Category Archives: Cloning

By Matt Monagan |

What do you do if you have a solid, up-and-coming prospect in your farm system? Do you trade him away for an experienced veteran? Do you play him every day, hoping that he alone can bring your franchise a World Series championship?

No, that's silly. Any forward-thinking GM would just keep cloning the player and build an army of young, tireless talent that takes them through the postseason.

The Angels seemed to be ahead of the curve during their 7-5 Spring Training win over the Cubs on Tuesday -- featuring a No. 97 at first and No. 97 at third in the eighth inning.

Soon to be.

Major kudos to Los Angeles' GM Billy Eppler. If they win, they'll have changed the fabric of -- oh wait, MLB.com's Maria Guardado reports that that's actually Chad Hinshaw at third base and Michael Barash at first. Hinshaw wears No. 97 at Minor League camp, while Barash sports the digits on the Major League fields. So, no clones. I guess that's probably a good thing.

But just imagine the possibilities...

This story was not subject to the approval of Major League Baseball or its clubs.

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The Angels had two No. 97s on the basepaths, may be cloning their players - MLB.com

Men's Health

20th Anniversary of Dolly the Cloned Sheep | Men's Health Men's Health 20 years after the world was introduced to Dolly, the Cloned Sheep, we take a look back at what we've learned about cloning. The clones are still among us - Gulf TimesGulf Times all 2 news articles »

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20th Anniversary of Dolly the Cloned Sheep | Men's Health - Men's Health

In 1997Dolly the sheep was introducedto the world by biologists Keith Campbell, Ian Wilmut and colleagues. Not just any lamb, Dolly was a clone. Rather than being made from a sperm and an egg, she originated from a mammary gland cell of another, no-longer-living, six-year-old Fynn Dorset ewe.

With her birth, a scientific and societal revolution was also born.

Some prominent scientistsraised doubts; it was too good to be true. But more animals were cloned: first thelaboratory mouse, thencows,goats,pigs,horses, evendogs,ferretsandcamels. By early 2000, the issue was settled: Dolly was real and cloning adults was possible.

The implications of cloning animals in our society were self-evident from the start. Our advancing ability to reprogram adult, already specialized cells and start them over as something new may one day be the key to creating cells and organs that match the immune system of each individual patient in need of replacements.

But what somehow got lost was the fact that a clone was born at day zero created from the cell of another animal that was six years old. Researchers have spent the past 20 years trying to untangle the mysteries of how clones age. How old, biologically, are these animals born from other adult animals cells?

Decades of cloning research

Dolly became an international celebrity, but she was not the first vertebrate to be cloned from a cell taken from the body of another animal. In 1962, developmental biologistJohn Gurdoncloned the first adult animalby taking a cell from the intestine of one frog and injecting it into an egg of another. Gurdons work did not go unnoticed he went on to share the2012 Nobel Prizein Physiology or Medicine. But it was Dolly who had captured our imagination. Was it because she was a warm-blooded animal, a mammal, much closer to human? If you could do it in a sheep, you could do it on us!

Dolly, along with Gurdons frogs from 35 years earlier and all the other experiments in between, redirected our scientific studies. It was amazing to see a differentiated cell an adult cell specialized to do its particular job transform into an embryonic one that could go on to give rise to all the other cells of a normal body. We researchers wondered if we could go further: Could we in the lab make an adult cell once again undifferentiated, without needing to make a cloned embryo?

A decade after Dolly was announced, stem cell researcherShynia Yamanakas teamdid just that. He went on to be the Nobel corecipient with Gurdon for showing that mature cells could bereprogrammed to become pluripotent: able to develop into any specialized adult cell.

Now we have the possibility of making individualized replacement cells potentially any kind to replace tissue damaged due to injury, genetic disorders and degeneration. Not only cells; we may soon be able to haveour own organs grown in a nonhuman host, ready to be transplanted when needed.

If Dolly was responsible for unleashing the events that culminate with new methods of making fully compatible cells and organs, then her legacy would be to improve the health of practically all human beings on this planet. And yet, I am convinced that there are even better things to come.

