that have only ever existed in science fiction are now within the realm of reality. Scientists have developed basic tools that may soon be used to prevent a myriad of debilitating and fatal genetic diseases including Cystic Fibrosis, Tay-Sachs, certain types of cancer, and hereditary forms of Parkinson’s Disease, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer’s Disease.

Despite the vast potential for good, gene editing for clinical purposes is controversial. Jennifer Doudna, a gene editing pioneer, stated she is “uncomfortable” with the clinical applications of the technology. She and others have previously argued for a moratorium on germline editing citing unknown risks, safety, and efficacy concerns.

However, the latest germline editing report suggests that many of the concerns against future use of gene editing technologies for gene repair in human embryos may be premature and overstated. The study sought to correct a mutated version of the MYBPC3 gene, which causes hypertrophic cardiomyopathy, a heritable disease that leads to sudden cardiac failure, often in young athletes.

The study revealed that co-injecting the CRISPRCas9 system and sperm carrying the faulty MYBPC3 into healthy donor eggs corrected the pathogenic mutation. Importantly, the researchers overcame many of the problems associated with editing of human embryos that Chinese teams have experienced since 2015.

By injecting the gene editing system before the first cell division, the researchers discovered that mosaicism a characteristic of embryos that have a mix of edited and unedited cellscould be avoided. This strategy led to highly precise and accurate editing, as evidenced by the lack of unintended off-target mutations in the embryos’ genomes.

Progress aside, germline editing is not yet ready for primetime. Further research and considerable technology optimization are essential prerequisites for clinical use. Laws that prohibit clinical trials may be reconsidered, in due course, as the technology develops. That all takes time.

Researchers know this. Unfortunately, scientific progress is frequently susceptible to sensationalism.

Unjustified debates concerning germline editing often conjure up eugenics. Alluring and frivolous claims that reproductive technologies will inevitably be used to create tall, beautiful, superhuman geniuses with superb athletic abilities circulate ad nauseam. The myth of “designer babies” has become an emblem of misinformation.

Never mind that the quest to uncover specific intelligence gene(s) has proven to be an exercise in futility. Research shows that, while heritable, highly polygenic traits those determined by multiple genesare often determined by the collective contribution of hundreds of genes. For instance, hundreds of genetic variants in at least 180 genetic loci have been reported to influence height in humans.

Knowledge concerning the genetics of complex polygenic traits is vastly incomplete. The notion that scientists can tinker with a few genes let alone hundreds of them simultaneously, and know precisely how such manipulation will affect an individual is simply preposterous at this time. And it will likely remain so during our lifetimes.

That scientific fact favors gradual and thoughtful measures including legislation and policymakingto address actual concerns raised by germline editing. Entertaining dubious hypotheticals is a dangerous endeavor. And seeking to ban a technology over far-fetched contingencies is bad policy.

So be skeptical when encountering views that aver humans are entering a Brave New World. Be skeptical when scientific progress is reduced to a Frankenstein-like fable engineered to pollute thoughtful debate. The designer baby canard must be confronted.

We are indeed entering a new exciting world. One in which human ingenuity can and will be used to eradicate disease and suffering by pushing the boundaries of knowledge.

We should all embrace this momentous time in human history.

Paul Enrquez is a lawyer and scientist. His work focuses on the intersection of science and law and has been featured in legal and scientific journals. He explores gene editing as it relates to eugenics and the genetics of human intelligence in his recently published article “Genome Editing and the Jurisprudence of Scientific Empiricism.”

The views expressed by contributors are their own and not the views of The Hill.

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Why we should all embrace gene editing in human embryos – The Hill (blog)

Midland to host community conference for genetic conditions – Baylor College of Medicine News (press release)

On Saturday, Sept. 16, Baylor College of Medicine will bring a community conference and resource fair to the Midland area to provide an educational seminar and support materials for children with special needs, as well as their parents.

Provided jointly by Baylor and Texas Childrens Hospital, in collaboration with SHARE West Texas, the conference will address the role genetic evaluations play in patients with autism spectrum disorders.

Dr. Daryl Scott, associate professor of molecular and human genetics at Baylor, will walk parents through the steps of a genetic evaluation and discuss what the findings mean, citing relevant case studies. The emphasis will be placed on common causes of autism, including Fragile X syndrome, chromosomal abnormalities and mutations affecting genes linked to autism.

Conference attendees will learn how new genetic tests have made it possible to determine why some children are affected by autism spectrum disorders. When a specific case is identified, it allows physicians to provide accurate counseling and improved medical care for all family members, Scott said.

The resource fair will offer current information on care, education and research as they relate to autism spectrum disorders and encourages networking within the community by connecting patients and their families with others in similar situations.

Our goal in introducing this program to the Midland community is to broaden the awareness of these disorders while also providing parents and families with the knowledge and resources they need to cope with the behavioral and developmental disabilities that often accompany them, said Susan Fernbach, director of genetic outreach at Baylor and Texas Childrens.

The program is free and open to the public, but registration is required. The seminar will be held at Midland Shared Spaces, at 3500 North A St. To register, email Traci Hopper at thopper@sharewtx.org, or call 432-818-1259. The resource fair begins at 9 am, and the conference will follow at 10 am. Lunch will be provided.

This conference is supported by the Texas Center for Disability Studies at the University of Texas at Austin and the Texas Department of State Health Services.

