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Researchers explore possible alternative to knee replacement – Scope (blog)

Posted: August 5, 2017 at 1:46 am

Replacing joints like knees or hips can relieve pain and boost quality of life. But these surgeries demand lengthy rehabs and may not restore full function.

Al Perez, 62, wanted to avoid such a procedure if at all possible. And after conducting some research, he discovered Jason Dragoo, MD. Dragoo is leading a study that is examining whether stem cell therapy can improve cartilage growth and decrease inflammation caused by osteoarthritis in the knee.

After 15 years of laboratory research, we have optimized our ability to harvest stem cells from the body and can unleash their potential to improve patients with conditions such as osteoarthritis. After all of this time in the laboratory, we are finally ready for human clinical trials to begin, Dragoo said in a recent Stanford Medicine News article.

The cells are extracted from the knee during surgery. They are then processed and returned to the knee, to help with healing. The article explains:

Perez is one of 100 patients who are expected to undergo the procedure. The trial surgeries started at Stanford in the summer of 2016 and are being performed at other national medical centers such as Harvard University, Rush University in Chicago and Ohio State University. After 100 patients have completed the procedure, the researchers will start evaluating whether those who received the stem cell treatments are better off than those who received the standard treatments.

Results are expected in late 2018.

For Perez, the procedure was a success. He can water ski and golf without suffering severe pain. Many other patients are also doing well, Dragoo said.

We believe this technique will yield more positive results than standard arthroscopy because we are using cell therapy to help the body heal itself, Dragoo said. We hope this may save many patients from having to undergo knee replacement.

Previously: Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure theyre making new kneesPhoto by Eric Kayne

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Unusual treatment for acne scars uses your own plasma – THV 11

Posted: August 5, 2017 at 1:46 am

Treatment for acne scars comes to central Arkansas

Winnie Wright , KTHV 10:58 PM. CDT August 01, 2017

LITTLE ROCK, Ark. (KTHV) - For those with acne scars, there can be a lot of problems. People deal with bigger pores, rosacea, even difficulty sweating, but sometimes find little to no solutions.

But a new treatment has shown up in central Arkansas that is a little unusual.

Acne scars have been an unfortunate part of April Bisbee's life for decades.

"I'm still carrying around things from when I was a teenager," said the 37-year-old. "I didn't really notice how much that affected me as an adult until I started doing something to improve it.

She began those improvements with two micro needling treatments, which are exactly what they sound like. A tool with tiny needles is drawn across the face to break up the scar tissue which helps to heal old wounds.

After seeing the results, she decided to take it a step further. Now she is trying a Platelet Rich Plasma (PRP) Facial. The process uses her own blood plasma to heal her scars.

"The way that I describe it to patients is that the plasma is our own body's liquid gold," said Monica Cooper, a license aesthetician at SeiBella Med Spa. "It is the closest thing that we have to stem cells. It regenerates faster. So as we are doing the micro needling, it's going to heal the wound much faster than anything used as a synthetic."

Bisbee's blood is drawn by a nurse and it is put into a centrifuge to separate the blood from the plasma.

"I'm going to take the first bit of the plasma and I'm just going to wipe it all in the area where we are going to start, at her forehead, Cooper explained.

As the needles break the surface of her skin, it bleeds a little, but Cooper said a little blood is good. That's how she knows she's made it below the scarring.

"It feels a bit like getting a tattoo without the ink," Bisbee said about the process.

If you're not too keen on the idea of having blood plasma rubbed on your face, Cooper said there are other formulas available to make you feel less like a vampire.

"It is still going to give you the scar reduction. It is going to help with aging, fine lines, she said.

Before the PRP facial, many with facial sensitivities had few options. Cooper explained that all patients need to be evaluated to be sure the PRP Facial is a fit. Those who are prone to keloid scars, for example, would not want to undergo this procedure.

In about a week, Bisbee will be fully healed, but even now, she can wear a special SPF makeup and go back to work.

"I'm feeling good. I'm glad I did it, Bisbee said.

She said that already her skin is less red with the treatment than it was with her previous micro needling treatments.

Each PRP Facial treatment is around $700. Cooper said she suggests Bisbee and other patients continue coming back for treatments every few weeks until they no longer see their skin progressing. She also said the results should be permanent unless new acne scars develop.

2017 KTHV-TV

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Stem Cell Therapy For Lung Fibrosis Conditions – ReliaWire

Posted: August 5, 2017 at 1:45 am

Promising research towards a possible stem cell treatment for several lung conditions has been developed by scientists from the UNC School of Medicine and North Carolina State University. The conditions include idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis often-fatal conditions that affect tens of millions of Americans.

The team of scientists showed that they could harvest lung stem cells from people using a relatively non-invasive, doctors-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, the team demonstrated that in rodents they could use the same type of lung cell to successfully treat a model of IPF a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function. The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with idiopathic pulmonary fibrosis.

Co-senior author of both papers Jason Lobo, MD, an assistant professor of medicine at UNC and medical director of lung transplant and interstitial lung disease, said:

This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens.

Co-senior author Ke Cheng, PhD, an associate professor in NCSUs Department of Molecular Biomedical Sciences and the UNC/NCSU Joint Department of Biomedical Engineering, added,

We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.

These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood.

Patients ultimately are at risk of early death from respiratory failure. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

The two FDA-approved drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.

Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases.

Stem cells are immature cells that can proliferate and turn into adult cells in order to, for example, repair injuries. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrosis diseases.

Cheng and Lobo have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture.

As the scientists reported in an initial paper in 2015, lung spheroid cells showed powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperformed other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.

In the first of the two new studies, Lobo and his team showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy.

We snip tiny, seed-sized samples of airway tissue using a bronchoscope, Lobo said. This method involves far less risk to the patient than does a standard, chest-penetrating surgical biopsy of lung tissue.

Cheng and his colleagues cultured lung spheroid cells from these tiny tissue samples until they were numerous enough in the tens of millions to be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals lungs.

