Biotech Breakthrough: Fully-Functioning Organ Grown

artificial-thymusOrgan transplants are one of the greatest medical advances of the 20th century. Where patients once faced disability or even death, they’ve been given a new lease on life in the form of donated organs. The problem is that the supply of suitable donor organs has always been in a state of severe shortage. Not only is it entirely dependent on accident victims who have signed their organ donor card, there is also the issue of genetic suitability.

For decades, scientists have worked on producing lab-grown organs to pick up the slack left by the donor system. The research has yielded some positive results in the form of simple organs, such as the artificial esophagus and “mini-kidneys.” Nevertheless, the creation of whole, complex, functional organs that can be swapped for damaged or destroyed ones has remained out of reach. That is, until now.

fibroblastScientists at the University of Edinburgh have grown a fully-functional organ inside a mouse, a breakthrough that opens up the possibility of one day manufacturing compatible organs for transplant without the need for donors. Using mouse embryo cells, scientists at the MRC Centre for Regenerative Medicine created an artificial thymus gland with the same structure and function as an adult organ.

The University of Edinburgh team produced the artificial thymus gland using a technique that the scientists call “reprogramming.” It involves fibroblast cells, which form connective tissue in animals, being removed from a mouse embryo and then treated with a protein called FOXN1 to change them into thymic epithelial cells (TEC). These were then mixed with other thymus cells and transplanted into living mice by grafting them to the animal’s kidneys.

T-cellThen, over a period of four weeks, the cells grew into a complete, functioning thymus gland that can produce T cells – an important part of the immune system. According to the scientists, this development goes beyond previous efforts because the thymus serves such a key part in protecting the body against infection and in eliminating cancer cells. This is clearly the first step on the road towards complete organ development.

The team is currently working on refining the reprogramming technique in the hope of developing a practical medical procedure, such as creating bespoke thymus glands made to match a patient’s own T cells. They see the development of a lab-grown thymus as a way of treating cancer patients whose immune system has been compromised by radiation or chemotherapy, and children born with malfunctioning thymuses.

bioprintingAccording to Rob Buckle, Head of Regenerative Medicine at the MRC, the potential is tremendous and far-reaching:

Growing ‘replacement parts’ for damaged tissue could remove the need to transplant whole organs from one person to another, which has many drawbacks – not least a critical lack of donors. This research is an exciting early step towards that goal, and a convincing demonstration of the potential power of direct reprogramming technology, by which one cell type is converted to another. However, much more work will be needed before this process can be reproduced in the lab environment, and in a safe and tightly controlled way suitable for use in humans.

Combined with “bioprinting” – where stem cells are printed into organs using a 3-D printer – organs transplants could very well evolve to the point where made-to-order replacements are fashioned from patient’s own genetic material. This would not only ensure that there is never any shortages or waiting lists, but that there would be no chance of incompatibility or donor rejection.

Another step on the road to clinical immortality! And be sure to check out this video of the artificial thymus gland being grown, courtesy of the Medical Research Council:


Source:
gizmag.com, crm.ed.ca.uk

Immortality Inc: Regrowing Body Parts

https://i0.wp.com/images.gizmag.com/hero/lizardtails-2.jpgAnyone who has ever observed a lizard must not have failed to notice that they are capable of detaching their tails, and then regenerating them from scratch. This propensity for “spontaneous regeneration” is something that few organisms possess, and mammals are sadly not one of them. But thanks to a team of Arizona State University scientists, the genetic recipe behind this ability has finally been unlocked.

This breakthrough is a small part of a growing field of biomedicine that seeks to improve human health by tampering with the basic components (i.e. our DNA). The research, which was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission, also involved scientists from the University of Arizona College of Medicine, Translational Genomic Research Institute, and Michigan State University.

dna_cancerAccording to Prof. Kenro Kusumi, lead author of a paper on the genetic study, lizards are the most closely-related animals to humans that can regenerate entire appendages. They also share the same genetic language as us, so it’s theoretically possible that we could do what they do, if only we knew which genes to use and in what amounts. As Kusumi explains in the paper, which was published Aug. 20 in the journal PLOS ONE. :

Lizards basically share the same toolbox of genes as humans. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals, and wound healing.

