Scientists Report First Success in Cloning Human Stem Cells

It’s been 17 years since Dolly the sheep was cloned from a mammary cell. And now scientists applied the same technique to make the first embryonic stem cell lines from human skin cells.

Ever since Ian Wilmut, an unassuming embryologist working at the Roslin Institute just outside of Edinburgh stunned the world by cloning the first mammal, Dolly, scientists have been asking – could humans be cloned in the same way? Putting aside the ethical challenges the question raised, the query turned out to involve more wishful thinking than scientific success. Despite the fact that dozens of other species have been cloned using the technique, called nuclear transfer, human cells have remained stubbornly resistant to the process.

Until now. Shoukhrat Mitalipov, a professor at Oregon Health & Science University and his colleagues report in the journal Cell that they have successfully reprogrammed human skin cells back to their embryonic state. The purpose of the study, however, was not to generate human clones but to produce lines of embryonic stem cells. These can develop into muscle, nerve, or other cells that make up the body’s tissues. The process, he says, took only a few months, a surprisingly short period to reach such an important milestone.

Nuclear transfer involves inserting a fully developed cell – in Mitalipov’s study, the cells came from the skin of fetuses – into the nucleus of an egg, and then manipulating the egg to start dividing, a process that normally only occurs after it has been fertilized by a sperm. After several days, the ball of cells that results contains a blanket of embryonic stem cells endowed with the genetic material of the donor skin cell, which have the ability to generate every cell type from that donor. In Dolly’s case, those cells were allowed to continue developing into an embryo that was then transferred to a ewe to produce a cloned sheep. But Mitalipov says his process with the human cells isn’t designed to generate a human clone, but rather just to create the embryonic stem cells. These could then be manipulated to create heart, nerve or other cells that can repair or treat disease.

“I think this is a really important advance,” says Dieter Egli, an investigator at the New York Stem Cell Foundation. “I have a very high confidence that versions of this technique will work very well; it’s something that the field has been waiting for.” Egli is among the handful of scientists who have been working to perfect the technique with human cells and in 2011, succeeded in producing human stem cells, but with double the number of chromosomes. In 2004, Woo Suk Hwang, a veterinary scientist at Seoul National University, claimed to have succeeded in achieving the feat, but later admitted to faking the data. Instead of generating embryonic stem cell lines via nuclear transfer, Hwang’s group produced the stem cells from days-old embryos, a technique that had already been established by James Thomson at University of Wisconsin in 1998.

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A femur damaged by rheumatism (by Lennart Nilsson)

Trade years of life to make the whole world healthier

To solve the tragedy of child mortality we need to set up an international market in ill health

ABOUT 6 million children under 5 die from infectious diseases each year. Most of those deaths occur in low-income countries as a result of diseases that can be prevented cheaply, such as diarrhoea, malaria or measles.

This tragedy is a result of two fundamental problems in global health: money and support from richer countries are insufficient; and the available funds are often not used efficiently.

Why does this happen? One important cause is that global health is a public good, and like many other public goods it suffers from the tragedy of the commons. The benefits of contributing – reduced risk of new emerging diseases, for example – are shared by free riders as well as contributors. You don’t have to pay into the system to reap the rewards.

At present, global health investment is voluntary and few countries make sizeable donations. Since the start of the global financial crisis, investment has stagnated.

Is there a way to improve the situation? We think so. Although the world does not have a lot of experience in managing global commons, there is an example we can learn from: carbon trading.

Battling climate change is also a public good that is vulnerable to free riding. In this case, however, the world has devised a system to try to prevent free riders: carbon credit markets. These are designed to reduce carbon emissions by channelling money to the places where emissions cuts are easiest.

In a typical carbon market, countries have their emissions capped and are issued tradeable permits. Those that want to emit more than their cap have to buy permits from others. The goal is to give countries an incentive to cut their emissions so they can sell surplus credits, meaning that the cheapest and easiest cuts to carbon dioxide emissions are made first.

Likewise, it is much cheaper to save a life in a poor country than it is in a rich country. And so at the National University of Singapore we have designed a prototype cap-and-trade system for global health that similarly gives incentives to high- and middle-income countries to save lives cheaply (PLoS Medicine, vol 10, e1001392).

For such a market to work, we need something to be traded. An obvious candidate is DALYs, or disability-adjusted life years. These are widely used to compare the effectiveness of different health interventions – one person living for a year in perfect health is worth zero DALYs, being dead before their life expectancy is worth one DALY, and being ill for a year somewhere in between.