These cells are from the lung, and so in a sense theyre happiest, so to speak, living and working in the lung, Cheng said.

In the second study, published in Stem Cell Translational Medicine, the researchers first induced a lung fibrosis condition in rats.

The condition closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats.

Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.

Also, the treatment was safe and effective whether the lung spheroid cells were derived from the recipients own lungs or from the lungs of an unrelated strain of rats, Lobo said. In other words, even if the donated stem cells were foreign, they did not provoke a harmful immune reaction in the recipient animals, as transplanted tissue normally does.

Lobo and Chen expect that when used therapeutically in humans, lung spheroid cells initially would be derived from the patient to minimize any immune-rejection risk.

Ultimately, however, to obtain enough cells for widespread clinical use, doctors might harvest them from healthy volunteers, as well as from whole lungs obtained from organ donation networks. The stem cells could later be used in patients as-is or matched immunologically to recipients in much the same way transplanted organs are typically matched.

Our vision is that we will eventually set up a universal cell donor bank, Cheng said.

Cheng, Lobo, and their teams are now planning an initial study of therapeutic lung spheroid cells in a small group of IPF patients and expect to apply later this year for FDA approval of the study.

In the long run, the scientists hope their lung stem cell therapy will also help patients with other lung fibrosis conditions of which there are dozens, including COPD, cystic fibrosis, and fibro-cavernous pulmonary tuberculosis.

Image: NC State / UNC

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Cell therapy firm in flurry of activity as hope nears for bone marrow … – The Times of Israel

Posted: August 5, 2017 at 1:45 am

The excitement at Jerusalem-based Gamida Cell, a maker of cell and immune therapy technologies, is palpable.

The biotechnology company has started enrolling patients for a last-stage clinical trial for a drug it believes will help increase the success of bone marrow transplants in blood cancer patients, and help them better withstand the ordeal of the lifesaving procedure.

The patients are being enrolled in the US, Spain, The Netherlands and Singapore. Should the results of the trial, as hoped, be positive, that would lead to the launch of a commercially available product in 2020, Gamida Cells CEO Yael Margolin said in an interview with The Times of Israel.

We are at an exciting transition point, and moving from being a research and development firm, based in Israel, to an international commercial firm, said Margolin who has headed the company for the past 12 years in her sun-drenched office at the biotech firms headquarters in Jerusalem. We need to prepare to commercialize the product. We are now looking at various sites in Israel for a new manufacturing facility and looking to employ some 100 people. These workers will be added to the 40 already employed in Jerusalem.

Gamida Cells CEO, Dr. Yael Margolin (Courtesy)

Preliminary clinical data has already revealed that the risk of their leading product for blood cancers, NiCord, not meeting its targets in the Phase 3 trial, is low, added Margolin.

The drug has already received a breakthrough therapy designation by the US Food and Drug Administration (FDA). The designation is given to a drug that is meant to treat a serious or life-threatening condition, and where preliminary clinical evidence indicates that it may demonstrate a substantial improvement on at least one clinically significant target (endpoint) over other available therapies. The designation also entitles the company to get more and closer FDA guidance to help bring the treatment faster to patients.

The combination of the low clinical risk based on the previous trial results and the lower regulatory risk, because the drug is being developed in close collaboration with the FDA, has spurred the company into a flurry of activity that is aimed at scaling up its production facilities to get ready for the day NiCord hits the markets.

The company said last month it raised $40 million from investors including Novartis, which is already a major shareholder in the firm. The funds will support the ongoing Phase 3 stage for NiCord. The company also announced, on July 20, that it received a $3.5-million grant from the Israeli government that will support the further development of NiCord and other drugs that the company is developing, including therapies for sickle cell disease and for blood and solid cancers. Gamida has also appointed a new chief medical officer, Ronit Simantov, who will be based in the US.

The first market for our drug will be the US, Margolin said.

The Gamida Cell lab in Jerusalem where umbilical cord blood is stored in tanks, July 16, 2017. (Shoshanna Solomon/Times of Israel)

NiCord, which would be the first drug developed by Gamida to hit the market if the trial goes well is believed to increase the chances of a successful bone marrow transplantation process for patients who do not have a rapidly available, fully matched, bone marrow donor.

Today some high-risk blood cancers cannot be cured unless patients undergo a bone marrow graft. For that purpose, a perfect 100-percent match needs to be found, a process that in the US takes an average of three to four months, if the patient is lucky. Sometimes, no match is found.

There are 70,000 patients a year globally with blood cancers who need a bone marrow transplant, Margolin said. It is a rare condition. But for that transplant, you need a donor with full tissue matching. As many as 50% dont get to the transplant phase, because they havent found a matching donor in time.

Umbilical cord blood collected from newborn babies contains stem cells, which can be used to treat diseases. Today cord-blood banks around the world store the cord blood. It great advantage is that because it is so young, there is no need for a full tissue matching.

The big advantage with umbilical blood is that you dont need full tissue matching; a partial match is enough, Margolin continued. Most patients generally find at least one unit of cord blood that partially matches them.

Stem cells in a bag in Gamida Cells Jerusalem lab, July 16, 2017 (Shoshanna Solomon/Times of Israel)

The problem is that the quantity of cells in each unit is not huge, and it is the number of stem cells in the cord blood that is critical to the success of transplantation.

Our idea is to leverage the advantages of the cord blood and overcome the limitations of the cell number by applying our own platform technology, called NAM Technology, added Margolin. This technology allows us to take one unit of umbilical cord blood and expand the number of stem cells within it and enhance their performance.

Gamida Cell selects the stem cells from the unit and puts them in a culture together with a molecule called Nicotinamide (NAM) a form of Vitamin B3 and adds other ingredients. This culture, to which the firm holds intellectual property rights, increases the number of stem cells, and enhances their functionality, Margolin said.