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Midland to host community conference for genetic conditions – Baylor College of Medicine News (press release)

The Search for the Missing AD Heritability Turns Up New Rare Variants – Alzforum

15 Aug 2017

Genetic forces drive a sizable portion of Alzheimers disease, yet only a fraction of cases thus far are explained by known mutations. A handful of recent papers used genomic sequencing to fish out new variants that, while exceedingly rare, pack a wallop in those who carry them. In the July 24 JAMA Neurology, researchers led by Margaret Pericak-Vance at the University of Miami in Florida reported that mutations in four endolysosomal transport genes boosted risk of early onset AD (EOAD). A few weeks earlier, a large collaboration of French researchers reported rare new TREM2, ABCA7, and SORL1 variants in Neurobiology of Aging, while scientists led by Henne Holstege at VU University Medical Center in Amsterdam characterized the pathogenicity of SORL1 variants and even proposed classifying this endosomal sorting protein as the fourth autosomal-dominant AD gene. A team led by Dominique Campion at University of Rouen, France, dug deep into the well-trodden territory of the three autosomal-dominant genesAPP, PS1, and PS2and uncovered de novo pathogenic variants that cropped up in people with no family history of AD. Last but not least, Anne Rovelet-Lecrux, also at Rouen, linked a duplication in the tau gene to people with an AD diagnosis who lacked Aplaques.

Together, the studies move the field a step closer to filling in the missing genetic influence on AD, and could provide new targets for therapeutic strategies, commented Liana Apostolova at the University of Indiana in Bloomington. There are more genetic risk factors in hiding that have yet to be discovered, and these studies suggest were on the right track, she toldAlzforum.

In the JAMA Neurology study, first author Brian Kunkle and colleagues report on their search for rare variants with large effects on AD risk. Reasoning that people with EOAD are likely carriers of damaging genetic mutations, they conducted whole-exome sequencing in 51 non-Hispanic white EOAD patients, plus 53 people from 19 Caribbean Hispanic families with EOAD; all had tested negative for known causal mutations in APP, PS1, and PS2. The scientists combed the exomes for variants predicted to have damaging effects, then attempted to validate each variants association with AD using exome genotyping data from a separate cohort of 1,500 EOAD patients, 7,000 LOAD patients, and 7,000 controls. Developed by the Alzheimers Disease Genetics Consortium (ADGC), the exome chip used to genotype this separate cohort contains more than 200,000 variants, most of which are functional, rare, single nucleotidemutations.

In their original sequencing cohort, the researchers identified mutations in known or suspected EOAD genes, including SORL1, PS1, PS2, TREM2, and MAPT. Some were known; others were new variants in genes previously tied to LOAD, including HLA-DRB1, ABCA7, and RIN3. Suspicious mutations also cropped up in genes without an AD record. A missense mutation in TCIRG1, present in a non-Hispanic white person with EOAD and segregating with EOAD in three Hispanic families, was twice as frequent in EOAD than in controls in the validation cohort. Deleterious mutations in PSD2 appeared in multiple unrelated cases in the sequencing cohort, and associated with EOAD in the validation cohort, at least when considered in the aggregate. Mutations in RIN3 and RUFY1 appeared in the discovery cohort, but their EOAD association in the validation group was nominal. Importantly, all four genes function in different parts of the endolysosomal transport pathway, which is essential for clearing cellular debris and unwanted proteins, includingA.

The researchers found additional rare mutations in EOAD patients, but these were not on the exome chip used for the validation cohort. For example, of 151 potentially damaging variants that appeared in the original exome sequencing cohort, only 43 were included on the exomechip.

While this filtering process allows researchers to test whether a variant is truly linked to disease, it also precludes consideration of totally new, potentially damaging mutations, said Holstege. The mutations that are most damaging are also the most rare, Holstege told Alzforum. If you filter them out in this way, you quench yoursignal.

Holstege took a different tack to find and classify rare SORL1 variants. Rather than filtering out undocumented variants, Holstege and colleagues made them their bread and butter. In the May 24 European Journal of Human Genetics, they reported 115 SORL1 variants from the exomes of a Dutch cohort of 640 AD cases and 1,268 controls. Fifteen of these variants were common, and not associated with AD. The other 100 were rare, occurring in less than 0.01 percent of the population. Of those, 19 were predicted to be strongly damaging, based on high scores on CADD, an algorithm that considers more than 100 variant characteristics to predict how likely a given mutation is to alter protein function orexpression.

Strikingly, 16 of these suspicious variants only appeared in a single person within the entire cohort, and 14 of those had AD. None of the variants were included in prior exome genotyping studies, so the researchers could not draw upon past data to validate whether they truly associated with the disease. Instead, the researchers developed a pathogenicity scale. Weaving in data from more than 3,000 exomes sequenced separately, the researchers classified a total 181 SORL1 variants based on their combined CADD scores and rarity. They categorized those that had high CADD scores and were very rare as pathogenic. Estimated pathogenicity decreased from likely pathogenic to uncertain to likely benign to benign as variants became less damaging and morecommon.

The scientists found that a combination of high CADD scores and extremely low allele frequency selected out those SORL1 variants that occurred much more often in cases than in controls. The 13 variants with the highest pathogenicity resulted in truncations of SORL1, and occurred only in AD cases. The researchers predicted they would cause dominantly inherited AD, though none have yet been traced in familypedigrees.

Holstege and colleagues proposed that SORL1 take a spot alongside PS1, PS2, and APP as an autosomal-dominant AD gene. Pathogenic SORL1 mutations occurred in 2 percent of the AD cases in this study, placing them at a higher frequency than other ADAD genes. Like PS1, PS2, and APP, SORL1 protein strongly influences A, as it protects APP from amyloidogenic processing and ushers A to lysosomes for disposal (see Sep 2007 news; Feb 2014 news).

