Genetic Engineering and Animals: A Short Summary of the Legal Terrain and Ethical ImplicationsAndrew B. Perzigian (2003)

With the advent and rapid development of genetic engineering technology, the animal rights movement is currently facing one of its greatest challenges and dilemmas. Proponents of the technology assert that transgenic animals, animals that have been genetically altered through the introduction of another plant's or animal's genes, may one day help solve many of our modern day problems in life, from starvation and ill health, to environmental degradation and the modern extinction crisis. Critics believe that bioengineering poses greater risks than it does benefits. They argue that genetic engineering threatens to increase animal suffering and decrease species integrity, while at the same time creating a potentially devastating impact on the balance and sustainability of the Earth's ecosystem. Regardless, the value judgments we make regarding the direction and scope that this technology should take are sure to have far reaching implications.

Transgenic animals are animals that have, through genetic engineering, genes from other plants and animals. Unlike controlled breeding, which is confined to the genetic material contained in a single species, modern genetic engineering permits an almost limitless scope of modification and introduction of otherwise foreign genetic material. This permits specific traits, and not the host of other traits common from crossbreeding, to be effectively introduced into new, transgenic animal species. Genetic engineering is able to create whole organisms that are not natural to the planet, and whose specific genetic make-up is as much a result of human manipulation as it is natural selection. (For further information on the basics of genetic engineering, see Detailed Discussion ).

With regard to the agricultural industry, transgenic farm animals can be created, that are better able to resist disease, grow faster, and more efficiently reproduce than current species of animals. Transgenic sheep can be created to produce better wool and cows can be engineered to more efficiently convert grain into higher quality milk and meat. Transgenic salmon, salmon that grow larger and at a faster rate than natural varieties, have already been created and farmed. (For further information on thepotential benefits, see Detailed Discussion ).

One of the more controversial uses of this technology is found in recent proposals to engineer farm animals to be non-sentient, without the "stress" genes that cause them great suffering during their lives on industrial factory farms. Since sentience, the ability to feel pain and experience suffering, is the basis upon which much animal rights ideology is based, some argue that these types of transgenic farm animals would help to solve many of the animal welfare issues posed by industrial factory farms. (For more information on the risks, see Detailed Discussion ).

The bio-medical research industry has been equally influenced by genetic engineering technology. Instead of relying on numerous test animals to research modern diseases and appropriate drug therapies, the bio-medical community can now rely on specifically engineered animal research models. Such animals are bred to have an increase susceptibility to modern diseases, like hereditary breast cancer. Transgenic animals have made research of such diseases more accurate, less expensive and faster, while at the same time permitting accurate results with the use of fewer individual animals in any given study.

Also, transgenic animals, like goats, sheep, and cattle, have been engineered to produce large amounts of complex human proteins in their milk, something very useful in the creation of therapeutic drugs. By engineering these animals to release these and other proteins in their milk, the mass production of high quality therapeutic drugs is made less costly, easier to manufacture, and at the expense of fewer animal lives than what was formerly the case. (For more information on the scientific andmedical potential of genetic engineering, see DetailedDiscussion ).

Biotechnology breakthroughs in whole animal cloning have led to many suggestions that such technology could be used to clone endangered species. Cloning provides a great support blanket for the modern extinction crisis and can help to ensure that critical numbers of endangered species will exist for generations to come.

In general, opponents of genetic engineering assert that such technology creates a huge diminution in the standing of animals, leaving them as nothing more than "test tubes with tails," only of benefit for the exploitive practices of factory farming, and drug and organ manufacturing. Creating more efficient agricultural animals threatens weaken the genetic diversity of the herd and thereby make them more susceptible to new strains of infectious disease. Also, if transgenic farm animals ever escape into wild populations, they can have profoundly disturbing effects on the natural environment, including a complete elimination of natural populations and the processes of natural selection.

Animal rights advocates also argue that each species should enjoy an inherent, natural right to be free of genetic manipulation in any form. This is especially the case when genetic engineering is used as a means of depriving animals of their sentience, of exacerbating the cruel, horrific conditions of the modern factory farm and biomedical lab. Although the sheer numbers may decline, the actual suffering experienced by agricultural and research animals may increase.

Cloning endangered species, although useful as a last resort, may unwisely shift our efforts away from protecting the critical habitat necessary to sustain viable endangered species populations. Habitat protection is as important to saving endangered species as is the specific renewal and maintenance of viable numbers within a population. Since limited funds exist, habitat protection, and not expensive cloning technology, should be the focus of our endangered species protection efforts. (For more information on the inherent dangers, see Detailed Discussion ).

Currently, there are few laws, in either the United States or the European Union (EU) regulating animal cloning and the creation of transgenic animals. In the United States, most research and farm animals are excluded from federal protection. While the European Union (EU) ensures that such animals are treated more humanely than is the case in the United States, both the U.S. and the EU extend patent protection to the owners and creators of transgenic animal species. This provides a huge incentive for the biotechnology industry to continually research and develop novel transgenic animal creations. With patents, researchers can now own and monopolize entire animal species, something unheard of prior to modern genetic engineering. The Supreme Court has upheld transgenic animal patents without any review of the potential ethical and environmental risks associated with the technology involved. (For moreon this important decision, click here ).

Most modern legislation regarding genetic engineering and cloning technology ensued following the birth of Dolly the sheep, the first multi-cellular organism cloned from adult cells. The primary objectives of the subsequent United States and EU legislation was to ban human cloning while at the same time ensuring that genetic engineering research continued unimpeded by such legislation. Patent protection effectively promotes genetic engineering research and helps to ensure its speedy development. (For more information on U.S. and European laws concerning biotechnology, see Detailed Discussion ).

There is no doubt that genetic engineering of animals will continue well into the future. Both the United States' and the EU's legal systems have been slow to respond with legislation specifically regulating bio
technology, and each have permitted their patent law to provide a supportive ground for genetic engineering research and development. One thing is for sure, we must not sit complacently by as this technology rapidly changes the fabric of our existence from the inside out. We must not wait and see what the effects are. We must form educated opinions, inspire legislative regulation, and hope that whatever direction that bioengineering takes us, is a positive step towards decreased animal suffering, increased environmental sustainability, and an overall compassionate regard for the earth and its precious life.

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Although much has occurred in this field since this article was written in 2000, the questions addressed by Dr. Bohlin are still timely and relevant. Is manipulating our genetic code simply a tool or does it deal with deeper issues? Dealing with genetic engineering must be done within the context of the broader ethical and theological issues involved. In the article, Dr. Bohlin provides an excellent summary driven from his biblical worldview perspective.

Genetic technology harbors the potential to change the human species forever. The soon to be completed Human Genome Project will empower genetic scientists with a human biological instruction book. The genes in all our cells contain the code for proteins that provide the structure and function to all our tissues and organs. Knowing this complete code will open new horizons for treating and perhaps curing diseases that have remained mysteries for millennia. But along with the commendable and compassionate use of genetic technology comes the specter of both shadowy purposes and malevolent aims.

For some, the potential for misuse is reason enough for closing the door completelythe benefits just arent worth the risks. In this article, Id like to explore the application of genetic technology to human beings and apply biblical wisdom to the eventual ethical quagmires that are not very far away. In this section well investigate the various ways humans can be engineered.

Since we have introduced foreign genes into the embryos of mice, cows, sheep, and pigs for years, theres no technological reason to suggest that it cant be done in humans too. Currently, there are two ways of pursuing gene transfer. One is simply to attempt to alleviate the symptoms of a genetic disease. This entails gene therapy, attempting to transfer the normal gene into only those tissues most affected by the disease. For instance, bronchial infections are the major cause of early death for patients with cystic fibrosis (CF). The lungs of CF patients produce thick mucus that provides a great growth medium for bacteria and viruses. If the normal gene can be inserted in to the cells of the lungs, perhaps both the quality and quantity of their life can be enhanced. But this is not a complete cure and they will still pass the CF gene on to their children.

In order to cure a genetic illness, the defective gene must be replaced throughout the body. If the genetic defect is detected in an early embryo, its possible to add the gene at this stage, allowing the normal gene to be present in all tissues including reproductive tissues. This technique has been used to add foreign genes to mice, sheep, pigs, and cows.

However, at present, no laboratory is known to be attempting this well-developed technology in humans. Princeton molecular biologist Lee Silver offers two reasons.{1} First, even in animals, it only works 50% of the time. Second, even when successful, about 5% of the time, the new gene gets placed in the middle of an existing gene, creating a new mutation. Currently these odds are not acceptable to scientists and especially potential clients hoping for genetic engineering of their offspring. But these are only problems of technique. Its reasonable to assume that these difficulties can be overcome with further research.

The primary use for human genetic engineering concerns the curing of genetic disease. But even this should be approached cautiously. Certainly within a Christian worldview, relieving suffering wherever possible is to walk in Jesus footsteps. But what diseases? How far should our ability to interfere in life be allowed to go? So far gene therapy is primarily tested for debilitating and ultimately fatal diseases such as cystic fibrosis.

The first gene therapy trial in humans corrected a life-threatening immune disorder in a two-year-old girl who, now ten years later, is doing well. The gene therapy required dozens of applications but has saved the family from a $60,000 per year bill for necessary drug treatment without the gene therapy.{2} Recently, sixteen heart disease patients, who were literally waiting for death, received a solution containing copies of a gene that triggers blood vessel growth by injection straight into the heart. By growing new blood vessels around clogged arteries, all sixteen showed improvement and six were completely relieved of pain.

In each of these cases, gene therapy was performed as a last resort for a fatal condition. This seems to easily fall within the medical boundaries of seeking to cure while at the same time causing no harm. The problem will arise when gene therapy will be sought to alleviate a condition that is less than life-threatening and perhaps considered by some to simply be one of lifes inconveniences, such as a gene that may offer resistance to AIDS or may enhance memory. Such genes are known now and many are suggesting that these goals will and should be available for gene therapy.

The most troublesome aspect of gene therapy has been determining the best method of delivering the gene to the right cells and enticing them to incorporate the gene into the cells chromosomes. Most researchers have used crippled forms of viruses that naturally incorporate their genes into cells. The entire field of gene therapy was dealt a severe setback in September 1999 upon the death of Jesse Gelsinger who had undergone gene therapy for an inherited enzyme deficiency at the University of Pennsylvania.{3} Jesse apparently suffered a severe immune reaction and died four days after being injected with the engineered virus.

The same virus vector had been used safely in thousands of other trials, but in this case, after releasing stacks of clinical data and answering questions for two days, the researchers didnt fully understand what had gone wrong.{4} Other institutions were also found to have failed to file immediate reports as required of serious adverse events in their trials, prompting a congressional review.{5} All this should indicate that the answers to the technical problems of gene therapy have not been answered and progress will be slowed as guidelines and reporting procedures are studied and reevaluated.

The simple answer is no, at least for the foreseeable future. Gene therapy currently targets existing tissue in a existing child or adult. This may alleviate or eliminate symptoms in that individual, but will not affect future children. To accomplish a correction for future generations, gene therapy would need to target the germ cells, the sperm and egg. This poses numerous technical problems at the present time. There is also a very real concern about making genetic decisions for future generations without their consent.

Some would seek to get around these difficulties by performing gene therapy in early embryos before tissue differentiation has taken place. This would allow the new gene to be incorporated into all tissues, including reproductive organs. However, this process does nothing to alleviate the condition of those already suffering from genetic disease. Also, as mentioned earlier this week, this procedure would put embryos at unacceptable risk due to the inherent rate of failure and potential damage to the embryo.

Another way to affect germ line gene therapy would involve a combination of gene therapy and cloning.{6} An embryo, fertilized in vitro, from the sperm and egg of a couple at risk for sickle-cell anemia, for example, could be tested for the sickle-cell gene. If the embryo tests positive, cells could be removed from this early embryo and grown in culture. Then the normal hemoglobin gene would be added to these cultured cells.

If the technique for human cloning could be perfected, then one of these cells could be cloned to create a new individual. If the cloning were successful, the resulting baby would be an identical twin of the original embryo, only with the sickle-cell gene replaced with the normal hemoglobin gene. This would result in a normal healthy baby. Unfortunately, the initial embryo was sacrificed to allow the engineering of its
identical twin, an ethically unacceptable trade-off.

So what we have seen, is that even human gene therapy is not a long-term solution, but a temporary and individual one. But even in condoning the use of gene therapy for therapeutic ends, we need to be careful that those for whom gene therapy is unavailable either for ethical or monetary reasons, dont get pushed aside. It would be easy to shun those with uncorrected defects as less than desirable or even less than human. There is, indeed, much to think about.

The possibility of someone or some government utilizing the new tools of genetic engineering to create a superior race of humans must at least be considered. We need to emphasize, however, that we simply do not know what genetic factors determine popularly desired traits such as athletic ability, intelligence, appearance and personality. For sure, each of these has a significant component that may be available for genetic manipulation, but its safe to say that our knowledge of each of these traits is in its infancy.

