Category Archives: Genetic Engineering

Let's stop drawing lines in the sand when it comes to genetically modifying people and talk about engineering everybody

Want to see what a genetically modified human looks like? Just glance in the mirror. You are the result of an experiment that randomly modified your DNA in at least 50 places.

No ethics committee in the world would approve such a dangerous practice. But hey, it's OK because the scientist in this case is nature. And nature is good, right? Never mind that some unlucky kids die horrible deaths because they end up with cruel and fatal mutations. Never mind that just about every one of us will suffer at some point because of the legacy of countless generations of this uncontrolled experiment.

What if we could put a stop to this? We have already begun in a small way. For the past three decades some communities have been screening would-be parents to ensure their children do not inherit one particularly cruel genetic modification Tay-Sachs disease. More recently, we have begun to screen IVF embryos before they are implanted in cases when we know children risk inheriting one or other of the nastiest results of nature's meddling.

And now, with the UK parliament's vote in favour of three-parent babies, we are about to go a step further and actively replace damaged genes with working versions that can be passed on to subsequent generations, breaking the chain of a range of inherited diseases. Great! This form of genetic engineering should result in the birth of healthy children and end much suffering... but wait! Gasp, horror! Did I write the e-word? I'm sorry, I meant "mitochondrial donation".

The decision to allow three-parent babies is right. But the fact is, opponents were also right to describe this as a step towards tinkering with the rest of our genome. Most supporters seemed to have convinced themselves otherwise, but let's look at the arguments.

One is that mitochondrial replacement is no big deal because mitochondria contain just 37 of the 23,000 or so human genes. Sure, but most genetically modified plants and animals have only one or two altered genes. If replacing genes is OK as long as it's only a small proportion, you could justify quite substantial alterations this way.

Ah, we are told, but the point is that these 37 genes do not affect children's characters or appearance. The "only known traits" that could come from the mitochondrial DNA concern energy production, proponents of the technique have argued in New Scientist. Fine. But most of our 23,000 genes are involved in fundamental processes such as cell division, and do not have any known effects on our character. So by this logic, it is OK to tinker with most of our genes.

Of course, replacing faulty mitochondria, which are self-contained organelles within the cell, is relatively simple and we think safe. Replacing or altering genes in the cell nucleus is much trickier. It involves editing DNA by cutting and pasting bits of it recombinant DNA technology and it is not safe at the moment. It would be utterly wrong to attempt in people with existing technology.

But the technology is advancing at a breathtaking pace. We're getting much better at editing DNA, with the help of easier and more precise techniques such as CRISPR, and we can now check those changes with whole-genome sequencing. It could be just decades before it is safe to attempt germ line genetic engineering using recombinant DNA technology.

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Crossing the germ line facing genetics' great taboo

In Focus: Bethany Dill
Bethany Dill is a senior fine arts, art history and marketing major from Long Island, NY. She currently has a prestigious internship at the Metropolitan Muse...

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David Cameron was among MPs who took the historic step today of approving what critics have called "three parent babies" in order to prevent devastating inherited diseases.

The MPs voted for a change in the law that means Britain is set to be the first country in the world to permit mitochondrial donation, which involves conceiving IVF babies with DNA from three different people.

But, speaking shortly before the vote, the Prime Minister insisted there was no question of "playing God".

The move to amend the 2008 Human Fertilisation and Embryology Act, which forbids IVF treatments that affect inherited "germline" DNA in eggs and sperm, was carried by 382 votes to 128.

Labour leader Ed Miliband and Deputy Prime Minister Nick Clegg also exercised their free vote to support the decision.

If the House of Lords ratifies the change - which seems likely - the first baby conceived with the procedure could be born by the end of next year.

The child would have "nuclear" DNA determining individual traits such as facial features and personality from its two parents, plus a tiny amount of mitochondrial DNA (mDNA) from an anonymous woman donor.

Research has shown that mitochondrial donation could potentially help almost 2,500 women of reproductive age in the UK.

All are at risk of transmitting harmful DNA mutations in the mitochondria, tiny rod-like power plants in cells, onto their children and future generations.

