[naturenews] from [nature.com]
[naturenews]
Published online 28 August 2009 | Nature | doi:10.1038/news.2009.873
News: Q&A
Top scientist's industry move heralds stem-cell shift
Stephen Minger tells Nature why he is leaving academia.
Daniel Cressey
Stephen Minger is one of the leading stem-cell scientists in the United Kingdom, known for his work both as a researcher and as a high-profile public advocate for the field. He gained one of the first UK licences for the derivation of human embryonic stem cells, and generated the first human embryonic stem-cell line in the country.
In September, he will leave his post as director of the Stem Cell Biology Laboratory at King's College London to take up a new role at GE Healthcare, the medical technologies company headquartered near Amersham, UK.
GE Healthcare announced on 30 June that it had struck a deal with biotechnology company Geron, based in Menlo Park, California, to develop drug-screening tests using cells derived from human embryonic stem cells. The project was widely touted as proof that the burgeoning field of stem-cell research was ready for broader applications in industry. Minger, who will lead that effort as head of GE Healthcare's Research and Development for Cell Technologies division, spoke to Nature about the job — and the future of stem-cell technologies.
Why are you making the move to industry?
I decided to move from King's to GE for the simple fact that it was a tremendous opportunity to take our academic, basic science research and really move it to a completely different level — to take stem cells and actually make parts from them, but also at the same time to avail myself of all the technology within GE.
Tell us more about the work you hope to be doing at GE Healthcare?
The basic idea initially is to develop cell lines derived from embryonic stem cells for drug screening and predictive toxicology.
One of the problems with big pharmaceutical companies and their development pipeline is that a number of compounds can go fairly far, even into clinical trials and in some cases even into licensing, where those drugs can begin to show unpredicted toxicological effects in humans. Most of the screening is done using animal cells — for example, rat liver cells — or is done using human tumour-cell lines that don't faithfully represent true primary human cells. In many cases, even if the screens do use human primary cells there are huge problems with the inconsistency of results.
The power of using embryonic-derived cells is consistency, both in terms of quality and genetic background. It allows you to reproducibly use the same population of cells week in, week out.
If you take a drug into the clinic and then it has to be withdrawn either from clinical trials or from licensing, you're looking at losing hundreds of millions if not billions of dollars. So we're really trying to reduce the costs of drug development.
Isn't this work that you could have done in an academic environment?
It's not so much that the work couldn't be done academically. It's about trying to garner the resources to be able to scale the work up, and to work more efficiently, running a very large group of scientists, engineers and cell biologists. It would be very difficult to do within an academic setting. I had no real interest in leaving academia but when you weigh everything up, it became almost impossible to say no.
Do you think your move is part of a growing trend towards commercializing stem cells?
It is clear that the field is maturing. If you look at the number of academic research groups who are pursuing this work, it's ten times what it was five or six years ago.
Whether or not other academic researchers will want to do what I am doing is really an individual decision, but I think it does represent a slight shift away from the research being at a really basic level, and moving towards commercial and clinical applications.
Do any of your colleagues think you're selling out by making this move?
I've yet to hear anyone say, "I think you're selling out". If anything, I feel like I'm taking advantage of an opportunity that will hopefully enhance the field and help develop tools that will support the entire stem-cell community.
[naturenews]
Published online 27 August 2009 | Nature | doi:10.1038/news.2009.864
News
Human mutation rate revealed
Next-generation sequencing provides the most accurate estimate to date.
Elie Dolgin
Every time human DNA is passed from one generation to the next it accumulates 100–200 new mutations, according to a DNA-sequencing analysis of the Y chromosome.
This number — the first direct measurement of the human mutation rate — is equivalent to one mutation in every 30 million base pairs, and matches previous estimates from species comparisons and rare disease screens.
