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Category Archives: Transhuman News

A Startup Is Creating Digital Human Servants to Work in the Metaverse – Futurism

Posted: November 1, 2021 at 7:12 am

Also, they're creepy as hell. Digital Workforce

While the metaverse might seem like a far off dream, more fit for the pages of a Neal Stephenson novel than reality, some are already attempting to cash in the concept and even provide a digital workforce for it.

Enter Soul Machines, a New Zealand-based company that says its designing AI-driven digital humans for clients to use for things like customer service, promotional videos, and education. However, the company also has its sights set on the future with co-founder Greg Cross saying it plans to create a digital workforce for a potential metaverse, according to The Verge.

When were playing a game, we adopt a certain persona or personality, when were coaching our kids football team we adopt another persona, we have a different personality when were at the pub having a beer with our mates, Cross told the Verge. As human beings, were always adjusting our persona and the role we have within those parameters. With digital people, we can create those constructs.

Soul Machines digital people run on a system thats creepily called Humans OS 2.0. Its an Autonomous Animation Platform with a digital brain that allows the AI to learn from its interactions with real people, according to its website. A video of the OS in action shows that the digital humans are ripped from the uncanny valley.

Cross hopes that the AI will be able to fulfill the future needs of flesh and blood humans, in and out of the metaverse or even duplicate them.

At some point in the future, you might be able to create a digital version of yourself or multiple versions of yourself, and they can go out and do stuff, make money for you, make money for your company, while youre doing something else thats a whole lot more fun, Cross told the Verge.

Creating digital people with the ability to learn for the sole purpose of working for real humans brings up a whole host of difficult ethical questions.

After all, if these digital people are indeed intelligent no matter how artificial having them work for us could be akin to a form of slavery or indentured servitude, especially if technological advances make them more intelligent as time goes on. It might also inadvertently create a new class structure of AI humans not unlike the video game Detroit: Become Human.

Cross, however, isnt deterred.

[Technology] has always been used by most of us to do incredibly good things and by a few of us to do the things that arent very nice or simply plain evil,he told the site. That is a reflection of the human condition.

READ MORE: This Company Is Making Digital Humans to Serve the Metaverse [The Verge]

More on digital people: This CGI Influencer Is Shilling for More than 100 Brands

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What is the metaverse? – fox4kc.com

Posted: at 7:12 am

Like it or not, its time to embrace the metaverse.

On Thursday, Facebook CEO Mark Zuckerberg confirmed his company Facebook Inc. would be rebranding itself as Meta, to better reflect its focus on building the metaverse, described by Zuckerberg as an embodied internet where youre in the experience, not just looking at it.

The concept of the metaverse, meanwhile, has been around long before Facebook even existed. Often described as the successor to the internet, futurists and tech experts have envisioned the metaverse as a place where our physical realities converge with various virtual experiences in a shared virtual space. This idea has been explored in some way or another by science-fiction authors or Hollywood filmmakers over the past several decades, generally depicted as a virtual-reality platform where users can create an avatar to interact with fellow members of the digital population.

The concepts name the metaverse was even adopted from the 1992 novel Snow Crash, in which the plot plays out in both virtual and physical realities.

The term predates the internet we know today, explains Trond Undheim, PhD, a futurist and author whose podcasts explore technological innovation and artificial intelligence, among other topics. But it has now become the term for the gradual shift in digital communication whereby the internet is becoming a hybrid reality, meaning its becoming physical and digital at the same time.

The easiest way to envision this concept, perhaps, is to observe the gaming community which is the closest any group has come to entering the so-called metaverse, as far as Undheim is concerned. These gamers have established virtual avatars of themselves, which interact with other virtual avatars across persistent online worlds. Theyre working together in real time, arranging meet-ups, even spending in-game currencies all while communicating via headsets or chat.

There have even been reports of people hosting their wedding inside the cutesy virtual world of Nintendos Animal Crossing and inviting their friends digital avatars to attend after the pandemic canceled their real-world receptions. More recently, Fortnite reimagined Washington D.C. circa 1963 to teleport players back to the Capitol to watch Martin Luther King, Jr. give his iconic I Have a Dream speech.

But the future of open-world gaming is just one of the many ways the metaverse will take hold of our lives. Big Tech, of course, is ready to take things a step further.

As Zuckerberg described in a video released Thursday, Meta is trying to build a part of the metaverse that would let users do almost anything you can imagine or at least be a place where they can interact, work, shop, play games, gather for social events or create content. He also claims Metas efforts will create millions of job opportunities, much like the internet eventually created jobs that were previously unheard of.

I expect that the metaverse is going to open up lots of opportunities for people in the exact same way, Zuckerberg said. But the reality is that no one knows exactly which models are going to work and make this sustainable.

In addition to Facebook, which had previously boasted its virtual playgrounds and boardrooms, Microsoft has also been discussing its own metaverse apps for creating, and connecting to, all-new shared digital spaces.

The pandemic only accelerated the need for at least some types of metaverse-adjacent experiences, with more folks working from home and relying on technology in order to be places that they cant physically be. Theres also growing interest in making virtual events more accessible, allowing users to attend art galleries or concerts with other online friends, or patronize virtual businesses where they can spend their hard-earned currency (or cryptocurrency) on goods or services real or digital.

The metaverse is different and much more powerful than a complete virtual reality, Undheim says, because it is combining the two without merging them all the way.

It doesnt truly exist yet, he adds. But well know it when we see it.

Much of the technology needed to create the metaverse already exists, or is currently in development. But there are still several hurdles to cross before the concept can be put into use, including bandwidth requirements, and getting enough people on board. Undheim also fears that the metaverse may become too commercialized very early on, making users feel alienated or exploited before the concept has a chance to reach its full potential.

What Undheim does know, though, its that the metaverse is coming relatively fast, too.

We will see this wash over us in the next five to seven years, Undheim believes. [Its here] the moment a reasonable person would say, I dont really know if I would value my physical reality over interacting online. Maybe they dont even recognize the distinction between the two.

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Nutritional supplements market Is Expected To Reach USD 140.3 billion in 2025 | Abbott Laboratories, Archer Daniels Midland (ADM), American Health,…

Posted: at 7:10 am

Increasing awareness about health benefits of nutritional supplements is driving growth of the global nutritional supplement market. Nutritional supplements are used in order to treat nutritional deficiency in the human body. Nutritional supplements consist of vitamins, minerals, proteins, and other necessary ingredients. Health benefits associated with consumption of nutritional supplements are reduction in signs of aging and improved cardiovascular health, among others.

The global dietary supplements market size was valued at USD 140.3 billion in 2020 and is expected to expand at a compound annual growth rate (CAGR) of 8.6%

The research report studies the Nutritional supplements Market using different methodologies and analyzers to provide accurate and in-depth information about the market. For a clearer understanding, it is divided into several parts to cover different aspects of the market. Each place is then elaborated to help the reader comprehend the growth potential of each region and its contribution to the global market. The data analysts have used primary and secondary methodologies to consolidate the information in the report.. They have also used the same data to generate the current business scenario.

Top Key Players inNutritional supplements market:Abbott Laboratories, Archer Daniels Midland (ADM), American Health, Inc., Amway Corporation, Arkopharma Laboratoires Pharmaceutiques, Ayanda, DuPont, DSM, the Natures Bounty Co., Herbalife International of America, Inc, Stepan Company, Pfizer Inc., Nestle S.A., Natures Sunshine, and GlaxoSmithKline.

Regional Analysis:

The market research report on the global Nutritional supplements market offers complete analysis across various regions around the globe. The report contains detailed country-level analysis, market revenue, market value and forecast analysis for the following countries and regions: Geographically, the comprehensive analysis of ingestion, revenue and Market share and growth speed, historical and forecast (2021-2027) of these regions are covered:

Influence of theNutritional supplements Market report:

Key questions answered in this report

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The Final Verdict on Whether You Should Take Vitamin D Supplements Eat This Not That – Eat This, Not That

Posted: at 7:10 am

Vitamin D is among the top three most common deficiencies in the US. So, that explains why a 2020 ConsumerLab.com survey found that vitamin D remains the most popular supplement, with 66% of respondents buying it. There's no denying vitamin D is important: it plays a key role in bone health, as well as supporting immune health, brain cell activity, and muscle function. But should you be taking vitamin D supplements? Are they actually effective?

