Monthly Archives: October 2019

Lupus Study Illustrates the Importance of Diversity in Genetic Research – Nature World News

Posted: October 30, 2019 at 1:42 pm

Scientists at theHudsonAlpha Institute for Biotechnologyhave pinpointed epigenetic differences in the way lupus affects black women compared to other lupus patients, revealing important mechanics of the puzzling disease. Epidemiologists have identified that lupus impacts black women with greater frequency and severity than other populations. Scientists inDevin Absher's Labat HudsonAlpha published findings in August showing that increased risk and harm to lupus patients can be linked to epigenetic differences--essentially, the degree to which certain genes are functioning.

The finding, published inArthritis & Rheumatology, helps create a more complete understanding of an often misunderstood disease, revealing some of the mechanisms that contribute to it. It also reveals a gap in genetic research, highlighting the lack of information scientists have regarding racial differences on the genetic level.

Devastating Disease

Lupus is an autoimmune disorder, meaning that the immune system attacks healthy cells in the body. It causes symptoms that are often difficult to quantify, including fatigue and extreme joint pain.

Lupus is one of the most historically chronicled diseases, having first been documented by Socrates in 400 BC. The disease gets its name from a common rash that forms on the face which is said to resemble the markings of wolves, hence the latin name "lupus" meaning wolf.

There are more than 200,000 cases of lupus in the US every year, yet there is no universally accepted cause or cure. The disease is chronic, meaning it can last for years or even an entire lifetime.

Megan Breitbach, PhD, is the lead author on the paper. She notes, "The diagnostic process can also prove long and tedious, because the symptoms come and go and often can only be observed through patient description."

"On average," she adds, "it takes six years to diagnose someone with lupus."

While treatment can help manage lupus, the condition cannot be cured. Instead, patients and their physicians try to address symptoms and take the edge off flare-ups.

Molecular Differences

While the disease on the whole remains a mystery, scientists hope to find some answers in the ways that the condition affects different populations. In the United States, lupus has a much higher prevalence in non-white populations. In fact, lupus is the 5th leading cause of death for black women ages 15-24.

Ancestry can dramatically impact disease genetics, so understanding why the disease affects populations differently could go a long way toward telling us what genetic factors play a part in developing the condition.

In the case of lupus, the body's immune B cells function distinctive epigenetic signatures of the disease are found in B cells, which are part of the immune system. The analysis performed by the Absher Lab revealed lupus-specific differences in methylation throughout B cell development between black and white women.

Methylation changes can alter the degree to which a stretch of DNA functions without changing the genetic code itself. This research shows the most significant changes in methylation occur around genes related to Interferons, which are proteins that regulate immune response.

These differences in B cell development could help explain the more severe symptoms and earlier age of onset for lupus in black women.

"What we found," explains Devin Absher, PhD, "was that there are a number of methylation changes we can link to lupus. When you isolate them, you see that the changes are far greater in black women. The population differences could be key to a more complete understanding of the disease on the whole."

Gaps in Understanding

The genetic gap between these two groups of patients with lupus illustrates a broader gap in knowledge. One key limitation of genetics stems from a lack of diverse data, which hurts all populations.

Disease genetics frequently relies on genome-wide association studies (GWAS) to link genes with various health conditions. However the most recent aggregations of GWAS show nearly 88% of participants come from European ancestry. These eurocentric results can make it harder to identify genetic components of diseases that disproportionately affect underrepresented populations.

A lack of diversity in genetic research slows progress across the board. The unique genetic factories of all kinds of ancestry can help us better understand the human genome and even find potential ways to share the benefits of natural resistance. For example, Americans of African descent were found to have mutations on their PCSK9 genes which led to lower levels of cholesterol in their bloodstream. With that information, researchers developed PCSK9 inhibitors to lower cholesterol and heart disease risk across ancestries.

This lupus research from the Devin Absher Lab further illustrates the importance of understanding racial diversity when examining genetic components for diseases.

Absher is involved in a number of efforts to drive greater diversity in genetic research, including the Alabama Genomic Health Initiative, which aims to bring the value of genetic sequencing to diverse populations across the state.

The Way Forward

This lupus research helps open the door for future exploration of methylation around Interferon sites as it relates to the disease. However, the finding is only possible because of an active consideration of the value of diversity in genetic research. HudsonAlpha remains dedicated to bringing the value of genomics to all, as a diverse approach to research opens doors that would otherwise remain closed.

2018 NatureWorldNews.com All rights reserved. Do not reproduce without permission.

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Interpace to Present Data at the ATA Annual Meeting – GlobeNewswire

Posted: October 30, 2019 at 1:42 pm

PARSIPPANY, NJ, Oct. 29, 2019 (GLOBE NEWSWIRE) -- Interpace (IDXG) announced today that it will be presenting new data on the performance of its molecular thyroid products at the upcoming 89th Annual Meeting of the American Thyroid Association (ATA), being held October 30th to November 3rd, 2019 in Chicago, IL. The ATA meeting is one of the largest gatherings of endocrinologists, ENTs, surgeons and other providers who focus on the diagnosis and treatment of thyroid cancer.

Interpace will be presenting three separate posters focused on the performance of the companys molecular tests for indeterminate thyroid nodules, ThyGeNEXT and ThyraMIR, and are titled:

Together these posters underline the clinical utility of ThyGeNEXT and ThyraMIR in assessing the risk of thyroid nodules with indeterminate cytology results progressing to cancer. They also highlight progress made by the Company to provide quality diagnostic information for the detection of aggressive forms of thyroid cancer.

Jack Stover, CEO of Interpace, stated, We are pleased that our data has been accepted for presentation in this prestigious forum and look forward to sharing our work with such an established group of attendees. Mr. Stover continued, The acceptance of our data supports our belief that our molecular products continue to add value to physicians and patients at risk of thyroid cancer.

About Thyroid Nodules, ThyGeNEXT and ThyraMIR Testing

According to the American Thyroid Association, approximately 20% of the 525,000 thyroid fine needle aspirations (FNAs) performed on an annual basis in the U.S. are indeterminate for malignancy based on standard cytological evaluation, and thus are candidates for ThyGeNEXT and ThyraMIR.

ThyGeNEXT and ThyraMIR reflex testing yields high predictive value in determining the presence and absence of cancer in thyroid nodules. The combination of both tests can improve risk stratification and surgical decision-making when standard cytopathology does not provide a clear diagnosis.