The cells are then harvested from the culture, frozen in a small blood-bag in a final formulation that is ready for infusion, and then shipped to hospitals via couriers. Doctors thaw the product by the bedside of the patients and infuse the fluid into them.

From start to finish, our process takes three weeks, Margolin said. The average search for a bone marrow match takes three to four months.

The clinical trial underway is enrolling patients aged 16 years and older.

An earlier trial of the drug showed that patients transplanted with NiCord showed a more rapid engraftment the amount of time needed for the development of a minimal amount of white blood cells, or neutrophils, in the blood. That minimum amount indicates the patient is now less vulnerable to infections and bleeding following the transplant, and is an indication of success.

In the pilot phase clinical trials, the median time to neutrophil engraftment with NiCord was 11 days, compared to three to four weeks in patients who received standard umbilical cord blood. The results in a study conducted at Duke University also showed a lower rate of infection 22% vs 54%; and a lower duration of hospitalization compared to standard umbilical cord engraftment, Margolin said.

Now the company is enrolling patients for its larger, Phase 3 multi-national, randomized controlled registration study. And in February it said it had already transplanted its first patient, as part of the trial.

We hope to publish positive topline data from the Phase3 study in the first half of 2019 and launch the product on the market in 2020, she said.

Metal barrel with a frozen bag of umbilical cord stem cells ready for delivery from Gamida Cells Jerusalem lab, July 16, 2017. (Shoshanna Solomon/Times of Israel)

A metal barrel within which was a frozen bag of umbilical cord stem cells was waiting to be picked by a courier in the lobby of the Gamida Cell offices, ready to be thawed and injected into a patient somewhere around the world.

We have a sophisticated infrastructure that coordinates everything between the cord bank blood and our manufacturing site and the hospital where the patient is to be treated, Margolin continued. This infrastructure is 100% robust, but we plan to scale this up toward commercialization.

The $40 million in funds the company raised last month is expected to last until late 2019. After that, she added, all options are on the table: an IPO, or teaming up with a strategic partner, are both possibilities for the future.

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Gene Editing for ‘Designer Babies’? Highly Unlikely, Scientists Say – New York Times

Posted: August 5, 2017 at 1:45 am

Thats because none of those talents arise from a single gene mutation, or even from an easily identifiable number of genes. Most human traits are nowhere near that simple.

Right now, we know nothing about genetic enhancement, said Hank Greely, director of the Center for Law and the Biosciences at Stanford. Were never going to be able to say, honestly, This embryo looks like a 1550 on the two-part SAT.

Even with an apparently straightforward physical characteristic like height, genetic manipulation would be a tall order. Some scientists estimate height is influenced by as many as 93,000 genetic variations. A recent study identified 697 of them.

A new technique known as Crispr has revolutionized humans ability to edit DNA. See you if you can identify whether a given development has already happened, could eventually happen or is pure fiction.

You might be able to do it with something like eye color, said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London.

But if people are worried about designer babies, theyre normally thinking of doing special different things than the normal genetic stuff.

The gene-modification process used in the new study also turns out to be somewhat restrictive. After researchers snipped the harmful mutation from the male gene, it copied the healthy sequence from that spot on the female gene.

That was a surprise to the scientists, who had inserted a DNA template into the embryo, expecting the gene to copy that sequence into the snipped spot, as occurs with gene editing in other body cells. But the embryonic genome ignored that template, suggesting that to repair a mutation on one parents gene in an embryo, a healthy DNA sequence from the other parent is required.

If you cant introduce a template, then you cant do anything wild, Dr. Lovell-Badge said. This doesnt really help you make designer babies.

Talents and traits arent the only thing that are genetically complex. So are most physical diseases and psychiatric disorders. The genetic message is not carried in a 140-character tweet it resembles a shelf full of books with chapters, subsections and footnotes.

So embryonic editing is unlikely to prevent most medical problems.

But about 10,000 medical conditions are linked to specific mutations, including Huntingtons disease, cancers caused by BRCA genes, Tay-Sachs disease, cystic fibrosis, sickle cell anemia, and some cases of early-onset Alzheimers. Repairing the responsible mutations in theory could eradicate these diseases from the so-called germline, the genetic material passed from one generation to the next. No future family members would inherit them.

But testing editing approaches on each mutation will require scientists to find the right genetic signpost, often an RNA molecule, to guide the gene-snipping tool.

In the study reported this week, it took 10 tries to find the right RNA, said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Dr. Greely noted that while scientists work to get human embryonic editing ready for clinical trials (currently illegal in the United States and many countries), alternate medical treatments for these diseases might be developed. They may be simpler and cheaper.

How good one technique is depends on how good the alternatives are, and there may be alternatives, he said.

The authors of the new study do not dismiss ethical implications of their work. In fact, Dr. Belmonte served on a committee of the National Academies of Science, Engineering and Medicine that in February endorsed research into gene editing of human embryos, but only to prevent serious diseases and conditions, and as a last resort.

In theory this could lead to the kind of intervention which, of course, Im totally against, said Dr. Belmonte. The possibility of moving forward not to create or prevent disease but rather to perform gene enhancement in humans.

For example, soon we will know more and more about genes that can increase your muscle activity, he said. The hormone EPO, which some athletes have been disciplined for taking, is produced by a gene, so you could in theory engineer yourself to produce more EPO.

That is the kind of genetic engineering that raises alarm.

Allowing any form of human germline modification leaves the way open for all kinds especially when fertility clinics start offering genetic upgrades to those able to afford them, Marcy Darnovsky, executive director of the Center for Genetics and Society, said in a statement. We could all too easily find ourselves in a world where some peoples children are considered biologically superior to the rest of us.

Scientists and ethicists share the concerns about access. Any intervention that goes to the clinic should be for everyone, Dr. Belmonte said. It shouldnt create inequities in society.

Unequal access is, of course, a question that arises with almost any new medical intervention, and already disparities deprive too many people of needed treatments.

But there is a flip side to ethical arguments against embryo editing.

