In the simplest terms, what actually is a virus?
Well, viruses are the smallest kinds of parasites or microbes that can infect
other living things. There are many kinds of viruses. Viruses cause disease
in humans; other kinds infect animals, plants. There are even viruses that
infect bacteria. They work by getting inside the living cells of their hosts
and making more of themselves inside those cells.
There are different classes of viruses. We're particularly interested in
Well, the most notorious retrovirus in the retrovirus family is HIV, which
causes AIDS. . . They're called retroviruses because they go backwards, so
to speak, in biological information flow. The central dogma of molecular
biology that holds up, by and large, is that the genes of almost all living
organisms, in the form of DNA, can make RNA, and RNA makes protein.
Viruses can be different. You can have viruses with DNA genes or viruses with
RNA genes. Examples of viruses with DNA genes are smallpox or herpes viruses.
There are many others. There are also many viruses that carry their genes in
the form of RNA. The viruses that cause human diseases such as measles and
mumps, rabies, and influenza have RNA genes.
Retroviruses carry their genetic information in the virus particle that goes
from one person to another, or from one animal to another . . . as RNA. But
when it gets inside the living cell, it makes a DNA copy of the RNA. That's
where it's gone into reverse; that's why it's retro, because normally, DNA can
make RNA, but RNA cannot make DNA. . .
Is there any sense of how long they've been around, and how they've
Well, how ancient are viruses? The kinds of viruses we know about today could
not have been around in the world before true living organisms evolved, because
they're all parasites. Many evolutionists accept that an RNA world came before
a DNA world, and they think that some RNA viruses may be relics from those
days. But we just don't know.
And obviously, there's no fossil record for something that's so small; you
can't even see it with a microscope. But we can look in the living organisms,
in the hosts that they infect, and say, well, how many different species harbor
similar viruses? What evidence is there that they've jumped around? How far
back do they go in evolution? And almost certainly, the major families of
viruses have been around for hundreds of millions of years, including
Do viruses and retroviruses always cause harm in their host?
I don't think all viruses necessarily cause disease in the hosts that they
naturally infect. Some viruses can be deadly, like smallpox, and others may be
almost harmless, just getting a free ride without causing much harm. There are
other viruses that do no harm, most of the time; but in certain conditions,
they may come up and cause disease. In the case of humans and animals, that's
usually because our immune system is pretty efficient at controlling viruses.
So we may get an initial disease and then clear the virus out. Or we may get
an initial disease that's very minor and put the virus to bed, or the virus may
put itself to bed.
Let's take herpes simplex virus as an example, which almost all of us pick up,
probably as infants. It may give us a cold sore and nothing much else, but we
never really get rid of it. Once it's given you a little sore on the lip, it
also travels up the sensory nerves and gets embedded in the nerve ganglia, and
there it can stay for the rest of our lives. Normally, it will cause no harm.
But if we are particularly stressed out, either because our immune system isn't
working properly -- as in AIDS patients or transplant patients, or due to
psychological stress -- you can break out in cold sores. And if you're
seriously immune-deficient, like advanced in AIDS, then something as innocent
as this cold sore virus can spread throughout the body and kill you.
Are there any viruses that have, in a sense, become evolved to permanently
establish themselves as part of the host animals they seem to infect?
I think there are some viruses that are so well adapted to the hosts that they
infect that they live with them, and co-evolve with them, over evolutionary
time. The herpes viruses I was just talking about are like that. Some of the
retroviruses have gone even one step smarter. On occasion during evolution --
at least during the evolution of vertebrates birds and mammals and amphibians,
and so on -- [the retroviruses] managed to insert their genes into the DNA of
the chromosomes in the host. And in fact, they have to do this in order to
replicate. It's an obligatory step in the reproductive cycle of the virus,
that once it's made its DNA copy [it] must integrate into the DNA of the cell.
Occasionally, these viruses have infected the cells . . . that are destined to
become the eggs and the sperm of the host species. And that's a clever thing
for a virus to do, in a sense, because if it's integrated latent, keeping quiet
there, it gets a free ride to the next generation. In this way, the virus
becomes inherited as a genetic trait, just as we might inherit blue eyes or
some other feature.
So these are a class of virus that is impossible to remove? They are part
and parcel of the very being of that animal?
Yes. This particular subset of retroviruses we call endogenous viruses,
because they are part and parcel of our own DNA. They are, therefore,
difficult to eradicate or eliminate. We have them on board ourselves as
humans. . . .
