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 Copyright © 2019 By Shanghai Science & Technology Development Foundation

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  • Admin
    Jun 11, 2018

    The Human Genome Project made big news in the early 2000s when an international group of scientists successfully completed a decade-long endeavor to map out the entirety of the human genome. Then, last month, genetic researchers caused some minor controversy when a group of about 150 scientists, lawyers and entrepreneurs met behind closed doors to discuss “writing” the human genome – that is, synthesizing the human DNA sequences from scratch. In response to the uproar, the group published a short article in Science this week, explaining the basic ideas behind their objectives. The project, HGP-write (human genome project – write), is led by Jef D. Boeke, Andrew Hessel, Nancy J. Kelley, and FLI science advisory board member George Church, though over 20 participants helped pen the Science article. In the article, they explain, “Genome synthesis is a logical extension of the genetic engineering tools that have been used safely within the biotech industry for ~40 years and have provided important societal benefits.” Recent advances in genetics and biotech, such as the explosion of CRISPR-cas9 and even the original Human Genome Project, have provided glimpses into a possible future in which we can cure cancer, ward off viruses, and generate healthy human organs. Scientists involved with HGP-write hope this project will finally help us achieve those goals. They wrote: Potential applications include growing transplantable human organs; engineering immunity to viruses in cell lines via genome-wide recoding ( 12 ); engineering cancer resistance into new therapeutic cell lines; and accelerating high-productivity, cost-efficient vaccine and pharmaceutical development using human cells and organoids. While there are clearly potential benefits to this technology, concerns about the project are to be expected, especially given the closed-door nature of the meeting. In response to the meeting last month, Drew Endy and Laurie Zoloth argued: Given that human genome synthesis is a technology that can completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real, like today’s Harvard conference, should not take place without open and advance consideration of whether it is morally right to proceed. The director of the National Institutes of Health, Francis S. Collins, was equally hesitant to embrace the project. In a statement to the New York Times , he said, “whole-genome, whole-organism synthesis projects extend far beyond current scientific capabilities, and immediately raise numerous ethical and philosophical red flags.” In the Science article, the researchers of HGP-write insist that “HGP-write will require public involvement and consideration of ethical, legal, and social implications (ELSI) from the start.” This is a point Church reiterated to the Washington Post, explaining that there were already ELSI researchers who participated in the original meeting and that he expects more researchers to join as a response to the Science article. The primary goal of the project is “to reduce the costs of engineering and testing large (0.1 to 100 billion base pairs) genomes in cell lines by over 1000-fold within 10 years.” The HGP-write initiative hopes to launch this year “with $100 million in committed support,” and they plan to complete the project for less than the $3 billion price tag of the original Human Genome Project.
  • Admin
    Jun 11, 2018

    The following article was written by John Min and George Church. Imagine for a moment, a world where we are able to perform genetic engineering on such large scales as to effectively engineer nature.  In this world, parasites that only cause misery and suffering would not exist, only minimal pesticides and herbicides would be necessary in agriculture, and the environment would be better adapted to maximize positive interactions with all human activities while maintaining sustainability.  While this may all sound like science fiction, the technology that might allow us to reach this utopia is very real, and if we develop it responsibly, this dream may well become reality. ‘Gene drive’ technology, or more specifically, CRISPR gene drives, have been heralded by the press as a potential solution for mosquito-borne diseases such as malaria, dengue, and most recently, Zika. In general, gene drive is a technology that allows scientists to bias the rate of inheritance of specific genes in wild populations of organisms. A gene is said to ‘drive’ when it is able to increase the frequency of its own inheritance higher than the expected probability of 50%. In doing so, gene drive systems exhibit unprecedented ability to directly manipulate genes on a population-wide scale in nature. The idea to use gene drive systems to propagate engineered genes in natural systems is not new.  Indeed, a proposal to construct gene drives using naturally occurring homing nucleases, genes that can specifically cut DNA and insert extra copies of itself, was published by Austin Burt in 2003 (Burt, 2013). In fact, the concept was discussed even before the earliest studies on naturally driving genetic elements — such as transposons, which are small sections of DNA that can insert extra copies of itself — over half a century ago (Serebrovskii, 1940) (Vanderplank, 1944). However, it is only with advances in modern genome editing technology, such as CRISPR, that scientists are finally able to digitally target gene drives to any desired location in the genome. Ever since the first CRISPR gene drive design was described in a 2014 publication by Kevin Esvelt and George Church (Esvelt, et al., 2014), man-made gene drive systems have been successfully tested in three separate species, yeast, fruit fly, and mosquitoes (DiCarlo, et al., 2015) (Gantz & Bier, 2015) (Gantz, et al., 2015) . The term ‘CRISPR’ stands for clustered regularly-interspaced short palindromic repeats and describes an adaptive immune system against viral infections originally discovered in bacteria.  Nucleases, or proteins that cut DNA, in the CRISPR family are generally able to cut DNA anywhere as specified by a short stretch of RNA sequence at high precision and accuracy. The nuclease cas9, in particular, has become a favorite among geneticists around the world since the publication of a series of high impact journal articles in late 2012 and early 2013 (Jinek, et al., 2012) (Cong, et al., 2013) (Hwang, et al., 2013). Using cas9, scientists are able to create ‘double-stranded breaks,’ or cuts in DNA, at nearly any location specified by a 20 nucleotide piece of RNA sequence. After being cut, we can take advantage of natural DNA repair mechanisms to persuade cells to incorporate new genetic information into the break. This allows us to introduce new genes into an organism or even bar-code it at a genetic level. By using CRISPR technology, scientists are also able to insert synthesized gene drive systems into a host organism’s genome with the same high level of precision and reliability. Potential applications for CRISPR gene drives are broad and numerous, as the technology is expected to work in any organism that reproduces sexually. While popular media attention is chiefly focused on the elimination of mosquito-borne diseases, applications also exist in the fight against the rise of Lyme disease in the U.S. Beyond public health, gene drives can be used to eliminate invasive species from non-native habitats, such as mosquitos in Hawaii. In this case, many native Hawaiian bird species, especially the many honeycreepers, are being driven to extinction by mosquito-borne avian malaria. The removal of mosquitos in Hawaii would both save the  bird populations, as well as make Hawaii even more attractive as a tropical paradise for tourists. With such rapid expansion of gene drive technology over the past year, it is only natural for there to be some concern and fear over attempting to genetically engineer nature at such a large scale. The only way to truly address these fears is to rigorously test the spreading properties of various gene drive designs within the safety of the laboratory — something that has also been in active development over the last year. It is also important to remember that mankind has been actively engineering the world around us since the dawn of civilization, albeit with more primitive tools. Using a mixture of breeding and mechanical tools, we have managed to transform teosinte into modern corn, created countless breeds of dogs and cats, and transformed vast stretches everything from lush forests to deserts into modern farmland. Yet, these amazing feats are not without consequence. Most products of our breeding techniques are unable to survive independently in nature, and countless species have become extinct as the result of our agricultural expansion and eco-engineering. It is imperative that we approach gene drives differently, with increased consideration for the consequences of our actions on both the natural world as well as ourselves. Proponents of gene drive technology would like to initiate a new research paradigm centered on collective decision making. As most members of the public will inevitably be affected by a gene drive release, it is only ethical to include the public throughout the research and decision making process of gene drive development.  Furthermore, by being transparent and inviting of public criticism, researchers are able to crowd-source the “de-bugging” process, as well as minimize the risk of a gene drive release going awry. We must come to terms with the reality that thousands of acres of habitat continue to be destroyed annually through a combination of chemical sprays, urban and agricultural expansion, and the introduction of invasive species, just to name a few. To improve up on this, I would like to echo the hopes of my mentor, Kevin Esvelt, toward the use of “more science, and fewer bulldozers for environmental engineering” in hopes of creating a more sustainable co-existence between man and nature. The recent advancements in CRISPR gene drive technology represent an important step toward this hopeful future. About the author: John Min is a PhD. Candidate in the BBS program at Harvard Medical School co-advised by Professor George Church and Professor Kevin Esvelt at MIT Media Labs.  He is currently working on creating a laboratory model for gene drive research.
  • Admin
    Jun 11, 2018

