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AgeX Therapeutics Reports Third Quarter 2019 Financial Results and Provides Business Update – BioSpace

Nov. 14, 2019 21:00 UTC

ALAMEDA, Calif.--(BUSINESS WIRE)-- AgeX Therapeutics, Inc.(AgeX; NYSE American: AGE), a biotechnology company developing therapeutics for human aging and regeneration, reported financial and operating results for the third quarter ended September 30, 2019.

Driven by our vision of being the leading biotechnology company with a focus on human aging, in the third quarter we advanced our product development on numerous fronts, said Michael D. West, Ph.D., founder and Chief Executive Officer. Our recent build-out of GMP-compliant manufacturing laboratory space will facilitate our manufacture of master cell banks such as those that carry the UniverCyteTM genetic modification for off-the-shelf cell-based regenerative therapy.

Recent Highlights

Second Quarter 2019 Operating Results

Revenues: Total revenues for the three months ended September 30, 2019 were $411,000, as compared with $380,000 in the same period in 2018. AgeX revenue is primarily generated from subscription and advertising revenues from the GeneCards online database through its subsidiary LifeMap Sciences, Inc. 2019 revenues also included $41,000 of grant revenue from the NIH. AgeX had no grant revenues in the same period in 2018.

Operating expenses: Operating expenses for the three months ended September 30, 2019 were $3.6 million, as compared with $2.6 million for the same period in 2018. On an as-adjusted basis, operating expenses for the three months ended September 30, 2019 were $2.9 million as compared to $2.2 million for the same period in 2018.

The reconciliation between operating expenses determined in accordance with accounting principles generally accepted in the United States (GAAP) and operating expenses, as adjusted, a non-GAAP measure, is provided in the financial tables included at the end of this press release.

Research and development expenses for the three months ended September 30, 2019 were $1.4 million, as compared with $1.3 million in the same period in 2018.

General and administrative expenses for the three months ended September 30, 2019 were $2.2 million, as compared with $1.3 million in the same period in 2018.

Net loss attributable to AgeX: The net loss attributable to AgeX for the three months ended September 30, 2019 was $3.2 million, or ($0.09) per share (basic and diluted) compared to $2.2 million, or ($0.06) per share (basic and diluted), for the same period in 2018.

Balance Sheet Highlights

Cash, and cash equivalents, including restricted cash totaled $3.8 million as of September 30, 2019, in addition to which we have $1.5 million remaining available for borrowing under a credit facility provided by Juvenescence Limited, which brought our total available capital to $5.3 million. However, under accounting standard ASC 205-40 Presentation of Financial Statements-Going Concern, AgeXs cash and cash equivalents of $3.8 million as of September 30, 2019 and the loan facility by Juvenescence may not be sufficient, without raising additional capital and reducing expenditures, to satisfy AgeXs anticipated operating and other funding requirements for the next twelve months from the issuance of its interim condensed consolidated interim financial statements.

About AgeX Therapeutics

AgeX Therapeutics, Inc. (NYSE American: AGE) is focused on developing and commercializing innovative therapeutics for human aging. Its PureStem and UniverCyte manufacturing and immunotolerance technologies are designed to work together to generate highly-defined, universal, allogeneic, off-the-shelf pluripotent stem cell-derived young cells of any type for application in a variety of diseases with a high unmet medical need. AgeX has two preclinical cell therapy programs: AGEX-VASC1 (vascular progenitor cells) for tissue ischemia and AGEX-BAT1 (brown fat cells) for Type II diabetes. AgeXs revolutionary longevity platform induced Tissue Regeneration (iTR) aims to unlock cellular immortality and regenerative capacity to reverse age-related changes within tissues. AGEX-iTR1547 is an iTR-based formulation in preclinical development. HyStem is AgeXs delivery technology to stably engraft PureStem cell therapies in the body. AgeX is developing its core product pipeline for use in the clinic to extend human healthspan and is seeking opportunities to establish licensing and collaboration agreements around its broad IP estate and proprietary technology platforms.

For more information, please visit http://www.agexinc.com or connect with the company on Twitter, Facebook, and YouTube.

Forward-Looking Statements

Certain statements contained in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not historical fact including, but not limited to statements that contain words such as will, believes, plans, anticipates, expects, estimates should also be considered forward-looking statements. Forward-looking statements involve risks and uncertainties. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the business of AgeX Therapeutics, Inc. and its subsidiaries, particularly those mentioned in the cautionary statements found in more detail in the Risk Factors section of AgeXs Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commissions (copies of which may be obtained at http://www.sec.gov). Subsequent events and developments may cause these forward-looking statements to change. AgeX specifically disclaims any obligation or intention to update or revise these forward-looking statements as a result of changed events or circumstances that occur after the date of this release, except as required by applicable law.

