Category Archives: Transhuman News

Jupiterimages/Thinkstock

On Aug. 3, the scientific article in Nature finally gave us some facts about the much-hyped experiments that involved editing the genomes of human embryos at the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. The story had broken in late July in Technology Review, spurring profuse hand-wringing and discussion. But until we saw the scientific paper, it was not clear what cells and methods were used, what genes were edited, or what the results were.

Now we know more, and while the paper demonstrates the possibility of genome editing of human embryos, it raises more questions than it answers. It is a useful demonstration of technical promise, though not an immediate prelude to the birth of a genome-edited baby. But the process by which the news emerged is also an ominous harbinger of the discombobulated way the debate about genetically altering human embryos is likely to unfold. We need open, vigorous debate that captures the many, often contradictory, moral views of Americans. Yet what we are likely to get is piecemeal, fragmented stories of breakthroughs with incomplete details, more sober publication in science journals that appear later, news commentary that lasts a few days, and very little systematic effort to think through what policy should be.

The science underlying this news cycle about human genome editing builds on a technique first developed six years ago by studying how bacteria alter DNA. CRISPR genome editing is the most recent, and most promising, way to introduce changes into DNA. It is faster, easier, and cheaper than previous methods and should eventually be more precise and controllablewhich is why it may one day be available for clinical use in people.

Though headlines about the study discussed designer babies, researchers prefer to emphasize how these techniques could help stop devastating genetic disorders. The Oregon experiments with human embryo cells corrected disease-associated DNA variants associated with heart muscle wasting that can cause heart failure. The treated embryos were alive for only a few days and were never intended to become a human baby. They were, however, human embryos deliberately created for the research.

U.S. guidance in this area is sparse and reflects the lack of societal consensus. In 1994, when the federal government was contemplating funding for research involving human embryos, the NIH Embryo Research Panel concluded that just this kind of experiment was ethically appropriate. But within hours of that reports release, then-President Bill Clinton announced he did not agree with creating embryos in order to do research on them.

The United States currently has just two policies relevant to genomic editing of human embryos. The first blocks federal funding: On April 28, 2015, Francis Collins, director of the National Institutes of Health, stated, NIH will not fund any use of gene-editing technologies in human embryos. This is not embedded in statute or formal executive order, but members of Congress are fully aware of it and it is, in effect, a federal policy. NIH can (and does) fund genome editing of nonembryonic cells that might be used to treat cancer and for other possible therapeutic purposes, but not embryonic cells that would have their effect by creating humans with germline alterations.

Second, Congress has prohibited the Food and Drug Administration from reviewing research in which a human embryo is intentionally created or modified to include a heritable genetic modification. This language comes from a rider to FDAs annual appropriations. Yet use of human embryonic cells for treatment should be subject to FDA regulation. So this language in effect means alterations of embryonic cells cannot be done in the United States if there is any intent to treat a human being, including implantation of an altered embryo into a womans uterus. This will remain true so long as the rider is included in FDAs annual appropriations. The federal government thus has two relevant policies, both of which take federal agencies out of the action: One removes NIH funding, and the other precludes FDA oversight of genome-edited human embryos.

This leaves privately funded research that has no direct therapeutic purpose, such as with the Oregon experiments. The funding came from OHSU itself; South Korean Basic Research Funds; the municipal government of Shenzhen, China; and several private philanthropies (Chapman, Mathers, Helmsley, and Moxie). The research complies with recommendations to study the basic cellular processes of genome editing, keeping an eye on possible future clinical use but only so long as the work does not attempt to create a human pregnancy.

By coincidence, on the same day the Nature paper came out, the American Journal of Human Genetics also published a thoughtful 10-page position statement about germline genome editing from the American Society for Human Genetics endorsed by many other genetic and reproductive medicine organizations from all over the world. It reviews recommendations of the National Academies of Sciences, Engineering, and Medicine, several international and U.S.-based organizations and commissions, and makes several recommendations of its own, concluding it is inappropriate to perform germline gene editing that culminates in human pregnancy, but also 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. Indeed, the statement argues for public funding. Finally, it urges research to proceed only with compelling medical rationale, strong oversight, and a transparent public process to solicit and incorporate stakeholder input.