Do endogenous retroviruses exist in the pig?
We think that most animal species amongst mammals, if not all of them, contain
some classes of endogenous retroviruses -- these retroviruses where the genes
are in the chromosomes. Most of these are not infectious, so they can't come
out again as infectious viruses. They've been there so long that they've
become defective. Chunks of the viral genes have come out, or they've mutated
in some way, so that they can't be regenerated as infectious virus. For
example, of all these many retrovirus sequences in human DNA, none have been
shown to be infectious, to come out again.
But in some species, they can become activated and emerge as potentially
infectious viruses. We first found this in chickens over 30 years ago. The
domestic chicken has a virus like that, which you can recover in infectious
form. Interestingly, it can't re-infect chickens, but it can infect turkeys
and quail and other species of birds. The same is true of mice and of cats,
and it turns out to be true of pigs. And that's why we're concerned about this
type of retrovirus in xenotransplantation.
Why did you first become interested in the pig retrovirus?
I first became interested in the question or the problem of pig retroviruses
really out of curiosity, because I'm a retrovirus aficionado. I've studied
retroviruses for most of my career. They're my pets, if you like. And there
were research reports published back in the early 1970s, over 25 years ago,
that gave some preliminary evidence -- as good as it was with the technology of
those days -- that pigs contained endogenous retroviruses, and even that they
could be recovered in infectious form.
The one experiment that tested whether they could infect human cells gave a
negative result. But it was only one cell type, and it wasn't continued for
very long. So we knew from these old reports that pig retroviruses existed,
and could be recovered as infectious virus particles. With the debate about
the use of pigs in xenotransplantation, of course this question popped up
again. . .
Did you and other experimenters set out to discover how many of these
endogenous retroviruses were actually in the pig DNA?
. . . I was able to persuade a very able student in our lab . . . to take on a
small project, to re-examine these pig endogenous retroviruses, using the kind
of modern technology for studying viruses that we have available to us today.
The upshot was that we found more than one strain. We know of three infectious
strains, and that two of those, there, at least, could infect human cells in
And we published that also in Nature Medicine in 1997, and that had an
immediate impact in the field. We also looked to see how many copies of these
porcine or pig endogenous retroviruses (PERV) were embedded in the chromosomes
of the pig. And we reckon there are roughly 50 copies in the average domestic
pig, if you add the three different strains of retrovirus together. There's
perhaps 30 of one strain, 15 of another, and 12 to 15 of the third strain,
although that third strain is more variable. . .
What experiment was actually involved to show that PERV could infect human
We went about this investigation first by looking at the handful of research
reports that had been published 25 years earlier. We obtained some pig cells
that grow permanently in culture from a repository . . . which had been
reported to release virus with reverse transcriptase activity -- that's the
marker enzyme for retroviruses. And we were able to confirm that, indeed,
these cells that were growing in flasks in the incubator were producing lots of
We then exposed human cells in culture to the semi-purified virus particles.
And we found only one human cell type, amongst about 15 or 20 that we tested,
which could readily become infected with this virus. However, if we took the
pig cells that were releasing this virus and cultured them in the same flask as
human cells, then we found that about half the different human cells we tested
were susceptible to infection. This means that human cells are not very highly
sensitive to infection. To put it another way, the virus wasn't a ripping hot
virus for human cells. But if you allowed the pig cells and the human cells to
be next to each other, given enough time, the virus would get in.
Think of the xenotransplantation setting, where human blood cells will be
coursing through the pig organ, where human cells that line blood vessels will
begin to invade and line the blood vessels of the organ. Then, of course, you
can see that that this co-cultivation experiment in culture was perhaps the
more significant one. And that really did show us that this virus had the
potential to infect humans.
What was the worldwide scientific reaction when news of that discovery was
Well, when our first report was published, showing that these pig viruses could
infect human cells, it really had an even bigger impact than I expected. It
raised the debate about possible animal infections in xenotransplantation onto
the front line. Prior to that, the FDA in America had really decided to
. . . leave decisions about whether to go ahead to local ethical committees
in the hospitals and research medical schools concerned.
Our report had an immediate effect. The FDA in America called their
xenotransplant committee together. They organized workshops to discuss this
virus more seriously. Other laboratories, including the FDA's own research
labs, became involved, as did the CDC. And much more effort was put into
studying these viruses. I think this is a welcome thing that the medical
community and the regulatory authorities responsible for these things were able
to respond fairly rapidly to new evidence, like the evidence we published. .