ThyGeNEXT utilizes state-of-the-art next-generation sequencing (NGS) to identify more than 100 genetic alterations associated with papillary and follicular thyroid carcinomas, the two most common forms of thyroid cancer, as well as Meduallary Thyroid Carcinoma. ThyraMIR is the first microRNA gene expression classifier. MicroRNAs are small, non-coding RNAs that bind to messenger RNA and regulate expression of genes involved in human cancers, including every subtype of thyroid cancer. ThyraMIR measures the expression of 10 microRNAs. Both ThyGeNEXT and ThyraMIR are covered by both Medicare and Commercial insurers, with more than 280 million patients covered.

About Interpace

Interpace is a leader in enabling personalized medicine, offering specialized services along the therapeutic value chain from early diagnosis and prognostic planning to targeted therapeutic applications.

Interpaces Diagnostic Business is a fully integrated commercial and bioinformatics business unit that provides clinically useful molecular diagnostic tests, bioinformatics and pathology services for evaluating risk of cancer by leveraging the latest technology in personalized medicine for improved patient diagnosis and management. Interpace has four commercialized molecular tests and one test in a clinical evaluation process (CEP): PancraGEN for the diagnosis and prognosis of pancreatic cancer from pancreatic cysts; ThyGeNEXT for the diagnosis of thyroid cancer from thyroid nodules utilizing a next generation sequencing assay; ThyraMIR for the diagnosis of thyroid cancer from thyroid nodules utilizing a proprietary gene expression assay; and RespriDX that differentiates lung cancer of primary vs. metastatic origin. In addition, BarreGEN for Barretts Esophagus, is currently in a clinical evaluation program whereby we gather information from physicians using BarreGEN to assist us in positioning the product for full launch, partnering and potentially supporting reimbursement with payers.

Interpaces Biopharma Business provides pharmacogenomics testing, genotyping, biorepository and other customized services to the pharmaceutical and biotech industries. The Biopharma Business also advances personalized medicine by partnering with pharmaceutical, academic, and technology leaders to effectively integrate pharmacogenomics into their drug development and clinical trial programs with the goals of delivering safer, more effective drugs to market more quickly, and improving patient care.

For more information, please visit Interpaces website at http://www.interpacediagnostics.com.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, relating to the Company's future financial and operating performance. The Company has attempted to identify forward looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "projects," "intends," "potential," "may," "could," "might," "will," "should," "approximately" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are based on current expectations, assumptions and uncertainties involving judgments about, among other things, future economic, competitive and market conditions and future business decisions, all of which are difficult or impossible to predict accurately and many of which are beyond the Company's control. These statements also involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from those expressed or implied by any forward-looking statement. Known and unknown risks, uncertainties and other factors include, but are not limited to the fact that there is no assurance the acquisition of the BioPharma business of Cancer Genetics, Inc. will be successfully integrated with the Company, or that the potential benefits of the acquisition, including future revenues, will be successfully realized. Additionally, all forward-looking statements are subject to the Risk Factors detailed from time to time in the Company's most recent Annual Report on Form 10-K, Current Reports on Form 8-K and Quarterly Reports on Form 10-Q. Because of these and other risks, uncertainties and assumptions, undue reliance should not be placed on these forward-looking statements. In addition, these statements speak only as of the date of this press release and, except as may be required by law, the Company undertakes no obligation to revise or update publicly any forward-looking statements for any reason.

CONTACTS:Investor Relations - Edison GroupJoseph Green(646) 653-7030jgreen@edisongroup.com

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Time to break the stigma on genetic modification, for the sake of the climate – Stuff.co.nz

Posted: October 28, 2019 at 12:46 pm

OPINION: Recently, there has been a shift in society's view of genetic modification and its potential applications in the fight against climate change. This has led to a call for changes in our current policies from farmers and MPs alike.However, due to the Green Party's current stance on this topic, New Zealand is unable to utilise genetic modification for anything that is not laboratory-based.

I am a member of the Emerging Scientists for Climate Action society, which involves students from universities all over New Zealand. We are writing an open letter to the Greens to encourage them to review their stance on genetic modification and the current laws and regulations around genetic engineering. Our overarching goal to tackle climate change aligns with the Greens, and they are in a position to make positive change. We have 155signatures from emerging scientists (aged under 30) in support.

Genetic modification is a controversial topic, and there is much misunderstandingabout its techniques and applications.Genetic modification (aka genetic engineering) uses gene editing technologies and knowledge of genetics to make changes in an organism for a specific outcome. For example, a plant could be genetically modified to grow bigger to produce a higher yield. There are many gene-editing techniques that can be utilised, which further adds to the misconceptions around its applications. There is warranted concern over the long-term impacts of manipulating organisms at the molecular level, however, does this mean that we should disregard genetic modification altogether?

READ MORE:* New Zealand's anti-science GMO laws need to change to tackle climate change* Gene-editing risks are still too great to warrant a change in the law* Time for a grown-up conversation about gene editing

Our laws and regulations around genetic modification were established in 2001 and fall under the Hazardous Substances and New Organisms Act. That lawregulates research and release of all living things that do not already exist in New Zealand, including those that are genetically modified. However, these regulations have not accounted for the rapid advances in gene editing technology over the last decade, leaving New Zealand behind in the biotechnological sector. The calls for law changes come from all over New Zealand, including government agents such as Professor Juliet Gerrard, the Prime Minister's Chief Science Advisor. Current legal and regulatory frameworks are struggling to keep up with current technologies.

The focus on genetic modification has largely been on food production, such as pesticide-resistant crops and increased growth for higher crop yields. But the scope of genetic engineering expands far beyond this. Genetic engineering techniques have many benefits,including to mitigate the effects of climate change. For example, there has been research into genetically modifying plants to sequester more carbon from the environment, which would assist with lowering rising temperatures.

SUPPLIED

Deborah PaullPostgraduate student - Masters of Science in Microbiology, at the University of Canterbury.

I have been working on projects involving genetic modification, specifically, around genetically modifying milk proteins to reduce the allergenicity. The goal is to produce these proteins through a cellular-agriculture based system that can produce milk products in a more sustainable fashion in comparison to current methods. When discussing this project with people within the dairy industry, the overall remark is that it's a great idea but it will never be produced in New Zealand. It is disheartening to see that the potential benefits of using technology such as this to address climate change hasn't been considered due to our laws.

But it is now 2019, and we have advanced our technology and understanding of genetics in ways we couldn't have imagined. A new generation of emerging scientists has new values and ethical drives, especially focused on preserving our planet for future generations. To mitigate the effects of climate change, we need new and optimised technologies, such as genetic engineering. This is a practical action that could be implemented through highly controlled policy.

It is time to reframe the conversation around genetic modificationIf we hope to reach the carbon neutral targets set in the UN by 2050 while meeting the demands of the increasing population in a sustainable fashion, this is a conversation that we need to have now. The Royal Society has started this discussion, identifying the cultural values involved with using genetic engineering technologies but emphasisinghow New Zealand needs to shift its current view of this technology.

