New gene-editing technology partially restores vision in blind animals

February 25, 2017

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Salk Institute researchers have discovered a holy grail of gene editing — the ability to, for the first time, insert DNA at a target location into the non-dividing cells that make up the majority of adult organs and tissues. The technique, which the team showed was able to partially restore visual responses in blind rodents, will open new avenues for basic research and a variety of treatments, such as for retinal, heart and neurological diseases.

“We are very excited by the technology we discovered because it’s something that could not be done before,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper published on November 16, 2016 in Nature. “For the first time, we can enter into cells that do not divide and modify the DNA at will. The possible applications of this discovery are vast.”

Until now, techniques that modify DNA — such as the CRISPR-Cas9 system — have been most effective in dividing cells, such as those in skin or the gut, using the cells’ normal copying mechanisms. The new Salk technology is ten times more efficient than other methods at incorporating new DNA into cultures of dividing cells, making it a promising tool for both research and medicine. But, more importantly, the Salk technique represents the first time scientists have managed to insert a new gene into a precise DNA location in adult cells that no longer divide, such as those of the eye, brain, pancreas or heart, offering new possibilities for therapeutic applications in these cells.

To achieve this, the Salk researchers targeted a DNA-repair cellular pathway called NHEJ (for “non-homologous end-joining”), which repairs routine DNA breaks by rejoining the original strand ends. They paired this process with existing gene-editing technology to successfully place new DNA into a precise location in non-dividing cells.

“Using this NHEJ pathway to insert entirely new DNA is revolutionary for editing the genome in live adult organisms,” says Keiichiro Suzuki, a senior research associate in the Izpisua Belmonte lab and one of the paper’s lead authors. “No one has done this before.”

First, the Salk team worked on optimizing the NHEJ machinery for use with the CRISPR-Cas9 system, which allows DNA to be inserted at very precise locations within the genome. The team created a custom insertion package made up of a nucleic acid cocktail, which they call HITI, or homology-independent targeted integration. Then they used an inert virus to deliver HITI’s package of genetic instructions to neurons derived from human embryonic stem cells.

“That was the first indication that HITI might work in non-dividing cells,” says Jun Wu, staff scientist and co-lead author. With that feat under their belts, the team then successfully delivered the construct to the brains of adult mice. Finally, to explore the possibility of using HITI for gene-replacement therapy, the team tested the technique on a rat model for retinitis pigmentosa, an inherited retinal degeneration condition that causes blindness in humans. This time, the team used HITI to deliver to the eyes of 3-week-old rats a functional copy of Mertk, one of the genes that is damaged in retinitis pigmentosa. Analysis performed when the rats were 8 weeks old showed that the animals were able to respond to light, and passed several tests indicating healing in their retinal cells.

“We were able to improve the vision of these blind rats,” says co-lead author Reyna Hernandez-Benitez, a Salk research associate. “This early success suggests that this technology is very promising.”

The team’s next steps will be to improve the delivery efficiency of the HITI construct. As with all genome editing technologies, getting enough cells to incorporate the new DNA is a challenge. The beauty of HITI technology is that it is adaptable to any targeted genome engineering system, not just CRISPR-Cas9. Thus, as the safety and efficiency of these systems improve, so too will the usefulness of HITI.

“We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart and liver,” says Izpisua Belmonte. “It allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting.”


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Materials provided by Salk Institute. Note: Content may be edited for style and length.

Artificial intelligence to generate new cancer drugs on demand

December 18, 2016

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Summary:

  • Clinical trial failure rates for small molecules in oncology exceed 94% for molecules previously tested in animals and the costs to bring a new drug to market exceed $2.5 billion
  • There are around 2,000 drugs approved for therapeutic use by the regulators with very few providing complete cures
  • Advances in deep learning demonstrated superhuman accuracy in many areas and are expected to transform industries, where large amounts of training data is available
  • Generative Adversarial Networks (GANs), a new technology introduced in 2014 represent the “cutting edge” in artificial intelligence, where new images, videos and voice can be produced by the deep neural networks on demand
  • Here for the first time we demonstrate the application of Generative Adversarial Autoencoders (AAEs), a new type of GAN, for generation of molecular fingerprints of molecules that kill cancer cells at specific concentrations
  • This work is the proof of concept, which opens the door for the cornucopia of meaningful molecular leads created according to the given criteria
  • The study was published in Oncotarget and the open-access manuscript is available in the Advance Open Publications section
  • Authors speculate that in 2017 the conservative pharmaceutical industry will experience a transformation similar to the automotive industry with deep learned drug discovery pipelines integrated into the many business processes
  • The extension of this work will be presented at the “4th Annual R&D Data Intelligence Leaders Forum” in Basel, Switzerland, Jan 24-26th, 2017