Even as knowledge of these areas grows, other genetic qualities may prevent their engineering. So far, few genes have only a single application in the body. Most genes are found to have multiple effects, sometimes in different tissues. Therefore, to engineer a gene for enhancement of a particular traitsay memorymay inadvertently cause increased susceptibility to drug addiction.

But what if in the next 50 to 100 years, many of these unknowns can be anticipated and engineering for advantageous traits becomes possible. What can we expect? Our concern is that without a redirection of the worldview of the culture, there will be a growing propensity to want to take over the evolution of the human species. The many people see it, we are simply upright, large-brained apes. There is no such thing as an independent mind. Our mind becomes simply a physical construct of the brain. While the brain is certainly complicated and our level of understanding of its intricate machinery grows daily, some hope that in the future we may comprehend enough to change who and what we are as a species in order to meet the future demands of survival.

Edward O. Wilson, a Harvard entomologist, believes that we will soon be faced with difficult genetic dilemmas. Because of expected advances in gene therapy, we will not only be able to eliminate or at least alleviate genetic disease, we may be able to enhance certain human abilities such as mathematics or verbal ability. He says, Soon we must look deep within ourselves and decide what we wish to become.{7} As early as 1978, Wilson reflected on our eventual need to decide how human we wish to remain.{8}

Surprisingly, Wilson predicts that future generations will opt only for repair of disabling disease and stop short of genetic enhancements. His only rationale however, is a question. Why should a species give up the defining core of its existence, built by millions of years of biological trial and error?{9} Wilson is naively optimistic. There are loud voices already claiming that man can intentionally engineer our evolutionary future better than chance mutations and natural selection. The time to change the course of this slow train to destruction is now, not later.

Many of the questions surrounding the ethical use of genetic engineering practices are difficult to answer with a simple yes or no. This is one of them. The answer revolves around the method used to determine the sex selection and the timing of the selection itself.

For instance, if the sex of a fetus is determined and deemed undesirable, it can only be rectified by termination of the embryo or fetus, either in the lab or in the womb by abortion. There is every reason to prohibit this process. First, an innocent life has been sacrificed. The principle of the sanctity of human life demands that a new innocent life not be killed for any reason apart from saving the life of the mother. Second, even in this country where abortion is legal, one would hope that restrictions would be put in place to prevent the taking of a life simply because its the wrong sex.

However, procedures do exist that can separate sperm that carry the Y chromosome from those that carry the X chromosome. Eggs fertilized by sperm carrying the Y will be male, and eggs fertilized by sperm carrying the X will be female. If the sperm sample used to fertilize an egg has been selected for the Y chromosome, you simply increase the odds of having a boy (~90%) over a girl. So long as the couple is willing to accept either a boy or girl and will not discard the embryo or abort the baby if its the wrong sex, its difficult to say that such a procedure should be prohibited.

One reason to utilize this procedure is to reduce the risk of a sex-linked genetic disease. Color-blindness, hemophilia, and fragile X syndrome can be due to mutations on the X chromosome. Therefore, males (with only one X chromosome) are much more likely to suffer from these traits when either the mother is a carrier or the father is affected. (In females, the second X chromosome will usually carry the normal gene, masking the mutated gene on the other X chromosome.) Selecting for a girl by sperm selection greatly reduces the possibility of having a child with either of these genetic diseases. Again, its difficult to argue against the desire to reduce suffering when a life has not been forfeited.

But we must ask, is sex determination by sperm selection wise? A couple that already has a boy and simply wants a girl to balance their family, seems innocent enough. But why is this important? What fuels this desire? Its dangerous to take more and more control over our lives and leave the sovereignty of God far behind. This isnt a situation of life and death or even reducing suffering.

But while it may be difficult to find anything seriously wrong with sex selection, its also difficult to find anything good about it. Even when the purpose may be to avoid a sex-linked disease, we run the risk of communicating to others affected by these diseases that because they could have been avoided, their life is somehow less valuable. So while it may not be prudent to prohibit such practices, it certainly should not be approached casually either.

Notes

1. Lee Silver, Remaking Eden: Cloning and Beyond in a Brave New World, New York, NY: Avon Books, p. 230-231. 2. Leon Jaroff, Success stories, Time, 11 January 1999, p. 72-73. 3. Sally Lehrman, Virus treatment questioned after gene therapy death, Nature Vol. 401 (7 October 1999): 517-518. 4. Eliot Marshall, Gene therapy death prompts review of adenovirus vector, Science Vol. 286 (17 December 1999): 2244-2245. 5. Meredith Wadman, NIH under fire over gene-therapy trials, Nature Vol. 403 (20 January 1999): 237. 6. Steve Mirsky and John Rennie, What cloning means for gene therapy, Scientific American, June 1997, p. 122-123. 7. Ibid., p. 277. 8. Edward Wilson, On Human Nature, Cambridge, Mass.: Harvard University Press, p. 6. 9. E. Wilson, Consilience, p. 277.

2000 Probe Ministries

On January 8, 2007, the Associated Press reported that scientists from Wake Forest University and Harvard University discovered a new type of stem cell found in the amniotic fluid within

Genetic Diseases The age of genetics has arrived. Society is in the midst of a genetic revolution that some futurists predict will have a greater impact on the culture than

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Human Genetic Engineering - Probe Ministries

I will be discussing the controversial topic of human genetic engineering and its pros and cons from a biological and social point of view while also trying to answer the question Should human genetic engineering be legal. Genes control health and disease, as well as human traits and behavior. Researchers are Just beginning to use genetic technology to unravel the secrets to these phenotypes (observable trait caused by a gene).

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They are also discovering a range of other potential applications for this technology.

For instance, ongoing advances make it more and more likely that scientists will soon be able to genetically engineer humans to have certain desired traits (this is already done on mice). Of course, the possibility of human genetic engineering raises a number of ethical and legal questions, although such questions almost never have a clear and straight forward answer. The research of bioethics, sociologists, anthropologists, and other social scientists can tell us about how different citizens, cultures, and religions view the moral boundaries or the uses of human genetic engineering.

If human genetic modification Is fully legalized It will be done on the early, early stages of reproduction: from when It Is Just a sperm and an egg to the fetus stage, maybe a slight amount later. At this point of time It Is only legal to perform two types of advance reproductive technologies on humans. The first Is foretelling the egg with sperm In a test tube. This is used to determine the sex and what genes the baby will have, therefore knowing if using a different sperm/egg will be a better choice since one of the genes n the first tested set might be a genetic disease or the parents might prefer a different sex.

The second technique is much like the first. Embryos for a genetic disease; only selected embryos are implanted back into the mothers womb. This is called Pre-implantation Genetic Diagnosis. Now I will discuss what good can come of legalizing human genetic engineering. Really the most useful application of human genetic engineering is preventing hereditary diseases, disabilities and defects/doodlers. Examples include: Down syndrome, Diabetes, color blindness and even allergies.

Stopping these diseases/doodlers before the baby Is even born can help prevent a lot of Issues from happening In the childs future and can possibly save lives. Eventually the disease/disorder will die out because the gene has been removed from the generations making it unable to be passed down. Another application could involve stimulating muscle growth/brain development in turn making the child more athletic or more brainy also changing your childs physical features and traits, such as eye color and hair color.

Now for the bad: Although changing your childs physical traits, deciding to make them more muscular or more smart can seem like a good thing to a some people it is also viewed as a bad thing to some people. Things like a perfect race could arise from these problems, or baby trends, where it Is trendier that year for your kids to have blonde hair then It Is for them to have black or blue eyes rather than green. This Is generally the topic that Is the most talked amongst the public when discussing human genetic engineering.

Other social Issues can be raised such as It Is against gods will, countries creating super human soldiers, countries becoming more like the class system e: people who run business, there is also the issue of the child not having the choice to be genetically modified, the individuality of humans and coasts of genetically modifying also comes into play, such as, can only the rich afford it? From a biological point of view genetic modification could eventually make some genes extinct in a way, where they are no longer needed/deemed useless or maybe they go out of fashion.

In my opinion, I think that genetic modification in humans should be legal, but should only be used for hereditary diseases, disabilities and disorders which help the child but things like letting the parent chose the childs traits do not help the child and he/she also loses their individuality. Also there is the fact that the child doesnt have a choice at what the parents will make them look like. Changing the traits of a child through genetic engineering does not benefit the child and only pleases the parents. In

Conclusion to this essay, there is a high chance that human genetic engineering will be available soon and when it does it will be a very controversial issue, both on a biological and a social point of view. Most social issues come from a negative stand point and are mainly on the regulation of it (coasts, who can use it, what countries can do with it). There is no straight forward answer to the question of should human genetic modification be legal. Although there is a large amount of health benefits, the negative social issues may outweigh them. Word Count: 839

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Research published in the journal Nature has analysed the DNA of 10,503 Pakistanis who were participating in a Pakistan Risk of Myocardial Infarction Study (PROMIS) and discovered 1,317 disabled or knocked-out genes.

People who are natural knockouts, that is, they were born missing one or more genes without any obvious medical problems are few and far between.

Humans inherit two copies of every gene one from the mother and one from the father.

If one copy is damaged or inactivated, then the presence of the other fully functional copy may help alleviate most problems.

However, if the parents are biologically related, then the chances of inheriting two inactivated copies are much higher.

The person with two inactivated copies may not have the functioning protein at all and will be a natural knockout for that specific gene.

The high number of human knockouts found in the country is due to the cultural tradition of cousin marriages that is prevalent here.

A search for human knockouts has also been conducted in other countries including Iceland and the United Kingdom.

In order to study what a particular gene does, scientists have traditionally made use of genetic engineering to breed mice with a mutation in that gene (as this type of experimentation is not possible with humans).

Once they have discovered what the gene does, it is possible to make new drugs that can either block a gene if it is harmful or enhance its positive functions if it turns out to be useful.

However, while such research is informative, evidence from studies in animal knockouts often does not hold for humans.

This is explained by a substantial number of failures seen in recent clinical trials that tested new drugs for the prevention of coronary heart disease.

Read more: The Tech Healthcare Revolution Pakistan Needs

Studies in human knockouts can provide data regarding whether natural inhibition of a given pathway is useful or not, says Dr. Danish Saleheen, lead author and principal investigator of the study published in Nature.

This evidence could be translated to develop new drugs, and prioritise or deprioritise existing drug programs.

Some knocked-out genes protect against disease.

Absence of the gene ALOX5 protects against stress-induced memory deficits, synaptic dysfunction and tauopathy which can help prevent Alzheimers disease or lower its progression.

The discovery of a human PCSK9 knockout who had astonishingly low levels of LDL cholesterol and up to 90 per cent less chances of getting a heart attack has resulted in the development of a new class of drugs that could prevent heart disease.

The Nature research study discovered that individuals without the gene APOC3 were protected against coronary heart disease.

The protein Apo-CIII is encoded by the APOC3 gene and inhibits hepatic uptake of fats called triglycerides.

The team was able to study a family of Pakistanis missing both copies of the APOC3 gene.

The human knockouts were given an oral fat load in the form of a milkshake.

When compared to other family members who had the gene, individuals with an absence of APOC3 didnt get a significant postprandial rise in their blood fat levels and were perfectly healthy.

This showed the human knockouts had little artery-clogging fat in their body and had a considerably lower risk of getting a heart attack.

So the research team was able to reason that ApoC-IIIblocking drugs that are currently in clinical trials could be beneficial in preventing heart disease.

The team was only able to make this discovery after identifying an entire family of natural knockouts for APOC3 in Pakistan.

They had been searching for the past four years for someone who was missing both copies of the gene but hadnt found a single person in the United States and Europe.

It was only in Pakistan that they were able to discover a family with both parents and nine children all of whom were missing the gene.

Read more: Is a permanent cure for diabetes on the cards?

This Pakistani research study is reportedly the first time where the knockouts found have been tested and their blood biomarkers like cholesterol have been studied to discover more about their health.

As part of this study, knockouts have been found that have not been seen anywhere else in the world.

This includes knockouts for NRG4, A3GALT2 and CYP2F1 among others.

In addition, the study found 734 genes where both copies were affected by predicted loss-of-function mutations (double knock-outs) which had never been described before.

This cohort of individuals provides a great opportunity for further study and more extensive phenotyping, says Dr. James Peters, Clinical Research Fellow at the British Heart Foundation.

A particular strength of this study is that individuals with a specific mutation can be contacted and brought back for further detailed measurements, he adds.

However, some geneticists caution that drugs made from this kind of genetic analysis might not be effective.

In an article, geneticist Stephen Rich from the University of Virginia in Charlottesville says that inhibiting ApoC-III late in life may not mimic being born with an APOC3 mutation, which protects for a lifetime.