I personally feel we are duty bound to explore what the technology can do in a safe, reliable manner to help people, Dr. Lovell-Badge said. If you have a way to help families not have a diseased child, then it would be unethical not to do it.

Genetic engineering doesnt have to be an all or nothing proposition, some scientists and ethicists say. There is a middle ground to stake out with laws, regulation and oversight.

For example, Dr. Lovell-Badge said, Britain highly regulates pre-implantation genetic diagnosis, in which a couples embryos are screened for certain harmful mutations so that only healthy ones are implanted in the womans womb.

They allow sensible things to be done, and they dont allow non-sensible things, he said. And every single embryo is accounted for. If someone tries to do something they shouldnt have done, they will find out, and the penalties for breaking the law are quite severe.

According to a 2015 article in the journal Nature, a number of countries, including the United States, restrict or ban genetic modification of human embryos.

Other countries, like China, have guidelines but not laws banning or restricting clinical use, the article noted. Chinese researchers have conducted the only previously published gene editing experiments on human embryos, which were much less successful.

In the future, will there be nations that allow fertility clinics to promise babies with genetically engineered perfect pitch or .400 batting averages? Its not impossible. Even now, some clinics in the United States and elsewhere offer unproven stem cell therapies, sometimes with disastrous consequences.

But R. Alta Charo, a bioethicist at University of Wisconsin-Madison, who co-led the national committee on human embryo editing, said historically ethical overreach with reproductive technology has been limited.

Procedures like I.V.F. are arduous and expensive, and many people want children to closely resemble themselves and their partners. They are likely to tinker with genes only if other alternatives are impractical or impossible.

You hear people talking about how this will make us treat children as commodities and make people more intolerant of people with disabilities and lead to eugenics and all that, she said.

While I appreciate the fear, I think we need to realize that with every technology we have had these fears, and they havent been realized.

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Penn Engineers Identify Protein Implicated in 3-D Epigenetics of Brain Development – Penn Current

Posted: August 5, 2017 at 1:45 am

Wednesday, August 2, 2017

The vast majority of genetic mutations that are associated with diseaseoccur at sites in the genome that arent genes. These sequences of DNA dont code for proteins themselves, but provide an additional layer of instructions that determine if and when particular genes are expressed. Researchers are only beginning to understand how the non-coding regions of the genome influence gene expression andmight be disrupted in disease.

Jennifer Phillips-Cremins, assistant professor in the Department of Bioengineering in the University of Pennsylvanias School of Engineering and Applied Science, studies the three-dimensional folding of the genome and the role it plays in brain development. When a stretch of DNA folds, it creates a higher-order structure called a looping interaction, or loop. In doing so , it brings non-coding sites into physicalcontact with their target genes to precisely regulate gene expression in space and time during development.

Phillips-Cremins and lab member Jonathan Beagan have led a new study identifying a new protein that connects loops in embryonic stem cells as they begin to differentiate into types of neurons. Though the study was conducted in mice, these findings inform aspects of human brain development, including how the genetic material folds in the 3-D nucleus and is reconfigured as stem cells become specialized. Better understanding of these mechanisms may be relevant to a wide range of neurodevelopmental disorders.

Cremins lab members Michael Duong, Katelyn Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline Lachanski and Daniel Gillis also contributed to the study, which was published in the journal Genome Research.

In this paper we create detailed maps of how the genetic material, the DNA, folds in three dimensions inside cells in the brain. We uncover a new class of looping interactions that emerge only when embryonic stem cells turn into neural stem cells in the brain, Phillips-Cremins said. These neural stem-cell-specific loops are important because they connect non-coding regulatory elements to their target genes at a developmental stage when brain-specific gene expression patterns are initially established.

We also discovered that most new neural stem-cell-specific loops arise within a larger framework of pre-existing loops that are established far earlier in development and present in most cell types in the body, Beagan said.

A protein named CTCF is known to be the main connector of loops that are stable throughout development. The researchers discovered that CTCF is sharply reduced in the transition from early development to neural stem cells, leading to a global pruning back of loops that dont matter for the brain and leaving only the stable framework in place.

The Cremins lab creates experimental heat maps of the higher-order structure of the genome. By fixing the DNA such that its 3-D folding patterns are preserved prior to sequencing, two distant parts of the linear sequence will end up in the same string of hybrid DNA and will thus be detected together when the DNA is sequenced.

In this study we integrated maps of protein binding to the DNA with our 3-D genome heat maps. We unexpectedly discovered that the traditional architectural protein CTCF does not connect brain-specific loops, Beagan said. Rather, we found a new protein, Ying Yang 1, or YY1, that is essential for connecting the 3D genome specifically in early stages of brain development. Disruption of this protein has been implicated in brain diseases in early human development.

At this early stage, we can only say YY1 plays an essential role in connecting brain-specific loops at the earliest stages of neurodevelopment. However, brain development and maturation is a complex process and were excited to continue to unravel the organizing principles governing genome folding in fully differentiated neurons in the human brain, Phillips-Cremins said. Because the large majority of disease-associated mutations are located in the non-coding regions of the genome, these results might eventually shed light on the mechanisms underlying the onset and progression of a wide range of neurodevelopmental diseases.

This research was supported by The New York Stem Cell Foundation, the Alfred P. Sloan Foundation, the National Institute of Mental Health through the NIH Director's New Innovator Award (1DP2MH11024701), the National Institutes of Health through a 4D Nucleome Common Fund grant (1U01HL12999801), and a joint National Science Foundation - National Institute of General Medical Sciences grant (1562665). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship grant (DGE-1321851).

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Gene therapy via skin may treat diabetes, obesity – Economic Times

Posted: August 5, 2017 at 1:45 am

New York, Aug 4 (IANS) A new form of gene therapy administered through skin transplants can help improve treatments for Type-2 diabetes and obesity, researchers have claimed.