Other animals, such as salamanders, frog tadpoles, and fish, can also regenerate their tails. During tail regeneration, they all turn on genes in what is called the ‘Wnt pathway’ — a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessel. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.

calico-header-640x353 It takes lizards more than 60 days to regenerate a functional tail — forming a complex regenerating structure with cells growing into different tissues at a number of sites along the tail. According to Katsumi, harnessing this would be a boon for medicine for obvious reasons:

Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail. By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future.

The researchers also hope their findings will also help repairing birth defects and treating diseases such as arthritis. Given time, and enough positive results, I think it would be fair to expect that Google’s Clinical Immortality subsidiary – known as Calico – will buy up all the necessary rights. Then, it shouldn’t be more than a decade before a gene treatments is produced that will allow for spontaneous regeneration and the elimination of degenerative diseases.

The age of post-mortal is looming people. Be scared/enthused!

Sources: kurzweil.net, gizmag.com

Immortality Inc: Google’s Kurzweil Talks Life Extension

calico-header-640x353Human life expectancy has been gradually getting longer and longer over the past century, keeping pace with advances made in health and medical technologies. And in the next 20 years, as the pace of technological change accelerates significantly, we can expect life-expectancy to undergo a similarly accelerated increase. So its only natural that one of the worlds biggest tech giants (Google) would decide to becoming invested in the business of post-mortality.

As part of this initiative, Google has been seeking to build a computer that can think like a human brain. They even hired renowed futurist and AI expert Ray Kurzweil last year to act as the director of engineering on this project. Speaking at Google’s I/O conference late last month, he detailed his prediction that our ability to improve human health is beginning to move up an “exponential” growth curve, similar to the law of accelerating returns that governs the information technology and communications sectors today.

raykurzweilThe capacity to sequence DNA, which is dropping rapidly in cost and ease, is the most obvious example. At one time, it took about seven years to sequence 1% of the first human genome. But now, it can be done in a matter of hours. And thanks to initiatives like the Human Genome Project and ENCODE, we have not only successfully mapped every inch of the human genome, we’ve also identified the function of every gene within.

But as Kurzweil said in the course of his presentation – entitled “Biologically Inspired Models of Intelligence” – simply reading DNA is only the beginning:

Our ability to reprogram this outdated software is growing exponentially. Somewhere between that 10- and 20-year mark, we’ll see see significant differences in life expectancy–not just infant life expectancy, but your remaining life expectancy. The models that are used by life insurance companies sort of continue the linear progress we’ve made before health and medicine was an information technology… This is going to go into high gear.

immortality_dnaKurzweil cited several examples of our increasing ability to “reprogram this outdated data” – technologies like RNA interference that can turn genes on and off, or doctors’ ability to now add a missing gene to patients with a terminal disease called pulmonary hypertension. He cited the case of a girl whose life was threatened by a damaged wind pipe, who had a new pipe designed and 3-D printed for her using her own stem cells.

In other countries, he notes, heart attack survivors who have lasting heart damage can now get a rejuvenated heart from reprogrammed stem cells. And while this procedure awaits approval from the FDA in the US, it has already been demonstrated to be both safe and effective. Beyond tweaking human biology through DNA/RNA reprogramming, there are also countless initiatives aimed at creating biomonitoring patches that will improve the functionality and longevity of human organs.

avatar_imageAnd in addition to building computer brains, Google itself is also in the business of extending human life. This project, called Calico, hopes to slow the process of natural aging, a related though different goal than extending life expectancy with treatment for disease. Though of course, the term “immortality” is perhaps a bit of misnomer, hence why it is amended with the word “clinical”. While the natural effects of aging are something that can be addressed, there will still be countless ways to die.

As Kurzweil himself put it:

Life expectancy is a statistical phenomenon. You could still be hit by the proverbial bus tomorrow. Of course, we’re working on that here at Google also, with self-driving cars.

Good one, Kurzweil! Of course, there are plenty of skeptics who question the validity of these assertions, and challenge the notion of clinical immortality on ethical grounds. After all, our planet currently plays host to some 7 billion people, and another 2 to 3 billion are expected to be added before we reach the halfway mark of this century. And with cures for diseases like HIV and cancer already showing promise, we may already be looking at a severe drop in mortality in the coming decades.

calico1Combined with an extension in life-expectancy, who knows how this will effect life and society as we know it? But one thing is for certain: the study of life has become tantamount to a study of information. And much like computational technology, this information can be manipulated, resulting in greater performance and returns. So at this point, regardless of whether or not it should be done, it’s an almost foregone conclusion that it will be done.