The goal is not to be carelessly modifying organisms for the benefit of a few -it is to utilise knowledge and technology so that as a country we can take a step forward. New Zealand is a world leader in green agricultural technologies. As a forward-thinking country, let's break the stigma surrounding genetic modification and create a better future for ourselves and the generations to come.

DeborahPaullis studying for aMasters of Science in Microbiologyat the University of Canterbury.

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Record-Time FDA Approval of Human Insulin In 1982: When Genetic Engineering Came of Age – American Council on Science and Health

Posted: October 28, 2019 at 12:46 pm

October 31stwill mark the 37th anniversary of one of biotechnologys most significant milestones -- the approval by the FDA of human insulin synthesized in genetically engineered bacteria.It launched a revolutionary new era in pharmaceutical development, and as the FDA medical reviewer of the product and the head of the evaluation team, I had a front-row seat.

The saga is remarkable in several ways, not least of which is that although both the drugmakers and regulators were exploring unknown territory, the development of the drug and its regulatory review progressed smoothly and rapidly.

Insulin in crude form was first produced in 1922 by Canadian researchers Frederick Banting and Charles Best, which lifted the death sentence that had previously been imposed on diabetics. By the end of that year drug company, Eli Lilly and Company had devised a method for much higher purification. Over the next half-century or so, the purified insulins obtained from pig or cow pancreases, which differ slightly in chemical composition from human insulin, were constantly improved in purity and formulated in ways that refined their performance.

During the early 1970s, as the supply of animal pancreases declined and the prevalence of insulin-requiring diabetes grew, there were widespread fears of possible future shortages of insulin.Fortuitously, around the same time, a new and powerful tool recombinant DNA technology, also known as genetic modification, genetic engineering, or gene-splicing became available and offered the promise of unlimited amounts of insulin that was identical to the molecule produced by humans.

The seminal molecular genetic engineering experiment wasreported in a 1973 research articleby academic scientists Stanley Cohen, Herbert Boyer and their collaborators. They isolated a ringlet of DNA called a plasmid from a bacterium, used certain enzymes to splice a gene from another bacterium into that plasmid, and then introduced the resulting recombinant, or chimeric, DNA intoE. colibacteria.

When these now recombinant bacteria reproduced, the plasmids containing the foreign DNA were likewise propagated and produced amplified amounts of the functional recombinant DNA. And because DNA contains the genetic code that directs the synthesis of proteins, this new methodology promised the ability to induce genetically modified bacteria (or other cells) to synthesize desired proteins in large amounts.

The scientists at Lilly immediately saw the promise of this technology for the production of unlimited quantities of human insulin in bacteria. After obtaining from startup Genentech, Inc., the recombinantE. colibacteria that contained the genetic blueprint for and that synthesized human insulin, they developed processes for the large-scale cultivation of the organism (in huge fermenters similar to those that make wine or beer) and for the purification and formulation of the insulin.

Insulins had long been Lillys flagship products, and the companys expertise was evident in the purification, laboratory testing and clinical trials of human insulin. The companys scientists painstakingly verified that their product was extremely pure and identical to pancreatic human insulin (which differs slightly in chemical composition from beef and pork insulin).

Lilly began clinical trials of its human insulin in July 1980. The product performed superbly. There were no systematic problems with treating naive patients (who had never before received injections of insulin) or those switched from animal to human insulin. A small number of patients who had had adverse reactions of some kind to the animal insulins tolerated the human insulin well.

The dossier that provided evidence of safety and efficacy was submitted in May 1982 to the FDA, where I was the medical reviewer and head of the evaluation team. Over many years the FDA had had prodigious experience with insulins and also with drugs derived from various microorganisms, so it was decided that no fundamentally new regulatory paradigms were necessary to evaluate the recombinant human insulin.

In other words, recombinant DNA techniques were viewed as an extension, or refinement, of long-used and familiar methods for making drugs. That proved to be a historic, precedent-setting decision.

Based on my teams exhaustive review of Lillys data, which were obtained from pre-clinical testing in animals and clinical trials in thousands of diabetics, FDA granted marketing approval for human insulin in October 1982. The review and approval took only five months when the agencys average approval time for new drugs was 30.5 months.

In retrospect, that rapid approval was particularly remarkable for a drug that was produced with a revolutionary new technology, and that after approval would be available in pharmacies nationwide to millions of American diabetics.

The back story, however, is revealing. My team and I were ready to recommend approvalafterfour months review. But when I took the packet to my supervisor, he said, Four months? No way! If anything goes wrong with this product down the road, people will say we rushed it, and well be toast. Thats the bureaucratic mind-set. I dont know how long he would have delayed it, but when he went on vacation a month later, I took the packet to his boss, the division director, and he signed off.

That anecdote illustrates Milton Friedmans observation that to understand the motivation of an individual or organization, you need to follow the self-interest. A large part of regulators self-interest lies in staying out of trouble. One way to do that, my supervisor understood, is not to approve in record time products that might experience unanticipated problems, even if it is the right thing to do.

The Humulin approval had significant effects. A New York Timesarticlementioned my prediction that the speedy approval was a major step forward in the scientific and commercial viability of recombinant DNA technology. We have now come of age, I said, and potential investors and entrepreneurs agreed. Seeing that biopharmaceuticals would compete with other medicines on a level playing field, the biotechnology industry was on the fast track.

Scores of genetically engineered drugs have been approved over the years, but the rapidity of the human insulin approval proved to be an anomaly. Even with a toolbox of improved technologies available to both the FDA and industry, bringing a new drug to market on average now takes 10-12 years and costs, on average, over$2.5 billion.Regulators are highly risk-averse, few new drugs are approved without convening extramural advisory committees, and decisions are sometimes hijacked by political forces exerted on the FDA.

Other FDA-regulated biotech sectors have fared worse.Incomprehensibly, the FDAdeclined to grant Generally Recognized As Safe (GRAS) statusto two proteins that would be life-saving as additives to oral rehydration solution administered to children with diarrhea.

In addition, FDA officials have made a horrendousmessof the regulation of genetically engineered animals, which FDA chose to regulate as new animal drugs, including a grotesquely prolonged, 20-plus year review of a faster-growing Atlantic salmon, and genetically engineered mosquitoes to control mosquitoes that carry viral diseases.(It took FDA more than five years to realize that the latter were actually pesticides which are outside the Agencys purview -- and that jurisdiction should, therefore, be turfed to EPA.)As a result, the entire biotech sector of genetically engineered animals is moribund.