Using CRISPR, researchers from the University of Chicago edited the skin stem cells from newborn mice which prompted the cells to secrete glucagon-like peptide 1 (GLP1) -- a hormone that stimulates the pancreas to secrete insulin and regulates blood sugar.

The cells when transplanted onto mice showed the grafts increased insulin secretion and reversed weight gain from a high-fat diet, as well as overturned insulin resistance.

"We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems," said Xiaoyang Wu, Assistant Professor at the University of Chicago.

"We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin," Wu added.

Further, the researchers inserted one mutation, designed to extend the hormone's half-life in the blood stream, and fused the modified gene to an antibody fragment so that GLP-1 would circulate in the blood stream longer.

They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline, the researchers said in the paper detailed in the journal Cell Stem Cell.

When the mice were fed minute amounts of doxycycline, they released GLP1 into the blood, which promptly increased blood-insulin levels and reduced blood-glucose levels.

When high-fat diet was combined with doxycycline, the mice secreted GLP1 and gained less weight, suggesting that "cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant".

"We think this can provide a long-term safe option for the treatment of many diseases. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect such as hemophilia. Or it could function as a metabolic sink, removing various toxins," Wu said.

--IANS

rt/py/vt

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Dark Matter Season 3 Episode 10 Review: Built, Not Born – Den of Geek US

Posted: August 5, 2017 at 1:44 am

This Dark Matter review contains spoilers.

For longtime viewers of Dark Matter, the story that unfolds in Built, Not Born is one that had been anticipated for quite awhile, and the payoff is quite satisfying. Tying the Dwarf Star transhumanist efforts with Two (whom they know as Rebecca) together with the origins of the Android seems obvious in retrospect, but it was a great resolution to one of the most enduring mysteries of the series so far. Although the season-long arcs were again put on hold just like last week, the interlude was a welcome one, and if previous experience holds true, it may all just relate in the end anyway.

To start off, Threes reluctance to help Androids robot friends must be applauded for several reasons. First, it reflected what would otherwise have been an awkward pivot from seemingly more important matters, like following up on Sixs idea of taking sides in the corporate war. Second, it allowed Three to have an ironic and painful discussion with Sarah about machines not being alive. And third, his later apology to Android for his prejudicial attitude and tendency to speak without thinking gave her the smile-inducing line, Its one of the things I like about you.

Of course, Android borrowed that line from Six who reminds her, and simultaneously the audience, that despite what we learn of her origins in this episode, shes far from an imperfect imitation but rather her own being with unique variations. When Six says, Youre more than just a series of programmed responses. Youre an original. And thats what we love about you, he might as well be speaking on behalf of the viewer.

Thats especially true once we find out that her creator and the creator of Victor and the others looks just like the Android we know and love for a reason. Dr. Irena Shaw was not only a disgruntled Dwarf Star employee who felt the super-soldier program that designed Rebecca was inhumane; she also grew to love the woman she helped create (fans of Zoie Palmer in Lost Girl were likely all a-flutter). That love likely allowed her to see the potential in giving emotional, self-aware androids the one last ingredient they needed to make them people: free will. The mystery of Androids origin could not have been more poignant, a story filled with romance and tragedy.

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The part that Victor plays is also wonderfully nuanced, both in his helpfulness in unlocking some of Androids memories and in his secretive motivation for calling for help in the first place. The first red flag that Victor wasnt telling the whole truth should have been when Ruac, who had been shot in the head, was revived and shouted, It was wrong! Clearly he had objections to Victor killing Anyas former owner. Did he remove Ruacs emotion chip to force the required self-termination? It even throws into doubt whether Anyas suicide was preventable! Does Victor have justification for his actions, or is he going down a dark path?

This is especially troubling given that he now has a Sarah android at his side. It wasnt his idea to use Dr. Shaws technology this way, but he obviously sees it as an opportunity. And the Galactic Authority wouldnt pop away from the corporate war or the conflict between Zairon and Pyr for no reason. So what is it about Sarah having a human mind combined with a stronger superior physical construct that will further Victors cause, whatever it might be? A truly compelling new mystery!

It was also a nice touch to have Dr. Shaws caretaker, Chase, look exactly like Arrian, the diplomatic android who had a bit of a crush on the blonde Five in Dark Matters season 2 finale. Chases suggestion that Android could be tweaked elicits an enjoyable defensiveness in Five, who rightly says that she likes this version better. So do we, Five; so do we.

But what do we make of the memories Victor unlocked for Android? Seeing Portia excited about Emilys nano-virus that initially woke up Androids hidden subroutines is an interesting transition point from the emotional Rebecca to the malevolent outlaw she became in Portia Lin. And Android telling Ryo-of-yore, You and the rest of the crew are self-seeking, ethically deficient, and morally barren, yet youre incongruously kind to me, gives us insightful character moments, but will it mean something more down the road? Time will tell.

In the meantime, this episode of Dark Matter was another welcome distraction from the corporate war and Ryos villainy. With three episodes left, those elements are sure to return with a vengeance, but it will be interesting to see how the time travel story and the android history lesson will inform the impending finale. If they were simply character building and tying up of loose ends from earlier seasons, great; if they end up tying in to what happens next, even better. Either way, Dark Matter fans cant help but be pleased although theyd be even happier with a season 4 renewal.

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Cells that stand in the way of HIV cure: Discovery expands understanding of marrow’s role – Medical Xpress

Posted: August 5, 2017 at 1:44 am

Illustration incorporating gene-expression maps and cell images from the new research. Credit: University of Michigan

Every day, 17 million HIV-infected people around the world swallow pills that keep the virus inside them at bay.

That is, as long as they swallow those pills every day for the rest of their life.

But no matter how many drugs they take, they'll always have the virus in them, lurking in their white blood cells like a fugitive from justice.

And if they ever stop, HIV will come out of hiding and bring down their immune system from the inside out, causing the disease known as AIDS and potentially spreading to others before killing them.