Classifying SORL1 as an ADAD gene would raise new questions. How to provide genetic counseling to affected families? Should mutation carriers be eligible to join the Dominantly Inherited Alzheimers Network (DIAN)? Clinical-grade genetic tests for SORL1 variants would be needed, a challenge developers may postpone until further data has confirmed the mutations are pathogenic, commented Apostolova. She added that while Holsteges pathogenicity scale is an exciting tool that should be used in future studies, validation of each mutation in other cohorts, as well as functional evidence in animal and cell culture studies, should be required to elevate SORL1 to ADAD status. Rovelet-Lecrux agreed that designating SORL1 an ADAD gene will have to await discovery of multigenerational families in which SORL1 segregates with disease in an autosomal-dominant pattern. Until we accumulate more genetic evidence, we cannot tell SORL1 mutation carriers how likely they are to develop disease, shesaid.

A new study led by Rouens Campion and co-authored by Rovelet-Lecrux further supports pathogenicity of SORL1 variants, even if it does not provide evidence of multigenerational segregation. As reported July 13 in the Neurobiology of Aging, the researchers detected SORL1 missense and protein-truncating variants that associated strongly with early onset disease by doing whole-exome and genome sequencing of a French cohort of 852 EOAD, 927 LOAD, and 1,273 control cases. All but one of 13 protein-truncating variants occurred only in EOAD cases, and eight of 10 cases with available family information had a history of the disease. Besides SORL1, TREM2 and ABCA7 also harbored potentially damaging EOAD-associated variants in this sample. The researchers estimated that variants in these three genes accounted for 1.42, 1.17, and 1.33 percent of EOAD heritability, respectively. By comparison, ApoE4 accounted for 9.12percent.

New Finds in Old Genes While many pathogenic mutations in PS1, PS2, and APP have been traced in family pedigrees, additional rare variants in these established ADAD genes may yet be discovered. In search of them, researchers led by Rouens Campion sequenced these genes in 129 sporadic cases of early onset AD, as well as in 53 affected families. Published March 28 in PLOS Medicine, the findings included data from participants who joined the ongoing French study after 2012, when the researchers had published a similar analysis (Wallon et al., 2012).In all, first author Hlne-Marie Lanoisele and colleagues identified 44 PS1, two PS2, and 20 APP mutations, as well as five APP duplications; 12 of the PS1 and one PS2 mutation had not been reportedpreviously.

The most striking finding was the existence of de novo mutations in PS1. Indeed, seven of 12 new mutations occurred in sporadic cases of EOAD. In three of these mutations, the researchers were able to confirm that the carriers parents did not carry the new mutation. Rovelet-Lecrux, a co-author on the paper, said that the prevalence of de novo mutations in ADAD genes is likely underestimated, because routine genetic screening for these mutations is done only in familial AD cases. The de novo find underscores the importance of checking for pathogenic mutations even in patients without a family history of AD, especially people with an early age at onset, Holstege commented. Similar to the situation with rare SORL1 variants, researchers will need to decide how to categorize carriers of new and de novo mutations in established ADAD genes, shesaid.

Finally, results from a slightly older study led by Rovelet-Lecrux pose a different kind of classification conundrum. The authors deployed whole-exome sequencing to hunt specifically for copy number variations (CNVs) such as duplications and deletions in 335 genes predicted to influence A processing, clearance, or aggregation. The researchers found CNVs in 30 out of 522 people with EOAD, but only 18 out of 584 controls. Most of these CNVs occurred in a single person in the cohort, and they included novel deletions in the PS1, ABCA7, and SLC30A3 genes previously tied toAD.

A surprising finding reared its head in four AD cases, who all had a duplicationin a region of chromosome 17 including MAPT, the gene encoding none other than tau. The duplication appeared in two sporadic cases of EOAD and two with a family history. DNA available from one of those families confirmed that the duplication segregated with EOAD. Even though these four carriers had symptoms consistent with AD, the three who underwent amyloid-PET imaging had negative scans, to Rovelet-Lecruxs surprise. All four duplication carriers had abnormal levels of CSF p-tau and tau, and three of them also had abnormal concentrations of A42. The researchers also found nearly double the amount of tau mRNA in the blood of carriers than incontrols.

Together, the findings suggest that despite the lack of A plaques visible on PET, carriers of a tau duplication have a clinical disorder markedly similar to AD. The abnormality of CSF A42 in three of the duplication carriers suggests that they could have accumulated A just below the level of PET detection, a sub-threshold aggregation the researchers speculated could even be somehow caused by elevatedtau.

Do these tau duplication carriers have AD? Not if you consider A accumulation as a defining feature of the disease, said Apostolova. Indeed, in the paper, the researchers defined their disease as a tau-related dementia, proposing that it could account for a significant proportion of early onset dementia cases with no genetic explanation. While some researchers view A as a mere forerunner to the more destructive tau pathology, which they consider the main event in AD, Rovelet-Lecrux shied away from separating A from AD, saying that AD is ultimately diagnosed via its neuropathological hallmarks of A plaques and tau tangles. She believes it will be important to screen EOAD patients without A plaques for tau pathology, especially in the future once both A- or tau-targeted therapies exist.JessicaShugart

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The Search for the Missing AD Heritability Turns Up New Rare Variants – Alzforum

Human Germline Genome Editing – Genetics bodies weigh in on debate with position paper – Lexology (registration)

In an article published in American Journal of Human Genetics on 3 August 2017, an international group of 11 organisations with genetics expertise has issued a joint position statement, setting out 3 key positions on the question of human germline genome editing:

(1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

(2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

(3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

This serendipitously timed statement comes on the heels of Shoukhrat Mitalipov and colleagues at Oregon Health and Science Universitys publication of an article in Nature reporting the successful use of CRISPR/Cas9 in human embryos to correct a mutation in a gene called MYBPC3 that causes a potentially fatal heart condition known as hypertrophic cardiomyopathy. The publication of this article has drawn the attention of the wider mainstream media and reignited the public debate as to the desirability, feasibility and ethics of editing the human genome in an inheritable way.

