Category Archives: Human Genetic Engineering

The rapid development of so-called NBIC technologies nanotechnology, biotechnology, information technology and cognitive science are giving rise to possibilities that have long been the domain of science fiction. Disease, ageing and even death are all human realities that these technologies seek to end.

They may enable us to enjoy greater morphological freedom we could take on new forms through prosthetics or genetic engineering. Or advance our cognitive capacities. We could use brain-computer interfaces to link us to advanced artificial intelligence (AI).

Nanobots could roam our bloodstream to monitor our health and enhance our emotional propensities for joy, love or other emotions. Advances in one area often raise new possibilities in others, and this convergence may bring about radical changes to our world in the near-future.

Transhumanism is the idea that humans should transcend their current natural state and limitations through the use of technology that we should embrace self-directed human evolution. If the history of technological progress can be seen as humankinds attempt to tame nature to better serve its needs, transhumanism is the logical continuation: the revision of humankinds nature to better serve its fantasies.

As David Pearce, a leading proponent of transhumanism and co-founder of Humanity+, says:

If we want to live in paradise, we will have to engineer it ourselves. If we want eternal life, then well need to rewrite our bug-ridden genetic code and become god-like only hi-tech solutions can ever eradicate suffering from the world. Compassion alone is not enough.

But there is a darker side to the naive faith that Pearce and other proponents have in transhumanism one that is decidedly dystopian.

There is unlikely to be a clear moment when we emerge as transhuman. Rather technologies will become more intrusive and integrate seamlessly with the human body. Technology has long been thought of as an extension of the self. Many aspects of our social world, not least our financial systems, are already largely machine-based. There is much to learn from these evolving human/machine hybrid systems.

Yet the often Utopian language and expectations that surround and shape our understanding of these developments have been under-interrogated. The profound changes that lie ahead are often talked about in abstract ways, because evolutionary advancements are deemed so radical that they ignore the reality of current social conditions.

In this way, transhumanism becomes a kind of techno-anthropocentrism, in which transhumanists often underestimate the complexity of our relationship with technology. They see it as a controllable, malleable tool that, with the correct logic and scientific rigour, can be turned to any end. In fact, just as technological developments are dependent on and reflective of the environment in which they arise, they in turn feed back into the culture and create new dynamics often imperceptibly.

Situating transhumanism, then, within the broader social, cultural, political, and economic contexts within which it emerges is vital to understanding how ethical it is.

Max More and Natasha Vita-More, in their edited volume The Transhumanist Reader, claim the need in transhumanism for inclusivity, plurality and continuous questioning of our knowledge.

Yet these three principles are incompatible with developing transformative technologies within the prevailing system from which they are currently emerging: advanced capitalism.

One problem is that a highly competitive social environment doesnt lend itself to diverse ways of being. Instead it demands increasingly efficient behaviour. Take students, for example. If some have access to pills that allow them to achieve better results, can other students afford not to follow? This is already a quandary. Increasing numbers of students reportedly pop performance-enhancing pills. And if pills become more powerful, or if the enhancements involve genetic engineering or intrusive nanotechnology that offer even stronger competitive advantages, what then? Rejecting an advanced technological orthodoxy could potentially render someone socially and economically moribund (perhaps evolutionarily so), while everyone with access is effectively forced to participate to keep up.

Going beyond everyday limits is suggestive of some kind of liberation. However, here it is an imprisoning compulsion to act a certain way. We literally have to transcend in order to conform (and survive). The more extreme the transcendence, the more profound the decision to conform and the imperative to do so.

The systemic forces cajoling the individual into being upgraded to remain competitive also play out on a geo-political level. One area where technology R&D has the greatest transhumanist potential is defence. DARPA (the US defence department responsible for developing military technologies), which is attempting to create metabolically dominant soldiers, is a clear example of how vested interests of a particular social system could determine the development of radically powerful transformative technologies that have destructive rather than Utopian applications.

The rush to develop super-intelligent AI by globally competitive and mutually distrustful nation states could also become an arms race. In Radical Evolution, novelist Verner Vinge describes a scenario in which superhuman intelligence is the ultimate weapon. Ideally, mankind would proceed with the utmost care in developing such a powerful and transformative innovation.

There is quite rightly a huge amount of trepidation around the creation of super-intelligence and the emergence of the singularity the idea that once AI reaches a certain level it will rapidly redesign itself, leading to an explosion of intelligence that will quickly surpass that of humans (something that will happen by 2029 according to futurist Ray Kurzweil). If the world takes the shape of whatever the most powerful AI is programmed (or reprograms itself) to desire, it even opens the possibility of evolution taking a turn for the entirely banal could an AI destroy humankind from a desire to produce the most paperclips for example?

Its also difficult to conceive of any aspect of humanity that could not be improved by being made more efficient at satisfying the demands of a competitive system. It is the system, then, that determines humanitys evolution without taking any view on what humans are or what they should be. One of the ways in which advanced capitalism proves extremely dynamic is in its ideology of moral and metaphysical neutrality. As philosopher Michael Sandel says: markets dont wag fingers. In advanced capitalism, maximising ones spending power maximises ones ability to flourish hence shopping could be said to be a primary moral imperative of the individual.

Philosopher Bob Doede rightly suggests it is this banal logic of the market that will dominate:

If biotech has rendered human nature entirely revisable, then it has no grain to direct or constrain our designs on it. And so whose designs will our successor post-human artefacts likely bear? I have little doubt that in our vastly consumerist, media-saturated capitalist economy, market forces will have their way. So the commercial imperative would be the true architect of the future human.

