- Email: [email protected]
4 Breast cancer
3 Condition:
Schizophrenia
Microbe:
Toxoplasma gondii (also called toxo) usually linked only with miscarriage
How you catch it:
From eating undercooked meat or from cat faeces
Medical implications:
Drugs to treat toxo in development
4
Schizophrenia Cat lovers, take note: a parasite that lurks in cat faeces could be linked with schizophrenia. Toxoplasma gondii (often called toxo) is estimated to infect around 30 per cent of the population. While it can trigger miscarriage, in most people it was thought to cause little more than a headache and sore throat. Over the past few years, however, evidence has emerged that toxo can have some rather sinister effects on our behaviour: some people infected with the parasite have odd symptoms, such as hallucinations and a tendency to take more risks. This isn’t as crazy as it sounds. In rodents, toxo’s natural hosts, the parasite gets into the brain and makes the animals less fearful, resulting in them taking more risks. This makes them more likely to be eaten by cats, thus completing the parasite’s life cycle. Toxo cysts have been found in the brains of people, too. In a 2007 meta-analysis of 42 studies, psychiatrist Fuller Torrey at the Stanley Medical Research Institute in Chevy Chase, Maryland, found that people with schizophrenia are nearly three times as likely to have antibodies to toxo compared with those who don’t have the condition. Torrey also found that people taking schizophrenia medication have lower levels of antibodies than those not taking such drugs. He suggests that the
”The toxo parasite could be making dopamine to directly manipulate its host’s nervous system”
Breast cancer
Condition:
Breast cancer
Microbe:
Mouse mammary tumour virus, a retrovirus
How you catch it:
Probably from mice
Medical implications:
A vaccine could one day be developed
48 | NewScientist | 17 October 2009
drugs may reduce symptoms in part by harming the parasite. They are known to do so in the test-tube. Torrey and others suspect that toxo affects the brain by somehow raising levels of the chemical signalling molecule dopamine. Excess dopamine has long been linked to schizophrenia, and it is also thought to increase risky behaviour. Earlier this year, a team led by geneticist Glenn McConkey at the University of Leeds in the UK discovered what may prove to be the smoking gun. The group found that the parasite has two genes that encode an enzyme that makes dopamine, which is normally only present in animals that have a nervous system (PLoS ONE, DOI: 10.1371/journal.pone.0004801). While it may have other functions, the parasite could be manufacturing dopamine to directly manipulate its host’s nervous system, the team say. “This is a very important breakthrough,” says Joanne Webster, an epidemiologist at Imperial College London, who has long studied toxo. Various groups are now trying to develop new schizophrenia drugs that work by eradicating the parasite. Existing medicines are of limited help against schizophrenia and can have nasty side effects, such as weight gain and facial spasms.
Why some women get breast cancer and others escape it is still a mystery – genes are to blame for only about 1 in 10 cases. Maybe the answer lies with the mouse mammary tumour virus (MMTV), which causes mammary cancer in mice. MMTV was first discovered in the 1930s, and the link to human cancers has been studied on and off ever since. In 1995, Beatriz Pogo, a cancer specialist at the Mount Sinai School of Medicine in New York, sparked enormous interest when she discovered part of a gene for MMTV in 38 per cent of human breast tumours. The sequence is rarely found in healthy tissue (New Scientist, 2 June
2007, p 38). This has been supported by Brian Salmons, a virologist at the University of Veterinary Medicine in Vienna, Austria, and his colleagues, who have shown that the virus can infect human breast cells in the lab (Retrovirology, DOI: 10.1186/17424690, vol 4, p 73). Like HIV, MMTV is a retrovirus, which means that it inserts itself into the host’s DNA. Other retroviruses cause cancer because their insertion disrupts genes that control cell division, so MMTV could do the same. Another theory, from microbiologist Susan Ross at the University of Pennsylvania in Philadelphia, is that an MMTV protein called env directly
5
Obsessivecompulsive disorder
Obsessive-compulsive disorder is a mental illness that involves repetitive, ritualistic behaviour. Some of those with the condition wash their hands every few minutes, frantically trying to rid themselves of germs, while others become locked in cycles of obsessively checking they have turned off the stove. Various causes have been proposed, ranging from genes to traumatic childhoods. More recently, interest has focused on a part of the brain called the basal ganglia, thought to be involved in decision making. Cases of OCD have arisen after injury to this area, for example, after a stroke or blow to the head. A small subset of cases, however, may have an infectious origin. In the 1990s, Susan Swedo, a neuroscientist at the US National Institutes of Health in Bethesda, Maryland, noted that a few children newly diagnosed with OCD had recently been infected by streptococcus bacterium, the
Condition:
Obsessive-compulsive disorder
Microbe:
Streptococcus bacteria, which normally cause sore throats
How you catch it:
Contact with the eyes, nose and mouth
Medical implications:
Antibiotics being investigated as a treatment, and various other strategies to dampen immune response
causes the cells to multiply. In mice, MMTV is spread through breast milk, but there is no such link between breast cancer and breastfeeding in women. Instead, it seems likely that MMTV hops straight from mice to humans. As Salmons points out: “Humans live in close contact with mice and processed food can contain mouse-derived material such as faeces and even body parts.” Creating an MMTV vaccine might be easier than making one against HIV, Salmons notes, because MMTV has a lower mutation rate and it doesn’t target our immune cells, as HIV does.
