Mini-pig clone and biotechnology

Mini-pig clone raises transplant hope


16:35 13 January 03


The cloning of a miniature pig lacking both copies of a gene involved in immediate immune rejection has brought the prospect of transplanting pig organs into people a little closer. The small pig's organs are similar in size to those of humans and the missing genes make the organs less likely to be rejected.

The birth of two-month-old Goldie, cloned by the US-based Immerge BioTherapeutics, was announced at a conference in New Zealand on Sunday. The cloning process is important because it ensures all the cells in all the pigs produced are missing the desired gene.

Thousands of people die every year while waiting for organ transplants and the company hopes to create a herd of miniature pigs that can be used as a source of organs for human transplantation.

Goldie lacks both copies of a gene called alpha-1-galactosyltransferase, which codes for an enzyme that adds a sugar to the surface of pig cells. It is this sugar that would be attacked by human antibodies after transplant. But with both copies of the gene deleted, the antibodies fail to attach and rejection is prevented.

Clinical studies of the double-knock-out pig tissue in primates are now planned, says Immerge.


Tailored to fit


However, Goldie is not the first double-knock-out pig to be cloned. In August 2002, UK-based PPL Therapeutics announced the birth of five normal-sized piglets lacking both copies of the gene.

Immerge believe its pigs will be a better source of donor organs due to their small size. This may be a slight advantage, but it does not rule out PPL's pigs, says Derek Gray, a professor of experimental surgery at the University of Oxford, UK.

One solution would be to take organs from young normal-sized pigs, which might stop growing further when transplanted to humans. "There is a fair chance the organ could tailor its size to meet demand," he told New Scientist.

Critics have argued that xenotranplantation could allow retroviruses in the pigs' DNA to be transmitted to humans. But laboratory tests done by Immerge on its miniature pigs suggest this will not happen.


Long term rejection


But while Goldie's creation may have solved the problem of immediate transplant rejection, there is a slower rejection in which the transplant is attacked by the recipient's white blood cells, says Gray.

The mechanism is not fully understood, but is probably caused by the human immune system recognising every single pig protein that is different.

Despite many years of research, placing pig organs in people still appears a distant prospect. But, says Gray, a breakthrough in solving the long term rejection problem could suddenly make xenotransplantation seem very viable. "A single advance in our understanding could transform the whole field - and we are getting close," he says.

In the longer term, xenotransplantation faces competition in some areas from tissue produced from human embryonic stem cells, which is much less likely to present rejection problems.

But David Ayares of PPL Therapeutics in the US argues that there is a 10-year window of opportunity for pig islet cells, transplants of which could treat diabetes. "And there is nothing on the immediate horizon that could take the place of a kidney or a heart," he says.


Natasha McDowell

What do you think about this article?. Should we be happy or worried?.

For convenient, we can use Cambridge Dictionary Online

http://dictionary.cambridge.org/

iem iem chả hiểu gì cả ? tiếng anh nà cái gì nhẩy , iem chỉ biết tiếng con lợn con gà thui

I have just read the article from beginning to end. But would you please explain me why the non genetically modified pig cell be rejected only because they have galactose.

Welcome khibo!

Every animal's cells, human's, pig's are surrounded by a membrane which controls substances enter or leave the cell. It's called the plasma membrane. The plasma membrane consists of phospholipid and many kind of proteins molecules.

On the outer side of the cell membrane, chains of carbohydrate are attached to proteins or phospholipids and acts as the cell antigen or cell-cell recognition.

Because pig cells have a specific carbohydrate( galactose). So human's white blood cells can recognite them

White blood cell: Ah Ah! Buddies, see those are pig cells. They don't belong to our community. Let's go Buddies, destroy them, rejects them.

Stem cells migrate from bone to brain


22:00 20 January 03



Autopsies on four dead women have shown for the first time that stem cells in bone marrow can develop into brain cells, not just blood and bone cells as previously thought.

The discovery suggests new approaches for repairing damaged or diseased brains. Stem cells themselves could be used, or the signalling chemicals that instruct them to become brain cells, although these have yet to be identified.

"I think it's very encouraging to know that there are cells in the human bone marrow that have the capability to reach the brain and become neurons," says Eva Mezey, who led the team that made the discovery at the US National Institute of Neurological Diseases and Stroke in Bethesda, Maryland.

The women whose brains were examined by autopsy had all been treated during their lives with bone marrow transplants from men. This meant that any cells the NINDS team found in the brain containing the male Y chromosome must have come from the donated bone marrow.

The researchers found such cells and not just in isolation, but in clumps. This suggests the bone marrow stem cells multiplied after reaching the brain.