Dollys secrets still unfolding

In the winter of 2013, I found myself driving on the wrong side of the road through the Nottingham countryside. In contrast to the luscious landscape, I was in a state gloom; I was on my way to see Keith Campbells family after his sudden death a few weeks earlier. Keith was a smart, fun, loving friend who, along with Ian Wilmut andcolleagues at the Roslin Institute, had brought us Dolly 15 years earlier. We had met at a conference in the early 1990s, when we were both budding scientists playing around with cloning, Keith with sheep, me with cows. An extrovert by nature, he quickly dazzled me with his wit, self-deprecating humor and nonstop chat, all delivered in a thick West Midlands accent. Our friendship that began then continued until his death.

When I knocked at the door of his quaint farmhouse, my plan was to stay just a few minutes, pay my respects to his wife and leave. Five hours and several Guinnesses later, I left feeling grateful. Keith could do that to you, but this time it wasnt him, it was his latest work speaking for him. Thats because his wife very generously told me the project Keith was working on at the time of his death. I couldnt hide my excitement: Could it be possible that after 20 years, the most striking aspect of Dollys legacy was not yet revealed?

See, when Dolly was cloned, she was created using a cell from a six-year-old sheep. Andshe died at age six and a half, a premature death for a breed that lives an average of nine years or more. People assumed that an offspring cloned from an adult was starting at an age disadvantage; rather than truly being a newborn, it seemed like a clones internal age would be more advanced that the length of its own life would suggest. Thus the notion that clones biological age and their chronological one were out of sync, and that cloned animals will die young.

Some of us were convinced that if the cloning procedure was done properly, the biological clock should be reset a newborn clone would truly start at zero. We worked very hard to prove our point. We were not convinced by a single DNA analysis done in Dolly showing slightly shortertelomeres the repetitive DNA sequences at the end of chromosomes that count how many times a cell divides. We presented strong scientific evidence showing that cloned cows had all thesame molecular signs of agingas a nonclone, predicting a normal lifespan. Othersshowed the same in cloned mice. But we couldnt ignore reports from colleagues interpretingbiological signs in cloned animalsthat they attributed toincomplete resetting of the biological clock. So the jury was out.

Aging studies are very hard to do because there are only two data points that really count: date of birth and date of death. If you want to know the lifespan of an individual you have to wait until its natural death. Little did I know, that is what Keith was doing back in 2012.

That Saturday afternoon I spent in Keiths house in Nottingham, I saw a photo of the animals in Keiths latest study: several cloned Dollies, all much older than Dolly at the time she had died, and they looked terrific. I was in awe.

The data were confidential, so I had to remain silent until late last year whenthe work was posthumously published. Keiths coauthors humbly said: For those clones that survive beyond the perinatal period [] the emerging consensus, supported by the current data, is that they are healthy and seem to age normally.

These findings became even more relevant when last December researchers at theScripps Research Institutefound that induced pluripotent stem cells reprogrammed using the Yamanaka factorsretain the aging epigenetic signature of the donor individual. In other words, using these four genes to attempt to reprogram the cells does not seem to reset the biological clock.

The new Dollies are now telling us that if we take a cell from an animal of any age, and we introduce its nucleus into a nonfertilized mature egg, we can have an individual born with its lifespan fully restored. They confirmed that all signs of biological and chronological age matched between cloned and noncloned sheep.

There seems to be a natural built-in mechanism in the eggs that can rejuvenate a cell. We dont know what it is yet, but it is there. Our group as well as others are hard at work, and as soon as someone finds it, the most astonishing legacy of Dolly will be realized.

The rest is here:

More lessons from Dolly the sheep: Is a clone really born at age zero ... - Salon

More than seven months earlier, on July 5, 1996, they had aided a Scottish Blackface sheep in giving birth to a Finn Dorset lamb codenamed 6LL3.

Using a breakthrough technique called somatic cell nuclear transfer, scientists at Roslin took a nucleus -- the part of the cell that contains most of its genetic information -- from cells within the mammary gland of an adult sheep and stuck it inside an unfertilized egg from which the nucleus had been removed.

They stimulated the egg to develop into an embryo and planted the embryo into a surrogate mother. The lamb was dubbed Dolly, a nod to country music legend Dolly Parton and her famously ample bosom.