cause of many a sore throat. Streptococcus was already known to cause other autoimmune diseases, such as rheumatic fever, in which molecules involved in the immune attack against the microbe cross-react with molecules from the human host. Swedo speculated that in this case the human molecules involved are in the basal ganglia or other circuits of the brain involved in OCD. Swedo’s group coined the term PANDAS, for paediatric autoimmune neuropsychiatric disorders associated with streptococcus infections, to describe the condition. Some small studies have found that children with suspected PANDAS have antibodies in their blood to certain proteins found in the brain, although other researchers have not found such antibodies. There have also been a few suspected cases in adults. The bacterial connection with OCD is still being debated, and a recent large study in Neurology found no link. But Swedo and others are already using it as a basis for new treatments aimed at people who do not respond to the standard treatment of therapy and antidepressants. Several techniques to rein in the autoimmune attack have been trialled so far, including filtering antibodies out of the blood, and antibiotics to prevent repeated streptococcus infections. A few small studies have shown success but other trials have not, and the approach remains controversial.
Condition:
Prostate cancer
Microbe:
Xenotropic murine leukaemia virus, a retrovirus that causes cancer in mice
How you catch it:
Probably from other people but no one knows exactly how
Medical implications:
Better ways to screen for prostate cancer, especially more aggressive forms
6
Prostate cancer The link between prostate cancer and an infection is perhaps the weakest of all those here, but if confirmed it could lead to better screening techniques. The existing screening method – testing men’s blood for prostatespecific antigen (PSA) – is notoriously unreliable, so some men undergo unnecessary surgery that can cause impotence and incontinence. In 2006, a team led by Joseph DeRisi, a biochemist at the Howard Hughes Medical Institute in San Francisco, examined prostate cancers for viruses and found that a few of the samples contained a new virus closely related to xenotropic murine leukaemia virus (XMRV), which is known to cause cancer in mice. At this stage few were convinced of the link as the virus was not found in the cancerous cells themselves but in the surrounding tissue. “The results were inconclusive,” says Greg Towers, a virologist at University College London. The case against XMRV has just been bolstered, however, by a study published last month by pathologist Ila Singh at the University of Utah in Salt Lake City . Her team found XMRV in prostate cancer cells themselves – in 29 per cent of cancerous cells compared with 6 per cent of healthy ones. And the more aggressive the tumour, the more likely they were to find the virus lurking within it (Proceedings of the National Academy of Sciences, vol 106 p 16351). Both groups believe that while the virus probably originated in a mouse, it can now spread from person to person, though there are no clues yet as to how. Nor is it clear how the virus causes cancer, although other retroviruses are known to do so by inserting themselves into the host cell’s DNA and disrupting the genes that normally control cell division. Singh now plans to develop a blood test for XMRV, which could be used as an adjunct to PSA testing, or perhaps even to identify fastgrowing prostate cancers. ■ Priya Shetty is a science journalist based in New York
17 October 2009 | NewScientist | 49
Schizophrenia
Microbe:
Toxoplasma gondii (also called toxo) usually linked only with miscarriage
How you catch it:
From eating undercooked meat or from cat faeces
Medical implications:
Drugs to treat toxo in development
4
Schizophrenia Cat lovers, take note: a parasite that lurks in cat faeces could be linked with schizophrenia. Toxoplasma gondii (often called toxo) is estimated to infect around 30 per cent of the population. While it can trigger miscarriage, in most people it was thought to cause little more than a headache and sore throat. Over the past few years, however, evidence has emerged that toxo can have some rather sinister effects on our behaviour: some people infected with the parasite have odd symptoms, such as hallucinations and a tendency to take more risks. This isn’t as crazy as it sounds. In rodents, toxo’s natural hosts, the parasite gets into the brain and makes the animals less fearful, resulting in them taking more risks. This makes them more likely to be eaten by cats, thus completing the parasite’s life cycle. Toxo cysts have been found in the brains of people, too. In a 2007 meta-analysis of 42 studies, psychiatrist Fuller Torrey at the Stanley Medical Research Institute in Chevy Chase, Maryland, found that people with schizophrenia are nearly three times as likely to have antibodies to toxo compared with those who don’t have the condition. Torrey also found that people taking schizophrenia medication have lower levels of antibodies than those not taking such drugs. He suggests that the