Whether the evolutionary process is determined by a super-intelligent AI or advanced capitalism, we may be compelled to conform to a perpetual transcendence that only makes us more efficient at activities demanded by the most powerful system. The end point is predictably an entirely nonhuman though very efficient technological entity derived from humanity that doesnt necessarily serve a purpose that a modern-day human would value in any way. The ability to serve the system effectively will be the driving force. This is also true of natural evolution technology is not a simple tool that allows us to engineer ourselves out of this conundrum. But transhumanism could amplify the speed and least desirable aspects of the process.

For bioethicist Julian Savulescu, the main reason humans must be enhanced is for our species to survive. He says we face a Bermuda Triangle of extinction: radical technological power, liberal democracy and our moral nature. As a transhumanist, Savulescu extols technological progress, also deeming it inevitable and unstoppable. It is liberal democracy and particularly our moral nature that should alter.

The failings of humankind to deal with global problems are increasingly obvious. But Savulescu neglects to situate our moral failings within their wider cultural, political and economic context, instead believing that solutions lie within our biological make up.

Yet how would Savulescus morality-enhancing technologies be disseminated, prescribed and potentially enforced to address the moral failings they seek to cure? This would likely reside in the power structures that may well bear much of the responsibility for these failings in the first place. Hes also quickly drawn into revealing how relative and contestable the concept of morality is:

We will need to relax our commitment to maximum protection of privacy. Were seeing an increase in the surveillance of individuals and that will be necessary if we are to avert the threats that those with antisocial personality disorder, fanaticism, represent through their access to radically enhanced technology.

Such surveillance allows corporations and governments to access and make use of extremely valuable information. In Who Owns the Future, internet pioneer Jaron Lanier explains:

Troves of dossiers on the private lives and inner beings of ordinary people, collected over digital networks, are packaged into a new private form of elite money It is a new kind of security the rich trade in, and the value is naturally driven up. It becomes a giant-scale levee inaccessible to ordinary people.

Crucially, this levee is also invisible to most people. Its impacts extend beyond skewing the economic system towards elites to significantly altering the very conception of liberty, because the authority of power is both radically more effective and dispersed.

Foucaults notion that we live in a panoptic society one in which the sense of being perpetually watched instils discipline is now stretched to the point where todays incessant machinery has been called a superpanopticon. The knowledge and information that transhumanist technologies will tend to create could strengthen existing power structures that cement the inherent logic of the system in which the knowledge arises.

This is in part evident in the tendency of algorithms toward race and gender bias, which reflects our already existing social failings. Information technology tends to interpret the world in defined ways: it privileges information that is easily measurable, such as GDP, at the expense of unquantifiable information such as human happiness or well-being. As invasive technologies provide ever more granular data about us, this data may in a very real sense come to define the world and intangible information may not maintain its rightful place in human affairs.

Existing inequities will surely be magnified with the introduction of highly effective psycho-pharmaceuticals, genetic modification, super intelligence, brain-computer interfaces, nanotechnology, robotic prosthetics, and the possible development of life expansion. They are all fundamentally inegalitarian, based on a notion of limitlessness rather than a standard level of physical and mental well-being weve come to assume in healthcare. Its not easy to conceive of a way in which these potentialities can be enjoyed by all.

Sociologist Saskia Sassen talks of the new logics of expulsion, that capture the pathologies of todays global capitalism. The expelled include the more than 60,000 migrants who have lost their lives on fatal journeys in the past 20 years, and the victims of the racially skewed profile of the increasing prison population.

In Britain, they include the 30,000 people whose deaths in 2015 were linked to health and social care cuts and the many who perished in the Grenfell Tower fire. Their deaths can be said to have resulted from systematic marginalisation.

Unprecedented acute concentration of wealth happens alongside these expulsions. Advanced economic and technical achievements enable this wealth and the expulsion of surplus groups. At the same time, Sassen writes, they create a kind of nebulous centrelessness as the locus of power:

The oppressed have often risen against their masters. But today the oppressed have mostly been expelled and survive a great distance from their oppressors The oppressor is increasingly a complex system that combines persons, networks, and machines with no obvious centre.

Surplus populations removed from the productive aspects of the social world may rapidly increase in the near future as improvements in AI and robotics potentially result in significant automation unemployment. Large swaths of society may become productively and economically redundant. For historian Yuval Noah Harari the most important question in 21st-century economics may well be: what should we do with all the superfluous people?

We would be left with the scenario of a small elite that has an almost total concentration of wealth with access to the most powerfully transformative technologies in world history and a redundant mass of people, no longer suited to the evolutionary environment in which they find themselves and entirely dependent on the benevolence of that elite. The dehumanising treatment of todays expelled groups shows that prevailing liberal values in developed countries dont always extend to those who dont share the same privilege, race, culture or religion.

In an era of radical technological power, the masses may even represent a significant security threat to the elite, which could be used to justify aggressive and authoritarian actions (perhaps enabled further by a culture of surveillance).

In their transhumanist tract, The Proactionary Imperative, Steve Fuller and Veronika Lipinska argue that we are obliged to pursue techno-scientific progress relentlessly, until we achieve our god-like destiny or infinite power effectively to serve God by becoming God. They unabashedly reveal the incipient violence and destruction such Promethean aims would require: replacing the natural with the artificial is so key to proactionary strategy at least as a serious possibility if not a likelihood [it will lead to] the long-term environmental degradation of the Earth.