Years later, that same cell cluster was used to make four other sheep just like Dolly.

The lab had kept her birth secret for seven months to make the announcement coincide with the publication of the scientific paper describing the experiments that produced her, they said.

Much of the news reports had focused not on cloning sheep but on its potential for humans, said Alan Colman, who is now a visiting scholar in the Harvard University Department of Stem Cell and Regenerative Biology.

"We'd underestimated the impact the announcement would make," he said. "It was something we had prepared for, but we had been totally overwhelmed by the response."

Previously, cloning had been done using only embryonic cells, and now researchers had showed that it was possible in cells from another part of the body -- an adult body.

"At the time she was born, I was ecstatic, because no one had previously been able to use nuclear transfer to make an adult vertebrate from an adult cell," Colman said.

Despite the headlines, cloning a mammal wasn't the team's main goal. They were out to develop a more efficient way to produce genetically modified livestock.

In fact, Dolly wasn't even the first to ever be cloned. She was the first mammal cloned from an adult cell.

But scientists have learned a lot since developing the technique, and somatic cell nuclear transfer has been used in more than 20 species to make clones.

But by and large, scientists don't see a need to clone humans.

Dolly herself lived out her days at the Roslin Institute and was able to produce six lambs.

But she was euthanized at age 6 after being diagnosed with progressive lung disease and after a long battle with arthritis.

Finn Dorset sheep usually live 10 to 11 years, and her health problems seemed to confirm fears that cloned animals would age faster and die prematurely compared with animals born naturally.

This was further exemplified by Dolly's four cloned "sisters," who were recently euthanized because they too began to show symptoms of osteoarthritis.

"OA, as you may know, is a progressive disease, and we took appropriate measures to manage the condition at the time under veterinary guidance," said Kevin Sinclair, a developmental biologist at the University of Nottingham who led research on the sheep.

"These animals were in their 10th year and so coming towards the end of their natural lifespan."

To investigate this further, the team at Nottingham will now conduct postmortem examinations to truly understand what's going on inside the animals.

"The final phase of our study ... involves detailed postmortem analyses of different tissues and organs in order to gain a better insight into the aging process in these animals," Sinclair said.

The Roslin Institute donated Dolly's body to the National Museum of Scotland, where she stands to this day.

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20 years after Dolly the sheep, potential of cloning remains unclear - CNN

Updated February 24, 2017 14:05:37

Graziers in central Queensland have cloned a prize cow, moving the technology from the lab to the paddock.

Owner of the new cloned calf, Bill Geddes, said the technology was becoming more viable for everyday producers and more graziers were using it.

Born via caesarean one week ago, Dasha was created by Richard Fry, of Clone International in Victoria.

He used a method called nuclear transfer, and his creation is the exact genetic copy of a cow from the Brangus breed (a cross between an Angus and a Brahman).

Mr Geddes said the decision to create a cloned calf rather than naturally breed an animal was made in an attempt to preserve the grey-colouring and Angus bloodline of the original Brangus cow.

"Over the years, we've bred quite a lot of calves from this old cow, and been able to breed her a number of different ways," he said.

"With the knowledge of what we've got and what we've bred, we thought it'd be a great opportunity to clone her, then breed from the new [cow], with the knowledge we learned from the old cow."

The Brangus's skin samples were taken to Melbourne and grown as embryos, before being impregnated through IVF into a recipient mother.

Of the 12 embryos implanted, only one survived, and went on to become Dasha.

"The percentage rate is always very low with the clones," Mr Geddes said.

"If you get one, you're very lucky and we got one."

Mr Geddes said he could see the potential for cloning in other areas of the commercial production cattle industry and he would not be surprised if the practice became more common.

He said there was great value in being able to re-create an animal after it had been processed through the abattoir and its full potential was known.

"With the [ability to] clone, they could slaughter the animal, find the one really good bull, and still be able to clone and breed from it," Mr Geddes said.

After the success of his first cloned calf on the property, Mr Geddes said he would definitely consider cloning in the future.

"You'd have to have an exceptional purpose to do it because it's quite expensive you wouldn't do it for practice," he said.