According to experts, most people could benefit from these supplementsparticularly vegans and those who get limited sun exposure because they live somewhere with long winters. It's also worth noting that your vitamin D needs increase after the age of 70, making it more difficult to meet the daily requirement.

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"People with low vitamin D levels may experience fatigue, mood changes, and muscle weakness," says Jamie Nadeau, RD. "Maintaining optimal vitamin D levels supports your immune system which is responsible for fighting bacteria and viruses, lowers your risk for osteoporosis, and studies have also shown that low vitamin D levels are associated with an increased risk for depression. The best thing you can do to determine whether or not you need a vitamin D supplement is to visit your doctor and ask to have your vitamin D levels checked."

Once your doctor has determined that you have a deficiency via blood tests, they may suggest taking a vitamin D supplement, or a multivitamin with vitamin D. The recommended dietary allowance (RDA) for vitamin D is 600 International Units (IU). However, Ana Reisdorf, MS, registered dietitian at Wellness Verge, says that's the minimumand she actually advises aiming for closer to 1,000 to 2,000 international units (IU).

"Overt signs of vitamin D deficiency, like weak bones or extreme fatigue, are rare," says Reisdorf. "But if you work inside and live in a colder climate, you likely need a vitamin D supplement. In fact, I think everyone should take a vitamin D supplement right now. Most of us spend way too much time indoors and don't get enough vitamin D, which comes from the sun."

Indeed, spending some time in the sunshine can trigger your skin to make vitamin Dbut how much it makes depends on a variety of different complicated factors, like the season, latitude of your location, your skin pigmentation, and the time of day. And unfortunately, wearing sunscreen can block the sun from penetrating your skin, which is what allows your body to synthesize vitamin D.

"Experts say that between 5 to 30 minutes of unprotected sun exposure of the face, arms, hands, and legs may be enough, however, unprotected sun exposure is not recommended due to skin cancer risk," says Nadeau.

Vitamin D is also found naturally in some foods, like salmon, tuna, sardines, egg yolks, and beef liverand it's also added to some foods, like fortified milk, orange juice, and cereal. Still, Reisdorf adds that vitamin D supplements may be more effective, simply because most foods don't fulfill the RDA, meaning you'd have to eat large quantities of them to meet your needs.

According to Reisdorf, a vitamin D supplement can not only improve bone health, but also help with your energy levels, weight management, and immunity. And if you still need more reasons to start supplementing, consider that a 2021 study published in the journal Nutrients found that you have a 0% chance of dying from COVID-19 if your vitamin D3 levels are 50 ng/mL.

The bottom line? A vitamin D supplement can offer numerous health benefits, and if you don't get enough vitamin D through your diet and/or sun exposure, it's definitely a good idea to take one. All that said, it is possible to have too much of a good thing. So, be careful not to take more than 2,000 IU of vitamin D supplements, says Reisdorf. Because it's a fat-soluble vitamin, it can cause toxicity at excessively high levels.

For even more vitamin D tips, read these next:

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The #1 Vitamin C Supplement to Take, Says Dietitian Eat This Not That – Eat This, Not That

Posted: at 7:10 am

Eat This, Not That! is reader-supported and every product we feature is independently vettedby our editors. When you buy through links on our site, we may earn a commission.

If you find yourself popping vitamin C supplements every year at the beginning of cold and flu season, you're not alone.

Vitamin C has a long list of benefits for your health. Research suggests that taking vitamin C may increase your body's ability to absorb iron, reduce your risk of heart disease, reduce your risk of dementia, and may make your body better equipped to fight off viruses and other pathogens.

RELATED: What Taking Vitamin C Every Day Does to Your Body

In fact, according to a 2018 study published in the Journal of Epidemiology and Community Health, study subjects with higher levels of vitamin C in their bloodstream were less likely to die of heart disease, cancer, and less likely to die from any cause. However, not all vitamin C supplements are created equal in terms of either their ability to be absorbedor their side effects. To reap the most benefits from vitamin C, you should be looking through the supplement aisle for liposomal vitamin C.

Liposomal vitamin C is a form of vitamin C encapsulated in liposomes, which are "small artificial vesicles of spherical shape" formed from phospholipids or cholesterol, according to research published in Nanoscale Research Letters.

The liposome's purpose is to protect the vitamin C from digestive acids and enzymes that might break it down within the digestive tract. "This protective phospholipid shield or barrier remains undamaged until the contents of the liposome are delivered to the exact target gland, organ, or system where the contents will be utilized," the Nanoscale Research Letters authors explain.

How does liposomal vitamin C compare to standard vitamin C supplements?

Is it really necessary to take this "special" type of vitamin C? Alicia Galvin, RD, a registered dietitian with Sovereign Laboratories says "yes."

"The typical challenges with vitamin C supplements are poor bioavailability and stomach irritation when supplemented in higher doses over a limited amount of time," Galvin explains.

On the other hand, liposomal vitamin C is more bioavailable than your standard vitamin C from supplements.

"With vitamin C supplements and vitamin C-rich foods, the actual amount of vitamin C that the body absorbs is quite low," says Galvin.

"The 'best' absorption rate of a supplement is only about 50%. [Liposomal vitamin C] meets this threshold, yet most other brands fall well below, as do vitamin C-rich foods," says Galvin.

RELATED: Major Effects of Taking Vitamin C Supplements After 50, Says Dietitian

You'll likely reap more benefits with any brand of liposomal vitamin C compared to your standard vitamin C pill, but Galvin specifically recommends Vital C-LD from Sovereign Laboratories.

"The technology used for Vital C-LD, the liposomal delivery and delayed-release capsules, allows the Vitamin C to be maximally absorbed, and also helps prolong the biological activity and antioxidant capacity without irritating the stomach or GI tract," Galvin adds.

$29.95 at Sovereign Laboratories

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When is the SpaceX Crew-3 launch?… – The Sun

Posted: at 6:49 am

DUE TO inclement weather conditions, Elon Musk's space transportation company had to delay their launch to the International Space Station.

The SpaceX Crew-3 launch was originally scheduled for Halloween morning.

2

The original SpaceX Crew-3 launch date was October 31, 2021, but because of current weather conditions, the team had to push the date of the launch.

On November 3, 2021, at 1.10am ET, Crew-3 is set to launch from the Kennedy Space Center in Florida.

Around 11pm the same day, they should arrive in space at the International Space Station.

The delay comes following reports of a storm set to travel across the Ohio Valley to the Northeast this weekend, resulting in elevated winds and waves in the Atlantic Ocean. This directly interferes with the flight path.

Live Blog

According to SpaceX, good weather is required up the Eastern Seaboard and across the North Atlantic for crew launches.

If something should go wrong, the crew might need to make an emergency splashdown.

SpaceX Crew-3 consists of NASA astronauts Raja Chari, Tom Marshburn, Kayla Barron and ESA astronaut Matthias Maurer.

The astronauts will launch from Launch Complex 39A at Kennedy Space Center on the SpaceX Crew Dragon and Falcon 9 rocket.

While in space, the crew is set for a long-duration science mission. They are scheduled to return to Earth in April of 2022.

Currently, in space, SpaceX Crew-2 astronauts Shane Kimbrough, Megan McArthur, Akihiko Hoshide, and Thomas Pesquet are set to return sometime in November.

On Twitter, Pesquet wrote:

"Mixed emotions Im sure but hey you get a few more days to soak in the sun , the wind on your face , showers , and normal food . Were waiting for you up here: the skies are always clear in orbit!"

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Founded in 2002 by Elon Musk, SpaceX is an American aerospace manufacturer, space transportation services, and communications corporation.