”The toxo parasite could be making dopamine to directly manipulate its host’s nervous system”
Breast cancer
Condition:
Breast cancer
Microbe:
Mouse mammary tumour virus, a retrovirus
How you catch it:
Probably from mice
Medical implications:
A vaccine could one day be developed
48 | NewScientist | 17 October 2009
drugs may reduce symptoms in part by harming the parasite. They are known to do so in the test-tube. Torrey and others suspect that toxo affects the brain by somehow raising levels of the chemical signalling molecule dopamine. Excess dopamine has long been linked to schizophrenia, and it is also thought to increase risky behaviour. Earlier this year, a team led by geneticist Glenn McConkey at the University of Leeds in the UK discovered what may prove to be the smoking gun. The group found that the parasite has two genes that encode an enzyme that makes dopamine, which is normally only present in animals that have a nervous system (PLoS ONE, DOI: 10.1371/journal.pone.0004801). While it may have other functions, the parasite could be manufacturing dopamine to directly manipulate its host’s nervous system, the team say. “This is a very important breakthrough,” says Joanne Webster, an epidemiologist at Imperial College London, who has long studied toxo. Various groups are now trying to develop new schizophrenia drugs that work by eradicating the parasite. Existing medicines are of limited help against schizophrenia and can have nasty side effects, such as weight gain and facial spasms.
Why some women get breast cancer and others escape it is still a mystery – genes are to blame for only about 1 in 10 cases. Maybe the answer lies with the mouse mammary tumour virus (MMTV), which causes mammary cancer in mice. MMTV was first discovered in the 1930s, and the link to human cancers has been studied on and off ever since. In 1995, Beatriz Pogo, a cancer specialist at the Mount Sinai School of Medicine in New York, sparked enormous interest when she discovered part of a gene for MMTV in 38 per cent of human breast tumours. The sequence is rarely found in healthy tissue (New Scientist, 2 June
2007, p 38). This has been supported by Brian Salmons, a virologist at the University of Veterinary Medicine in Vienna, Austria, and his colleagues, who have shown that the virus can infect human breast cells in the lab (Retrovirology, DOI: 10.1186/17424690, vol 4, p 73). Like HIV, MMTV is a retrovirus, which means that it inserts itself into the host’s DNA. Other retroviruses cause cancer because their insertion disrupts genes that control cell division, so MMTV could do the same. Another theory, from microbiologist Susan Ross at the University of Pennsylvania in Philadelphia, is that an MMTV protein called env directly
5
Obsessivecompulsive disorder
Obsessive-compulsive disorder is a mental illness that involves repetitive, ritualistic behaviour. Some of those with the condition wash their hands every few minutes, frantically trying to rid themselves of germs, while others become locked in cycles of obsessively checking they have turned off the stove. Various causes have been proposed, ranging from genes to traumatic childhoods. More recently, interest has focused on a part of the brain called the basal ganglia, thought to be involved in decision making. Cases of OCD have arisen after injury to this area, for example, after a stroke or blow to the head. A small subset of cases, however, may have an infectious origin. In the 1990s, Susan Swedo, a neuroscientist at the US National Institutes of Health in Bethesda, Maryland, noted that a few children newly diagnosed with OCD had recently been infected by streptococcus bacterium, the
Condition:
Obsessive-compulsive disorder
Microbe:
Streptococcus bacteria, which normally cause sore throats
How you catch it:
Contact with the eyes, nose and mouth
Medical implications:
Antibiotics being investigated as a treatment, and various other strategies to dampen immune response
causes the cells to multiply. In mice, MMTV is spread through breast milk, but there is no such link between breast cancer and breastfeeding in women. Instead, it seems likely that MMTV hops straight from mice to humans. As Salmons points out: “Humans live in close contact with mice and processed food can contain mouse-derived material such as faeces and even body parts.” Creating an MMTV vaccine might be easier than making one against HIV, Salmons notes, because MMTV has a lower mutation rate and it doesn’t target our immune cells, as HIV does.