Topics: beef-cattle, cloning, rural, livestock, rockhampton-4700, vic

First posted February 24, 2017 08:39:00

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Another cloning success shows technology being used by everyday graziers - ABC Online

Dolly was an important milestone, inspiring scientists to continue improving cloning technology as well as to pursue new concepts in stem cell research. The endgame was never meant to be armies of genetically identical livestock: Rather, researchers continue to refine the techniques and combine them with other methods to turbocharge traditional animal breeding methods as well as gain insights into aging and disease.

Before the decades of experiments that led to Dolly, it was thought that normal animals could be produced only by fertilisation of an egg by a sperm. Thats how things naturally work. These germ cells are the only ones in the body that have their genetic material all jumbled up and in half the quantity of every other kind of cell. That way when these so-called haploid cells come together at fertilisation, they produce one cell with the full complement of DNA. Joined together, the cell is termed diploid, for twice, or double. Two halves make a whole.

From that moment forward, nearly all cells in that body have the same genetic makeup. When the one-cell embryo duplicates its genetic material, both cells of the now two-cell embryo are genetically identical. When they, in turn, duplicate their genetic material, each cell at the four-cell stage is genetically identical. This pattern goes on so that each of the trillions of cells in an adult is genetically exactly the same whether its in a lung or a bone or the blood.

In somatic cell nuclear transfer, all the DNA comes from a single adult cell. Belkorin, CC BY-SA

In contrast, Dolly was produced by whats called somatic cell nuclear transfer. In this process, researchers remove the genetic material from an egg and replace it with the nucleus of some other body cell. The resulting egg becomes a factory to produce an embryo that develops into an offspring. No sperm is in the picture; instead of half the genetic material coming from a sperm and half from an egg, it all comes from a single cell. Its diploid from the start.

Dolly demonstrated that adult somatic cells also could be used as parents. Thus, one could know the characteristics of the animal being cloned.

By my calculations, Dolly was the single success from 277 tries at somatic cell nuclear transfer. Sometimes the process of cloning by somatic cell nuclear transfer still produces abnormal embryos, most of which die. But the process has greatly improved so success rates now are more like 10 percent; its highly variable, though, depending on the cell type used and the species.

More than 10 different cell types have been used successfully as parents for cloning. These days most cloning is done using cells obtained by biopsying skin.

Environment plays a huge role for some characteristics. Food availability can influence weight. Diseases can stunt growth. These kinds of lifestyle, nutrition or disease effects can influence which genes are turned on or off in an individual; these are called epigenetic effects. Even though all the genetic material may be the same in two identical clones, they might not be expressing all the same genes.

Cloning a winner doesnt guarantee success for the next generation. AP Photo/Darron Cummings

Consider the practice of cloning winning racehorses. Clones of winners sometimes also will be winners but most of the time theyre not. This is because winners are outliers; they need to have the right genetics, but also the right epigenetics and the right environment to reach that winning potential. For example, one can never exactly duplicate the uterine conditions a winning racehorse experienced when it was a developing fetus. Thus, cloning champions usually leads to disappointment. On the other hand, cloning a stallion that sires a high proportion of race-winning horses will result very reliably in a clone that similarly sires winners. This is a genetic rather than a phenotypic situation.

Even though the genetics are reliable, there are aspects of the cloning procedure that mean the epigenetics and environment are suboptimal. For example, sperm have elegant ways of activating the eggs they fertilise, which will die unless activated properly; with cloning, activation usually is accomplished by a strong electric shock. Many of the steps of cloning and subsequent embryonic development are done in test tubes in incubators. These conditions are not perfect substitutes for the female reproductive tract where fertilisation and early embryonic development normally occur.

Sometimes abnormal fetuses develop to term, resulting in abnormalities at birth. The most striking abnormal phenotype of some clones is termed large offspring syndrome, in which calves or lambs are 30 or 40 percent larger than normal, resulting in difficult birth. The problems stem from an abnormal placenta. At birth, these clones are genetically normal, but are overly large, and tend to be hyperinsulinemic and hypoglycemic. (The conditions normalise over time once the offspring is no longer influenced by the abnormal placenta.)

