Medical marvels
Drugs treat symptoms. Stem cells can cure you. One day soon, they may even stop us ageing.
Thomas B Okarma sat in his office in the San Francisco Bay area three days after the inauguration of President Barack Obama and announced a new dawn. In a global teleconference, the chief executive of Geron Corporation told the world it was on the cusp of a revolution in medical science that "will enable living cells to become tomorrow's pills". He foresaw stem cell therapies being manufactured, bottled and stacked in hospital freezers.
Geron had just won permission from the US regulator to inject embryonic stem cells into the damaged spines of people suffering total paralysis from the chest down. It was, he said, "an extraordinarily exciting event" that "marks the dawn of a new era in medical therapeutics".
Nobody thinks that these patients will pick up their blankets and walk, but trials in animals have been impressive. Paralysed rats have regained some use of their hind legs. And while the first-ever human study will involve just eight or 10 patients and focus on safety - not on whether it works - there is no doubt that yet another massive milestone on the road to stem cell or regenerative medicine has been passed.
"This places Geron at the forefront of the medical revolution," said Okarma. He was not talking about expensive, individually tailored one-off treatments, but about the mass production of stem cell therapies that would heal wounds and repair damaged organs and tissues, treat strokes, diabetes, heart disease and blindness. These would be, he said, products frozen in a vial in a hospital pharmacy ready for off-the-shelf use - just like a pill.
Ask how far away that day is, and most scientists will demur, urge caution and talk about decades. Okarma is a doctor, but he is also CEO of a Nasdaq-listed biotech company. Things, though, are undoubtedly moving fast and are set to speed up if President Obama, as is widely expected, lifts the Bush ban on federal funding for embryonic stem cell research. Geron won the race for permission to carry out the first human trial using embryonic stem cells, but not by much. Hot on Okarma's heels is Professor Pete Coffey at the London Project to Cure Blindness, who is knocking on the doors of the British and European regulatory authorities, looking for permission to trial embryonic stem cells to save the sight of people with age-related macular degeneration, the most common cause of sight loss. And across the Channel, Philippe Menasché in Paris may be the first to use embryonic stem cells in people with heart failure.
Controversy over embryonic stem cells was predictable from the moment that Louise Brown, the first baby created through in-vitro fertilisation, was born in 1978. The IVF technique meant that embryos could exist outside the womb. Inevitably more embryos are created than are needed, and many couples are willing to donate the surplus to science if they understand that the research could lead to cures for killer diseases.
These embryos are allowed to develop for only a few days, to the stage known as "blastocyst", when they are a ball of cells the size of a full stop. At that point, the crucial stem cells can be removed and kept in a culture, where they multiply prolifically without differentiating (turning into cells with a specific function, be it in the blood, the leg or the eye). Scientists can then trick them into becoming the specific cells they need, before injecting or inserting them into the right bit of the body.
Inevitably, there are many people, most of them with religious beliefs, who believe this is experimentation on an unborn child. While the UK has broadly accepted embryonic stem cell research, with strict regulation, President Bush in 2001 refused federal funding on any except some 60 existing stem cell lines.
But stem cells are not only found in embryos. Recently there have also been some striking developments using adult stem cells, the sort we all have in our bone marrow, which are still capable of becoming certain sorts of blood and tissue. In November it was revealed that Claudia Castillo, a 30-year-old mother of two whose lungs were so damaged by tuberculosis that she could hardly climb stairs, now goes dancing following a pioneering operation in Barcelona to transplant a section of her windpipe, made out of her own stem cells.
Castillo's operation involved the removal of stem cells from the bone marrow in her hip, which were engineered to turn into cartilage and then seeded on to a piece of donated windpipe. Because her body recognised the organ as her own, she was spared a lifetime of drugs to suppress the immune system.
Spectacular as it was, this cost a small fortune. Doctors and scientists from world-class centres in Spain, the UK and Italy took part with all the enthusiasm and disregard of expense that goes with proving a point in cutting-edge science. Afterwards, Professor Anthony Hollander of Bristol University, and one of the scientists involved, reflected, as well he might, that "the trick is to develop ways of scaling up".
Stem cell science is beginning to move from the lab into the hospital, and with remarkable results, but one of the big questions that exercises more pragmatic scientists is whether it can be affordable for most of us. The occasional tour de force, such as Castillo's return to the dancefloor, shows what is possible but will change outcomes for only a lucky few.