Its too bad that government regulation hasnt aged as gracefully as genetic engineering technology itself.

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Stream It Or Skip It: ‘Unnatural Selection’ On Netflix, A Docuseries About The Ethics And Ease Of Editing DNA – Decider

Posted: October 28, 2019 at 12:46 pm

With everything youve been hearing about genetic engineering over the years, starting with the idea of genetically-modified fruits and vegetables all the way through gene editing in humans, youve heard a lot about why itshouldnt be done. But what are the positives? And what might happen if gene editing goes mainstream and available to (gulp) everyone? A new Netflix docuseries examines that issue.

Opening Shot: At night, we see a large cage full of barking dogs, likely pit bulls. The location is Mendenhall, Mississippi.

The Gist: The dogs are owned by Paul Ishee, an oil field tech who breeds dogs on the side. He collects sperm from the dogs (in just the way youd expect) because he wants to genetically engineer a better dog. How does he do that? Via CRISPR, a small protein that can be injected via a bacteria into an organism to edit its DNA. One of the big features with CRISPR, which was perfected only a few years ago, is that the protein is easily obtainable. So genetic modifications can be done in expensive labs by trained scientists or by biohackers in their garages.

Unnatural Selection, a docuseries produced and directed by Leeor Kaufman and Joe Egender, examines the new frontier of genetic engineering, and what ethical stumbling blocks there are to adapting gene editing on a wider basis.

The filmmakers interview a mixture of scientists and biohackers, some of whom are both. Dr. Jennifer Doudna, widely regarded as the inventor of the CRISPR method, seems to be in the middle of the debate; she knows how powerful using CRISPR can be when it comes to curing genetic-based diseases and other conditions, but is wary of people who want to use it to engineer superior organisms. Biohackers like Dr. Josiah Zayner, a biophysicist who used to work for NASA, is in favor of the democratization of genetic engineering, sending $140 CRISPR kits to people via Priority Mail. One of those people is Ishee, who wants to make a glowing dog as his first experiment, just to prove that the engineering worked.

Others, such as Dr. Kevin Esvelt, an evolutionary engineer at MIT, want to put genetic engineering into practice by modifying mice to be immune to the bite of Lyme-carrying ticks and then releasing them to breed on a small island in Marthas Vineyard. What will the consequences of that be? Even Esvelt really doesnt know for sure. And thats the problem, and where the ethical issues take hold. Sending genetically modified mice, dogs, or humans into the world may introduce unintended consequences, or might be deadly in the wrong hands. But are people who think its dangerous just being alarmist?

Our Take: Genetic engineering and all of its advantages and ethical quandaries is a complex topic to cover, and in the first part of their four-part docuseries, Kaufman and Egender try to lay out the issue in as balanced a way as possible. But what we got during the feature-length (70-minute) first episode was more of a sense of fear than one of wonder.

Why? Because, while the filmmakers are giving biohackers like Ishee and Dr. Zayner as much time as the more legit scientists, it doesnt help matters when you see Dr. Zayner concocting CRISPR samples in his kitchen or see Ishee looking at YouTube videos of glowing mice and luminescent monkeys for inspiration.

But then we see Jackson Kennedy, a boy from New Jersey who is autistic and was born with poor vision, and we become hopeful again. His parents got genetic testing for him that showed that hes missing a gene that would help him see. And hes going to go for treatment that fixes that gene, which should restore his sight if it works. This is where genetic engineering could make a huge positive impact on the world. But, whether the filmmakers intended it this way or not, there seems to be a whole lot scarier ways the use of CRISPR could go haywire, which makes us as cautious as the anti-engineering activists they interview for the first episode.

Sleeper Star: When Jasons mother talked about how he wanted to be an astronaut and how heartbroken he was when he heard that astronauts need 20-20 vision, it almost broke our hearts. While his story will be a through-line through the limited series, were disappointed that there isnt a documentary just about him.

Most Pilot-y Line: There are actually two scenes of Ishee collecting sperm from his dogs. Yuck.

Our Call: STREAM IT. Were wondering how much of what were going to see during the rest ofUnnatural Selection will be more crackpots and less of the positive stuff like Jasons treatment. If its the former, wed likely end up skipping it.

Your Call:

Joel Keller(@joelkeller) writes about food, entertainment, parenting and tech, but he doesnt kid himself: hes a TV junkie. His writing has appeared in the New York Times, Slate, Salon,VanityFair.com,Playboy.com, FastCompany.com,RollingStone.com, Billboard and elsewhere.

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British Biotech Company Sees Hope In Reducing Mosquito-Borne Diseases And Deaths With GMOs – Forbes

Posted: October 28, 2019 at 12:46 pm

Women wait with their malaria-struck babies for treatment in Angola. Will opponents of gene ... [+] engineering deny prevention to families like these?

Mosquitoes are not just obnoxious summer pests they are a serious health threat to most of the world. In fact, the WHO calls mosquitoes one of the deadliest animals in the world.

Why? Mosquitoes carry and spread diseases to humans that cause millions of deaths every year. The biggest threat is malaria: a half a million lives are lost annually, and Africa alone loses $12 billion in health care, productivity, investment, and tourism to the disease. Then theres Zika, dengue, chikungunya, and yellow fever each carried by mosquitoes, and each extracting their toll in human lives and livelihood.

But now, there is hope that biotechnology can help solve this crisis. The solution lies in genetically modifying a small population of mosquitoes and releasing them into malaria-prone areas. These mosquitoes carry a lethal gene that kills larvae before they reach adulthood and carry malaria to others, just stunting human illness.

Oxitec is a British biotechnology company doing just this. Over the last fifteen years or so the company has introduced Friendly Technology. Oxitecs latest results back up historic successes in Brazil, which saw dengue cases in one area reduced by 91% in a small trial. Their latest study showed a 96% reduction in mosquito numbers, this time using a more effective strategy of targeting the biting, egg-laying females - albeit leaving non-biting males to survive and reproduce. A great success, on the face of it.

The anti-GM backlash

However, Oxitec and others are taking a lot of flak from the anti-GM lobby, which according to the Genetic Literacy Project spent $850 million in the last five years alone opposing everything from the way we label genetically engineered food to fabric thats fermented from sugar.

The backlash was triggered by a paper that, ironically, seems likely to be retracted (or at least highly modified) due to exaggerated predictions of more robust mosquitoes, among others. Though reports of genetic mixing between surviving introduced mosquitoes and local mosquitoes were valid, the lethal gene was not actually present - which was the most likely outcome considering the lethality of the gene in question. A lethal gene will naturally diminish in frequency among a population.

But another consideration is to ask: does it even matter, all things considered, when eradication of disease should be the goal?