The extent of suffering they would be willing to gamble in their cosmic casino is only fully evident when analysing what their project would mean for individual human beings:

A proactionary world would not merely tolerate risk-taking but outright encourage it, as people are provided with legal incentives to speculate with their bio-economic assets. Living riskily would amount to an entrepreneurship of the self [proactionaries] seek large long-term benefits for survivors of a revolutionary regime that would permit many harms along the way.

Progress on overdrive will require sacrifices.

The economic fragility that humans may soon be faced with as a result of automation unemployment would likely prove extremely useful to proactionary goals. In a society where vast swaths of people are reliant on handouts for survival, market forces would determine that less social security means people will risk more for a lower reward, so proactionaries would reinvent the welfare state as a vehicle for fostering securitised risk taking while the proactionary state would operate like a venture capitalist writ large.

At the heart of this is the removal of basic rights for Humanity 1.0, Fullers term for modern, non-augmented human beings, replaced with duties towards the future augmented Humanity 2.0. Hence the very code of our being can and perhaps must be monetised: personal autonomy should be seen as a politically licensed franchise whereby individuals understand their bodies as akin to plots of land in what might be called the genetic commons.

The neoliberal preoccupation with privatisation would so extend to human beings. Indeed, the lifetime of debt that is the reality for most citizens in developed advanced capitalist nations, takes a further step when you are born into debt simply by being alive you are invested with capital on which a return is expected.

Socially moribund masses may thus be forced to serve the technoscientific super-project of Humanity 2.0, which uses the ideology of market fundamentalism in its quest for perpetual progress and maximum productivity. The only significant difference is that the stated aim of godlike capabilities in Humanity 2.0 is overt, as opposed to the undefined end determined by the infinite progress of an ever more efficient market logic that we have now.

Some transhumanists are beginning to understand that the most serious limitations to what humans can achieve are social and cultural not technical. However, all too often their reframing of politics falls into the same trap as their techno-centric worldview. They commonly argue the new political poles are not left-right but techno-conservative or techno-progressive (and even techno-libertarian and techno-sceptic). Meanwhile Fuller and Lipinska argue that the new political poles will be up and down instead of left and right: those who want to dominate the skies and became all powerful, and those who want to preserve the Earth and its species-rich diversity. It is a false dichotomy. Preservation of the latter is likely to be necessary for any hope of achieving the former.

Transhumanism and advanced capitalism are two processes which value progress and efficiency above everything else. The former as a means to power and the latter as a means to profit. Humans become vessels to serve these values. Transhuman possibilities urgently call for a politics with more clearly delineated and explicit humane values to provide a safer environment in which to foster these profound changes. Where we stand on questions of social justice and environmental sustainability has never been more important. Technology doesnt allow us to escape these questions it doesnt permit political neutrality. The contrary is true. It determines that our politics have never been important. Savulescu is right when he says radical technologies are coming. He is wrong in thinking they will fix our morality. They will reflect it.

Link:
Super-intelligence and eternal life: transhumanism's faithful follow it blindly into a future for the elite - The Conversation UK

Plant species blooming blue flowers are relatively rare, Naonobu Noda, a plant biologist at the National Agriculture and Food Research Organization in Japan who led the research, noted in an email.

It took Dr. Noda and his colleagues years to create their blue chrysanthemum. They got close in 2013, engineering a bluer-colored one by splicing in a gene from Canterbury bells, which naturally make blue flowers. The resulting blooms were violet. This time, they added a gene from another naturally blue flower called the butterfly pea.

Both of these plants produce pigments for orange, red and purple called delphinidin-based anthocyanins. (Theyre present in cranberries, grapes and pomegranates, too.) Under a few different conditions, these pigments, which are sensitive to changes in pH, can start a chemical transformation within a flower, rendering it blue.

The additional gene did the trick. It added a sugar molecule to the pigment, shifting the plants pH and altering the chrysanthemums color. The researchers confirmed the color as blue by testing its wavelengths in the lab.

What they did was already being done in nature: No blue flowers actually have blue pigment. Neither do blue eyes or blue birds. They all get help from a few clever design hacks.

Blue flowers tend to result from the modification of red pigments shifting their acidity levels, switching up their molecules and ions, or mixing them with other molecules and ions.

Some petunias, for example, have a genetic mutation that breaks pumps inside their cells, altering their pH and turning them blue. Some morning glories shift from blue upon opening to pink upon closing, as acidity levels in the plant fluctuate. Many hydrangeas turn blue if the soil is acidified, as many gardeners know.

In vertebrates, blue coloring often is more about structure. Blue eyes exist because, lacking pigments to absorb color, they reflect blue light. Blue feathers, like those of the kingfisher, would be brown or gray without a special structural coating that reflects blue.

Reflection is also the reason for the most intense color in the world, the shiny blue of the marble-esque Pollia fruit in Africa.

Despite widespread blue-philia, the new chrysanthemums may meet a cool reception. A permit is required to sell genetically modified organisms in the United States, and there isnt one for these transgenic flowers.

Officials are wary of transgenic plants that might take root in the environment, because of their possible impacts on other plants and insects. Dr. Noda and his colleagues are working on blue chrysanthemums that cant reproduce, but its unlikely youll see them in the flower shop anytime soon.

See the original post:
Scientists Give a Chrysanthemum the Blues - New York Times

GOP lawmakers, White House outline tax plan WSJ

The final blow [to the Border Adjustment Tax] came Thursday, in a broad statement of principles released by party leaders to build Republican unity on tax policy and create momentum for advancing legislation this fall.