Gene editing – putting the paper in context

Whilst debates about the ethics of gene editing (both somatic and germline) go back decades, human germline genome editing has never before been realistically possible from a technical standpoint. That has changed with the advent of the CRISPR/Cas9 system, whose efficiency and ease of use has not only opened up the field of gene editing to a far larger number of companies and laboratories than previously, but has brought the editing of specific genes in a human embryo out of the realms of fantasy into reality. The potential for such technology to improve quality of life and prevent suffering caused by debilitating genetically inherited diseases has captured the imagination of many, particularly people living with currently intractable genetic conditions, their friends and family. However, the power of the technology has also conjured up the familiar spectres of playing God, the uncertainty of long term effects on individuals (and what it means to be human itself), marginalisation of the disabled or genetically inferior and the potential for inequality to manifest itself genetically as well as socioeconomically.

Germline cell editing poses significantly more concerning ethical and regulatory issues than somatic cell editing. The latter will only result in uninheritable changes to the genome of a population of cells in the particular individual treated, whilst the former involves genetic changes that will be passed down, for better or worse, to the individuals offspring.

In early 2015, the first study demonstrating that CRISPR/Cas9 could be used to modify genes in early-stage human embryos was published. Although the embryos employed for those experiments were not capable of developing to term, the work clearly demonstrated that genome editing with CRISPR/Cas9 in human embryos can readily be performed. That report stimulated many scientists and organisations to clarify their stance on the use of genome-editing methods. The United Kingdom and Sweden have both approved experiments for editing DNA of a human embryo but not those that involve implanting embryos. In the UK, Human Fertilisation and Embryology Authority (HFEA) has approved an application by developmental biologist Kathy Niakan, at the Francis Crick Institute in London, to use CRISPR/Cas9 in healthy human embryos. Currently, such experiments cannot be done with federal funding in the United States given a congressional prohibition on using taxpayer funds for research that destroys human embryos. Congress has also banned the U.S. Food and Drug Administration from considering a clinical trial of embryo editing. As would be expected, the safety requirements for any human clinical genome-editing application are extremely stringent.

However, earlier this year, US-based National Academy of Sciences (NAS) and the National Academy of Medicine (NAM), published a report that concluded using genome-editing technology, such as CRISPR/Cas9, to make alterations to the germline would be acceptable if the intention was to treat or prevent serious genetic disease or disorders, and the procedure was proven to be safe ( significant and, to an extent, subjective hurdles to be overcome).

The ASHG position paper

The position paper was the product of a working group established by the American Society of Human Genetics (ASHG), including representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counsellors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counsellors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The group, composed of a combination of research and clinical scientists, bioethicists, health services researchers, lawyers and genetic counsellors, worked together to integrate the scientific status of and socio-ethical views towards human germline genome editing.

As part of this process, the working group reviewed and summarised nine existing policy statements on gene editing and embryo research and interventions from national and international bodies, including The International Society for Stem Cell Research (2015) Statement on Human Germline Genome Modification, The Hinxton Group (2015) Statement on Genome Editing Technologies and the statement released following the International Summit on Human Gene Editing (2015) co-hosted by the National Academy of Sciences, National Academy of Medicine, Chinese Academy of Sciences and The Royal Society (UK). It was observed that differences in these policies include the very definition of what constitutes a human embryo or a reproductive cell, the nature of the policy tool adopted to promote the positions outlined, and the oversight/enforcement mechanisms for the policy. However, by and large, the majority of available statements and recommendations restrict applications from attempting to initiate a pregnancy with an embryo or reproductive cell whose germline has been altered. At the same time, many advocate for the continuation of basic research (and even preclinical research in some cases) in the area. One notable exception is the US National Institutes of Health, which refuses to fund the use of any gene-editing technologies in human embryos. Accordingly, due to the lack of public funding in the US, work such as that done by Mitalipovs group must be privately funded.

The working group considered that ethical issues around germline genome editing largely fall into two broad categories those arising from its potential failure and those arising from its success. Failure exposes individuals to a variety of health consequences, both known and unknown, while success could lead to societal concerns about eugenics, social justice and equal access to medical technologies.

The 11 organisations acknowledged numerous ethical issues arising from human germline genome editing, including:

Having touched on each of these issues, the group then outlined its consensus positions:

1. At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

It was noted that there is not yet a high quality evidence base to support the use of germline genome editing, with unknown risk of health consequences and ethical issues still to be explored and resolved by society.

The group observed that two major categories of safety concerns are (i) the effect of unwanted or off-target mutations, and (ii) the potential unintended effects of the desired on-target base changes (edits) being made. It noted that it is reasonable to presume that any human genome-editing therapeutic application will require stringent monitoring of off-target mutation rates, but there remains no consensus on which methods would be optimal for this, or what a desirable maximum off-target mutation rate would be when these techniques are translated clinically. The working-group thus outlined its views on the minimum necessary developments that would be required (at least from a safety perspective) before germline genome editing could be used clinically:

2. Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

The group agreed that conducting basic scientific [techniques?] involving editing of human embryos and gametes can be performed ethically via compliance with applicable laws and policies, and that any study involving in vitro genome editing on human embryos and gametes should be conducted under rigorous and independent governance mechanisms, including approval by ethics review boards and meeting any other policy or regulatory requirements. Public funding for such research was seen as important in ensuring that such research is not driven overseas or underground, where it would be subject to less regulation, oversight and transparency.

3. Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

Even if the technical data from preclinical research reaches a stage where it supports clinical translation of human germline genome editing, the working group stresses that many more things need to happen before translational research in human germline genome editing is considered. The criteria identified by the group in this position cut across medical, ethical, economic and public participation issues and represent the setting of an appropriately high and comprehensive standard to be met before human germline genome editing may be applied clinically. The group acknowledges the challenges of public engagement with such technical subject matter but encourages new approaches to public engagement and engagement of broader stakeholder groups in the public discussion.