Come here!


Mezey's hunch is that the raw stem cells circulate all the time, until they are summoned to sites of injury. Once there, they are fashioned into tissue that heals the damage.

"There's something that recruits these cells," says Mezey. "There's some factor that says: 'Come in here, we need you'. Then, they receive further orders as to what type of cell to become."

"We must now find out what these signals are," she says. Doctors could potentially accelerate healing by injecting extra signalling molecules into damaged tissue.


Look and learn


Mezey's proposed strategy for finding the important signals would begin by identifying all the receptors on the surfaces of stem cells. This would reveal which signalling substances the cells are equipped to receive. The next step would be to expose stem cells to each substance in turn, and observe the type of cell they develop into.

The NINDS team had already shown that bone marrow cells turn into brain cells in rodents. The new work now shows the same happens in humans.

The findings corroborate experiments by Catherine Verfaillie of the University of Minnesota. These showed that special cells with stem-cell like properties, called "multipotent adult progenitor cells", could be isolated from the bone marrow of mice and humans. In mice, Verfaillie showed they turned into virtually any type of tissue.

Verfaillie's discovery was reported by New Scientist in January 2002 and raised hopes that, for medical purposes, cells from an adult's bone marrow would be as suitable as the more controversial stem cells harvested from embryos.


Andy Coghlan

Ha! No one like biotechnology? Is there anyone like Biology and Chemistry?. Biotechnology is my "most-wanted".

Stem cell, DNA structure, Proteins structure, GM crop (Genetically modifided crop)... are the centre of most heated debates.
Does anyone concern?

Special Report: The birth of biotechnology

EUGENE RUSSO


According to one account, biotechnology was born during a meeting at a Hawaiian delicatessen in 1972. The shop has long since been torn down, and there is no plaque to mark biotech's inception — but its legacy lives on. And the two pioneers who met there blazed distinct career paths that have become well trodden

Stanford medical professor Stanley Cohen and biochemist Herbert Boyer from the University of California, San Francisco, were in Honolulu to attend a meeting on plasmids, the ringlets of DNA contained in bacteria. Cohen reported on the ability to introduce plasmid DNA into Escherichia coli, which allowed researchers to propagate and clone the plasmids in the bacteria. Boyer told the meeting about his work with a revolutionary enzyme called EcoRI that could cleave the double-stranded DNA molecule to produce single-stranded ends with identical termini.

Both saw the potential for combining the two discoveries into what would become genetic engineering. First, use EcoRI to slice both plasmid DNA and the DNA of choice. Then, with the identical DNA termini exposed, attach the DNA fragment to the plasmid DNA, and clone the whole in E. coli.

The two men first discussed collaboration at a deli near Waikiki Beach. Their chat over a late-night snack led to a scientific achievement that later rocked the world of science. Within a year, they had cloned DNA molecules made by splicing together DNA fragments of two different plasmids, thus creating recombinant DNA. The foundations for biotechnology were established.

Boyer and Cohen chose different paths, both affected by concerns about the safety of recombinant DNA technology (which would lead in 1975 to the Asilomar conference, where scientists, ethicists and journalists pondered the implications of genetic engineering). While Cohen stayed in academia and defended recombinant DNA technology in US congressional hearings, Boyer saw the potential for profit. In South San Francisco in 1976, Boyer and venture-capitalist Robert Swanson set up Genentech, the world's first biotechnology company.

Pioneers at Genentech and their collaborators at the California Institute of Technology were the first to synthesize DNA in the lab. But they wanted to use E. coli as a factory to synthesize mammalian proteins. Proof of principle had been demonstrated earlier by Cohen and his colleagues at Stanford, when they used the bacteria to produce a functioning mouse-cell protein. The Genentech scientists eventually succeeded, producing a human hormone called somatostatin in the bacteria — and so heralded the era of commercial biotechnology. The production of insulin and growth hormone followed soon after.

In the following years, a flood of biotech firms entered the scene. Harvard professor Walter Gilbert and Phillip Sharp at the Massachusetts Institute of Technology, now both Nobel laureates, set up Biogen in Geneva in 1978. Cetus, of Emeryville, California — founded in 1971 as a 'bioengineering company' — made the push towards biotechnology and, within ten years, developed the polymerase chain reaction, which amplifies DNA. Biotech firm Amgen of Thousand Oaks, California, started up in 1980 with less than 50 employees — it now has more than 10,000 worldwide.