Thursday, 22nd of December Baltimore, MD – Scientists at the Pharmaceutical Artificial Intelligence (pharma.AI) group of Insilico Medicine, Inc, today announced the publication of a seminal paper demonstrating the application of generative adversarial autoencoders (AAEs) to generating new molecular fingerprints on demand. The study was published in Oncotarget on 22nd of December, 2016. The study represents the proof of concept for applying Generative Adversarial Networks (GANs) to drug discovery. The authors significantly extended this model to generate new leads according to multiple requested characteristics and plan to launch a comprehensive GAN-based drug discovery engine producing promising therapeutic treatments to significantly accelerate pharmaceutical R&D and improve the success rates in clinical trials.

Since 2010 deep learning systems demonstrated unprecedented results in image, voice and text recognition, in many cases surpassing human accuracy and enabling autonomous driving, automated creation of pleasant art and even composition of pleasant music.

GAN is a fresh direction in deep learning invented by Ian Goodfellow in 2014. In recent years GANs produced extraordinary results in generating meaningful images according to the desired descriptions. Similar principles can be applied to drug discovery and biomarker development. This paper represents a proof of concept of an artificially-intelligent drug discovery engine, where AAEs are used to generate new molecular fingerprints with the desired molecular properties.

“At Insilico Medicine we want to be the supplier of meaningful, high-value drug leads in many disease areas with high probability of passing the Phase I/II clinical trials. While this publication is a proof of concept and only generates the molecular fingerprints with the very basic molecular properties, internally we can now generate entire molecular structures according to a large number of parameters. These structures can be fed into our multi-modal drug discovery pipeline, which predicts therapeutic class, efficacy, side effects and many other parameters. Imagine an intelligent system, which one can instruct to produce a set of molecules with specified properties that kill certain cancer cells at a specified dose in a specific subset of the patient population, then predict the age-adjusted and specific biomarker-adjusted efficacy, predict the adverse effects and evaluate the probability of passing the human clinical trials. This is our big vision”, said Alex Zhavoronkov, PhD, CEO of Insilico Medicine, Inc.

Previously, Insilico Medicine demonstrated the predictive power of its discovery systems in the nutraceutical industry. In 2017 Life Extension will launch a range of natural products developed using Insilico Medicine’s discovery pipelines. Earlier this year the pharmaceutical artificial intelligence division of Insilico Medicine published several seminal proof of concept papers demonstrating the applications of deep learning to drug discovery, biomarker development and aging research. Recently the authors published a tool in Nature Communications, which is used for dimensionality reduction in transcriptomic data for training deep neural networks (DNNs). The paper published in Molecular Pharmaceutics demonstrating the applications of deep neural networks for predicting the therapeutic class of the molecule using the transcriptional response data received the American Chemical Society Editors’ Choice Award. Another paper demonstrating the ability to predict the chronological age of the patient using a simple blood test, published in Aging, became the second most popular paper in the journal’s history.

“Generative AAE is a radically new way to discover drugs according to the required parameters. At Pharma.AI we have a comprehensive drug discovery pipeline with reasonably accurate predictors of efficacy and adverse effects that work on the structural data and transcriptional response data and utilize the advanced signaling pathway activation analysis and deep learning. We use this pipeline to uncover the prospective uses of molecules, where these types of data are available. But the generative models allow us to generate completely new molecular structures that can be run through our pipelines and then tested in vitro and in vivo. And while it is too early to make ostentatious claims before our predictions are validated in vivo, it is clear that generative adversarial networks coupled with the more traditional deep learning tools and biomarkers are likely to transform the way drugs are discovered”, said Alex Aliper, president, European R&D at the Pharma.AI group of Insilico Medicine.

Recent advances in deep learning and specifically in generative adversarial networks have demonstrated surprising results in generating new images and videos upon request, even when using natural language as input. In this study the group developed a 7-layer AAE architecture with the latent middle layer serving as a discriminator. As an input and output AAE uses a vector of binary fingerprints and concentration of the molecule. In the latent layer the group introduced a neuron responsible for tumor growth inhibition index, which when negative it indicates the reduction in the number of tumour cells after the treatment. To train AAE, the authors used the NCI-60 cell line assay data for 6252 compounds profiled on MCF-7 cell line. The output of the AAE was used to screen 72 million compounds in PubChem and select candidate molecules with potential anti-cancer properties.