The research team is now calling for a human knockout project to make one complete database for all the information coming from new genetics studies.

The project would make it possible to systematically conduct deep phenotyping studies on human knockouts and learn more about the natural deletion of those genes in humans.

In the future, the team plans on testing the genomes of 200,000 participants from Pakistan to find knockouts of approximately 8,000 genes.

Such studies provide unprecedented opportunities to understand the function of genes and provide important insights into the development of drugs, says Dr. Saleheen.

This research study was the result of an international collaboration between scientists from Pakistan, the United Kingdom and the United States.

This story originally appeared on MIT Tech Review Pakistan and has been reproduced with permission.

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Study finds 1317 knocked-out genes in DNA samples from Pakistanis - DAWN.com

In BriefCRISPR technology is transforming biomedical research and isat the heart of numerous recent discoveries but if no one can payfor treatments it produces, how will we make use of it? Expertshave a range of ideas to solve this knotty problem. Paying For Cures

CRISPR, a gene editing tool, is at the heart of numerous new medical treatments and technologies. Some of the incredible uses of CRISPR weve seen in the past year alone include editing phagesto kill antibiotic-resistant bacteria; targeting cancers command centerin mice, boosting survival rates from 0 to 100 percent; repairing the gene defects that cause sickle cell disease; and copying the T-cells of naturally HIV-immune individuals.

However, even as CRISPR moves toward clinical trials and practical use, its future remains unclear. This is due to the extreme cost of CRISPR treatments; most people simply cannot afford them, and whether insurance carriers will pay the tab is uncertain. Some insurance companies have already implemented no coverage policies for gene therapies; the American healthcare system is ever-changing, and its seeming increasingly likely that these extremely expensive therapies might be out of reach even for people with insurance.

StatNews reports that oncologist and author Dr. Siddhartha Mukherjee, who wrote the bestseller Emperor of All Maladies, told the American Society of Clinical Oncology in spring that the world would soon be divided into the rich who can afford personalized cancer treatment and the poor who cannot. The case of Glybera, a gene therapy infamously called the most expensive drug in the world, adds more credence to this concern. At a whopping $1.4 million per patient, Glybera was sold only once in Germany, abandoned in the EU, and never came to the US market due to its cost.

Much of the issue arises as we try to treat and cure rare diseases, which the United States defines as diseases that affect fewer than 200,000 people and the European Union defines as one that affects fewer than 1 in 2,000 people. However, cumulatively, rare diseases effect an estimated 25 to 30 million Americans, and there could be up to7,000 rare diseases.

The tension comes at the nexus between multiple market forces: drug companies who want to invest in research and profit from their investment; insurance companies who must maximize profit for shareholders while insuring as many people as possible; governments and leaders with different policies about intervention into the system; scientists who may have independent interest in conducting research but must find a way to fund it; and patients (some with insurance, some without) who are interested or, in some cases, desperate for treatments and cures. How to relieve the tension and allow science to progress in the best way for the most people is a difficult question, but various experts have ideas.

University of Alberta law and policy expert Tania Bubela suggests toStatNews that insurers should be allowed to reimburse drug companies for gene therapies before they receive FDA approval, requiring them to amass more data before increasing drug costs to full price. Another partial solution might be to grant CRISPR licenses one gene at a time rather than issuing exclusive patents on tools like CRISPR. Other creative intellectual property strategies have been proposed by the Rare Genomics Institute. Pediatric oncologist Stuart Orkin and Phillip Reilly, a Third Rock Ventures partner, along with FDA commissioner Scott Gottlieb, advocate for spreading insurer payments to companies out over years of time contingent upon the drugs continued performance, a sort of annuities structure; this would recognize the value in paying for even expensive drugs rather than years of care and treatment for expensive diseases.

Some form of government intervention is probably inevitable, according to most experts. The US Orphan Drug Act, for example, facilitates the development of treatments and drugs for rare diseases; Orkin and Reilly argue that funds from the Act could pay for gene therapies. The 2009 Biologics Price Competition and Innovation Act made generic biologics, called biosimilars, possible. However, generic forms of CRISPR are not likely to come for decades. Where does this leave us?

StatNews writer Jim Kozubek frames the ultimate issue, suggesting two possible outcomes. One of two things will happen: either we will embrace a national health care system with broad access but that severely limits expensive new drugs, gene therapies, and CRISPR-based biologics; or these treatments will be available to only the wealthiest among us who can pay for them, a dystopian vision which is perverse but perhaps more realistic considering the pressures for a return on investment.

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Is Getting Genetically Engineered a Human Right? - Futurism

A new study by Transparency Market Research indicates that the degree of competitive rivalry in genome engineering rivalry market is likely to remain moderate over the forecast period owing to the presence of a limited number of international and regional players. Sigma-Aldrich Corporation, Thermo Fisher Scientific Inc., and Sangamo Biosciences Inc. are among the prominent revenue contributors to the market. The entry of small regional players in the arena is prompting global players to pay high attention to product innovation.

To develop innovative, technologically advanced and differentiated products, the leading companies are banking on agreements with laboratories and research institutes and pouring funds into ongoing research and development projects, says the author of the report. The global market for Genome Engineering is anticipated to reach a valuation of US$7.21 bn by 2023 from US$2.30 bn in 2015, expanding at a remarkable CAGR of 14.2% from 2015 to 2023.

North America to Remain Ahead through 2023, thanks to Upswing in Research and Development Activities

By end user, the market will be dominated by the biotechnology and pharmaceutical companies throughout the forecast period. The growth of the segment can be attributed to the rising use of genome engineering technologies in drug discovery and therapeutics. North America will continue to be the frontrunner in the global arena until 2023, rising to a valuation of US$3.68 bn. The widening applications of genome engineering resulting from the increasing research and development activities are contributing to the growth of the region. Asia Pacific will be the most promising regional market, thanks to the increasing government incentives.

Increasing Funding by Biotechnology and Pharmaceutical Organizations to Augment Genome Engineering Market

Pharmaceutical and biotechnology companies worldwide are increasingly realizing the need for advanced gene editing technologies for detecting genetic anomalies. As a result, the number of research and development activities is rising at a significant pace. Large organizations are focusing towards cell mutation to curb genetic and cell diseases. To encourage the development of technologies relating to gene editing, pharmaceutical companies are either funding ongoing projects of medical firms or entering into a collaboration with them, says a TMR analyst. Therefore, the increasing research and development activities in the field of gene editing is paving for genome engineered techniques.

The growing investments by governments and non-government organizations in genome research and technological advancements along with the funding by pharmaceutical and biotechnology are providing a fillip to the global genome engineering market.

Rising Opposition on Ethical Grounds to Hamper Growth Prospects

Over the past few years, genetic engineering has received a lot of opposition on ethical grounds from several health, social, and religious organizations. According to the U.S. National Institute of Health (NIH), genetic engineering of human embryos leads to complications in human genes and has, therefore, prohibited its funding. In addition, various social organizations are persistent about the ban of genetic engineering as the alteration in animal genes can adversely affect the genetic makeup of the coming generations of the animal along with hampering the lifespan of the genetically engineered animal.

Along with the rising ethical concerns, the stringent regulatory framework for the approval of genetic modifications in plants, animals, and human genome are acting as a major bottleneck in the growth of the global genome engineering market. Nevertheless, the growing adoption of genome engineering technologies in agriculture for crop improvement is opening new avenues for players in the market.

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Genome Engineering Market: Leading Players Need to Focus on Product Innovation to Maintain their Prominence - Edition Truth

The team's results, posted as a preprint in BioRxiv earlier this month, proposed a handful of ACE2 variants suspected of boosting SARS-CoV-2 binding and, potentially, host susceptibility, along with several variants predicted to dial down ACE2 interactions with the viral spike protein that may be protective.

"What we can conclude is that this new virus has evolved new modality to interact with the ACE2 receptor," Jura noted. "Unfortunately, it seems like there are polymorphisms in the human population that will make some individuals more susceptible to binding this virus because these mutations are enhancing this unique part of the interface."

Seshagiri noted that such insights might make it possible to design potential therapeutic versions of ACE2 that are particularly adept at binding coronavirus spike proteins, thereby preventing the viruses from interacting with an individual's own ACE2 receptors, for example.

In a recent Cell paper, a team from Sweden, Spain, Austria, and Canada proposed its own strategy for engineering soluble, clinical-grade forms of the human ACE2 protein that appeared to dial down early-stage infections by SARS-CoV-2 in otherwise susceptible cell types.

"We are not the first to come up with the idea of saying ACE2 could be a therapeutic," he said, though he suggested that engineering soluble forms of the receptors protein that bind well to SARS-CoV-2 may serve as a strategy for "future proofing" against the emergence of these and other related viruses down the road.

The researchers plan to profile ACE2 polymorphisms in still more human samples for the final version of the study, which will likely be submitted for peer review in the coming weeks, Seshagiri said.

He and MedGenome CEO Rayman Mathoda noted that the diagnostic company, which is active in India and other emerging markets, is also a founding member of a GenomeAsia 100K project.

"We've made a very intentional effort to build on a data-focused set of efforts, where we take our proprietary data as we grow, but build in other data source," Mathoda said.

The investigators are not alone in attempting to establish a baseline understanding of ACE2 variation across and within populations.

At the University of Siena in northern Italy, Alessandra Renieri and her colleagues have been delving into ACE2 genetic variation using available exome sequences for some 7,000 healthy participants in the Network of Italian Genomes project. As they reported in a preprint posted to MedRxiv in early April, the investigators saw significant variation in ACE2 in that retrospective dataset, including both common and rare, missense variants predicted to influence the protein's stability and its interactions with the coronavirus viral spike.

"There is pretty wide genetic variability," Renieri said. "There are both polymorphisms, so variants found in a percentage of the population, and there are also rare variants a lot of rare variants."

It may be possible for the individual centers participating in the Network of Italian Genomes to recontact individuals in the future to try to find out who became infected with SARS-CoV-2 and to assess ACE2 variation alongside clinical outcomes, Renieri noted, though she cautioned that "ACE2 is just one of the many genes that could be involved."

For the reCOVID project, members of the team are seeking funding through the European Commission's Innovative Medicines Initiative IMI2 call for proposals to do functional analyses on ACE2 and other genes, for example, in the hopes of developing candidate therapeutics.

Renieri is also part of a team that been working since mid-March to prospectively collect samples from 2,000 COVID-19 patients at least 21 different hospitals in Italy as part of the GEN-COVID study, part of the COVID-19 Host Genetics Initiative.

For that project, researchers in Italy will use whole-exome sequencing to assess patient samples collected in conjunction with very detailed clinical information, she explained, while collaborators in Finland will genotype the samples for a related genome-wide association study.

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A gene that could unlock the mysteries of COVID-19 - ModernHealthcare.com

References

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2. B. Zhang et al., Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis, Nat. Materials 15, 669678 (2016), doi:10.1038/nmat4570.

3. S. Shukla et al., Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1, Nat. Methods 14(5), 531-538 (May 2017),doi: 10.1038/nmeth.4258. Epub Apr 10, 2017.

4. M.M. Pakulska, S. Miersch, and M.S. Shoichet, Designer protein delivery: from natural occurring to engineered affinity controlled release systems, Science 351(6279):aac4750, doi: 10.1126/science.aac4750.

5. M.M. Pakulska, C.H. Tator, and M.S. Shoichet, Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1 promotes functional repair in the injured rat spinal cord, Biomaterials (accepted April 2017).

6. TissueGene, TissueGene to Highlight Invossa, the Worlds First Cell-Mediated Gene Therapy for Degenerative Osteoarthritis, at JP Morgan Healthcare Conference, Press Release,accessed June 12, 2017.

7. O.J.L. Rackham et al., A predictive computational framework for direct reprogramming between human cell types, Nat. Genetics 48, 331335 (2016), doi:10.1038/ng.3487.

8. D.B. Kolesky et al., Three-dimensional bioprinting of thick vascularized tissue, Proc. Natl. Acad. Sci. U.S.A. 113 (12), 31793184, doi: 10.1073/pnas.1521342113.

9. M.M. Laronda et al., A Bioprosthetic Ovary Created Using 3D Printed Microporous Scaffolds Restores Ovarian Function in Sterilized Mice, Nat. Commun. 8, 15261 (May 16, 2017).

10. I. Sagi et al., Derivation and differentiation of haploid human embryonic stem cells, Nature 532, 107111 (April 7, 2016), doi:10.1038/nature17408.

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GEN Roundup: Top Trends in Tissue Engineering - Genetic Engineering & Biotechnology News

Structure of the nCoV trimeric spike

The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryoelectron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV.