The ethical implications of altering the human germline has been the subject of intense discussion in recent years, with calls for such work to be put on hold until the process of genome editing is better understood. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time.

The working group concludes that Many scientific, medical, and ethical questions remain around the potential for human germline genome editing. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time. We encourage ethical and social consideration in tandem with basic science research in the upcoming years.

This appears a reasonable position largely in line with the recommendations from the major national and international groups surveyed by the working group. It balances the need to encourage further basic research and validation with strong awareness of the ethical and societal implications of human germline genome editing, setting a high bar before such technology should be translated to the clinic. No doubt, however, the debate will continue, particularly in respect of public funding for such work. Whether the US will maintain their stance against public funding, in the face of international competition, and potential loss of talent and investment, remains to be seen.

For more information about the science of CRISPR, its wide range of applications in life sciences and beyond, and latest developments in the field, please see Allen & Overys dedicated CRISPR microsite.

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Human Germline Genome Editing – Genetics bodies weigh in on debate with position paper – Lexology (registration)

Blood test uncovers hidden diseases – Medical Xpress

August 14, 2017

Sufferers of rare mitochondrial disease have new hope with a new method developed at the University of Sydney. The method provides a diagnosis within weeks instead of months or years through a simple blood sample.

Mitochondrial diseases are rare and hard to diagnose. They can affect any organ, at any age and are often ‘hidden’ in other diseases such as diabetes, blindness, liver and kidney failure and even Autism.

The new method has already led to two new disease gene discoveries where the patients suffered from lactate build-up and hyperglycemia (CYC1), and deafness and organ failure (MRPS7). The research published in the American Journal of Human Genetics and Human Molecular Genetics.

“One in 200 people will carry a mitochondrial genetic defect which means nearly 120,000 Australians are at risk of developing serious illness,” says Minal. “And yet mitochondrial diseases are extremely difficult to diagnose. They are often referred to as the ‘notorious masquerader'”.

With the faster diagnosis, some people can be treated for what had previously been thought to be untreatable disease.

For others even if not treatment is available, the diagnosis gives them a cause for the illness and the possibility to enrol in clinical trials. This can result in enormous improvements in quality of life.

Families can also receive genetic counselling and many may choose to use IVF when building a family, with medical staff able to quantify the risk of the disease being passed on.

Explore further: New genetic analysis approach could improve diagnosis for mitochondrial disease

More information: Pauline Gaignard et al. Mutations in CYC1, Encoding Cytochrome c1 Subunit of Respiratory Chain Complex III, Cause Insulin-Responsive Hyperglycemia, The American Journal of Human Genetics (2013). DOI: 10.1016/j.ajhg.2013.06.015

Minal J. Menezes et al. Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia, Human Molecular Genetics (2015). DOI: 10.1093/hmg/ddu747

Newcastle researchers have developed a genetic test providing a rapid diagnosis of mitochondrial disorders to identify the first patients with inherited mutations in a new disease gene.

French scientists have discovered that supposedly rare mutations in the mitochondria, the ‘power plants’ of human cells responsible for creating energy, account for more than 7% of patients with a mitochondrial disease manifesting …

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Blood test uncovers hidden diseases – Medical Xpress

LHS Foundation names 9 more Distinguished Alumni – Lockport Union-Sun & Journal

Nine more graduates of Lockport High School have been named “Distinguished Alumni” by the LHS Foundation.

The 11th annual recognition ceremony for honorees will be held at 7 p.m. Aug. 24 at the high school auditorium. A reception precedes the ceremony at 6:30 p.m. in the art gallery and foyer. All community members are welcome.

The 2017 honorees are listed here.

Anthony Caridi

Anthony Caridi, class of 1980, is recognized as the state of West Virginias most popular sports voice.As the play-by-play announcer of the West Virginia University Mountaineers, he has described the action of some of the schools greatest athletic accomplishments including victories in the Orange, Sugar and Fiesta bowls, along with an NCAA Final Four appearance.

A multiple winner of the West Virginia Sportscaster of the Year award, Caridi has hosted his own nightly statewide sports talk show on the Metro News Radio Network since 1986.

As a founding member of Emmy Award-winning Pikewood Creative, Caridi is responsible for generating new business development, fostering client relationships and directing the Pikewood team in its creative trajectory.

Caridi was raised in his familys grocery business in Lockport. He attended Syracuse University and graduated from the S.I. Newhouse School of Public Communication with a degree in broadcast journalism.

This past December, he released his first childrens book, Where, Oh Where, Oh Where Could we Go? which takes readers on a whimsical trek around West Virginia.

Tony and his wife Joan have three children: Michael, who has a degree in finance and works in Morgantown, and twins Andrew and Matthew, who just finished their freshman year at WVU.

Mary E. Poole Dale

The late Mary Elizabeth (Bette) Poole Dale, class of 1935, was a pioneer in the elder care field and her legacy lives on through the local not-for-profit Dale Association.

Dale was an early advocate for the elderly. She created the first senior center in the United States that provided direct mental health services for adults. Lockport Senior Centre became a national model of the multi-purpose senior center.Dale was an acclaimed speaker at conferences and seminarswell beyond the limits of New York state.In 1995, Lockport Senior Centre was renamed in her honor.

Dale died in 2007.

Jack J. Florio Jr.

Jack J. Florio Jr., class of 1979, and his wife Rebecca are the owners of Micro Graphics, a printing and sign company on Main Street. Florio founded the business in 1989, while he was attending college in Florida, studying computer engineering and working in the college computer lab.

Florio paid close attention to the graphic design classes taught in the lab and mastered the curriculum quickly. The college soon hired him as a technical adviser, to help instruct computer graphics. Seeing the industry’s potential, Florio invested in a Xerox copier and a laser printer and landed clients includingShands Teaching Hospital, University of Florida and Daytona International Speedway.