Mitochondrial DNA (mDNA) is only involved in metabolism and makes up just 0.1% of a person's genetic code.

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TIME Ideas health Three-Parent IVF Deserves a Chance in the U.S. All new fertility methods sound crazy at first

In a historic vote that rocked the world of fertility medicine Tuesday, British lawmakers approved the use of a controversial IVF practice that would take genetic material from three people to create a single embryo.

The promising technique, which involves replacing the defective cellular material of a womans eggs with that from a healthy donor, aims to prevent patients from passing down crippling genetic diseases to their offspring. It also might hold the key to other groundbreaking applications, such as extending womens fertility by rehabilitating old eggs.

The decision is inspiring because members of Parliament chose science over a firestorm of often ill-informed debate questioning whether weve gone too far in experimenting with genetic engineering. Hopefully, they will motivate the U.S. Food and Drug Administration, which held public hearings on the topic last year but declined to move forward with human trials citing lack of safety data, to follow suit. New research published in the New England Journal of Medicine estimated that more than 12,000 women in the U. S. of childbearing age risk passing down such mitochondrial diseases, which have been linked to everything from poor growth, blindness, neurological problems and heart and kidney problems.

The world is right to be cautious about this latest mind-boggling advance in reproductive medicine. It does sound like science fiction: If youre a woman who suffers from a mutation in her mitochondrial DNAthe part of our cells that generate energyscientists can take your egg, extract the nucleusthe part containing your most important genetic instructions, such as hair and eye colorand insert it into a new egg that has been provided by another woman. (The nucleus would have already been removed from the donor egg.) This newly renovated egg is then fertilized by your partners sperm and implanted into your uterus. You carry on with your pregnancy, just like billions of women before you. (Another version of the technique switches out the nucleus of a newly fertilized egg.)

Have we pushed the boundaries too far in innovative baby-making? Think back to when critics charged that the inventors of in-vitro fertilization recklessly played God by daring to combine a sperm and an egg in a lab to create Louise Brown in 1978. Now some 5 million of the worlds babies have been conceived via IVF. But its one thing to get used to combining reproductive parts in a lab; its a lot less comfortable to imagine tinkering with those parts beforehand. In an open letter to the U.K. Parliament, Paul Knoepfler, stem cell and developmental biology researcher at the University of California Davis School of Medicine, warned that supporters could well find themselves on the wrong side of history with horrible consequences.

Yet its important to understand that mitochondrial replacement isnt genetic engineering run amok, cautions Debra Mathews of the Berman Institute of Bioethics at Johns Hopkins University. The mitochondrial energy-making material of an egg accounts for a mere 37 genes, compared to the nucleus, which contains about 23,000 genes. No one is messing directly with genes, she says. Scientists are replacing damaged mitochondria with healthy mitochondria. Its a specific technology for a specific application. Were modifying eggs to avoid serious diseases. So far, researchers havent attempted a pregnancy using the technique, but a study published in 2012 in Nature found that resulting embryos appeared to develop normally with the nucleus intact and did not contain any of the mutated mitochondria from patients previous eggs. And scientists at Oregon Health and Science University transferred the mitochondria between rhesus-monkey eggs and created four healthy monkey babies.

Yet determining when a technology is safe is especially challenging in fertility medicine because the only way to find out is to create another human. The FDAs prudence is a welcome change from the early wild west days of reproductive medicine when many scientists implanted and prayed that their experiments wouldnt lead to the horrible consequences Knoepfler is warning against. So far, weve been incredibly lucky.

We dont want to risk holding up progress by being too cautious, especially when some 1,000 to 4,000 babies are estimated to be born every year with mitochondrial disease, according to the United Mitochondrial Disease Foundation.

Yet what should the threshold be? The FDA shut down other such research being done more than a decade ago. Scientists at several fertility clinics were responsible for 30 pregnancies from eggs that had been injected with donor cytoplasm that contained mitochondria. The kids havent been tracked over the long term, and its unknown whether the procedure contributed to two cases of chromosomal abnormalities that resulted in one miscarriage and one abortion. And researchers at New York Universitys Langone Medical Center tried a similar mitochondrial transfer technique using younger eggs for three women in their 40s suffering from age-related infertility. Although the embryos developed naturally, none got pregnant. A Chinese team later used the NYU method to achieve a triplet pregnancy, but the patient lost the entire pregnancy after she tried to abort one fetus to give the other two a better chance of survival.

