Category Archives: Human Genetic Engineering

A Japanese and a British scientist were awarded the 2012 Nobel Prize in physiology or medicine Monday for their groundbreaking work in turning adult cells into immature ones that might be tweaked further to treat a wide spectrum of diseases. Such research is being aggressively pursued at scientific institutions across San Diego County.

Shinya Yamanaka of Japan and John Gurdon of Great Britain showed that it is possible to alter adult cells to the point where they are very similar to human embryonic stem cells. But the process does not involved the destruction of embryos.

In essence, scientists can now take cells from, say, a person's skin and turn back the clock, making the cell essentially act as though it were new.

The Nobel Assembly at the Karolinska Institute issued a statement today saying, "These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

"The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

"Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

"For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies."

Gurdon -- who was working in his lab today when he learned that he'd won a Nobel -- made the initial breakthrough about 50 years ago, and Yamanaka built on that work, accelerating the process through genetic engineering.

The Sanford-Burnham Medical Research Institute was created in La Jolla, in part, to probe exactly this area of research.

Will La Jolla scientists win this year's Nobel Prizes?

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Nobel Prize awarded for work on stem cells

MIT biological engineers created new genetic circuits using genes found in Salmonella (seen here) and other bacteria. Credit: NIH

Using genes as interchangeable parts, synthetic biologists design cellular circuits that can perform new functions, such as sensing environmental conditions. However, the complexity that can be achieved in such circuits has been limited by a critical bottleneck: the difficulty in assembling genetic components that don't interfere with each other.

Unlike electronic circuits on a silicon chip, biological circuits inside a cell cannot be physically isolated from one another. "The cell is sort of a burrito. It has everything mixed together," says Christopher Voigt, an associate professor of biological engineering at MIT.

Because all the cellular machinery for reading genes and synthesizing proteins is jumbled together, researchers have to be careful that proteins that control one part of their synthetic circuit don't hinder other parts of the circuit.

Voigt and his students have now developed circuit components that don't interfere with one another, allowing them to produce the most complex synthetic circuit ever built. The circuit, described in the Oct. 7 issue of Nature, integrates four sensors for different molecules. Such circuits could be used in cells to precisely monitor their environments and respond appropriately.

"It's incredibly complex, stitching together all these pieces," says Voigt, who is co-director of the Synthetic Biology Center at MIT. Larger circuits would require computer programs that Voigt and his students are now developing, which should allow them to combine hundreds of circuits in new and useful ways.

Expanding the possibilities

Previously, Voigt has designed bacteria that can respond to light and capture photographic images, and others that can detect low oxygen levels and high cell densityboth conditions often found in tumors. However, no matter the end result, most of his projects, and those of other synthetic biologists, use a small handful of known genetic parts. "We were just repackaging the same circuits over and over again," Voigt says.

To expand the number of possible circuits, the researchers needed components that would not interfere with each other. They started out by studying the bacterium that causes salmonella, which has a cellular pathway that controls the injection of proteins into human cells. "It's a very tightly regulated circuit, which is what makes it a good synthetic circuit," Voigt says.

The pathway consists of three components: an activator, a promoter and a chaperone. A promoter is a region of DNA where proteins bind to initiate transcription of a gene. An activator is one such protein. Some activators also require a chaperone protein before they can bind to DNA to initiate transcription.

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Researchers build most complex synthetic biology circuit yet

BRUSSELS--(BUSINESS WIRE)--

Delphi Genetics SA (Delphi) has announced today a broad licensing agreement with a subsidiary of Merck & Co., Inc., known as MSD outside the United States and Canada, for the use of the StabyExpress technology, which allows high yield, cost effective protein expression without the use of antibiotics.

Under the agreement, Merck receives a non-exclusive license to use the StabyExpress technology for protein expression in research and product development. In exchange, Delphi is eligible to receive milestone payments associated with the development of Merck product candidates that utilize the StabyExpress technology, as well as royalties on sales of such products. The financial details of the agreement were not disclosed.

Cdric Szpirer PhD, Delphi Genetics Founder and CEO, explained: This is Delphi's first broad-based licensing agreement that covers potential use of the StabyExpress technology for protein based product in the areas of human and animal health.