“I am very happy to work alongside the Pharma.AI scientists at Insilico Medicine on getting the GANs to generate meaningful leads in cancer and, most importantly, age-related diseases and aging itself. This is humanity’s most pressing cause and everyone in machine learning and data science should be contributing. The pipelines these guys are developing will play a transformative role in the pharmaceutical industry and in extending human longevity and we will continue our collaboration and invite other scientists to follow this path”, said Artur Kadurin, the head of the segmentation group at Mail.Ru, one of the largest IT companies in Eastern Europe and the first author on the paper.

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About Insilico Medicine, Inc

Insilico Medicine, Inc. is a bioinformatics company located at the Emerging Technology Centers at the Johns Hopkins University Eastern campus in Baltimore with Research and Development (“R&D”) resources in Belgium, UK and Russia hiring talent through hackathons and competitions. The company utilizes advances in genomics, big data analysis, and deep learning for in silico drug discovery and drug repurposing for aging and age-related diseases. The company pursues internal drug discovery programs in cancer, Parkinson’s Disease, Alzheimer’s Disease, sarcopenia, and geroprotector discovery. Through its Pharma.AI division, the company provides advanced machine learning services to biotechnology, pharmaceutical, and skin care companies. Brief company video: https://www.youtube.com/watch?v=l62jlwgL3v8

From: https://eurekalert.org/pub_releases/2016-12/imi-ait122016.php

Ageing process may be reversible, scientists claim

December 18, 2016

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Wrinkles, grey hair and niggling aches are normally regarded as an inevitable part of growing older, but now scientists claim that the ageing process may be reversible.

The team showed that a new form of gene therapy produced a remarkable rejuvenating effect in mice. After six weeks of treatment, the animals looked younger, had straighter spines and better cardiovascular health, healed quicker when injured, and lived 30% longer.

Juan Carlos Izpisua Belmonte, who led the work at the Salk Institute in La Jolla, California, said: “Our study shows that ageing may not have to proceed in one single direction. With careful modulation, ageing might be reversed.”

The genetic techniques used do not lend themselves to immediate use in humans, and the team predict that clinical applications are a decade away. However, the discovery raises the prospect of a new approach to healthcare in which ageing itself is treated, rather than the various diseases associated with it.

The findings also challenge the notion that ageing is simply the result of physical wear and tear over the years. Instead, they add to a growing body of evidence that ageing is partially – perhaps mostly – driven by an internal genetic clock that actively causes our body to enter a state of decline.

The scientists are not claiming that ageing can be eliminated, but say that in the foreseeable future treatments designed to slow the ticking of this internal clock could increase life expectancy.

“We believe that this approach will not lead to immortality,” said Izpisua Belmonte. “There are probably still limits that we will face in terms of complete reversal of ageing. Our focus is not only extension of lifespan but most importantly health-span.”

Wolf Reik, a professor of epigenetics at the Babraham Institute, Cambridge, who was not involved in the work, described the findings as “pretty amazing” and agreed that the idea of life-extending therapies was plausible. “This is not science fiction,” he said.

On the left is muscle tissue from an aged mouse. On the right is muscle tissue from an aged mouse that has been subjected to “reprogramming”.
Photograph: Salk Institute
On the left is muscle tissue from an aged mouse. On the right is muscle tissue from an aged mouse that has been subjected to “reprogramming”.

The rejuvenating treatment given to the mice was based on a technique that has previously been used to “rewind” adult cells, such as skin cells, back into powerful stem cells, very similar to those seen in embryos. These so-called induced pluripotent stem (iPS) cells have the ability to multiply and turn into any cell type in the body and are already being tested in trials designed to provide “spare parts” for patients.

The latest study is the first to show that the same technique can be used to partially rewind the clock on cells – enough to make them younger, but without the cells losing their specialised function.

“Obviously there is a logic to it,” said Reik. “In iPS cells you reset the ageing clock and go back to zero. Going back to zero, to an embryonic state, is probably not what you want, so you ask: where do you want to go back to?”

The treatment involved intermittently switching on the same four genes that are used to turn skin cells into iPS cells. The mice were genetically engineered in such a way that the four genes could be artificially switched on when the mice were exposed to a chemical in their drinking water.