Located in Hawthorne, California, SpaceX strives to reduce space-traveling costs to one day enable the colonization of Mars.

In 2001, Musk announced a project known as Mars Oasis, in which he hoped to grow plants on Mars.

Following a trip to Russia to buy cheap rockets for the project, Musk left empty-handed.

It was then he realized he could create his own company to build the affordable rockets he was looking for.

His main goal for the company is reportedly to decrease the cost and improve the reliability of travel into space.

SpaceX has earned several achievements throughout the years, including being the first private company to send a spacecraft to the International Space Station in 2012.

The company is currently developing Starship, a reusable launch system for spaceflight.

Starship is set to debut sometime in the early 2020s.

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Genetic Engineering – Courses, Subjects, Eligibility …

Posted: at 6:39 am

Genetic Engineering additionally called genetic modification or genetic manipulation is the immediate control of a living being's genes using biotechnology. It is an arrangement of innovations used to change the hereditary forms of cells, including the exchange of qualities inside and across species limits to create enhanced or novel living beings.

Genetic Engineering has been connected in various fields including research, medicine, industrial biotechnology and agriculture. In research, GMOs are utilized to contemplate quality capacity and articulation through loss of function, gain of function, tracking and expression experiments. By thumping out genes responsible for specific conditions it is possible to create animal model organisms of human diseases. And in addition to producing hormones, immunizations and different drug genetic engineering can possibly fix hereditary diseases through quality treatment. Similar strategies that are utilized to create medications can likewise have mechanical applications, for example, producing enzymes for detergents, cheeses and different products.

The ascent of commercialised genetically modified crops has given a financial advantage to agriculturists in a wide range of nations, however, has additionally been the wellspring of a large portion of the debate encompassing the innovation. This has been available since its initial implementation, the primary field trials were destroyed by anti-GM activists. In spite of the fact that there is a logical accord that at presently accessible sustenance got from GM crops represents no more serious hazard to human wellbeing than regular nourishment, GM sustenance security is the main concern with critics.

Genetic engineering is the study of genes and the science of heredity. Genetic engineers or geneticists study living organisms ranging from human being to crops and even bacteria.

These professionals also conduct researches which is a major part of their work profile. The experiments are conducted to determine the origin and governing laws of a particular inherited trait. These traits include medical condition, diseases etc. The study is further used to seek our determinants responsible for the inherited trait.

Genetic engineers or Geneticists keep on finding ways to enhance their work profile depending on the place and organization they are working with. In manufacturing, these professionals will develop new pharmaceutical or agricultural products while in a medical setting, they advise patients on the diagnosed medical conditions that are inherited and also treat patients on the same.

Skill sets for Genetic engineers or Geneticists

Strong understanding of scientific methods and rules

complex problem solving and critical thinking

ability to use computer-aided design (CAD)

graphics or photo imaging

PERL, Python

word processing software programs

excellent mathematical, deductive and inductive reasoning, reading, writing, and oral comprehension skills

ability to use lasers spectrometers, light scattering equipment, binocular light compound microscopes, bench top centrifuges, or similar laboratory equipment

Typical responsibilities of a Genetic Engineering or Geneticist includes:

When a genetic engineer gains a year of experience, one of the regions they can indulge into is hereditary advising, which includes offering data, support and counsel on hereditary conditions to your patients.

An individual aspiring to pursue a professional degree in Genetic Engineering can begin the BTech course after his/her 10+2 Science with Physics, Chemistry, Maths and Biology.

Admission to BTech in Genetic Engineering is made through entrance tests conducted in-house by various universities or through the scores of national engineering entrance examination like JEE for IITs/NITs & CFTIs across the country.

Genetic Engineering professionals require a bachelors or masters degree in Genetic Engineering or Genetic Sciences for entry-level careers. In any case, a doctoral qualification is required for those looking for free research professions. Important fields of study in Genetic Engineering incorporate natural chemistry, biophysics or related fields.

Genetic Engineers require a solid comprehension of logical techniques and guidelines, and in addition complex critical thinking and basic reasoning aptitudes. Phenomenal scientific, deductive and inductive thinking aptitudes, and in addition perusing, composing, and oral cognizance abilities are additionally expected to work in this field.

A semester- wise breakup of the course is tabulated below

SEMESTER I

SEMESTER II

Mathematics 1

Mathematics 2

English

Material Science

Physics

Principles of Environmental Science

Chemistry

Biochemistry

Basic Engineering 1

Basic Engineering 2

-

Cell Biology

-

Value Education

SEMESTER III

SEMESTER IV

Enzyme Technology

Basic Molecular Techniques

Genetics & Cytogenetics

Molecular Biology

Immunology

Stoichiometry and Engineering Thermodynamics

Microbiology

Bio-press Principles

Mechanical Operations & heat Transfer

Biostatistics

German Language Phase 1/French Language Phase 1/Japanese Language Phase 1

German Language Phase 2/Japanese Language Phase 2/French Language Phase 2

-

SEMESTER V

SEMESTER VI

Advanced Molecular Techniques

Recombinant DNA Technology

Functional Genomics and Microarray Technology

Bioinformatics

Momentum Transfer

Chemical Reaction Engineering

Bioprocess Engineering

Gene Therapy

Biophysics

Biosensors and Biochips

Plant Tissue Culture and Transgenic Technology

-

Personality Development

-

SEMESTER VII

SEMESTER VIII

Bio-separation Technology

Project Work

Animal Cell Culture and Transgenic Technology

Bio-Safety, Bio-ethics, IPR & Patients

Nano-biotechnology in Healthcare

-

Stem Cell Biology

-

Aspirants who wish to join the engineering industry as a genetic engineer can apply for the following jobs profiles available:

JOB PROFILE

JOB DESCRIPTION

Genetic Engineer

They apply their knowledge ofengineering, biology, and biomechanical principles into the design, development, and evaluation of biological and health systems and products, such as artificial organs, prostheses, instrumentation, medical information systems, and health care and management.

Lecturer/Professor

They teach at undergraduate and graduate level in areas allocated and reviewed from time to time by the Head of Department.

Research Scientist

They are responsible for designing, undertaking and analyzing information from controlled laboratory-based investigations, experiments and trials.

Scientific/Medical Writer

The research, prepare and coordinate scientific publications. The medical writer is responsible for researching, writing and editing clinical/statistical reports and study protocols, and summarizing data from clinical studies.

Most of the engineering educational institutes shortlist candidates for admission Into BTech in Genetic Engineering course on the basis of engineering entrance exams. These entrance exams are either conducted at the national level like JEE or held in-house by various engineering institutes in the country.

Some of the popular engineering entrance examinations aspirants should consider appearing for admissions to UG and PG level Automobile engineering courses are:

Q. Which college is best for genetic engineering?

A. SRM University Chennai Tamil Nadu, Bharath University Chennai Tamil Nadu, Aryabhatta Knowledge University Patna Bihar, Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore are some of the institutes offering genetic engineering

Q. Is Jee required for genetic engineering?

A. NITs and IITs across India does not offer genetic engineering. But there are 23 collages which take admission on the basis of JEE main

Q. What is the qualification for genetic engineering?

A. For admission to BTech Genetic Engineering course, the candidate is needed to have passed the Higher Secondary School Certificate (10+2) examination from a recognized Board of education with Biology, Physics and Chemistry as main subjects with a minimum aggregate score of 60%.

Q. Does IIT offer genetic engineering?

A. No, IIT directly does not offer genetic engineering. Candidates have to take Life Sciences in graduation or Biotechnology from any engineering college in India.

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Genetic engineering of animals: Ethical issues, including …

Posted: at 6:39 am

Can Vet J. 2011 May; 52(5): 544550.