The risk of inaction

Mosquitoes are utterly deadly, and even when theyre not they provide among the largest disease burden on the planet. Tuberculosis may kill more people (around 1.3 million per year, compared with around 450,000 for malaria). But malaria infects 20 times that number of people.

Those 219 million annual malaria cases cost low income countries a significant chunk of their GDP up to 1.3% in the worst affected while just a 10% reduction in malaria was associated with a 0.3% growth in a much cited study on the economic burden of malaria. For Uganda, the economic gain from eradicating malaria would total around $50 million USD.

This doesnt take into account emerging diseases such as dengue and Zika virus, among others. In Brazil, the focus of Oxitecs recent trials aiming to reduce numbers of Aedes aegypti, 1.2 million people were infected with dengue in the first six months of 2019 six times more than in 2018 with an associated 388 deaths. Zika virus, carried by the same mosquito, exploded onto the scene in 2015 and has been associated with a range of effects on babies born to infected mothers in 10% of cases.

Yes, there are likely some knock-on ecosystem effects of releasing Oxitec mosquitoes. There might well be reduced prey for fish that eat the larvae, or less food for some of the birds that eat the flying insects. However, mosquitoes are not irreplaceable as far as the wider ecosystem is concerned, especially pests such as Aedes aegypti. There are another 3000 species of mosquito other than the three which primarily cause disease in people.

The World Health Organization (WHO) brands Aedes aegypti mosquitoes as being exquisitely adapted to city life, and that they prefer to breed in artificial containers. Given this information, it makes it even less important that lethal genes might persist among the wider population of these costly pests, less so that they might be eradicated - an opinion seemingly shared by researchers who have looked into the potential environmental costs associated with getting rid of the worst species of disease-bearing mosquitoes.

It all boils down to a cost/benefit analysis. Is the risk of some genetically modified mosquitoes passing on transgenes to wild populations worse than the risk of millions of people being infected with haemorrhagic fever and malaria, or babies being born with abnormally small heads (microcephaly)?

In any case, we will always have to take measures to reduce the burden of disease. What about the alternative forms of pest control and their relatively indiscriminate, off-target effects?

What is natural?

Oxitec, the company responsible for releasing genetically modified mosquitoes, have always known and stated - explicitly so - that some mosquitoes would survive to breed and pass on their genes. They have also taken measures to ensure that populations containing the lethal gene eventually go their predestined way.

In fact, their latest mosquitoes are meant to pass on genes to wild populations, this time to reverse the naturally occurring genetic mechanisms that render mosquitoes resistant to pesticides such as DEET. (Incidentally, multi drug resistance in the malaria parasite itself is also increasing).

To put our collective minds at ease, its worth pointing out that nature is weirder than what Oxitec is doing. mosquitoes perform their own version of enforced sterilisation, whereby male tiger mosquitoes (of the species Aedes albopictus) can mate with, and sterilize, female Aedes aegypti mosquitoes.

The fact that diseases such as Zika and dengue are present in Brazil in the first place is evidence that we are about as far removed from whatever natural used to mean as we can possibly be. Zika was introduced by a traveller from French Polynesia. The only way it got to Brazil was by aeroplane.

Its not just Zika traversing the globe in such a manner. There are emergent diseases popping up left, right and center, and it is not an easy task to keep them in check. The WHO warned us over ten years ago that infectious diseases are emerging at a rate not seen before. (One example is West Nile Virus, a mosquito-borne disease first described in 1937 in Uganda but discovered in New York in the summer of 1999. It is becoming more prevalent in California and will soon reach Silicon Valley and the San Francisco biotech region.)

It is no wonder. We live in a globally connected world with a rapidly expanding population that is a hotbed for disease-causing agents to emerge, mix, and spread (from viruses and bacteria to malaria parasites), which means that we need highly innovative, modern solutions to control them. Its an evolutionary arms race, and we need all the tools we can muster. If one of them happens to include lethal genes that successfully wipe out local populations of disease-causing mosquitoes, so be it.

Mosquito-borne diseases already threaten half of the global population.And as the climate warms and favors the mosquito, these diseases could spread to a billion more people.

Clearly, our current methods of control havent quite been enough to stop 219 million people becoming afflicted with malaria each year, or an increasing number suffering and dying from dengue and other diseases. Its not genes escaping that is the problem, but the sheer difficulty in eradicating mosquitoes and their diseases at all.

We must proceed carefully with new genetic engineering technologies, but we must also weigh the risks of inaction: each year hundreds of millions of people mostly children needlessly die, get sick, or suffer genetic defects. GMO mosquitoes are something we can do about it.

So what would you rather have: GMO mosquitoes or dying babies?

Acknowledgement: Thank you to Peter Bickerton for additional research and reporting in this post.

Please note: I am the founder ofSynBioBeta, and some of the companies that I write about are sponsors of theSynBioBeta conference(click herefor a full list of sponsors).

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British Biotech Company Sees Hope In Reducing Mosquito-Borne Diseases And Deaths With GMOs - Forbes

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AgriTech: 3+ Ways We Plan to Feed the Future – Interesting Engineering

Posted: October 28, 2019 at 12:46 pm

When we hear technology we think of electronic gadgets and a hundred types of software. But the problems of the future are going to be more basic.

Food, water, and shelter are important to talk about. Theyre essential to sustain human life and limited in availability. Moreover, the increasing population and concentration of population in major cities will possibly lead to scarcity unless we take due action.

RELATED: 11 INNOVATIONS THAT COULD BUILD THE FOOD OF THE FUTURE

This is not the first time we are seeing a population surge. Farming methods have evolved over the years to meet these growing demands in the form of farming tools, chemical fertilizers, and pesticides, etc.

The earliest known tools were sticks and stones which were later replaced by knives, scythes, and plows. It wasnt until the industrial revolution that modern machines were used in agriculture.

Wheeled harvesters and threshers paved the way for steam-powered tractors. But the introduction of gasoline and diesel engines was the last great invention in agriculture technology.

Similarly, manure was partially replaced by chemical fertilizers such as Ammonium Sulphates and Urea.

The increase in yield due to the adoption of these devices has helped sustain the population growth so far. But society has never been this conscious about health or the environment.

The fact is, if we keep relying on the same methods to increase the yield, it will lead to an environmental catastrophe. Moreover, trends like organic food are also going to impact agricultural practices of the future.

These trends are partially based on research that chemicals used in food get deposited in our bodies over time. The chemicals that go unabsorbed by the plants get washed away and pollute the water bodies.

Apart from these crops, animal husbandry, and farming of cotton and other non-edible plants are also undergoing similar trends and challenges.