After all? While very few people would dare to live forever, there is virtually no one who wouldn’t want to live a little longer. And in the meantime, if you’ve got the time and feel like some “light veiwing”, be sure to check out Kurzweil’s full Google I/O 2014 speech in which he addresses the topics of computing, artificial intelligence, biology and clinical immortality:


Sources: fastcoexist.com, kurzweilai.net

Accelerando: A Review

posthumanIt’s been a long while since I did a book review, mainly because I’ve been immersed in my writing. But sooner or later, you have to return to the source, right? As usual, I’ve been reading books that I hope will help me expand my horizons and become a better writer. And with that in mind, I thought I’d finally review a book I finished reading some months ago, one which was I read in the hopes of learning my craft.

It’s called Accelerando, one of Charle’s Stross better known works that earned him the Hugo, Campbell, Clarke, and British Science Fiction Association Awards. The book contains nine short stories, all of which were originally published as novellas and novelettes in Azimov’s Science Fiction. Each one revolves around the Mancx family, looking at three generations that live before, during, and after the technological singularity.

https://i0.wp.com/1a3kls1q8u5etu6z53sktyqdif.wpengine.netdna-cdn.com/wp-content/uploads/2011/06/Charles-Stross.jpgThis is the central focus of the story – and Stross’ particular obsession – which he explores in serious depth. The title, which in Italian means “speeding up” and is used as a tempo marking in musical notation, refers to the accelerating rate of technological progress and its impact on humanity. Beginning in the 21st century with the character of Manfred Mancx, a “venture altruist”; moving to his daughter Amber in the mid 21st century; the story culminates with Sirhan al-Khurasani, Amber’s son in the late 21st century and distant future.

In the course of all that, the story looks at such high-minded concepts as nanotechnology, utility fogs, clinical immortality, Matrioshka Brains, extra-terrestrials, FTL, Dyson Spheres and Dyson Swarms, and the Fermi Paradox. It also takes a long-view of emerging technologies and predicts where they will take us down the road.

And to quote Cory Doctorw’s own review of the book, it essentially “Makes hallucinogens obsolete.”

Plot Synopsis:
https://i1.wp.com/upload.wikimedia.org/wikipedia/en/0/0b/Accelerando_%28book_cover%29.jpg
Part I, Slow Takeoff, begins with the short story “Lobsters“, which opens in early-21st century Amsterdam. Here, we see Manfred Macx, a “venture altruist”, going about his business, making business ideas happen for others and promoting development. In the course of things, Manfred receives a call on a courier-delivered phone from entities claiming to be a net-based AI working through a KGB website, seeking his help on how to defect.

Eventually, he discovers the callers are actually uploaded brain-scans of the California spiny lobster looking to escape from humanity’s interference. This leads Macx to team up with his friend, entrepreneur Bob Franklin, who is looking for an AI to crew his nascent spacefaring project—the building of a self-replicating factory complex from cometary material.

In the course of securing them passage aboard Franklin’s ship, a new legal precedent is established that will help define the rights of future AIs and uploaded minds. Meanwhile, Macx’s ex-fiancee Pamela pursues him, seeking to get him to declare his assets as part of her job with the IRS and her disdain for her husband’s post-scarcity economic outlook. Eventually, she catches up to him and forces him to impregnate and marry her in an attempt to control him.

The second story, “Troubador“, takes place three years later where Manfred is in the middle of an acrimonious divorce with Pamela who is once again seeking to force him to declare his assets. Their daughter, Amber, is frozen as a newly fertilized embryo and Pamela wants to raise her in a way that would be consistent with her religious beliefs and not Manfred’s extropian views. Meanwhile, he is working on three new schemes and looking for help to make them a reality.

These include a workable state-centralized planning apparatus that can interface with external market systems, a way to upload the entirety of the 20th century’s out-of-copyright film and music to the net. He meets up with Annette again – a woman working for Arianspace, a French commercial aerospace company – and the two begin a relationship. With her help, his schemes come together perfectly and he is able to thwart his wife and her lawyers. However, their daughter Amber is then defrosted and born, and henceforth is being raised by Pamela.

The third and final story in Part I is “Tourist“, which takes place five years later in Edinburgh. During this story, Manfred is mugged and his memories (stored in a series of Turing-compatible cyberware) are stolen. The criminal tries to use Manfred’s memories and glasses to make some money, but is horrified when he learns all of his plans are being made available free of charge. This forces Annabelle to go out and find the man who did it and cut a deal to get his memories back.