The British-Chinese research team that came up with the estimate sequenced ten million base pairs on the Y chromosome from two men living in rural China who were distant relatives. These men had inherited the same ancestral male-only chromosome from a common relative who was born more than 200 years ago. Over the subsequent 13 generations, this Y chromosome was passed faithfully from father to son, albeit with rare DNA copying mistakes.
The researchers cultured cells taken from the two men, and using next-generation sequencing technologies found 23 candidate mutations. Then they validated twelve of these mutations using traditional sequencing techniques. Eight of these mutations, however, had arisen in their cell-culturing process, which left just four genuine, heritable mutations. Extrapolating that result to the whole genome gives a mutation rate of around one in 30 million base pairs.
"It was very reassuring that our application of the new sequencing technologies seems to give a reliable result and that the number we've been using for the mutation rate is pretty much the right one," says Chris Tyler-Smith of the Wellcome Trust Sanger Institute in Hinxton, UK, who led the study, published today in Current Biology1.
Tyler-Smith says that direct measurement of the mutation rate can be used to infer events in our evolutionary past, such as when humans first migrated out of Africa, more accurately than previous methods. But before that's possible, researchers will need a more precise estimate, notes Laurent Duret, an evolutionary biologist at the University of Lyon in France. "The confidence interval for the mutation rate is still quite wide," he says. Sequencing more pairs of Y chromosomes from distant male cousins in other families should provide a more robust measurement and reveal how mutation rates vary between individuals, Duret adds.
Most of the Y chromosome doesn't mix with any other chromosomes, which makes estimating its mutation rate easier. But the mutation rate might be somewhat different on other chromosomes, points out Adam Eyre-Walker, an evolutionary biologist at the University of Sussex in Brighton, UK. Other projects that involve sequencing parents and their offspring, such as the 1000 Genomes Project, should start to illuminate how DNA changes across the rest of the genome.
"I'm sure this is just the first of many papers that will be doing the same sort of thing," says Tyler-Smith.
References
1. Xue, Y. et al. Curr. Biol. 19, 1-5 (2009). | Article | PubMed | ChemPort |
[naturenews]
Published online 28 August 2009 | Nature | doi:10.1038/news.2009.873
News: Q&A
Top scientist's industry move heralds stem-cell shift
Stephen Minger tells Nature why he is leaving academia.
Daniel Cressey
Stephen Minger is one of the leading stem-cell scientists in the United Kingdom, known for his work both as a researcher and as a high-profile public advocate for the field. He gained one of the first UK licences for the derivation of human embryonic stem cells, and generated the first human embryonic stem-cell line in the country.
In September, he will leave his post as director of the Stem Cell Biology Laboratory at King's College London to take up a new role at GE Healthcare, the medical technologies company headquartered near Amersham, UK.
GE Healthcare announced on 30 June that it had struck a deal with biotechnology company Geron, based in Menlo Park, California, to develop drug-screening tests using cells derived from human embryonic stem cells. The project was widely touted as proof that the burgeoning field of stem-cell research was ready for broader applications in industry. Minger, who will lead that effort as head of GE Healthcare's Research and Development for Cell Technologies division, spoke to Nature about the job — and the future of stem-cell technologies.
Why are you making the move to industry?
I decided to move from King's to GE for the simple fact that it was a tremendous opportunity to take our academic, basic science research and really move it to a completely different level — to take stem cells and actually make parts from them, but also at the same time to avail myself of all the technology within GE.
Tell us more about the work you hope to be doing at GE Healthcare?
The basic idea initially is to develop cell lines derived from embryonic stem cells for drug screening and predictive toxicology.
One of the problems with big pharmaceutical companies and their development pipeline is that a number of compounds can go fairly far, even into clinical trials and in some cases even into licensing, where those drugs can begin to show unpredicted toxicological effects in humans. Most of the screening is done using animal cells — for example, rat liver cells — or is done using human tumour-cell lines that don't faithfully represent true primary human cells. In many cases, even if the screens do use human primary cells there are huge problems with the inconsistency of results.