"Are we investing a lot of money in something that in the end could only be used by an elite group in society?" asks Austin Smith, Medical Research Council professor of stem cell biology at Edinburgh University. "That's a concern. It would be very frustrating for us if, at the end of all of that, it is not really taken up."
But, he says, he could see situations where society simply would not be able to say no. "If there really was a cure for muscular dystrophy, or for diabetes - which I think is the one for which we are most likely to see a cell therapy - almost whatever the cost, society will have to find a way of providing it and it won't be acceptable if it is only for rich people. But how that will be achieved is difficult to see at the moment."
No other breakthrough would have quite the impact in the public mind as that of healing spinal injury, not least because of the tragic case of Christopher Reeve, the actor best known for playing Superman, who was paralysed after falling from a horse and devoted all his money and the rest of his life to urging scientists on and who opposed the Bush funding ban. "No obstacle should stand in the way of responsible investigation of their [stem cells] possibilities," he wrote shortly before his death in 2004.
But it is likely that the first embryonic stem cell therapy to become widely available will come from Britain, and will change the lives of grandparents by turning back the clock and enabling those who were going blind to see. The work being done by Coffey, who is based at the University College London Institute of Ophthalmology, has the beauty of simplicity. Age-related macular degeneration (AMD) is caused by the deterioration of retinal pigment epithelial (RPE) cells at the back of the eye. These cells form a layer that processes light, and do not need to be linked in to the nervous system and the brain. "We're not having to reconnect cells to a neural network," says Coffey. "This is a carpet of cells." He and his team have done it very successfully in animals, he says. They have persuaded embryonic stem cells to turn into RPE cells and in effect laid a new carpet.
"We're now manufacturing the cells to clinical standard so we can go into trials in 2010/11," he says, adding with enthusiasm that it is do-able because they need relatively few. "We only need 40,000 cells. It sounds an awful lot but if you think of a computer mouse," he says, looking around the room for something the right size, "if you grew the cells in it you could provide easily enough for 100,000 patients. The scale-up is relatively simple."
Coffey thinks this therapy has a good chance of success. A quarter of pensioners will hope he is right. That's how many over-65s get AMD. And while there is a new (very expensive) drug called Lucentis for one form of the disease, it is not a cure. AMD is, as he says, "a huge problem".
But funding has not been easy. Coffey was kept afloat by the UK's Macular Disease Society, which gave him £50,000 at a tricky point. Otherwise the money has come from philanthropic donors in the US, of whom Bush's ban made sure there was no shortage.
Interestingly, if it proves to be a cure for macular degeneration, this therapy is likely to be affordable. Not only that, it will save the NHS a lot of money. The costs of surgery, Coffey reckons, will be about £4,000-£5,000, but the patch of cells itself could cost as little as £250. Lucentis costs £800 to £1,500 for each injection every four to six weeks. "But this is a cure - not like Lucentis," says Coffey. That's the argument that has at last caused the big pharma companies to sit up and take notice. For years they steered clear of biotechnology. Living tissue was of far less interest to them than chemical compounds that patients would take for years. But a new reality is dawning. Stem cell therapies could drive their drugs off the market.
"We are changing the paradigm," says Professor Chris Mason of University College London, who is on the steering committee of the UK National Stem Cell Network which co-ordinates research. "Until now, pharmaceutical companies did wonder drugs that treated symptoms. What we really want is a cure."
So instead of drugs for life following heart failure, we could have stem cell therapies that repair the tissue so that drugs are not needed. Instead of drugs for Parkinson's, we could have neural cells dropped into the brain. Instead of insulin for diabetes, we could replace the malfunctioning pancreatic beta islet cells that are supposed to produce the insulin with new ones. This is why scientists now prefer the term regenerative medicine to stem cell therapy. The aim is to regenerate organs and tissues that have stopped working properly.
The writing is on the wall. "Big pharma has woken up to the fact that here is something that could displace the therapies they have got," says Mason. "If beta islet cells work, it would wipe out the market for insulin overnight." What they have also realised, he says, is that although you don't have patients on drugs for life, you can charge more for a cure than for a drug to treat symptoms.
One of the most significant recent developments is the interest from multinationals such as Pfizer, which announced before Christmas that it was investing $100m in regenerative medicine, setting up one business in Cambridge, UK, and another in Cambridge, Massachusetts. This takes regenerative medicine out of the realms of the theoretical. Where big pharma goes, products end up on the market.