Meanwhile, the Lobsters are thriving in colonies situated at the L5 point, and on a comet in the asteroid belt. Along with the Jet Propulsion Laboratory and the ESA, they have picked up encrypted signals from outside the solar system. Bob Franklin, now dead, is personality-reconstructed in the Franklin Collective. Manfred, his memories recovered, moves to further expand the rights of non-human intelligences while Aineko begins to study and decode the alien signals.

http://garethstack.files.wordpress.com/2006/12/url-3.jpegPart II, Point of Inflection, opens a decade later in the early/mid-21st century and centers on Amber Macx, now a teen-ager, in the outer Solar System. The first story, entitled “Halo“, centers around Amber’s plot (with Annette and Manfred’s help) to break free from her domineering mother by enslaving herself via s Yemeni shell corporation and enlisting aboard a Franklin-Collective owned spacecraft that is mining materials from Amalthea, Jupiter’s fourth moon.

To retain control of her daughter, Pamela petitions an imam named Sadeq to travel to Amalthea to issue an Islamic legal judgment against Amber. Amber manages to thwart this by setting up her own empire on a small, privately owned asteroid, thus making herself sovereign over an actual state. In the meantime, the alien signals have been decoded, and a physical journey to an alien “router” beyond the Solar System is planned.

In the second story Router“, the uploaded personalities of Amber and 62 of her peers travel to a brown dwarf star named Hyundai +4904/-56 to find the alien router. Traveling aboard the Field Circus, a tiny spacecraft made of computronium and propelled by a Jupiter-based laser and a lightsail, the virtualized crew are contacted by aliens.

Known as “The Wunch”, these sentients occupy virtual bodies based on Lobster patterns that were “borrowed” from Manfred’s original transmissions. After opening up negotiations for technology, Amber and her friends realize the Wunch are just a group of thieving, third-rate “barbarians” who have taken over in the wake of another species transcending thanks to a technological singularity. After thwarting The Wunch, Amber and a few others make the decision to travel deep into the router’s wormhole network.

In the third story, Nightfall“, the router explorers find themselves trapped by yet more malign aliens in a variety of virtual spaces. In time, they realize the virtual reaities are being hosted by a Matrioshka brain – a megastructure built around a star (similar to a Dyson’s Sphere) composed of computronium. The builders of this brain seem to have disappeared (or been destroyed by their own creations), leaving an anarchy ruled by sentient, viral corporations and scavengers who attempt to use newcomers as currency.

With Aineko’s help, the crew finally escapes by offering passage to a “rogue alien corporation” (a “pyramid scheme crossed with a 419 scam”), represented by a giant virtual slug. This alien personality opens a powered route out, and the crew begins the journey back home after many decades of being away.

https://storiesbywilliams.files.wordpress.com/2014/06/d622e-charles_stross_accelerando_magyar.jpgPart III, Singularity, things take place back in the Solar System from the point of view of Sirhan – the son of the physical Amber and Sadeq who stayed behind. In “Curator“, the crew of the Field Circus comes home to find that the inner planets of the Solar System have been disassembled to build a Matrioshka brain similar to the one they encountered through the router. They arrive at Saturn, which is where normal humans now reside, and come to a floating habitat in Saturn’s upper atmosphere being run by Sirhan.

The crew upload their virtual states into new bodies, and find that they are all now bankrupt and unable to compete with the new Economics 2.0 model practised by the posthuman intelligences of the inner system. Manfred, Pamela, and Annette are present in various forms and realize Sirhan has summoned them all to this place. Meanwhile, Bailiffs—sentient enforcement constructs—arrive to “repossess” Amber and Aineko, but a scheme is hatched whereby the Slug is introduced to Economics 2.0, which keeps both constructs very busy.

In “Elector“, we see Amber, Annette, Manfred and Gianna (Manfred’s old political colleague) in the increasingly-populated Saturnian floating cities and working on a political campaign to finance a scheme to escape the predations of the “Vile Offspring” – the sentient minds that inhabit the inner Solar System’s Matrioshka brain. With Amber in charge of this “Accelerationista” party, they plan to journey once more to the router network. She loses the election to the stay-at-home “conservationista” faction, but once more the Lobsters step in to help by offering passage to uploads on their large ships if the humans agree to act as explorers and mappers.