The scientists tested the treatment in mice with a genetic disorder, called progeria, which is linked to accelerated ageing, DNA damage, organ dysfunction and dramatically shortened lifespan.

After six weeks of treatment, the mice looked visibly younger, skin and muscle tone improved and they lived 30% longer. When the same genes were targeted in cells, DNA damage was reduced and the function of the cellular batteries, called the mitochondria, improved.

“This is the first time that someone has shown that reprogramming in an animal can provide a beneficial effect in terms of health and extend their lifespan,” said Izpisua Belmonte.

Crucially, the mice did not have an increased cancer risk, suggesting that the treatment had successfully rewound cells without turning them all the way back into stem cells, which can proliferate uncontrollably in the body.

The potential for carcinogenic side-effects means that the first people to benefit are likely to be those with serious genetic conditions, such as progeria, where there is more likely to be a medical justification for experimental treatments. “Obviously the tumour risk is lurking in the background,” said Reik.

The approach used in the mice could not be readily applied to humans as it would require embryos to be genetically manipulated, but the Salk team believe the same genes could be targeted with drugs.

“These chemicals could be administrated in creams or injections to rejuvenate skin, muscle or bones,” said Izpisua Belmonte. “We think these chemical approaches might be in human clinical trials in the next ten years.”

The findings are published in the journal Cell.
This article was amended on 16 December 2016. A previous version erroneously gave Wolf Reik’s affiliation as the University of Cambridge. This has now been corrected to the Babraham Institute, Cambridge.

https://www.theguardian.com/science/2016/dec/15/ageing-process-may-be-reversible-scientists-claim#img-1

Mark Zuckerberg and Priscilla Chan’s $3 billion effort aims to rid world of major diseases by end of century

September 24, 2016

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Facebook co-founder Mark Zuckerberg and his wife, Priscilla Chan, on Wednesday announced a $3 billion effort to accelerate scientific research with the wildly ambitious goal of “curing all disease in our children’s lifetime.”

The many components of the initiative include creating universal technology “tools” based on both traditional science and engineering on which all researchers can build, including a map of all cell types, a way to continuously monitor blood for early signs of illness, and a chip that can diagnose all diseases (or at least many of them). The money will also help fund what they referred to as 10 to 15 “virtual institutes” that will bring together investigators from around the world to focus on individual diseases or other goals — an idea that has the potential to upend biomedical science.

Being a scientist in academia today can often be a solitary endeavor as the system is set up to encourage colleagues to keep data exclusive in the hopes that this strategy helps them be more competitive at getting publications and grants. But as more Silicon Valley entrepreneurs like Zuckerberg are seeking to make their mark in the biological sciences, they are emphasizing the power of collaboration and openness.

A centerpiece of the new effort, called Chan Zuckerberg Science, involves creating a “Biohub” at the University of California at San Francisco (UCSF) Mission Bay campus that will bring together scientists from Stanford, the University of California at Berkeley and UCSF.

Zuckerberg and Chan, among the world’s 10 wealthiest couples, with a net worth of $55.2 billion, emphasized that their timeline is long — by the end of the century.

“We have to be patient. This is hard stuff,” Zuckerberg said.

Chan said, “That doesn’t mean no one will ever get sick, but it means our children and their children should get sick a lot less.”

Many of themes articulated by Zuckerberg and Chan on Wednesday in San Francisco echo ideas furthered by other technology philanthropists who have donated substantial amounts of money to medical science. Sean Parker, a Napster co-founder, earlier this year set up a multi-center, $250 million effort to bring together top researchers from around the country to focus on immunotherapy for cancer. Microsoft’s Paul Allen has already invested $100 million in a cell-biology institute to try to create models of the fundamental building blocks of life.

https://www.washingtonpost.com/news/to-your-health/wp/2016/09/21/mark-zuckerberg-and-priscilla-chans-3-billion-scientific-effort-aims-to-rid-world-of-major-diseases-by-end-of-century/

Scientists Talk Privately About Creating a Synthetic Human Genome

July 10, 2016

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George Church, a professor of genetics at Harvard Medical School and an organizer of the proposed project, said there had been a misunderstanding. The project was not aimed at creating people, just cells, and would not be restricted to human genomes, he said. Rather it would aim to improve the ability to synthesize DNA in general, which could be applied to various animals, plants and microbes.

“They’re painting a picture which I don’t think represents the project,” Dr. Church said in an interview.