Science, this issue p. 1260

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryoelectron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

The novel coronavirus 2019-nCoV has recently emerged as a human pathogen in the city of Wuhan in Chinas Hubei province, causing fever, severe respiratory illness, and pneumoniaa disease recently named COVID-19 (1, 2). According to the World Health Organization (WHO), as of 16 February 2020, there had been >51,000 confirmed cases globally, leading to at least 1600 deaths. The emerging pathogen was rapidly characterized as a new member of the betacoronavirus genus, closely related to several bat coronaviruses and to severe acute respiratory syndrome coronavirus (SARS-CoV) (3, 4). Compared with SARS-CoV, 2019-nCoV appears to be more readily transmitted from human to human, spreading to multiple continents and leading to the WHOs declaration of a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 (1, 5, 6).

2019-nCoV makes use of a densely glycosylated spike (S) protein to gain entry into host cells. The S protein is a trimeric class I fusion protein that exists in a metastable prefusion conformation that undergoes a substantial structural rearrangement to fuse the viral membrane with the host cell membrane (7, 8). This process is triggered when the S1 subunit binds to a host cell receptor. Receptor binding destabilizes the prefusion trimer, resulting in shedding of the S1 subunit and transition of the S2 subunit to a stable postfusion conformation (9). To engage a host cell receptor, the receptor-binding domain (RBD) of S1 undergoes hinge-like conformational movements that transiently hide or expose the determinants of receptor binding. These two states are referred to as the down conformation and the up conformation, where down corresponds to the receptor-inaccessible state and up corresponds to the receptor-accessible state, which is thought to be less stable (1013). Because of the indispensable function of the S protein, it represents a target for antibody-mediated neutralization, and characterization of the prefusion S structure would provide atomic-level information to guide vaccine design and development.

Based on the first reported genome sequence of 2019-nCoV (4), we expressed ectodomain residues 1 to 1208 of 2019-nCoV S, adding two stabilizing proline mutations in the C-terminal S2 fusion machinery using a previous stabilization strategy that proved effective for other betacoronavirus S proteins (11, 14). Figure 1A shows the domain organization of the expression construct, and figure S1 shows the purification process. We obtained ~0.5 mg/liter of the recombinant prefusion-stabilized S ectodomain from FreeStyle 293 cells and purified the protein to homogeneity by affinity chromatography and size-exclusion chromatography (fig. S1). Cryoelectron microscopy (cryo-EM) grids were prepared using this purified, fully glycosylated S protein, and preliminary screening revealed a high particle density with little aggregation near the edges of the holes.

(A) Schematic of 2019-nCoV S primary structure colored by domain. Domains that were excluded from the ectodomain expression construct or could not be visualized in the final map are colored white. SS, signal sequence; S2, S2 protease cleavage site; FP, fusion peptide; HR1, heptad repeat 1; CH, central helix; CD, connector domain; HR2, heptad repeat 2; TM, transmembrane domain; CT, cytoplasmic tail. Arrows denote protease cleavage sites. (B) Side and top views of the prefusion structure of the 2019-nCoV S protein with a single RBD in the up conformation. The two RBD down protomers are shown as cryo-EM density in either white or gray and the RBD up protomer is shown in ribbons colored corresponding to the schematic in (A).

After collecting and processing 3207 micrograph movies, we obtained a 3.5--resolution three-dimensional (3D) reconstruction of an asymmetrical trimer in which a single RBD was observed in the up conformation. (Fig. 1B, fig. S2, and table S1). Because of the small size of the RBD (~21 kDa), the asymmetry of this conformation was not readily apparent until ab initio 3D reconstruction and classification were performed (Fig. 1B and fig. S3). By using the 3D variability feature in cryoSPARC v2 (15), we observed breathing of the S1 subunits as the RBD underwent a hinge-like movement, which likely contributed to the relatively poor local resolution of S1 compared with the more stable S2 subunit (movies S1 and S2). This seemingly stochastic RBD movement has been captured during structural characterization of the closely related betacoronaviruses SARS-CoV and MERS-CoV, as well as the more distantly related alphacoronavirus porcine epidemic diarrhea virus (PEDV) (10, 11, 13, 16). The observation of this phenomenon in 2019-nCoV S suggests that it shares the same mechanism of triggering that is thought to be conserved among the Coronaviridae, wherein receptor binding to exposed RBDs leads to an unstable three-RBD up conformation that results in shedding of S1 and refolding of S2 (11, 12).

Because the S2 subunit appeared to be a symmetric trimer, we performed a 3D refinement imposing C3 symmetry, resulting in a 3.2--resolution map with excellent density for the S2 subunit. Using both maps, we built most of the 2019-nCoV S ectodomain, including glycans at 44 of the 66 N-linked glycosylation sites per trimer (fig. S4). Our final model spans S residues 27 to 1146, with several flexible loops omitted. Like all previously reported coronavirus S ectodomain structures, the density for 2019-nCoV S begins to fade after the connector domain, reflecting the flexibility of the heptad repeat 2 domain in the prefusion conformation (fig. S4A) (13, 1618).

The overall structure of 2019-nCoV S resembles that of SARS-CoV S, with a root mean square deviation (RMSD) of 3.8 over 959 C atoms (Fig. 2A). One of the larger differences between these two structures (although still relatively minor) is the position of the RBDs in their respective down conformations. Whereas the SARS-CoV RBD in the down conformation packs t
ightly against the N-terminal domain (NTD) of the neighboring protomer, the 2019-nCoV RBD in the down conformation is angled closer to the central cavity of the trimer (Fig. 2B). Despite this observed conformational difference, when the individual structural domains of 2019-nCoV S are aligned to their counterparts from SARS-CoV S, they reflect the high degree of structural homology between the two proteins, with the NTDs, RBDs, subdomains 1 and 2 (SD1 and SD2), and S2 subunits yielding individual RMSD values of 2.6 , 3.0 , 2.7 , and 2.0 , respectively (Fig. 2C).

(A) Single protomer of 2019-nCoV S with the RBD in the down conformation (left) is shown in ribbons colored according to Fig. 1. A protomer of 2019-nCoV S in the RBD up conformation is shown (center) next to a protomer of SARS-CoV S in the RBD up conformation (right), displayed as ribbons and colored white (PDB ID: 6CRZ). (B) RBDs of 2019-nCoV and SARS-CoV aligned based on the position of the adjacent NTD from the neighboring protomer. The 2019-nCoV RBD is colored green and the SARS-CoV RBD is colored white. The 2019-nCoV NTD is colored blue. (C) Structural domains from 2019-nCoV S have been aligned to their counterparts from SARS-CoV S as follows: NTD (top left), RBD (top right), SD1 and SD2 (bottom left), and S2 (bottom right).

2019-nCoV S shares 98% sequence identity with the S protein from the bat coronavirus RaTG13, with the most notable variation arising from an insertion in the S1/S2 protease cleavage site that results in an RRAR furin recognition site in 2019-nCoV (19) rather than the single arginine in SARS-CoV (fig. S5) (2023). Notably, amino acid insertions that create a polybasic furin site in a related position in hemagglutinin proteins are often found in highly virulent avian and human influenza viruses (24). In the structure reported here, the S1/S2 junction is in a disordered, solvent-exposed loop. In addition to this insertion of residues in the S1/S2 junction, 29 variant residues exist between 2019-nCoV S and RaTG13 S, with 17 of these positions mapping to the RBD (figs. S5 and S6). We also analyzed the 61 available 2019-nCoV S sequences in the Global Initiative on Sharing All Influenza Data database (https://www.gisaid.org/) and found that there were only nine amino acid substitutions among all deposited sequences. Most of these substitutions are relatively conservative and are not expected to have a substantial effect on the structure or function of the 2019-nCoV S protein (fig. S6).

Recent reports demonstrating that 2019-nCoV S and SARS-CoV S share the same functional host cell receptor, angiotensin-converting enzyme 2 (ACE2) (22, 2527), prompted us to quantify the kinetics of this interaction by surface plasmon resonance. ACE2 bound to the 2019-nCoV S ectodomain with ~15 nM affinity, which is ~10- to 20-fold higher than ACE2 binding to SARS-CoV S (Fig. 3A and fig. S7) (14). We also formed a complex of ACE2 bound to the 2019-nCoV S ectodomain and observed it by negative-stain EM, which showed that it strongly resembled the complex formed between SARS-CoV S and ACE2 that has been observed at high resolution by cryo-EM (Fig. 3B) (14, 28). The high affinity of 2019-nCoV S for human ACE2 may contribute to the apparent ease with which 2019-nCoV can spread from human to human (1); however, additional studies are needed to investigate this possibility.

(A) Surface plasmon resonance sensorgram showing the binding kinetics for human ACE2 and immobilized 2019-nCoV S. Data are shown as black lines, and the best fit of the data to a 1:1 binding model is shown in red. (B) Negative-stain EM 2D class averages of 2019-nCoV S bound by ACE2. Averages have been rotated so that ACE2 is positioned above the 2019-nCoV S protein with respect to the viral membrane. A diagram depicting the ACE2-bound 2019-nCoV S protein is shown (right) with ACE2 in blue and S protein protomers colored tan, pink, and green.

The overall structural homology and shared receptor usage between SARS-CoV S and 2019-nCoV S prompted us to test published SARS-CoV RBD-directed monoclonal antibodies (mAbs) for cross-reactivity to the 2019-nCoV RBD (Fig. 4A). A 2019-nCoV RBD-SD1 fragment (S residues 319 to 591) was recombinantly expressed, and appropriate folding of this construct was validated by measuring ACE2 binding using biolayer interferometry (BLI) (Fig. 4B). Cross-reactivity of the SARS-CoV RBD-directed mAbs S230, m396, and 80R was then evaluated by BLI (12, 2931). Despite the relatively high degree of structural homology between the 2019-nCoV RBD and the SARS-CoV RBD, no binding to the 2019-nCoV RBD could be detected for any of the three mAbs at the concentration tested (1 M) (Fig. 4C), in contrast to the strong binding that we observed to the SARS-CoV RBD (fig. S8). Although the epitopes of these three antibodies represent a relatively small percentage of the surface area of the 2019-nCoV RBD, the lack of observed binding suggests that SARS-directed mAbs will not necessarily be cross-reactive and that future antibody isolation and therapeutic design efforts will benefit from using 2019-nCoV S proteins as probes.

(A) SARS-CoV RBD shown as a white molecular surface (PDB ID: 2AJF), with residues that vary in the 2019-nCoV RBD colored red. The ACE2-binding site is outlined with a black dashed line. (B) Biolayer interferometry sensorgram showing binding to ACE2 by the 2019-nCoV RBD-SD1. Binding data are shown as a black line, and the best fit of the data to a 1:1 binding model is shown in red. (C) Biolayer interferometry to measure cross-reactivity of the SARS-CoV RBD-directed antibodies S230, m396, and 80R. Sensor tips with immobilized antibodies were dipped into wells containing 2019-nCoV RBD-SD1, and the resulting data are shown as a black line.

The rapid global spread of 2019-nCoV, which prompted the PHEIC declaration by WHO, signals the urgent need for coronavirus vaccines and therapeutics. Knowing the atomic-level structure of the 2019-nCoV spike will allow for additional protein-engineering efforts that could improve antigenicity and protein expression for vaccine development. The structural data will also facilitate the evaluation of 2019-nCoV spike mutations that will occur as the virus undergoes genetic drift and help to define whether those residues have surface exposure and map to sites of known antibody epitopes for other coronavirus spike proteins. In addition, the structure provides assurance that the protein produced by this construct is homogeneous and in the prefusion conformation, which should maintain the most neutralization-sensitive epitopes when used as candidate vaccine antigens or B cell probes for isolating neutralizing human mAbs. Furthermore, the atomic-level detail will enable the design and screening of small molecules with fusion-inhibiting potential. This information will support precision vaccine design and the discovery of antiviral therapeutics, accelerating medical countermeasure development.

Acknowledgments: We thank J. Ludes-Meyers for assistance with cell transfection, members of the McLellan laboratory for critical reading of the manuscript, and A. Dai from the Sauer Structural Biology Laboratory at the University of Texas at Austin for assistance with microscope alignment. Funding: This work was supported in part by a National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grant awarded to J.S.M. (R01-AI127521) and by intramural funding from NIAID to B.S.G. The Sauer Structural Biology Laboratory is supported by the University of Texas College of Natural Sciences and by award RR160023 from the Cancer Prevention and Research Institute of Texas (CPRIT). Author contributions: D.W. collected and processed cryo-EM data. D.W., N.W., and J.S.M. built and refined the atomic model. N.W. designed and cloned all constructs. D.W., N.W., K.S.C., J.A.G., and O.A. expressed and purified proteins. D.W., J.A.G., and C.-L.H. performed binding studies. B.S.G. and J.S.M. supervised experiments. D.W., B.S.G., and J.S.M. wrote the manuscript with input from all authors. Competing interests: N.W., K.
S.C., B.S.G., and J.S.M. are inventors on U.S. patent application no. 62/412,703 (Prefusion Coronavirus Spike Proteins and Their Use), and D.W., N.W., K.S.C., O.A., B.S.G., and J.S.M. are inventors on U.S. patent application no. 62/972,886 (2019-nCoV Vaccine). Data and materials availability: Atomic coordinates and cryo-EM maps of the reported structure have been deposited in the Protein Data Bank under accession code 6VSB and in the Electron Microscopy Data Bank under accession codes EMD-21374 and EMD-21375. Plasmids are available from B.S.G. under a material transfer agreement with the NIH or from J.S.M. under a material transfer agreement with The University of Texas at Austin.