AGEX THERAPEUTICS, INC. AND SUBSIDIARIES

CONDENSED CONSOLIDATED BALANCE SHEETS

(IN THOUSANDS, EXCEPT PAR VALUE AMOUNTS)

September 30, 2019

December 31, 2018

(Unaudited)

ASSETS

CURRENT ASSETS

Cash and cash equivalents

$

3,768

$

6,707

Accounts and grants receivable, net

234

131

Prepaid expenses and other current assets

688

1,015

Total current assets

4,690

7,853

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INDIA Indian doctor: Medical innovation should not try to replace the Creator – AsiaNews

Dr Pascoal Carvalho addressed the 21st convention of Indias Catholic nurses in Mumbai. He spoke about the ethical aspects of genetic engineering, citing the doctrine of the Church towards human cloning and stem cells. Respect for human dignity must prevail from conception to natural death.

Mumbai (AsiaNews) Medical innovation, which increasingly uses modern technologies to improve life, should not attempt to artificially replicate creation, said Dr Pascoal Carvalho, a doctor from Mumbai and a member of the Pontifical Academy for Life, speaking at the 21st convention of Catholic nurses (8-10 November).

In his address on 9 November, he referred to therapeutic cloning, stem cells and modified human DNA before an audience of more than 200 Catholic health workers.

"[W]e can rest assured in the wisdom of the Church," he said, because for her, The dignity of a person must be recognized in every human being from conception to natural death.

Some areas of medical research that raise serious moral and ethical questions touch stem cells, embryos and DNA.

In his view, today There is a growing threat of overestimating genetic modification techniques and underestimating the repercussions of cloning and human gene therapy.

On the one hand, we have the positive results of therapeutic cloning aimed at organ and tissues reconstructed in laboratory for transplanting into patients to reduce the risk of rejection; on the other, reproductive cloning, like in the case of Dolly the sheep, seeks to reproduce living beings.

He warns against research that leads to alterations in an organisms DNA, like the famous case of the Chinese scientist who in 2018 said that he had created two twins in the laboratory immune to the HIV virus. This kind of experiment can reduce life expectancy and increase susceptibility to other, and perhaps more common, diseases.

The doctor cites the Dignitas Personae, which defines any attempt at human cloning as unacceptable, because it represents a serious offense to the dignity of the person and fundamental equality between men.

As for therapeutic cloning, To create embryos with the intention of destroying them, even with the intention of helping the sick, is completely incompatible with human dignity, because it makes the existence of a human being at the embryonic stage nothing more than a means to be used and destroyed. It is gravely immoral to sacrifice a human life for therapeutic ends.

Citing the doctrine of the Church, Dr Carvalho stresses the importance of the method with which stem cells are taken. In his view, Methods which do not cause serious harm to the subject from whom the stem cells are taken are to be considered licit.

This is generally the case when tissues are taken from: a) an adult organism; b) the blood of the umbilical cord at the time of birth; c) foetuses who have died of natural causes.

Overall, the doctor believes that modern gene technologies raise new moral questions, whilst attempts to create a new type of human being contains an ideological element in which man tries to take the place of his Creator.

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This wristband tells you what food to buy based on your DNA – World Economic Forum

When an undiagnosed rare genetic disease caused his young sons kidneys to fail, Professor Chris Toumazou vowed to find a way of uncovering hidden health risks.

The professor of biomedical engineering realised that, although his sons condition could not have been prevented, the family could have managed his lifestyle very differently had they known about his condition.

So, he embarked on a mission to help people change their lifestyles and avoid getting sick.

Lifestyle, he says, has a huge impact on many undiagnosed conditions such as diabetes and high blood pressure. Changing behaviour could save lives.

The result of his research is a simple wristband that uses your DNA to help you make healthy choices as you shop for groceries.

By analysing the part of your genetic code determining susceptibility to nutrition-related health conditions like diabetes, DNANudge tells you which foods are best for you, and which you should avoid.

DNANudge analyses your genetic code and tells you which foods are best for you, and which you should avoid.

Image: DNANudge

The wristband scans shop barcodes and shows a green light if a product is OK and red if it may be harmful in the long run. The wristband's linked smartphone app suggests healthier alternatives when the red light comes on.

Following his sons acute illness, Toumazou also invented a microchip that can read an individuals DNA from a simple mouth swab sample. Its now used to upload a DNA profile to the new wristband a process that takes an hour instead of up to eight weeks for a conventional DNA test.