This demand is not only affected by the world population but also by the economy and quality of life. People living a prosperous life tend to consume more, both in terms of quantity and variety.

On the other hand, it is projected that the number of farmers is going to decrease further. Growers who are older than 65 already outnumber the younger ones less than 45 years of age.

This shows the extent of urbanization and the receding interest of the youth in farming. At the same time, farming land is also decreasing as the cities are growing and more industries are being set up to feed them.

To address these issues, the field of farm management has emerged and brought forth approaches such as precision farming.

Precision farming is the use of future farm technologies to distribute water, fertilizers, and pesticide in regulated amounts. Each plant gets the precise measure of substances required.

This reduces the cost by reducing excess amounts and increasing yield. It also moderates the use of chemicals, leading to healthier crops and better overall environmental impact.

The emerging research on agriculture technology can be used to achieve this and more.

OpenAg is a project by MIT's Media Lab that uses botany, machine-learning algorithms, and chemistry to optimize farm produce. The remarkable thing is that without using any genetic modification, the team was able to improve the flavor and medicinal qualities of plants such as Basil by simply controlling the environment.

Computer algorithms determine the optimal growing conditions to maximize the volatile compounds, which are primarily responsible for the taste.

The next challenge for OpenAg is to help farmers adapt to climate change. They plan on achieving this by using controlled simulations of the plants in hydroponic containers called food computers.

The use of drones is not a new concept in farming. Drones have seen experimental use in spraying fertilizers and pesticides.

The problem is still at large. A UN estimate suggests that 2040% of global crop yields are destroyed due to pests and diseases.

Some universities and research groups such as Carnegie Mellon are experimenting with a combination of technologies to identify the problem at its inception and eliminate it.

Cameras mounted on drones can be used to survey the field for pests in the morning and suggest or even directly apply the counter-measures. Using cameras also lets us image infrared pictures that can pinpoint a disease before it spreads.

Scientists from Carnegie Mellon are already doing field tests with sorghum (Sorghum bicolor), a staple in many parts of Africa and a potential biofuel.

Agribotix is another example of drones being used in agriculture. Agribotix uses the principles of precision farming by applying pesticides just where it is needed and in the required quantity, reducing pesticide use to 0.1%.

The topsoil is the most important agricultural resource. While there are factors such as soil erosion and moisture loss at play, one avoidable factor is the use of heavy equipment.

Large harvesters damage and compact the soil. Overusing fertilizers has a disastrous long term impact.

Bonirob is set to reduce this by taking the farmer out of the cockpit. As no one is needed to drive the machine, the size is reduced. This leads to a reduction in engine power and consequently, the weight.

What you get then, is a robot that can be used to measure soil quality, weed, harvest, thresh or even interbreed plants to maximize yield without leaving a footprint of its own. Robots such as Bonirob, RIPPA, or Ecorobotix are taking the farms forward to the future.

Another application of farming tech is in animal husbandry. A Glasgow start-up, Silent Herdsman, is manufacturing smart collars based on the concept of smartwatches. The collar monitors fertility and disease by tracking various bodily parameters and activities.

The biggest hurdle to the adoption of such tech is surprisingly not farmers, but big-machinery manufacturers who resist the kind of change it would require in their business models to use this technology.

The other problem is that of intellectual property. Most of these technologies are of great impact and the labs developing them do not want to share their research and findings.

RELATED: IoT AND SMART AGRICULTURE ARE BUILDING OUR FUTURE CITIES TODAY

This is possibly slowing down the development of agritech. Fortunately, some universities, such as MIT, are taking the initiative to make their research publicly available under open source licenses.

They say that necessity is the mother of invention. Today, we can witness this saying in action as researchers around the world are coming together to solve the problem of world hunger.

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Karen Burnham Reviews Short Fiction: Lightspeed, New York Times, Tor.com, Big Echo, and Terraform – Locus Online

Posted: October 28, 2019 at 12:46 pm

Lightspeed 7/19New York Times 5/27/19Tor.com 6/5/19Big Echo 1/19Terraform 5/13/19

The science fiction stories in Julys Lightspeed catch characters at very different phases of their lives. The Null Space Conundrum by Violet Allen is an over-the-top story of Aria, a supercool (and very self-conscious about that coolness) cosmic cyborg entity helping the living song entity Kantikle on a mission to save the Universe from a destructive force. They are cooped up on a spaceship and getting on each others nerves, and things get really trippy when weird mind-warping weaponry comes into play. Whether you find this story fabulous or annoying will hinge on how much you appreciate Arias super-arch tone as the viewpoint character. In Miles and Miles and Miles, by contrast, Andrew Penn Romine gives us Noah Stubbs, a down-on-his-luck Moon resident who gets involved in scams of varying levels of illegality as his wife dies from cancer, likely due to the increased-radiation environment. As it seems like Noah is skipping back and forth in time, it becomes clear that hes suffering from dementia, possibly accelerated by that same radiations effect on his brain. His disorientation, sometimes becoming violent, and the concern of those around him, is palpable.

The New York Times invited Ted Chiang to submit an Op Ed from the future, and he delivered. Its 2059, and the Rich Kids Are Still Winning appeared in May. The premise is that genetic engineering has allowed wealthy parents to boost their childrens intelligence. In an effort to balance the scales, some poorer children were given the same enhancements, but no other assistance. Unsurprisingly, they did not come close to achieving the same educational or life outcomes as the enhanced rich kids. Chiang points out just how much the scales are weighted towards the affluent, as they can invest resources into any of their kids ventures, multiplying the potential that is already there. This is a punchy piece that cuts right through a huge swath of comforting myths we tell ourselves about living in a meritocratic society.

The publisher Tor approached the end of an era this spring as it finally moved out of the Flatiron Building, its long-time home in New York. In June Seanan McGuire provided a fitting tribute for Tor.com in the fun steampunk story Any Way the Wind Blows. Her Majestys Stalwart Trumpet of Glory, affectionately known as Stubby, is a dimension-hopping airship out to survey parallel universes, focused on New York. Many versions of New York have a version of the Flatiron Building, it turns out, so theres no way of knowing who might be inside when the scouts go to investigate. Captain Isabelle Langford has been out on mission for a long time and is heartily looking forward to being done with her tour; we also get to meet several of the entertainingly diverse beings that make up Stubbys crew. The Captain doesnt particularly appreciate it when shes called down to vouch for her away team, but its entirely necessary to assure the buildings inhabitants that theyre not just fans in town for a convention. This is shameless fan service, all in good fun and well executed.

