Fossil Fuels Just Lost the Race Against Renewables

April 27, 2014

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The race for renewable energy has passed a turning point. The world is now adding more capacity for renewable power each year than coal, natural gas, and oil combined. And there’s no going back.

The shift occurred in 2013, when the world added 143 gigawatts of renewable electricity capacity, compared with 141 gigawatts in new plants that burn fossil fuels, according to an analysis presented Tuesday at the Bloomberg New Energy Finance annual summit in New York. The shift will continue to accelerate, and by 2030 more than four times as much renewable capacity will be added.

“The electricity system is shifting to clean,” Michael Liebreich, founder of BNEF, said in his keynote address. “Despite the change in oil and gas prices there is going to be a substantial buildout of renewable energy that is likely to be an order of magnitude larger than the buildout of coal and gas.”

The Beginning of the End

Power generation capacity additions (GW)

Bloomberg New Energy Finance

The price of wind and solar power continues to plummet, and is now on par or cheaper than grid electricity in many areas of the world. Solar, the newest major source of energy in the mix, makes up less than 1 percent of the electricity market today but could be the world’s biggest single source by 2050, according to the International Energy Agency.

The question is no longer if the world will transition to cleaner energy, but how long it will take. In the chart below, BNEF forecasts the billions of dollars that need to be invested each year in order to avoid the most severe consequences of climate change, represented by a benchmark increase of more than 2 degrees Celsius.

The blue lines are what’s needed, in billions; the red lines show what’s actually being spent. Since the financial crisis, funding has fallen well short of the target, according to BNEF.

Investment Needed to Minimize Climate Change

Source: Bloomberg New Energy Finance

An earlier version of this story represented the IEA’s scenario for solar in 2050 as a forecast when it was in fact one of several possible scenarios. The IEA does not make any forecasts for specific expectations after the 5-year mark, according to spokesman Greg Frost.

http://www.bloomberg.com/news/articles/2015-04-14/fossil-fuels-just-lost-the-race-against-renewables

Immune System Drugs Melt Tumors In New Study, Leading A Cancer Revolution

April 27, 2015

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“I’ve been in immunotherapy for a long time, and we’ve talked and fantasized about reactions like this, but I’ve never seen anything this quickly,” he says. She has no detectable melanoma – amazing for a disease that has long been considered close to untreatable.

The 49-year-old woman had had three melanoma growths removed from her skin, but now the disease was spreading further. A several-centimeter-sized growth under her left breast went deep into her chest wall. Some of the tissue in the tumor was dying because of lack of blood flow.

Doctors at Memorial Sloan Kettering Cancer Center offered her an experimental combination of two drugs: Opdivo and Yervoy, both manufactured by Bristol-Myers Squibb, both among a vanguard of new medicines that boost the immune system to attack tumors. Three weeks later she came back for her second dose.

“She didn’t say anything and when I examined her, I said, ‘Wait a minute!’” says Paul Chapman, the doctor who was treating her. “She said,  ‘Yeah, it kind of just dissolved.’”

Where the tumor was before was, literally, a hole – a wound doctors hope will heal with time. Chapman took some fluid from it, and found there were no melanoma cells there. “I’ve been in immunotherapy for a long time, and we’ve talked and fantasized about reactions like this, but I’ve never seen anything this quickly,” he says. He skipped her next dose, and gave her two more before she stopped treatment because of the diarrhea the drug combination was causing. She has no detectable melanoma – amazing for a disease that has long been considered close to untreatable.

The story, published as a case report this morning in the New England Journal of Medicine, alongside a 142-patient study that tested the combination of Opdivo and Yervoy against Yervoy alone. The results show that the anonymous woman’s case was anything but a fluke, as the combination of the two drugs had unprecedented cancer-fighting potency, but also caused toxicity: 50% of patients had side effects that were severe or life-threatening. But an amazing 22% of patients – 16 of them – had what’s called a complete response. As with Chapman’s patient, all their cancer seemed to melt away.

“To me it’s a really graphic demonstration that the immune system is sitting there, waiting,” says Jedd Wolchok, Director, Ludwig Collaborative Laboratory at Memorial Sloan Kettering and lead author of the new study. “And there are immune cells which are fully prepared to get rid of these tumors. But they are being held in check.”

These new drugs release the body’s own weapons: killer white blood cells called T cells. And that approach is one of several bringing a huge amount of excitement to the field of cancer research, one that can be palpably felt here at the annual meeting of the American Association for Cancer Research in Philadelphia, where researchers are unveiling advances large and small. They are priming the immune system not only with drugs but also with genetically engineered cells and viruses. And they are using powerful genetic sequencing technologies not only to classify tumors and pick drugs, but to create blood tests that will allow doctors to monitor cancer in real time, catching it early and knowing rapidly which medicines will prove effective.

Analysts at Piper Jaffray were swept up in the excitement. “We are attending the AACR cancer meeting in Philadelphia, and are awestruck by the speed at which the oncology field is evolving,” they wrote. The combination of immune-boosting and genetic tools, they argue, could in 20 years make the market for cancer treatment as big as all of health care is now: half a trillion dollars a year.

That could, in part, be the wishful thinking of Wall Streeters who don’t want the current biotech boom (the Nasdaq iShares Biotechnology Index is up 116% in two years) to end. In fact, part of the worry about all these new technologies is their cost: the combination of Opdivo and Yervoy could have a wholesale cost of $270,000 if the patient stays on Opdivo for a full year. How we’re going to pay for all this innovation remains a big question. Other immune therapies that use a patient’s own genetically modified cells could cost even more.