"We're not telling people they can't eat biscuits, that they should eat grapes. No, they can eat biscuits, but eat the better biscuits based upon your DNA and lifestyle," says Toumazou.

"It's using biology to nudge and guide you to have a healthier lifestyle in the long term."

The World Economic Forum was the first to draw the worlds attention to the Fourth Industrial Revolution, the current period of unprecedented change driven by rapid technological advances. Policies, norms and regulations have not been able to keep up with the pace of innovation, creating a growing need to fill this gap.

The Forum established the Centre for the Fourth Industrial Revolution Network in 2017 to ensure that new and emerging technologies will helpnot harmhumanity in the future. Headquartered in San Francisco, the network launched centres in China, India and Japan in 2018 and is rapidly establishing locally-run Affiliate Centres in many countries around the world.

The global network is working closely with partners from government, business, academia and civil society to co-design and pilot agile frameworks for governing new and emerging technologies, including artificial intelligence (AI), autonomous vehicles, blockchain, data policy, digital trade, drones, internet of things (IoT), precision medicine and environmental innovations.

Learn more about the groundbreaking work that the Centre for the Fourth Industrial Revolution Network is doing to prepare us for the future.

Want to help us shape the Fourth Industrial Revolution? Contact us to find out how you can become a member or partner.

The device also helps to promote overall health by warning if you are inactive for too long. An orange light means it's time to get up and move about.

One in 10 people with pre-diabetes, a reversible condition, will go on to develop type 2 diabetes, which affects more than 400 million people worldwide. Early diagnosis can enable people to change their lifestyles and avoid developing the full-blown condition.

And what about Toumazous son Marcus? Well, his story has a happy ending. After months in dialysis he received a kidney transplant and is now in good health.

He even met the Queen at the opening of his fathers new lab in London. He told her his father was changing healthcare by making microchips for the human body.

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World Economic Forum articles may be republished in accordance with our Terms of Use.

The views expressed in this article are those of the author alone and not the World Economic Forum.

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How Gene Editing Is Changing the World – The Wire

Across the US, more than 100,000 people are awaiting organ transplants. But there simply arent enough hearts, lungs, livers, and kidneys to meet demand, and 20 people die every day without the organs they need. For decades, scientists have dreamed of using animals to help fill the gap. Theyve been particularly interested in harvesting organs from pigs, whose physiology is similar to our own. Unfortunately, pigs also present some big biological challenges, including the fact that their genomes are chock full of genes that code for what are known as retroviruses, which could pose a serious threat to patients who receive porcine organs.

In 2015, George Church, a geneticist at Harvard University, announced a stunning breakthrough: Working with pig cells, he and his colleagues had managed to disable 62 copies of a retrovirus gene in one fell swoop. This would have been virtually impossible and a logistical nightmare with older forms of genetic modification, writes Nessa Carey in her new book, Hacking the Code of Life: How Gene Editing Will Rewrite Our Futures. But by using the new gene editing technology known as Crispr, the task was a relative cinch.

Nessa CareyHacking the Code of LifeIcon Books

Its just one example of how gene editing is giving us the power to alter the genome with unprecedented speed and precision. Carey, a biologist with a background in the biotech and pharmaceutical industry, offersa brisk, accessible primer on the fast-moving field, a clear-eyed look at a technology that is already driving major scientific advances and raising complex ethical questions

Its giving every biologist in the world the tools to answer in a few months questions that some scientists have spent half their careers trying to address, Carey writes. Its fueling new ways to tackle problems in fields as diverse as agriculture and cancer treatments. Its a story that began with curiosity, accelerated with ambition, will make some individuals and institutions extraordinarily wealthy, and will touch all our lives.

Though there are several different approaches to gene editing, the most prominent and the one that really supercharged the field is Crispr. The technique, based on an anti-viral defence system thats naturally present in bacteria, requires two pieces of biological material: an enzyme that acts as a pair of minuscule scissors, slicing strands of DNA in two; and a guide molecule that tells the enzyme where to cut.

In bacteria, these guide molecules direct the enzyme to chop up the genomes of invading viruses, preventing them from replicating.

But in 2012 and 2013, two teams of scientists reported that it was possible to hack this system to slice into any strand of DNA, at any complementary location they chose. Researchers could, for instance, create a guide molecule that steered the enzyme to one specific gene in the mouse genome and insert the editing machinery into a mouse cell; the enzyme would then make its cut at that exact spot.

Also Read: Is There More to Gene Editing Than Creating Designer Humans?

The cell would repair the severed DNA, but it would do so imperfectly, disabling the gene in question. In the years that followed, scientists refined the technique, learning to use it not only to inactivate genes but also to insert new genetic material at specific locations along the genome.