Recent improvements in cloning procedures have greatly reduced these abnormalities, which also occur with natural reproduction, but at a much lower incidence.

Removing genetic material from the nucleus of a cell. AP Photo/Thomas Terry

But the cloning research landscape is changing fast. The driving force for producing Dolly was not to produce genetically identical animals. Rather researchers want to combine cloning techniques with other methods in order to efficiently change animals genetically much quicker than traditional animal breeding methods that take decades to make changes in populations of species such as cattle.

One recent example is introducing the polled (no horns) gene into dairy cattle, thus eliminating the need for the painful process of dehorning. An even more striking application has been to produce a strain of pigs that is incapable of being infected by the very contagious and debilitating PRRS virus. Researchers have even made cattle that cannot develop Mad Cow Disease. For each of these procedures, somatic cell nuclear transplantation is an essential part of the process.

To date, the most valuable contribution of these somatic cell nuclear transplantation experiments has been the scientific information and insights gained. Theyve enhanced our understanding of normal and abnormal embryonic development, including aspects of aging, and more. This information is already helping reduce birth defects, improve methods of circumventing infertility, develop tools to fight certain cancers and even decrease some of the negative consequences of aging in livestock and even in people. Two decades since Dolly, important applications are still evolving.

This article was originally published on The Conversation. Read the original article.

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20 years after Dolly: Everything you always wanted to know about ... - Bizcommunity.com

Twenty years ago today, the worlds first clone made from the cells of an adult mammal made her public debut. Dolly, a Finn Dorset sheep, was introduced to the public in 1997 after scientists at the Roslin Institute at the University of Edinburgh in Scotland implanted the cell nucleus from a sheep into an egg that was subsequently fertilized to create a clone.

Dollys debut set off a firestorm about both the practical value and ethics of cloning, including the possibility of human cloning. Currently, more than 40 countries including the UK, France, Germany and Japan formally ban human cloning. In other countries, including the U.S. and China, there is no legal prohibition on it.

On the anniversary of Dollys unveiling, here are five noteworthy findings about cloning and public opinion:

1 No one has ever cloned ahuman being, though scientists have cloned animals other than Dolly, including dogs, pigs, cows, horses and cats. Part of the reason is that cloning can introduce profound genetic errors, which can result in early and painful death. At the same time, labs in a variety of countries have successfully cloned human embryos for the purpose of producing stem cells that can be used in medical therapies.

2 Eight-in-ten American adults (81%) say cloning a human being is not morally acceptable, according to a May 2016 Gallup poll. There has been overwhelming opposition to human cloning since 2001. Just 13% of adults in 2016 say cloning is morally acceptable.

3 Americans are divided as to whether humans will be cloned in the near future. In a 2010 Pew Research Center survey, 48% of adults said that a human being would definitely or probably be cloned by 2050, compared with 49% who said such an event would not happen.

4 The public is divided about the prospect of using cloning to bring back to life species of animals that are currently extinct, such as the carrier pigeon or even the woolly mammoth. While bringing back dinosaurs, la Jurassic Park, might not possible due to the fact that dinosaurs have been dead for tens of millions of years, scientists could conceivably use fresher tissue samples to bring back more recently extinct species. In a 2013 Pew Research Center poll, half of all adults surveyed (50%) said that by 2050 researchers will be able to use cloning to bring back extinct species, with 48% predicting such a development wont occur.

5 Fewer Americans are concerned with cloning animals than with the prospect of cloning humans, according to the same 2016 Gallup survey. Still, a majority of adults (60%) say cloning animals like Dolly is morally wrong, compared with 34% who say its morally acceptable. Since 2001, there has been little to no change in these numbers.

Topics: Emerging Technology Impacts, Religion and Society, Religious Beliefs and Practices, Science and Innovation

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20 years after Dolly the sheep's debut, Americans remain skeptical ... - Pew Research Center

Windows Central

How to clone your PC hard drive using Macrium Reflect Windows Central Creating a complete backup of your hard drive by cloning it is never a bad idea. Hardware can fail, and it's a pain losing your data. There are also times where you'd like to swap out a hard drive whether in a laptop or a desktop for something ...

