Category Archives: Transhuman News

It appears, by all accounts, to be a momentous scientific achievement and possibly a turning point in human evolution. In a study released last week, scientists at Oregon Health and Science University confirmed they were able to modify genes in viable human embryos, proving the potential to permanently alter the makeup of a genetic line.

In this case, that meant replacing and repairing a mutated gene that causes a common and deadly heart disorder. But the possibilities heralded by gene-editing technology are endless, the scenarios as divided as they are bold. In some visions, it leads to a population of designer babies or consumer eugenics. Others imagine a utopia of scientific advancement where humans live free of disease, and devastating conditions are eradicated for the betterment of humanity. What direction the technology will take is the topic of much debate.

The big thing which is making the scientific and ethics community get excited, and on the other hand a little bit hot and bothered, is its a mechanism to change genes for multiple generations, says Dr. Alice Virani, a genetic counsellor and director of ethics at British Columbias Provincial Health Services Authority. There are two ways to look at it, the more realistic ramifications and the sci-fi, if-this-was-out-of-control ramifications.

Opinion: Gene editing is not about designer babies

The team at the Oregon universitys Center for Embryonic Cell and Gene Therapy used technology called CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, to repair or edit the gene carrying the heart disorder, seemingly with greater success than previous attempts by scientists in China.

News of the research has been anxiously anticipated by many in the field, both for what it means for the potential eradication of a disease such as hypertrophic cardiomyopathy and for the fundamental questions it raises about human reproduction, health and society.

When the study was leaked days before its publication in the journal Nature, its lead scientist, Dr. Shoukhrat Mitalipov, attributed the release to likely a combination of hot words: CRISPR, gene-editing, and designer babies.

The study and its combination of hot words didnt disappoint.

The New York Times hailed the milestone in research, while The New York Post cried BABE NEW WORLD and described an amazing and slightly terrifying breakthrough. A headline on Vox declared simply, This Is Huge.

Even actor Ashton Kutcher tweeted enthusiastically about the scientific breakthrough, writing: Scientists successfully used CRISPR to fix a mutation that causes disease. This is why I wanted to be a geneticist!

The tweet ignited among his followers the same range of responses that are always so keenly tied to the issue of changing human genes, from hope that devastating conditions such as muscular dystrophy will be eradicated, to fear about the unknown consequences of playing God.

Dr. Timothy Caulfield, a Canada Research Chair in Health Law and Policy and professor at the University of Alberta, says the polarized and dramatic response he has seen in recent days reminds him of early reaction to stem-cell science, where, he says, It was either going to be cloned armies, or we were going to eradicate all disease.

In fact, neither has turned out to be the case, and so it may be with gene editing as well.

We need to be cautious not to hype the benefits and be cautious not to hype the ethical concerns, he says. There are real issues on both sides of the debate but lets make sure our discourse is evidence-formed.

He described the new research as a genuinely exciting area, and said the potential of CRISPR which is used not only in human genetics, but also has potentially revolutionary applications for agriculture, animals, plants and food has introduced both exciting possibilities and reasons for deep policy reflection.

Erika Kleiderman, a lawyer and academic whose work focuses on gene-editing technologies, stem-cell research and regenerative medicine at the Centre of Genomics and Policy at McGill University, says the Oregon teams research is exciting because it confirms the ability of CRISPR technology to repair genetic mutations, and establishes the basic safety of the technique in a research context. And while she said people often go straight to thinking about the potential for manipulating genes to create so-called designer babies, a concept that is cool but also quite frightening, the medical implications could be equally staggering, and are far more likely.

For example, something like Huntington disease, she says. Being able to prevent that or treat that one day, in my opinion, would be a fantastic leap for our scientific knowledge and medical advancement. That being said, people will raise the eugenics argument. Is that a possibility? Yes. Are we close to that? I dont think so.

Canada has strict laws around genetic modification and editing, and altering genes in a way that could be passed on to future generations is a criminal offence under the Assisted Human Reproduction Act, punishable with fines up to $500,000 or 10 years in prison.

But as the technology takes a large step forward, Ms. Kleiderman and Dr. Caulfield and are among a group of Canadian scientists and academics calling for less regulation around genetic science and research in Canada, not more.