Now, new research into HIV's hiding places reveals new clues about exactly how it persists in the body for years. The discovery could speed the search for drugs that can flush HIV out of its long-term hideouts and cure an infection for good.

In a new paper in PLoS Pathogens, a team led by University of Michigan researcher Kathleen Collins, M.D., Ph.D. reports that HIV hides in more types of bone marrow cells than previously thought - and that when these cells divide, they can pass the virus's genetic material down to their "daughter" cells intact.

This keeps the infection going for years, without tipping off the armed guards of the immune system.

Collins and her colleagues made the discovery in bone marrow samples donated by dozens of long-term HIV patients treated at U-M's academic medical center, Michigan Medicine, and at Henry Ford Health System in Detroit.

Using funding from the National Institutes of Health, they found that HIV can hide in hematopoietic progenitor cells (HPCs), which also serve as the parents of new blood cells that replace worn-out ones on a regular basis. HIV tricks the cells into incorporating the virus's genetic material into the cells' own DNA.

"Looking for the cells that harbor functional HIV is like searching for a needle in a haystack. Our new results expand our understanding of the type of cells that can do it," says Collins, a professor of Microbiology and Immunology and of Infectious Disease at the U-M Medical School. "It's like a cancer biology problem, only the 'mutation' in the cells is the inserted viral genome."

HPCs are made by hematopoietic stem cells, the "master cells" of blood production found in the marrow. Previous research had shown that HIV can hide for years in the bone marrow.

But it was not known whether the virus persisted only in stem cells or whether the reservoir could include more differentiated progenitor cells. Demonstrating that progenitor cells form a long-lived reservoir of virus expands the number of cell types that need to be targeted.

By demonstrating that HIV genetic material can lurk in blood progenitor cells, the researchers extend other recent studies indicating that such cells can live for years, says Collins, whose lab team included lead author Nadia Sebastian, a U-M M.D./Ph.D. student.

She notes that from the point of view of the virus, finding a harbor in this kind of cell means it can hedge its bets, giving it a chance at survival and eventual reproduction if its host's defenses weaken. The virus that causes chicken pox - varicella - also does this, hiding out in nerve cells just under the skin for years until it awakens and causes the painful condition called shingles.

Knowing exactly what cells harbor HIV over the long-term is crucial to battling persistent infections. Other research has focused on the T cells that carry out key immune system functions.

"Having established this, now we're poised to ask if we can treat HIV infection by targeting hematopoietic progenitor cells," she explains. The team is evaluating potential drugs that could kill just these cells.

The research team on the new paper also includes former U-M stem cell researcher Sean Morrison, Ph.D., who now leads a research center at the University of Texas Southwestern Medical Center. Morrison's lab uses mice as a model to study stem and progenitor cells.

They find in the new paper that in order for HIV to infect a progenitor cell, that cell must have a type of receptor on its surface, called CD4, that the virus can attach to. Additionally, the researchers show that two subtypes of HIV can infect these cells: those that use the CXCR4 co-receptor to enter cells as well as those that use CCR5, which expands the types of HIVs that can potentially cause reservoirs.

Finding those progenitor cells in the marrow of the human patients who agreed to undergo a biopsy for the sake of pure research was tricky, Collins says. But thanks to them, researchers are a step closer to a day when HIV infection is no longer a life sentence for millions of people around the world.

"Moving from the state we're in, where patients will always have to be on these drugs, to a better form of therapy where they can stop, would have a huge effect," she says. "Today's medications have side effects, as well as financial costs. To get to the next step, we need to target the types of cells that form a latent infection, including these progenitor cells."

Explore further: Scientists find that persistent infections in mice exhaust progenitors of all blood cells

More information: Nadia T. Sebastian et al, CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo, PLOS Pathogens (2017). DOI: 10.1371/journal.ppat.1006509

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Transhumanists May Lead Us Into a Dystopian Future – Inverse

Posted: August 4, 2017 at 1:52 am

By Alexander Thomas, University of East London

The rapid development of so-called NBIC technologies nanotechnology, biotechnology, information technology and cognitive science are giving rise to possibilities that have long been the domain of science fiction. Disease, ageing and even death are all human realities that these technologies seek to end.

They may enable us to enjoy greater morphological freedom we could take on new forms through prosthetics or genetic engineering. Or advance our cognitive capacities. We could use brain-computer interfaces to link us to advanced artificial intelligence (AI).

Nanobots could roam our bloodstream to monitor our health and enhance our emotional propensities for joy, love or other emotions. Advances in one area often raise new possibilities in others, and this convergence may bring about radical changes to our world in the near-future.

Transhumanism is the idea that humans should transcend their current natural state and limitations through the use of technology that we should embrace self-directed human evolution. If the history of technological progress can be seen as humankinds attempt to tame nature to better serve its needs, transhumanism is the logical continuation: the revision of humankinds nature to better serve its fantasies.

As David Pearce, a leading proponent of transhumanism and co-founder of Humanity+, says:

If we want to live in paradise, we will have to engineer it ourselves. If we want eternal life, then well need to rewrite our bug-ridden genetic code and become god-like only hi-tech solutions can ever eradicate suffering from the world. Compassion alone is not enough.

But there is a darker side to the naive faith that Pearce and other proponents have in transhumanism one that is decidedly dystopian.

There is unlikely to be a clear moment when we emerge as transhuman. Rather technologies will become more intrusive and integrate seamlessly with the human body. Technology has long been thought of as an extension of the self. Many aspects of our social world, not least our financial systems, are already largely machine-based. There is much to learn from these evolving human/machine hybrid systems.

Yet the often Utopian language and expectations that surround and shape our understanding of these developments have been under-interrogated. The profound changes that lie ahead are often talked about in abstract ways, because evolutionary advancements are deemed so radical that they ignore the reality of current social conditions.

In this way, transhumanism becomes a kind of techno-anthropocentrism, in which transhumanists often underestimate the complexity of our relationship with technology. They see it as a controllable, malleable tool that, with the correct logic and scientific rigour, can be turned to any end. In fact, just as technological developments are dependent on and reflective of the environment in which they arise, they in turn feed back into the culture and create new dynamics often imperceptibly.