cause of many a sore throat. Streptococcus was already known to cause other autoimmune diseases, such as rheumatic fever, in which molecules involved in the immune attack against the microbe cross-react with molecules from the human host. Swedo speculated that in this case the human molecules involved are in the basal ganglia or other circuits of the brain involved in OCD. Swedo’s group coined the term PANDAS, for paediatric autoimmune neuropsychiatric disorders associated with streptococcus infections, to describe the condition. Some small studies have found that children with suspected PANDAS have antibodies in their blood to certain proteins found in the brain, although other researchers have not found such antibodies. There have also been a few suspected cases in adults. The bacterial connection with OCD is still being debated, and a recent large study in Neurology found no link. But Swedo and others are already using it as a basis for new treatments aimed at people who do not respond to the standard treatment of therapy and antidepressants. Several techniques to rein in the autoimmune attack have been trialled so far, including filtering antibodies out of the blood, and antibiotics to prevent repeated streptococcus infections. A few small studies have shown success but other trials have not, and the approach remains controversial.
Condition:
Prostate cancer
Microbe:
Xenotropic murine leukaemia virus, a retrovirus that causes cancer in mice
How you catch it:
Probably from other people but no one knows exactly how
Medical implications:
Better ways to screen for prostate cancer, especially more aggressive forms
6
Prostate cancer The link between prostate cancer and an infection is perhaps the weakest of all those here, but if confirmed it could lead to better screening techniques. The existing screening method – testing men’s blood for prostatespecific antigen (PSA) – is notoriously unreliable, so some men undergo unnecessary surgery that can cause impotence and incontinence. In 2006, a team led by Joseph DeRisi, a biochemist at the Howard Hughes Medical Institute in San Francisco, examined prostate cancers for viruses and found that a few of the samples contained a new virus closely related to xenotropic murine leukaemia virus (XMRV), which is known to cause cancer in mice. At this stage few were convinced of the link as the virus was not found in the cancerous cells themselves but in the surrounding tissue. “The results were inconclusive,” says Greg Towers, a virologist at University College London. The case against XMRV has just been bolstered, however, by a study published last month by pathologist Ila Singh at the University of Utah in Salt Lake City . Her team found XMRV in prostate cancer cells themselves – in 29 per cent of cancerous cells compared with 6 per cent of healthy ones. And the more aggressive the tumour, the more likely they were to find the virus lurking within it (Proceedings of the National Academy of Sciences, vol 106 p 16351). Both groups believe that while the virus probably originated in a mouse, it can now spread from person to person, though there are no clues yet as to how. Nor is it clear how the virus causes cancer, although other retroviruses are known to do so by inserting themselves into the host cell’s DNA and disrupting the genes that normally control cell division. Singh now plans to develop a blood test for XMRV, which could be used as an adjunct to PSA testing, or perhaps even to identify fastgrowing prostate cancers. ■ Priya Shetty is a science journalist based in New York
17 October 2009 | NewScientist | 49