The statement emphasized a common goal of reducing individual and corporate rates and individual tax rates as much as possible. It also called for faster writeoffs for capital expenses, an idea meant to promote investment, though it stopped short of a House Republican proposal for immediate writeoffs.

The shared principles in effect represent a starting point for the approaching debate. Party leaders willingness to release a framework is also a sign of their confidence in getting a bill written and passed.

Still, Thursdays statement left critical questions unanswered, such as how much individual and corporate rates would be cut, and avoided addressing many of the tough trade-offs Republicans would need to make to achieve substantial reductions in tax rates, such as what deductions to eliminate.

Taken together, it included less detail than President Donald Trumps campaign plan, the House GOPs June 2016 blueprint or the one-page White House offering in April.

Shell prepares for lower forever oil prices WSJ

Read more on this, here.

Unions urge slow-down as self-driving car laws pick up speed Bloomberg

A simple way to help low-income students: Make everyone take the SAT NYT

And now the weeks eeriest news, with some reactions:

First human embryos edited in the US Technology Review

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few daysand there was never any intention of implanting them into a wombthe experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

We need to talk about genetic engineering Commentary

It is incumbent upon Americans of all political stripesnot just conservatives or the faithfulto consider the moral implications of embryonic genetic engineering. In April of 2015, National Institutes of Health Director Dr. Francis Collins issued a statement pledging that NIH will not fund any use of gene-editing technologies in human embryos, but this prohibition does not apply to private endeavors. Public ethos guides private industry, but what is public philosophy regarding the interference with genetic destiny?

Are we obliged to eradicate genetic disorders? Is it unethical not to intervene in the development of an embryo if we have the capacity to alleviate future suffering and hardship? Is it morally questionable to select for various cosmetic traits that prospective parents might find desirable? Do we engage in this process of upending the natural order without knowing the long-term effects of genetic manipulation? Is a modified population a form of eugenics?

If you could design your own child, would you? The Washington Post

We have arrived at a Rubicon. Humans are on the verge of finally being able to modify their own evolution. The question is whether they can use this newfound superpower in a responsible way that will benefit the planet and its people. And a decision so momentous cannot be left to the doctors, the experts or the bureaucrats.

Failing to figure out how to ensure that everyone will benefit from this breakthrough risks the creation of a genetic underclass who must struggle to compete with the genetically modified offspring of the rich. And failing to monitor and contain how we use it may spell global catastrophe. Its up to us collectively to get this right.

Gene editing: new technology, old moral questions The New Atlantis

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Links for July 28, 2017: Outlining the GOP tax plan, the ethics of ... - American Enterprise Institute

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In brief

Synthetic biologists have been creating the genomes of organisms such as viruses and bacteria for the past 15 years. They aim to use these designer genetic codes to make cells capable of producing novel therapeutics and fuels. Now, some of these scientists have set their sights on synthesizing the human genomea vastly more complex genetic blueprint. Read on to learn about this initiative, called Genome Project-write, and the challenges researchers will faceboth technical and ethicalto achieve success.

Nineteenth-century novels are typically fodder for literature conferences, not scientific gatherings. Still, at a high-profile meeting of about 200 synthetic biologists in May, one presenter highlighted Mary Shelleys gothic masterpiece Frankenstein, which turns 200 next year.

Frankensteins monster, after all, is what many people think of when the possibility of human genetic engineering is raised, said University of Pennsylvania ethicist and historian Jonathan Moreno. The initiative being discussed at the New York City meetingGenome Project-write (GP-write)has been dogged by worries over creating unnatural beings. True, part of GP-write aims to synthesize from scratch all 23 chromosomes of the human genome and insert them into cells in the lab. But proponents of the project say theyre focused on decreasing the cost of synthesizing and assembling large amounts of DNA rather than on creating designer babies.

The overall project is still under development, and the projects members have not yet agreed on a specific road map for moving forward. Its also unclear where funding will come from.

What the members of GP-write do agree on is that creating a human genome from scratch is a tremendous scientific and engineering challenge that will hinge on developing new methods for synthesizing and delivering DNA. They will also need to get better at designing large groups of genes that work together in a predictable way, not to mention making sure that even larger assembliesgenomescan function.

GP-write consortium members argue that these challenges are the very thing that should move scientists to pick up the DNA pen and turn from sequence readers to writers. They believe writing the entire human genome is the only way to truly understand how it works. Many researchers quoted Richard Feynman during the meeting in May. The statement What I cannot create, I do not understand was found on the famed physicists California Institute of Technology blackboard after his death. I want to know the rules that make a genome tick, said Jef Boeke, one of GP-writes four coleaders, at the meeting.

To that end, Boeke and other GP-write supporters say the initiative will spur the development of new technologies for designing genomes with software and for synthesizing DNA. In turn, being better at designing and assembling genomes will yield synthetic cells capable of producing valuable fuels and drugs more efficiently. And turning to human genome synthesis will enable new cell therapies and other medical advances.

In 2010, researchers at the Venter Institute, including Gibson, demonstrated that a bacterial cell controlled by a synthetic genome was able to reproduce. Colonies formed by it and its sibling resembled a pair of blue eyes.