The approach is cheaper, easier, and faster than older methods of genetic engineering, which were first developed in the 1970s. In addition, as Carey explains, it can be used to create smaller modifications to the genome, and leaves fewer extraneous genetic elements. In its most technically exquisite form, gene editing leaves no molecular trace at all. It may just change, in a precisely controlled manner, one letter of the genetic alphabet.

But in 2012 and 2013, two teams of scientists reported that it was possible to slice into any strand of DNA. Photo: qimono/pixabay

The applications are almost endless. Gene editing has immense potential for basic research; scientists can learn a lot about what genes do by selectively disabling them. In addition, researchers have used the technology to create a wide variety of organisms that could become valuable agricultural commodities, including mushrooms that dont brown; wheat that produces fewer gluten proteins; drought tolerant, high-yield rice and corn; disease-resistant pigs; and super muscular goats.

How these products will do on the market if they ever reach it remains uncertain. Globally, gene-edited organisms are regulated by a patchwork of conflicting rules. For instance, in 2018, the US Department of Agriculture announced that it would not regulate gene-edited crops that could otherwise have been developed through traditional breeding techniques. A few months later, however, the European Union said that it would subject gene-edited plants to stringent restrictions.

Beyond agriculture, gene editing has enormous potential for medicine. It might, for instance, become a much-needed treatment for sickle cell disease. That painful, debilitating disease results from a genetic mutation that causes patients to produce a deformed version of haemoglobin, a protein that helps red blood cells transport oxygen. In a clinical trial currently underway, scientists are removing stem cells from the bone marrow of sickle cell patients, using Crispr to edit them, and then infusing the edited cells back into patients.

Also Read: Explainer: What Is CRISPR and How Does It Work?

Even if this trial succeeds, however, gene editing will not be a cure-all. It doesnt always work perfectly and can be challenging to administer directly to living humans (which is why some scientists are instead editing patients cells outside the body). Moreover, many diseases are caused by complex interactions between multiple genes, or genes and the environment. In fact, many of the most common and debilitating conditions arent likely to be good candidates for gene editing any time soon, Carey writes.

And, of course, the ethics of human gene editing can be enormously fraught. Thats especially true when scientists modify sperm cells, egg cells, or early embryos, making tweaks that could be passed down to subsequent generations. This kind of gene editing could theoretically cure some absolutely devastating genetic conditions, but we still have a lot to learn about its safety and effectiveness. It also raises a host of difficult questions about consent (an embryo obviously cannot give it), inequality (who will have access to the technology?), and discrimination (what will the ability to edit a gene related to deafness mean for deaf people, deaf culture, and the disability rights movement more broadly?).

Even in the face of these questions, at least one scientist has already forged ahead. In November 2018, He Jiankui, a researcher then at the Southern University of Science and Technology in China, shocked the world by announcing that the worlds first gene-edited babies twin girls, who He called Nana and Lulu had already been born. Months earlier, when Nana and Lulu were just embryos, He had edited their CCR5 genes, which code for a protein that allows HIV to infect human cells. By disabling the gene, He hoped to engineer humans who would be protected from HIV infection.

Also Read: How a Rogue Chinese Experiment Might Affect Gene-Based Therapies in India

The outcry was swift and harsh. Scientists alleged that Hes science was sloppy and unethical, putting two human beings at unnecessary risk. After all, there are already plenty of ways to prevent HIV transmission, and the CCR5 protein is known to have some benefits, including protecting against the flu. And He had raced ahead of the experts who were still trying to work out careful ethical guidelines for editing human embryos. He Jiankui has shot this measured approach to pieces with his announcement, and now the rest of the scientific community is on the back foot, trying to reassure the public and to create consensus rapidly, Carey writes.

Scientist He Jiankui attends the International Summit on Human Genome Editing at the University of Hong Kong on November 28, 2018. Photo: REUTERS/Stringer/File Photo

Hacking the Code of Lifedoesnt break much new ground, and for readers who have been paying attention to Crispr over the past few years, little in the book will come as a surprise. But it does provide a broad, even-handed overview of how much has already happened in a field that is less than ten years old.

Carey swats down the most dystopian dreams about Crispr, like the prospect that criminals might edit their own DNA to evade justice. Shes similarly skeptical that well end up using the technology to create super-beings with enhanced genomes that will make them taller, faster, more attractive.

We actually understand very little about the genetic basis of these traits and what we do know suggests that it will be very difficult to enhance humans in this way, she writes.

But she also acknowledges real risks, including the possibility that the technique could be used to create dangerous bioweapons, that gene-edited organisms could destabilise natural ecosystems, and that our new, hardy crops could prompt us to convert even more of the Earths undeveloped places into farmland.

