Daily Archives: August 3, 2017

John Sotos, the Chief Medical Officer at Intel, has a wild, scary thought experiment: What if, by investing in hacking the human genome for good, weve opened it up to be hacked for evil?

Sotos gave a talk this weekend at the DEF CON hacker convention in Las Vegas titled, in full, Genetic Diseases to Guide Digital Hacks of the Human Genome: How the Cancer Moonshot Program will Enable Almost Anyone to Crash the Operating System that Runs You or to End Civilization.

Sotos, whose employer allowed him to give the talk but not to do interviews about it, believes that it may one day be possible to create terrifying bioweapons using genetics. He hypothesized several attacks that could be devastating if the capability to execute them fell into the hands of adversaries, especially ideological ones. They ranged from targeted pandemics, meaning viruses that only affect people with a certain gene, to altering sexual preferences.

These attacks could become possible thanks to the Human Genome Project, a government-funded effort to map all the genes in human DNA, and the Cancer Moonshot, another government program that is investing in precision medicine as well as emerging DNA and RNA technologies.

Sotos is assuming that the Cancer Moonshot, a $1.6 billion program authorized in 2016, will succeed in its goals. The ideal cancer treatment would go something like this: biopsy a tumor, tabulate its genetic signature, create a virus that kills cells with that signature, inject it into the patients body. A few days later, the patient is cancer-free.

Imagine such precise gene editing technology is possible, and then imagine that its also possible to use a computer program to simulate and tinker with everything thats going on in the genome another emerging technology called digital biology. Eventually, Sotos believes, it will be possible to digitally reprogram the human genome in a living human.

The problems that arise from these advancements now start to resemble those in the existing information security industry, except that the genome has no protection and the locations of its weaknesses are publicly documented. The human genome is full of potential exploits, Sotos said, using the infosec term for a vulnerability that a hacker can leverage to take over a system. The genome is basically an open-source operating system, he said, full of security vulnerabilities.

In theory, hackers who were militant vegans could induce meat intolerance in others, while hackers who oppose drinking could force alcohol intolerance. Hackers who were interested in, say, controlling women, could induce chastity by creating a hyper-susceptibility to STDs, or extreme sun sensitivity that would force women to wear veils. Hackers could also supercharge pharmaceutical sales by spreading the genes for treatable illness, a way to make money on the stock market (or perhaps, in this dystopian future, the pharma companies will be morally bankrupt enough to do it themselves). Based on what we already know about which genes are located where and cause what, hackers in this thought experiment could induce deafness, blindness, night blindness, strong fishy body odor, total baldness, intractable diarrhea, massive weight gain, shouting involuntary obscenities, physical fragility, or a susceptibility to death from excitement. There are things worse than death, he said.

The talk was riveting, but Sotos started getting pushback immediately from scientists who said it amounted to baseless fear-mongering.

Former U.S. Chief Data Scientist DJ Patil tweeted that the scenarios Sotos posited were a real risk. Creating noise & sounding alarms this way isn't helpful to saving lives, he tweeted. The risk is really small. It's really hard to mass produce these. The real risk we should be focusing on is drug resistant TB and pandemics.

Talks at DEF CON often tend to exaggerate a threat to get attention on a topic. There is widespread agreement that genetic information must be protected, but there isnt much in the way of legislation or market forces that would make that happen. Thought experiments play a role in prompting government to take defensive action, Sotos said.

The Cobra Event, a novel Sotos cited in his talk about a highly contagious brain-pox cooked up by a genetics wizard named Archimedes, reportedly influenced Bill Clinton to start stockpiling antibiotics and training public health authorities to deal with a chemical or biological weapons attack. It would probably be better if we could get forward-looking public policy without having to scare it into politicians, but unfortunately the human brain is hardwired to be reactive at least until we hack it to be otherwise.

The Future

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MIT Tech Review

Go here to see the original:
Worse than death: The far-future dystopia of genome hacking - The Outline

C

reating designer babies with a revolutionary new genome-editing technique would be extremely difficult, according to the first U.S. experiment that tried to replace a disease-causing gene in a viable human embryo.

Partial results of the study hadleaked out last week, ahead of its publication in Nature on Wednesday, stirring critics fears that genes for desired traits from HIV resistance to strong muscles might soon be easily slipped into embryos. In fact, the researchers found the opposite: They were unable to insert a lab-made gene.

Biologist Shoukhrat Mitalipov of Oregon Health and Science University, who led the first-of-its-kind experiment, described the key result as very surprising and dramatic.

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The external DNA provided to fertilized human eggs developing in a lab dish was never used, he told STAT. The scientists excised a mutated, heart-disease-causing gene from the embryos agene thatcame from sperm used to create them through in vitro fertilization and supplied them with a healthy replacement. But every single one of the 112 embryos ignored it. Instead, they copied the healthy gene from their mother and incorporated that into their genome to replace the fathers.

This is the main finding from our study, Mitalipov said: Embryos natural preference for a parents gene is very strong, and they wont use anything else.