In the third and final chapter, “Survivor“, things fast-forward to a few centuries after the singularity. The router has once again been reached by the human ship and humanity now lives in space habitats throughout the Galaxy. While some continue in the ongoing exploration of space, others (copies of various people) live in habitats around Hyundai and other stars, raising children and keeping all past versions of themselves and others archived.

Meanwhile, Manfred and Annette reconcile their differences and realize they were being manipulated all along. Aineko, who was becoming increasingly intelligent throughout the decades, was apparently pushing Manfred to fulfill his schemes to help bring the humanity to the alien node and help humanity escape the fate of other civilizations that were consumed by their own technological progress.

Summary:
Needless to say, this book was one big tome of big ideas, and could be mind-bendingly weird and inaccessible at times! I’m thankful I came to it when I did, because no one should attempt to read this until they’ve had sufficient priming by studying all the key concepts involved. For instance, don’t even think about touching this book unless you’re familiar with the notion of the Technological Singularity. Beyond that, be sure to familiarize yourself with things like utility fogs, Dyson Spheres, computronium, nanotechnology, and the basics of space travel.

You know what, let’s just say you shouldn’t be allowed to read this book until you’ve first tackled writers like Ray Kurzweil, William Gibson, Arthur C. Clarke, Alastair Reynolds and Neal Stephenson. Maybe Vernon Vinge too, who I’m currently working on. But assuming you can wrap your mind around the things presented therein, you will feel like you’ve digested something pretty elephantine and which is still pretty cutting edge a decade or more years after it was first published!

But to break it all down, the story is essentially a sort of cautionary tale of the dangers of the ever-increasing pace of change and advancement. At several points in the story, the drive toward extropianism and post-humanity is held up as both an inevitability and a fearful prospect. It’s also presented as a possible explanation for the Fermi Paradox – which states that if sentient life is statistically likely and plentiful in our universe, why has humanity not observed or encountered it?

According to Stross, it is because sentient species – which would all presumably have the capacity for technological advancement – will eventually be consumed by the explosion caused by ever-accelerating progress. This will inevitably lead to a situation where all matter can be converted into computing space, all thought and existence can be uploaded, and species will not want to venture away from their solar system because the bandwidth will be too weak. In a society built on computronium and endless time, instant communication and access will be tantamount to life itself.

All that being said, the inaccessibility can be tricky sometimes and can make the read feel like its a bit of a labor. And the twist at the ending did seem like it was a little contrived and out of left field. It certainly made sense in the context of the story, but to think that a robotic cat that was progressively getting smarter was the reason behind so much of the story’s dynamic – both in terms of the characters and the larger plot – seemed sudden and farfetched.

And in reality, the story was more about the technical aspects and deeper philosophical questions than anything about the characters themselves. As such, anyone who enjoys character-driven stories should probably stay away from it. But for people who enjoy plot-driven tales that are very dense and loaded with cool technical stuff (which describes me pretty well!), this is definitely a must-read.

Now if you will excuse me, I’m off to finish Vernor Vinge’s Rainbow’s End, another dense, sometimes inaccessible read!

Year-End Health News: Anti-Aging and Artificial Hearts

medtechHere we have two more stories from last year that I find I can’t move on without posting about them. And considering just how relevant they are to the field of biomedicine, there was no way I could let them go unheeded. Not only are developments such as these likely to save lives, they are also part of a much-anticipated era where mortality will be a nuisance rather than an inevitability.

The first story comes to us from the University of New South Wales (UNSW) in Australia and the Harvard Medical School, where a joint effort achieved a major step towards the dream of clinical immortality. In the course of experimenting on mice, the researchers managed to reverse the effects of aging in mice using an approach that restores communication between a cell’s mitochondria and nucleus.

MitochondriaMitochondria are the power supply for a cell, generating the energy required for key biological functions. When communication breaks down between mitochondria and the cell’s control center (the nucleus), the effects of aging accelerate. Led by David Sinclair, a professor from UNSW Medicine at Harvard Medical School, the team found that by restoring this molecular communication, aging could not only be slowed, but reversed.

Responsible for this breakdown is a decline of the chemical Nicotinamide Adenine Dinucleotide (or NAD). By increasing amounts of a compound used by the cell to produce NAD, Professor Sinclair found that he and his team could quickly repair mitochondrial function. Key indicators of aging, such as insulin resistance, inflammation and muscle wasting, showed extensive improvement.

labmiceIn fact, the researchers found that the tissue of two-year-old mice given the NAD-producing compound for just one week resembled that of six-month-old mice. They said that this is comparable to a 60-year-old human converting to a 20-year-old in these specific areas. As Dr Nigel Turner, an ARC Future Fellow from UNSW’s Department of Pharmacology and co-author of the team’s research paper, said:

It was shocking how quickly it happened. If the compound is administered early enough in the aging process, in just a week, the muscles of the older mice were indistinguishable from the younger animals.