None of this means that the technology should be abandoned; it has immense potential to improve our lives, as the book makes clear. But it does mean we need to proceed with caution. As Carey writes, Ideally, ethics should not be dragged along in the wake of scientific advances; the two should progress together, informing one another.

Emily Anthes, who has written for Undark, The New York Times, The New Yorker, Wired, and Scientific American, among other publications, is the author of the forthcoming book The Great Indoors.

This article was originally published on Undark. Read the original article.

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From self-drive cars to IoT, these next-wave techs will rule 2020s decade – Business Standard

For the first time human life changed significantly in the 20th century after several centuries of incremental progress. After hundreds of years of social, economic and political change, technology was the harbinger of a complete transformation. Commercial electricity, automobiles, aircraft, refrigeration, radar, sound recording, radio, film, television, x-rays, rayon, aspirin, antibiotics, organ transplants, transistors, microchips, nuclear power, spaceflights, genetic engineering, ATMs, credit cards, mobile phone, computers, robotics Internet and the whole gamut of digital services, around which our lives revolve all in the course of a few decades altered our human society. The speed of change has only increased. Since the turn of the millennium, we have already discarded some of the things which came into existence in our childhood. E-commerce shared services and AI are creating a new ecosystem of 24 & 7 engagement and consumption. What will come in the next 10 years will supersede a lot of what came in fifty years earlier, including some products and services we consider au courant and new age today.

The most obvious change in the next decade will still be in the digital domain. While it may seem that we are already submerged in a sea of devices and media constantly glaring at us through various screens. The next iteration of all such familiar services will be smarter, effective and personal. With faster and more powerful microchips AI (Artificial Intelligence) will be the framework of tomorrow's mindscape. What exactly is AI? Simply put AI is the use of massive amounts of data that is processed through machine learning to mimic human intelligence. A computer or any other device with a microchip to process data acquires an ability to respond to certain actions and behavior through the use of algorithms in a manner the user would have in a similar situation. We already see AI being used in several home appliances or even websites like Google, Facebook, Amazon, and online news services. Depending on your viewing pattern content is served (and suggested) for you to read, listen or watch. Newer models of cars have AI embedded in their navigation system. In the years to come most of our mundane and routine tasks will be done by machines, often very inexpensive and omnipresent. Much of the tedium and often dangerous work will be tackled by AI-assisted service providers and devices. Smart homes and cities which for example Prime Minister Modi keeps talking about are not some Utopian dreams but tomorrow's reality.

Sine 2015-16 we are using Web 3.0 as the overlay of our digital universe. This is a Semantic web that incorporates Big Data, Artificial Intelligence, Data Mining, Natural Language Search and Machine Learning technologies, Social Media, Internet of Things (IoT) and other customized online services including social media and streaming services. By 2025 we should usher in Web 4.0. This next development of the Internet will create services that will be autonomous, proactive, self-learning, collaborative and safe and secure, interacting with sensors and implants, natural-language services, or virtual reality. In simple terms, it means self-driving cars, remote diagnostics, and surgery, instant accounting, virtual reality in films and gaming, curated content and commerce, voice-activated devices and services, virtual assistants, digital concierge, and smart homes and offices. Blockchain ensures flawless data analytics and transparency in every transaction. From utility bills to land records, banking to governance all enabled seamlessly. The role of JAM (Jandhan Bank Account, Aadhar, and Mobile) along with India stack is what will enable the big leap forward in India-similar initiatives at different scales elsewhere too. While most are familiar with JAM, India Stack is less known. This truly empowering technology is the creation of a unified software platform that brings a billion-plus Indians into the digital age. A set of API (application programming interface)s that allows governments, businesses, start-ups, shop keepers, merchants and traders and soon farmers to utilize a unique digital Infrastructure to solve India's hard problems. Initially championed by Nandan Nilekani India Stacks is going to be a force multiplier in our lives tomorrow. Almost any service can be used anywhere in the world using a particular API and this infrastructure is cheap and convenient. There are concerns about privacy and data theft which I will tackle later in this article.