Credit: Science

Genome writers have already synthesized a few complete genomes, all of them much less complex than the human genome. For instance, in 2002, researchers chemically synthesized a DNA-based equivalent of the poliovirus RNA genome, which is only about 7,500 bases long. They then showed that this DNA copy could be transcribed by RNA polymerase to recapitulate the viral genome, which replicated itselfa demonstration of synthesizing what the authors called a chemical [C332,652H492,388N98,245O131,196P7,501S2,340] with a life cycle (Science 2002, DOI: 10.1126/science.1072266).

After tinkering with a handful of other viral genomes, in 2010, researchers advanced to bacteria, painstakingly assembling a Mycoplasma genome just over about a million bases in length and then transplanting it into a host cell.

Last year, researchers upped the ante further, publishing the design for an aggressively edited Escherichia coli genome measuring 3.97 million bases long (Science, DOI: 10.1126/science.aaf3639). GP-write coleader George Church and coworkers at Harvard used DNA-editing softwarea kind of Google Docs for writing genomesto make radical systematic changes. The so-called rE.coli-57 sequence, which the team is currently synthesizing, lacks seven codons (the three-base DNA words that code for particular amino acids) compared with the normal E. coli genome. The researchers replaced all 62,214 instances of those codons with DNA base synonyms to eliminate redundancy in the code.

Status report International teams of researchers have already synthesized six of yeast's 16 chromosomes, redesigning the organism's genome as part of the Sc2.0 project.

Bacterial genomes are no-frills compared with those of creatures in our domain, the eukaryotes. Bacterial genomes typically take the form of a single circular piece of DNA that floats freely around the cell. Eukaryotic cells, from yeast to plants to insects to people, confine their larger genomes within a cells nucleus and organize them in multiple bundles called chromosomes. An ongoing collaboration is now bringing genome synthesis to the eukaryote realm: Researchers are building a fully synthetic yeast genome, containing 17 chromosomes that range from about 1,800 to about 1.5 million bases long. Overall, the genome will contain more than 11 million bases.

The synthetic genomes and chromosomes already constructed by scientists are by no means simple, but to synthesize the human genome, scientists will have to address a whole other level of complexity. Our genome is made up of more than 3 billion bases across 23 paired chromosomes. The smallest human chromosome is number 21, at 46.7 million baseslarger than the smallest yeast chromosome. The largest, number 1, has nearly 249 million. Making a human genome will mean making much more DNA and solving a larger puzzle in terms of assembly and transfer into cells.

Today, genome-writing technology is in what Boeke, also the director for the Institute of Systems Genetics at New York University School of Medicine, calls the Gutenberg phase. (Johannes Gutenberg introduced the printing press in Europe in the 1400s.) Its still early days.

DNA synthesis companies routinely create fragments that are 100 bases long and then use enzymes to stitch them together to make sequences up to a few thousand bases long, about the size of a gene. Customers can put in orders for small bits of DNA, longer strands called oligos, and whole geneswhatever they needand companies will fabricate and mail the genetic material.

Although the technology that makes this mail-order system possible is impressive, its not prolific enough to make a human genome in a reasonable amount of time. Estimates vary on how long it would take to stitch together a more than 3 billion-base human genome and how much it would cost with todays methods. But the ballpark answer is about a decade and hundreds of millions of dollars.

Synthesis companies could help bring those figures down by moving past their current 100-base limit and creating longer DNA fragments. Some researchers and companies are moving in that direction. For example, synthesis firm Molecular Assemblies is developing an enzymatic process to write long stretches of DNA with fewer errors.

Synthesis speeds and prices have been improving rapidly, and researchers expect they will continue to do so. From my point of view, building DNA is no longer the bottleneck, says Daniel G. Gibson, vice president of DNA technology at Synthetic Genomics and an associate professor at the J. Craig Venter Institute (JCVI). Some way or another, if we need to build larger pieces of DNA, well do that.

Gibson isnt involved with GP-write. But his research showcases what is possible with todays toolseven if they are equivalent to Gutenbergs movable type. He has been responsible for a few of synthetic biologys milestones, including the development of one of the most commonly used genome-assembly techniques.

The Gibson method uses chemical means to join DNA fragments, yielding pieces thousands of bases long. For two fragments to connect, one must end with a 20- to 40-base sequence thats identical to the start of the next fragment. These overlapping DNA fragments can be mixed with a solution of three enzymesan exonuclease, a DNA polymerase, and a DNA ligasethat trim the 5 end of each fragment, overlap the pieces, and seal them together.

To make the first synthetic bacterial genome in 2008, that of Mycoplasma genitalium, Gibson and his colleagues at JCVI, where he was a postdoc at the time, started with his eponymous in vitro method. They synthesized more than 100 fragments of synthetic DNA, each about 5,000 bases long, and then harnessed the prodigious DNA-processing properties of yeast, introducing these large DNA pieces to yeast three or four at a time. The yeast used its own cellular machinery to bring the pieces together into larger sequences, eventually producing the entire Mycoplasma genome.

Next, the team had to figure out how to transplant this synthetic genome into a bacterial cell to create what the researchers called the first synthetic cell. The process is involved and requires getting the bacterial genome out of the yeast, then storing the huge, fragile piece of circular DNA in a protective agarose gel before melting it and mixing it with another species of Mycoplasma. As the bacterial cells fuse, some of them take in the synthetic genomes floating in solution. Then they divide to create three daughter cells, two containing the native genomes, and one containing the synthetic genome: the synthetic cell.