Disease burden in DALYs is very high in poor countries largely because of high mortality rates in children, who die very early in comparison to the average life expectancy.

In our scheme, donor countries would be required to buy DALYs on a market, by paying for a measles vaccination programme or contributing to malaria control in Africa, for example. Donors would have to buy a set number of DALYs rather than spend a set sum of money, so would have an incentive to buy the cheapest DALYs on the market, which ought to channel donations most efficiently to poorer countries.

How many DALYs would donors need to buy? Various possibilities exist, such as pegging donations to per-capita GDP. We propose linking donations to domestic health expenditure.

Here’s how. The World Health Organization judges a health intervention be cost-effective if the money it takes to avert one DALY is less than three years of per-capita income in the country where it is carried out. In Australia, for example, per capita income is US$38,000, so any health intervention that costs US$114,000 or less to gain one DALY is deemed cost-effective.

We propose changing this to a universal cost-effectiveness threshold, set to three times the per-capita income in a typical country on the boundary between low and middle-income, which comes to $3015.

If a high-income country wanted an intervention that was less cost-effective than this – for example, if Australia spent $5 million on a vaccine programme with a cost per DALY averted of about $100,000 – it would have to buy DALY credits from a low-income country to compensate.

How many? If spent in a poor or middle-income country, $5 million should buy about 1650 DALYs. Australia’s plan would gain just 50, so it would have to buy 1600 from elsewhere to compensate. One option would be to spend $8050 on measles vaccination in sub-Saharan Africa, which costs a measly $5 per DALY averted. That increases the overall cost of the project by less than 0.2 per cent.

If this system was implemented across the board it would supply the estimated extra $36 billion to $45 billion worth of DALYs required each year to reach the Millennium Development Goals for health – a two-thirds reduction in child mortality, three-quarters reduction of maternal mortality and a reversal of the spread of HIV and malaria.

Most rich countries would end up paying more than they do now. But for comparison, the international carbon market grew out of nothing to be worth $140 billion in 2009, and has held up despite the financial crisis. If a health market were to obtain wide support, attaining the Millennium Development Goals seems eminently feasible.

To implement such a system would require a nucleus of willing countries to take the initiative. Such countries exist: Norway, Luxembourg, the UK and the United Arab Emirates already pay their fair share or more. As global citizens, we should all be ready to implement the most powerful strategies to protect the global commons. The alternative is to sit back and accept 6 million child deaths every year.

This article appeared in print under the headline “A cure for global ills”

Punch Leaves Man With Star-Shaped Cataract

A man in Austria developed a cataract shaped like a star in his eye after he was punched, according to a report of his case.

The 55-year-old went to his doctor because his vision in that eye had progressively worsened over the previous six months, according to doctors who treated the man.

The patient said he’d been punched nine months earlier, the doctors wrote in their report.

Talk about seeing stars, sheesh.

Monounsaturated fats reduce metabolic syndrome risk

Canola oil and high-oleic canola oils can lower abdominal fat when used in place of other selected oil blends, according to a team of American and Canadian researchers. The researchers also found that consuming certain vegetable oils may be a simple way of reducing the risk of metabolic syndrome, which affects about one in three U.S. adults and one in five Canadian adults.

“The monounsaturated fats in these vegetable oils appear to reduce abdominal fat, which in turn may decrease metabolic syndrome risk factors,” said Penny Kris-Etherton, Distinguished Professor of Nutrition, Penn State.

In the randomized, controlled trial, 121 participants at risk for metabolic syndrome received a daily smoothie containing 40 grams (1.42 ounces) of one of five oils as part of a weight maintenance, heart-healthy, 2000-calorie per day diet. Members of the group had five risk factors characterized by increased belly fat, low “good” hdl cholesterol and above average blood sugar, blood pressure and triglycerides that increase the risk of heart disease, stroke and type 2 diabetes. The researchers repeated this process for the remaining four oils.

The results were presented at the American Heart Association’s EPI/NPAM 2013 Scientific Sessions in New Orleans.

Results showed that those who consumed canola or high-oleic canola oils on a daily basis for four weeks lowered their belly fat by 1.6 percent compared to those who consumed a flax/safflower oil blend. Abdominal fat was unchanged by the other two oils, which included a corn/safflower oil blend and high-oleic canola oil enriched with an algal source of the omega-3 DHA. Both the flax/safflower and corn/safflower oil blends were low in monounsaturated fat.