SCIENCE AND JUDGEMENT
Gilbert, who is now a biotech start-up specialist, says that those who have survived in the industry made astute predictions. The industry began with a focus on human proteins made in bacteria and on antibodies, he says. It then moved on to immunological treatments for cancer, and small-molecule treatments for disease. In the 1990s came a wave of neurobiology companies, followed by a wave of genomics companies. "The people who made it are the ones who guessed right," he says.

"Partly it was really good biology, but partly it was really good judgment about doing problems that were going to work," says Leroy Hood, founder of the Institute for Systems Biology in Seattle, Washington.

New technologies have fuelled the biotechnology fire. Hood and Applied Biosystems, the company he founded in 1981 in Foster City, California, came up with the automated protein synthesizer, protein sequencer, DNA synthesizer and DNA sequencer. The first three Hood calls "sophisticated plumbing" problems, as they just involved engineering a series of valves to mix the correct quantities of reagents. The last was more sophisticated; it needed the integration of biology, chemistry, engineering and computer science.

Researchers also became more integrated. Many biologists joined the chemists working for big drug companies, and technological needs opened the field up to researchers with skills outside biology.

Such powerful technologies have changed the way biologists do science. 'Big science', once unique to chemistry and physics, has entered biology. Now, researchers no longer have to start their gene search with a hypothesis — with whole genomes at their disposal, they can find a gene by doing a quick database search, and then use those data in a hypothesis-driven manner for some further discovery.

A CYCLICAL INDUSTRY
Although the proliferation of big science and genomic data sparked a revolution, firms that depended too much on the human genome have faltered. Celera of Rockville, Maryland, which sequenced a draft of the human genome, has shed jobs in its effort to become a pharmaceutical company. And DoubleTwist of Oakland, California, which hoped to sell a 'superior' annotation of the human genome, went bankrupt last year.

According to Gilbert, stocks in the industry languished last year — but the industry itself did not. So small companies that are 3–5 years old are having trouble raising money at the exaggerated levels that they managed a few years ago. Gilbert says that promising new companies can still raise money — just in smaller amounts.

As a result, Steve Burrill, chief executive of Burrill & Company, a San Francisco-based biotech venture-capital firm, sees an industry with fewer jobs than in the past year, although some downsizing by older biotechs may have been offset by new start-ups. The demand for pharmacogenomics and bioinformatics expertise continues to grow, he says, along with the companies featuring them — much more than the rest of the industry. Burrill, who sees the industry as cyclical, expects both stock value and job opportunities to rebound within a year or two.

Richard Scheller, vice-president of research at Genentech, says that the company is not feeling much of a pinch, as it has a good number of products on the market. It recently hired ten new staff, and is building a new facility in South San Francisco. But even so, it is not hiring as many people as it did three years ago.

Burrill asserts that much of the restructuring in the drug industry has been good for biotech. Merging companies often shed staff, products and preclinical ideas that firms can pick up. And with pharmaceutical firms now bigger and more marketing-driven than ever, biotech companies remain important engines of innovation.

New technologies, meanwhile, continue to infuse the industry. Nanotechnology and pharmacogenomics, for example, are both areas of potential job growth. Gilbert sees 'lifestyle drugs' such as Viagra as the wave of the future — companies such as Memory Pharmaceuticals in Montvale, New Jersey, are trying to develop drugs that enhance memory and attention. Such prospects seem a far cry from the ideas raised at that Hawaiian deli more than a quarter of a century ago.

IVF links to increased cancer risk


11:01 24 January 03


Children conceived by in vitro fertilization (IVF) may have a greater chance of developing a rare form of childhood eye cancer, according to new Dutch research.

The finding comes soon after work in the US revealed that IVF may be associated with an increased risk of rare birth defects characterised by excessive growth of various tissues.

An increasing number of women are having children via IVF, meaning that any health problems the procedure may lead must be investigated, say doctors.

But the authors of both studies caution that their findings are preliminary and should not scare parents away from undergoing the treatment.


Ovulation-inducing drugs


The eye cancer research was prompted when Dutch doctors diagnosed the disease, called retinoblastoma, in five children within a 15-month period. Normally, one child in 17,000 is expected to develop the disease.

They compared the incidence of the disease in IVF-conceived children with that in the general population. They calculated that the risk in IVF children may be between five and seven times higher, though the disease would still be rare.

Annette Moll, at VU University Medical Centre, led the study, published in The Lancet. She thinks the ovulation-inducing drugs used in IVF treatment could be a possible cause. Other possibilities include a genetic link between infertility and the eye cancer, or a general genetic problem resulting from the egg and sperm being joined in a test tube.

However, it is also possible that there is no link to IVF itself, but that serious disorders are simply diagnosed earlier in IVF children because the receive close medical surveillance.