Canadian Council on Animal Care, 1510-130 Albert Street, Ottawa, Ontario K1P 5G4 (Ormandy, Dale, Griffin); The University of British Columbia, Animal Welfare Program, 2357 Main Mall, Vancouver, British Columbia V6T 1Z4 (Ormandy)

The genetic engineering of animals has increased significantly in recent years, and the use of this technology brings with it ethical issues, some of which relate to animal welfare defined by the World Organisation for Animal Health as the state of the animalhow an animal is coping with the conditions in which it lives (1). These issues need to be considered by all stakeholders, including veterinarians, to ensure that all parties are aware of the ethical issues at stake and can make a valid contribution to the current debate regarding the creation and use of genetically engineered animals. In addition, it is important to try to reflect societal values within scientific practice and emerging technology, especially publicly funded efforts that aim to provide societal benefits, but that may be deemed ethically contentious. As a result of the extra challenges that genetically engineered animals bring, governing bodies have started to develop relevant policies, often calling for increased vigilance and monitoring of potential animal welfare impacts (2). Veterinarians can play an important role in carrying out such monitoring, especially in the research setting when new genetically engineered animal strains are being developed.

Several terms are used to describe genetically engineered animals: genetically modified, genetically altered, genetically manipulated, transgenic, and biotechnology-derived, amongst others. In the early stages of genetic engineering, the primary technology used was transgenesis, literally meaning the transfer of genetic material from one organism to another. However, with advances in the field, new technology emerged that did not necessarily require transgenesis: recent applications allow for the creation of genetically engineered animals via the deletion of genes, or the manipulation of genes already present. To reflect this progress and to include those animals that are not strictly transgenic, the umbrella term genetically engineered has been adopted into the guidelines developed by the Canadian Council on Animal Care (CCAC). For clarity, in the new CCAC guidelines on: genetically-engineered animals used in science (currently in preparation) the CCAC offers the following definition of a genetically engineered animal: an animal that has had a change in its nuclear or mitochondrial DNA (addition, deletion, or substitution of some part of the animals genetic material or insertion of foreign DNA) achieved through a deliberate human technological intervention. Those animals that have undergone induced mutations (for example, by chemicals or radiation as distinct from spontaneous mutations that naturally occur in populations) and cloned animals are also considered to be genetically engineered due to the direct intervention and planning involved in creation of these animals.

Cloning is the replication of certain cell types from a parent cell, or the replication of a certain part of the cell or DNA to propagate a particular desirable genetic trait. There are 3 types of cloning: DNA cloning, therapeutic cloning, and reproductive cloning (3). For the purposes of this paper, the term cloning is used to refer to reproductive cloning, as this is the most likely to lead to animal welfare issues. Reproductive cloning is used if the intention is to generate an animal that has the same nuclear DNA as another currently, or previously existing animal. The process used to generate this type of cloned animal is called somatic cell nuclear transfer (SCNT) (4).

During the development of the CCAC guidelines on: genetically- engineered animals used in science, some key ethical issues, including animal welfare concerns, were identified: 1) invasiveness of procedures; 2) large numbers of animals required; 3) unanticipated welfare concerns; and 4) how to establish ethical limits to genetic engineering (see Ethical issues of genetic engineering). The different applications of genetically engineered animals are presented first to provide context for the discussion.

Genetic engineering technology has numerous applications involving companion, wild, and farm animals, and animal models used in scientific research. The majority of genetically engineered animals are still in the research phase, rather than actually in use for their intended applications, or commercially available.

By inserting genes from sea anemone and jellyfish, zebrafish have been genetically engineered to express fluorescent proteins hence the commonly termed GloFish. GloFish began to be marketed in the United States in 2003 as ornamental pet fish; however, their sale sparked controversial ethical debates in California the only US state to prohibit the sale of GloFish as pets (5). In addition to the insertion of foreign genes, gene knock-out techniques are also being used to create designer companion animals. For example, in the creation of hypoallergenic cats some companies use genetic engineering techniques to remove the gene that codes for the major cat allergen Fel d1: (http://www.felixpets.com/technology.html).

Companion species have also been derived by cloning. The first cloned cat, CC, was created in 2002 (6). At the time, the ability to clone mammals was a coveted prize, and after just a few years scientists created the first cloned dog, Snuppy (7).

With the exception of a couple of isolated cases, the genetically engineered pet industry is yet to move forward. However, it remains feasible that genetically engineered pets could become part of day-to-day life for practicing veterinarians, and there is evidence that clients have started to enquire about genetic engineering services, in particular the cloning of deceased pets (5).

The primary application of genetic engineering to wild species involves cloning. This technology could be applied to either extinct or endangered species; for example, there have been plans to clone the extinct thylacine and the woolly mammoth (5). Holt et al (8) point out that, As many conservationists are still suspicious of reproductive technologies, it is unlikely that cloning techniques would be easily accepted. Individuals involved in field conservation often harbour suspicions that hi-tech approaches, backed by high profile publicity would divert funding away from their own efforts. However, cloning may prove to be an important tool to be used alongside other forms of assisted reproduction to help retain genetic diversity in small populations of endangered species.

As reviewed by Laible (9), there is an assorted range of agricultural livestock applications [for genetic engineering] aimed at improving animal productivity; food quality and disease resistance; and environmental sustainability. Productivity of farm animal species can be increased using genetic engineering. Examples include transgenic pigs and sheep that have been genetically altered to express higher levels of growth hormone (9).

Genetically engineered farm animals can be created to enhance food quality (9). For example, pigs have been genetically engineered to express the 12 fatty acid desaturase gene (from spinach) for higher levels of omega-3, and goats have been genetically engineered to express human lysozyme in their milk. Such advances may add to the nutritional value of animal-based products.

Farm species may be genetically engineered to create disease-resistant animals (9). Specific examples include conferring immunity to offspring via antibody expression in the milk of the mother; disruption of the virus entry mechanism (which is applicable to diseases such as pseudorabies); resistance to prion diseases; parasite control (especially in sheep); and mastitis resistance (particularly in cattle).

Genetic engineering has also been applied with the aim of reducing agricultural pollution. The best-known example is the EnviropigTM; a pig that is genetically engineered to produce an enzyme that breaks down dietary phosphorus (phytase), thus limiting the amount of phosphorus released in its manure (9).

Despite resistance to the commercialization of genetically engineered animals for food production, primarily due to lack of support from the public (10), a recent debate over genetically engineered AquAdvantageTM Atlantic salmon may result in these animals being introduced into commercial production (11).

Effort has also been made to generate genetically engineered farm species such as cows, goats, and sheep that express medically important proteins in their milk. According to Dyck et al (12), transgenic animal bioreactors represent a powerful tool to address the growing need for therapeutic recombinant proteins. In 2006, ATryn became the first therapeutic protein produced by genetically engineered animals to be approved by the Food and Drug Administration (FDA) of the United States. This product is used as a prophylactic treatment for patients that have hereditary antithrombin deficiency and are undergoing surgical procedures.

Biomedical applications of genetically engineered animals are numerous, and include understanding of gene function, modeling of human disease to either understand disease mechanisms or to aid drug development, and xenotransplantation.

Through the addition, removal, or alteration of genes, scientists can pinpoint what a gene does by observing the biological systems that are affected. While some genetic alterations have no obvious effect, others may produce different phenotypes that can be used by researchers to understand the function of the affected genes. Genetic engineering has enabled the creation of human disease models that were previously unavailable. Animal models of human disease are valuable resources for understanding how and why a particular disease develops, and what can be done to halt or reverse the process. As a result, efforts have focused on developing new genetically engineered animal models of conditions such as Alzheimers disease, amyotrophic lateral sclerosis (ALS), Parkinsons disease, and cancer. However, as Wells (13) points out: these [genetically engineered animal] models do not always accurately reflect the human condition, and care must be taken to understand the limitation of such models.

The use of genetically engineered animals has also become routine within the pharmaceutical industry, for drug discovery, drug development, and risk assessment. As discussed by Rudmann and Durham (14): Transgenic and knock out mouse models are extremely useful in drug discovery, especially when defining potential therapeutic targets for modifying immune and inflammatory responsesSpecific areas for which [genetically engineered animal models] may be useful are in screening for drug induced immunotoxicity, genotoxicity, and carcinogenicity, and in understanding toxicity related drug metabolizing enzyme systems.