Situating transhumanism, then, within the broader social, cultural, political, and economic contexts within which it emerges is vital to understanding how ethical it is.

Max More and Natasha Vita-More, in their edited volume The Transhumanist Reader, claim the need in transhumanism for inclusivity, plurality and continuous questioning of our knowledge.

Yet these three principles are incompatible with developing transformative technologies within the prevailing system from which they are currently emerging: advanced capitalism.

One problem is that a highly competitive social environment doesnt lend itself to diverse ways of being. Instead it demands increasingly efficient behaviour. Take students, for example. If some have access to pills that allow them to achieve better results, can other students afford not to follow? This is already a quandary. Increasing numbers of students reportedly pop performance-enhancing pills. And if pills become more powerful, or if the enhancements involve genetic engineering or intrusive nanotechnology that offer even stronger competitive advantages, what then? Rejecting an advanced technological orthodoxy could potentially render someone socially and economically moribund (perhaps evolutionarily so), while everyone with access is effectively forced to participate to keep up.

Going beyond everyday limits is suggestive of some kind of liberation. However, here it is an imprisoning compulsion to act a certain way. We literally have to transcend in order to conform (and survive). The more extreme the transcendence, the more profound the decision to conform and the imperative to do so.

The systemic forces cajoling the individual into being upgraded to remain competitive also play out on a geo-political level. One area where technology R&D has the greatest transhumanist potential is defence. DARPA (the US defence department responsible for developing military technologies), which is attempting to create metabolically dominant soldiers, is a clear example of how vested interests of a particular social system could determine the development of radically powerful transformative technologies that have destructive rather than Utopian applications.

The rush to develop super-intelligent AI by globally competitive and mutually distrustful nation states could also become an arms race. In Radical Evolution, novelist Verner Vinge describes a scenario in which superhuman intelligence is the ultimate weapon. Ideally, mankind would proceed with the utmost care in developing such a powerful and transformative innovation.

There is quite rightly a huge amount of trepidation around the creation of super-intelligence and the emergence of the singularity the idea that once AI reaches a certain level it will rapidly redesign itself, leading to an explosion of intelligence that will quickly surpass that of humans (something that will happen by 2029 according to futurist Ray Kurzweil). If the world takes the shape of whatever the most powerful AI is programmed (or reprograms itself) to desire, it even opens the possibility of evolution taking a turn for the entirely banal could an AI destroy humankind from a desire to produce the most paperclips for example?

Its also difficult to conceive of any aspect of humanity that could not be improved by being made more efficient at satisfying the demands of a competitive system. It is the system, then, that determines humanitys evolution without taking any view on what humans are or what they should be. One of the ways in which advanced capitalism proves extremely dynamic is in its ideology of moral and metaphysical neutrality. As philosopher Michael Sandel says: markets dont wag fingers. In advanced capitalism, maximising ones spending power maximises ones ability to flourish hence shopping could be said to be a primary moral imperative of the individual.

Philosopher Bob Doede rightly suggests it is this banal logic of the market that will dominate:

If biotech has rendered human nature entirely revisable, then it has no grain to direct or constrain our designs on it. And so whose designs will our successor post-human artefacts likely bear? I have little doubt that in our vastly consumerist, media-saturated capitalist economy, market forces will have their way. So the commercial imperative would be the true architect of the future human.

Whether the evolutionary process is determined by a super-intelligent AI or advanced capitalism, we may be compelled to conform to a perpetual transcendence that only makes us more efficient at activities demanded by the most powerful system. The end point is predictably an entirely nonhuman though very efficient technological entity derived from humanity that doesnt necessarily serve a purpose that a modern-day human would value in any way. The ability to serve the system effectively will be the driving force. This is also true of natural evolution technology is not a simple tool that allows us to engineer ourselves out of this conundrum. But transhumanism could amplify the speed and least desirable aspects of the process.

For bioethicist Julian Savulescu, the main reason humans must be enhanced is for our species to survive. He says we face a Bermuda Triangle of extinction: radical technological power, liberal democracy and our moral nature. As a transhumanist, Savulescu extols technological progress, also deeming it inevitable and unstoppable. It is liberal democracy and particularly our moral nature that should alter.

The failings of humankind to deal with global problems are increasingly obvious. But Savulescu neglects to situate our moral failings within their wider cultural, political and economic context, instead believing that solutions lie within our biological make up.

Yet how would Savulescus morality-enhancing technologies be disseminated, prescribed and potentially enforced to address the moral failings they seek to cure? This would likely reside in the power structures that may well bear much of the responsibility for these failings in the first place. Hes also quickly drawn into revealing how relative and contestable the concept of morality is:

We will need to relax our commitment to maximum protection of privacy. Were seeing an increase in the surveillance of individuals and that will be necessary if we are to avert the threats that those with antisocial personality disorder, fanaticism, represent through their access to radically enhanced technology.

Such surveillance allows corporations and governments to access and make use of extremely valuable information. In Who Owns the Future, internet pioneer Jaron Lanier explains:

Troves of dossiers on the private lives and inner beings of ordinary people, collected over digital networks, are packaged into a new private form of elite money It is a new kind of security the rich trade in, and the value is naturally driven up. It becomes a giant-scale levee inaccessible to ordinary people.

Crucially, this levee is also invisible to most people. Its impacts extend beyond skewing the economic system towards elites to significantly altering the very conception of liberty, because the authority of power is both radically more effective and dispersed.

Foucaults notion that we live in a panoptic society one in which the sense of being perpetually watched instils discipline is now stretched to the point where todays incessant machinery has been called a superpanopticon. The knowledge and information that transhumanist technologies will tend to create could strengthen existing power structures that cement the inherent logic of the system in which the knowledge arises.