So is there a problem here? It is truly wonderful that medical and scientific organizations have addressed genome editing. It is, however, far from sufficient. Reports and scientific consensus statements inform the policy debate but cannot resolve it. All of the reports on genome editing call for robust public debate, but the simple fact is that embryo research has proven highly divisive and resistant to consensus, and it is far from clear how to know when there is enough thoughtful deliberation to make policy choices. Its significant that none of the reports have emerged from a process that embodied such engagement. The Catholic Church, evangelical Christians, and concerned civic action groups who view embryo research as immoral are not likely to turn to the National Academies of Sciences, Engineering and Medicine, the American Society for Human Genetics, the Hinxton Group, the Nuffield Council on Bioetics, or other scientific and medical organizations for their primary counsel. They may well listen to scientists, but religious and moral doctrine will get greater weight. Yet religious groups highly critical of embryo research are part of the political systemand whether we embrace this sort of genome editing in the United States is a political question, not a purely technical one.

Reports and scientific consensus statements inform the policy debate but cannot resolveit.

Addressing the political questions will be extremely difficult. The U.S. government is poorly positioned to mediate the policy debate in a way that recognizes and addresses our complex moral pluralism. NIH and FDA are two of the most crucial agencies, but current policies remove them from line authority, and with good reason, given that engaging in this debate could actually endanger the agencies other vital missions. International consensus about genome editing of human embryos remains no more likely than about embryo research in general: Some countries ban it while others actively promote and fund it. Private foundations dont have the mandate or incentive to mediate political debate about a controversial technology that rouses the politics of abortion. What private philanthropic organization would willingly take on such a thankless and politically perilous task, and what organization would be credible to the full range of constituencies?

So who can carry out the public engagement that everyone seems to agree we need? The likely answer is no one. This problem occurs with all debate about fraught scientific and technical innovations, but its particularly acute when it touches on highly ossified abortion politics.

The debate about genomic editing of human embryos is unlikely to follow the recommendations for systematic forethought proposed by illustrious research bodies and reports. Given the reactions weve seen to human embryonic stem-cell research in the past two decades, we have ample reason for pessimism. Rather, debate is more likely to progress by reaction to events as researchers make newsoften with the same lack of information we lived with for the last week of July, based on incomplete media accounts and quotes from disparate experts who lacked access to the details. Most of the debate will be quote-to-quote combat in the public media, leavened by news and analysis in scientific and medical journals, but surrounded by controversy in religious and political media. It is not what anyone designing a system would want. But the recommendations for robust public engagement and debate feel a bit vacuous and vague, aspirations untethered to a concrete framework.

Our divisive political system seems fated to make decisions about genomic editing of human embryos mainly amidst conflict, with experts dueling in the public media rather than through a thoughtful and well-informed debate conducted in a credible framework. As the furor over the Oregon experiments begins to dissipate, we await the event that will cause the next flare-up. And so it will continue, skipping from news cycle to news cycle.

History shows that sometimes technical advances settle the issues, at least for most people and in defined contexts. Furor about in vitro fertilization after Louise Brown, the first test tube baby, was born in 1978 gave way to acceptance as grateful parents gave birth to more and more healthy babies and welcomed them into their families. Initial revulsion at heart transplants gave way in the face of success. Anger about prospects for human embryonic stem-cell research might similarly attenuate if practical applications emerge.

Such historical examples show precisely why reflective deliberation remains essential, despite its unlikely success. Momentum tends to carry the research forward. Yet at times we should stop, learn more, and decide actively rather than passively whether to proceed, when, how, and with what outcomes in mind. In the case of genome editing of human embryos, however, it seems likely that technology will make the next move.