But the innovation is real. Here’s a roundup:

Immune-boosting drugs

The combination of Opdivo and Yervoy had stunning efficacy. Yesterday, Merck announced that its Keytruda, a PD-1 blocker much like Opdivo, beat Yervoy as a melanoma treatment. In both trials, Yervoy caused tumors in about 11% of patients to shrink. Keytruda caused tumors in 33% of patients to shrink. The Opdivo-Yervoy combination caused tumor shrinkage in 66% of patients. It’s not clear how long patients live on the new treatment – the study hasn’t gone on long enough – but it’s much longer than the average 4.4-month survival on Yervoy alone.

Doctors will debate whether this treatment should be used for all melanoma patients or whether the side effects mean patients should try Keytruda or Opdivo alone first. But Wolchok says the standard treatment he offers melanoma patients is an expanded access clinical trial providing the combination. A larger trial testing the combo is expected in a few months. Bristol-Myers Squibb would not say when it will ask the Food and Drug Administration to approve the new therapy.

Meanwhile, advances have come so fast that they’re hard to catalogue. Merck and Bristol have both announced positive results for Keytruda and Opdivo in non-small cell lung cancer, and Keytruda has shown benefit in mesothelioma, the rare cancer that can be caused by asbestos. In an early trial, a similar AstraZeneca drug caused tumors to shrink in 19% of patients with the hard-to-treat triple-negative form of breast cancer.

Killer cells

Some of the most dramatic stories in immunotherapy have come from the field of CAR-T, in which a protein chimeric antigen receptor (CAR) is used to modify a white blood cell (or T-cell) so that it attacks tumors. This has led to stories of patients with blood cancer where tumors literally melt away through an immune response that, like the complete responses seen with the Opdivo-Yervoy combination, could actually be dangerous. (You can hear one such story here.) The excitement around these cells has resulted in the formation of a number of biotechnology startups, including Juno Therapeutics and Kite Pharma.

But so far CARTs have only worked in blood cancer, which is in many ways an easier target. Today, researchers at the University of Pennsylvania, who are working with Novartis, presented data on a CART that targets mesothelin, a protein on the surface of many tumor cells, in two patients with serous ovarian cancer, two with epithelial mesothelioma, and one with pancreatic cancer.

The good news is that nothing particularly terrible happened when the cells were infused (although these patients were sick, and developed conditions including sepsis, fluid in the lung, and anemia). There were no cases of the cytokine release syndrome – the extreme, potentially deadly immune response that occurred in some blood cancer patients.

The CART cells seemed to go to where the tumors were, including in the fluid around the heart, without causing damage and inflammation. It’s still too early, though, to know whether the CART cells are damaging the tumors. All researchers could say was that four of the patients had remained stable – there are no melting tumors this time.

Michel Sadelain, a researcher at Memorial Sloan Kettering and one of the co-founders of Juno Therapeutics, was hopeful but cautious. “With advanced stable disease at four weeks, it’s encouraging but you can’t over-interpret that,” he said. Still, he holds out hope for meso-CARTs, which JUNO is developing to. “If the toxicities are manageable I believe it’s going to be something big,” he says.

Researchers also presented data on using T-cells to treat a rare condition called Epstein-Barr Virus-associated lymphoproliferative disorder. This disease occurs when the virus that causes mononucleosis causes a kind of secondary cancer in patients after a transplant, often a bone marrow transplant. This is a rare disease, but perfect for cell therapy: white blood cells are great at attacking cells infected with viruses, and the patients don’t have immune systems. Using T-cells donated from other patients, researchers were able to reduce or eliminate the cancer cells in 63% of patients. The treatment has received breakthrough designation from the Food and Drug Administration, but has not yet been licensed by a drug company. Atara Biotherapeutics has an exclusive option to license it.

A blood test for cancer?

Another big idea is what’s called a liquid biopsy, in which free bits of cancer DNA are detected via a blood test. Here at AACR, researchers from the Department of Radiation Sciences at Umeå University in Sweden used the technique to determine when patients with lung cancer would stop responding to Xalkori, a Pfizer lung cancer drug. But the implications of the test are much bigger.

Last year at the Forbes Healthcare Summit in New York, Richard Klausner, the chief medical officer of DNA sequencing leader Illumina and the former head of the National Cancer Institute, gave an early look at the promise of this technology.

“There’s a phenomena that we now know that tumors put out, at very early stages, their DNA into the circulation,” Klausner said. “We can now measure that with incredible precision. I think one of the biggest breakthroughs we can see in cancer in the next few years is this possibility that there could be a blood test or a urine test that detects early stage cancer.”

Many of these advances could be years away from the market. And doctors’ ardor is predicated partly on how grim things have been in the past. Even in the Opdivo-Yervoy study, 126 of 142 patients did not see their cancer vanish entirely. And even with the best studies of CART therapy in leukemia, two or three out of every ten patients are not helped, and are likely to die. But in the world of cancer research, where it often seemed that arduous research was only adding mere months to patients lives, this counts as reason for hope.

“We are in the middle of a revolution,” said Louis Weiner, of Georgetown University, at an AACR press conference about the immunotherapies. “I don’t think that is hyperbolic. Those are the kinds of observations that we’ve rarely seen in our business. What really makes it exciting is that it is not just one disease.”

http://www.forbes.com/sites/matthewherper/2015/04/20/immune-system-drugs-melt-tumors-leading-a-cancer-revolution/

World’s first genetic modification of human embryos reported: Experts consider ethics

April 27, 2015

Chinese scientists say they’ve genetically modified human embryos for the very first time. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. Gene editing is a recently developed type of genetic engineering in which DNA is inserted, replaced, or removed.