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How to clone your PC hard drive using Macrium Reflect - Windows Central

Terrific value investor Mohnish Pabrai teamed up with quant Fei Li to test a cloning strategy. Mohnish Pabrai is a fervent proponent and practitioner of cloning and mostly confines his investment universe to 13-F's of investors he thinks of as highly capable. Studies like this one on Buffett have shown 13-F's can be valuable sources of Alpha although these usually do have an important defect I'll address later. Pabrai created an ETF called the Dhandho Junoon ETF (NYSEARCA:JUNE) based on three distinct strategies of which cloning is one:

To prove his cloning strategy works Pabrai and Fei Li set up an experiment. Pabrai selected eight value managers and himself and Fei Li designed a randomization method to pick five stocks from a random portfolio between these nine managers':

Manager Number

Value Manager

1

Appaloosa Management

2

Cedar Rock Capital

3

FPA Capital

4

Greenlight Capital

5

Markel Insurance

6

Pabrai Investment Funds

7

Sequoia Fund

8

TCI Fund Management

9

ValueAct Capital

The algorithm always selected the largest (highest conviction) pick unless it was disqualified by the additional rules of the algorithm or it had already been selected.

The additional rules further weaken the test results:

Selection Criteria

No utilities, no REITs, no oil and gas exploration, no metals and mining and no multiline retailers.

Positive trailing-12-month net income

The random portfolios ended up doing really well:

Source: Forbes

Criticism

Even though the margin of outperformance is large I wouldn't put too much faith in this 10% outperformance holding up in the future.

Why didn't they run this backtest a gazillion times and publish aggregated results? It seems strange to run it just once as it is clearly a very volatile method because of the limited number of stocks chosen, the concentration in the value strategy.

What invalidates all these types of backtests is the researcher, or in this case Pabrai, starts out with a known big winner or winning group and subsequently comes up with the result they outperformed.

They use this to argue 13-F's contain valuable information that can be arbitraged and I believe that's true. But it is a flawed argument because we didn't know these managers were this good back in 2000. Some didn't even file 13-F's yet at the start date of the experiment.

When Warren Buffett wanted to make a point Hedge Funds wouldn't beat the S&P 500 he didn't say here's proof "look at my backtest". He said let's bet a million dollars to a hedge fund guy.

Source: Longbets

The additional selection criteria have nothing to do with the original premise. Why taint the results by including these. Pabrai could easily have knowledge of a particular spectacular failure by one of these 9 managers. For example the positive trailing 12 month net income criteria heightened the odds of the algorithm avoiding the spectacular Valeant (NYSE:VRX) disaster a prominent Sequoia position for a long time. Even with Valeant Sequoia outperformed but without it, the record is truly outstanding.

In addition most of the industries Pabrai selected for exclusion have underperformed the S&P 500 by a sizeable margin most especially in the later years which greatly influences compounded returns:

^SPXTR data by YCharts

^SPXTR data by YCharts

^SPXTR data by YCharts

^DJUSIM data by YCharts

^MSACMRTTR data by YCharts

My final point of criticism being that is seems a little bit unfair to include long/short managers like David Einhorn. We don't know how Einhorn manages risk exactly but he had only two down years ever. Short books generally limit volatility and it may have enabled Einhorn to be very aggressive with his long book due to eliminating some market risk. When we know after the fact, a managers bets have panned out and we can select from the great half of his portfolio as shorts aren't disclosed on 13-F's outperforming the S&P 500 starts to become easy game.

Even after my critical aside I do believe Pabrai's ETF is going to work and the 13-F strategy will work if you are good at identifying the right investors to follow.

The ETF combines strong strategies where there's compelling evidence they have been working and credible behavioral, systematic and other explanations of why they could continue to outperform.

Pabrai brandished his experiment the Shameless Portfolio and the algorithmic picks for 2017 are:

Oracle (NASDAQ:ORCL)

Berkshire Hathaway (NYSE:BRK.A) (NYSE:BRK.B)

Apple (NASDAQ:AAPL)

Microsoft (NASDAQ:MSFT)

Charter Communications (NYSE:CTR)

Apple continues to be a David Einhorn top pick and represents 14% of his long book. He's been long for a long time in addition to successfully trading the position. If you're an Apple long he's a guy worth checking on.

