Nov 15, 2008
DAEDALUS: TECHNOLOGICAL TRIUMPHS & CHALLENGES
By Andy Ho
HUMANISED pig organs will be ready for tests in humans within two or three years, British and American scientists announced this week.
Baboon and pig organs have been tried in humans before, with uniformly poor results. But new organs will come from pigs genetically modified to trick the human immune system into thinking they are human ones and not reject them.
Once people get over the yuck factor, the scientists expect widespread adoption of these organs, or xenografts, within a decade. That would help alleviate organ shortages the world over.
However, all is not so simple. Any patient who undergoes a medical procedure can choose not to be followed up if he is foolhardy. By contrast, even if a xenograft fails and is removed, the recipient will have to be followed up for as long as he lives. In fact, his intimates will have to be monitored for life as well.
The reason for this is that animal organs may carry unidentified animal viruses or just the genes of these viruses. These can infect the human recipient of the animal organ. The fear is that such individuals may then spread the animal viruses, if any, into the general population.
There has been some experience with xenografts in this respect. Two patients who received baboon livers, one in 1992 and another in 1993, were reported in 1998 to be carrying the simian foamy virus and baboon endogenous virus, respectively, in tissues far outside the liver.
Similarly, in 1999, a study was reported in Science of 60 patients in nine countries whose blood had been passed through pig organs or tissues for minutes to hours. Followed up for up to 12 years, pig genes could still be found in 30 of them while whole pig cells persisted in 23 patients for over eight years.
The genes, called porcine endogenous retroviral (PERV) genes, can switch on a specific human gene that causes cells to multiply in an unregulated fashion. This can lead to disorderliness in the renewal and replacement of normal cells, including immune cells. In this way, PERVs can tune down human immune defences, thus leading to a state of immunodeficiency.
Furthermore, should PERVs be integrated into a recipient's sperms or eggs, they can be transmitted to his or her offspring. Also, through the exchange of body fluids, PERVs may also be transmitted to intimates and subsequently into the general population.
Moreover, the immune processes that cause our bodies to reject animal organs are the same ones that kill viruses. This means that the genetic modifications to pig organs that trick the human immune system into believing they are human ones also render PERVs resistant to destruction by the same processes. So PERVs can linger for a long time.
Apart from PERVs, other agents that have been identified in pig xenografts include the porcine cytomegalo virus, porcine lymphotrophic herpes virus, porcine circovirus type 2, encephalo-myocarditis virus and hepatitis E virus.
The possibility of mutated animal viruses spreading in human populations is to be greatly feared. Bird flu and Sars aside, the Ebola virus mutated and crossed over from animals (primates) into humans and caused devastating epidemics in Africa.
It may take decades for animal viruses that have jumped into humans to manifest themselves. For example, the human immunodeficiency virus (HIV) came from wild primates in Africa carrying the simian immunodeficiency virus (SIV). It mutated and crossed over into humans, and lay low for a long time before surprising the world with an Aids epidemic.
Between 1955 and 1963, many individuals were administered poorly made polio vaccines that were contaminated with SV40. The virus has been found in some human cancers although it is not known if SV40 actually caused them.
All in all, the fear is that humanised animal organs may introduce novel or mutated animal infectious agents into human populations. According to the United States Institute of Medicine, 'although the degree of risk cannot be quantified, it is unequivocally greater than zero'.
Thus, the International Xenotransplantation Association urges that only those who are 'capable of fully understanding the potential impact of their behaviour on the rest of society, and who seem genuinely motivated to minimise these risks' be allowed to receive humanised animal organs in any trial. After all, such patients and their families will need to be monitored for life.
Indeed, sex partners of xenograft recipients will have to agree to undergo lifelong surveillance. The invasion of privacy this would entail would be unprecedented in scale and scope.
It is a very basic legal principle that no one may sign away his fundamental liberties, including the freedom of association. But a xenograft recipient will, in effect, be compelled to associate with a group of researchers for life. The authorities could, of course, argue that public health concerns trump individual liberties in this instance.
But such a contract could be thrown out if ever challenged in a court of law. This difficulty could bring down the whole edifice of xeno-transplantation.
All in all, despite our perennial organ shortage, Singapore would be better off if it imposed a permanent moratorium on this whole unsavoury deal.
andyho@sph.com.sg
[Okay, apart from the chuckle factor of discovering how PERVs are transmitted, Dr Ho paints a scary picture and makes a compelling argument for a permanent moratorium on xeno-transplants. This is way more dangerous than GM foods.]