Both were involved in the creation of an editorial published in the journal Regenerative Medicine in January calling for new consideration of the issues and ethics involved in gene editing, and a revision of Canadian legal policy.

A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes, the editorial read. It was signed by seven other experts and ethicists, and came out of a think tank on the future of human gene editing in Canada held at McGill last summer.

Dr. Caulfield says legal prohibition of certain genetic research doesnt make sense when we dont yet know or understand where the science is going, or what the benefits or harms could be. Instead, he says he believes in regulation in problematic areas, while allowing for studies and trials. He says that some of the slippery slope scenarios people fear such as using genetic modification for human enhancement and to achieve superficial traits such as height remain distant possibilities given the complexity of the science.

That is not to say there are not risks or issues to be addressed as the technology continues to evolve. Ms. Kleiderman says that includes consideration of the potential risk to future generations, the safety of the technology and other irrevocable, if unintended, consequences, although she says those risks are not unique to gene modification but true of all technologies.

When it comes to CRISPR, one of the areas it would be most beneficial is with the treatment of prevention of disease which I think most people would be in agreement with, she says. Of course, we need to be mindful of doing not-so-positive things with it, like going down the enhancement route.

She said other potential issues, such as the preservation of human diversity and individuality, the welfare of children born from this technology and the potential for creating new forms of inequality, discrimination or societal conflict, all require significant consideration and research.

There is time. Although the technology is moving quickly, there is still a long way before gene editing is used in clinical human trials. Even after that, Dr. Virani says for the foreseeable future the technology will most likely be used by a small group of people in specific scenarios related to the prevention of serious genetic disease.

Im not saying we shouldnt be concerned about those potential issues, but sometimes we make that leap too quickly, she said. We dont necessarily [think] that the most likely scenario is that couples will use this technology on a very limited basis if they know their child may potentially have a devastating genetic condition. Thats not something that suddenly everyone is going to start to do. I think theres sometimes that leap to, Oh, we can create designer babies, but I think were very much in the lessening-burden-of-disease phase rather than the designer-baby phase, though thats where peoples minds go.

Dr. Virani said one of her own concerns is the possibility of off-target effects, where changing a gene unexpectedly alters something else in the genome. Other concerns are more social reality than science fiction, including that the technology and the ability to prevent disease may only be available to those who can pay for it. Eradicating a horrible disease is one thing. Eradicating it only for families who can afford it is another.

So is it going to look like just the wealthy are going to be able to afford this type of technology? she asks. Thats very problematic in my eyes from an ethics point of view, and thinking about fairness in society. If only poor people get Huntington disease, then the lobby to support Huntington disease research is greatly diminished. Its kind of like a two-fold negative effect.

On Thursday, the American Journal of Human Genetics ran a policy statement signed by 11 organizations from around the world, including the Canadian Association of Genetic Counsellors, urging a cautious but pro-active approach as the science moves forward. The statement includes an agreement that gene editing should not yet be performed in embryos carried on to human pregnancy. (The embryos used in the Oregon research were created only for the research, and were not developed further.) It also outlines a number of criteria that should be met before clinical trials take place, and supports public funding for the research. The U.S. government does not allow federal funding for genetic research on embryos. The Oregon research was funded by the university.

We dont want it to go speeding ahead, said Kelly Ormond, the lead author of the policy statement and a genetics professor at Stanford University in California. We want people to be very transparent about whats happening and we want things to undergo good ethics review, and for society to actually be engaged in these dialogues now while this research is just starting to happen.

She said she believes its important to be pro-active in talking and thinking about the issues related to the technology, and starting a broader conversation of how gene editing should and will be used.

We can all agree that that world [of eugenics and designer babies] doesnt feel very comfortable, and I think most of us dont want to go there, she said. So we need to find ways to prevent that from happening.

Follow Jana G. Pruden on Twitter: @jana_pruden

Link:
Modification of genes in human embryos could mark turning point in human evolution - The Globe and Mail

August 7, 2017 New disease classifications created by analyzing genetic and environmental correlations among family members. Credit: Kanix Wang, et al

Using health insurance claims data from more than 480,000 people in nearly 130,000 families, researchers at the University of Chicago have created a new classification of common diseases based on how often they occur among genetically-related individuals.