He said the meeting was closed to the news media, and people were asked not to tweet because the project organizers, in an attempt to be transparent, had submitted a paper to a scientific journal. They were therefore not supposed to discuss the idea publicly before publication. He and other organizers said ethical aspects have been amply discussed since the beginning.

The project was initially called HGP2: The Human Genome Synthesis Project, with HGP referring to the Human Genome Project. An invitation to the meeting at Harvard said that the primary goal “would be to synthesize a complete human genome in a cell line within a period of 10 years.”

George Church, one of the organizers of the proposed project, at his lab at Harvard Medical School in 2013. Credit Jessica Rinaldi/Reuters

But by the time the meeting was held, the name had been changed to “HGP-Write: Testing Large Synthetic Genomes in Cells.”

The project does not yet have funding, Dr. Church said, though various companies and foundations would be invited to contribute, and some have indicated interest. The federal government will also be asked. A spokeswoman for the National Institutes of Health declined to comment, saying the project was in too early a stage.

Besides Dr. Church, the organizers include Jef Boeke, director of the institute for systems genetics at NYU Langone Medical Center, and Andrew Hessel, a self-described futurist who works at the Bay Area software company Autodesk and who first proposed such a project in 2012.

Scientists and companies can now change the DNA in cells, for example, by adding foreign genes or changing the letters in the existing genes. This technique is routinely used to make drugs, such as insulin for diabetes, inside genetically modified cells, as well as to make genetically modified crops. And scientists are now debating the ethics of new technology that might allow genetic changes to be made in embryos.

But synthesizing a gene, or an entire genome, would provide the opportunity to make even more extensive changes in DNA.

For instance, companies are now using organisms like yeast to make complex chemicals, like flavorings and fragrances. That requires adding not just one gene to the yeast, like to make insulin, but numerous genes in order to create an entire chemical production process within the cell. With that much tinkering needed, it can be easier to synthesize the DNA from scratch.

Right now, synthesizing DNA is difficult and error-prone. Existing techniques can reliably make strands that are only about 200 base pairs long, with the base pairs being the chemical units in DNA. A single gene can be hundreds or thousands of base pairs long. To synthesize one of those, multiple 200-unit segments have to be spliced together.

But the cost and capabilities are rapidly improving. Dr. Endy of Stanford, who is a co-founder of a DNA synthesis company called Gen9, said the cost of synthesizing genes has plummeted from $4 per base pair in 2003 to 3 cents now. But even at that rate, the cost for three billion letters would be $90 million. He said if costs continued to decline at the same pace, that figure could reach $100,000 in 20 years.

J. Craig Venter, the genetic scientist, synthesized a bacterial genome consisting of about a million base pairs. The synthetic genome was inserted into a cell and took control of that cell. While his first synthetic genome was mainly a copy of an existing genome, Dr. Venter and colleagues this year synthesized a more original bacterial genome, about 500,000 base pairs long.

Dr. Boeke is leading an international consortium that is synthesizing the genome of yeast, which consists of about 12 million base pairs. The scientists are making changes, such as deleting stretches of DNA that do not have any function, in an attempt to make a more streamlined and stable genome.

But the human genome is more than 200 times as large as that of yeast and it is not clear if such a synthesis would be feasible.

Jeremy Minshull, chief executive of DNA2.0, a DNA synthesis company, questioned if the effort would be worth it.

“Our ability to understand what to build is so far behind what we can build,” said Dr. Minshull, who was invited to the meeting at Harvard but did not attend. “I just don’t think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need.”

Japanese scientists have used skin cells to restore a patient’s vision for the first time

July 10, 2016

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Japanese scientists have reported the first successful skin-to-eye stem cell transplant in humans, where stem cells derived from a patient’s skin were transplanted into her eye to partially restore lost vision.

The patient, a 70-year-old woman diagnosed with age-related macular degeneration (AMD) – the leading cause of vision impairment in older people – received the experimental treatment back in 2014 as part of a pilot study. Now, closing in on two years after the transplant took place, the scientists are sharing the results.

The researchers took a small piece of skin from her arm (4 mm in diameter) and modified its cells, effectively reprogramming them into induced pluripotent stem cells (iPSC).

Pluripotent stem cells have the ability to differentiate into almost any type of tissue within the body, which is why skin cells taken from an arm can be repurposed into retinal tissue.