One of the fundamental principles of anything which is shared is trust. In a networked society that is increasingly based on a transactional economy or shared information, it is imperative that this trust is not only apparent but is inbuilt in the architecture of all contracts, monetary or otherwise. Today and in future blockchain provides trust and transparency. In a way similar to how Wikipedia is built where anyone can identify herself and participate in creating a shared resource, a blockchain, too, is just an immutable of record of data that is managed by cluster (or more) of computers and every bit of this data is simultaneously visible to all who are a part of the particular blockchain. It's a shared ledger that transparently records every transaction in real-time. Since each block of data is secured and bound to each other using cryptography it is entirely trustworthy. Blockchain is now used in social networks, banking, e-commerce, governance, Industry, security, trade, taxation, storage platforms, Intellectual Property Protection (IPR), education, content production, and distribution. In the next few years, blockchain will be the digital backbone of our existence. Cryptocurrency Bitcoin was the first to popularize blockchain but even in 2019, it is a bit unconventional to find mass acceptance. In India for example blockchain in the years to come will allow instant polling in a fully transparent manner eliminating a lot of costs and political bickering. Internet of Things (IoT) is dependent on blockchain as is autonomous mobility.

In the last 50 years owing to advances in science and technology-enabled healthcare humans are living longer. Thus for the first time, the world is faced with a demographic dilemma. How to take care of an increased number of geriatrics even as it grapples to treat millions of people suffering from various small and terminal ailments. There have been substantial breakthroughs in medicine. Vaccines for diseases like smallpox, measles, rotavirus, polio, yellow fever, rabies, hepatitis, HIV to common ailments like influenza and pneumonia are saving millions of lives every year. Digital technology is now routinely used for diagnostics. CAT Scan, MRI, Ultra Sound Scan, Doppler have in the recent past changed both the speed and accuracy of curative and palliative care. In the coming years, not only smartphones but other inexpensive wearables will allow almost anyone to monitor body functions. Blockchain will allow a healthcare professionals with access to a mobile phone to access the most advanced advice. Robotic surgery will in the next decade become miniaturized and much more ubiquitous. The most pressing need for the healthcare industry is to upgrade skills. Medical education has to move beyond Gray's Anatomy and stethoscope to next-gen healthcare. 60 percent of the world's population still has little access to a doctor or a hospital. Broadband and blockchain will empower even a paramedic or midwife to be able to provide first point care to the sick and injured. New digital tools paired with AI analytics will almost certainly boost diagnosticians' accuracy and speed, improving disease detection at early stages and thus raising the odds of successful treatment or cure.

Living well and longer are two primordial human obsessions. Helping us to be healthier for longer in the next decade will be rapid advances in genetic engineering, new age diagnostics, and stem cell therapy. As more research is done in genomics, microbiome and molecular biology we can expect the beginning of a new range of pharmaceuticals. Although we have had pacemakers and other simple implantable devices like contact lenses and cochlear aids for years the next decade will see the advent of IEMDs such as phrenic nerve stimulation to restore breathing function in patients with breathing disorders, glucose sensors for diabetics, sacral nerve stimulation for patients with bladder disorders, and implantable drug delivery systems. Epilepsy, Alzheimer's and other neurological illnesses will be treated by electrochemical sensors and miniature tissue oxygenators and drug delivery systems will be introduced within the next decade. Immunology, 3 D printed organs and Cancer treatment are other areas where data analytics and web-based tools will help tomorrow's healthcare professionals a lot. For billions of people around the world, these small scientific interventions may be the difference between life and death. However, the physical presence and skill of a doctor will be the basis of all technological advancements in medicine. In fact, technology is opening up several new opportunities for employment in diagnostic centers in small towns, even villages, online supply and delivery of medicines and other medical goods. Riding on Internet schemes like Ayushman Bharat will not only provide affordable healthcare to the poorer sections of India but also provide employment to young paramedics, nurses, pharmacists and other health professionals across various touchpoints.

There are other changes in the offing. Most of these too are web-based technologies like cloud computing, AI, VR, Blockchain, Robotics, and Machine learning. According to a McKinsey report released in 2017, 800 million people around the world will lose their jobs in ten years due to automation. I believe while the actual job losses will exceed a billion, several hundred million will get redeployed in other jobs that the digital value chain creates. We have seen while e-commerce has displaced traditional merchants and shopkeepers, it has created perhaps a larger number of jobs in logistics, customer experience, and transportation. In India hundreds of thousands of artisans, craftspeople and small merchants were getting bogged down by a shortage of capital or changing of customer preferences. I recently bought a handcrafted lace table cloth from Amazon. After that, I got a message from an artisan based in South India who was the actual supplier. He messaged me a list of other items he could custom make for me and I did place a small order with him directly. When I called him up he said Amazon has changed his life by enlarging his customer base manifold that he now employs 12 people in his new workshop. In the last decade, we have seen how mobile phones empowered our neighborhood vegetable seller or fisherwoman. I spend regular periods in a village in Himachal. I am surprised at the speed which phones and the Internet are transforming the lives of these simple hill folk especially youngsters. This non-formal economy is where the growth will happen in the next decade. So expect more services like home improvement, repair & maintenance and sundry other service providers riding the digital infrastructure. So more Urban Claps, Zomatos, Just Dials, Swiggys, Groffers, Country Delight, Home Advisors, Prato, 1mg, etc all offering convenience to consumers and employment to others.