The technique has implications for treating cancer, type 2 diabetes, muscle wasting, inflammatory and mitochondrial diseases as well as anti-aging. Sinclair and his team are now looking at the longer-term outcomes of the NAD-producing compound in mice and how it affects them as a whole. And with the researchers hoping to begin human clinical trials in 2014, some major medical breakthroughs could be just around the corner.

carmat_artificialheartIn another interesting medical story, back in mid-December, a 75 year-old man in Paris became the  recipient of the world’s first Carmat bioprosthetic artificial heart. Now technically, artificial hearts have been in use since the 1980’s. But what sets this particular heart apart, according to its inventor – cardiac surgeon Alain Carpentier – is the Carmat is the first artificial heart to be self-regulating.

In this case, self-regulating refers to the Carmat’s ability to speed or slow its flow rate based on the patient’s physiological needs. For example, if they’re performing a vigorous physical activity, the heart will respond by beating faster. This is made possible via “multiple miniature embedded sensors” and proprietary algorithms running on its integrated microprocessor. Power comes from an external lithium-ion battery pack worn by the patient, and a fuel cell is in the works.

carmat_2Most other artificial hearts beat at a constant unchanging rate, which means that patients either have to avoid too much activity, or risk becoming exhausted quickly. In the course of its human trials, it will be judged based on its ability to keep patients with heart failure alive for a month, but the final version is being designed to operate for five years.

The current lone recipient is reported to be recuperating in intensive care at Paris’ Georges Pompidou European Hospital, where he is awake and carrying on conversations. “We are delighted with this first implant, although it is premature to draw conclusions given that a single implant has been performed and that we are in the early postoperative phase,” says Carmat CEO Marcello Conviti.

medical-technologyAccording to a Reuters report, although the Carmat is similar in size to a natural adult human heart, it’s is somewhat larger and almost three times as heavy – weighing in at approximately 900 grams (2 lb). It should therefore fit inside 86 percent of men, but only 20 percent of women. That said, the company has stated that a smaller model could be made in time.

In the meantime, it’s still a matter of making sure the self-regulating bioprosthetic actually works and prolongs the life of patients who are in the final stages of heart failure. Assuming the trials go well, the Carmat is expected to be available within the European Union by early 2015, priced at between 140,000 and 180,000 euros, which works out to $190,000 – $250,000 US.

See what I mean? From anti-aging to artificial organs, the war on death proceeds apace. Some will naturally wonder if that’s a war meant to be fought, or an inevitably worth mitigating. Good questions, and one’s which we can expect to address at length as the 21st century progresses…

Sources: gizmodo.com, newsroom.unsw.edu.au, (2), carmatsa.com, reuters.com

The Future is… Worms: Life Extension and Computer-Simulations

genetic_circuitPost-mortality is considered by most to be an intrinsic part of the so-called Technological Singularity. For centuries, improvements in medicine, nutrition and health have led to improved life expectancy. And in an age where so much more is possible – thanks to cybernetics, bio, nano, and medical advances – it stands to reason that people will alter their physique in order slow the onset of age and extend their lives even more.

And as research continues, new and exciting finds are being made that would seem to indicate that this future may be just around the corner. And at the heart of it may be a series of experiments involving worms. At the Buck Institute for Research and Aging in California, researchers have been tweaking longevity-related genes in nematode worms in order to amplify their lifespans.

immortal_wormsAnd the latest results caught even the researchers by surprise. By triggering mutations in two pathways known for lifespan extension – mutations that inhibit key molecules involved in insulin signaling (IIS) and the nutrient signaling pathway Target of Rapamycin (TOR) – they created an unexpected feedback effect that amplified the lifespan of the worms by a factor of five.

Ordinarily, a tweak to the TOR pathway results in a 30% lifespan extension in C. Elegans worms, while mutations in IIS (Daf-2) results in a doubling of lifespan. By combining the mutations, the researchers were expecting something around a 130% extension to lifespan. Instead, the worms lived the equivalent of about 400 to 500 human years.

antiagingAs Doctor Pankaj Kapahi said in an official statement:

Instead, what we have here is a synergistic five-fold increase in lifespan. The two mutations set off a positive feedback loop in specific tissues that amplified lifespan. These results now show that combining mutants can lead to radical lifespan extension — at least in simple organisms like the nematode worm.