    X-risk = Existential Risk. The risk that we could accidentally (hopefully accidentally) wipe out all of humanity. X-hope = Existential Hope. The hope that we will all flourish and live happily ever after. If you keep up with science news at all, then you saw the headlines splashed all over news sources on Monday: The UK has given researchers at the Francis Crick Institute permission to edit the genes of early-stage human embryos. This is huge news, not only in genetics and biology fields, but for science as a whole. No other researcher has ever been granted permission to perform gene editing on viable human embryos before. The usual fears of designer babies and slippery slopes popped up, but as most of the general news sources reported, those fears are relatively unwarranted for this research. In fact, this project, with is led by Dr. Kathy Niakan , could arguably be closer to the existential hope side of the spectrum. Niakan’s objective is to try to understand the first seven days of embryo development, and she’ll do so by using CRISPR to systematically sweep through genes in embryos that were donated from in vitro fertilization (IVF) procedures. While research in mice and other animals has given researchers an idea of the roles different genes play at those early stages of development, there many genes that are uniquely human and can’t be studied in other animals. Many causes of infertility and miscarriages are thought to occur in some of those genes during those very early stages of development, but we can only determine that through this kind of research. Niakan explained to the BBC , “We would really like to understand the genes needed for a human embryo to develop successfully into a healthy baby. The reason why it is so important is because miscarriages and infertility are extremely common, but they’re not very well understood.” It may be hard to see how preventing miscarriages could be bad, but this is a controversial research technique under normal circumstances, and Niakan’s request for approval came on the heels of human embryo research that did upset the world. Last year, outrage swept through the scientific community after scientists in China chose to skip proper approval processes to perform gene-editing research on nonviable human embryos. Many prominent scientists in the field, including FLI’s Scientific Advisory Board Member George Church, responded by calling for a temporary moratorium on using the CRISPR/Cas-9 gene-editing tool in human embryos that would be carried to term. An important distinction to make here is that Dr. Niakan went through all of the proper approval channels to start her research. Though the UK’s approval process isn’t quite as stringent as that in the US – which prohibits all research on viable embryos – the Human Fertilisation and Embryology Authority, which is the approving body, is still quite strict, insisting, among other things, that the embryos be destroyed after 14 days to ensure they can’t ever be taken to term. The team will also only use embryos that were donated with full consent by the IVF patients. Max Schubert , a doctoral candidate of Dr. George Church’s lab at Harvard, explained that one of the reasons for the temporary moratorium was to give researchers time to study the effects of CRISPR first to understand how effective and safe it truly is. “I think [Niakan’s research] represents the kind of work that you need to do to understand the risks that those scientists are concerned about,” said Schubert. John Min , also a PhD candidate in Dr. Church’s lab, pointed out that the knowledge we could gain from this research will very likely lead to medications and drugs that can be used to help prevent miscarriages, and that the final treatment could very possibly not involve any type of gene editing at all. This would eliminate, or at least limit, concerns about genetically modified humans. Said Min, “This is a case that illustrates really well the potential of CRISPR technology … CRISPR will give us the answers to [Niakan’s] questions much more cheaply and much faster than any other existing technology.”