Transport is another area that will see a radical change. In 10 years more than half the automobiles in the world will switch to non-fossil fuel engines, largely electric. Of course, solar-powered vehicles, hydrogen cell cars will also appear on the road before the end of the next decade. Autonomous mobility should be a reality in the next five years. A switch to shared self-driving vehicles is already exciting for the large automakers to innovate and customize their product portfolio. The self-driving car market should start coming into its own in 10 years. In India, the Metro network will grow exponentially even as shared mobility expands. Maglev trains and vehicles and Hyperloop should be visible in some countries. Traffic management will be entirely managed by computers and GPS will sit on the AI engine. However, there is a limit to how many more vehicles the existing infrastructure even after upgradation can support. Obviously by the end of decade reverse migration from large metropolises will begin as newer towns and cities emerge. More airports and intra-city helicopter services will necessary. Smaller air ambulances will make an appearance. Drones will be a common form of delivery for various kinds of packages besides being used for security and surveillance.

Disclaimer: The views expressed in this column are strictly those of the author.

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The Dawn of Cheap and Easy DNA Writing – NEO.LIFE

The 4,000-square-foot suite, tucked into a small office park in the heart of San Diegos biotech corridor, is about as small and unassuming as a university biology-lab classroom. But the 16 people who work here at Molecular Assemblies are chasing a goal that could revolutionize synthetic biology: the ability to write DNA molecules using enzymes.

The field of synthetic biology has, for years, been promising the ability to custom-design organisms that serve as everything from new antibiotics to plastic eaters. But despite substantial advances in both sequencing and editing DNA, one of the big holdups in fulfilling this potential is that whipping up DNA to order is slow andespecially for long moleculesexpensive. In truth, the way scientists write DNA hasnt changed much since the process was first developed in 1981. Its slow, laborious, and environmentally hazardous.

But several startup companies believe they can do it cheaper, faster, and more accurately with a new method. They believe that using enzymes, which is how DNA is written in nature, is the way to go.

Molecular Assemblies recently raised $12.2 million in an initial round of funding, though its far from alone in its quest to use enzymes for building DNA. At least seven startups are trying to do it. Researchers at the University of California at Berkeley, who have published the only paper so far to describe a successful enzymatic approach, founded Ansa Biotechnologies to commercialize it. Ansa, like Molecular Assemblies, is building its business model around providing DNA to customers who send in orders. But another contender, DNA Script, recently announced $38.5 million in a second round of funding for a benchtop machine that would enable labs and hospitals to build DNA themselves.

Today, commercially available DNA synthesis uses a process called phosphoramidite chemistry, which relies on toxic, flammable reagents that create hazardous waste. The process has important limitationsmost companies that build DNA this way top off at lengths of about 100 to 150 base pairs, which isnt even as long as many genes, and the harsh chemistry involved in adding each A, G, C, or T can start to degrade the already-written part as the molecule grows longer. This method also produces molecules that arent compatible with water-based biology. Thats acceptable if you want to use DNA as a form of data storage, but to be useful in biological applications, DNA made through phosphoramidite chemistry has to be put through additional processing, which increases the cost.

Its amazing that they get chemical synthesis of DNA to work, says Andrew Hessel, president of Humane Genomics, which is developing new cancer therapies by reprogramming viruses, and co-founder of Genome Project-write. GP-write, as its known, an international effort to explore the prospects of redesigning human cells, just concluded its annual meeting in New York City. The reality is that nature uses enzymes to write DNA, and that is an incredibly complex process. Every time a cell in your body divides, it has to write a whole human genome perfectly without any additional modifications.

As synthetic biology advances, researchers want longer and longer segments of DNAideally, at least the length of genes. The longer the DNA molecule, the fewer the segments that scientists have to stitch together to make a desired sequence, which should reduce the cost and the chances for errors to be introduced.

Those involved in Hessels GP-write project have their sights set on writing full genomes, which would allow them to engineer human cells (and other organisms cells) so as to better understand health and disease. For example, some scientists involved in GP-write are exploring ways of making cells resistant to viruses. Others are investigating how cells could produce essential nutrients that people now have to derive from food. But making genome-length DNAeven bacterial genomesusing chemical synthesis is currently cost-prohibitive.

William Efcavitch, chief science officer and co-founder of Molecular Assemblies, helped lead the development and commercialization of the original phosphoramidite method in the early 1980s, but now he says its clear a better approach is required. Rather than trying to push 35-year-old chemistry to make longer strands, we said: Lets start with an enzymatic process that can already make long strands and teach it to do it in a user-friendly fashion, says Efcavitch.