The positive feedback loop, say the researchers, originates in the germline tissue of worms – a sequence of reproductive cells that may be passed onto successive generations. This may be where the interactions between the two mutations are integrated; and if correct, might apply to the pathways of more complex organisms. Towards that end, Kapahi and his team are looking to perform similar experiments in mice.

DNA_antiagingBut long-term, Kapahi says that a similar technique could be used to produce therapies for aging in humans. It’s unlikely that it would result in the dramatic increase to lifespan seen in worms, but it could be significant nonetheless. For example, the research could help explain why scientists are having a difficult time identifying single genes responsible for the long lives experienced by human centenarians:

In the early years, cancer researchers focused on mutations in single genes, but then it became apparent that different mutations in a class of genes were driving the disease process. The same thing is likely happening in aging. It’s quite probable that interactions between genes are critical in those fortunate enough to live very long, healthy lives.

A second worm-related story comes from the OpenWorm project, an international open source project dedicated to the creation of a bottom-up computer model of a millimeter-sized nemotode. As one of the simplest known multicellular life forms on Earth, it is considered a natural starting point for creating computer-simulated models of organic beings.

openworm-nematode-roundworm-simulation-artificial-lifeIn an important step forward, OpenWorm researchers have completed the simulation of the nematode’s 959 cells, 302 neurons, and 95 muscle cells and their worm is wriggling around in fine form. However, despite this basic simplicity, the nematode is not without without its share of complex behaviors, such as feeding, reproducing, and avoiding being eaten.

To model the complex behavior of this organism, the OpenWorm collaboration (which began in May 2013) is developing a bottom-up description. This involves making models of the individual worm cells and their interactions, based on their observed functionality in the real-world nematodes. Their hope is that realistic behavior will emerge if the individual cells act on each other as they do in the real organism.

openworm-nematode-roundworm-simulation-artificial-life-0Fortunately, we know a lot about these nematodes. The complete cellular structure is known, as well as rather comprehensive information concerning the behavior of the thing in reaction to its environment. Included in our knowledge is the complete connectome, a comprehensive map of neural connections (synapses) in the worm’s nervous system.

The big question is, assuming that the behavior of the simulated worms continues to agree with the real thing, at what stage might it be reasonable to call it a living organism? The usual definition of living organisms is behavioral, that they extract usable energy from their environment, maintain homeostasis, possess a capacity to grow, respond to stimuli, reproduce, and adapt to their environment in successive generations.

openworm-nematode1If the simulation exhibits these behaviors, combined with realistic responses to its external environment, should we consider it to be alive? And just as importantly, what tests would be considered to test such a hypothesis? One possibility is an altered version of the Turing test – Alan Turing’s proposed idea for testing whether or not a computer could be called sentient.

In the Turing test, a computer is considered sentient and sapient if it can simulate the responses of a conscious sentient being so that an auditor can’t tell the difference. A modified Turing test might say that a simulated organism is alive if a skeptical biologist cannot, after thorough study of the simulation, identify a behavior that argues against the organism being alive.

openworm-nematode2And of course, this raises an even larger questions. For one, is humanity on the verge of creating “artificial life”? And what, if anything, does that really look like? Could it just as easily be in the form of computer simulations as anthropomorphic robots and biomachinery? And if the answer to any of these questions is yes, then what exactly does that say about our preconceived notions about what life is?

If humanity is indeed moving into an age of “artificial life”, and from several different directions, it is probably time that we figure out what differentiates the living from the nonliving. Structure? Behavior? DNA? Local reduction of entropy? The good news is that we don’t have to answer that question right away. Chances are, we wouldn’t be able to at any rate.

Brain-ScanAnd though it might not seem apparent, there is a connection between the former and latter story here. In addition to being able to prolong life through genetic engineering, the ability to simulate consciousness through computer-generated constructs might just prove a way to cheat death in the future. If complex life forms and connectomes (like that involved in the human brain) can be simulated, then people may be able to transfer their neural patterns before death and live on in simulated form indefinitely.