Once the cells were coaxed to develop into retinal pigment epithelium (RPE), they were cultured in the lab to grow into an ultra-thin sheet, which was then transplanted behind the retina of the patient.

“I am very pleased that there were no complications with the transplant surgery,” said project leader Masayo Takahashi from the Riken Centre for Developmental Biology in 2014. “However, this is only the first step for use of iPSC in regenerative medicine. I have renewed my resolve to continue forging ahead until this treatment becomes available to many patients.”

While it’s definitely still early days for this experimental procedure, the signs so far are promising.

The team held off on reporting their results until now to monitor the patient’s progress and gauge how successfully the modified cells lasted, but they’ve just reported that the transplanted cells survived without any adverse events for over a year, resulting in slightly improved vision for the patient.

“The transplanted RPE sheet survived well without any findings [or] indication of immune rejections nor adverse unexpected proliferation for one and a half years, achieving our primary purpose of this pilot study,” the team said in a statement this week.

“I am glad I received the treatment,” the patient told The Japan Times last year. “I feel my eyesight has brightened and widened.”

While it’s not a complete restoration of the patient’s vision, the study shows a significant step forward in the use of induced pluripotent stem cells – which scientists think might be used to treat a range of illnesses, such as Parkinson’s and Alzheimer’s disease, not just vision problems.

A number of other studies are also showing positive results in restoring sight with stem cell treatments. Earlier in the year, researchers in China and the US were able to improve the vision of babies with cataracts by manipulating protein levels in stem cells.

Even more remarkably, a woman in Baltimore who was blind for more than five years had some of her vision restored after stem cells were extracted from her bone marrow and injected into her eyes. While many questions remain about that particular treatment, there’s no denying that stem cell research is a hugely exciting field of study.

The findings were presented at the 2016 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle.

http://www.sciencealert.com/japanese-scientists-have-used-skin-cells-to-restore-a-patient-s-vision-for-the-first-time

We’re Closer Than Ever to Bringing the Dead Back to Life

July 10, 2016

The 2,500 year-old mummified body an Egyptian female known as 'Tahemaa' is scanned at the Saad Centre of Radiography at City Univeristy in central London, on July 30, 2009. Tahemaa is believed to have been 28 years-old when she died and is thought to have lived in Luxor in Egypt. Specialists at City University hope to learn more about how she died. The mummy was donated to the Bournemouth Natural Sciences Society in 1922. Nothing is known of how she arrived in England. AFP PHOTO/LEON NEAL (Photo credit should read Leon Neal/AFP/Getty Images)

The 2,500 year-old mummified body an Egyptian female known as ‘Tahemaa’ is scanned at the Saad Centre of Radiography at City Univeristy in central London, on July 30, 2009. AFP PHOTO/LEON NEAL (Photo credit should read Leon Neal/AFP/Getty Images)

 

Across religions and cultures, humans have attempted to bridge the gap between life and death. The human death rate is 100%. Everybody dies. Yet, that hasn’t stopped us from trying to postpone death or to find ways to reverse it.

In countless works spanning every genre of literature and film, death and exploration of the afterlife has been a recurring theme. Orpheus, a Greek mythological figure, ventures to the underworld to retrieve his recently departed wife, Eurydice. One of the hallmark works of the Renaissance is Dante Alighieri’s Divine Comedy, a poem detailing the journey through hell, purgatory and heaven. While the humanities have served to muse on the magnitude of our ignorance when it comes to death, science has steadily progressed in finding ways to beat it.

The biotech firm BioQuark was recently granted permission by the National Institutes of Health to begin clinical trials on 20 brain-dead patients on life support. In an attempt to bring them back from the dead, scientists will test a variety of therapies over the course of a month—from injecting stem cells to deploying nerve-stimulating techniques often used on coma patients.

“Even if you could get cells to grow—even if you could replicate some semblance of the architecture which existed previously—replicating all of those neurons and all of those connections in a way that makes it possible even for basic brain function to continue, that is a huge challenge,” cautioned Dr. David Casarett, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, in an interview with the Observer. In 2014, Dr. Casarett wrote Shocked: Adventures in Bringing Back The Recently Dead. The clinical trials, he noted, also raise ethical concerns.

“You don’t really know what is going to happen when they start trying to regrow neurons,” he explained. “One possibility is absolutely nothing happens. Another possibility is function increases to varying degrees in varying people, leaving people in a strange in-between state.” These are decisions to be made by consenting family members, as one potential outcome could leave participants in a state somewhere in between brain-dead and comatose. “You wouldn’t necessarily be doing the patient or their family any favors by creating that condition.”