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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation - Science Magazine

Space exploration has long been a source of fascination. Since the stars first captured our attention, we have obsessed over that vast curtain of darkness that lies beyond our atmosphere. But to what end? What ultimate goal does mankind strive towards, if not the ability to visit and colonize other worlds?

Before we can take our first steps out into the universe, we have to answer a critical question: Do we have the ability to adapt to other environments very different from what we have on Earth to not only survive, but to thrive? Instead of focusing on how we might terraform other planets to suit us, perhaps we should consider how we might use genetic engineering to alter own bodies to suit those other planets.

As a jumping off point, lets consider the feasibility of using the popular gene-editing tool CRISPR to alter human physiology to tolerate parameters outside of Earths norms. If we take a look at common factors that are significant to human health, gleaned from our experience with space exploration, the most obvious choices for our attention are variations in gravity, atmospheric pressure and gas ratios, and solar radiation levels.

If we consider Mars as our template, because of its relative suitability for colonization, then we must compensate for two-thirds less gravity than Earth. A lack of gravity results in a number of ill effects on human health, including a decrease in bone mass and density over time, particularly in the large bones of the lower extremities, as well as the spine. While we do not have research showing the impact of living on a planet with one-third Earths gravity, we do know that we can expect losses in bone density somewhere under 1-2 percent per month, the amount lost in the microgravity environment of space.

For comparison, the elderly lose 1-1.5 percent per month in Earth gravity. Atmospheric pressure that is either too high or too low also results in complications; low atmospheric pressure results in less oxygen available and causes altitude sickness and possible death. Radiation levels from the sun are another variable that is well known to have upper and lower thresholds for optimal human health, where low levels can lead to vitamin D deficiency and high levels increase cell death and cancer.

It would stand to reason that the human body has a minimum threshold for healthy physiology as regards the environment in which it grows, develops and lives. To colonize other planets successfully, we must consider solutions to overcome these thresholds; for example: prostheses, domed colonies recreating an ideal or near ideal environment, or, as this author suggests, the permanent genetic alteration of humanity as a species. This applies to our four chosen variables of gravitational forces, atmospheric pressure, atmospheric gas ratios, and solar radiation levels. While science fiction might have us consider surgical and biomedical prostheses or the more far-fetched use of animal DNA to change ourselves for this purpose, the key to human adaptation for other planets lies in our own genetics and it may well be CRISPR, the use of the enzyme Cas9 for introduction of altered DNA sequences or CRISPRs to existing cells to change how those cells function, that will make this possible.

Human genetic variation provides a veritable treasure trove of adaptations if one looks at the less common but heritable variations that on Earth may seem irrelevant, nonessential, or even maladaptive, but on another planet could be essential to survival. One example of a gene that, with engineering, could help humanity adapt to higher or lower gravity is the LRP5 gene. Recent research into the LRP5 gene shows that mutations of the gene are responsible for both low bone density and elevated bone density in the case of the later, from increased bone formation. A family of individuals in Nebraska carrying the mutation for elevated bone density have never experienced broken bones even well into old age. A whole colony of such individuals or ones engineered to enhance this mutation further could be expected to fare much better during prolonged space travel in zero gravity as well as in the low gravity environment on a planet like Mars.

While an atmospheric pressure and gas makeup very similar to Earths would be required for humans to survive and thrive outside of a spacesuit, Nepals Sherpas, high altitude dwellers in Ethiopia, and the Collas people in the Central Andes , as well as the deep sea divers of Bajau, may provide a solution to living on planets with differences in atmospheric pressure and oxygen availability. The three groups of high-altitude dwellers appear to have separate adaptations for thriving in low oxygen environments. Recent research indicates that there are genetic mutations in each of these groups. Sherpas mutations allow for more efficient use of available oxygen and resistance to ill effects from hypoxia.

Sherpas experience less of an increase in red blood cells than others and therefore avoid the ill-effects caused, such as edema and brain swelling. Sherpas instead have mitochondria in their cells that make more efficient use of the available oxygen, as well as having more efficient anaerobic metabolism in the absence of oxygen. The Collas show genetic differences in genes that control heart morphology, as well as cerebral vascular flow, as a means to withstand an elevated hematocrit in response to high altitude living. The Amhara people living in high altitudes in Ethiopia unlike the Sherpas do have lower oxygen saturation and higher hemoglobin levels compared to lowland dwellers in the region.

Research has yet to determine what adaptation favors the Amhara, but several genes that may play a role have been isolated. Another group, the Bajau of Thailand, may have complementary genetic variations that help them resist hypoxia and survive the high pressures of deep sea diving. Researchers found them to have 50% larger spleens and also a gene, PDE10A, that controls a thyroid hormone thought to affect spleen size. Capitalizing on any of these genetic features would improve our ability to survive with a lower oxygen content atmosphere, perhaps on a newly terraformed Mars or under domes with oxygen rationing.

While we cannot yet determine how comparable an atmosphere we can create on Mars, it stands to reason that achieving an exact replica atmosphere to Earths could be difficult. An atmosphere that lets in less radiation could impede our production of vitamin D, while a thinner atmosphere would admit an excess of radiation. Vitamin D deficiency could perhaps be handled by supplementation, or instead addressed by increasing our cells response to ultraviolet light to increase vitamin D synthesis. On the other side of the coin, a thinner atmosphere opens us up to higher UVR, which would result in higher rates of skin cancer.

It would stand to reason that, while skin pigmentation has high cultural and historical significance, it could make our species more suitable for colonization of high radiation planets; darker skin with larger melanocytes that react proactively to UVA and UVB radiation through tanning and higher antioxidant and free-radical counteraction would be protective and provide an advantage if we are to branch out into our solar system and beyond. At the same time, this solution poses the problem of vitamin D production.

The answer could lie in isolating and using the genes responsible for East Asian populations lower skin pigmentation coupled with lower skin cancer rates than European populations. A study headed by Pennsylvania university has isolated gene mutations responsible for skin pigmentation differences, SLC24A5, MFSD12, OCA2, and HERC2, by studying African, South Asian Indian, and Australo-Melanesian populations, some of which are associated with vitiligo and a form of albinism common in African populations. These mutations that confer higher vitamin D production to Europeans are not present in East Asians, indicating a different mutation responsible, and, while both populations have higher
vitamin D production than African populations, Europeans have a 10-20 percent higher rate of cancer than both Africans and East Asians. Further research into these genes could provide targets for CRISPR to modify the protective factors in our skin without sacrificing vitamin D production of potential colonists.

The question remains: is CRISPR a feasible route to including some of these adaptations to create a new, more suitable colonist? To answer this question we look at the current status of CRISPR research.

While some experiments using CRISPR gene editing were conducted in the technologys infancy, including the controversial creation of twin girls in China designed to be resistant to HIV, we are still quite a bit of research away from using CRISPR with high success rates and full confidence, especially considering the repercussions of rushing into human trials, including the death of trial participants and long-term side-effects of cancer, both of which have occurred in gene-therapy trials.

According to information revealed by the FDA and NIH, 691 trial volunteers died in gene-editing trials prior to the tragic and high-profile death of Jesse Gelsinger in a 1999 trial to treat his OTCD, a rare metabolic disorder. The death was blamed on ethical oversights and a rush to make gene editing pan out before it was ready. The result was a long period of gene-editing fear and oversight but also, in the case of James Wilson, director of the University of Pennsylvanias Institute for Human Gene Therapy responsible for the trials that led to Gelsingers death, greater caution in research methodology. He has put safety at the forefront of his research and asserts that even still the risks of gene editing with CRISPR and other methods brings enough risk to justify human trials only for those diseases that are severe and debilitating enough for patients to accept the risks of gene editing.

What does all this mean for our hypothetical future of using CRISPR to edit the DNA of human colonists for space colonization? Is the technology too far off to serve our purpose or fraught with too much risk? Is it beyond our knowledge and skill to accomplish? The answer to each of these questions is undoubtedly, no.

Weve had too much success in treating complex genetic conditions, like the creation of an immune system for Ashanthi Desilva born with severe combined immunodeficiency (SCVID). Weve unlocked too many keys to making gene therapy safer and more effective to discount the possibility of future use for the advancement of our species into harsher environments. While subsequent uses of gene therapy for SCVID resulted in development of Leukemia years later, further advancements in the research have revealed the need to find the best delivery system for each body system. Adeno-associated viruses, and lentiviruses are being looked at in place of the more aggressive adenovirus or retroviruses for delivery of DNA segments both of which are less likely to provoke an immune response and less likely to trigger cell death by way of the B35 gene in healthy cells, and later cancer.

Regardless of the work ahead and the bumpy road that gene therapy has traveled, vast potential remains at our fingertips whether it is through use of CRISPR or future gene therapy tools. It is a sure eventuality that we will one day have these skills at the ready to spread our species into other worlds, well-equipped to survive and thrive in harsher environments.

Cherrie Newman is a writer and student of human reproduction and biological sciences. She is the author of a science fiction novel series entitled Progeny under the pseudonym CL Fors. Follow her on her blogor on Twitter @clfors

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Building 'better' astronauts through genetic engineering could be key to colonizing other planets - Genetic Literacy Project

DUBLIN, March 12, 2020 /PRNewswire/ -- The "Cell Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

The cell-based markets was analyzed for 2018, and projected to 2028. The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair as well as diabetes mellitus will be other major markets.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 309 of these are profiled in part II of the report along with tabulation of 302 alliances. Of these companies, 170 are involved in stem cells.

Profiles of 72 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 67 Tables and 25 Figures. The bibliography contains 1,200 selected references, which are cited in the text.

This report contains information on the following:

The report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. Role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. Current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

Key Topics Covered

Part I: Technologies, Ethics & RegulationsExecutive Summary 1. Introduction to Cell Therapy2. Cell Therapy Technologies3. Stem Cells4. Clinical Applications of Cell Therapy5. Cell Therapy for Cardiovascular Disorders6. Cell Therapy for Cancer7. Cell Therapy for Neurological Disorders8. Ethical, Legal and Political Aspects of Cell therapy9. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions10. Markets and Future Prospects for Cell Therapy11. Companies Involved in Cell Therapy12. Academic Institutions13. References

For more information about this report visit https://www.researchandmarkets.com/r/sy4g72

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

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Worldwide Cell Therapy Market Projections to 2028 - The Largest Expansion Will Be in Diseases of the Central Nervous System, Cancer and Cardiovascular...

Reported Initial Clinical Data from FT500 Phase 1 Study in Advanced Solid Tumors, Supporting Safety and Tolerability of Multi-dose Treatment Paradigm for Off-the-shelf, iPSC-derived NK Cells

First Patients Treated with FT516, the First-ever Engineered iPSC-derived Cellular Immunotherapy, for AML and for B-cell Lymphoma in Combination with Rituximab

Initiated Enrollment of First-in-human Clinical Trial of FT596, the First-ever Cellular Immunotherapy Engineered with Three Active Anti-tumor Modalities

Ended Quarter with $261 Million in Cash, Cash Equivalents and Marketable Securities

SAN DIEGO, March 02, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, today reported business highlights and financial results for the fourth quarter ended December 31, 2019.

In 2019, we made tremendous progress in pioneering the clinical development of off-the-shelf, iPSC-derived cancer immunotherapy. Our FT500 program demonstrated that multiple doses of iPSC-derived NK cells can be delivered off-the-shelf to a patient in a safe manner without patient matching. Additionally, our FT516 program provided initial clinical evidence that engineered iPSC-derived NK cells may confer anti-tumor activity and deliver clinically meaningful benefit to patients. We also showed the unmatched scalability of our proprietary iPSC product platform, having manufactured hundreds of cryopreserved, infusion-ready doses of our iPSC-derived NK cell product candidates at a low cost per dose in our new GMP manufacturing facility, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. In 2020, we look forward to additional clinical data from our FT500 and FT516 programs, and initial clinical data from FT596, our ground-breaking iPSC-derived CAR NK cell product candidate for the treatment of B-cell malignancies designed to overcome many of the limitations inherent in current CAR T-cell immunotherapies. We also expect to begin clinical investigation of our off-the-shelf, iPSC-derived NK cell programs in multiple myeloma with planned IND submissions for FT538, the first-ever CRISPR-edited, iPSC-derived cell therapy, and for FT576, our multi-antigen targeted, CAR-BCMA product candidate. Finally, under our collaboration with Memorial Sloan Kettering, we strive to be the first group in the world to bring off-the-shelf, iPSC-derived CAR T-cell therapy to patients.