Upon his return to Western New York, Florio went to work for Roswell Park Cancer Institute, developing the Gilda Radner Ovarian Cancer Registry and the AIDS Database Registry and utilizing his skills for various departments from radiology and pathology to medical illustration, marketing and the print shop. Simultaneously, he was rebuilding Micro Graphics, with which he eventually went full time.

While building up his business, it was normal for Florio to work two or three jobs at a time. He did CAD for General Motors and EDS and has worked as an auto mechanic for Texaco and Gulf Oil, a pre-press and web press operator for the Union-Sun & Journal, a software instructor for DuPont Paint, and a manager of CopyMax and the old Friendly’s restaurant in Lockport.

Florio and his wife have been the sole organizers of the Mother’s Day Breast Cancer Canal Walk for over 20 years. The walk has raised over $500,000 for cancer support. Florio also partners with the Salvation Army every year to send oversized Christmas cards to U.S. troops overseas.

The Florios’ son Michael works in the computer animation field in New York City.

Ronald Franco

Ronald Franco, class of 1982, met his future wife and fellow Distinguished Alumnus, Deborah Qualiana, while attending track practice as an eighth grader.He graduated as senior class president, then attended the Air Force Academy and Syracuse University, and earned a degree in aerospace engineering.

A graduate of Officer Training School, Franco flew supersonic jets during his year at undergraduate pilot training and qualified for Fighter-Attack-Reconnaissance assignment. He returned to Western New York to serve with the Niagara Falls-based 328th Tactical Airlift Squadron and flew: combat missions to liberate Kuwait during Desert Storm and in Iraq and Afghanistan during Operation Iraqi Freedom; humanitarian aid flights to Somalia and the Kurds; UN support missions in Bosnia and Serbia; international cooperation missions in Egypt and Japan; and Special Forces support in Central and South America. He was awarded the USAF Air Medal and Aerial Achievement Medal.

In 1999, Franco was hired by American Airlines. He is a recipient of the Outstanding Checkride Award and recently upgraded to Captain on the Airbus 321 aircraft. He has over 8,000 hours of flight time in jet aircraft.

Last year, Francospent two months at NASAs Johnston Space Center in Houston taking part in the Human Exploration Research Analog. He and three other men completed a simulated deep-space mission to help facilitate the national space program’s goal of sending a manned mission to Mars.

Franco is a past member for the Lockport Common Council, representing the 2nd Ward. Currently he serves on the board of directors of Challenger Learning Center and is a member of the Explorers Club in Manhattan.

Franco has completed two marathons was a member of the winning team in the Lockport 100 Mile Relay Race, which commemorated the 1967 world record. He also has volunteered with the disabled veterans sled hockey team.

Julie Zenger Hain

Julie Zenger Hain, class of 1980, is an expert in the field of genetics.

She’s a graduate of St. Lawrence University, where she earned a degree in biology and psychology and was inducted in Phi Beta Kappa. Subsequently, she earned a Ph.D. in human genetics and a bachelor’s degree in nursing at the Medical College of Virginia of Virginia Commonwealth University. Her post-doctoral work in medical genetics and cytogenetics was completed at Henry Ford Hospital in Detroit, and she achieved board certification from the American Board of Medical Genetics. From there she developed the genetics program at Oakwood Hospital in Dearborn, Michigan, which provides laboratory and clinical genetic services to the Oakwood Health System, now Beaumont Health.

Since her career at Oakwood, Zenger Hain has worked to educate physicians, patients and the public regarding the power of genetics in health care. She has been an active participant with the Michigan Department of Health and Human Services genetic and genomic initiatives, volunteering her time to assist the development and implementation of public policy aimed at enhancing genetic services to all Michigan residents.

Zenger Hain is co-chair of the Michigan Cancer Genetics Alliance, a collaborative network of genetics professionals, patient advocates, oncology experts, health plan employees, state and local public health workers and others with an interest in cancer genomics. She has collaborated on multiple state and community grants aimed at delivering genetic services to underserved populations and served on the Wayne State Institutional Review Board to foster safe research practices for human study participants.

She is also a mentor for the Womens Institute for National Global Success, which provides guidance to young women seeking to enter careers in the sciences.

Zenger Hainand her husband, Jon, have a son and daughter. They currently reside in Troy, Michigan.

Cindi McEachon

Cindi McEachon, class of 2000,defied the odds as a teenage mother. After giving birth to her daughter, Emilee, in her sophomore year, she stayed in school and earned her diploma, then went on to complete post graduate studies. Today she’s a volunteer youth mentor with numerous organizations and serves as the executive director of Peaceprints of WNY.

After high school, McEachon earned an associate’s degree from Niagara County Community College, a bachelor’s degree from the University of Buffalo and a Master of Business and Science degree from Medaille College.

According to her nominator, McEachon is passionate and often bull-headed; when she sets her mind to something, she never looks back. When she was 17, she moved out on her own and balanced full-time work, school and parenting, motivated by the “teen parent” stigma that she carried.

McEachon was appointed director of Peaceprints in 2014. Peaceprints works with incarcerated men, youths and their families. McEachon hopes to raise awareness about the U.S. epidemic of mass incarceration and put a stop to “school-to-prison pipeline” in Buffalo.

Currently, McEachon is the executive vice president of the Junior League of Buffalo and board secretary of Homespace Corporation and For Our Daughters Inc. She’s an active member of Women on the Rise and the Erie County Reentry Task Force, a volunteer coach for Girls on the Run Buffalo, a teen mentor for Homespace Corporation and coordinator of the annual Christmas cookie drive for Buffalo City Mission. She has been a Kenan Center youth soccer coach, a Brownie troop leader and a life coach mentor; and enjoys running marathons and half marathons.