Big Echos eleventh issue labels itself the SF and Religion issue, although, based on the four original stories here, I might have said philosophy rather than religion. It starts with It Is a Rare Thing the Emperor Requireth by Wm Henry Morris. The narrator is a scout from a deeply religious society, who has been captured by aliens. He can only communicate with one of them, the Weaver, via a gestural language that they develop together. This means they have a limited vocabulary and miss each others nuances; its very realistic but also quite a bit more challenging to read than the average universal translator style of SF. The captive is forced to create stories that his alien companion then weaves into silks; these are then ingested in some way by the Emperor. During the course of the story the captive tries to figure out to what extent he can subvert the Emperor by what he includes in his stories; then he starts to be more concerned for the physical and spiritual well-being of the Weaver. This is a story about different modes of communication and how vast gulfs between cultures and individuals might be spanned.

Famous as the Moon by Ethan Mills is a delightful story of a planet where Buddhist monks have recreated the personas of the worlds great philosophers to stage public debates for the edification of all. The author obviously had a great deal of fun imagining scenes such as a Acharya Vasubandhu vs. Bertrand Russell showdown. The plot involves some of the AIs going rogue and ceasing to provide life support for different parts of the complex. Josel Hamsa is an expert summoned from off-world to work on the problem discreetly. It turns out the AIs have made a momentous discovery out in the Ether one which is challenging their own notions of reality that is appropriate for any consciousness trained to think about the really big picture questions. Hamsa has to figure out a way to convince them back to their duties. When I See the Skylark Rise by A.J. Hammer also sends consciousnesses out into the void in search of the ineffable. In this universe, starships carry Seers to let the crews know if theyre about to be caught in a catastrophe. The Captain of the Lauzeta learns from her Seer that if she lands on the planet Ortyon, not just her crew will die, but a huge swath of the planets population as well. She does the right thing and stays away, even though her ship doesnt have enough food or fuel to get to any other port. As the crew makes their preparations for the end, the Seer decides to send her consciousness farther out into that realm where her visions come from, either to end her life that way or to find help out in the transcendent void. The final story is a short parable, translated by Toshiya Kamei from the original Spanish, New Testament by Fernando Schekaiban. This piece of eschatological flash fiction imagines Man at the height of His potential greatness, which is also the End of the Universe. It reminded me a little bit of Isaac Asimovs The Last Question, although Schekaibans story/Kameis translation is quite a bit more poetic.

In Terraform in May I particularly appreciated their publication of the first section of the story The Training Commission by Ingrid Burrington & Brendan Byrne. After reading the first chapter on Terraform, I signed up for their newsletter, where I received the rest of the story in installments over a few weeks. The story is told by emails and newsletter entries from freelance architectural journalist Aiofe, writing in 2038 in the aftermath of a second American Civil War, colloquially known as the National Shitstorm. The country is now largely run by supposedly benign algorithms and theres a Truth and Reconciliation process ongoing of which the titular Training Commission is part. At the start of the story Aiofe is ambushed by a visceral re-enactment of her brothers martyrdom as part of a Smithsonian exhibit on the Shitstorm, and she writes about it angrily for her newsletter followers, then in emails with other journalists, her sister, and mother. The plot turns thriller as she is handed an old-fashioned USB drive by a man at the Smithsonian, who later turns up dead in the Potomac. I enjoyed it enough, and especially appreciated the worldbuilding enough, to stick with the whole run. Id say the story suffered a little bit by being serialized; it was easy to forget some of the characters and relationships in the spaces between installments. I should admit, though, that the authors also posted a lot of supplementary material online that I didnt have a chance to follow through on. This was definitely an interesting use of the newsletter format for storytelling, and Id be interested to see more from this team.

Recommended Stories

Its 2059, and the Rich Kids Are Still Winning, Ted Chiang (New York Times 5/27/19)It Is a Rare Thing the Emperor Requireth, Wm Henry Morris (Big Echo 1/19)

Karen Burnham is an electromagnetics engineer by way of vocation, and a book reviewer/critic by way of avocation. She has worked on NASA projects including the Dream Chaser spacecraft and currently works in the automotive industry in Michigan. She has reviewed for venues such as Locus Magazine, NYRSF, Strange Horizons, SFSignal.com, and Cascadia Subduction Zone. She has produced podcasts for Locusmag.com and SFSignal.com, especially SF Crossing the Gulf with Karen Lord. Her book on Greg Egan came out from University of Illinois Press in 2014, and she has twice been nominated in the Best Non Fiction category of the British SF Awards.

This review and more like it in the August 2019 issue of Locus.

While you are here, please take a moment to support Locus with a one-time or recurring donation. We rely on reader donations to keep the magazine and site going, and would like to keep the site paywall free, but WE NEED YOUR FINANCIAL SUPPORT to continue quality coverage of the science fiction and fantasy field.

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How to save the worlds coral reefs – The Economist

Posted: October 28, 2019 at 12:46 pm

CORALS ARE comeback creatures. As the world froze and melted and sea levels rose and fell over 30,000 years, Australias Great Barrier Reef, which is roughly the size of Italy, died and revived five times. But now, thanks to human activity, corals face the most complex concoction of conditions they have yet had to deal with. Even these hardy invertebrates may struggle to come through their latest challenge without a bit of help.

According to the Intergovernmental Panel on Climate Change, a rise in global temperatures of 1.5C relative to pre-industrial times could cause coral reefs to decline by 70-90%. The planet is about 1C hotter than in the 19th century and its seas are becoming warmer, stormier and more acidic. This is already affecting relations between corals and the single-celled algae with which they live symbiotically, and which give them their colour. When waters become unusually warm, corals eject the algae, leaving reefs a ghostly white. This bleaching is happening five times as often as it did in the 1970s. The most recent such event, between 2014 and 2017, affected about three-quarters of the worlds reefs. Meanwhile the changing chemistry of the oceans lowers the abundance of carbonate ions, making it harder for corals to form their skeletons.

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If corals go, divers and marine biologists are not the only people who will miss them. Reefs take up a fraction of a percent of the sea floor, but support a quarter of the planets fish biodiversity. The fish that reefs shelter are especially valuable to their poorest human neighbours, many of whom depend on them as a source of protein. Roughly an eighth of the worlds population lives within 100km of a reef. Corals also protect 150,000km of shoreline in more than 100 countries and territories from the oceans buffeting, as well as generating billions of dollars in tourism revenue. In the Coral Triangle, an area of water stretching across South-East Asia and into the Pacific which is home to three-quarters of known coral species, more than 130m people rely on reefs for food and for their livelihoods in fishing and tourism.

Measures to mitigate climate change are needed regardless of coral, but even if the worlds great powers were to put their shoulder to the problem, global warming would not be brought to a swift halt. Coral systems must adapt if they are to survive, and governments in countries with reefs can help them do so.