Clinical Programs

Preclinical Pipeline

Fourth Quarter 2019 Financial Results

Today's Conference Call and Webcast

The Company will conduct a conference call today, Monday, March 2, 2020 at 5:00 p.m. ET to review financial and operating results for the quarter ended December 31, 2019. In order to participate in the conference call, please dial 877-303-6229 (domestic) or 631-291-4833 (international) and refer to conference ID 9879730. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company's website at http://www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

Story continues

About FT500

FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (NCT03841110). The study is designed to assess the safety and tolerability of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies nivolumab, pembrolizumab or atezolizumab in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or their disease progresses on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.

About FT516

FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, the FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial in combination with monoclonal antibody therapy, including PDL1-, PD1-, EGFR- and HER2-targeting therapeutic antibodies, across a broad range of solid tumors.

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain
and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label Phase 1 clinical trial as a monotherapy, and in combination with rituximab, for the treatment of advanced B-cell lymphoma and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia (NCT04245722).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Companys results of operations, financial condition and sufficiency of its cash and cash equivalents to fund its operations, as well as statements regarding the advancement of and plans related to its product candidates, clinical studies and preclinical research and development programs, the Companys progress, plans and timelines for the manufacture and clinical investigation of its product candidates, the timing for the Companys receipt of data from its clinical trials and preclinical studies, the Companys development and regulatory strategy, and the therapeutic and market potential of the Companys product candidates. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in prior studies of the Companys product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Companys product candidates or in the initiation of, or enrollment of patients in, any clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in patient enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that the Companys expenditures may exceed current expectations for a variety of reasons. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Availability of Other Information about Fate Therapeutics, Inc.

Investors and others should note that the Company routinely communicates with investors and the public using its website (www.fatetherapeutics.com) and its investor relations website (ir.fatetherapeutics.com) including, without limitation, through the posting of investor presentations, SEC filings, press releases, public conference calls and webcasts on these websites. The information posted on these websites could be deemed to be material information. As a result, investors, the media, and others interested in Fate Therapeutics are encouraged to review this information on a regular basis. The contents of the Companys website, or any other website that may be accessed from the Companys website, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.

Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)(unaudited)

Condensed Consolidated Balance Sheets(in thousands)(unaudited)

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

Continued here:
Fate Therapeutics Reports Fourth Quarter 2019 Financial Results and Operational Progress with 2020 Outlook - Yahoo Finance

By John Stonestreet, Christian Post Guest Columnist | Tuesday, March 03, 2020 A Catholic faithful participates in the traditional Ash Wednesday service at the 20 de Julio Church in Bogota, Colombia, February 10, 2016. Wednesday marked the first day of the 40-day period of Lent during which Roman Catholics are called to make some form of sacrifice, usually by fasting for a short period of time. | (Photo: Reuters/John Vizcaino)

As Western culture becomes more and more secular, or to use Charles Taylors fascinating word disenchanted, traditions and practices once largely normal seem more and more strange. Large families, choosing church over Little League, or smudged foreheads just arent as normal as they used to be, and the second glances or raised eyebrows they create reveal more than a confusion about the thing itself.

In fact, Im not sure there is a Christian observance that more directly collides with the widely accepted values of secularism than the imposition of the ashes, a tradition that goes back about ten centuries and marks the beginning of the season of Lent on the Church calendar.

Like Advent, the season of Lent is about preparation. Before Christmas, our Christian forebears thought it wise to prepare a bit, and that by diving deeply into Old Testament promises and prophecies wed better understand the birth of Christ in the full context of redemptive history. So too, in Lent, our Christian forbears thought it wise to prepare for Holy week, especially for celebrating the resurrection on Easter Sunday.

A key distinction is that Lenten disciplines, beginning with Ash Wednesdays reminder that You are dust and to dust you shall return, place our celebration of resurrection in the context of our humanity, both ourmortalityand ourfallenness. Even if the church calendar and its accompanying disciplines is not part of your church tradition, these two aspects of our humanity deserve our focused, intentional, and extended reflection.

Of course, most Christians would quickly reply that,of course,sin and death affect us all post-Eden. The problem is, in a secular culture, these beliefs that are crucial to a Christian worldview can be subtly secularized in our own hearts and minds.

Years ago, when my grandfather was dying, he suffered terribly for three or four months. In sorrow, I asked my pastor, Why doesnt God just take him? I expected him to say something along the lines of, Well, God has His ways, and His own timing, but instead he said something Ill never forget: Because your grandfather needs to know his mortality before he meets his maker.

What Ponce de Leon once sought in the waters of a Fountain of Youth, we still seek today via genetic engineering, eugenics, and other technologies. In other words, we seek control over this world and even over death itself.

Despite our search, death remains the universal problem of the human condition, one that afflicts us all. A secular culture is led by the reality of death to fear death itself, so that we either attempt to control death or distract ourselves from the thought of it. As a result, we learn to live life in light of the moment, rather than eternity.

The reality of death should, instead, remind us to fear God. That after death, we will meet the maker of life, is worth pondering, not just at the moment of death, but constantly throughout our lives.

Theologian Craig Gay warned in his book The Way of the Modern World that many of us who believe in God live as if God were largely irrelevant to most of life. The reminder of our mortality in the words, You are but dust and to dust you shall return, is a wonderful antidote for what he called practical atheism.

Just like with the idea ofmortality,our understanding of our ownsinfulnessis also under threat of being secularized in our own minds. In a culture committed, in the name of freedom, to removing the categories of sin or guilt, one quick to give away nearly universal get-out-of-jail-free cards in the name of sexual freedom, too many Christians lose any abhorrence for that which ought shock and shame us.

Perhaps this is why the salvation brought by Christs life, death, and resurrection is so often described as a wonderful example of love and sacrifice or how to gain purpose and perspective, but so rarely in the terms of judicial forgiveness and cosmic victory that Paul and Peter and Jesus Himself so often used.

Being confronted with our ownsinfulnessis certainly no fun, but God graciously does it. After all, the cruelest thing to tell someone whos not okay is that they are, as both secularized cultures and secularized churches too often do. Repentance is a gift, the only way forward for those on the edge of the moral abyss. Its proof that God is kind, the Scriptures say.

We just dont hear these things often enough. So, thank God for Lent.

Originally posted at breakpoint.org

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Lent, the reality of death, and fearing God - Christian Post

As the labour market rapidly changes, new, nearly real-time data and metrics give us better insight than ever before into what the jobs of the future will look like.

The kinds of jobs emerging in the global economy span a wide range of professions and skills, reflecting the opportunities for workers of all backgrounds and educational levels to take advantage of emerging jobs and the new economy. Identifying emerging jobs and the skills that they require provides valuable insights to inform training investments, and paves the way for a Reskilling Revolution, as individuals seek new skills to keep pace with change.

But for all of the opportunities that the new economy will bring, there are stark skills gaps and gender gaps that must be addressed. If we dont, they will continue to widen in the future.

Here are five things we can learn from this new data:

Not every emerging job requires hard tech skills, but every emerging job does require basic tech skills such as digital literacy, web development or graphic design. Three of the jobs in the World Economic ForumsJobs of Tomorrowreport cloud, engineering and data clusters, which are also among the fastest-growing overall require disruptive tech skills like artificial intelligence (AI), robotics, or cloud computing. Because technologies like AI are so pervasive, many roles in areas like sales and marketing will require a basic understanding of AI.

These disruptive tech skills are in high demand across the board. Blockchain, cloud computing, analytical reasoning and AI are among themost in-demand tech skillswe see on LinkedIn.

While they arent growing as quickly as tech-dominated jobs, new sales, content production and HR roles are also emerging as a complement to the rapidly growing tech industry. Our research shows talent acquisition specialists, customer success specialists and social media assistants among the fastest growing professions all roles that rely on more diverse skills sets, especially soft skills.

Demand for soft skills is likely to continue to increase as automation becomes more widespread. Our latestGlobal Talent Trends Reportshows that HR professionals are identifying the demand for soft skills as the most important trend globally. Skills like creativity, persuasion, and collaboration which all top our list ofmost in-demand soft skills are all virtually impossible to automate, which means if you have these skills youll be even more valuable to organizations in the future.

While the data reflects a diversity of opportunities for workers of all backgrounds and educational levels, further analysis shows a worrying imbalance in those obtaining the latest skills. In our ongoingresearch on gender with the World Economic Forum, we found that the largest gender gaps among emerging jobs are in roles that rely heavily on disruptive tech skills, with the share of women represented across cloud, engineering and data jobs below 30% (for cloud computing its as low as 12%). Its critical to close this gap because these disruptive tech skills will have an outsized impact on the direction of society and the economy.

While there is certainly room to improve gender parity by embracing greater diversity in hiring and more inclusive managerial practices, our data suggests that those gains, while important, will not be sufficient to achieve parity.

We have to think creatively about ways to fill these emerging skills and roles so that we prevent these gaps from intensifying in the future. Our research to understand these issues has uncovered some very achievable, scalable solutions.

Firstly, taking advantage of existing and adjacent talent can make a massive contribution to the rapid expansion of talent pipelines. Our research reveals thattraining and up-skilling near AI talent could double the pipeline of AI talentin Europe.

Taking a similar approach with the gender gap, weve found that sub-groups of disruptive tech skills where women have higher representation genetic engineering, data science, nanotechnology and human-computer interaction could expand the pipeline of talent for the broader set of tech roles that rely heavily on disruptive tech skills.

While both of these approaches can help us make meaningful progress, closing the skills and gender gaps depends on a lot more than just making sure talent has the right skills. Its a simple truth that who you know matters, so we also have to close the network gap the advantage some people have over others based purely on who they know.

Ourresearch on the network gapshows that living in a high-income neighbourhood, going to a top school and working at a top company can lead to a 12x advantage in accessing opportunities. This means that two people with the exact same skills, but who were born into different neighbourhoods, may be worlds apart when it comes to the opportunities afforded them.

All of these new metrics and insights can help us pinpoint the skills and jobs of the future, but its going to take more than data to ensure that the Fourth Industrial Revolution is an equitable one. If we are going to make meaningful change, we need businesses and political leaders to re-evaluate the norms through which we shape policy, make hiring decisions and ultimately level the playing field for those who face barriers to opportunity.

As we convene at the Annual Meeting of the World Economic Forum in Davos, Im asking leaders to join us in making progress towards closing these gaps. It will create better, more innovative businesses, stronger economies and ultimately help create fairer societies.

Allen Blue,Co-Founder and Vice President, Product Management, LinkedIn

This article was originally published in World Economic Forum

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5 things we know about the jobs of the future - Qrius

ASC20 set up Quantum Computing tasks for the first time. Teams are going to use the QuEST (Quantum Exact Simulation Toolkit) running on supercomputers to simulate 30 qubits in two cases: quantum random circuits (random.c), and quantum fast Fourier transform circuits (GHZ_QFT.c). Quantum computing is a disruptive technology, considered to be the next generation high performance computing. However the R&D of quantum computers is lagging behind due to the unique properties of quantum. It adds extra difficulties for scientists to use real quantum computers to solve some of the most pressing problems such as particle physics modeling, cryptography, genetic engineering, and quantum machine learning. From this perspective, the quantum computing task presented in the ASC20 challenge, hopefully, will inspire new algorithms and architectures in this field.

The other task revealed is Language Exam Challenge. Teams will take on the challenge to train AI models on an English Cloze Test dataset, vying to achieve the highest test scores. The dataset covers multiple levels of English language tests in China, including the college entrance examination, College English Test Band 4 and Band 6, and others. Teaching the machines to understand human language is one of the most elusive and long-standing challenges in the field of AI. The ASC20 AI task signifies such a challenge, by using human-oriented problems to evaluate the performance of neural networks.

Wang Endong, ASC Challenge initiator, member of the Chinese Academy of Engineering and Chief Scientist at Inspur Group, said that through these tasks, students from all over the world get to access and learn the most cutting-edge computing technologies. ASC strives to foster supercomputing & AI talents of global vision, inspiring technical innovation.

Dr. Lu Chun, Vice President of SUSTech host of the ASC20 Finals, commented that supercomputers are important infrastructure for scientific innovation and economic development. SUSTech makes focused efforts on developing supercomputing and hosting ASC20, hoping to drive the training of supercomputing talent, international exchange and cooperation, as well as inter discipline development at SUSTech.