Researchers hope the work, published this week in Nature Genetics, will help physicians make better diagnoses and treat root causes instead of symptoms.

"Understanding genetic similarities between diseases may mean that drugs that are effective for one disease may be effective for another one," said Andrey Rzhetsky, PhD, the Edna K. Papazian Professor of Medicine and Human Genetics at UChicago who was the paper's senior author. "And for those diseases with a large environmental component, that means we can perhaps prevent them by changing the environment."

The results of the study suggest that standard disease classifications-called nosologies-based on symptoms or anatomy may miss connections between diseases with the same underlying causes. For example, the new study showed that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome, an inflammatory disorder of the intestine.

Rzhetsky and a team of researchers analyzed records from Truven MarketScan, a database of de-identified patient data from more than 40 million families in the United States. They selected a subset of records based on how long parents and their children were covered under the same insurance plan within a time frame most likely to capture when children were living in the same home with their parents. They used this massive data set to estimate genetic and environmental correlations between diseases.

Next, using statistical methods developed to create evolutionary trees of organisms, the team created a disease classification based on two measures. One focused on shared genetic correlations of diseases, or how often diseases occurred among genetically-related individuals, such as parents and children. The other focused on the familial environment, or how often diseases occurred among those sharing a home but who had no or partially matching genetic backgrounds, such as spouses and siblings.

The results focused on 29 diseases that were well represented in both children and parents to build new classification trees. Each "branch" of the tree is built with pairs of diseases that are highly correlated with each other, meaning they occur frequently together, either between parents and children sharing the same genes, or family members sharing the same living environment.

"The large number of families in this study allowed us to obtain precise estimates of genetic and environmental correlations, representing the common causes of multiple different diseases," said Kanix Wang, a graduate student at UChicago and lead author of the study. "Using these shared genetic and environmental causes, we created a new system to classify diseases based on their intrinsic biology."

Genetic similarities between diseases tended to be stronger than their corresponding environmental correlations. For the majority of neuropsychiatric diseases, such as schizophrenia, bipolar disorder and substance abuse, however, environmental correlations are nearly as strong as genetic ones. This suggests there are elements of the shared, family environment that could be changed to help prevent these disorders.

The researchers also compared their results to the widely used International Classification of Diseases Version 9 (ICD-9) and found additional, unexpected groupings of diseases. For example, type 1 diabetes, an autoimmune endocrine disease, has a high genetic correlation with hypertension, a disease of the circulatory system. The researchers also saw high genetic correlations across common, apparently dissimilar diseases such as asthma, allergic rhinitis, osteoarthritis and dermatitis.

Explore further: Diseases that run in families not all down to genes, study shows

More information: Classification of common human diseases derived from shared genetic and environmental determinants, Nature Genetics (2017). DOI: 10.1038/ng.3931

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Big data yields surprising connections between diseases - Medical Xpress

August 7, 2017 These population trees with embedded gene trees show how mutations can generate nucleotide site patterns. The four branch tips of each gene tree represent genetic samples from four populations: modern Africans, modern Eurasians, Neanderthals, and Denisovans. In the left tree, the mutation (shown in blue) is shared by the Eurasian, Neanderthal and Denisovan genomes. In the right tree, the mutation (shown in red) is shared by the Eurasian and Neanderthal genomes. Credit: Alan Rogers, University of Utah

Hundreds of thousands of years ago, the ancestors of modern humans diverged from an archaic lineage that gave rise to Neanderthals and Denisovans. Yet the evolutionary relationships between these groups remain unclear.

A University of Utah-led team developed a new method for analyzing DNA sequence data to reconstruct the early history of the archaic human populations. They revealed an evolutionary story that contradicts conventional wisdom about modern humans, Neanderthals and Denisovans.

The study found that the Neanderthal-Denisovan lineage nearly went extinct after separating from modern humans. Just 300 generations later, Neanderthals and Denisovans diverged from each other around 744,000 years ago. Then, the global Neanderthal population grew to tens of thousands of individuals living in fragmented, isolated populations scattered across Eurasia.