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.

Read more from the original source:
Listening for the Public Voice - Slate Magazine

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.

Like Retraction Watch? Consider making a tax-deductible contribution to support our growth. You can also follow us on Twitter, like us on Facebook, add us to your RSS reader, sign up on our homepage for an email every time theres a new post, or subscribe to our daily digest. Click here to review our Comments Policy. For a sneak peek at what were working on, click here.

Read more:
Genetic disorder gets name change, but patient's father still not happy - Retraction Watch (blog)

I

t was a strange moment of triumph against racism: The gun-slinging white supremacist Craig Cobb, dressed up for daytime TV in a dark suit and red tie, hearing that his DNA testing revealed his ancestry to be only 86 percent European, and 14 percent Sub-Saharan African. The studio audience whooped and laughed and cheered. And Cobb who was, in 2013, charged with terrorizing people while trying to create an all-white enclave in North Dakota reacted like a sore loser in the schoolyard.

Wait a minute, wait a minute, hold on, just wait a minute, he said, trying to put on an all-knowing smile. This is called statistical noise.

Then, according to the Southern Poverty Law Center, hetook to the white nationalist website Stormfront to dispute those results. Thats not uncommon: With the rise of spit-in-a-cup genetic testing, theres a trend of white nationalists using these services to prove their racial identity, and then using online forums to discuss the results.

advertisement

But like Cobb, many are disappointed to find out that their ancestry is not as white as theyd hoped. In a new study, sociologists Aaron Panofsky and Joan Donovan examined years worth of posts on Stormfront to see how members dealt with the news.

Its striking, they say, that white nationalists would post these results online at all. After all, as Panofsky put it, they will basically say if you want to be a member of Stormfront you have to be 100 percent white European, not Jewish.

But instead of rejecting members who get contrary results, Donovan said, the conversations are overwhelmingly focused on helping the person to rethink the validity of the genetic test. And some of those critiques while emerging from deep-seated racism are close to scientists own qualms about commercial genetic ancestry testing.

Panofsky and Donovan presented their findings at a sociology conference in Montreal on Monday. The timing of the talk some 48 hours after the violent white nationalist rally in Charlottesville, Va. was coincidental. But the analysis provides a useful, if frightening, window into how these extremist groups think about their genes.

Stormfront was launched in the mid-1990s byDon Black, a former grand wizard of the Ku Klux Klan. His skills in computer programming were directly related to his criminal activities: He learned them while in prison for trying to invade the Caribbean island nation of Dominica in 1981, and then worked as a web developer after he got out. That means this website dates back to the early years of the internet, forming a kind of deep archive of online hate.

To find relevant comments in the 12 million posts written by over 300,000 members, the authors enlisted a team at the University of California, Los Angeles, to search for terms like DNA test, haplotype, 23andMe, and National Geographic. Then the researchers combed through the posts they found, not to mention many others as background. Donovan, who has moved from UCLA to the Data & Society Research Institute, estimated that she spent some four hours a day reading Stormfront in 2016. The team winnowed their results down to 70 discussion threads in which 153 users posted their genetic ancestry test results, with over 3,000 individual posts.

About a third of the people posting their results were pleased with what they found. Pretty damn pure blood, said a user with the username Sloth. But the majority didnt find themselves in that situation. Instead, the community often helped them reject the test, or argue with its results.

Some rejected the tests entirely, saying that an individuals knowledge about his or her own genealogy is better than whatever a genetic test can reveal. They will talk about the mirror test, said Panofsky, who is a sociologist of science at UCLAs Institute for Society and Genetics. They will say things like, If you see a Jew in the mirror looking back at you, thats a problem; if you dont, youre fine.' Others, he said, responded to unwanted genetic results by saying that those kinds of tests dont matter if you are truly committed to being a white nationalist. Yet otherstried to discredit the genetic tests as a Jewish conspiracy that is trying to confuse true white Americans about their ancestry, Panofsky said.