The power of using embryonic-derived cells is consistency, both in terms of quality and genetic background. It allows you to reproducibly use the same population of cells week in, week out.
If you take a drug into the clinic and then it has to be withdrawn either from clinical trials or from licensing, you're looking at losing hundreds of millions if not billions of dollars. So we're really trying to reduce the costs of drug development.
Isn't this work that you could have done in an academic environment?
It's not so much that the work couldn't be done academically. It's about trying to garner the resources to be able to scale the work up, and to work more efficiently, running a very large group of scientists, engineers and cell biologists. It would be very difficult to do within an academic setting. I had no real interest in leaving academia but when you weigh everything up, it became almost impossible to say no.
Do you think your move is part of a growing trend towards commercializing stem cells?
It is clear that the field is maturing. If you look at the number of academic research groups who are pursuing this work, it's ten times what it was five or six years ago.
Whether or not other academic researchers will want to do what I am doing is really an individual decision, but I think it does represent a slight shift away from the research being at a really basic level, and moving towards commercial and clinical applications.
Do any of your colleagues think you're selling out by making this move?
I've yet to hear anyone say, "I think you're selling out". If anything, I feel like I'm taking advantage of an opportunity that will hopefully enhance the field and help develop tools that will support the entire stem-cell community.
[naturenews]
Published online 27 August 2009 | Nature | doi:10.1038/news.2009.864
News
Human mutation rate revealed
Next-generation sequencing provides the most accurate estimate to date.
Elie Dolgin
Every time human DNA is passed from one generation to the next it accumulates 100–200 new mutations, according to a DNA-sequencing analysis of the Y chromosome.
This number — the first direct measurement of the human mutation rate — is equivalent to one mutation in every 30 million base pairs, and matches previous estimates from species comparisons and rare disease screens.
The British-Chinese research team that came up with the estimate sequenced ten million base pairs on the Y chromosome from two men living in rural China who were distant relatives. These men had inherited the same ancestral male-only chromosome from a common relative who was born more than 200 years ago. Over the subsequent 13 generations, this Y chromosome was passed faithfully from father to son, albeit with rare DNA copying mistakes.
The researchers cultured cells taken from the two men, and using next-generation sequencing technologies found 23 candidate mutations. Then they validated twelve of these mutations using traditional sequencing techniques. Eight of these mutations, however, had arisen in their cell-culturing process, which left just four genuine, heritable mutations. Extrapolating that result to the whole genome gives a mutation rate of around one in 30 million base pairs.
"It was very reassuring that our application of the new sequencing technologies seems to give a reliable result and that the number we've been using for the mutation rate is pretty much the right one," says Chris Tyler-Smith of the Wellcome Trust Sanger Institute in Hinxton, UK, who led the study, published today in Current Biology1.
Tyler-Smith says that direct measurement of the mutation rate can be used to infer events in our evolutionary past, such as when humans first migrated out of Africa, more accurately than previous methods. But before that's possible, researchers will need a more precise estimate, notes Laurent Duret, an evolutionary biologist at the University of Lyon in France. "The confidence interval for the mutation rate is still quite wide," he says. Sequencing more pairs of Y chromosomes from distant male cousins in other families should provide a more robust measurement and reveal how mutation rates vary between individuals, Duret adds.
Most of the Y chromosome doesn't mix with any other chromosomes, which makes estimating its mutation rate easier. But the mutation rate might be somewhat different on other chromosomes, points out Adam Eyre-Walker, an evolutionary biologist at the University of Sussex in Brighton, UK. Other projects that involve sequencing parents and their offspring, such as the 1000 Genomes Project, should start to illuminate how DNA changes across the rest of the genome.
"I'm sure this is just the first of many papers that will be doing the same sort of thing," says Tyler-Smith.
References
1. Xue, Y. et al. Curr. Biol. 19, 1-5 (2009). | Article | PubMed | ChemPort |
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