The discovery suggests that opportunities for disease prevention are more limited than scientists assumed and that enhancement giving a days-old embryo better genes is unlikely to succeed, at least with current methods. Genetic tinkering can, however, eliminate a bad gene that an embryo got from one parent and replace it with a good gene from the other parent. And the experiment showed for the first time in a large number of embryos that this can be done efficientlyand without harming other genes.

That offers the prospect of preventing inherited diseases such as cystic fibrosis, Huntingtons disease, and some cancers, as long as one parent carries a healthy gene to replace the disease-causing one. (The age-old desire of many couples to choose which parents traits their child inherits could also become a reality, though probably not for years.)

Polls show greater public support for using germline editing changing the DNA of very early embryosto prevent disease than for giving embryos souped-up genes for, say, extraordinary memories or unbreakable bones. Such traits would be passed on to all subsequent generations. Although some studies have identifiedgenes associated with those enhanced traits, they are extraordinarily rare. To bestow the traits on an embryo would require creating the genes in a lab and injecting them the exact thing that failed completely in the new study.

The surprise finding showed that to introduce a novel gene is [an] issue, said Fredrik Lanner, of Karolinska University Hospital in Sweden, who was not involved in the Oregon study. (Lanner received permissionlast year to conduct similar experiments editing the genome of human embryos). More research would be needed to really know how efficiently a new gene version can be introduced.

The discovery that human embryos mighthave natural barriers to accepting introduced DNA something other kinds of human cells, and other animal embryos, have no problem doing offers some assurance that designer babies are not in the offing anytime soon. But critics of editing the human germline were not mollified.

Marcy Darnovsky, executive director of the Center for Genetics and Society, argued that there are other ways for couples to have a biological child free of the known genetic defects carried by one parent or both: Screening the DNA of IVF embryos through a technique called preimplantation genetic diagnosis (PGD) lets parents choose only healthy embryos to implant.

We have to weigh the medical benefit to a few from correcting an embryos mutation against the social risks for all of us, she said, adding that enhancement-type alterations might in fact be possible. I dont see any reason to doubt that Mitalipov or others will pursue other new wrinkles in these procedures, to enable more extensive genetic alterations.

The research hit other hot buttons.Mitalipov (a skilled reproductive biologist known for pushing boundaries) and his colleagues created human embryos. Doing that for research is legal in Oregon and some other states but illegal in others and ardently opposed by many religious groups. And the scientists destroyed them after a few days, which some critics regard as murder. (The researchers had no intention of implanting the altered embryos in a uterus.)

A 1995 law prohibits the use of U.S. funds to create human embryos for research or to destroy them, and the National Institutes of Health bansuse of its grants to edit the genome of human embryos, but this study was funded by private foundations and university funds.

At first glance, the experiment ran according to script. The scientists created embryos by fertilizing (in lab dishes) eggs from a dozen healthy donors with sperm from a man with the mutation that causes the rare heart disorder called hypertrophic cardiomyopathy. At the same time, the scientists injected CRISPR-Cas9.

This revolutionary genome-editing technology typically has three components. A targeting molecule carries the CRISPRcomplex to the target gene within a cell. A molecular scissors snips out the target gene. A healthy gene is supposed to replace the excised one. In experiment after experiment in regular human cells (not embryos), this now-classic use of CRISPR-Cas9 shreds the targeted DNA and the double helix stitches in a replacement like a seamstress darning a sock.

Thats what happened when Mitalipov injected CRISPR into stem cells produced from the man with hypertrophic cardiomyopathy. The incurable disorder strikes about 1 in 500 people, said Dr. Carolyn Yung Ho of Brigham and Womens Hospital in Boston, making the hearts left ventricle abnormally thick; mutations in any of several genes, including one called MYBPC3, can cause it. As expected, CRISPR efficiently snipped out the mutated MYBPC3 gene, and the cells replaced it with the healthy version that was slipped in with the CRISPR complex. We supplied a repair template and the cells used it, Mitalipov said.

The research ethics committee at OHSU, which vets studies, questioned Mitalipovs proposal to next CRISPR embryos.They told me, You have your answer [from the stem cell experiment]; why do you have to do embryos? Mitalipov recalled. I told themI had a hunch that the results might be different. I said, Let me do embryos.

His hunch was right. CRISPR seemed to work like a charm in the embryos. It excised the cardiomyopathy gene in 22 of the 112 embryos, an exceptionally high efficiency for CRISPR. It excised no unintended targets, contrary to what had happened in a CRISPR experiment in China, which got many such off-target effects. And CRISPR worked in all of the cells the embryo eventually divided into, probably because it was injected into the egg at the same time as the sperm.

But the embryos did not insert the healthy, lab-made heart gene in place of the CRISPRd mutated one. The reason is a mystery, but bioengineer Neville Sanjana of the New York Genome Center said, I dont think it is a complete surprise. After all, this is likely how DNA repair evolved in the first place to repair a damaged chromosome by using the other, intact one.

Mitalipov suspects that an embryo responds to CRISPRs snipping out one of its genes by looking up and down and around the genome and somehow recognizing maternal DNA and inserting that in place of the snipped-out paternal gene. If so, then any replacement gene that scientists offer stands little chance of getting accepted.