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Three-Parent IVF Deserves a Chance in the U.S.

The coral reefs of the world are in serious danger. A recent scientific report on corals in the Caribbean Sea, for instance, found that coral cover declined from 34.8 percent to 16.3 percent from 1970 to 2012.

One of the chief threats to corals is climate change. Not only do warmer waters stress the species, leading to bleaching events like the one pictured above. Climate change provides a double blow to corals because it also brings on ocean acidification, driven by increasing concentrations of carbon dioxide (caused by the burning of fossil fuels) dissolved in seawater. As sea waters acidify, corals have a harder time producing calcium carbonate, which is crucial to reef formation.

Thats why, in the latest issue of Proceedings of the National Academy of Sciences, a group of researchers from the Australian Institute of Marine Science and the Hawaii Institute of Marine Biology now tentatively propose something that they admit is extremely novel in conservation circles. Namely, they suggest that humans may need to intervene in the breeding of corals so as to assist their evolution.

Such anthropogenically enhanced corals may survive better, the researchers suggest, in a world of warming and acidifying seas. Moreover, this environmental engineering may be necessary as a last-ditch effort since, to be blunt, climate change is proceeding so fast with so much change already locked in that there may be no other choice.

So what are they planning to do? This isgenetic alteration, to be sure evolution always is but it isnot what we typically think of as genetic engineering.Although the development of GMO corals might be contemplated in extremis at a future time, we advocate less drastic approaches, notes the study.

Theyre not proposing Frankenstein coral, stressesNancy Knowlton, a marine scientist at the Smithsonian Institution who edited the paper.

Rather, assisted evolution entails a series of strategies that are perhaps best likened to the domestic breeding of anything from dogs to cows to pigeons to change their attributes. Charles Darwin called it artificial selection, as opposed to natural selection, which usually plays out over much longer periods of time.

For corals, heres how it might work. The researchers propose a number of strategies,some affecting corals and some affecting the communities of microbes that live with them in a symbiotic relationship.

For instance, scientists might identify strains of the appropriately namedSymbiodinium tiny microbes that live inside corals and are essentialto reef growth that are more resistant to temperatures. Then they could introduce this strain into corals in the wild that are struggling.

Yet anotherproposal, meanwhile, is actually guiding the evolution of Symbiodinium in the lab by using x-rays or chemicals that would lead the organisms to evolve and adapt more quickly.

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Coral reefs are in such bad shape that scientists may have to speed up their evolution

The House of Commons in the U.K. has now voted to permit mitochondrial DNA replacement, which enables babies to be born who have DNA from three people.

Mitochondria are the batteries of our cells that provide energy for cell division and growth. We get ours from our mothers genes. If there is a defect in a mothers mitochondria, it can have devastating consequences for her children, resulting in almost certain death. But, by extracting a mitochondrion from a healthy donor egg, scientists are now able to conduct a miniature organ transplant on the cellular level to create a healthy baby through in vitro fertilization. Such a baby has its parents genes, except for one small but crucial portion obtained from a donor.

The need for the procedure is real. Somewhere around 4,000 children per year in the United States are born with a type of mitochondrial disease. Many do not survive more than a few months. Mitochondrial transplants would help prevent these diseases. So why not use them?

Critics give three main reasons; safety; creating babies with three parents; and the danger of opening the door to more genetic engineering. None of these objections provides a convincing reason against trying to treat what are often lethal diseases.

Is the procedure safe? When it was first tried by my NYULMC colleague, Jamie Grifo, at NYULMC in 2003 he was widely denounced as doing something unsafe with an embryo. The FDA brought his work to a halt. Grifo said he had plenty of data in rodents to show the technique was safe but decided not to push against the FDAs opposition. So what is different now that makes safety less of an issue?