According to the American Heart Association, many of the factors that contribute to metabolic syndrome can be addressed by a healthy diet, exercise and weight loss, which can significantly reduce health risks of this condition.

“It is evident that further studies are needed to determine the mechanisms that account for belly fat loss on a diet high in monounsaturated fatty acids,” said Kris-Etherton. “Our study indicates that simple dietary changes, such as using vegetable oils high in monounsaturated fatty acids, may reduce the risk of metabolic syndrome and therefore heart disease, stroke and type 2 diabetes.”

The Secret to Olive Oil’s Anti-Alzheimer’s Powers:

People living in the Mediterranean have a much lower risk of contracting Alzheimer’s disease than those of us stuck in other parts of the world. Researchers looking for an explanation nailed down an association between extra virgin olive oil and low rates of the disease. They attributed olive oil’s disease-fighting power to high amounts of monounsaturated fats. But now, however, new research shows that a natural substance found in olive oil called oleocanthal is the real hero, Phys.org writes.

Past studies have identified oleocanthal as the likely candidate behind olive oil’s protective effects, but this study helped fill in the blanks of how specifically it bestows that advantage. In trials with mice, oleocanthal protected nerve cells from the kind of damage that occurs from Alzheimer’s disease. It decreased the accumulation of beta-amyloids—the amino acid–based plaques that scientists believe cause Alzheimer’s—in the brain and boosted production of the proteins and enzymes that researchers think play roles in removing those same plaques. 

In their paper, published in ACS Chemical Neuroscience, the researchers write:

This study provides conclusive evidence for the role of oleocanthal on Aβ degradation as shown by the up-regulation of Aβ degrading enzymes IDE and possibly NEP. Furthermore, our results show that extra-virgin olive oil-derived oleocanthal associated with the consumption of Mediterranean diet has the potential to reduce the risk of AD or related neurodegenerative dementias.

As if deliciousness and protection against Alzheimer’s were not enough to recommend it, other researchers have found that extra virgin olive oil helps to clarify thinking and improve memory.

Sperm Works Best in the Winter, Study Finds

Researchers at Israel’s Ben-Gurion University of the Negev found that sperm concentration and the percentage of fast motility—the ability to move spontaneously and independently—decreased significantly from spring into summer and fall, rebounding in the winter.

The physical structure of the sperm cells was also the healthiest in the winter months, according to the study, which tested 6,455 semen samples over the course of three years.

“This study was aimed to explore the possibility that changing weather is somehow related to the quality of sperm, a phenomenon well known from the animal world,” study leader Eliahu Levitas said in an email.

Health and The Gut Flora: Improving Health by Targeting Gut Bacteria: A Q&A with Jeremy Nicholson

The body and its intestinal flora produce all sorts of chemicals that hold clues about a person’s health. Jeremy Nicholson is deciphering the signals, which could lead to new kinds of medicines

One of the hottest biomedical fields right now is metabolomics—the study of the metabolites and other chemicals that the body and its bacteria produce. The goal is to find out how the compounds can serve as indicators of health and disease. For the Insights story, “Going with His Gut Bacteria,” in the July 2008 Scientific American, Melinda Wenner talked with Jeremy Nicholson of Imperial College London. One of the founders of the field, Nicholson thinks that metabolomics may prove that the best medicine actually targets intestinal flora rather than cells of the body. Here is an edited excerpt from the interview.

You were one of the first scientists to study the metabolome, the collection of chemicals produced by human metabolism. Was it hard getting people to take the idea seriously?

Nobody was in the slightest bit interested. I had terrible difficulties getting funding throughout the 1980s in this area. I remember sending a paper to Nature in 1987 that showed how you could use nuclear magnetic resonance and computational pattern recognition to look at urine from animals that had been poisoned with lots of different sorts of drugs. The editor said, “There’s no interest [in this] to anybody whatsoever.” That would have been 10 years in advance of the first paper that would really call itself metabolomics or metabonomics.

Over the 10 years that followed, I built up a hell of a laboratory, so when our work started to get noticed, we were already one of the best-equipped labs in the world.

Why was no one interested back then?