McEachon has two daughters, Emilee, 19, and Lily, 12. She and Christopher Summers will be married on Sept. 9.

James Sansone

James Sansone, class of 1960, is a local attorney, accomplished musician and tireless civic booster.

Sansone earned a bachelor’s degree in linguistics from SUNY at Buffalo in 1964, then went to Buffalo Law School where he received a Bachelor of Laws degree and, in 1968, a Juris Doctorate. He has been a practicing attorney ever since; and has been a confidential law clerk to the Niagara County and Surrogates Court judges, an administrative law judge for New York State. Currently he’s the Newfane town attorney and town prosecutor, mortgage counsel to Cornerstone Community FCU and pro bono counsel to Olcott Volunteer Fire Company and EquiStar Therapeutic Riding in Newfane.

Sansone, an accomplished trumpet player, has played professionally since he was 12 years old. He has been a volunteer bugler for American Legion and VFW since 1953, playing Taps on Veterans Day and Memorial Day and at servicemen’s funerals. He’s a teacher and mentor to young trumpet players and has played in many high school musicals throughout Western New York. Every year, with his trumpet, he leads the (July 4) Patriots Day children’s parade in Olcott. He organizes the summertime Olcott Beach Gazebo Concert Series and volunteers his music services for an array of charitable organizations including Olcott Beach Carousel Park, Olcott Lions Club,Batavia School for the Blindand Lawyers for the Arts.

Sansone has been a member of the Newfane Tourism Board since 2003. He’s a member of Olcott Lions Club,a life member of Local 97-106 of the musicians’ union,a past Eucharistic Minister for St. Josephs church in Lockport and Niagara USA Chamber’s 2012 Small Business Person of the Year.

Jack B. Walters

Jack B. Walters, class of 1946, is an engineer, retired Iowa state public servant and the author of four books.

Waltersenlisted in the Army Air Corps when he turned 18, on July 30, 1946, and served in Japan for three years. He was the lead enlisted officer of a statistical control unit where he advanced to the rank of staff sergeant. Using the G.I. Bill, he obtained a bachelor’s degree in electrical engineering at the University of Buffalo.

Walters married fellow LHS graduate Carolyn Highhouse in 1954 and began a lengthy career with Firestone. He was a staff engineer in Akron, Ohio, a senior engineer in Pottstown, Pa., a plant engineer in Hamilton, Ontario, and a plant manager in Calgary, Alberta, Akron, Ohio, and Firestone’s largest tire factory in Des Moines, Iowa. The Walters had three children, Amy, Andy and Steve, who died in a plane accident in 1997.

Walters became director of general services for the state of Iowa in 1983, upon appointment by Gov. Terry Branstad. Hismost notable efforts included starting exterior restoration of the Capitol building and design and construction of the $25 million Historical and Library Building. He served in the post for eight years, until his wife died from cancer.

Walters retired to Tucson, Arizona, where he discoveredthe Southern Arizona Hiking Club. The goal of members is to climb to the top of 315 area mountains and Walters did it in five years. Afterward, he became a guide and helped others in their quest. Later, the club set a 400-peak goal; and with encouragement from his friend Roxanna Baker, he accomplished the new goal in 2008, at age 79. Walters still hikes today.

Copies of Walters’ four published books are available at Lockport Public Library.

Edward C. Weeks

The late Edward C. Weeks, class of 1953, was an innovator in the adult care field in New York state.

At LSHS, Weeks played football and was a member of the swim team. He went on to the University of Buffalo, where he earned a degree in physical therapy, andmarried Margaret Reddington in 1958. (They had four children, Sean, Patricia, Bridge and Mark. Margaret Weeks died in 1979.)

Weeks did a tour of duty with the Army from 1958 to 1960, serving as a physical therapistat the 98th General Hospital in Neubrucke, Germany.After his discharge, he worked as a physical therapist at Mercy Hospital in Buffalo, St. Josephs Hospital in Cheektowaga and Niagara Lutheran Home, where he established a physical therapy department. Impressed by his leadership skills, home management persuaded him to move into an administrative role.

After three years at Niagara Lutheran, Weeks was appointed administrator of Carlton House Nursing Home; and when that facility was sold to becomepart of what is now Roswell Park Cancer Institute, he became the administrator of Newfane Health Care Facility. In 1976, Weeks took over as administrator of Episcopal Church Home, where he rose to president and chief executive officer.

As an administrator, Weeks was always looking for better ways to care for elderly with illness and dementia. He developed many “firsts” in Western New York and New York state: respite care, long-term home health care, HIV/AIDS home care, restraint-free nursing home care, adult day health care, inter-generational child care and, ultimately, the first Continuing Care Retirement Community (CCRC) in the state.

Weeks lobbied for state legislation to permit operation of life-care communities, which resulted in him developing Canterbury Woods in Amherst. The project introduced the area to continuing care, which offers a range of options from independent living to skilled nursing, all on one campus.

Weeks married Alana Parisi in 1997 and added five stepchildren to his family: Jason, Cale, Aron, Matthew and Ryan. His hobbies included golfing and sailing. He died in 2015.

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LHS Foundation names 9 more Distinguished Alumni – Lockport Union-Sun & Journal

Orphan Black Was Never About Cloning – Slate Magazine

From the opening scene, questions of identityboth existential and scientificprovide the shows narrative thrust.

BBC America

This article contains spoilers about the series finale of Orphan Black.