Perhaps the most controversial use of genetically engineered animals in science is to develop the basic research on xenotrans-plantation that is, the transplant of cells, tissues, or whole organs from animal donors into human recipients. In relation to organ transplants, scientists have developed a genetically engineered pig with the aim of reducing rejection of pig organs by human recipients (15). This particular application of genetic engineering is currently at the basic research stage, but it shows great promise in alleviating the long waiting lists for organ transplants, as the number of people needing transplants currently far outweighs the number of donated organs. However, as a direct result of public consultation, a moratorium is currently in place preventing pig organ transplantation from entering a clinical trial phase until the public is assured that the potential disease transfer from pigs to humans can be satisfactorily managed (16). According to Health Canada, xenotransplantation is currently not prohibited in Canada. However, the live cells and organs from animal sources are considered to be therapeutic products (drugs or medical devices)No clinical trial involving xenotransplantation has yet been approved by Health Canada (see http://www.hc-sc.gc.ca for details).

Ethical issues, including concerns for animal welfare, can arise at all stages in the generation and life span of an individual genetically engineered animal. The following sections detail some of the issues that have arisen during the peer-driven guidelines development process and associated impact analysis consultations carried out by the CCAC. The CCAC works to an accepted ethic of animal use in science, which includes the principles of the Three Rs (Reduction of animal numbers, Refinement of practices and husbandry to minimize pain and distress, and Replacement of animals with non-animal alternatives wherever possible) (17). Together the Three Rs aim to minimize any pain and distress experienced by the animals used, and as such, they are considered the principles of humane experimental technique. However, despite the steps taken to minimize pain and distress, there is evidence of public concerns that go beyond the Three Rs and animal welfare regarding the creation and use of genetically engineered animals (18).

The generation of a new genetically engineered line of animals often involves the sacrifice of some animals and surgical procedures (for example, vasectomy, surgical embryo transfer) on others. These procedures are not unique to genetically engineered animals, but they are typically required for their production.

During the creation of new genetically engineered animals (particularly mammalian species) oocyte and blastocyst donor females may be induced to superovulate via intraperitoneal or subcutaneous injection of hormones; genetically engineered embryos may be surgically implanted to female recipients; males may be surgically vasectomized under general anesthesia and then used to induce pseudopregnancy in female embryo recipients; and all offspring need to be genotyped, which is typically performed by taking tissue samples, sometimes using tail biopsies or ear notching (19). However, progress is being made to refine the genetic engineering techniques that are applied to mammals (mice in particular) so that less invasive methods are feasible. For example, typical genetic engineering procedures require surgery on the recipient female so that genetically engineered embryos can be implanted and can grow to full term; however, a technique called non-surgical embryo transfer (NSET) acts in a similar way to artificial insemination, and removes the need for invasive surgery (20). Other refinements include a method referred to as deathless transgenesis, which involves the introduction of DNA into the sperm cells of live males and removes the need to euthanize females in order to obtain germ line transmission of a genetic alteration; and the use of polymerase chain reaction (PCR) for genotyping, which requires less tissue than Southern Blot Analysis (20).

Many of the embryos that undergo genetic engineering procedures do not survive, and of those that do survive only a small proportion (between 1% to 30%) carry the genetic alteration of interest (19). This means that large numbers of animals are produced to obtain genetically engineered animals that are of scientific value, and this contradicts efforts to minimize animal use. In addition, the advancement of genetic engineering technologies in recent years has lead to a rapid increase in the number and varieties of genetically engineered animals, particularly mice (21). Although the technology is continually being refined, current genetic engineering techniques remain relatively inefficient, with many surplus animals being exposed to harmful procedures. One key refinement and reduction effort is the preservation of genetically engineered animal lines through the freezing of embryos or sperm (cryopreservation), which is particularly important for those lines with the potential to experience pain and distress (22).

As mentioned, the number of research projects creating and/or using genetically engineered animals worldwide has increased in the past decade (21). In Canada, the CCACs annual data on the numbers of animals used in science show an increase in Category D procedures (procedures with the potential to cause moderate to severe pain and distress) at present the creation of a new genetically engineered animal line is a Category D procedure (23). The data also show an increase in the use of mice (24), which are currently the most commonly used species for genetic engineering, making up over 90% of the genetically engineered animals used in research and testing (21). This rise in animal use challenges the Three Rs principle of Reduction (17). It has been reasoned that once created, the use of genetically engineered animals will reduce the total number of animals used in any given experiment by providing novel and more accurate animal models, especially in applications such as toxicity testing (25). However, the greater variety of available applications, and the large numbers of animals required for the creation and maintenance of new genetically engineered strains indicate that there is still progress to be made in implementation of the Three Rs principle of Reduction in relation to the creation and use of genetically engineered animals (21).

Little data has been collected on the net welfare impacts to genetically engineered animals or to those animals required for their creation, and genetic engineering techniques have been described as both unpredictable and inefficient (19). The latter is due, in part, to the limitations in controlling the integration site of foreign DNA, which is inherent in some genetic engineering techniques (such as pro-nuclear microinjection). In such cases, scientists may generate several independent lines of genetically engineered animals that differ only in the integration site (26), thereby further increasing the numbers of animals involved. This conflicts with efforts to adhere to the principles of the Three Rs, specifically Reduction. With other, more refined techniques that allow greater control of DNA integration (for example, gene targeting), unexpected outcomes are attributed to the unpredictable interaction of the introduced DNA with host genes. These interactions also vary with the genetic background of the animal, as has frequently been observed in genetically engineered mice (27). Interfering with the genome by inserting or removing fragments of DNA may result in alteration of the animals normal genetic homeostasis, which can be manifested in the behavior and well-being of the animals in unpredictable ways. For example, many of the early transgenic livestock studies produced animals with a range of unexpected side effects including lameness, susceptibility to stress, and reduced fertility (9).

A significant limitation of current cloning technology is the prospect that cloned offspring may suffer some degree of abnormality. Studies have revealed that cloned mammals may suffer from developmental abnormalities, including extended gestation; large birth weight; inadequate placental formation; and histological effects in organs and tissues (for example, kidneys, brain, cardiovascular system, and muscle). One annotated review highlights 11 different original research articles that documented the production of cloned animals with abnormalities occurring in the developing embryo, and suffering for the newborn animal and the surrogate mother (28).

Genetically engineered animals, even those with the same gene manipulation, can exhibit a variety of phenotypes; some causing no welfare issues, and some causing negative welfare impacts. It is often difficult to predict the effects a particular genetic modification can have on an individual animal, so genetically engineered animals must be monitored closely to mitigate any unanticipated welfare concerns as they arise. For newly created genetically engineered animals, the level of monitoring needs to be greater than that for regular animals due to the lack of predictability. Once a genetically engineered animal line is established and the welfare concerns are known, it may be possible to reduce the levels of monitoring if the animals are not exhibiting a phenotype that has negative welfare impacts. To aid this monitoring process, some authors have called for the implementation of a genetically engineered animal passport that accompanies an individual animal and alerts animal care staff to the particular welfare needs of that animal (29). This passport document is also important if the intention is to breed from the genetically engineered animal in question, so the appropriate care and husbandry can be in place for the offspring.

With progress in genetic engineering techniques, new methods (30,31) may substantially reduce the unpredictability of the location of gene insertion. As a result, genetic engineering procedures may become less of a welfare concern over time.

As pointed out by Lassen et al (32), Until recently the main limits [to genetic engineering] were technical: what it is possible to do. Now scientists are faced with ethical limits as well: what it is acceptable to do (emphasis theirs). Questions regarding whether it is acceptable to make new transgenic animals go beyond consideration of the Three Rs, animal health, and animal welfare, and prompt the discussion of concepts such as intrinsic value, integrity, and naturalness (33).