Berkshire Hathaway is the top position of Sequoia Fund. They have recently blemished their track record with the Valeant debacle and the Berkshire position has been maintained for a long time. It is actually fairly small given their historic position. It represents about 8% of the long book after Valeant cured them of an appetite for huge bets.

Chris Hohn's TCI Fund is betting big on Charter Communications with a 38% position according to the 13-F. TCI is London based however and they do a lot of European investments, only U.S. listed positions are revealed on the 13-F, which means the position is likely a much smaller part of the entire portfolio.

Oracle represents a 6.6% position for L.A. based First Pacific Advisors. Oracle is a popular holding among super investors of the value school but positions are generally small compared to some of the jumbo bets we've observed on the other picks.

Microsoft represents 20% of Value Act's U.S. long book. Value Act is an activist investor and they have been on the board of Microsoft for some time. They did very, very well with Microsoft but most recently added to other positions.

You can do a lot worse than buying any of these or checking out Pabrai's interesting Junoon ETF.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Pabrai And The Shameless Cloning Portfolio - Seeking Alpha

By George Seidel, Colorado State University

Its been 20 years since scientists in Scotland told the world about Dolly the sheep, the first mammal successfully cloned from an adult body cell. What was special about Dolly is that her parents were actually a single cell originating from mammary tissue of an adult ewe. Dolly was an exact genetic copy of that sheep a clone.

Dolly captured peoples imaginations, but those of us in the field had seen her coming through previous research. Ive been working with mammalian embryos for over 40 years, with some work in my lab specifically focusing on various methods of cloning cattle and other livestock species. In fact, one of the coauthors of the paper announcing Dolly worked in our laboratory for three years prior to going to Scotland to help create the famous clone.

Dolly was an important milestone, inspiring scientists to continue improving cloning technology as well as to pursue new concepts in stem cell research. The endgame was never meant to be armies of genetically identical livestock: Rather, researchers continue to refine the techniques and combine them with other methods to turbocharge traditional animal breeding methods as well as gain insights into aging and disease.

Dolly was a perfectly normal sheep who became the mother of numerous normal lambs. She lived to six and a half years, when she was eventually put down after a contagious disease spread through her flock, infecting cloned and normally reproduced sheep alike. Her life wasnt unusual; its her origin that made her unique.

Before the decades of experiments that led to Dolly, it was thought that normal animals could be produced only by fertilization of an egg by a sperm. Thats how things naturally work. These germ cells are the only ones in the body that have their genetic material all jumbled up and in half the quantity of every other kind of cell. That way when these so-called haploid cells come together at fertilization, they produce one cell with the full complement of DNA. Joined together, the cell is termed diploid, for twice, or double. Two halves make a whole.

From that moment forward, nearly all cells in that body have the same genetic makeup. When the one-cell embryo duplicates its genetic material, both cells of the now two-cell embryo are genetically identical. When they in turn duplicate their genetic material, each cell at the four-cell stage is genetically identical. This pattern goes on so that each of the trillions of cells in an adult is genetically exactly the same whether its in a lung or a bone or the blood.

In contrast, Dolly was produced by whats called somatic cell nuclear transfer. In this process, researchers remove the genetic material from an egg and replace it with the nucleus of some other body cell. The resulting egg becomes a factory to produce an embryo that develops into an offspring. No sperm is in the picture; instead of half the genetic material coming from a sperm and half from an egg, it all comes from a single cell. Its diploid from the start.

Dolly was the culmination of hundreds of cloning experiments that, for example, showed diploid embryonic and fetal cells could be parents of offspring. But there was no way to easily know all the characteristics of the animal that would result from a cloned embryo or fetus. Researchers could freeze a few of the cells of a 16-cell embryo, while going on to produce clones from the other cells; if a desirable animal was produced, they could thaw the frozen cells and make more copies. But this was impractical because of low success rates.

Dolly demonstrated that adult somatic cells also could be used as parents. Thus, one could know the characteristics of the animal being cloned.