DAEDALUS: TECHNOLOGICAL TRIUMPHS & CHALLENGES
By Andy Ho
HUMANISED pig organs will be ready for tests in humans within two or three years, British and American scientists announced this week.
Baboon and pig organs have been tried in humans before, with uniformly poor results. But new organs will come from pigs genetically modified to trick the human immune system into thinking they are human ones and not reject them.
Once people get over the yuck factor, the scientists expect widespread adoption of these organs, or xenografts, within a decade. That would help alleviate organ shortages the world over.
However, all is not so simple. Any patient who undergoes a medical procedure can choose not to be followed up if he is foolhardy. By contrast, even if a xenograft fails and is removed, the recipient will have to be followed up for as long as he lives. In fact, his intimates will have to be monitored for life as well.
The reason for this is that animal organs may carry unidentified animal viruses or just the genes of these viruses. These can infect the human recipient of the animal organ. The fear is that such individuals may then spread the animal viruses, if any, into the general population.
There has been some experience with xenografts in this respect. Two patients who received baboon livers, one in 1992 and another in 1993, were reported in 1998 to be carrying the simian foamy virus and baboon endogenous virus, respectively, in tissues far outside the liver.
Similarly, in 1999, a study was reported in Science of 60 patients in nine countries whose blood had been passed through pig organs or tissues for minutes to hours. Followed up for up to 12 years, pig genes could still be found in 30 of them while whole pig cells persisted in 23 patients for over eight years.
The genes, called porcine endogenous retroviral (PERV) genes, can switch on a specific human gene that causes cells to multiply in an unregulated fashion. This can lead to disorderliness in the renewal and replacement of normal cells, including immune cells. In this way, PERVs can tune down human immune defences, thus leading to a state of immunodeficiency.
Furthermore, should PERVs be integrated into a recipient's sperms or eggs, they can be transmitted to his or her offspring. Also, through the exchange of body fluids, PERVs may also be transmitted to intimates and subsequently into the general population.
Moreover, the immune processes that cause our bodies to reject animal organs are the same ones that kill viruses. This means that the genetic modifications to pig organs that trick the human immune system into believing they are human ones also render PERVs resistant to destruction by the same processes. So PERVs can linger for a long time.
Apart from PERVs, other agents that have been identified in pig xenografts include the porcine cytomegalo virus, porcine lymphotrophic herpes virus, porcine circovirus type 2, encephalo-myocarditis virus and hepatitis E virus.
The possibility of mutated animal viruses spreading in human populations is to be greatly feared. Bird flu and Sars aside, the Ebola virus mutated and crossed over from animals (primates) into humans and caused devastating epidemics in Africa.
It may take decades for animal viruses that have jumped into humans to manifest themselves. For example, the human immunodeficiency virus (HIV) came from wild primates in Africa carrying the simian immunodeficiency virus (SIV). It mutated and crossed over into humans, and lay low for a long time before surprising the world with an Aids epidemic.
Between 1955 and 1963, many individuals were administered poorly made polio vaccines that were contaminated with SV40. The virus has been found in some human cancers although it is not known if SV40 actually caused them.
All in all, the fear is that humanised animal organs may introduce novel or mutated animal infectious agents into human populations. According to the United States Institute of Medicine, 'although the degree of risk cannot be quantified, it is unequivocally greater than zero'.
Thus, the International Xenotransplantation Association urges that only those who are 'capable of fully understanding the potential impact of their behaviour on the rest of society, and who seem genuinely motivated to minimise these risks' be allowed to receive humanised animal organs in any trial. After all, such patients and their families will need to be monitored for life.
Indeed, sex partners of xenograft recipients will have to agree to undergo lifelong surveillance. The invasion of privacy this would entail would be unprecedented in scale and scope.
It is a very basic legal principle that no one may sign away his fundamental liberties, including the freedom of association. But a xenograft recipient will, in effect, be compelled to associate with a group of researchers for life. The authorities could, of course, argue that public health concerns trump individual liberties in this instance.
But such a contract could be thrown out if ever challenged in a court of law. This difficulty could bring down the whole edifice of xeno-transplantation.
All in all, despite our perennial organ shortage, Singapore would be better off if it imposed a permanent moratorium on this whole unsavoury deal.
andyho@sph.com.sg
[Okay, apart from the chuckle factor of discovering how PERVs are transmitted, Dr Ho paints a scary picture and makes a compelling argument for a permanent moratorium on xeno-transplants. This is way more dangerous than GM foods.]
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