Suspected association

The second study, published in the January issue of the American Journal of Human Genetics, looked at a national US registry of patients with Beckwith-Wiedemann Syndrome (BWS). Children born with BWS have an increased risk of developing various cancers.

Up to June 2001, four of the 279 BWS patients in the registry were known to have been conceived by IVF. Suspecting an association, the investigators began collecting details about conception methods for new patients entering the registry.

They found that three of the 65 new patients were conceived by IVF. This represents an incidence of 4.6 per cent, nearly six times higher than the 0.8 per cent incidence of assisted births in the general US population. But the researchers caution that, although they did not specifically recruit parents who had used IVF, such parents may have been more likely to participate in the study. And, again, even if their findings are confirmed, BWS would still be very rare even among IVF babies.


Natasha McDowell

Stem cells migrate from bone to brain



Autopsies on four dead women have shown for the first time that stem cells in bone marrow can develop into brain cells, not just blood and bone cells as previously thought.

The discovery suggests new approaches for repairing damaged or diseased brains. Stem cells themselves could be used, or the signalling chemicals that instruct them to become brain cells, although these have yet to be identified.

"I think it's very encouraging to know that there are cells in the human bone marrow that have the capability to reach the brain and become neurons," says Eva Mezey, who led the team that made the discovery at the US National Institute of Neurological Diseases and Stroke in Bethesda, Maryland.

The women whose brains were examined by autopsy had all been treated during their lives with bone marrow transplants from men. This meant that any cells the NINDS team found in the brain containing the male Y chromosome must have come from the donated bone marrow.

The researchers found such cells and not just in isolation, but in clumps. This suggests the bone marrow stem cells multiplied after reaching the brain.


Come here!


Mezey's hunch is that the raw stem cells circulate all the time, until they are summoned to sites of injury. Once there, they are fashioned into tissue that heals the damage.

"There's something that recruits these cells," says Mezey. "There's some factor that says: 'Come in here, we need you'. Then, they receive further orders as to what type of cell to become."

"We must now find out what these signals are," she says. Doctors could potentially accelerate healing by injecting extra signalling molecules into damaged tissue.


Look and learn


Mezey's proposed strategy for finding the important signals would begin by identifying all the receptors on the surfaces of stem cells. This would reveal which signalling substances the cells are equipped to receive. The next step would be to expose stem cells to each substance in turn, and observe the type of cell they develop into.

The NINDS team had already shown that bone marrow cells turn into brain cells in rodents. The new work now shows the same happens in humans.

The findings corroborate experiments by Catherine Verfaillie of the University of Minnesota. These showed that special cells with stem-cell like properties, called "multipotent adult progenitor cells", could be isolated from the bone marrow of mice and humans. In mice, Verfaillie showed they turned into virtually any type of tissue.

Verfaillie's discovery was reported by New Scientist in January 2002 and raised hopes that, for medical purposes, cells from an adult's bone marrow would be as suitable as the more controversial stem cells harvested from embryos.



Andy Coghlan

Ultimate stem cell discovered


19:00 23 January 02


A stem cell has been found in adults that can turn into every single tissue in the body. It might turn out to be the most important cell ever discovered.

Until now, only stem cells from early embryos were thought to have such properties. If the finding is confirmed, it will mean cells from your own body could one day be turned into all sorts of perfectly matched replacement tissues and even organs.

If so, there would be no need to resort to therapeutic cloning - cloning people to get matching stem cells from the resulting embryos. Nor would you have to genetically engineer embryonic stem cells (ESCs) to create a "one cell fits all" line that does not trigger immune rejection. The discovery of such versatile adult stem cells will also fan the debate about whether embryonic stem cell research is justified.

"The work is very exciting," says Ihor Lemischka of Princeton University. "They can differentiate into pretty much everything that an embryonic stem cell can differentiate into."


Remarkable findings


The cells were found in the bone marrow of adults by Catherine Verfaillie at the University of Minnesota. Extraordinary claims require extraordinary proof, and though the team has so far published little, a patent application seen by New Scientist shows the team has carried out extensive experiments.

These confirm that the cells - dubbed multipotent adult progenitor cells, or MAPCs - have the same potential as ESCs. "It's very dramatic, the kinds of observations [Verfaillie] is reporting," says Irving Weissman of Stanford University. "The findings, if reproducible, are remarkable."

At least two other labs claim to have found similar cells in mice, and one biotech company, MorphoGen Pharmaceuticals of San Diego, says it has found them in skin and muscle as well as human bone marrow. But Verfaillie's team appears to be the first to carry out the key experiments needed to back up the claim that these adult stem cells are as versatile as ESCs.