Guy Hlin, CBO, added: This is the third licensing agreement that we have announced with a world leading healthcare company. The non-exclusive nature of this agreement enables us to consider similar collaborations with other strategic partners, including partners in other fields than biopharma production.

Delphi also has licensing agreements with Sanofi-Pasteur, announced in June 2009, and with GSK, announced in September 2010.

About StabyExpress

StabyExpress technology can be applied to any industrial protein production process that involves bacterial fermentation. Biopharmaceutical production represents a rapidly growing market and its share of the overall medication market today is estimated at 15%. Moreover, the technology is consistent with the recommendations of the FDA and the EMA with regard to the elimination of Antibiotic Resistance Genes in protein production processes for both human and veterinary uses. Currently, Antibiotic Resistance Genes are used as selection markers for the design of the majority of the genetic systems enabling protein production. The technology is also usable to produce DNA vaccines in order to avoid completely the use of antibiotics resistance genes from DNA cloning to DNA production.

About Delphi Genetics SA

Founded at the end of 2001, Delphi Genetics develops more effective products and technologies for genetic engineering and for protein expression in bacteria by using its unique expertise in the field of plasmid stabilisation systems. Delphi Genetics patented StabyExpress technology increases the recombinant protein production output without the use of antibiotics, which is the traditional approach. In January 2012, together with academic and Biotech key-players, Delphi Genetics announced its participation in a research project during the next 3 years for the development of DNA vaccines using the technology. Other research projects are under way to adapt the technology to mammalian cells and yeast.

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Delphi Genetics Grants Merck License for the Use of the StabyExpress™ System

SOUTH SAN FRANCISCO, Calif. & PALO ALTO, Calif.--(BUSINESS WIRE)--

Trellis Bioscience LLC (Trellis) and Open Monoclonal Technology, Inc. (OMT) today announced a new collaboration where the companies will join forces to generate human antibodies against therapeutic targets identified by Trellis and its partners using OMTs OmniRat platform. Trellis will apply its CellSpot antibody screening technology to libraries of OmniRat-generated B cells to discover high affinity, ultra rare antibodies with precisely defined specificity. Trellis will advance and partner each program and share the deal economics with OMT depending on the stage of development.

Stote Ellsworth, Trellis CEO and President, said: Trellis CellSpot platform has shown in four consecutive programs the unique ability to mine rare, best-in-class therapeutic antibodies directly from human blood. In addition to our native human approach, the collaboration with OMT will leverage Trellis powerful multiplexed screening in the context of antibody libraries generated with the OmniRat platform. This will allow Trellis to expand into new therapeutic areas and expand its commercial opportunities, particularly in the field of cancer.

Dr. Roland Buelow, OMT CEO and Founder, continued: "We are pleased to collaborate with Trellis to capture the synergies of our complementary antibody discovery technologies. This collaboration further illustrates OMTs ability to partner with a range of companies to produce human therapeutic antibodies.

About Trellis Bioscience LLC

Trellis is a venture funded therapeutic antibody company formed around a breakthrough, high throughput discovery platform capable of isolating ultra-rare therapeutic-grade antibodies directly from the blood of humans and other mammals, and from other antibody library sources including hybridomas. Trellis CellSpot technology has generated a robust pipeline of early-stage programs targeting respiratory syncytial virus (RSV), cytomegalovirus (CMV), influenza, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus A (GAS) and cancer.

Open Monoclonal Technology, Inc. naturally optimized human antibodies

Open Monoclonal Technology, Inc. (OMT) is a leader in genetic engineering of animals for development of human therapeutic antibodies. OMT has developed OmniRat, the first fully human monoclonal antibody platform using transgenic rats. OmniRat is based on an improved understanding of B cell development and a novel approach to inactivation of endogenous antibody expression. These transgenic animals make antibodies as efficiently as wild type animals. OmniRat is a new and proprietary technology with unrestricted development options for fully human monoclonal antibodies for all targets and indications worldwide.

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Trellis and OMT Announce Therapeutic Antibody Discovery Collaboration

An interesting pair of news posts caught my eye this week, and theyre worth presenting for general discussion. First, VentureBeat has an interview with futurologist Ray Kurzweil, who made waves in 2005 with his book The Singularity Is Near. In it, Kurzweil posits that were approaching a point at which human intelligence will begin to evolve in ways we cannot predict.