Where is this all heading? Regenerating the eyes of the elderly, the spinal cords of the paralysed and the insulin-producing cells of the diabetic is undoubtedly wonderful medicine. But you can't help wondering whether there is a point at which regeneration would stop. Will we be able one day - in centuries to come - be able to replace any ageing tissue? At the very least, regenerative medicine offers the prospect of a far longer life. Immortality - should we want it - may take a little longer.
Know your stem cells
Embryonic stem cells
These come from surplus embryos created during fertility treatment. At four or five days old, the embryo is a ball of cells called a blastocyst, from which around 30 stem cells can be removed. These grow and divide under special conditions to stop them differentiating to become specific body tissues. By six months they have produced millions of embryonic stem cells.
Adult stem cells
There are stem cells in our bone marrow, brain, babies' cord blood, skin and liver - but few of them. They sit quietly until an injury, and then divide to become tissue to repair that part of the body. But some adult stem cells are more versatile. There are two sorts in bone marrow; one type can become blood cells and the other can become bone, fat, cartilage and connective tissue.
Induced pluripotent stem cells
Scientists are very excited by these, created by re-programming ordinary skin cells - basically, turning back the clock through genetic modification until the skin cell is restored to its original stem cell state. It was first done in late 2007, so much more needs to be done before they could safely be used in humans. The advantage is that people could be treated with their own cells and embryos are not involved; the disadvantage is that such therapies would have to be tailor-made and would therefore be more expensive.
The next targets for treatment
Strokes
British company ReNeuron has regulatory approval to start human trials this year using stem cells derived from those normally found in the brain. They will be injected into the brains of disabled people in a one-year trial of 12 patients, to test primarily for safety.
Diabetes
San Diego company Novocell has made pancreatic beta islet cells from embryonic stem cells, and are now in late animal studies. This treatment could mean diabetics no longer needed to inject insulin.
Crohn's disease
US company Osiris is in human trials using stem cells from bone marrow. The stem cells appear to combat inflammation in the gut, which is responsible for the disease.
Cornea transplants
People suffering from eye burns are being given adult stem cells from donated eyes. The cells repair the damage. Around 500 people have benefited so far.
Sarah Boseley
The Guardian, Friday 30 January 2009
guardian.co.uk © Guardian News and Media Limited 2009
Drugs treat symptoms. Stem cells can cure you. One day soon, they may even stop us ageing.
Thomas B Okarma sat in his office in the San Francisco Bay area three days after the inauguration of President Barack Obama and announced a new dawn. In a global teleconference, the chief executive of Geron Corporation told the world it was on the cusp of a revolution in medical science that "will enable living cells to become tomorrow's pills". He foresaw stem cell therapies being manufactured, bottled and stacked in hospital freezers.
Geron had just won permission from the US regulator to inject embryonic stem cells into the damaged spines of people suffering total paralysis from the chest down. It was, he said, "an extraordinarily exciting event" that "marks the dawn of a new era in medical therapeutics".
Nobody thinks that these patients will pick up their blankets and walk, but trials in animals have been impressive. Paralysed rats have regained some use of their hind legs. And while the first-ever human study will involve just eight or 10 patients and focus on safety - not on whether it works - there is no doubt that yet another massive milestone on the road to stem cell or regenerative medicine has been passed.
"This places Geron at the forefront of the medical revolution," said Okarma. He was not talking about expensive, individually tailored one-off treatments, but about the mass production of stem cell therapies that would heal wounds and repair damaged organs and tissues, treat strokes, diabetes, heart disease and blindness. These would be, he said, products frozen in a vial in a hospital pharmacy ready for off-the-shelf use - just like a pill.
Ask how far away that day is, and most scientists will demur, urge caution and talk about decades. Okarma is a doctor, but he is also CEO of a Nasdaq-listed biotech company. Things, though, are undoubtedly moving fast and are set to speed up if President Obama, as is widely expected, lifts the Bush ban on federal funding for embryonic stem cell research. Geron won the race for permission to carry out the first human trial using embryonic stem cells, but not by much. Hot on Okarma's heels is Professor Pete Coffey at the London Project to Cure Blindness, who is knocking on the doors of the British and European regulatory authorities, looking for permission to trial embryonic stem cells to save the sight of people with age-related macular degeneration, the most common cause of sight loss. And across the Channel, Philippe Menasché in Paris may be the first to use embryonic stem cells in people with heart failure.