Now we have data from monkeys. Convincing data. The creation of healthy primates was shown in 2009. And we have data from the creation of human embryos. A team of scientists at the Oregon National Primate Research Center and the Oregon Health & Science University proved in 2012 that the transplanted mitochondria made viable embryos. Safety is always an issue but the case for moving forward in the UK and the USA is strong.

Some say three parent babies are weird. It is true that a mitochondrion is taken from a donor but why this makes the donor in any way a parent is beyond me. If I give the battery from my car to a friend whose battery has died does that make me an owner of her car? And even if logic were stretched to say yes, it is not as if this is the first time we have seen babies with three parents. Sperm, egg, and embryo donation and surrogacynot to mention adoptionhave been around a long time without fracturing the nature of the family. This objection gets no traction.

Lastly some say mitochondrial transplants cross a bright ethical line. Changing genes in the lungs of people with immune disease or in the eyes of people with macular degeneration may fix the broken body part but, critics point out, the change is not passed on to future generations. When you change the mitochondria in an egg with a transplant, you make a change that is inherited by every single offspring of any child created from that egg. That is called germline engineering. Germline engineering of mitochondria moves beyond using genetic engineering to fix our body parts into directly engineering the traits of our children. It is a road that could lead, the critics warn, to eugenics.

Well, thats where they are wrong. Transplanting mitochondria is not going to be the method used to create enhanced babies. Traits like height, intelligence, strength, balance, and vision dont reside in the battery part of our cells.

We may well want to draw the line at genetic engineering aimed at making superbabies but all that is involved with mitochondria transplants is trying to prevent dead or very disabled ones. The latter goal is noble, laudable and ought to be praised not condemned.

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Is It Ethical to Create Babies From Three DNA Sources? Absolutely

All life processes depend on genes turning on and off. Cornell scientists have created a new on switch to control gene expression a breakthrough that could revolutionize genetic engineering.

Synthetic biologists led by Julius Lucks, assistant professor of chemical and biomolecular engineering, have created a new genetic control mechanism made exclusively of ribonucleic acids (RNA). They call their engineered RNAs STARS Small Transcription Activating RNAs described online in Nature Chemical Biology, Feb. 2.

Weve created a whole new toolset of regulation, said Lucks, who describes RNA as the most engineerable molecule on the planet.

RNA is a single-stranded version of its close cousin, DNA, which makes up the double-stranded genome of all living organisms. While DNA acts as natures hard drive, storing the genes that make up our genome, RNA is part of the cellular computer that activates the hard drive by helping the cell tune the expression of specific genes, Lucks says. While RNA is known to do this in many ways, one thing it cant do in nature is start the process by turning on, or activating, transcription the first step in gene expression, and the core of many cellular programs.

In the lab, Lucks and colleagues have assigned RNA this new role. Theyve engineered an RNA system that acts like a genetic switch, in which RNA tells the cell to activate the transcription of a specific gene. The STAR system involves placing a special RNA sequence upstream of a target gene that acts as a blockade and prevents the cell from transcribing that gene. When the STAR is present, it removes this blockade, turning on the downstream gene by allowing transcription to take place. The effect is like a lock-and-key system for turning genes on, with STARs acting as a set of genetic keys for unlocking cellular genetic programs.

RNA is like a molecular puzzle, a crazy Rubiks cube that has to be unlocked in order to do different things, Lucks said. Weve figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock.

RNA is Lucks favorite molecule because its simple much simpler than a protein and its function can be engineered by designing its structure. In fact, new experimental and computational technologies, some developed by Lucks lab, are now giving quick access to their structures and functions, enabling a new era of biomolecular design that is much more difficult to do with proteins.

Lucks envisions RNA-only, LEGO-like genetic circuits that can act as cellular computers. RNA-engineered gene networks could also offer diagnostic capabilities, as similar RNA circuits have been shown to activate a gene only if, for example, a certain virus is present.

This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well, Lucks said.

The paper is called Creating Small Transcription Activating RNAs, and its co-authors are postdoctoral associate James Chappell and graduate student Melissa Takahashi. Supporters include the National Science Foundation, the Defense Advanced Research Projects Agency and the Office of Naval Research.