The assumption is that our superintelligent computers (or brains) will allow us to effectively reinvent what being human means. In our present state, we are, by definition, incapable of understanding what human society would look like after such a shift.

Mrow

Meanwhile, Google is working to put its neural network technology to work on different sorts of problems. This past summer, the company taught its network how to recognize a cat by showing it YouTube videos. Specifically, it showed 16,000 processors enough cat videos that the network itself learned how to see cat without human intervention. Total visual accuracy, according to the initial paper, is about 16%. The announcement is about applying similar strategies to language processing and how computers can learn to understand the specifics of human speech.

Kurzweil, as you can see in the video at the bottom, is a persuasive speaker and Googles success with teaching a network to recognize cats really is impressive. Reading stories like these, however, I come away skeptical. Its not that I doubt the individual achievements, or that they can be improved, but focusing on specific achievements ignores the greater problem:We have no idea how to build a brain.

Kurzweil uses advances in scanning resolution and genetic engineering together as proof that at some point, well be able to either program cell structures to do the things we want far more effectively than we can currently, or that well simply be able to build mechanical analogs. On some scale, this is probably true. The nematode worm Caenorhabditis elegans has 302 neurons. We could build a neural network (or neural network analog) with 302 nodes fairly easily Googles neural node structure is far more complex than that.

Unfortunately, just having nodes isnt enough. The human brain has an estimated 100 billion neurons and 100 trillion synapses. Different neurons are designed for different tasks and they respond to different stimuli. They respond to and release an incredibly complex series of neurotransmitters, the functions of which we dont entirely understand. Its not enough to say Yes, the brain is complex the brain is complex in ways that dwarf the best CPUs we can build, and it does its work while consuming an average of 20W.

Thats a monkey brain. Weve got more.

This is where Moores Law is typically trotted out, but its a wretchedly terrible comparison. Scientists have already demonstrated transistors as small as 10 atoms wide. Your average neuron is between 4 and 100 microns. If groups of transistors equals neural networks, brains would be no problem. Its not that simple. We dont know how to build synapse networks at anything like the appropriate densities. We dont even know if consciousness is an emergent property of sufficiently dense neural structures or not.

Self-driving cars (an example Kurzweil mentions) are a sophisticated application of refined models, meshed with sensor networks on the vehicle and additional positional data gathered from orbit. Theyre an example of how being able to gather more information and correlate that information more quickly allows us to create a better program but they arent smart. Our best neural networks are single-task predictors that gather information at a glacial pace compared to the brain.

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The vast gulf between current technology and theoretical singularity