After five seasons of clone cabals, the BBC America/Space series Orphan Black has come to a mostly happy end. Yet an ellipsis follows wrapping of the show, hinting at bigger questions that transcend the characters storylines. Orphan Blacks conspiracies, camp, and Tatiana Maslanys riveting performances as a dozen different clones make it easy to overlook its prescience and profundity. From the opening scene in which Sarah Manning sees her clone kill herself by stepping in front of a train, questions of identityboth existential and scientificprovide the shows narrative thrust. Who created the clones? How? Why? How much control do their creators have over them? The shows final season provides answers while raising questions that transcend science fiction. What role should ethics play in science? Do scientific subjects have the right to self-determination?

If you stopped watching a few seasons back, heres a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest peoples genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.

In the final season, we meet the man behind the curtain: P.T. Westmoreland, who claims to be 170 years old thanks to life-extension treatments such as parabiosis (transfusions of young blood). Westmoreland wants to harness the healing powers of the particular LIN28A gene mutation found in the fertile clones kids. (Real-world studies suggest that while LIN28A mutations are linked to cancer, its RNA-binding protein promotes self-renewal of embryotic stem cells.)

Westmorelandultimately discovered to be a fraud who assumed the original Westmorelands identity after he diedpersonifies one of the shows messages: that pseudoscience and megalomania can masquerade as science. Just because someone has a genetic sequencer and a lab coat doesnt mean hes legitimate, and just because someones a scientist doesnt mean hes ethical.

Orphan Black demonstrates Carl Sagans warning of a time when awesome technological powers are in the hands of a very few. Neolutionists do whatever they want, pausing only to consider whether theyre missing an opportunity to exploit. Their hubris is straight out of Victor Frankensteins playbook. Frankenstein wonders whether he ought to first reanimate something of simpler organisation than a human, but starting small means waiting for glory. Orphan Blacks evil scientists embody this belief: if theyre going to play God, then theyll control not just their own destinies, but the clones and, ultimately, all of humanitys. Any sacrifices along the way are for the greater goodreasoning that culminates in Westmorelands eugenics fantasy to genetically sterilize 99 percent of the population he doesnt enhance.

Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmorelands goal to sell Neolution to the 1 percent seems frighteningly plausibletranshumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. Critics raise many objections to transhumanism, including overpopulation and the socioeconomic divide between mortals and elite immortals, which some think might beget dystopia. Researchers are exploring ways to extend the human lifespan whether by genetic modification, reversing senescence (cellular deterioration with age), nanobots, or bio-printed tissues and organs, but in the world of Orphan Black we dont have to speculate about the consequences of such work.

The show depicts the scientists dehumanization of the clones from its first scene, when Beth, unable to cope with the realities of her cloned existence, commits suicide. When another clone, Cosima, tries to research her DNA, she gets a patent statement: This organism and derivative genetic material is restricted intellectual property. It doesnt matter that Cosima is sick or that shes in love. Shes not a person: Shes a trademarked product, as are the other clones.

Orphan Black warns us that money, power, and fear of death can corrupt both people and science.

The shows most tragic victim is Rachel, the evil clone. Shes the cautionary tale: Frankensteins monster, alone, angry, and cursed. The only one raised with the awareness of what she is, Rachel grows up assured of her own importance and motivated to expand it by doing Neolutions dirty work. Westmoreland signs a document giving Rachel sovereignty, but later she sees computer files in which shes still referred to by her patent number. Despite her leadership, cunning, and bravery, even those working with her never regard her as human. Her willingness to hurt her sisters and herself shows what happens to someone whose experience of nature and nurture is one and the same.

We, the viewers, also dehumanize Rachel by writing her off as one of them. When she lands on the side of her sisters, she does so not out of morality but out of vengeance. At the end, Westmoreland, the closest thing she has to a father, taunts her: its fitting you return to your cage. All lab rats do. But her childhood flashbacks suggest she doesnt want others to experience what she has. When Neolutionists take 9-year-old Kira from her home at gunpoint, Rachel initially supports the plan to load Kira with fertility drugs and then harvest her eggs to access her mutated gene. But when Kira gives Rachel a friendship bracelet (and perhaps her first friendship), Rachels haunted expression suggests that beneath her usually unflappable demeanor, shes still a frightened little girl. When Kira asks, Who hurt you? Rachel responds, They all did.

Whether motivated by retaliation, morality, or both, Rachel helps save Kira and takes down Neolution. Yet its unclear whats left for her as shell never be welcomed into Clone Club. Her last act is to provide a list of clones around the world so Cosima and former Dyad researcher Delphine can cure them. Rachel gives the clones control over their livesand in so doing, asserts control over her own.

Ultimately, Orphan Black is all about choice. Theres much in life we cant choose: our parents, the circumstances of our birth, our DNA. Its no surprise that a show that espouses girl power (the future is female is both spoken and seen on a T-shirt in the final two episodes) dwells on the importance of choice. The finale flashes back to Sarah in front of Planned Parenthood debating whether to have an abortion. Reckless, rough Sarah surprises herself (and Mrs. S, her foster mother) by deciding to keep the baby. Years before she learns how many decisions others have made about her body, she makes a decision for herself.

On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The shows message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be irresponsible to proceed without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isnt farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanityof both the scientists and the subjectsis inevitable.

In Carl Sagans dark vision of the future, people have lost the ability to set their own agendas or knowledgeably question those in authority. This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. The lab rats assert their humanity and refuse to run the maze. Freedom looks different to everyone, Sarah says in the finale. As she struggles to figure out what freedom will look like for hershould she get her GED? Sell the house? Get a job?its easy to see how overwhelming such options would be for someone whose value has always been wrapped in a double helix. But no matter what uncertainties their futures hold, the clones dismantle their cages and make their own choices, proving what weve known all alongtheir humanity.

This article is part of Future Tense, a collaboration among Arizona State University, New America, and Slate. Future Tense explores the ways emerging technologies affect society, policy, and culture. To read more, follow us on Twitter and sign up for our weekly newsletter.

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Orphan Black Was Never About Cloning – Slate Magazine


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