Less ambitious—but just as controversial—are other research projects testing death as a means to buy valuable time to mend life-threatening injuries.

clinical trial is currently underway at the University of Pittsburgh Medical Center, in which emergency room patients have their blood drawn and replaced with a cold saline solution to induce hypothermia, thereby slowing metabolism—ideally for transport and resuscitation efforts to be more effective. Similar procedures have found have high success rates on dogs and pigs without functional complications. Hydrogen sulfide has also been used to induce the same effect in mice, which doesn’t demand the equipment and cooling process needed to induce hypothermia. The jury is still out as to whether this method could be applied to humans.

The use of cryogenics, for now, borders on science fiction—but that hasn’t stopped scientists and wealthy enthusiasts from trying to make it a reality.

Humai, an L.A.-based robotics company, hopes to freeze human brains after death with the expectation that technology will soon catch up—allowing the brain to be resurrected in an artificial body. Neuroscientists have excessively cautioned about lending cryogenics credence, but scientific research has blurred the definition of death and the consensus on when it occurs.

For centuries, death was called at the moment the heart stopped beating. However, medicine has evolved to the point that cardiopulmonary resuscitation (CPR) is now a common life-saving technique incorporated in basic first aid training, along with more advanced forms of resuscitation—like defibrillators—that can restart the heart. Several cases have been cited where a person under cardiac arrest has been brought back to life hours after they’ve technically died, when cooling processes and correct resuscitation procedures are implemented. According to a 2012 study published in Nature, skeletal muscle stem cells can retain their ability to regenerate for up to 17 days after death, redefining death as occurring in steps rather than at one single moment.

Despite groundbreaking progress in the medical field to extend life expectancy and cure illnesses and ailments which were once considered to be fatal, the human imagination will always far outpace the realms of what is logically applicable. Efforts to bring back the dead and prolong life are embedded in our biology, as exhibited by humanity’s obsession with mortality. There will always be limitations to how far science can push back against death, but the ways we figure out how to do so—in theory, fantasy and practical application—are certainly thought provoking.

We’re Closer Than Ever to Bringing the Dead Back to Life

Why We Should Teach Kids to Code Biology, Not Just Software

June 04, 2016

Binary tunnel and DNA Strand

Almost ten years ago, Freeman Dyson ventured a wild forecast:

“I predict that the domestication of biotechnology will dominate our lives during the next fifty years at least as much as the domestication of computers has dominated our lives during the previous fifty years.”

Just recently, MIT researchers created a programming language for living cells that can be used by even those with no previous genetic engineering knowledge. This is part of a growing body of evidence pointing to a undeniable trend—Dyson’s vision is starting to come true.

Over the next several decades we will develop tools that will make biotechnology affordable and accessible to anyone—not just in a university or even biohacking lab—but literally at home.

“Domesticating” Computers

To appreciate the power of Dyson’s forecast, let’s first go back in time. Not so long ago, the only computers around were massive things that took up entire rooms or even floors of a building. They were complicated to use and required multiple university degrees just to make them do simple tasks.

Over the last 50 years, humans have collectively engineered countless tools—from programming languages to hardware and software—that allow anyone to operate a computer with no prior knowledge. Everyone from the age of 3 to 95 can pick up an iPad and intuitively begin using it.

The personal computer brought an explosion of business, art, music, movies, writing, and connectivity between people the likes of which we had never seen before.

Given accessible and affordable tools, the average person found lots of uses for her personal computer—uses that several decades ago we couldn’t even have imagined.

Now, we’re seeing a similar “domestication” happening in biotechnology. And likewise, we have no idea what our children will create with the biotech equivalent of a personal computer.

“Domesticating” Biotechnology

Since 2003, when the human genome was sequenced and the cost of sequencing began to plummet, scientists and a rising number of citizen scientists have been building upon this accomplishment to create new tools that read, write, and edit DNA.

A lot of these tools have been built with “serious” science in mind, but many are also built for the casual tinkerer and biotech novice.