But some took a more scientific angle in their critiques, calling into doubt the method by which these companies determine ancestry specifically how companies pick those people whose genetic material will be considered the reference for a particular geographical group.

And that criticism, though motivated by very different ideas, is one that some researchers have made as well, even as other scientists have used similar data to better understand how populations move and change.

There is a mainstream critical literature on genetic ancestry tests geneticists and anthropologists and sociologists who have said precisely those things: that these tests give an illusion of certainty, but once you know how the sausage is made, you should be much more cautious about these results, said Panofsky.

Companies like Ancestry.com and 23andMe are meticulous in how they analyze your genetic material. As points of comparison, they use both preexisting datasets as well as some reference populations that they have recruited themselves. The protocol includes genetic material from thousands of individuals, and looks at thousands of genetic variations.

When a 23andMe research participant tells us that they have four grandparents all born in the same country and the country isnt a colonial nation like the U.S., Canada, or Australia that person becomes a candidate for inclusion in the reference data, explained Jhulianna Cintron, a product specialist at 23andMe. Then, she went on, the company excludes close relatives, as that could distort the data, and removes outliers whose genetic data dont seem to match with what they wrote on their survey.

But specialists both inside and outside these companies recognize that the geopolitical boundaries we use now are pretty new, and so consumers may be using imprecise categorieswhen thinking about their own genetic ancestry within the sweeping history of human migration. And users ancestry results can change depending on the dataset to which their genetic material is being compared a fact which some Stormfront users said they took advantage of, uploading their data to various sites to get a more white result.

J. Scott Roberts, an associate professor at the University of Michigan, who has studied consumer use of genetic tests and was not involved with the study, said the companies tend to be reliable at identifying genetic variants. Interpreting them in terms of health risk or ancestry, though, is another story. The science is often murky in those areas and gives ambiguous information, he said. They try to give specific percentages from this region, or x percent disease risk, and my sense is that that is an artificially precise estimate.

For the study authors, what was most interesting was to watch this online community negotiating its own boundaries, rethinking who counts as white. That involved plenty of contradictions.They saw people excluded for their genetic test results, often in very nasty (and unquotable) ways, but that tended to happen for newer members of the anonymous online community, Panofsky said, and not so much for longtime, trusted members. Others were told that they could remain part of white nationalist groups, in spite of the ancestry they revealed, as long as they didnt mate, or only had children with certain ethnic groups. Still others used these test results to put forth a twisted notion of diversity, one that allows them to say, No, were really diverse and we dont need non-white people to have a diverse society,' said Panofsky.

Thats a far cry from the message of reconciliation that genetic ancestry testing companies hope to promote.

Sweetheart, you have a little black in you, the talk show host Trisha Goddard told Craig Cobb on that day in 2013. But that didnt stop him from redoing the test with a different company, trying to alter or parse the data until it matched his racist worldview.

General Assignment Reporter

Eric is a general assignment reporter.

Trending

Democrats in Congress to explore creating an expert panel

Democrats in Congress to explore creating an expert panel on Trumps mental health

CMS moves to cancel Medicare programs overhauling some hospital

CMS moves to cancel Medicare programs overhauling some hospital payments

Newer method of open-heart surgery carries more risks, study

Newer method of open-heart surgery carries more risks, study finds

Recommended

Express Scripts to limit opioids, concerning doctors

Express Scripts to limit opioids, concerning doctors

This 6-year-old suddenly had trouble reading. Why was she

This 6-year-old suddenly had trouble reading. Why was she going blind?

In one night, she lost two sons to opioids.

In one night, she lost two sons to opioids. Shes on a mission to spare others

View original post here:
White nationalists are flocking to genetic ancestry tests. Some don't like what they find - STAT

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.

Go here to read the rest:
Beating the Odds for Lucky Mutations - Quanta Magazine