Verfaillie extracted the MAPCs from the bone marrow of mice, rats and humans in a series of stages. Cells that do not carry certain surface markers, or do not grow under certain conditions, are gradually eliminated, leaving a population rich in MAPCs. Verfaillie says her lab has reliably isolated the cells from about 70 per cent of the 100 or so human volunteers who donated marrow samples.


Indefinite growth


The cells seem to grow indefinitely in culture, like ESCs. Some cell lines have been growing for almost two years and have kept their characteristics, with no signs of ageing, she says.

Given the right conditions, MAPCs can turn into a myriad of tissue types: muscle, cartilage, bone, liver and different types of neurons and brain cells. Crucially, using a technique called retroviral marking, Verfaillie has shown that the descendants of a single cell can turn into all these different cell types - a key experiment in proving that MAPCs are truly versatile.

Also, Verfaillie's group has done the tests that are perhaps the gold standard in assessing a cell's plasticity. She placed single MAPCs from mice into very early mouse embryos, when they are just a ball of cells. Analyses of mice born after the experiment reveal that a single MAPC can contribute to all the body's tissues.

MAPCs have many of the properties of ESCs, but they are not identical. Unlike ESCs, for example, they do not seem to form cancerous masses if you inject them into adults. This would obviously be highly desirable if confirmed. "The data looks very good, it's very hard to find any flaws," says Lemischka. But it still has to be independently confirmed by other groups, he adds.


Fundamental questions

Meanwhile, there are some fundamental questions that must be answered, experts say. One is whether MAPCs really form functioning cells.

Stem cells that differentiate may express markers characteristic of many different cell types, says Freda Miller of McGill University. But simply detecting markers for, say, neural tissue does not prove that a stem cell really has become a working neuron.

Verfaillie's findings also raise questions about the nature of stem cells. Her team thinks that MAPCs are rare cells present in the bone marrow that can be fished out through a series of enriching steps. But others think the selection process actually creates the MAPCs.

"I don't think there is 'a cell' that is lurking there that can do this. I think that Catherine has found a way to produce a cell that can behave this way," says Neil Theise of New York University Medical School.


Sylvia Pagán Westphal, Boston

Shorter telomeres mean shorter life



Old people can expect to die sooner if they have shorter telomeres, pieces of DNA that protect the ends of chromosomes.

Researchers have long suspected that telomeres act as molecular clocks governing the process of ageing in cells, but until now nobody has proven the link.

"There has been a lot of hot air and prediction based on animal models. This really is the first time that facts have replaced that," says Catherine Blackburn of the University of California, San Francisco, discoverer of the telomere-building enzyme telomerase. But she cautions that the new research does not necessarily imply that shortened telomeres cause early death.

Some cloned mammals, such as the sheep Dolly, have shorter telomeres than other animals of the same age, leading some scientists to speculate that they will have shorter lifespans.


Unravelled shoelaces


Geneticist Richard Cawthon and colleagues at the University of Utah measured the telomeres in a randomly-chosen group of 150 patients aged 60 or over. Those with shorter telomeres were eight times as likely to die from an infectious disease and three times more likely to suffer a fatal heart attack.

A telomere is a repeated sequence of five bases that preserve the integrity of genes during DNA replication, rather like the glue that prevents the ends of shoelaces unravelling.

Its length at birth varies from person to person. But each time cells replicate, daughter cells have slightly shorter telomeres than their parents. Over time, after many replications, a DNA strand's sealant erodes.

In healthy people, telomeres do not shrink significantly until old age because the enzyme telomerase ensures regeneration. But eventually telomeres get so short that the DNA strands either stop replicating or, worse still, start fusing together, often encouraging tumours to grow.


Slow response


White blood cells' rely on their ability to replicate quickly to mount attacks on infections. Retarded replication caused by shorter telomeres might explain why those patients were much more likely to die of an infectious disease, says Cawthon.

He admits that it is not clear whether short telomeres actually cause age-related diseases and death or whether they are just a symptom of some other process responsible for aging. Either way, there are other forces at work - earth worms and fruit flies get old long before their telomeres shrink significantly.

Inducing telomere growth by somehow injecting telomerase might seem like a potential way to extend life. But this would risk causing cells to replicate uncontrollably, leading to cancer.

In fact, Titia De Lange, a telomere expert at Rockefeller University, New York, believes the correlation between telomere shrinkage and old age has evolved to retard cell replication. This would provide a "tumour suppressor pathway" in the older cells most likely to turn cancerous.




Celeste Biever, Boston