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A STAR is born: Engineers devise genetic 'on' switch

6 hours ago

All life processes depend on genes turning on and off. Cornell University scientists have created a new "on" switch to control gene expression - a breakthrough that could revolutionize genetic engineering.

Synthetic biologists led by Julius Lucks, assistant professor of chemical and biomolecular engineering, have created a new genetic control mechanism made exclusively of ribonucleic acids (RNA). They call their engineered RNAs STARS - Small Transcription Activating RNAs - described online in Nature Chemical Biology, Feb. 2.

"We've created a whole new toolset of regulation," said Lucks, who describes RNA as "the most engineerable molecule on the planet."

RNA is a single-stranded version of its close cousin, DNA, which makes up the double-stranded genome of all living organisms. While DNA acts as nature's hard drive, storing the genes that make up our genome, RNA is part of the cellular computer that activates the hard drive by helping the cell tune the expression of specific genes, Lucks says. While RNA is known to do this in many ways, one thing it can't do in nature is start the process by turning on, or activating, transcription - the first step in gene expression, and the core of many cellular programs.

In the lab, Lucks and colleagues have assigned RNA this new role. They've engineered an RNA system that acts like a genetic switch, in which RNA tells the cell to activate the transcription of a specific gene. The STAR system involves placing a special RNA sequence upstream of a target gene that acts as a blockade and prevents the cell from transcribing that gene. When the STAR is present, it removes this blockade, turning on the downstream gene by allowing transcription to take place. The effect is like a lock-and-key system for turning genes on, with STARs acting as a set of genetic keys for unlocking cellular genetic programs.

"RNA is like a molecular puzzle, a crazy Rubik's cube that has to be unlocked in order to do different things," Lucks said. "We've figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock."

RNA is Lucks' favorite molecule because it's simple - much simpler than a protein - and its function can be engineered by designing its structure. In fact, new experimental and computational technologies, some developed by Lucks' lab, are now giving quick access to their structures and functions, enabling a new era of biomolecular design that is much more difficult to do with proteins.

Lucks envisions RNA-only, LEGO-like genetic circuits that can act as cellular computers. RNA-engineered gene networks could also offer diagnostic capabilities, as similar RNA circuits have been shown to activate a gene only if, for example, a certain virus is present.

"This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well," Lucks said.

More here:
Engineers devise genetic 'on' switch made exclusively of RNA

To retain and attract top talent, a quarter of UK businesses would extend health screening into genetic testing but fear of legal repercussions is an inhibiting factor for 76% of employers

With the price of full DNA testing plummeting, and in anticipation of personalised medicines fine-tuned to a patient's genetic make-up, one in four (24%) UK businesses say that they are likely to extend health screening into genetic testing as they strive to retain and attract top talent, a new survey has found.

UK businesses could soon offer employees a complete readout of their genetic blueprint, and hence unprecedented insight into their current and future health, but, amidst all the excitement, Baroness Helena Kennedy, QC, Vice President of the Patients Association and former Chair of the Human Genetics Committee, urges businesses to consider the wider implications, suggesting that genetic screening of employees may be more of a Pandoras box than a panacea.

More than 600 UK business leaders were questioned for the Astellas Innovation DebateTM 2015, which on Thursday 29th January brings together a panel of world-renowned experts at The Royal Institution of Great Britain to discuss the implications of the revolutions in DNA and data for our health.1

Currently, one in four (24%) business leaders say they would offer full genetic screening to their employees though this rises to nearly a third (29%) in the IT and banking sectors, where talent often seems in short supply. But most employers (76%) the fear of legal repercussions is an inhibiting factor.

Of employers who said that their business would be unlikely to offer genetic screening to employees, 43% said they might reconsider their view in the future if better legislation were introduced to protect the rights of employers (19%) and employees (24%). 16% said they would re-consider their view if the results of genetic testing could serve to reduce the cost of key person insurance, while a further 16% said that businesses would need access to advice on dealing with employees found to be at higher genetic risk of developing serious illness. Only 5% said they might choose to offer genetic screening if their business could access genetic data from test results.