The team injected 86 embryos and 71 survived, of which 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. Analysis also revealed a number of ‘off-target’ mutations assumed to be caused by the technique acting in other areas of the genome. The results reveal serious obstacles to using the method in medical applications.

The scientists have tried to head off ethical concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. However, the work is very controversial, with some warning it could be the start of a slippery slope towards designer babies.

Below, some experts weigh-in with ethical questions and considerations.

Prof Robin Lovell Badge, Crick Institute, on the science: “The experiments reported by Junjiu Huang and colleagues (Liang et al) in the journal Protein Cell on gene editing in abnormally fertilised human embryos are, I expect, the first of several that we will see this year. There has been much excitement among scientists about the power of these new gene editing methods, and particularly about the CRISPR/Cas9 system, which is relatively simple to use and generally very efficient. The possibility of using such methods to genetically modify human embryos, and therefore humans, has been on the cards since these methods were first described, and recently these prospects have been brought to the attention of the public through several commentaries made by senior scientists and commentators, some of whom have called for a moratorium to halt any attempts.”

Dr Yalda Jamshidi, Senior Lecturer in Human Genetics, St George’s University Hospital Foundation Trust, said: “Inherited genetic conditions often result because the function of a gene is disrupted. In theory replacing the defective gene with a healthy one would be the ideal solution. This type of treatment is what we call gene therapy and researchers have been working on developing techniques to accomplish this for many years.

“Techniques to correct defective genes in ‘non-reproductive’ cells are already at various stages of clinical development and promise to be a powerful approach for many human diseases which don’t yet have an effective treatment. However, altering genes in human embryos can have unpredictable effects on future generations. Furthermore the study by Huang et al showed that the although the CRISPR/Cas9 technique they used can work in the embryo, it can miss the target in the gene and is too inefficient.

“Future research on the technique may improve the accuracy and efficiency, however scientists still don’t fully understand the role of the DNA, and all of its genes. Therefore it is impossible to assess the risks from mis-targeted changes in the DNA sequence, which would affect both the treated embryo and any future generations.”

Prof Shirley Hodgson, Professor of Cancer Genetics, St George’s University of London, said: “I think that this is a significant departure from currently accepted research practice. This is because any manipulation of the germline of human embryos is potentially heritable. Can we be certain that the embryos that the researchers were working on were indeed non-viable? In the past all the gene therapy research that has been approved by regulatory bodies has been somatic, not germline, because of the potentially unpredictable and heritable effects of germline research. The fact that these researchers found that there were a number of “off target” mutations resulting from the technique they used is clearly a worry in this context. Any proposal to do germline genetic manipulation should be very carefully considered by international regulatory bodies before it should be considered as a serious research prospect. This is because of the obvious concerns about the heritability of the genetic alterations induced, and the way in which such research could spread from work on “non-viable” embryos, to work on viable ones once this type of research had been accepted in principle by international regulatory bodies.”

Prof Darren Griffin, Professor of Genetics, University of Kent, said: “Given the widespread use of the CRISPR/Cas9 system, such announcement was inevitable, sooner rather than later. We clearly have a lot of thinking to do. Germline manipulation is currently illegal in the UK but the question is bound to be asked whether this should change, especially if the safety concerns are allayed.”

Associate Professor Peter Illingworth is Medical Director at IVFAustralia: “This is a fascinating piece of experimental science. Using abnormally-fertilised human embryos (I.e. With three sets of DNA instead of two), they have studied whether the a human gene can be modified. They have demonstrated that, in some embryos, but not all, they can change the abnormal human gene. They also find that other genes are affected which may be a serious concern. What they have shown is that it is technically possible, not that it is practically feasible or safe.”

Further information:

http://www.sciencemediacentre.org/expert-reaction-to-the-application-of-genome-editing-techniques-to-human-embryos/

http://www.smc.org.au/expert-reaction-worlds-first-genetic-modification-of-human-embryos-reported-protein-cell/


Story Source:

The above story is based on materials provided by ResearchSEA. Note: Materials may be edited for content and length.

Journal Reference:

  1. Puping Liang, Yanwen Xu, Xiya Zhang, Chenhui Ding, Rui Huang, Zhen Zhang, Jie Lv, Xiaowei Xie, Yuxi Chen, Yujing Li, Ying Sun, Yaofu Bai, Zhou Songyang, Wenbin Ma, Canquan Zhou, Junjiu Huang.CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell, 2015; DOI: 10.1007/s13238-015-0153-5

Google patents robots with personalities in first step towards the singularity

April 27, 2015

 

Google has been awarded a patent for the ‘methods and systems for robot personality development’, a glimpse at a future where robots react based on data they mine from us and hopefully don’t unite and march on city hall.

The company outlines a process by which personalities could be downloaded from the cloud to “provide states or moods representing transitory conditions of happiness, fear, surprise, perplexion, thoughtfulness, derision and so forth. ”

Its futuristic vision seems to be not of a personalised robot for each human but a set of personality traits that can be transferred between different robots.

“The personality and state may be shared with other robots so as to clone this robot within another device or devices,” it said in the patent.

“In this manner, a user may travel to another city, and download within a robot in that city (another “skin”) the personality and state matching the user’s “home location” robot. The robot personality thereby becomes transportable or transferable.”

It doesn’t sound dissimilar from the opening of a Will Smith sci-fi movie, with one robot’s evil data genes spreading via the cloud to all its other robot brethren.

While this sounds far-fetched, the technological singularity – the point at which artificial intelligence exceeds man’s intellectual capacity and produces a runaway effect – is something that Stephen Hawking, Bill Gates and Elon Musk have all expressed concern over.