Furthermore, during January 15-16, 2020, the ASC20 organizing committee held a competition training camp in Beijing to help student teams prepare for the ongoing competition. HPC and AI experts from the State Key Laboratory of High-end Server and Storage Technology, Inspur, Intel, NVIDIA, Mellanox, Peng Cheng Laboratory and the Institute of Acoustics of the Chinese Academy of Sciences gathered to provide on-site coaching and guidance. Previous ASC winning teams also shared their successful experiences.

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ASC20 Finals to be Held in Shenzhen, Tasks Include Quantum Computing Simulation and AI Language Exam January 21, 2020 - Quantaneo, the Quantum...

A nearly invisible bite delivered by a tiny mosquito has the capacity to trigger the fear of dengue in a human being who is millions of times larger than the insect. Such is the deadliness of the disease. However, one may not have to be harrowed by the fear of contracting the disease anymore.

In an effort to combat the spread of dengue, and counter the virus causing it, scientists at CSIRO, and the University of California San Diego have created a breed of genetically modified mosquito that is resistant to spreading all the four serotypes of the disease.

Talking about the research that is the first engineered approach towards targeting all the four serotypes, Dr Prasad Paradkar, senior research scientist, said in a statement, "In this study we used recent advances in genetic engineering technologies to successfully genetically modify a mosquito, the Aedes aegypti, with reduced ability to acquire and transmit the dengue virus."

Why genetically engineer a mosquito?

Over 390 million people are infected with dengue every year. It is caused by the Dengue virusDENV. Mosquitoes are the only known vectors carrying the disease, only other exception being transmission from mother to foetus. The virus has four serotypes: DENV1, DENV2, DENV3 and DENV4. Therefore, an individual can contract the disease four times due to the prevalence of four distinct strains.

Over half of the world population is at the risk of infection, and the rate of infection has seen an alarming rise over the years. Globally, nearly be $40 billion are lost as a result of dengue every year. This the primary motivation behind the development of the new mosquito, as a resistant vector will be unable to carry the virus.

"Mosquito-transmitted viruses are expected to climb over the coming years, which is why CSIRO is focussed on developing new ways to help solve this global challenge," said Paradkar.

Unlike previous attempts at synthetically engineering mosquitoes that were limited by the ability to target only one or two of the major serotypes, this breed of mosquito has shown the ability to resist all the four. As the scientists point out, this presents the future potential to fight all forms of mosquito-borne illnesses.

"This breakthrough work also has the potential to have broader impacts on controlling other mosquito-transmitted viruses," said Omar Akbari, co-author of the study.

Akbari also added that the research is in the preliminary stages of testing procedures to simultaneously negate mosquitoes against dengue and an array of mosquito-borne viruses such as chikungunya, Zika, and yellow fever.

The disease is typically characterised by symptoms such as severe fever, muscle aches, and headaches. More severe forms of the disease can cause shock, vomiting, haemorrhage, and sometimes, death.

There is no known treatment for specific neutralisation of the disease. Also, there are no vaccinations available against the disease. Treatment includes prescription of drugs such as acetaminophen, also known as paracetamol, to soothe the pain. Hydration through intake of fluids and occasionally intravenously is another remedy.

Stressing on this immediate need for a cure, Paradkar concluded, "There is a pressing global demand for effective strategies to control the mosquitoes that spread the dengue virus, as there are currently no known treatments and the vaccine that is available is only partially effective."

See the article here:
Dengue breakthrough: Scientists develop genetically engineered mosquito to combat the disease - International Business Times, Singapore Edition

When I first heard about JBS Haldane years ago, I only knew about the final act of his life: that he was a British biologist who moved to India, became a citizen there and died there in 1964. Even that sliver of detail was intriguing. Scientists usually moved from India to the West. What prompted this man to travel in the reverse direction?

Four years ago, I started to examine his life in more detail and grew steadily more fascinated. Here was a man who, as a boy, was often a guinea pig for his scientist father; who wrote his first scientific paper when he was in the trenches during the First World War; who went repeatedly to Spain to help fight Francisco Francos fascist forces; who ruined his body in experiments for Britain's Royal Navy during the Second World War; who got into constant tussles with every kind of authority figure; and who wrote reams of elegant essays on science for the lay reader.

But where Haldane really spoke to me, across the years, was in his astute thinking about how science and politics intersect. Over the past few decades, we have lived in a time when scientific objectivity is often confused for apolitical neutrality. Climate change aside, scientists hardly ever took political stances, or expressed their views on matters of ideology, or occupied the sphere of the public-interest intellectual.

This was not always the case, though. In the first half of the 20th century, during Haldanes time, scientists were vociferous about their politics and their stances on social issues Haldanes own voice the loudest of them all. He decried imperialism and exploitative capitalism. He criticised British and American government policies. He never made a secret of his radical politics and eventually became a card-carrying member of the British Communist Party.

His own scientific field genetics was perhaps the most politicised area of study in his time, and he recognised that. Even while the fundamentals of genetics were being established, the West fretted about their implications. Britain and America worried that the white race was being diluted because the feeble-minded and feeble-bodied were allowed to reproduce, or because immigrants and people of colour were having children with white men and women. The state machinery moved to prevent this. In Britain, about 65,000 people were segregated because they were considered unfit to reproduce. In America, an equal number of people were sterilised.

Haldane lambasted these measures, calling them not only unethical but also unscientific. Similarly, when Nazi Germany formulated racial purity laws and marched towards ethnic cleansing, Haldane excoriated that false science as well. The Nazi doctrine of "blut und boden" blood and soil was rubbish, he wrote witheringly. The only way blood differed was in its basic groups A, B, O and AB so the characteristic of a race is not membership of a particular blood group". And none of the soils of Germany were unique to it, he added. Friesland is not unlike northern Holland, Brandenburg is like western Poland.

Race was not a meaningful category in any sense, Haldane argued. The genes of people can vary more within a so-called race than between two racial groups a fact science has repeatedly confirmed

Like other members of his class and nation, Haldane grew up believing that some races were inferior to others. But as genetics progressed and its implications became clearer, he changed his views. Race was not a meaningful category in any sense, he argued. In fact, the genes of people can vary more within a so-called race than between two racial groups, he wrote a fact that science has repeatedly confirmed.

In his most famous essay, Daedalus, Haldane warned that as humanity refines its skills to manipulate its own genes, it will have to construct a new morality to deal with these powers responsibly. He recognised a fundamental truth: genetics is the science of differences and with such a science, the invasion of politics is inevitable.

Haldanes ideas ring with increased urgency today. All around us, we see the rise of identity politics of an exclusionary politics based on who belongs, or does not belong, to a nation. Who should or should not cross a border. Who should or should not be thought of as a citizen.

In India, Haldanes adopted home, the government has just passed a bill to expedite the citizenship process for refugees fleeing religious persecution from three of its neighbouring countries. Refugees of every faith except Islam have been promised a quick track to citizenship. The signal is loud and clear: Muslims do not belong here.

Around the world, communities and groups have come to believe that they are distinct, or special, or superior, even though science emphasises that this is false

Echoes of this are everywhere. In China, Uighurs are being segregated. In America, the president wants to build a wall to keep out Mexican and South American immigrants and refugees. In Britain, a narrative that the country should turn inward rather than ally itself with a larger union has conclusively won. There is sectarian strife in Lebanon and Iraq, and white nationalism in Europe. Around the world, communities and groups have come to believe that they are distinct, or special, or superior, even though science emphasises that this is false.

Toss genetic engineering into this mix and things only get more incendiary. Haldane was unequivocal in his belief that the social differences of class need to be stripped away. But at the moment, the danger is that if and when scientists figure out how to re-tailor the human genome, the rich will first buy themselves better genes. The inequalities of wealth will be compounded by new inequalities of ability and physiology. If we are not cautious, the gaps in human society will yawn wider and wider.

At a time like this, Haldanes life and work offer us plenty of guidance. He urged his readers and his students to adopt the scientists perspective of sceptical rationality: to question authority, to demand proof for received wisdom, to make decisions based on evidence.

But Haldane was not a proponent of scientism; he did not believe that peace and progress could be delivered exclusively through science.Haldanes university degree was in the classics, not in biology or chemistry or any other scientific discipline, and he always saw his field with the eyes of a humanist who had wandered into it.

He believed, therefore, that we have to consider our societys frailties and foibles, even as we decide what to do with new science and technology. We have to find ways to live with each other before we discover how science can best improve the human condition. And this is an urgent task. The march of science does not wait for us to grow mature enough to know how to use it wisely. He believed, therefore, that we have to consider our societys frailties and foibles, even as we decide what to do with new science and technology.

Haldane was, in his country and in his time, one of the most famous scientists around perhaps even as well-known as Einstein, and certainly the most politically vocal in his profession. Since then, he has sunk somewhat into obscurity. The 21st century, though, is an appropriate time to remember him and through his work, to rediscover lessons for our own age.

Samanth Subramanian is a regular contributor for The National. His latest book is titled A Dominant Character: The Radical Science and Restless Politics of JBS Haldane

Updated: December 21, 2019 11:17 AM

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The rise of identity politics is a reminder of Haldane's worst fears about genetic manipulation - The National

As the 2010s draw to a close and we look forward to the new 2020s, Bronwyn Williams takes a quick trip in a hypothetical time machine back to the start of the last decade of disruption and the technological milestones that defined it.

2010

NEW HIEROGLYPHICS

Although, thanks to Brexit and that wall, the utopian globalist agenda may be showing strain at the moment, we can find comfort in the emergence of our new favourite international language the emoji.

In 2010, the first emoji character library was accepted into Unicode, thereby recognising the little symbols we are all so familiar with today as an official universal internet language.

Our contemporary hieroglyphics unite generations and nations in a common visual tongue.

They could also, however, mark the beginning of the end of the age of literacy as we know it today. After all, who needs to text letters when a picture says a thousand words?

Emojis

2011

WHO NEEDS A CAR ANYWAY?

In 2011, the first Uber drivers took to the streets, accelerating both the on-demand and the sharing economy. Commuters could catch a ride at the touch of a button on their smartphones and no longer needed to own their own vehicles to benefit from the convenience of having their own cars.

Today, the e-economy has evened out to allow us to share anything from housing to handbags thanks to companies such as Airbnb and Rent. The take away is that we no longer need to own an object to enjoy it. Also worth considering is how Uber and its fellow gig economy firms are work and law.

Society is still grappling with how to deal with gig workers who report to an app, rather than a human boss, and are not covered by traditional labour laws.

2012

TO THE LEFT, TO THE LEFT

Tinder

The world is in the middle of a sex recession. Teenagers and young adults are more likely to be virgins than their parents and grandparents were at the same age. This phenomenon may or may not be linked to the way interactions are increasingly taking place online, rather than in person.

Tinder, the infamous dating app which launched in 2012, is just one example of how people are turning to technology to help connect with each other with varying degrees of success.

Clearly, though, we are missing something from our fellow humans in our digitally connected world. More and more people are turning to artificially intelligent chat bots, such as Microsofts Xiaoice, which has more than 100 million friends for companionship.

2013

HOLD THE BEEF

The move towards veganism and vegetarianism is a growing global trend. In the US, for example, one in four 25- to 34-year-olds do not eat meat.

Then in 2013, science gave us a way to have our cow and eat it too in the form of synthetic, cruelty-free lab-grown burger patties that look and taste just like the real deal.

Looking ahead, as startups such as Future Meat Technologies make high-tech foods become more accessible, acceptable and affordable, it is likely future generations will view killing animals for food to be a barbaric, embarrassing relic of human history.

Other faux food firms such as Perfect Day and Clara Foods are replacing milk and eggs with artificial imitations indistinguishable from the real product.

2014

WHATS YOUR NUMBER?

In 2014 China started piloting its ambitious, ubiquitous social credit score system to track and rank citizens based on online and offline behaviour.

Built around a national surveillance network, the system rewards good citizens and punishes offenders. Individuals with low scores are denied access to services and freedoms such as using public transport or attending top schools.

Similar human quantification systems can be found in capitalist countries, where consumers are tracked, rated and rewarded by the companies that serve and sell to them. South Africans are familiar with behavioural rewards (and punishment) systems employed by medical and vehicle insurers. Rule by behavioural economics, or nudge is set to grow.

2015

HELLO COMPUTER

Alpha Go

In October 2015, Alphabets artificially intelligent computer programme AlphaGo, beat a professional human Go player for the first time.

This impressive feat of computing prowess reignited the global conversation around the future of artificial intelligence (AI), and the possibility of the so-called Singularity that is when an AI becomes smarter than the entirety of human intelligence. It also reawakened concerns about artificially intelligent machines and algorithms replacing human jobs and perhaps leading to a global post-work economy.

Since then, AI and machine learning have progressed to the point that the worlds top Go player, Lee Se-dol, has retired in defeat, stating that AI cannot be defeated.