You have to control the enzyme and tell it what to write. And thats tricky.

The challenge is that in their natural habitat within a cell, enzymes dont create DNA from scratch. Instead, they duplicate a pre-existing strand by pulling nucleic acids, one by one, to the growing molecule. So Molecular Assemblies and most of the other companies have turned to the only enzyme known to build DNA without a template. This DNA-creating enzyme, or polymerase, is called terminal deoxynucleotidyl transferase (TdT). Typically found in vertebrate immune cells, it is responsible for building the new and ever-changing antigen receptors a cell needs to fight unfamiliar viruses and bacteria.

TdT evolved to make long strands of DNA in a random fashion, but the new breed of DNA-writing startups think they can program it. All of them, however, are still working to figure out exactly how. The challenge with enzymatic synthesis from scratch is that you have to control the enzyme and tell it what to write, Hessel says. And thats tricky.

Chemical synthesis uses a computer to control a system that adds A, G, C, or Tone drop at a timein a four-step process: The DNA molecule is extended by one nucleotide held in place with an unstable bond; then the incomplete end is capped off; then the newly linked nucleotide is stabilized; and then the molecule is prepared for the next addition. Enzymatic synthesis eliminates two of those steps: the polymerase just needs to be stopped and started for each additional nucleotide. Right now, Efcavitch says, were trying to optimize those two steps.

The enzymatic synthesis startups have shown modest success. Ansa has built short DNA fragments called oligonucleotides (or oligos) of 50 base pairs. DNA Script has hit 200, and another companyCamena Biosciencerecently announced it had reached 300. Molecular Assemblies wont specify how long its oligos have gotten other than to say they havent yet reached 150.

The companies claims remain largely untested by the synthetic biology community.

There have been almost no publications, says Calin Plesa, a synthetic biology researcherat the University of Oregon. Its been very difficult to know whats beengoing on inside these companies.

Plesa himself is a heavy user of synthetic DNA for building DNA libraries, as is Sri Kosuri, a synthetic biologist at the University of California, Los Angeles, and co-founder of a startup called Octant. Kosuri describes himself as a synthetic DNA addict whose lab consumes large amounts of oligonucleotides to explore the relationship between DNA sequences and their functions. He appreciates how the companies pursuing enzymatic DNA synthesis are trying to improve the accuracy of the technology. Accuracy is an issue. Its what limits even our own work, Kosuri says. But he adds that it doesnt yet appear that the DNA-writing startups have gotten the enzymatic process near the accuracy of phosphoramidite chemistry.

George Church, a geneticist at Harvard University who is a cofounder of both the Human Genome Project and GP-write, says chemical DNA synthesis methods generally induce an error every 1 in 300 bases. Error-correction methods can improve the figure to 1 in 10,000. When enzymes naturally copy a strand of DNA in cells, however, the error rate is close to one in a billion. But he agrees with Kosuri that no enyzmatic synthesis company has come even close to such low error rates. Right now, theres no evidence than enzymatics is more accurate [than chemical synthesis]. I think its likely but not proven, Church says.

Today, the longest oligonucleotides being produced are coming out of South San Francisco-based Twist Bioscience, which has miniaturized the chemistry using a silicon chip with thousands of tiny wells, creating a platform that that can make one million oligos simultaneously. They are used for screening, diagnostics, therapeutics, and genetic research. Twist can now make oligos up to 300 base pairs long in these wells, more than twice what most enzymatic companies are capable of at the moment.

But Twist Bioscience CEO Emily Leproust saysthat if a better method of synthesizing DNA presents itself, Twists method canaccommodate it. We dont really have a dog in the fight, she says. If thereis better [synthesis through] enzyme chemistry, Ill be the first customer. Oncethe approach reaches one of any number of milestoneslonger, fewer errors, orfaster productionshed be on board. Ill take cheaper but frankly Ill paymore if its faster or better or longer.

Shes confident that one or more of the companies pursingthe enzymatic approach will hit the target eventually. I dont think they haveto break any rule of physics to get thereI think its just engineering, shesays. Its a question of how much money do you need, and how much time do youneed, and can you recoup that investment in commercialization.

Church and Hessel both agree that enzymatic synthesis will start to gain traction soon. I fully expect that bacterial-scale genomes will be within anyones reach within the next 10 years, Hessel says. And that would be just the start. I dont think weve started to unlock the possibilities here. I cant wait to see how these tools and technologies change the world.

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The Dawn of Cheap and Easy DNA Writing - NEO.LIFE

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