When Gibsons group at JCVI started building the synthetic cell in 2004, we didnt know what the limitations were, he says. So the scientists were cautious about overwhelming the yeast with too many DNA fragments, or pieces that were too long. Today, Gibson says he can bring together about 25 overlapping DNA fragments that are about 25,000 bases long, rather than three or four 5,000-base segments at a time.

Gibson expects that existing DNA synthesis and assembly methods havent yet been pushed to their limits. Yeast might be able to assemble millions of bases, not just hundreds of thousands, he says. Still, Gibson believes it would be a stretch to make a human genome with this technique.

One of the most ambitious projects in genome writing so far centers on that master DNA assembler, yeast. As part of the project, called Sc2.0 (a riff on the funguss scientific name, Saccharomyces cerevisiae), an international group of scientists is redesigning and building yeast one synthetic chromosome at a time. The yeast genome is far simpler than ours. But like us, yeasts are eukaryotes and have multiple chromosomes within their nuclei.

Synthetic biologists arent interested in rebuilding existing genomes by rote; they want to make changes so they can probe how genomes work and make them easier to build and reengineer for practical use. The main lesson learned from Sc2.0 so far, project scientists say, is how much the yeast chromosomes can be altered in the writing, with no apparent ill effects. Indeed, the Sc2.0 sequence is not a direct copy of the original. The synthetic genome has been reduced by about 8%. Overall, the research group will make 1.1 million bases worth of insertions, deletions, and changes to the yeast genome (Science 2017, DOI: 10.1126/science.aaf4557).

So far, says Boeke, whos also coleader of Sc2.0, teams have finished or almost finished the first draft of the organisms 16 chromosomes. Theyre also working on a neochromosome, one not found in normal yeast. In this chromosome, the designers have relocated all DNA coding for transfer RNA, which plays a critical role in protein assembly. The Sc2.0 group isolated these sequences because scientists predicted they would cause structural instability in the synthetic chromosomes, says Joel Bader, a computational biologist at Johns Hopkins University who leads the projects software and design efforts.

The team is making yeast cells with a new chromosome one at a time. The ultimate goal is to create a yeast cell that contains no native chromosomes and all 17 synthetic ones. To get there, the scientists are taking a relatively old-fashioned approach: breeding. So far, theyve made a yeast cell with three synthetic chromosomes and are continuing to breed it with strains containing the remaining ones. Once a new chromosome is in place, it requires some patching up because of recombination with the native chromosomes. Its a process, but it doesnt look like there are any significant barriers, Bader says. He estimates it will take another two to three years to produce cells with the entire Sc2.0 genome.

So far, even with these significant changes to the chromosomes, the yeast lives at no apparent disadvantage compared with yeast that has its original chromosomes. Its surprising how much you can torture the genome with no effect, Boeke says.

Boeke and Bader have founded a start-up company called Neochromosome that will eventually use Sc2.0 strains to produce large protein drugs, chemical precursors, and other biomolecules that are currently impossible to make in yeast or E. coli because the genetic pathways used to create them are too complex. With synthetic chromosomes well be able to make these large supportive pathways in yeast, Bader predicts.

Whether existing genome-engineering methods like those used in Sc2.0 will translate to humans is an open question.

Bader believes that yeast, so willing to take up and assemble large amounts of DNA, might serve as future human-chromosome producers, assembling genetic material that could then be transferred to other organisms, perhaps human cells. Transplanting large human chromosomes would be tricky, Synthetic Genomics Gibson says. First, the recipient cell must be prepped by somehow removing its native chromosome. Gibson expects physically moving the synthetic chromosome would also be difficult: Stretches of DNA larger than about 50,000 bases are fragile. You have to be very gentle so the chromosome doesnt breakonce its broken, its not going to be useful, he says. Some researchers are working on more direct methods for cell-to-cell DNA transfer, such as getting cells to fuse with one another.

Once the scientists solve the delivery challenge, the next question is whether the transplanted chromosome will function. Our genomes are patterned with methyl groups that silence regions of the genome and are wrapped around histone proteins that pack the long strands into a three-dimensional order in cells nuclei. If the synthetic chromosome doesnt have the appropriate methylation patterns, the right structure, it might not be recognized by the cell, Gibson says.

Biologists might sidestep these epigenetic and other issues by doing large-scale DNA assembly in human cells from the get-go. Ron Weiss, a synthetic biologist at Massachusetts Institute of Technology, is pushing the upper limits on this sort of approach. He has designed methods for inserting large amounts of DNA directly into human cells. Weiss endows human cells with large circuits, which are packages of engineered DNA containing groups of genes and regulatory machinery that will change a cells behavior.

In 2014, Weiss developed a landing pad method to insert about 64,000-base stretches of DNA into human and other mammalian cells. First, researchers use gene editing to create the landing pad, which is a set of markers at a designated spot on a particular chromosome where an enzyme called a recombinase will insert the synthetic genetic material. Then they string together the genes for a given pathway, along with their regulatory elements, add a matching recombinase site, and fashion this strand into a circular piece of DNA called a plasmid. The target cells are then incubated with the plasmid, take it up, and incorporate it at the landing site (Nucleic Acids Res. 2014, DOI: 10.1093/nar/gku1082).

This works, but its tedious. It takes about two weeks to generate these cell lines if youre doing well, and the payload only goes into a few of the cells, Weiss explains. Since his initial publication, he says, his team has been able to generate cells with three landing pads; that means they could incorporate a genetic circuit thats about 200,000 bases long.

Weiss doesnt see simple scale-up of the landing pad method as the way forward, though, even setting aside the tedium. He doesnt think the supersized circuits would even function in a human cell because he doesnt yet know how to design them.