When discussing the nature of an animal, it may be useful to consider the Aristotelian concept of telos, which describes the essence and purpose of a creature (34). Philosopher Bernard Rollin applied this concept to animal ethics as follows: Though [telos] is partially metaphysical (in defining a way of looking at the world), and partially empirical (in that it can and will be deepened and refined by increasing empirical knowledge), it is at root a moral notion, both because it is morally motivated and because it contains the notion of what about an animal we ought to at least try to respect and accommodate (emphasis Rollins) (34). Rollin has also argued that as long as we are careful to accommodate the animals interests when we alter an animals telos, it is morally permissible. He writes, given a telos, we should respect the interests which flow from it. This principle does not logically entail that we cannot modify the telos and thereby generate different or alternative interests (34).

Views such as those put forward by Rollin have been argued against on the grounds that health and welfare (or animal interests) may not be the only things to consider when establishing ethical limits. Some authors have made the case that genetic engineering requires us to expand our existing notions of animal ethics to include concepts of the intrinsic value of animals (35), or of animal integrity or dignity (33). Veerhoog argues that, we misuse the word telos when we say that human beings can change the telos of an animal or create a new telos that is to say animals have intrinsic value, which is separate from their value to humans. It is often on these grounds that people will argue that genetic engineering of animals is morally wrong. For example, in a case study of public opinion on issues related to genetic engineering, participants raised concerns about the nature of animals and how this is affected (negatively) by genetic engineering (18).

An alternative view put forward by Schicktanz (36) argues that it is the human-animal relationship that may be damaged by genetic engineering due to the increasingly imbalanced distribution of power between humans and animals. This imbalance is termed asymmetry and it is raised alongside ambivalence as a concern regarding modern human-animal relationships. By using genetically engineered animals as a case study, Schicktanz (36) argues that genetic engineering presents a troubling shift for all human-animal relationships.

Opinions regarding whether limits can, or should, be placed on genetic engineering are often dependent on peoples broader worldview. For some, the genetic engineering of animals may not put their moral principles at risk. For example, this could perhaps be because genetic engineering is seen as a logical continuation of selective breeding, a practice that humans have been carrying out for years; or because human life is deemed more important than animal life. So if genetic engineering creates animals that help us to develop new human medicine then, ethically speaking, we may actually have a moral obligation to create and use them; or because of an expectation that genetic engineering of animals can help reduce experimental animal numbers, thus implementing the accepted Three Rs framework.

For others, the genetic engineering of animals may put their moral principles at risk. For example costs may always be seen to outweigh benefits because the ultimate cost is the violation of species integrity and disregard for the inherent value of animals. Some may view telos as something that cannot or should not be altered, and therefore altering the telos of an animal would be morally wrong. Some may see genetic engineering as exaggerating the imbalance of power between humans and animals, whilst others may fear that the release of genetically engineered animals will upset the natural balance of the ecosystem. In addition, there may be those who feel strongly opposed to certain applications of genetic engineering, but more accepting of others. For example, recent evidence suggests that people may be more accepting of biomedical applications than those relating to food production (37).

Such underlying complexity of views regarding genetic engineering makes the setting of ethical limits difficult to achieve, or indeed, even discuss. However, progress needs to be made on this important issue, especially for those genetically engineered species that are intended for life outside the research laboratory, where there may be less careful oversight of animal welfare. Consequently, limits to genetic engineering need to be established using the full breadth of public and expert opinion. This highlights the importance for veterinarians, as animal health experts, to be involved in the discussion.

Genetic engineering also brings with it concerns over intellectual property, and patenting of created animals and/or the techniques used to create them. Preserving intellectual property can breed a culture of confidentiality within the scientific community, which in turn limits data and animal sharing. Such limits to data and animal sharing may create situations in which there is unnecessary duplication of genetically engineered animal lines, thereby challenging the principle of Reduction. Indeed, this was a concern that was identified in a recent workshop on the creation and use of genetically engineered animals in science (20).

It should be noted that no matter what the application of genetically engineered animals, there are restrictions on the methods of their disposal once they have been euthanized. The reason for this is to restrict the entry of genetically engineered animal carcasses into the natural ecosystem until the long-term effects and risks are better understood. Environment Canada (http://www.ec.gc.ca/) and Health Canada (http://www.hc-sc.gc.ca/) offer specific guidelines in this regard.

As genetically engineered animals begin to enter the commercial realm, it will become increasingly important for veterinarians to inform themselves about any special care and management required by these animals. As animal health professionals, veterinarians can also make important contributions to policy discussions related to the oversight of genetic engineering as it is applied to animals, and to regulatory proceedings for the commercial use of genetically engineered animals.

It is likely that public acceptance of genetically engineered animal products will be an important step in determining when and what types of genetically engineered animals will appear on the commercial market, especially those animals used for food production. Veterinarians may also be called on to inform the public about genetic engineering techniques and any potential impacts to animal welfare and food safety. Consequently, for the discussion regarding genetically engineered animals to progress effectively, veterinarians need to be aware of the current context in which genetically engineered animals are created and used, and to be aware of the manner in which genetic engineering technology and the animals derived from it may be used in the future.

Genetic engineering techniques can be applied to a range of animal species, and although many genetically engineered animals are still in the research phase, there are a variety of intended applications for their use. Although genetic engineering may provide substantial benefits in areas such as biomedical science and food production, the creation and use of genetically engineered animals not only challenge the Three Rs principles, but may also raise ethical issues that go beyond considerations of animal health, animal welfare, and the Three Rs, opening up issues relating to animal integrity and/or dignity. Consequently, even if animal welfare can be satisfactorily safeguarded, intrinsic ethical concerns about the genetic engineering of animals may be cause enough to restrict certain types of genetically engineered animals from reaching their intended commercial application. Given the complexity of views regarding genetic engineering, it is valuable to involve all stakeholders in discussions about the applications of this technology.

The authors thank the members of the Canadian Veterinary Medicine Association Animal Welfare Committee for their comments on the draft, and Dr. C. Schuppli for her insight on how the issues discussed may affect veterinarians.

Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office (gro.vmca-amvc@nothguorbh) for additional copies or permission to use this material elsewhere.

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CRISPR: A game-changing genetic engineering technique …

Posted: at 6:39 am

Have you heard? A revolution has seized the scientific community. Within only a few years, research labs worldwide have adopted a new technology that facilitates making specific changes in the DNA of humans, other animals, and plants. Compared to previous techniques for modifying DNA, this new approach is much faster and easier. This technology is referred to as CRISPR, and it has changed not only the way basic research is conducted, but also the way we can now think about treating diseases [1,2].

CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat. This name refers to the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms. While seemingly innocuous, CRISPR sequences are a crucial component of the immune systems [3] of these simple life forms. The immune system is responsible for protecting an organisms health and well-being. Just like us, bacterial cells can be invaded by viruses, which are small, infectious agents. If a viral infection threatens a bacterial cell, the CRISPR immune system can thwart the attack by destroying the genome of the invading virus [4]. The genome of the virus includes genetic material that is necessary for the virus to continue replicating. Thus, by destroying the viral genome, the CRISPR immune system protects bacteria from ongoing viral infection.

Figure 1 ~ The steps of CRISPR-mediated immunity. CRISPRs are regions in the bacterial genome that help defend against invading viruses. These regions are composed of short DNA repeats (black diamonds) and spacers (colored boxes). When a previously unseen virus infects a bacterium, a new spacer derived from the virus is incorporated amongst existing spacers. The CRISPR sequence is transcribed and processed to generate short CRISPR RNA molecules. The CRISPR RNA associates with and guides bacterial molecular machinery to a matching target sequence in the invading virus. The molecular machinery cuts up and destroys the invading viral genome. Figure adapted from Molecular Cell 54, April 24, 2014 [5].

Interspersed between the short DNA repeats of bacterial CRISPRs are similarly short variable sequences called spacers (FIGURE 1). These spacers are derived from DNA of viruses that have previously attacked the host bacterium [3]. Hence, spacers serve as a genetic memory of previous infections. If another infection by the same virus should occur, the CRISPR defense system will cut up any viral DNA sequence matching the spacer sequence and thus protect the bacterium from viral attack. If a previously unseen virus attacks, a new spacer is made and added to the chain of spacers and repeats.