Google is probably just safeguarding for the future, however, and is unlikely to release any products that require the patent to be employed anytime soon. We’ve still yet to create a robot that can convincingly walk up stairs, so an apocalyptic army is probably a long way off.

 

http://www.independent.co.uk/life-style/gadgets-and-tech/news/google-patents-robots-with-personalities-in-first-step-towards-the-singularity-10151817.html

 

What If One Country Achieves the Singularity First?

April 27, 2015

Zoltan Istvan is a futurist, author of The Transhumanist Wager, and founder of and presidential candidate for the Transhumanist Party. He writes an occasional column for Motherboard in which he ruminates on the future beyond natural human ability.

The concept of a technological singu​larity is tough to wrap your mind around. Even experts have differing definitions. Vernor Vinge, responsible for spreading the idea in the 1990s, believes it’s a moment when growing superintelligence renders our human models of understanding obsolete. Google’s Ray Kurzweil says it’s “a future period during which the pace of technological change will be so rapid, its impact so deep, that human life will be irreversibly transformed.” Kevin Kelly, founding editor of Wired, says, “Singularity is the point at which all the change in the last million years will be superseded by the change in the next five minutes.” Even Christian theologians have chimed in, sometimes referring to it as “the rapture of the nerds.”

My own definition of the singularity is: the point where a fully functioning human mind radically and exponentially increases its intelligence and possibilities via physically merging with technology.

All these definitions share one basic premise—that technology will speed up the acceleration of intelligence to a point when biological human understanding simply isn’t enough to comprehend what’s happening anymore.

That also makes a technological singularity something quasi-spiritual, since anything beyond understanding evokes mystery. It’s worth noting that even most naysayers and luddites who disdain the singularity concept don’t doubt that the human race is heading towards it.

No matter how you look at this, it’s bizarre futurist stuff

In March 2015, I published a Motherboard article titled A Global Arms Race to Create a Superintelligent AI is Looming. The article argued a concept I call the AI Imperative, which says that nations should do all they can to develop artificial intelligence, because whichever country produces an AI first will likely end up ruling the world indefinitely, since that AI will be able to control all other technologies and their development on the planet.

The article generated many thoughtful comments on Red​dit Futurology, Less​Wrong, and elsewhere. I tend not to comment on my own articles in an effort to stay out of the way, but I do always carefully read comment sections. One thing the message boards on this story made me think about was the possibility of a “nationalistic” singularity—what might also be called an exclusive, or private singularity.

If you’re a technophile like me, you probably believe the key to reaching the singularity is two-fold: the creation of a superintelligence, and the ability to merge humans with that intelligence. Without both, it’s probably impossible for people to reach it. With both, it’s probably inevitable.

Currently, the technology to merge the human brain with a machine is already underway. In fact, hundreds of thousands of people around the world already have brain implants of some sort, and last year telepathy was performed between researchers in different countries. Thoughts were passed from one mind to another using a machine interface, without speaking a word.

Fast forward 25 years in the future, and some experts like Kurzweil believe we might already be able to upload our entire consciousness into a machine. I tend to agree with him, and I even think it could occur sooner, such as in 15 to 20 years time.

Here’s the crux: If an AI exclusively belonged to one nation (which is likely to happen), and the technology of merging human brains and machines grows sufficiently (which is also likely to happen), then you could possibly end up with one nation controlling the pathways into the singularity.

As insane as this sounds, it’s possible that the controlling nation could start offering its citizens the opportunity to be uploaded fully into machines, in preparation to enter the singularity. Whether there would then be two distinct entities—one biological and one uploaded—for every human who choses to do this is a natural question, and it’s only one that could be decided at the time, probably by governments and law. Furthermore, once uploaded, would your digital self be able to interact with your biological self? Would one self be able to help the other? Or would laws force an either-or situation, where uploaded people’s biological selves must remain in cryogenically frozen states or even be eliminated altogether?

No matter how you look at this, it’s bizarre futurist stuff. And it presents a broad array of challenging ethical issues, since some technologists see the singularity as something akin to a totally new reality or even a so-called digital heaven. And to have one nation or government controlling it, or even attempting to limit it exclusively to its populace, seems potentially morally dubious.

For example, what if America created the AI first, then used its superintelligence to pursue a singularity exclusively for Americans?

(Historically, this wouldn’t be that far off from what many Abrahamic world religions advocate for, such as Christianity or Islam. In both religions, only certain types of people get to go to heaven. Those left behind get tortured for eternity. This concept of exclusivity is the single largest reason I became an atheist at 18.)

Worse, what if a government chose only to allow the super wealthy to pursue its doorway to the singularity—to plug directly into its superintelligent AI? Or what if the government only gave access to high-ranked party officials? For example, how would Russia’s Vladimir Putin deal with this type of power? And it is a tremendous power. After all, you’d be connected to a superintelligence and would likely be able to rewrite all the nuclear arms codes in the world, stop dams and power plants from operating, and create a virus to shut down Wi-Fi worldwide, if you wanted.

And at some point, we won’t see a difference between matter, energy, judgment, and ourselves.

Of course, given the option, many people would probably choose not to undergo the singularity at all. I suspect many would choose to remain as they are on Earth. However, some of those people might be keen on acquiring the technology of getting to the singularity. They might want to sell that tech, and offer paid one-way trips for people who want to have a singularity. For that matter, individuals or corporations might try to patent it. What you’d be selling is the path to vast amounts of power and immortality.

Such moral leanings and concepts that someone or group could control, patent, or steal the singularity ultimately lead us to another imperative: the Singularity Disparity.