Corals need protection from local sources of harm. Their ecosystems suffer from coastal run-off, whether sewage or waste from farms, as well as the sediment dumped from beach-front building sites. Plastic and other debris block sunlight and spread hostile bacteria. Chunks of reef are blown up by blast fishing; algae grow too much whenever fishing is too intensive. Governments need to impose tighter rules on these industries, such as tougher local building codes, and to put more effort into enforcing rules against overfishing.

Setting up marine protected areas could help reefs. Locals who fear for their livelihoods could be given work as rangers with the job of looking after the reserves. Levies on visitors to marine parks, similar to those imposed in parts of the Caribbean, could help pay for such schemes. So too could a special tax on coastal property developers.

Many reefs that have been damaged could benefit from restoration. Corals biodiversity offers hope, because the same coral will grow differently under different conditions. Corals of the western Pacific near Indonesia, for example, can withstand higher temperatures than the same species in the eastern Pacific near Hawaii. Identifying the hardiest types and encouraging them to grow in new spots is a way forward, though an expensive one. A massive project of this sort is under way in Saudi Arabia as part of a tourism drive. Scientists working alongside the Red Sea Development Company want to discover why the areas species seem to thrive in its particularly warm waters.

More drastic intervention to head off the larger threats corals face should also attract more research. Shading reefs using a polymer film as a sunscreen to cool them is under discussion for parts of the Great Barrier Reef. Other schemes to help corals involve genetic engineering, selective breeding and brightening the clouds in the sky above an area of the reef by spraying specks of salt into the lowest ones, so that they deflect more of the suns energy. These measures may sound extreme, but people need to get used to thinking big. Dealing with the problems caused by climate change will call for some radical ideas.

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Watchmen Theory: Jeremy Irons’ Butler Is Doctor Manhattan – Screen Rant

Posted: October 28, 2019 at 12:46 pm

Warning: This article contains SPOILERS from Watchmen episode 2.

The nature of Adrian Veidt's (Jeremy Irons) creepy servants is one of the biggest questions inWatchmen, but it's possible that Mr. Phillips (Tom Mison) could actually be Doctor Manhattan, or rather, a clone of his human alter ego Jon Osterman. Phillips and Veidt's maid, Ms. Crookshanks (Sara Vickers), appeared in Watchmen's pilot happily serving their master in his ornate castle. This includes acting in a bizarre play Adrian wrote called "The Watchmaker's Son". However, their twisted performance gives the powerful impression that Veidt is mocking Doctor Manhattan and his dead girlfriend Janey Slater via Phillips and Crookshanks, who could be their genetically-engineered doppelgangers.

Though Watchmen hasn't explicitly declared that Jeremy Irons' is playing Adrian Veidt, the second episode, "Martial Feats of Comanche Horsemanship", leaves little doubt that Irons' mystery man is indeed Ozymandias. HBO's tie-in website, Peteypedia, contains supplemental materials about the series, including a news clipping dated September 9, 2019 titled "Veidt Declared Dead". The article states that Adrian Veidt vanished in 2012 - 7 years before Watchmen begins - but in the premiere episode, Irons' character is celebrating some sort of anniversary, complete with a special gold and purple cake, which are the colors of Ozymandias. Further erasing doubts that Irons is Veidt, he declared he was writing a play - a tragedy in five acts called "The Watchmaker's Son" - and now that it has been performed by Phillips and Crookshanks, it's absolutely about Doctor Manhattan's tragic origin - a tale Veidt knows very well.

Related: Watchmen: A Theory About Jeremy Irons' Ozymandias

Every fan of Alan Moore and Dave Gibbons' graphic novel or Zack Snyder's Watchmen movie remembers how Doctor Manhattan was created and "The Watchmaker's Son" picks up at the story's tragic end: in 1959 at the Gila Flats research lab, physicist Dr. Jon Osterman (Phillips) and his girlfriend Janey Slater (Vickers) are desperately in love but Jon mistakenly left his father's pocket watch in their creation, the Intrinsic Field Generator. After going in to retrieve the watch, Osterman is sealed inside and is disintegrated, only to re-emerge weeks later as the superpowered being Doctor Manhattan. "The Watchmaker's Son" bombastically mocks Jon's ordeal, with Veidt in the crowd urging Crookshanks/Slater that he wants to "see those tears!"as Phillips/Osterman dies horribly. Seconds later, a nude Phillips painted blue emerges from the sealing as Doctor Manhattan, accompanied by Wagner's "Ride of the Valkyries" (a nod to Snyder's film). The play concludes with Veidt resignedly joining Phillips/Manhattan in reciting the ominous final words, "Nothing ever ends".

To make the play believable, Veidt actually has Phillips roasted alive in his mock "Intrinsic Field Generator", which leads to the next big shock: there are multiple Mr. Phillips and Ms. Crookshanks because they are indeed all clones. This makes sense since Ozymandias is a master of genetic engineering; in the 1980s, his prized pet was a giant cloned lynx named Bubastis and Veidt made a fortune selling his cloning technology in the 1990s. Veidt's expertise must have expanded to creating (not quite perfect) humans.

But since Phillips and Crookshanks are clones, who did Veidt model them after? It's quite possible he chose to base his disposable servants on Jon Osterman and Janey Slater. After all, Ozymandias knew both of them quite well; he first met Doctor Manhattan and Slater at the ill-fated only meeting of the Crime Busters superhero team in the 1960s. In 1985, he conspired to infect Slater with cancer as part of his scheme to force Doctor Manhattan to leave the planet, paving the way for his hoax that would ultimately save the worldin Watchmen's ending. Given what he did to the real Janey, he clearly would have no qualms about killing their duplicates. Further, Watchmen has teased Doctor Manhattan will appear in the series but has not announced who plays the blue super-being - could it be because Tom Mison is already 'cast' in a version of the role and is right there in plain sight?

If the servants really are clones of Jon Osterman and Janey Slater, then Adrian Veidt must despise Doctor Manhattan enough so that in his exile, wherever he is, Ozymandias could have chosen to make replicas of his nemesis and his girlfriend to literally dote on him hand and foot - and then kill them for his own amusement. "The Watchmaker's Son" feels like a kind of excessively petty revenge by a bitter old man who is powerless against the real Doctor Manhattan. But nothing ever ends in Watchmen, including Veidt's ire at Doctor Manhattan, so much so that it looks like Ozymandias ruthlessly murders clones of Jon Osterman and Janey Slater as a sick form of recreation and catharsis.

Next: Everything That Happened Between The Watchmen Graphic Novel And HBO Series

Watchmen airs Sundays @ 9pm on HBO.

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What Wilmer Valderrama Has Done Since That 70s Show

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