The CRISPR immune system works to protect bacteria from repeated viral attack via three basic steps [5]:

Step 1) Adaptation DNA from an invading virus is processed into short segments that are inserted into the CRISPR sequence as new spacers.

Step 2) Production of CRISPR RNA CRISPR repeats and spacers in the bacterial DNA undergo transcription, the process of copying DNA into RNA (ribonucleic acid). Unlike the double-chain helix structure of DNA, the resulting RNA is a single-chain molecule. This RNA chain is cut into short pieces called CRISPR RNAs.

Step 3) Targeting CRISPR RNAs guide bacterial molecular machinery to destroy the viral material. Because CRISPR RNA sequences are copied from the viral DNA sequences acquired during adaptation, they are exact matches to the viral genome and thus serve as excellent guides.

The specificity of CRISPR-based immunity in recognizing and destroying invading viruses is not just useful for bacteria. Creative applications of this primitive yet elegant defense system have emerged in disciplines as diverse as industry, basic research, and medicine.

In Industry

The inherent functions of the CRISPR system are advantageous for industrial processes that utilize bacterial cultures. CRISPR-based immunity can be employed to make these cultures more resistant to viral attack, which would otherwise impede productivity. In fact, the original discovery of CRISPR immunity came from researchers at Danisco, a company in the food production industry [2,3]. Danisco scientists were studying a bacterium called Streptococcus thermophilus, which is used to make yogurts and cheeses. Certain viruses can infect this bacterium and damage the quality or quantity of the food. It was discovered that CRISPR sequences equipped S. thermophilus with immunity against such viral attack. Expanding beyond S. thermophilus to other useful bacteria, manufacturers can apply the same principles to improve culture sustainability and lifespan.

In the Lab

Beyond applications encompassing bacterial immune defenses, scientists have learned how to harness CRISPR technology in the lab [6] to make precise changes in the genes of organisms as diverse as fruit flies, fish, mice, plants and even human cells. Genes are defined by their specific sequences, which provide instructions on how to build and maintain an organisms cells. A change in the sequence of even one gene can significantly affect the biology of the cell and in turn may affect the health of an organism. CRISPR techniques allow scientists to modify specific genes while sparing all others, thus clarifying the association between a given gene and its consequence to the organism.

Rather than relying on bacteria to generate CRISPR RNAs, scientists first design and synthesize short RNA molecules that match a specific DNA sequencefor example, in a human cell. Then, like in the targeting step of the bacterial system, this guide RNA shuttles molecular machinery to the intended DNA target. Once localized to the DNA region of interest, the molecular machinery can silence a gene or even change the sequence of a gene (Figure 2)! This type of gene editing can be likened to editing a sentence with a word processor to delete words or correct spelling mistakes. One important application of such technology is to facilitate making animal models with precise genetic changes to study the progress and treatment of human diseases.

Figure 2 ~ Gene silencing and editing with CRISPR. Guide RNA designed to match the DNA region of interest directs molecular machinery to cut both strands of the targeted DNA. During gene silencing, the cell attempts to repair the broken DNA, but often does so with errors that disrupt the geneeffectively silencing it. For gene editing, a repair template with a specified change in sequence is added to the cell and incorporated into the DNA during the repair process. The targeted DNA is now altered to carry this new sequence.

In Medicine

With early successes in the lab, many are looking toward medical applications of CRISPR technology. One application is for the treatment of genetic diseases. The first evidence that CRISPR can be used to correct a mutant gene and reverse disease symptoms in a living animal was published earlier this year [7]. By replacing the mutant form of a gene with its correct sequence in adult mice, researchers demonstrated a cure for a rare liver disorder that could be achieved with a single treatment. In addition to treating heritable diseases, CRISPR can be used in the realm of infectious diseases, possibly providing a way to make more specific antibiotics that target only disease-causing bacterial strains while sparing beneficial bacteria [8]. A recent SITN Waves article discusses how this technique was also used to make white blood cells resistant to HIV infection [9].

Of course, any new technology takes some time to understand and perfect. It will be important to verify that a particular guide RNA is specific for its target gene, so that the CRISPR system does not mistakenly attack other genes. It will also be important to find a way to deliver CRISPR therapies into the body before they can become widely used in medicine. Although a lot remains to be discovered, there is no doubt that CRISPR has become a valuable tool in research. In fact, there is enough excitement in the field to warrant the launch of several Biotech start-ups that hope to use CRISPR-inspired technology to treat human diseases [8].

Ekaterina Pak is a Ph.D. student in the Biological and Biomedical Sciences program at Harvard Medical School.

1. Palca, J. A CRISPR way to fix faulty genes. (26 June 2014) NPR < http://www.npr.org/blogs/health/2014/06/26/325213397/a-crispr-way-to-fix-faulty-genes> [29 June 2014]

2. Pennisi, E. The CRISPR Craze. (2013) Science, 341 (6148): 833-836.

3. Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 17091712.

4. Brouns, S.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J., Snijders, A.P., Dickman, M.J., Makarova, K.S., Koonin, E.V., and van der Oost, J. (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960964.

5. Barrangou, R. and Marraffini, L. CRISPR-Cas Systems: Prokaryotes Upgrade to Adaptive Immunity (2014). Molecular Cell 54, 234-244.

6. Jinkek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. (2012) 337(6096):816-21.

7. CRISPR reverses disease symptoms in living animals for first time. (31 March 2014). Genetic Engineering and Biotechnology News. <http://www.genengnews.com/gen-news-highlights/crispr-reverses-disease-symptoms-in-living-animals-for-first-time/81249682/> [27 July 2014]

8. Pollack, A. A powerful new way to edit DNA. (3 March 2014). NYTimes < http://www.nytimes.com/2014/03/04/health/a-powerful-new-way-to-edit-dna.html?_r=0> [16 July 2014]

9. Gene editing technique allows for HIV resistance? <http://sitn.hms.harvard.edu/flash/waves/2014/gene-editing-technique-allows-for-hiv-resistance/> [13 June 2014]

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Genetics in fiction – Wikipedia

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Aspects of genetics including mutation, hybridisation, cloning, genetic engineering, and eugenics have appeared in fiction since the 19th century.

Genetics is a young science, having started in 1900 with the rediscovery of Gregor Mendel's study on the inheritance of traits in pea plants. During the 20th century it developed to create new sciences and technologies including molecular biology, DNA sequencing, cloning, and genetic engineering. The ethical implications were brought into focus with the eugenics movement.

Since then, many science fiction novels and films have used aspects of genetics as plot devices, often taking one of two routes: a genetic accident with disastrous consequences; or, the feasibility and desirability of a planned genetic alteration. The treatment of science in these stories has been uneven and often unrealistic. The film Gattaca did attempt to portray science accurately but was criticised by scientists.