European legislation prohibits businesses from gaining access to their employees genetic data, and most businesses (72%) support this principle. Despite that, one in five bosses (22%) admitted that an employee who revealed his/her greater genetic risk of serious illness would consequently also run a greater risk of redundancy and become less eligible for promotion.

Baroness Helena Kennedy, QC, a panellist at the Astellas Innovation Debate Vice President of the Patients Association, and former Chair of the Human Genetics Commission, where she successfully pushed for a moratorium on access to genetic records for insurance companies and persuaded the Government to make it a criminal offence to test DNA without an individuals consent, commented:

Of course its a testament to mankinds ingenuity that genetics and technology are combining to bring the prospect of personalised medicine much closer. But knowing the facts about our genes can also bring challenges. For example, our genetic information could be misused by insurers, who could over-interpret the information in our genes, wrongly suspect we are susceptible to some disease, and so not provide us with the kind of insurance we need. Similarly, if an employee shared some genetic information with his or her boss that indicated a higher risk of, say, cancer or a neurological disease, as this survey shows the employee would be at higher risk of discrimination in the workplace in the form of redundancy or being passed over for promotion. This in turn leaves the employer vulnerable to accusations of discrimination. And then, on a personal level, employees might well need professional support if they become distressed at the prospect of a disease that they might or might not develop.

Some US technology companies are offering employees DNA screening to identify the risk of cancers, and holding out the promise of personalised treatment based on their genetic make-up should they need it. However, I would urge UK businesses not to follow suit certainly not without thinking very carefully about the wider implications to them and their employees. It is not just a matter of potential discrimination and lawsuits, but also of the health benefits to those being tested. Of course, we all recognise the importance of screening people with a family history of certain diseases and rare genetic disorders as the 100,000 Genomes Project is currently doing but there is little benefit to widespread genetic testing if it cant tell you when or even if you will develop the disease.

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Genetic screening for workers: A panacea or a pandora's box?

IMAGE:Big Data, published quarterly in print and online, facilitates and supports the efforts of researchers, analysts, statisticians, business leaders, and policymakers to improve operations, profitability, and communications within... view more

Credit: Mary Ann Liebert, Inc., publishers

New Rochelle, January 28, 2015 - EMBERS is a large-scale big data analytics system designed to use publically available data to predict population-level societal events such as civil unrest or disease outbreaks. The usefulness of this predictive artificial intelligence system over the past 2 years is reviewed in an article in Big Data, the highly innovative, peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Big Data website.

In the article "Forecasting Significant Societal Events Using the EMBERS Streaming Predictive Analytics System," Andy Doyle and coauthors, CACI, Inc. (Lanham, MD), Virginia Tech (Arlington, VA), and BASIS Technology (Herndon, VA), describe the structure and function of the Early Model Based Event Recognition using Surrogates (EMBERS) system. They describe EMBERS as a working example of a big data streaming architecture that processes large volumes of social media data and uses a variety of modeling approaches to make predictions.

"EMBERS represents a significant advance in our ability to make sense of large amounts of unstructured data in an automated manner," says Big Data Editor-in-Chief Vasant Dhar, Co-Director, Center for Business Analytics, Stern School of Business, New York University. "The authors present an architecture that provides a scalable method for dealing with large streams of social media data emanating from Twitter. Although the focus of the paper is on predicting social unrest globally, the methods should be usable for processing these type of data for a variety of applications."

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About the Journal

Big Data, published quarterly in print and online, facilitates and supports the efforts of researchers, analysts, statisticians, business leaders, and policymakers to improve operations, profitability, and communications within their organizations. Spanning a broad array of disciplines focusing on novel big data technologies, policies, and innovations, the Journal brings together the community to address the challenges and discover new breakthroughs and trends living within this information. Complete tables of content and a sample issue may be viewed on the Big Data website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative medical and biomedical peer-reviewed journals, including OMICS: A Journal of Integrative Biology, Journal of Computational Biology, New Space, and 3D Printing and Additive Manufacturing. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's more than 80 journals, newsmagazines, and books is available on the Mary Ann Liebert, Inc., publishers website.

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Large-scale analytics system for predicting major societal events described in Big Data Journal