This is in part evident in the tendency of algorithms toward race and gender bias, which reflects our already existing social failings. Information technology tends to interpret the world in defined ways: it privileges information that is easily measurable, such as GDP, at the expense of unquantifiable information such as human happiness or well-being. As invasive technologies provide ever more granular data about us, this data may in a very real sense come to define the world and intangible information may not maintain its rightful place in human affairs.

Existing inequities will surely be magnified with the introduction of highly effective psycho-pharmaceuticals, genetic modification, super intelligence, brain-computer interfaces, nanotechnology, robotic prosthetics, and the possible development of life expansion. They are all fundamentally inegalitarian, based on a notion of limitlessness rather than a standard level of physical and mental well-being weve come to assume in healthcare. Its not easy to conceive of a way in which these potentialities can be enjoyed by all.

Sociologist Saskia Sassen talks of the new logics of expulsion, that capture the pathologies of todays global capitalism. The expelled include the more than 60,000 migrants who have lost their lives on fatal journeys in the past 20 years, and the victims of the racially skewed profile of the increasing prison population.

In Britain, they include the 30,000 people whose deaths in 2015 were linked to health and social care cuts and the many who perished in the Grenfell Tower fire. Their deaths can be said to have resulted from systematic marginalisation.

Unprecedented acute concentration of wealth happens alongside these expulsions. Advanced economic and technical achievements enable this wealth and the expulsion of surplus groups. At the same time, Sassen writes, they create a kind of nebulous centrelessness as the locus of power:

The oppressed have often risen against their masters. But today the oppressed have mostly been expelled and survive a great distance from their oppressors The oppressor is increasingly a complex system that combines persons, networks, and machines with no obvious centre.

Surplus populations removed from the productive aspects of the social world may rapidly increase in the near future as improvements in AI and robotics potentially result in significant automation unemployment. Large swaths of society may become productively and economically redundant. For historian Yuval Noah Harari the most important question in 21st-century economics may well be: what should we do with all the superfluous people?

We would be left with the scenario of a small elite that has an almost total concentration of wealth with access to the most powerfully transformative technologies in world history and a redundant mass of people, no longer suited to the evolutionary environment in which they find themselves and entirely dependent on the benevolence of that elite. The dehumanising treatment of todays expelled groups shows that prevailing liberal values in developed countries dont always extend to those who dont share the same privilege, race, culture or religion.

In an era of radical technological power, the masses may even represent a significant security threat to the elite, which could be used to justify aggressive and authoritarian actions (perhaps enabled further by a culture of surveillance).

In their transhumanist tract, The Proactionary Imperative, Steve Fuller and Veronika Lipinska argue that we are obliged to pursue techno-scientific progress relentlessly, until we achieve our god-like destiny or infinite power effectively to serve God by becoming God. They unabashedly reveal the incipient violence and destruction such Promethean aims would require: replacing the natural with the artificial is so key to proactionary strategy at least as a serious possibility if not a likelihood [it will lead to] the long-term environmental degradation of the Earth.

The extent of suffering they would be willing to gamble in their cosmic casino is only fully evident when analysing what their project would mean for individual human beings:

A proactionary world would not merely tolerate risk-taking but outright encourage it, as people are provided with legal incentives to speculate with their bio-economic assets. Living riskily would amount to an entrepreneurship of the self [proactionaries] seek large long-term benefits for survivors of a revolutionary regime that would permit many harms along the way.

The economic fragility that humans may soon be faced with as a result of automation unemployment would likely prove extremely useful to proactionary goals. In a society where vast swaths of people are reliant on handouts for survival, market forces would determine that less social security means people will risk more for a lower reward, so proactionaries would reinvent the welfare state as a vehicle for fostering securitised risk taking while the proactionary state would operate like a venture capitalist writ large.

At the heart of this is the removal of basic rights for Humanity 1.0, Fullers term for modern, non-augmented human beings, replaced with duties towards the future augmented Humanity 2.0. Hence the very code of our being can and perhaps must be monetised: personal autonomy should be seen as a politically licensed franchise whereby individuals understand their bodies as akin to plots of land in what might be called the genetic commons.

The neoliberal preoccupation with privatisation would so extend to human beings. Indeed, the lifetime of debt that is the reality for most citizens in developed advanced capitalist nations, takes a further step when you are born into debt simply by being alive you are invested with capital on which a return is expected.

Socially moribund masses may thus be forced to serve the technoscientific super-project of Humanity 2.0, which uses the ideology of market fundamentalism in its quest for perpetual progress and maximum productivity. The only significant difference is that the stated aim of godlike capabilities in Humanity 2.0 is overt, as opposed to the undefined end determined by the infinite progress of an ever more efficient market logic that we have now.

Some transhumanists are beginning to understand that the most serious limitations to what humans can achieve are social and cultural not technical. However, all too often their reframing of politics falls into the same trap as their techno-centric worldview. They commonly argue the new political poles are not left-right but techno-conservative or techno-progressive (and even techno-libertarian and techno-sceptic. Meanwhile Fuller and Lipinska argue that the new political poles will be up and down instead of left and right: those who want to dominate the skies and became all powerful, and those who want to preserve the Earth and its species-rich diversity. It is a false dichotomy. Preservation of the latter is likely to be necessary for any hope of achieving the former.

Transhumanism and advanced capitalism are two processes which value progress and efficiency above everything else. The former as a means to power and the latter as a means to profit. Humans become vessels to serve these values. Transhuman possibilities urgently call for a politics with more clearly delineated and explicit humane values to provide a safer environment in which to foster these profound changes. Where we stand on questions of social justice and environmental sustainability has never been more important. Technology doesnt allow us to escape these questions it doesnt permit political neutrality. The contrary is true. It determines that our politics have never been more important. Savulescu is right when he says radical technologies are coming. He is wrong in thinking they will fix our morality. They will reflect it.

Alexander Thomas, PhD Candidate, University of East London

This article was originally published on The Conversation. Read the original article here.

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