Modern genetics began with the work of the monk Gregor Mendel in the 19th century, on the inheritance of traits in pea plants. Mendel found that visible traits, such as whether peas were round or wrinkled, were inherited discretely, rather than by blending the attributes of the two parents.[1] In 1900, Hugo de Vries and other scientists rediscovered Mendel's research; William Bateson coined the term "genetics" for the new science, which soon investigated a wide range of phenomena including mutation (inherited changes caused by damage to the genetic material), genetic linkage (when some traits are to some extent inherited together), and hybridisation (crosses of different species).[2]

Eugenics, the production of better human beings by selective breeding, was named and advocated by Charles Darwin's cousin, the scientist Francis Galton, in 1883. It had both a positive aspect, the breeding of more children with high intelligence and good health; and a negative aspect, aiming to suppress "race degeneration" by preventing supposedly "defective" families with attributes such as profligacy, laziness, immoral behaviour and a tendency to criminality from having children.[3][4]

Molecular biology, the interactions and regulation of genetic materials, began with the identification in 1944 of DNA as the main genetic material;[5] the genetic code and the double helix structure of DNA was determined by James Watson and Francis Crick in 1953.[6][7] DNA sequencing, the identification of an exact sequence of genetic information in an organism, was developed in 1977 by Frederick Sanger.[8]

Genetic engineering, the modification of the genetic material of a live organism, became possible in 1972 when Paul Berg created the first recombinant DNA molecules (artificially assembled genetic material) using viruses.[9]

Cloning, the production of genetically identical organisms from some chosen starting point, was shown to be practicable in a mammal with the creation of Dolly the sheep from an ordinary body cell in 1996 at the Roslin Institute.[10]

Mutation and hybridisation are widely used in fiction, starting in the 19th century with science fiction works such as Mary Shelley's 1818 novel Frankenstein and H. G. Wells's 1896 The Island of Dr Moreau.[11]

In her 1977 Biological Themes in Modern Science Fiction, Helen Parker identified two major types of story: "genetic accident", the uncontrolled, unexpected and disastrous alteration of a species;[12][13] and "planned genetic alteration", whether controlled by humans or aliens, and the question of whether that would be either feasible or desirable.[12][13] In science fiction up to the 1970s, the genetic changes were brought about by radiation, breeding programmes, or manipulation with chemicals or surgery (and thus, notes Lars Schmeink, not necessarily by strictly genetic means).[13] Examples include The Island of Dr Moreau with its horrible manipulations; Aldous Huxley's 1932 Brave New World with a breeding programme; and John Taine's 1951 Seeds of Life, using radiation to create supermen.[13] After the discovery of the double helix and then recombinant DNA, genetic engineering became the focus for genetics in fiction, as in books like Brian Stableford's tale of a genetically modified society in his 1998 Inherit the Earth, or Michael Marshall Smith's story of organ farming in his 1997 Spares.[13]

Comic books have imagined mutated superhumans with extraordinary powers. The DC Universe (from 1939) imagines "metahumans"; the Marvel Universe (from 1961) calls them "mutants", while the Wildstorm (from 1992) and Ultimate Marvel (20002015) Universes name them "posthumans".[14] Stan Lee introduced the concept of mutants in the Marvel X-Men books in 1963; the villain Magneto declares his plan to "make Homo sapiens bow to Homo superior!", implying that mutants will be an evolutionary step up from current humanity. Later, the books speak of an X-gene that confers powers from puberty onwards. X-men powers include telepathy, telekinesis, healing, strength, flight, time travel, and the ability to emit blasts of energy. Marvel's god-like Celestials are later (1999) said to have visited Earth long ago and to have modified human DNA to enable mutant powers.[15]

James Blish's 1952 novel Titan's Daughter (in Kendell Foster Crossen's Future Tense collection) featured stimulated polyploidy (giving organisms multiple sets of genetic material, something that can create new species in a single step), based on spontaneous polyploidy in flowering plants, to create humans with more than normal height, strength, and lifespans.[16]

Cloning, too, is a familiar plot device. Aldous Huxley's 1931 dystopian novel Brave New World imagines the in vitro cloning of fertilised human eggs.[17][18] Huxley was influenced by J. B. S. Haldane's 1924 non-fiction book Daedalus; or, Science and the Future, which used the Greek myth of Daedalus to symbolise the coming revolution in genetics; Haldane predicted that humans would control their own evolution through directed mutation and in vitro fertilisation.[19] Cloning was explored further in stories such as Poul Anderson's 1953 UN-Man.[20] In his 1976 novel, The Boys from Brazil, Ira Levin describes the creation of 96 clones of Adolf Hitler, replicating for all of them the rearing of Hitler (including the death of his father at age 13), with the goal of resurrecting Nazism. In his 1990 novel Jurassic Park, Michael Crichton imagined the recovery of the complete genome of a dinosaur from fossil remains, followed by its use to recreate living animals of an extinct species.[11]

Cloning is a recurring theme in science fiction films like Jurassic Park (1993), Alien Resurrection (1997), The 6th Day (2000), Resident Evil (2002), Star Wars: Episode II (2002) and The Island (2005). The process of cloning is represented variously in fiction. Many works depict the artificial creation of humans by a method of growing cells from a tissue or DNA sample; the replication may be instantaneous, or take place through slow growth of human embryos in artificial wombs. In the long-running British television series Doctor Who, the Fourth Doctor and his companion Leela were cloned in a matter of seconds from DNA samples ("The Invisible Enemy", 1977) and thenin an apparent homage to the 1966 film Fantastic Voyageshrunk to microscopic size in order to enter the Doctor's body to combat an alien virus. The clones in this story are short-lived, and can only survive a matter of minutes before they expire.[21] Films such as The Matrix and Star Wars: Episode II Attack of the Clones have featured human foetuses being cultured on an industrial scale in enormous tanks.[22]

Cloning humans from body parts is a common science fiction trope, one of several genetics themes parodied in Woody Allen's 1973 comedy Sleeper, where an attempt is made to clone an assassinated dictator from his disembodied nose.[23]

Genetic engineering features in many science fiction stories.[16] Films such as The Island (2005) and Blade Runner (1982) bring the engineered creature to confront the person who created it or the being it was cloned from, a theme seen in some film versions of Frankenstein. Few films have informed audiences about genetic engineering as such, with the exception of the 1978 The Boys from Brazil and the 1993 Jurassic Park, both of which made use of a lesson, a demonstration, and a clip of scientific film.[11][24] In 1982, Frank Herbert's novel The White Plague described the deliberate use of genetic engineering to create a pathogen which specifically killed women.[16] Another of Herbert's creations, the Dune series of novels, starting with Dune in 1965, emphasises genetics. It combines selective breeding by a powerful sisterhood, the Bene Gesserit, to produce a supernormal male being, the Kwisatz Haderach, with the genetic engineering of the powerful but despised Tleilaxu.[25]

Genetic engineering methods are weakly represented in film; Michael Clark, writing for The Wellcome Trust, calls the portrayal of genetic engineering and biotechnology "seriously distorted"[24] in films such as Roger Spottiswoode's 2000 The 6th Day, which makes use of the trope of a "vast clandestine laboratory ... filled with row upon row of 'blank' human bodies kept floating in tanks of nutrient liquid or in suspended animation". In Clark's view, the biotechnology is typically "given fantastic but visually arresting forms" while the science is either relegated to the background or fictionalised to suit a young audience.[24]

Eugenics plays a central role in films such as Andrew Niccol's 1997 Gattaca, the title alluding to the letters G, A, T, C for guanine, adenine, thymine, and cytosine, the four nucleobases of DNA. Genetic engineering of humans is unrestricted, resulting in genetic discrimination, loss of diversity, and adverse effects on society. The film explores the ethical implications; the production company, Sony Pictures, consulted with a gene therapy researcher, French Anderson, to ensure that the portrayal of science was realistic, and test-screened the film with the Society of Mammalian Cell Biologists and the American National Human Genome Research Institute before its release. This care did not prevent researchers from attacking the film after its release. Philim Yam of Scientific American called it "science bashing"; in Nature Kevin Davies called it a ""surprisingly pedestrian affair"; and the molecular biologist Lee Silver described the film's extreme genetic determinism as "a straw man".[26][27]

The geneticist Dan Koboldt observes that while science and technology play major roles in fiction, from fantasy and science fiction to thrillers, the representation of science in both literature and film is often unrealistic.[28] In Koboldt's view, genetics in fiction is frequently oversimplified, and some myths are common and need to be debunked. For example, the Human Genome Project has not (he states) immediately led to a Gattaca world, as the relationship between genotype and phenotype is not straightforward. People do differ genetically, but only very rarely because they are missing a gene that other people have: people have different alleles of the same genes. Eye and hair colour are controlled not by one gene each, but by multiple genes. Mutations do occur, but they are rare: people are 99.99% identical genetically, the 3 million differences between any two people being dwarfed by the hundreds of millions of DNA bases which are identical; nearly all DNA variants are inherited, not acquired afresh by mutation. And, Koboldt writes, believable scientists in fiction should know their knowledge is limited.[29]

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Genetics in fiction - Wikipedia

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