The first person or group to experience the singularity will protect and preserve the power and intelligence they’ve acquired in the singularity process—which ultimately means they will do whatever is necessary to lessen the power and intelligence accumulation of the singularity experience for others. That way the original Singularitarians can guarantee their power and existence indefinitely.

In my philosophical novel The Transhumanist Wager, this type of thinking belongs to the Omnipotender, someone who is actively seeking and contending for as much power as possible, and bases their actions on such endeavors.

I’m not trying to argue any of this is good or bad, moral or immoral. I’m just explaining how this phenomena of the singularity likely could unfold. Assuming I’m correct, and technology continues to grow rapidly, the person who will become the leading omnipotender on Earth is already born.

Of course, religions will appreciate that fact, because such a person will fulfill elements of either the Antichrist or the Second Coming of a Jesus, which is important to both the apocalyptic beliefs in Christianity and Isla​m. At least the “End Times” are really here, faith-touters will be able to finally say.

The good news, though, is that maybe a singularity is not an exclusive event. Maybe there can be many singularities.

A singularity is likely to be mostly a consciousness phenomenon. We will be nearly all digital and interconnected with machines, but we will still able to recognize ourselves, values, memories, and our purposes—otherwise I don’t think we’d go through with it. On the cusp of the singularity, our intelligence will begin to grow tremendously. I expect the software of our minds will be able to be rewritten and upgraded almost instantaneously in real time. I also think the hardware we exist through—whatever form of computing it’ll be—will also be able to be reshaped and remade in real time. We’ll learn how to reassemble processors and their particles in the moment, on-demand, probably with the same agility and speed we have when thinking about something, such as figuring out a math problem. We’ll understand the rules and think about what we want, and the best answer, strategy, and path will occur. We’ll get exceedingly efficient at such things, too. And at some point, we won’t see a difference between matter, energy, judgment, and ourselves.

What’s important here is the likely fact that we won’t care much about what’s left on Earth. In just days or even hours, the singularity will probably render us into some form of energy that can organize and advance itself superintelligently, perhaps into a trillion minds on a million Earths.

If the singularity occurs like this, then, on the surface, there’s little ethically wrong with a national or private singularity, because other nations or groups could implement their own in time. However, the larger issue is: How would people on Earth protect themselves from someone or some group in the singularity who decides the Earth and its inhabitants aren’t worth keeping around, or worse, wants to enslave everyone on Earth? There’s no easy answer to this, but the question itself makes me frown upon the singularity idea, in exactly the same way I frown upon an omnipotent God and heaven. I don’t like any other single entity or group having that much possible power over another.

 

http://motherboard.vice.com/read/what-if-one-country-achieves-the-singularity-first

 

3D-Printed Kidney Tissue Is Here

April 13, 2015

kidney

Just like you would hope, something very cool was revealed at the 2015 Experimental Biology conference in Boston: the biomedical company Organovo showed off its technique for 3D printing human kidney tissue.

Organovo has been working on printing functional human tissue since being incorporated in 2007, and first printed a cellular blood vessel in 2010. Since January 2014, it has offered bioprinted liver tissue (marketed as exVive3D™ liver tissue) for companies to use in drug trials and disease modeling, and it looks as though its bioprinted human kidney tissue will be used for the same tasks, starting sometime in the latter half of 2016.

“Kidney represents an ideal extension of capabilities to 3D bioprint organ tissues that can be tremendously useful in pharmaceutical research,” Keith Murphy, Organovo’s chairman and CEO, said via press release. “The product that we intend to build from these initial results can be an excellent expansion for our core customers in toxicology, who regularly express to us an interest in having better solutions for the assessment of human kidney toxicity.”

Organovo’s website has a video that sort of explains how they take human cells and put them into, in this case, a matrix to grow into human tissue. An email with follow-up questions has yet to be answered, but as the Wall Street Journal explained in February, Organovo prints organs in much the same way, putting cells in as “bio-ink” and then printing them in layers, initially held together by hydrogel until the cells grow together.

The most common type of kidney cancer is renal cell carcinoma, so it’s probably no surprise that Organovo demonstrated how it printed multiple “tissue-relevant cell types” to recapitulate the renal tubes themselves.

So far Organovo’s 3D-printed liver tissue is used for preclinical drug trials, because the tissue responds like a real life human liver would for 42 days. That’s much longer than the single layers of cells previously used in tests, which wilt in a few days. There are mixed views on how far off printing functional organs for transplant is. Growing tissue is one thing, but growing an organ and integrating it into a living body is another.

“Everybody’s dream is the 3D-printed organ. Are we ever going to get there?” asked Gabor Forgacs, whose research forms the basis of Organovo’s method. “I’m not so sure,” he told the Select Biosciences Tissue Engineering & Bioprinting Conference, which was also held in Boston.

In the course of his keynote speech Forgacs argued that there was no reason functional organs couldn’t be made eventually, but that printing replacement organs on demand was still decades away.

With the cost of bringing new drugs to market extremely high, and the price being passed on to consumers in dramatic and unfortunate ways, lowering the cost of pharmaceutical tests is still very useful. Like biopaper covered in collagen and a protein matrix, it’s a place to grow.

http://motherboard.vice.com/read/3d-printed-kidney-tissue-is-here

 

Fountain of youth uncovered in mammary glands of mice, by breast cancer researchers

April 13, 2015

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The Fountain of Youth has been discovered and it’s not in Florida as Ponce de Leon claimed. Instead, it was found in the mammary glands of genetically modified mice.