The limiting factor in the size of the circuit is not the construction of DNA, but the design, Weiss says. Instead of working completely by trial and error, bioengineers use computer models to predict how synthetic circuits or genetic edits will work in living cells of any species. But the larger the synthetic element, the harder it is to know whether it will work in a real cell. And the more radical the deletion, the harder it is to foresee whether it will have unintended consequences and kill the cell. Researchers also have a hard time predicting the degree to which cells will express the genes in a complex synthetic circuita lot, a little, or not at all. Gene regulation in humans is not fully understood, and rewriting on the scale done in the yeast chromosome would have far less predictable outcomes.

Besides being willing to take up and incorporate DNA, yeast is relatively simple. Upstream from a yeast gene, biologists can easily find the promoter sequence that turns it on. In contrast, human genes are often regulated by elements found in distant regions of the genome. That means working out how to control large pathways is more difficult, and theres a greater risk that changing the genetic sequencesuch as deleting what looks like repetitive nonsensewill have unintended, currently unpredictable, consequences.

Gibson notes that even in the minimal cell, the organism with the simplest known genome on the planet, biologists dont know what one-third of the genes do. Moving from the simplest organism to humans is a leap into the unknown. One design flaw can change how the cell behaves or even whether the cells are viable, Gibson says. We dont have the design knowledge.

Many scientists believe this uncertainty about design is all the more reason to try writing human and other large genomes. People are entranced with the perfect, Harvards Church says. But engineering and medicine are about the pretty good. I learn much more by trying to make something than by observing it.

Others arent sure that the move from writing the yeast genome to writing the human genome is necessary, or ethical. When the project to write the human genome was made public in May 2016, the founders called it Human Genome Project-write. They held the first organizational meeting behind closed doors, with no journalists present. A backlash ensued.

In the magazine Cosmos, Stanford University bioengineer Drew Endy and Northwestern University ethicist Laurie Zoloth in May 2016 warned of unintended consequences of large-scale changes to the genome and of alienating the public, potentially putting at risk funding for the synthetic biology field at large. They wrote that the synthesis of less controversial and more immediately useful genomes along with greatly improved sub-genomic synthesis capacities should be pursued instead.

GP-write members seem to have taken such criticisms to heart, or come to a similar conclusion on their own. By this Mays conference, human was dropped from the projects name. Leaders emphasized that the human genome would be a subproject proceeding on a conservative timescale and that ethicists would be involved at every step along the way. We want to separate the overarching goal of technology development from the hot-button issue of human genome writing, Boeke explains.

Bringing the public on board with this kind of project can be difficult, says Alta Charo, a professor of law and bioethics at the University of Wisconsin, Madison, who is not involved with GP-write. Charo cochaired a National Academy of Sciences study on the ethics and governance of human gene editing, which was published in February.

She says the likelihood of positive outcomes, such as new therapies or advances in basic science, must be weighed against potential unintended consequences or unforeseen uses of genome writing. People see their basic values at stake in human genetic engineering. If scientists achieve their goalsmaking larger scale genetic engineering routine and more useful, and bringing it to the human genomemajor changes are possible to what Charo calls the fabric of our culture and society. People will have to decide whether they feel optimistic about that or not. (Charo does.)

Given humans cautiousness, Charo imagines in early times we might have decided against creating fire, saying, Lets live without that; we dont need to create this thing that might destroy us. People often see genetic engineering in extreme terms, as a fire that might illuminate human biology and light the way to new technologies, or one that will destroy us.

Charo says the GP-write plan to keep ethicists involved going forward is the right approach and that its difficult to make an ethical or legal call on the project until its leaders put forward a road map.

The group will announce a specific road map sometime this year, but it doesnt want to be restrictive ahead of time. You know when youre done reading something, Boeke said at the meeting in May. But writing has an artistic side to it, he added. You never know when youre done.

Katherine Bourzac is a freelance science writer based in San Francisco.

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Writing the human genome - The Biological SCENE

Four years ago, mega technology trends revolved around big data, the cloud, mobility, and the start of the Internet of Things (IoT). Fast forward to 2017, technology have been built on the foundation of these mega trends, and has seen a massive breakthrough with innovations that have and will continue to disrupt businesses, modernize economies and accelerate growth across industries.

As we journey through this year, we will see technology and our everyday lives be intertwined more than ever before, with organizations undergoing digital transformations at different scales across the world. The technology framework for the future is taking shape to revolutionize how we conduct businesses and take on new challenges in an increasing digitalized economy.

The question is, what is the endpoint to which we see technology being part of our lives? Lets take a simple example of fitness tracker devices embedded with IoT sensors. It can track your steps and exercise routines, sync it with your smartphone and translate all that data into insights on your progress. Pretty amazing, when it became mainstream in the late 2000s at least. But like many other technologies, we are starting to get used to moving on quite rapidly, wanting something better, more powerful, more useful. We crave for innovative technology simply because we can. Because of such rapid changes and our hunger for more, companies have been forced to accelerate innovation and pay more attention to preparing ourselves for the future. Which is why technology today has become increasingly scalable and easily adaptable to future environments. With software primarily at its core, its become nimble. So, to the earlier question, the simple answer is that there is no endpoint to what technology can offer in this day and age, and we must prepare ourselves for the perpetual journey of innovation.