Controversy over embryonic stem cells was predictable from the moment that Louise Brown, the first baby created through in-vitro fertilisation, was born in 1978. The IVF technique meant that embryos could exist outside the womb. Inevitably more embryos are created than are needed, and many couples are willing to donate the surplus to science if they understand that the research could lead to cures for killer diseases.
These embryos are allowed to develop for only a few days, to the stage known as "blastocyst", when they are a ball of cells the size of a full stop. At that point, the crucial stem cells can be removed and kept in a culture, where they multiply prolifically without differentiating (turning into cells with a specific function, be it in the blood, the leg or the eye). Scientists can then trick them into becoming the specific cells they need, before injecting or inserting them into the right bit of the body.
Inevitably, there are many people, most of them with religious beliefs, who believe this is experimentation on an unborn child. While the UK has broadly accepted embryonic stem cell research, with strict regulation, President Bush in 2001 refused federal funding on any except some 60 existing stem cell lines.
But stem cells are not only found in embryos. Recently there have also been some striking developments using adult stem cells, the sort we all have in our bone marrow, which are still capable of becoming certain sorts of blood and tissue. In November it was revealed that Claudia Castillo, a 30-year-old mother of two whose lungs were so damaged by tuberculosis that she could hardly climb stairs, now goes dancing following a pioneering operation in Barcelona to transplant a section of her windpipe, made out of her own stem cells.
Castillo's operation involved the removal of stem cells from the bone marrow in her hip, which were engineered to turn into cartilage and then seeded on to a piece of donated windpipe. Because her body recognised the organ as her own, she was spared a lifetime of drugs to suppress the immune system.
Spectacular as it was, this cost a small fortune. Doctors and scientists from world-class centres in Spain, the UK and Italy took part with all the enthusiasm and disregard of expense that goes with proving a point in cutting-edge science. Afterwards, Professor Anthony Hollander of Bristol University, and one of the scientists involved, reflected, as well he might, that "the trick is to develop ways of scaling up".
Stem cell science is beginning to move from the lab into the hospital, and with remarkable results, but one of the big questions that exercises more pragmatic scientists is whether it can be affordable for most of us. The occasional tour de force, such as Castillo's return to the dancefloor, shows what is possible but will change outcomes for only a lucky few.
"Are we investing a lot of money in something that in the end could only be used by an elite group in society?" asks Austin Smith, Medical Research Council professor of stem cell biology at Edinburgh University. "That's a concern. It would be very frustrating for us if, at the end of all of that, it is not really taken up."
But, he says, he could see situations where society simply would not be able to say no. "If there really was a cure for muscular dystrophy, or for diabetes - which I think is the one for which we are most likely to see a cell therapy - almost whatever the cost, society will have to find a way of providing it and it won't be acceptable if it is only for rich people. But how that will be achieved is difficult to see at the moment."
No other breakthrough would have quite the impact in the public mind as that of healing spinal injury, not least because of the tragic case of Christopher Reeve, the actor best known for playing Superman, who was paralysed after falling from a horse and devoted all his money and the rest of his life to urging scientists on and who opposed the Bush funding ban. "No obstacle should stand in the way of responsible investigation of their [stem cells] possibilities," he wrote shortly before his death in 2004.
But it is likely that the first embryonic stem cell therapy to become widely available will come from Britain, and will change the lives of grandparents by turning back the clock and enabling those who were going blind to see. The work being done by Coffey, who is based at the University College London Institute of Ophthalmology, has the beauty of simplicity. Age-related macular degeneration (AMD) is caused by the deterioration of retinal pigment epithelial (RPE) cells at the back of the eye. These cells form a layer that processes light, and do not need to be linked in to the nervous system and the brain. "We're not having to reconnect cells to a neural network," says Coffey. "This is a carpet of cells." He and his team have done it very successfully in animals, he says. They have persuaded embryonic stem cells to turn into RPE cells and in effect laid a new carpet.
"We're now manufacturing the cells to clinical standard so we can go into trials in 2010/11," he says, adding with enthusiasm that it is do-able because they need relatively few. "We only need 40,000 cells. It sounds an awful lot but if you think of a computer mouse," he says, looking around the room for something the right size, "if you grew the cells in it you could provide easily enough for 100,000 patients. The scale-up is relatively simple."
Coffey thinks this therapy has a good chance of success. A quarter of pensioners will hope he is right. That's how many over-65s get AMD. And while there is a new (very expensive) drug called Lucentis for one form of the disease, it is not a cure. AMD is, as he says, "a huge problem".