So… anti-aging, artificial life forms, and the potential for living indefinitely. And to think that it all begins with the simplest multicellular life form on Earth – the nemotode worm. But then again, all life – nay, all of existence – depends upon the most simple of interactions, which in turn give rise to more complex behaviors and organisms. Where else would we expect the next leap in biotechnological evolution to come from?

And in the meantime, be sure to enjoy this video of the OpenWorm’s simulated nemotode in action


Sources:
IO9, cell.com, gizmag, openworm

The Future of Medicine: Gene Therapy and Treatments

DNA-1Imagine a world where all known diseases were curable, where health problems could be treated in a non-invasive manner, and life could be extended significantly? Thanks to ongoing research into the human genome, and treatments arising out of it, that day may be coming soon. That’s the idea behind gene therapy and pharmacoperones – two treatment procedures that may make disease obsolete in the near future.

The first comes to us from the Utah School of Medicine, where researcher Amit Patel recently developed a non-invasive, naked DNA approach to deal with treating heart problems. His process was recently tested o Ernie Lively, an actor suffering from heart damage, who made a full recovered afterwards without ever having to go under the knife.

gene_therapyIn short, Patel’s method relies on a catheter, which he used to access the main cardiac vein (or coronary sinus), where a balloon is inflated to halt the flow of blood and isolate the area. A high dose of naked DNA, which codes for a protein called SDF-1, is then delivered. SDF-1, which stands for stromal cell-derived factor, is a potent attractant both for stem cells circulating in the bloodstream, and for those developing in the bone marrow.

Stromal cells, which manufacture SDF-1, are the creative force which knit together our fibrous connective tissues. The problem is they do not make enough of this SDF-1 under normal conditions, nor do specifically deliver it in just the right places for repair of a mature heart. By introducing a dose of these cells directly into the heart, Patel was able to give Lively what his heart needed, where it needed it.

gene_therapy1Compared to other gene therapies, the introduction of SDF-1 into cells was done without the assistance of a virus. These “viral vector” method have had trouble in the past due to the fact that after the virus helps target specific cells for treatment, the remnant viral components can draw unwanted attention from the immune system, leading to complications.

But of course, there is still much to be learned about the SDF-1 treatment and others like it before it can be considered a viable replacement for things like open-heart surgery. For one, the yield – the number or percentage of cells that take up the DNA – remains unknown. Neither are the precise mechanisms of uptake and integration within the cell known here.

Fortunately, a great deal of research is being done, particularly by neuroscientists who are looking to control brain cells through the use of raw DNA as well. Given time, additional research, and several clinical trials, a refined version of this process could be the cure for heart-related diseases, Alzheimer’s, and other disorders that are currently thought to be incurable, or require surgery.

pharmacoperones-protein-foldingAnother breakthrough treatment that is expected to revolutionize medicine comes in the form of pharmacoperones (aka. “protein chaperones”). a new field of drugs that have the ability to enter cells and fix misfolded proteins. These kind of mutations usually result in proteins becoming inactive; but in some cases, can lead to toxic functionality or even diseases.

Basically, proteins adopt their functional 3-D structure by folding linear chains of amino acids, and gene mutation can cause this folding process to go awry, resulting in “misfolding”. Up until recently, scientists believed these proteins were simply non-functional. But thanks to ongoing research, it is now known their inactivity is due to the cell’s quality control system misrouting them within the cell.

protein1Although this process has been observed under a microscope in recent years, a team led by Doctor P. Michael Conn while at Oregon Health & Science University (OHSU) was the first to demonstrate it in a living laboratory animal. The team was able to cure mice of a disease that makes the males unable to father offspring, and believe the technique will also work on human beings.

The team says neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington’s, as well as certain types of diabetes, inherited cataracts and cystic fibrosis are just a few of the diseases that could potentially be cured using the new approach. Now working at the Texas Tech University Health Sciences Center (TTUHSC), Conn and his team are looking to conduct human trials.

DNA-molecule2One of the hallmarks of the coming age of science, technology and medicine is the idea that people will be living in post-mortality age, where all diseases and conditions are curable and life can be extended almost indefinitely. Might still sound like science fiction, but all of this research is indicative of the burgeoning trend where things that were once thought to be “treatable but not curable” is a thing of the past.

It’s an exciting time to be living in, almost as exciting as the world our children will be inhabiting – assuming things go according to plan. And in the meantime, check out this video of the SDF-1 gene therapy in action, courtesy of the University of Utah School of Medicine:


Sources: extremetech.com, gizmag.com