"This hypothesis is against conventional wisdom, but it makes more sense than the conventional wisdom." said Alan Rogers, professor in the Department of Anthropology and lead author of the study that will publish online on August 7, 2017 in the Proceedings of the National Academy of Sciences.

A different evolutionary story

With only limited samples of fossil fragments, anthropologists assemble the history of human evolution using genetics and statistics.

Previous estimates of the Neanderthal population size are very smallaround 1,000 individuals. However, a 2015 study showed that these estimates underrepresent the number of individuals if the Neanderthal population was subdivided into isolated, regional groups. The Utah team suggests that this explains the discrepancy between previous estimates and their own much larger estimate of Neanderthal population size.

"Looking at the data that shows how related everything was, the model was not predicting the gene patterns that we were seeing," said Ryan Bohlender, post-doctoral fellow at the M. D. Anderson Cancer Center at the University of Texas, and co-author of the study. "We needed a different model and, therefore, a different evolutionary story."

The team developed an improved statistical method, called legofit, that accounts for multiple populations in the gene pool. They estimated the percentage of Neanderthal genes flowing into modern Eurasian populations, the date at which archaic populations diverged from each other, and their population sizes.

A family history in DNA

The human genome has about 3.5 billion nucleotide sites. Over time, genes at certain sites can mutate. If a parent passes down that mutation to their kids, who pass it to their kids, and so on, that mutation acts as a family seal stamped onto the DNA.

Scientists use these mutations to piece together evolutionary history hundreds of thousands of years in the past. By searching for shared gene mutations along the nucleotide sites of various human populations, scientists can estimate when groups diverged, and the sizes of populations contributing to the gene pool.

"You're trying to find a fingerprint of these ancient humans in other populations. It's a small percentage of the genome, but it's there," said Rogers.

They compared the genomes of four human populations: Modern Eurasians, modern Africans, Neanderthals and Denisovans. The modern samples came from Phase I of the 1000-Genomes project and the archaic samples came from the Max Planck Institute for Evolutionary Anthropology. The Utah team analyzed a few million nucleotide sites that shared a gene mutation in two or three human groups, and established 10 distinct nucleotide site patterns.

Against conventional wisdom

The new method confirmed previous estimates that modern Eurasians share about 2 percent of Neanderthal DNA. However, other findings questioned established theories.

Their analysis revealed that 20 percent of nucleotide sites exhibited a mutation only shared by Neanderthals and Denisovans, a genetic timestamp marking the time before the archaic groups diverged. The team calculated that Neanderthals and Denisovans separated about 744,000 years ago, much earlier than any other estimation of the split.

"If Neanderthals and Denisovans had separated later, then there ought to be more sites at which the mutation is present in the two archaic samples, but is absent from modern samples," said Rogers.

The analysis also questioned whether the Neanderthal population had only 1,000 individuals. There is some evidence for this; Neanderthal DNA contains mutations that usually occur in small populations with little genetic diversity.

However, Neanderthal remains found in various locations are genetically different from each other. This supports the study's finding that regional Neanderthals were likely small bands of individuals, which explains the harmful mutations, while the global population was quite large.

"The idea is that there are these small, geographically isolated populations, like islands, that sometimes interact, but it's a pain to move from island to island. So, they tend to stay with their own populations," said Bohlender.

Their analysis revealed that the Neanderthals grew to tens of thousands of individuals living in fragmented, isolated populations.

"There's a rich Neanderthal fossil record. There are lots of Neanderthal sites," said Rogers. "It's hard to imagine that there would be so many of them if there were only 1,000 individuals in the whole world."

Rogers is excited to apply the new method in other contexts.

"To some degree, this is a proof of concept that the method can work. That's exciting," said Rogers. "We have remarkable ability to estimate things with high precision, much farther back in the past than anyone has realized."

Explore further: DNA of early Neanderthal gives timeline for new modern human-related dispersal from Africa

More information: Alan R. Rogers el al., "Early history of Neanderthals and Denisovans," PNAS (2017). http://www.pnas.org/cgi/doi/10.1073/pnas.1706426114

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New look at archaic DNA rewrites human evolution story - Phys.Org