I don’t think it was necessarily willful resistance; there was a lot of other stuff going on. In the ’80s molecular biology had just come in. You couldn’t get a grant in the U.K. unless you were doing molecular biology, because everybody thought that was going to solve everything. Then, also, in the late ’80s you had the idea of genomics coming in.

Why do you think that the metabolome is more likely than the genome to give scientists the answers they want?

Genomics only takes you part of the journey to real biological discovery. The genome is a blueprint for life, but it doesn’t tell you how the thing works. If you had a blueprint for a nuclear power station, it would tell you exactly how to build one, but it wouldn’t tell you anything about quantum mechanics, physics, the idea of nuclear fission, radioactive decay or anything that made it work. You can look at the genome the same way. It may well have a blueprint for building life, but it doesn’t tell you how the parts fit together.

And your work has shown that the environment makes a huge contribution to your health.

People talk about the genes that make you fat, but really, if you sit on your butt eating pork rinds and Big Macs and watching television, you will get fat, no matter what your genes say. What you do to yourself is really important. Metabolism captures environmental signatures as well as genetic. Your environment involves things like drugs you’re exposed to, the pollutants you’re exposed to, the products of your gut microbes, the metabolic products of your diet—so when we do a broad-screen metabolic profile, we’re capturing all of that information, plus information that links to genome variation. For me, metabonomics is the most holistic of the “-omics.” In principle, it can capture the signature of everything.

We’ve found that humans are far more metabolically diverse than genetically diverse. For instance, Chinese and Japanese people are actually metabolically very distinct, despite the fact they’re genetically near identical. And they have very different incidences of diseases.

How could scientists use this information to inform medicine?

I have this new concept of metabolome-wide association study. It will allow us to sample the genetic and the environmental things that cause diseases in people. We’ve found metabolic biomarkers that link to things like blood pressure in humans. Using this approach, we can generate new hypotheses in physiology that can be tested and may ultimately result in new drug discovery.

And you believe many of our metabolic differences have to do with gut bacteria. How did you come to realize that these microbes were so important for our health?

I’ve always known, ever since we started working on metabolic profiling, that there were metabolites that came from the gut microbes. We never really paid a lot of attention to it until maybe about seven or eight years ago, though. It was not just me—it was also Professor Ian Wilson [a scientist at AstraZeneca in England]. He became intrigued because he looked at colonies of rats—supposedly very, very similar groups of rats—but some produced one set of metabolites and others produced a different set. And yet they were from the same breeder; they were the same genetic strains. The differences were down to different gut microbial populations in rats residing in different parts of the laboratory.

The more we looked into it, the more we realized that microbes were so intimately involved in animal metabolic processes that they might have contributions to disease development in ways that hadn’t really been thought of before. We’re really just starting to expand this now, thinking about how gut microbes influence all sorts of things. They have influences on liver diseases and gut pathology like Crohn’s disease and irritable bowel syndrome; there’s even evidence that autistic children have very, very different gut microflora [than other children]. Almost every sort of disease has a gut–bug connection somewhere. It’s quite remarkable.

What, ultimately, are you hoping to achieve with metabolomics?

We want to be able to take a set of biological data from a human being, and then, based on what we know about the metabolic makeup of that person, say how long they’re going to live, what diseases they’re likely to suffer from, how to treat those diseases, and how to manage their lifestyle and drug therapy optimally. We’re opening up sets of doors here into the future of health care—the manipulation of biology that would be just unimaginable five years ago.

Any funny or surprising moments you’d like to share from your research?

We did some work about 10 years ago at another person’s laboratory on something called magic-angle spinning spectroscopy [a kind of NMR spectroscopy that relies on spinning the sample to achieve higher resolution data]. What I was interested in was whether or not we could get some extra information out of lipoprotein signals by spinning the probe very, very fast. I put the blood plasma sample in and the spectrum that came out was totally nothing like plasma is normally. I thought, absolutely fantastic! We’ve liberated all this new information! We tried several more samples and the same thing happened, and so I started to chat with one of the guys in this laboratory. I said, “We got an amazing spectrum, it looks nothing like plasma spectra should be.” And he said, “Oh, show me!” And I showed him and he said, “Hmm, that looks very familiar.” To cut a long story short, what happened was that the previous week the guy had been running samples of blue cheese—a food science company had been conducting experiments. Rather than discovering a new part of the fundamental dynamics of lipoproteins, we discovered how to detect blue cheese in plasma.