By my calculations, Dolly was the single success from 277 tries at somatic cell nuclear transfer. Sometimes the process of cloning by somatic cell nuclear transfer still produces abnormal embryos, most of which die. But the process has greatly improved so success rates now are more like 10 percent; its highly variable, though, depending on the cell type used and the species.

More than 10 different cell types have been used successfully as parents for cloning. These days most cloning is done using cells obtained by biopsying skin.

Genetics is only part of the story. Even while clones are genetically identical, their phenotypes the characteristics they express will be different. Its like naturally occurring identical twins: They share all their genes but theyre not really exactly alike, especially if reared in different settings.

Environment plays a huge role for some characteristics. Food availability can influence weight. Diseases can stunt growth. These kinds of lifestyle, nutrition or disease effects can influence which genes are turned on or off in an individual; these are called epigenetic effects. Even though all the genetic material may be the same in two identical clones, they might not be expressing all the same genes.

Consider the practice of cloning winning racehorses. Clones of winners sometimes also will be winners but most of the time theyre not. This is because winners are outliers; they need to have the right genetics, but also the right epigenetics and the right environment to reach that winning potential. For example, one can never exactly duplicate the uterine conditions a winning racehorse experienced when it was a developing fetus. Thus, cloning champions usually leads to disappointment. On the other hand, cloning a stallion that sires a high proportion of race-winning horses will result very reliably in a clone that similarly sires winners. This is a genetic rather than a phenotypic situation.

Even though the genetics are reliable, there are aspects of the cloning procedure that mean the epigenetics and environment are suboptimal. For example, sperm have elegant ways of activating the eggs they fertilize00071-4/abstract), which will die unless activated properly; with cloning, activation usually is accomplished by a strong electric shock. Many of the steps of cloning and subsequent embryonic development are done in test tubes in incubators. These conditions are not perfect substitutes for the female reproductive tract where fertilization and early embryonic development normally occur.

Sometimes abnormal fetuses develop to term, resulting in abnormalities at birth. The most striking abnormal phenotype of some clones is termed large offspring syndrome, in which calves or lambs are 30 or 40 percent larger than normal, resulting in difficult birth. The problems stem from an abnormal placenta30217-5/abstract). At birth, these clones are genetically normal, but are overly large, and tend to be hyperinsulinemic and hypoglycemic. (The conditions normalize over time once the offspring is no longer influenced by the abnormal placenta.)

Recent improvements in cloning procedures have greatly reduced these abnormalities, which also occur with natural reproduction, but at a much lower incidence.

Many thousands of cloned mammals have been produced in nearly two dozen species. Very few of these concern practical applications, such as cloning a famous Angus bull named Final Answer (who recently died at an old age) in order to produce more high-quality cattle via his clones sperm.

But the cloning research landscape is changing fast. The driving force for producing Dolly was not to produce genetically identical animals. Rather researchers want to combine cloning techniques with other methods in order to efficiently change animals genetically much quicker than traditional animal breeding methods that take decades to make changes in populations of species such as cattle.

One recent example is introducing the polled (no horns) gene into dairy cattle, thus eliminating the need for the painful process of dehorning. An even more striking application has been to produce a strain of pigs that is incapable of being infected by the very contagious and debilitating PRRS virus. Researchers have even made cattle that cannot develop Mad Cow Disease. For each of these procedures, somatic cell nuclear transplantation is an essential part of the process.

To date, the most valuable contribution of these somatic cell nuclear transplantation experiments has been the scientific information and insights gained. Theyve enhanced our understanding of normal and abnormal embryonic development, including aspects of aging, and more. This information is already helping reduce birth defects, improve methods of circumventing infertility, develop tools to fight certain cancers and even decrease some of the negative consequences of aging in livestock and even in people. Two decades since Dolly, important applications are still evolving.

George Seidel, Professor of Biomedical Sciences, Colorado State University.

This article was originally published on The Conversation. Read the original article.

Photos via Belkorin, AP Photo/Darron Cummings, AP Photo/Thomas Terry, Getty Images / Jeff J Mitchell

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20 Years After Dolly, Where Are We With Cloning? - Inverse