But funding has not been easy. Coffey was kept afloat by the UK's Macular Disease Society, which gave him £50,000 at a tricky point. Otherwise the money has come from philanthropic donors in the US, of whom Bush's ban made sure there was no shortage.
Interestingly, if it proves to be a cure for macular degeneration, this therapy is likely to be affordable. Not only that, it will save the NHS a lot of money. The costs of surgery, Coffey reckons, will be about £4,000-£5,000, but the patch of cells itself could cost as little as £250. Lucentis costs £800 to £1,500 for each injection every four to six weeks. "But this is a cure - not like Lucentis," says Coffey. That's the argument that has at last caused the big pharma companies to sit up and take notice. For years they steered clear of biotechnology. Living tissue was of far less interest to them than chemical compounds that patients would take for years. But a new reality is dawning. Stem cell therapies could drive their drugs off the market.
"We are changing the paradigm," says Professor Chris Mason of University College London, who is on the steering committee of the UK National Stem Cell Network which co-ordinates research. "Until now, pharmaceutical companies did wonder drugs that treated symptoms. What we really want is a cure."
So instead of drugs for life following heart failure, we could have stem cell therapies that repair the tissue so that drugs are not needed. Instead of drugs for Parkinson's, we could have neural cells dropped into the brain. Instead of insulin for diabetes, we could replace the malfunctioning pancreatic beta islet cells that are supposed to produce the insulin with new ones. This is why scientists now prefer the term regenerative medicine to stem cell therapy. The aim is to regenerate organs and tissues that have stopped working properly.
The writing is on the wall. "Big pharma has woken up to the fact that here is something that could displace the therapies they have got," says Mason. "If beta islet cells work, it would wipe out the market for insulin overnight." What they have also realised, he says, is that although you don't have patients on drugs for life, you can charge more for a cure than for a drug to treat symptoms.
One of the most significant recent developments is the interest from multinationals such as Pfizer, which announced before Christmas that it was investing $100m in regenerative medicine, setting up one business in Cambridge, UK, and another in Cambridge, Massachusetts. This takes regenerative medicine out of the realms of the theoretical. Where big pharma goes, products end up on the market.
Where is this all heading? Regenerating the eyes of the elderly, the spinal cords of the paralysed and the insulin-producing cells of the diabetic is undoubtedly wonderful medicine. But you can't help wondering whether there is a point at which regeneration would stop. Will we be able one day - in centuries to come - be able to replace any ageing tissue? At the very least, regenerative medicine offers the prospect of a far longer life. Immortality - should we want it - may take a little longer.
Know your stem cells
Embryonic stem cells
These come from surplus embryos created during fertility treatment. At four or five days old, the embryo is a ball of cells called a blastocyst, from which around 30 stem cells can be removed. These grow and divide under special conditions to stop them differentiating to become specific body tissues. By six months they have produced millions of embryonic stem cells.
Adult stem cells
There are stem cells in our bone marrow, brain, babies' cord blood, skin and liver - but few of them. They sit quietly until an injury, and then divide to become tissue to repair that part of the body. But some adult stem cells are more versatile. There are two sorts in bone marrow; one type can become blood cells and the other can become bone, fat, cartilage and connective tissue.
Induced pluripotent stem cells
Scientists are very excited by these, created by re-programming ordinary skin cells - basically, turning back the clock through genetic modification until the skin cell is restored to its original stem cell state. It was first done in late 2007, so much more needs to be done before they could safely be used in humans. The advantage is that people could be treated with their own cells and embryos are not involved; the disadvantage is that such therapies would have to be tailor-made and would therefore be more expensive.
The next targets for treatment
Strokes
British company ReNeuron has regulatory approval to start human trials this year using stem cells derived from those normally found in the brain. They will be injected into the brains of disabled people in a one-year trial of 12 patients, to test primarily for safety.
Diabetes
San Diego company Novocell has made pancreatic beta islet cells from embryonic stem cells, and are now in late animal studies. This treatment could mean diabetics no longer needed to inject insulin.
Crohn's disease
US company Osiris is in human trials using stem cells from bone marrow. The stem cells appear to combat inflammation in the gut, which is responsible for the disease.
Cornea transplants
People suffering from eye burns are being given adult stem cells from donated eyes. The cells repair the damage. Around 500 people have benefited so far.
Sarah Boseley
The Guardian, Friday 30 January 2009
guardian.co.uk © Guardian News and Media Limited 2009