2016

FAKE NEWS

In 2016, the website BuzzFeed coined the term fake news in response to a spate of plainly inaccurate, yet intriguingly titled, web articles originating from Macedonia.

Since then, the lies have continued to spread around the world, influencing elections from the US to the UK and South Africa, while the truth limps along behind trying to clean up the fallout.

Fake news, spread via viral clickbait articles shared on social media, has become a global phenomenon with wide-reaching consequences.

Its impact can be felt everywhere from the growing anti-vaccination movement to blame for the re-emergence of once-eradicated measles outbreaks, to the spread of dangerous populist political ideas and the rise of extremist political parties globally.

2017

DEEPFAKE

If fake news was problematic, it was only the start. In 2017 a Reddit user came up with the term deepfake to describe a series of videos he had edited, using a machine-learning algorithm, to transpose famous peoples faces on to porn footage to create convincingly realistic fake movies. In the age of the deepfake we can no longer trust our eyes or ears, as sitting presidents and corporate leaders have discovered to their detriment. Unscrupulous agents can now literally place fake words into real peoples mouths, and put real people into really compromising situations.

Seeing is no longer believing.

2018

SUPERHUMANS

Last year, the first genetically engineered human babies, twin girls, were born in China, ushering in the age of intelligent designer babies.

The girls had been edited using CRISPR Cas-9 technology while still embryos. As the technology progresses, and as more and more governments allow genetic engineering of humans and human embryos, we are sitting on the precipice between natural selection (evolution) and intelligent design.

The ethics of what should be allowed (for example, the eradication of genetic illnesses) and what should be restricted (such as selecting and editing human embryos for good looks or superior intelligence) will be some of the most important questions the human race needs to answer in the years ahead.

2019

REAL WEIRD, REAL FAST

If you thought the last decade was disruptive, just wait until you see what comes next.

This year, Google announced that it had achieved quantum supremacy in other words that the company had managed to demonstrate a successful application of quantum computing.

Should the technology continue to progress from this early sign of success, quantum computing could dramatically increase the processing power and speed of computers as we know them today.

Then add 5G speed internet which is set to roll out in China in early next year to the mix and we can look forward to another decade of superspeed disruptions.

Bronwyn Williams is trend translator at FluxTrends.com

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The decade that disrupted us - News24

Like many Americans, I was shocked that our president ran what amounts to a transnational mafia in bed with Russian and Ukrainian oligarchs who benefit from Russian President Vladimir Putins war for totalitarian control of Ukraine against a free people who have struggled and suffered so much for their freedom.

We might be even more shocked if we had the transcript of Trumps call with Recep Tayyip Erdogan, president of Turkey and friend of Putin, which led to our betrayal of the Kurdish allies who did most of the hard ground fighting against ISIS for us. The ethnic cleansing of Kurds out of northern Syria is a crime against humanity and should have been included in the articles of impeachment.

But while we are focused on the vileness of Rudolph Guiliani and other mobsters, experts and pundits discussing these events completely ignore the massive, glaring questions of how to prevent such things from happening again. Even impeachment and conviction in the Senate, which will never happen, would not solve problems far bigger than Donald Trumps serious abuses of powers.

We need amendments to protect the professional civil service (especially in law enforcement and foreign affairs), to counter corruption in the federal government (e.g. by requiring tax-return disclosure), to clarify grounds for impeachment, and to limit pardon powers. It is staggering that even these problems so directly linked with current controversies never come up in mainstream coverage.

And this is only the beginning: We all really need to stop focusing solely on this impeachment, despite the cowardly way many Republicans are trying to defend Trump with conspiracy-spins drawn directly from Russian propaganda.

To solve the roots of this polarization that is making too many Americans on the political extremes prefer ideology to reality, we need constitutional change to end the dominance of two major parties with automatic runoffs, to rotate primaries between all states so Iowa and New Hampshire no longer go first every time, to prevent gerrymandering and dark money in our elections, to establish uniform national voting and count procedures, set Supreme Court terms and ban the filibuster in Congress. It is colossal collective folly that we focus only on the symptoms while ignoring the root problems that prevent fair elections and perpetuate endless gridlock in D.C.

Even before the Ukraine news broke, we were largely ignoring many other urgent issues that will have much profounder effects on our children and grandchildren. Climate change gets deserved attention, but there are several other dangers that, taken together, could harm human prospects even more than climate change, although they get virtually no attention in this country.

The regime in China, which now holds more than a million of its people in concentration camps in a genocidal effort to erase an entire minority culture, is creating a nightmare of totalitarian control a hundred times worse than anything Orwell ever imagined. At home, its facial-recognition cameras are everywhere and all its people will be increasingly monitored via data collection.

China also is pressuring many other countries in Asia and Africa to obey its commands, and the strong-arm tactics we have seen used against the NBA and Asian journalists are only the tip of the iceberg. It will not help our grandchildren much to be saved from climate change only to live as slaves under a global tyranny run from Beijing and Moscow.

Yet, almost no Americans understand that we are going to wake up in a couple years to discover that China has invaded Taiwan and that NATO will not do anything to stop it because we want the money from trade.

Similarly, because of the gridlock in D.C. caused by constitutional flaws, you may wake up one day a decade from now to discover that the American government is defaulting on a federal debt that maybe exceeds $50 trillion ($50,000 billion) in 15 years or less, sending the world into a new Great Depression which finally cements Chinas dominance in the aftermath.

That is, if loose nukes getting to terrorists or pandemic diseases originating in the worlds poorest nations or cybercrime viruses running rampant do not take us into economic armageddon first. Remember this as Democrats and Republicans promote the new brand of moronic isolationism rather than seeking new arrangements to share essential tasks effectively among our allies.

This staggering collective blindness is a result of the deepest flaw of all in our social system: In the 20th century, as television and radio appeared, we were content to allow mass media to be delivered on a for-profit basis. For a long time, editors and producers felt responsible to cover stories that people needed to hear because of their objective importance, whether they grabbed high ratings or not.

Today, that ethic is so completely gone that CNN, which I have watched since it was founded, covers almost no global news at all. In fact, for more than four years, it has covered almost nothing but American federal politics.

Fox also has focused almost solely on American federal politics, with a few other cherry-picked stories to appeal to its base like an occasional immigrant committing some crime or some stupid campus activists trying to no-platform a right-wing speaker. Their international coverage is limited to things that might seem to boost Trump, such as a happy Turkish general proclaiming the safe zone in northern Syria that is, a zone made safe from Kurds in the same way that the Trail of Tears made eastern states safe from the Cherokee. This propaganda machine heavily influences the nation now.

More broadly, internet medias focus entirely and solely on what is trending or popular with its group of viewers, which will include few events beyond our shores. Most Americans never see a major newspaper with fact-checked journalism; they finish high school without learning about current world affairs or even the basics of American civics, such as key numbers for parts of the federal budget or the history of main tax rates, the federal deficit, projections for Medicare, etc. let alone elementary critical thinking that would enable them to distinguish reliable sources from total crap.

Combined, these problems mean the death of democracy through completely manipulable voters. Both could be fixed by fairly simple constitutional reforms to improve our mass medias and education requirements.

The stupidity resulting from only-trendy media is so colossal today that even domestic issues that are massively in our face everywhere get only the most superficial analysis. Federal anti-monopoly laws have not been seriously updated in almost 100 years, and yet we wonder how Amazon, Microsoft, Google and Facebook can own more and more parts of supply chains, buy up all competitors and abuse power in service of profit.

When a small handful of corporations own most of the systems on which our lives totally depend, sell all our private information to insurance companies and marketers, and crush any dissenting opinion with their ability to manipulate what people view, it will be much harder to unwind this plutocracy. Yet it never even occurs to us to discuss the smallest countermeasures, like EU-style laws protecting data privacy.

Of course, this will not matter much if Google has unleashed a smart Artificial Intelligence system that does more damage than climate change. Or if genetic engineering to enhance human capacities has become so common among the richest 5 percent across the world that they have become a new species poised to control the rest more decisively than was possible in the past.

Our chance to control these threats with smart laws and global partnerships will be distant memories by then. But you did not know about this danger because not enough celebrities have tweeted about it!

We all need to refocus on the fundamental structural flaws that are disabling our political system from making effective laws and preventing too many America
ns from learning the most basic things they need to be responsible citizens. We cannot fix the substantive problems without working political tools, and our tools are so broken that we neither diagnose most of the problems nor fix them.

What would we think of a mechanic who is so outraged by an expensive broken car headlight that he does not notice that the steering column is broken and that the tools he is taking to the headlight are rusted through? First things first: fix the political system and fix the education of citizens by fixing the Constitution.

Link:
COMMENTARY: Obsessed with Trump, our blindness to urgent issues grows - New Jersey Hills

Milestone, an organisation for the welfare of persons with disabilities (PWDs), was established in 1993 focusing mainly on mainstream inclusion of PWDs into the society by incorporating the concept of independent living (IL), a barrier-free society, awareness and capacity building. We speak to Shafiq ur Rehman, president of Milestone, on employing the concept of IL for improving the lives of PWDs.

The News on Sunday: When we talk about social integration of persons with disabilities (PWDs) there is talk of independent living (IL). How essential is it to mainstream PWDs through IL?

Shafiq ur Rehman: According to the concept of independent living (IL), PWDs are neither gods who have to be worshipped nor children who need to be taken care of. Instead, they are human beings who can and should take responsibility for their own lives and can make responsible decisions about their lives.

Our challenge is that PWDs are treated as some kind of a social disaster, a tragedy. World over there is a struggle to end disability through genetic engineering or the like. In reality, disability is not something that human beings suffer from. It is caused by the unavailability of required services in the environment of the PWDs. In developed countries, PWDs are not only contributing to economies but are also playing active roles due to practical implementation of IL. In Japan, PWDs have started services using the concept of IL where they have set up centres providing attendant services. In this way, they have become active members of the economy. In underdeveloped countries, PWDs are limited to basic survival activities such as eating and sleeping, and are not engaged as useful members of the society.

TNS: How much social acceptance is there towards independent living of PWDs? How willing are they to take control of their lives in a society like ours?

SR: Our societys attitude towards PWDs has largely been that of pity. This is the general behaviour of people in Pakistan. It is because of this that they often acquire the habit of taking pity on themselves, especially those who have a physical disability from birth. For some of these individuals, living on charity offered by others becomes the easiest solution. They lead their lives without taking any responsibility. When we talk of a lack of social acceptance regarding independent living it is because there is very little PWD visibility.

Courage and fortitude are often portrayed as desirable traits in our society, particularly for those faced with various disabilities. Self realisation and acceptance are the core values that should be focused upon. People dont understand this. We need to understand what resources we have, the environment we live in and how we can improve our lives through technologies. What could be better than learning this basic principle right at the start instead of trying to make the same mistakes over and over again? How is repeated failure an accomplishment?

TNS: What sort of work is being done regarding employment opportunities for the PWDs?

SR: The Lahore Businessmen Association for Rehabilitation of the Disabled (LABARD) has done a lot in the area of providing employment opportunities for PWDs. Run by the Lahore Chamber of Commerce and Industry (LCCI), the institution offers several vocational training programmes. The Punjab Skills Development Programme has also started offering various six-month vocational training programmes, including cooking, cutting and the like. This is a good initiative. The first session of this programme started four months ago so we have yet to see the results, which we should be able to judge in a year.

TNS: In terms of policy regarding the PWDs and their employment, how has the government fared?

SR: This debate surrounding PWDs started during the era of Gen Zia ul Haq whose daughter had a disability. That is when it all began in Pakistan. The Disabled Persons (Employment and Rehabilitation) Ordinance 1981 set aside an employment quota as well. To our misfortune, however, that is where the debate pretty much ended. Unfortunately, after Zia, none of the presidents and prime ministers of this country had an offspring who was disabled. And I say this with regret, because from our experience we have learned that this is how legislations have been addressed in this country. Today, legislative cover on this front remains weak a dilemma for the remaining PWDs who could have been an actively contributing segment of the society.

TNS: How can the IL model be implemented by the government on a larger scale?

SR: Independent living is a low-cost solution to making PWDs independent. If theres a single PWD in a family it paralyses the entire family. But look at this situation from a different angle: it creates job opportunities for caregivers and attendants. In a traditional set up, parents are left worrying about the well being of their child with disability. Through affordable caregivers, there is opportunity for creating new jobs while making the rest of the family of a PWD more independent through affordable attendant services.

In Japan alone, there is a need for 500,000 attendants for their PWDs population. There is great potential to create an entire industry surrounding the concept of IL within Pakistan by employing the younger population to further development in the social sector. There is a huge opportunity in this population of PWDs that is hidden away in homes by their own families, away from the gaze of the society that thinks of it as a burden. Only if we can think rationally, all this could change.

The writer is a staff member

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Our challenge is that persons with disabilities are treated as a tragedy - The News on Sunday