With todays youths being the driving force for tomorrows economy, it is more pertinent now than ever before for youths to embrace new technology innovations, to be able to leverage technology effectively in the future. In fact, we recently conducted a survey of 1,400 youth across Asia Pacific to understand how they view their digital future, and what they found as the three most exciting technologies are Artificial Intelligence, Mixed Reality and Internet of Things.

The study also found that the top benefits they wanted out of these technologies were to help them increase their productivity, facilitate the way they connect with people and improve their physical and mental health. This indicates an understanding on the deeper impact they will have on our lives.

Let us take a closer look at these technologies that will continue to evolve and why they stand out as some of the most important in our future.

Artificial Intelligence

Artificial intelligence (AI) may still seem like stuff of science fiction for some of us, but it is already present in our everyday lives and work. And we are not talking about robots with limbs, but rather technology that can already understand what humans can do, like language, facial recognition, virtual personal assistants or predictive services like identifying what we like to read and making appropriate recommendations.

That said, AI is indeed evolving quickly and is now being used in much more advanced ways, and is being developed and run with even more precision to address deeper issues like healthcare, poverty, terrorism and autonomous vehicles. Today, self-driving cars are already being tested on roads in some cities, smart homes are being marketed, capabilities in biology and genetic engineering are starting to change not only human health and the healthcare industry, but also the way we think about and manage livestock.

Industries will need to continue to leverage machine learning as an ally rather than a threat (to potential job losses, for example). With AI capabilities driving their digital transformation initiatives in an expanding digital economy, AI will to gain more prominence, giving new meaning to automation and breaking grounds for real time solutions and powered by cloud technology.

Mixed Reality

For as long as one could remember, interactions with PCs, tablets and phones have always been a simple point and click, or touch and flick. The introduction of Mixed Reality devices has transformed the way we live, engage and connect. As physical and virtual worlds intersect in new ways, mixed reality allows for a more immersive experience for working remotely or supporting future workplaces to improve collaboration, and tackle organizational challenges anytime, from anywhere.

Beyond the immersive experience however, mixed reality has gone much further in redefining how we can break down geographical barriers. Think about NASAs Mars exploration project and how they have virtually brought Mars to Earth through mixed reality, for an entirely new way of exploration and learning experience.

Internet of Things

Internet of Things (IoT) continues to solicit indelible support from industries worldwide as businesses undergo digital transformation. The global IoT market is expected to reach USD724.2 billion by 2023, according to a report by Research Nester. With the proliferation of technology and rapid growth of urbanization, organizations will continue to adopt and adapt to new technological solutions that will drive business to new frontiers.

New IoT solutions will leverage AI and machine learning to interact with humans and the surroundings, such as drones, self-driving cars, smart kitchens/homes which will be increasingly integrated into daily living.

IoT will also push businesses a step further by offering them immeasurable insights into customers minds, and organizations will be able to create, change and ensure customers value from these insights.

Looking Ahead

We can only look forward to an exciting and smarter future, with many technologies inevitably shaping our global economies and our future. The notion that change is the only constant holds true especially in the wake of our fast paced, innovative and increasingly digitalized economy.

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The perpetual journey of innovation - Enterprise Innovation

In BriefThe age of gene editing and creation will be upon us in thenext few decades, with the first lifeform having already beenprinted. Stanford University questions the ethics of prospectivestudents by asking a question we should all be thinking about. Stanfords Moral Pickle

When bioengineering students sit down to take their final exams for Stanford University,they are faced with a moral dilemma, as well as a series of grueling technical questions that are designed to sort the intellectual wheat from the less competent chaff:

If you and your future partner are planning to have kids, would you start saving money for college tuition, or for printing the genome of your offspring?

The question is a follow up to At what point will the cost of printing DNA to create a human equal the cost of teaching a student in Stanford? Both questions refer to the very real possibility that it may soon be in the realm of affordability to print off whatever stretch of DNA you so desire, using genetic sequencing and a machine capable of synthesizing the four building blocks of DNA A, C, G, and T into whatever order you desire.

The answer to the time question, by the way, is 19 years, given that the cost of tuition at Stanford remains at $50,000 and the price of genetic printing continues the 200-fold decrease that has occurred over the last 14 years. Precursory work has already been performed; a team lead by Craig Venter created the simplest life form ever known last year.

Stanfords moral question, though, is a little trickier. The question is part of a larger conundrum concerning humans interfering with their own biology; since the technology is developing so quickly, the issue is no longer whether we can or cant,but whether we should or shouldnt. The debate has two prongs: gene editing and life printing.

With the explosion of CRISPR technology many studies are due to start this year the ability to edit our genetic makeup will arrive soon. But how much should we manipulate our own genes? Should the technology be a reparative one, reserved for making sick humans healthy again, or should it be used to augment our current physical restrictions, making us bigger, faster, stronger, and smarter?

The question of printing life is similar in some respects; rather than altering organisms to have the desired genetic characteristics, we could print and culture them instead billions have already been invested. However, there is theadditional issue of playing God by sidestepping the methods of our reproduction that have existed since the beginning of life. Even if the ethical issue of creation was answered adequately, there are the further questions ofwho has the right to design life, what the regulations would be, and the potential restrictions on the technology based on cost; if its too pricey, gene editing could be reserved only for the rich.

It is vital to discuss the ethics of gene editing in order to ensure that the technology is not abused in the future. Stanfords question is praiseworthy because it makes todays students, who will most likely be spearheading the technologys developments, think about the consequences of their work.

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Stanford's Final Exams Pose Question About the Ethics of Genetic Engineering - Futurism