A research team led by Professor Rama Khokha has found that when two factors that control tissue development are removed, you can avoid the impact of aging.

Think of tissue as a building that is constantly under renovation. The contractors would be “metalloproteinases,” which are constantly working to demolish and reconstruct the tissue. The architects in this case, who are trying to reign in and direct the contractors, are known as “tissue inhibitors of metalloproteinases” — or TIMPs. When the architect and the contractors don’t communicate well, a building can fall down. In the case of tissue, the result can be cancer.

To understand how metalloproteinases and TIMPs interact, medical researchers breed mice that have one or more of the four different types of TIMPs removed. Khokha’s team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice. The results are presented in Nature Cell Biology.

In the normal course of aging, your tissue losses its ability to develop and repair as fast as it did when you were young. That’s because stem cells, which are abundant in your youth, decline with the passing of time. The U of T team found that with the TIMP1 and TIMP3 architects missing, the pool of stem cells expanded and remained functional throughout the lifetime of these mice.

“Normally you would see these pools of stem cells, which reach their peak at six months in the mice, start to decline. As a result, the mammary glands start to degenerate, which increases the risk of breast cancer occurring,” explains Khokha. “However, we found that in these particular mice, the stem cells remained consistently high when we measured them at every stage of life.”

The team also found that despite large number of stem cells, there was no increased risk of cancer.

“It’s generally assumed that the presence of a large number of stem cells can lead to an increased cancer risk,” says Khokha. “However, we found these mice had no greater predisposition to cancer.”

The next step in this research is to understand why this is happening. Khokha is also working with her colleagues at Princess Margaret to see how altered tissue remodeling might prevent cancer development or lead to a new therapeutic treatment for patients.

Khokha is a Professor in the departments of Medical Biophysics and Laboratory Medicine and Pathobiology, as well as a Senior Scientist at the Princess Margaret Cancer Centre. Her work is supported by the Canadian Breast Cancer Foundation and the Canadian Cancer Society Research Institute.

She was drawn to this research by the complexity of breast tissue.

“It’s a fundamental tissue that is constantly reorganizing. It develops at puberty. It goes through cycles of change in the adult female. New structures appear and regress,” she explains. “It is therefore a good system to explore in order to understand tissue maintenance and epithelial cell turnover — the cells that underlie carcinomas, the most frequent type of cancer.”

She worked closely with the paper’s lead author, Dr. Hartland Jackson, who earned his PhD under her supervision. He is now completing a post-doctoral fellowship at the University of Zurich’s Institute of Molecular Life Sciences.

“He’s continuing his work in breast cancer and learning some really interesting techniques that, I hope, he’ll bring back here,” says Khokha, who beams with pride at her former student’s success.


Story Source:

The above story is based on materials provided by University of Toronto. The original article was written by Liam Mitchell. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hartland W. Jackson, Paul Waterhouse, Ankit Sinha, Thomas Kislinger, Hal K. Berman, Rama Khokha. Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice. Nature Cell Biology, 2015; 17 (3): 217 DOI: 10.1038/ncb3118

Genetically Engineering Almost Anything

April 13, 2015

dna-repair-machinery-1024x575

When it comes to genetic engineering, we’re amateurs. Sure, we’ve known about DNA’s structure for more than 60 years, we first sequenced every A, T, C, and G in our bodies more than a decade ago, and we’re becoming increasingly adept at modifying the genes of a growing number of organisms.

But compared with what’s coming next, all that will seem like child’s play. A new technology just announced today has the potential to wipe out diseases, turn back evolutionary clocks, and reengineer entire ecosystems, for better or worse. Because of how deeply this could affect us all, the scientists behind it want to start a discussion now, before all the pieces come together over the next few months or years. This is a scientific discovery being played out in real time.

Today, researchers aren’t just dropping in new genes, they’re deftly adding, subtracting, and rewriting them using a series of tools that have become ever more versatile and easier to use. In the last few years, our ability to edit genomes has improved at a shockingly rapid clip. So rapid, in fact, that one of the easiest and most popular tools, known as CRISPR-Cas9, is just two years old. Researchers once spent months, even years, attempting to rewrite an organism’s DNA. Now they spend days.

Soon, though, scientists will begin combining gene editing with gene drives, so-called selfish genes that appear more frequently in offspring than normal genes, which have about a 50-50 chance of being passed on. With gene drives—so named because they drive a gene through a population—researchers just have to slip a new gene into a drive system and let nature take care of the rest. Subsequent generations of whatever species we choose to modify—frogs, weeds, mosquitoes—will have more and more individuals with that gene until, eventually, it’s everywhere.

Cas9-based gene drives could be one of the most powerful technologies ever discovered by humankind. “This is one of the most exciting confluences of different theoretical approaches in science I’ve ever seen,” says Arthur Caplan, a bioethicist at New York University. “It merges population genetics, genetic engineering, molecular genetics, into an unbelievably powerful tool.”

We’re not there yet, but we’re extraordinarily close. “Essentially, we have done all of the pieces, sometimes in the same relevant species.” says Kevin Esvelt, a postdoc at Harvard University and the wunderkind behind the new technology. “It’s just no one has put it all together.”

It’s only a matter of time, though. The field is progressing rapidly. “We could easily have laboratory tests within the next few months and then field tests not long after that,” says George Church, a professor at Harvard University and Esvelt’s advisor. “That’s if everybody thinks it’s a good idea.”

It’s likely not everyone will think this is a good idea. “There are clearly people who will object,” Caplan says. “I think the technique will be incredibly controversial.” Which is why Esvelt, Church, and their collaborators are publishing papers now, before the different parts of the puzzle have been assembled into a working whole.