ANATOLIA, 9,000BC - The rising sun advanced over the hills, engulfing the arid land in a blaze of warmth. Below the amber sky lay a patchwork of wheat fields, in which a scattering of stooped figures silently harvested their crops. Later, their harvest would be scrutinised, and only the largest grains selected for planting in the autumn. A revolution was occurring. For the first time in 3.6 billion years, life had subverted the evolutionary process and began to steer it not with natural selection, but artificial selection. Selection pressures became synonymous with the needs of the architects; the farmers. The technique led to a widespread transition from hunter-gathering to agriculture, a shift that would transform human culture and lay the foundations for the first civilisations. Moreover, in their efforts to permanently remodel the characteristics of a species, early farmers were pioneers of genetic modification. The modification of plants would later be followed by the domestication of animals, and perhaps eventually, human beings. From the promotion of eugenics to justify genocide in Nazi Germany, to the mass-produced and homogenous population of Aldous Huxley's dystopian future in the novel 'Brave New World', to 'Frankenfood', genetic engineering has amassed a reputation as a treacherous pursuit. However, a recent development appears to have slipped under the public radar: human pre-natal diagnosis. Screening foetal genomes to eliminate genetic 'defects' may lead to incremental changes in the human genetic reservoir, a permanent shift in our characteristics and eventually, self-domestication. The technique involves testing for diseases in a human embryo or foetus, and may be performed to determine if it will be aborted, or in high-risk pregnancies, to enable the provision of immediate medical treatment on delivery. Until recently, pre-natal screening required invasive procedures such as amniocentesis, in which the fluid from the sac surrounding the foetus, the amnion, is sampled and the DNA examined for genetic abnormalities. The procedure can only be performed after the 15th week of pregnancy, and carries a 1% risk of miscarriage and the possibility of complications. In the light of such limitations and risks, the technique hasn't gained widespread popularity. However, a research group based at the University of Washington in Seattle has developed an alternative. Their simple test can be performed weeks earlier than current pre-natal screening, and crucially, requires only a maternal blood sample and DNA from both parents. The technique exploits the fragments of foetal DNA in the mother's blood plasma, which can be strung together by sequencing each nucleotide many times, and then differentiated from maternal and paternal DNA by statistical comparison. It's quick, harmless, and may soon become widely available. Therein lies the problem. Such a tool is a powerful new route gleaning information about unborn offspring. The object of the exercise: to identify foetuses with the earmarks of genetic disease as candidates for abortion. Inevitably, the technique is vulnerable to abuse and will empower parents to discriminate the characteristics of their progeny pre-emptively, in a step towards 'designer babies'. Nevertheless, there is a more immediate concern. Screening for inheritable disorders requires knowledge of their genetic basis, which can be dangerously precarious. Some conditions, such as Down's syndrome; characterised by the presence of an extra chromosome, are glaringly obvious. Others have more subtle and complex genetic origins. Just as the invention of vaccines to prevent infectious diseases was followed by attempts at total eradication, our efforts to eliminate genetic characteristics may have permanent consequences. Autism spectrum disorder (ASD) has already been singled out as a potential target for the screening technology. The disorder, which is characterised by difficulties in communication and social interaction, and repetitive or stereotyped behaviours and interests, has a strong but elusive genetic basis. Intriguingly, there has been much speculation that the genes involved in the development of ASD may be linked to mathematical and scientific ability. The theory has roots in the overlap between certain useful aptitudes in technical professions, and behaviour typical of ASD. An obsessive attention to detail, the ability to understand predictable rule- based systems, 'systemising', and a narrow range of interests, are traits characteristic of both groups. Professor Baron Cohen of the University of Cambridge is a strong proponent of the idea, and has suggested that scientist couples are more likely to have children with the disorder. It's a compelling idea with intuitive plausibility, but the evidence isn't there (yet). Until we know better, perhaps restraint is needed in eliminating these potentially important genes from our gene pool. There has been speculation that Einstein and Newton were 'on the spectrum'- what if we inadvertently 'cured' the future world of similar talent? Will our descendants be less than human? Another candidate for remedy with reproductive technology is schizophrenia. The disorder affects cognition, and can lead to chronic problems with emotional responsiveness. The 1% prevalence of schizophrenia makes it an apt target for prevention. However, the globally consistent and high incidence of this disease may be an indicator of its association with advantageous genetic characteristics. The 'social brain hypothesis', the main theory to explain the evolution of schizophrenia, suggests that the human brain evolved to select for genes associated with schizophrenia in a trade for higher order cognitive traits. These include language and the ability to interpret the thoughts and emotions of others. Schizophrenia is the cost that humans pay for being able to communicate, and as such, the genes responsible may be an essential component of the human gene pool. As with ASD, the elimination of the disease may have unintended consequences, and permanently alter the social dynamics within our species. This mechanism, termed a 'heterozygote advantage', can arise from the benefits of carrying different forms of a gene, as opposed to two of the same variant, or 'alleles'. The phenomenon has been proposed for a wide variety of genetic diseases; however usefulness is often dependent on environmental context. Because human lifestyles have diversified to such an extent from those of our ancestors, certain advantages may be outdated. The malaria protection conferred by carrying a single sickle-cell gene is hardly worth the risk of debilitating anaemia if you end up with two- especially in a modern world where anti-malarial medication is widely available. The systematic eradication of this disorder, and many others, will be a welcome and significant medical advancement. But caution is needed. Following a recent project to build a comprehensive map of the functional elements in the human genome, ENCODE, a function was assigned to 80% of our DNA sequence. However, our genomes are still poorly understood. Many sequences are multi-functional, and knowledge of mechanisms of gene expression is essential to any meaningful model. We urgently need a regulatory framework for the use of procedures such as pre-natal screening, and to exercise restraint in gene eradication. A detailed assessment and forecast of the long- term consequences is essential before a potentially corrosive procedure become entrenched in modern society. The alternative: we might just end up domesticating ourselves. DNA image: Altered from original by Sponk on Wikimedia Commons.

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Warning: Genetically Modified Humans