Today, just about anyone (even high school students) can…

  • Have their DNA sequenced
    You can learn about your ancestry composition and predisposition to certain inherited conditions like cystic fibrosis and sickle cell anemia at 23andMe.
  • Read BioBuilder
    Biobuilder is a recent book designed to teach high school and college students the fundamentals of biodesign and DNA engineering, complete with instructions on how to make your own glowing bacteria and other experiments.
  • Learn to use CRISPR
    Take a class on how to use CRISPR for your own experiments at Genspace, a citizen science lab in NYC (or a similar class in many community science labs across the world). No experience necessary.
  • Join iGEM
    iGEM is a worldwide synthetic biology organization initially created for college students and now open to entrepreneurs, community labs, and high schools.
  • Get started with “drag-and-drop” genetic engineering for free
    Download Genome Compiler software for free and experiment with “drag-and-drop genetic engineering.”
  • Order synthetic DNA built to design or from the registry of standard biological parts online
  • Buy equipment for your home biotech lab like OpenqPCR or Open Trons

The Next Generation of Biohackers

For most people, the words genetic engineering and biotechnology do not bring to mind a vision of a new generation of artists designing a new variety of flower or a new breed of pet.

If this trend of biotechnology “domestication” continues, however, the next generation of engineers might be writing code not just for apps, but also new species of plants and animals.

And the potential here is much larger and more important than tinkering with the color of bacteria and flowers or designing new pets.

Last year, an iGEM team from Israel proposed a project to “develop cancer therapy that is both highly specific for cancer cells, efficient, and personalized for each tumor and patient genetics.” (You can read about their results here.) Another team proposed to upcycle methanol into a universal carbon source. And last year’s first prize winner at the high school level set out to prevent tissue damage from chronic inflammation in the human body.

To be clear, these are lofty goals—but the point is young people are already working towards them. And if they are working to solve huge challenges using synthetic biology today, imagine what they will be able to achieve given improved tools as adults?

Not only are teenagers already rewriting the code of life, their interest in doing more and learning more is quickly growing. So far, 18,000 people have participated in iGem. The competition has grown from 5 teams in 2004 to 245 teams in more than 32 countries in 2014.

What Could Go Wrong?

If Dyson’s prediction proves to be correct, we are already raising a generation of designers, engineers, and artists who will use amazing new toolsets to create on a new canvas—life itself.

So, what could possibly go wrong?

In a 2007 New York Times article “Our Biotech Future,” Dyson questions the ethics of domesticating biology. He asks: Can it or should it be stopped? If we’re not going to stop it, what limits should be imposed? If so, by whom and how should the limits be enforced?

The comparison to computers is useful to a point, but biology is obviously much more complicated and there were fewer ethical questions when we were building the first microchips. 

Domesticating biotechnology means bringing it to the masses, and that means we’d have even less control over it than when it was limited to university or government funded labs.

The answer to Dyson’s first question seems clear: This trend is not going to stop. There’s too much momentum. We have learned too much about how to control our own biology to turn back.

And this is all the more reason to teach the next generation early on about the power and ethics of rewriting the code of life.

http://singularityhub.com/2016/04/07/we-should-be-teaching-kids-to-code-biology-not-just-software/

Video

Riccardo Sabatini: How to read the genome and build a human being

May 04, 2016

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Secrets, disease and beauty are all written in the human genome, the complete set of genetic instructions needed to build a human being. Now, as scientist and entrepreneur Riccardo Sabatini shows us, we have the power to read this complex code, predicting things like height, eye color, age and even facial structure — all from a vial of blood. And soon, Sabatini says, our new understanding of the genome will allow us to personalize treatments for diseases like cancer. We have the power to change life as we know it. How will we use it?

Mayo Clinic Taps Silicon Valley to Help People Age Gracefully

April 23, 2016

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Could there be a recipe for a longer, healthier life?

Pop a pill and live a long, healthy life. It might not be quite that easy yet, but researchers at Mayo Clinic believe they have found a cell that could hold the secret to aging extra gracefully.

Their research, published in the journal Nature Wednesday, helped patients live longer, healthier lives. The only catch is their patients are mice. But the researchers believe they could someday translate it into a recipe for human longevity, too.

In fact, the research has been so convincing that Mayo Clinic invested in Unity Biotechnology, a San Francisco-based startup built around the researchers’ approach. Other investors in the company include ARCH Venture Partners, Venrock, and Chinese WuXi, and the study’s lead author Jan van Deursen is listed as a Unity co-founder.

The anti-aging method works like this: scientists inject the mice with a drug that pushes out toxic, worn-out cells called “senescent cells.” The senescent cells are old and stressed and don’t behave properly anymore. Instead, they “litter the body with aging” as van Deursen puts it.