“If we’re going to talk about it at all in advance, rather than in the past tense,” Church says, “now is the time.”

“Deleterious Genes”

The first organism Esvelt wants to modify is the malaria-carrying mosquito Anopheles gambiae. While his approach is novel, the idea of controlling mosquito populations through genetic modification has actually been around since the late 1970s. Then, Edward F. Knipling, an entomologist with the U.S. Department of Agriculture, published a substantial handbook with a chapter titled “Use of Insects for Their Own Destruction.” One technique, he wrote, would be to modify certain individuals to carry “deleterious genes” that could be passed on generation after generation until they pervaded the entire population. It was an idea before its time. Knipling was on the right track, but he and his contemporaries lacked the tools to see it through.

The concept surfaced a few more times before being picked up by Austin Burt, an evolutionary biologist and population geneticist at Imperial College London. It was the late 1990s, and Burt was busy with his yeast cells, studying their so-called homing endonucleases, enzymes that facilitate the copying of genes that code for themselves. Self-perpetuating genes, if you will. “Through those studies, gradually, I became more and more familiar with endonucleases, and I came across the idea that you might be able to change them to recognize new sequences,” Burt recalls.

Other scientists were investigating endonucleases, too, but not in the way Burt was. “The people who were thinking along those lines, molecular biologists, were thinking about using these things for gene therapy,” Burt says. “My background in population biology led me to think about how they could be used to control populations that were particularly harmful.”

In 2003, Burt penned an influential article that set the course for an entire field: We should be using homing endonucleases, a type of gene drive, to modify malaria-carrying mosquitoes, he said, not ourselves. Burt saw two ways of going about it—one, modify a mosquito’s genome to make it less hospitable to malaria, and two, skew the sex ratio of mosquito populations so there are no females for the males to reproduce with. In the following years, Burt and his collaborators tested both in the lab and with computer models before they settled on sex ratio distortion. (Making mosquitoes less hospitable to malaria would likely be a stopgap measure at best; the Plasmodium protozoans could evolve to cope with the genetic changes, just like they have evolved resistance to drugs.)

Burt has spent the last 11 years refining various endonucleases, playing with different scenarios of inheritance, and surveying people in malaria-infested regions. Now, he finally feels like he is closing in on his ultimate goal. “There’s a lot to be done still,” he says. “But on the scale of years, not months or decades.”

Cheating Natural Selection

Cas9-based gene drives could compress that timeline even further. One half of the equation—gene drives—are the literal driving force behind proposed population-scale genetic engineering projects. They essentially let us exploit evolution to force a desired gene into every individual of a species. “To anthropomorphize horribly, the goal of a gene is to spread itself as much as possible,” Esvelt says. “And in order to do that, it wants to cheat inheritance as thoroughly as it can.” Gene drives are that cheat.

Without gene drives, traits in genetically-engineered organisms released into the wild are vulnerable to dilution through natural selection. For organisms that have two parents and two sets of chromosomes (which includes humans, many plants, and most animals), traits typically have only a 50-50 chance of being inherited, give or take a few percent. Genes inserted by humans face those odds when it comes time to being passed on. But when it comes to survival in the wild, a genetically modified organism’s odds are often less than 50-50. Engineered traits may be beneficial to humans, but ultimately they tend to be detrimental to the organism without human assistance. Even some of the most painstakingly engineered transgenes will be gradually but inexorably eroded by natural selection.

Some naturally occurring genes, though, have over millions of years learned how to cheat the system, inflating their odds of being inherited. Burt’s “selfish” endonucleases are one example. They take advantage of the cell’s own repair machinery to ensure that they show up on both chromosomes in a pair, giving them better than 50-50 odds when it comes time to reproduce.

gene-drive-family-tree

A gene drive (blue) always ends up in all offspring, even if only one parent has it. That means that, given enough generations, it will eventually spread through the entire population.

Here’s how it generally works. The term “gene drive” is fairly generic, describing a number of different systems, but one example involves genes that code for an endonuclease—an enzyme which acts like a pair of molecular scissors—sitting in the middle of a longer sequence of DNA that the endonculease is programmed to recognize. If one chromosome in a pair contains a gene drive but the other doesn’t, the endonuclease cuts the second chromosome’s DNA where the endonuclease code appears in the first.

The broken strands of DNA trigger the cell’s repair mechanisms. In certain species and circumstances, the cell unwittingly uses the first chromosome as a template to repair the second. The repair machinery, seeing the loose ends that bookend the gene drive sequence, thinks the middle part—the code for the endonuclease—is missing and copies it onto the broken chromosome. Now both chromosomes have the complete gene drive. The next time the cell divides, splitting its chromosomes between the two new cells, both new cells will end up with a copy of the gene drive, too. If the entire process works properly, the gene drive’s odds of inheritance aren’t 50%, but 100%.

gene-drive-schematic

Here, a mosquito with a gene drive (blue) mates with a mosquito without one (grey). In the offspring, one chromosome will have the drive. The endonuclease then slices into the drive-free DNA. When the strand gets repaired, the cell’s machinery uses the drive chromosome as a template, unwittingly copying the drive into the break.

Most natural gene drives are picky about where on a strand of DNA they’ll cut, so they need to be modified if they’re to be useful for genetic engineering.