Chinese researchers reported earlier this year on anexperimentin which they got about 10 percent of CRISPRd human embryos to accept an introduced gene, but it used only a few embryos and had other limitations. The U.S. study suggests that the insert-a-gene recipe for designer babies will be tougher than expected: To introduce a novel gene, said Karolinskas Lanner, you would [have to] target both DNA copies moms and dads with CRISPR. That might be possible, butmore research would be needed to really know how efficiently a new gene version can be introduced.

Even if CRISPRing embryos can only cause a child to inherit a mothers trait and not the fathers, or vice versa, that should be enough to eliminate a disease-causing mutation from an embryo and future generations. The vast majority of patients with a disease-causing mutation have a partner with the [healthy] gene, Mitalipov said. That healthy gene, with an assist from CRISPR, could replace the mutated one in an embryo, giving children only the healthy gene.

Every generation on would carry this repair because weve removed the disease-causing gene variant from that familys lineage, he said.

That would obviate the need to screen IVF embryos to find a mutation-free one to implant. Unwanted embryos are usually destroyed. When the OHSU ethics committee pressed Mitalipov about destroying embryos in his experiment, he had an answer: If CRISPR can eliminate disease-causing mutations from embryos, as he hoped his research would help make possible, Im going to rescue the [IVF] embryos that are now thrown away.

But not soon, and probably not in the United States. Federal law prohibits regulators from even considering a request to launch a clinical trial in which embryos would be genetically altered and implanted in a uterus.

Mitalipov has another hunch, this time about where that will lead: Unfortunately, this technology will just be shifted to unregulated countries.

Senior Writer, Science and Discovery

Sharon covers science and discovery.

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View post:
US scientists edit genome of human embryo, but cast doubt on possibility of 'designer babies' - STAT

August 2, 2017 by Franoise Baylis, The Conversation

Mitalipov's team is not the first to genetically modify human embryos. This was first accomplished in 2015 by a group of Chinese scientists led by Junjiu Huang. Mitalipov's team, however, may be the first to demonstrate basic safety and efficacy using the CRISPR technique.

This has serious implications for the ethics debate on human germline modification which involves inserting, deleting or replacing the DNA of human sperm, eggs or embryos to change the genes of future children.

Ethically controversial

Those who support human embryo research will argue that Mitalipov's research to alter human embryos is ethically acceptable because the embryos were not allowed to develop beyond 14 days (the widely accepted international limit on human embryo research) and because the modified embryos were not used to initiate a pregnancy. They will also point to the future potential benefit of correcting defective genes that cause inherited disease.

This research is ethically controversial, however, because it is a clear step on the path to making heritable modifications - genetic changes that can be passed down through subsequent generations.

Beyond safety and efficacy

Internationally, UNESCO has called for a ban on human germline gene editing. And the "Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine" the Oviedo Convention specifies that "an intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants."

In a move away from the positions taken by UNESCO and included in the Oviedo Convention, in 2015 the 12-person Organizing Committee of the first International Summit on Human Gene Editing (of which I was a member) issued a statement endorsing basic and preclinical gene editing research involving human embryos.

The statement further stipulated, however, that: "It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application."

Mitalipov's research aims to address the first condition about safety and efficacy. But what of the second condition which effectively recognizes that the human genome belongs to all of us and that it is not for scientists or other elites to decree what should or should not happen to it?

Modification endorsed

Since the 2015 statement was issued, many individuals and groups have tried to set aside the recommendation calling for a broad societal consensus.

For example, in February 2017, the U.S. National Academy of Sciences and National Academy of Medicine published a report endorsing germline modification. It states unequivocally that "clinical trials using heritable germline genome editing should be permitted" provided the research is only for compelling reasons and under strict oversight limiting uses of the technology to specified criteria.

Seeds of change in Canada

In Canada, it is illegal to modify human germ cells. Altering "the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants" is among the activities prohibited in the 2004 Assisted Human Reproduction Act.

Worried that "Canadian researchers may fall behind on the international scene" and that "restrictive research policies may lead to medical tourism," the Canadian Institutes for Health Research (with input from the Canadian Stem Cell Network) has begun to plant the seeds of change.

In its Human Germline Gene Editing report, CIHR hints at the benefits of changing the legislation. It also suggests professional self-regulation and research funding guidelines could replace the current federal statutory prohibition.

Future of the species

With the recent announcement of Mitalipov's technological advances and increasing suggestions from researchers that heritable modifications to human embryos be permitted, it is essential that citizens be given opportunities to think through the ethical issues and to work towards broad societal consensus.

We are talking about nothing less than the future of the human species. No decisions about the modification of the germline should be made without broad societal consultation.

Nothing about us without us!

Explore further: Genome editing in human cells

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

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Human cells or embryos that undergo a process of gene-editing must not be used to establish a pregnancy, an international scientific panel said Thursday, urging strict limits on the controversial research.

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Now I can see this research as far as understanding EXACTLY how to make those changes in case of some unforeseen global emergency/need in the future.

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The rest is here:
Opinion: Human genome editingwe should all have a say - Phys.org - Phys.Org