For the last few years, geneticists have tried using genome-editing tools to build custom gene drives, but the process was laborious and expensive. With the discovery of CRISPR-Cas9 as a genome editing tool in 2012, though, that barrier evaporated. CRISPR is an ancient bacterial immune system which identifies the DNA of invading viruses and sends in an endonuclease, like Cas9, to chew it up. Researchers quickly realized that Cas9 could easily be reprogrammed to recognize nearly any sequence of DNA. All that’s needed is the right RNA sequence—easily ordered and shipped overnight—which Cas9 uses to search a strand of DNA for where to cut. This flexibility, Esvelt says, “lets us target, and therefore edit, pretty much anything we want.” And quickly.

Gene drives and Cas9 are each powerful on their own, but together they could significantly change biology. CRISRP-Cas9 allows researchers to edit genomes with unprecedented speed, and gene drives allow engineered genes to cheat the system, even if the altered gene weakens the organism. Simply by being coupled to a gene drive, an engineered gene can race throughout a population before it is weeded out. “Eventually, natural selection will win,” Esvelt says, but “gene drives just let us get ahead of the game.”

Beyond Mosquitoes

If there’s anywhere we could use a jump start, it’s in the fight against malaria. Each year, the disease kills over 200,000 people and sickens over 200 million more, most of whom are in Africa. The best new drugs we have to fight it are losing ground; the Plasmodium parasite is evolving resistance too quickly. And we’re nowhere close to releasing an effective vaccine. The direct costs of treating the disease are estimated at $12 billion, and the economies of affected countries grew 1.3% less per year, a substantial amount.

Which is why Esvelt and Burt are both so intently focused on the disease. “If we target the mosquito, we don’t have to face resistance on the parasite itself. The idea is, we can just take out the vector and stop all transmission. It might even lead to eradication,” Esvelt says.

Esvelt initially mulled over the idea of building Cas9-based gene drives in mosquitoes to do just that. He took the idea to to Flaminia Catteruccia, a professor who studies malaria at the Harvard School of Public Health, and the two grew increasingly certain that such a system would not only work, but work well. As their discussions progressed, though, Esvelt realized they were “missing the forest for the trees.” Controlling malaria-carrying mosquitoes was just the start. Cas9-based gene drives were the real breakthrough. “If it let’s us do this for mosquitos, what is to stop us from potentially doing it for almost anything that is sexually reproducing?” he realized.

In theory, nothing. But in reality, the system works best on fast-reproducing species, Esvelt says. Short generation times allow the trait to spread throughout a population more quickly. Mosquitoes are a perfect test case. If everything were to work perfectly, deleterious traits could sweep through populations of malaria-carrying mosquitoes in as few as five years, wiping them off the map.

Other noxious species could be candidates, too. Certain invasive species, like mosquitoes in Hawaii or Asian carp in the Great Lakes, could be targeted with Cas9-based gene drives to either reduce their numbers or eliminate them completely. Agricultural weeds like horseweed that have evolved resistance to glyphosate, a herbicide that is broken down quickly in the soil, could have their susceptibility to the compound reintroduced, enabling more farmers to adopt no-till practices, which help conserve topsoil. And in the more distant future, Esvelt says, weeds could even be engineered to introduce vulnerabilities to completely benign substances, eliminating the need for toxic pesticides. The possibilities seem endless.

The Decision

Before any of that can happen, though, Esvelt and Church are adamant that the public help decide whether the research should move forward. “What we have here is potentially a general tool for altering wild populations,” Esvelt says. “We really want to make sure that we proceed down this path—if we decide to proceed down this path—as safely and responsibly as possible.”

To kickstart the conversation, they partnered with the MIT political scientist Kenneth Oye and others to convene a series of workshops on the technology. “I thought it might be useful to get into the room people with slightly different material interests,” Oye says, so they invited regulators, nonprofits, companies, and environmental groups. The idea, he says, was to get people to meet several times, to gain trust and before “decisions harden.” Despite the diverse viewpoints, Oye says there was surprising agreement among participants about what the important outstanding questions were.

As the discussion enters the public sphere, tensions are certain to intensify. “I don’t care if it’s a weed or a blight, people still are going to say this is way too massive a genetic engineering project,” Caplan says. “Secondly, it’s altering things that are inherited, and that’s always been a bright line for genetic engineering.” Safety, too, will undoubtedly be a concern. As the power of a tool increases, so does its potential for catastrophe, and Cas9-based gene drives could be extraordinarily powerful.

There’s also little in the way of precedent that we can use as a guide. Our experience with genetically modified foods would seem to be a good place to start, but they are relatively niche organisms that are heavily dependent on water and fertilizer. It’s pretty easy to keep them contained to a field. Not so with wild organisms; their potential to spread isn’t as limited.

Aware of this, Esvelt and his colleagues are proposing a number of safeguards, including reversal drives that can undo earlier engineered genes. “We need to really make sure those work if we’re proposing to build a drive that is intended to modify a wild population,” Esvelt says.

There are still other possible hurdles to surmount—lab-grown mosquitoes may not interbreed with wild ones, for example—but given how close this technology is to prime time, Caplan suggests researchers hew to a few initial ethical guidelines. One, use species that are detrimental to human health and don’t appear to fill a unique niche in the wild. (Malaria-carrying mosquitoes seem fit that description.) Two, do as much work as possible using computer models. And three, researchers should continue to be transparent about their progress, as they have been. “I think the whole thing is hugely exciting,” Caplan says. “But the time to really get cracking on the legal/ethical infrastructure for this technology is right now.”

Church agrees, though he’s also optimistic about the potential for Cas9-based gene drives. “I think we need to be cautious with all new technologies, especially all new technologies that are messing with nature in some way or another. But there’s also a risk of doing nothing,” Church says. “We have a population of 7 billion people. You have to deal with the environmental consequences of that.”

http://www.pbs.org/wgbh/nova/next/evolution/crispr-gene-drives/