Is it possible to have any kind of xenotransplant -- xenograft, cellular,
whole organ, regular or transgenic -- without being exposed to the pig
The problem of possible infection through xenotransplantation is quite complex.
We've got to weigh the benefit of the transplant and the risk of infection to
the individual patients. But we also must consider if an animal virus
transfers to the patient, whether it might take off and spread in the human
population. We have to weigh that possibility, too. So it's quite difficult
to come to a sensible decision about this, because these are unlikely events,
but not impossible events.
By and large, pigs that are going to be used as sources of tissues or organs
for transplantation are going to be very carefully screened that they are free
and clean of the known pig viruses. So they will be derived from special herds
of pigs that are kept behind barriers with filtered air intake. The ancestors
to these herds will probably be born by cesarean section, so that no virus on
the surface of the mother pig can get across to them. And in this way, one can
exclude the majority of viruses and other microbes that might be there in the
average farm pig, that almost certainly are there.
The problem with endogenous retroviruses is that they are sitting there in the
DNA of the pig chromosomes, so it doesn't matter how clean the pigs are; the
viruses are sitting there right inside them. And it's not going to be easy to
get rid of them. . .
Do you feel that the cellular transplants that are going on at the moment
pose a risk, in terms of possible infections from endogenous pig
There's a question of whether all forms of xenotransplantation are equally
dangerous, in respect to endogenous retroviruses and other microbes. In a
sense, because the virus is sitting in the DNA of all pig cells, it doesn't
matter which organ you take or which tissue you take; they're going to be
there. In terms of saying, are they going to come out as infectious viruses,
there may be differences between one tissue and another. So they might perhaps
pop out less regularly from, say, nerve cells in the brain that are being used
for Parkinson's disease, than, perhaps, cells in the pancreas that could be
used for diabetes, or perhaps from putting a whole kidney into a transplant
But at the moment, we don't have enough detail about this. We cannot say for
sure. I think I could say for sure that it would be rash, that it would be
unwise, to say that any particular tissue or organ is safe.
The committees that are trying to decide about relative risk and dangers
tend to say that implanting whole organs that are going to last for years in
people is likely to be more dangerous than being exposed to a few pig cells, or
taking the human blood circulation outside the body and perfusing it over pig
tissues. . . . I think that's right, in the common sense sort of way. A whole
organ lasting a long time gives you a higher potential dose of virus. But they
might all be over the threshold. It might only require a few minutes' exposure
to do the trick. We simply don't know yet.
Regardless of circumstances, does exposure to the pig retrovirus always
inevitably lead to infection? Do we know what will happen, in that
Exposure to an infectious agent doesn't necessarily lead to infection. You
could have sexual intercourse with an HIV-positive person, and you might well
get away with it. The calculations are that you do not get transmission except
in a small percentage of such sexual encounters. But it sure does happen, or
we wouldn't have the worldwide epidemic of AIDS in front of us. So mere
exposure doesn't guarantee infection.
I mentioned HIV because it's also a retrovirus. It's a distant relative of the
pig retrovirus, a second cousin, so to speak. It looks to me, from the
knowledge we have at this time, that the pig retrovirus is going to be
substantially less contagious for humans. So I think it's going to struggle to
infect xenotransplant patients, and I don't think it's that readily going to
adapt to pass on from person to person.
But life is full of surprises. It might well adapt inside the first patient,
as, presumably, HIV had to adapt when it got into the first human, and then
take off. So we're looking at quite a long time horizon before we can decide
whether such viruses are safe to have on board, or might evolve to become less
safe. These are all unknowns at the present time.
Given the class of virus that PERV is, do you have any idea what kind of
illnesses it would cause if it did become a hot virus in humans?
We could ask whether PERVs are likely to cause any disease at all. The most
sensible way to consider that is to look at the closest animal relatives to the
pig virus, which are viruses of mice and dogs, and also of a species of ape .
. . and say, "Well, when they get a hot virus infection, what do they go down
with?" And, by and large, the most common disease that occurs is a type of
cancer, usually a lymphoid cancer. They develop lymphoma or leukemia.
For this to happen, the animal has to have quite a high dose of virus on board.
The virus that gets introduced may be a low dose, but it then propagates within
the infected animal to produce lots of virus. And the disease only appears
after quite a long latent period. So if we extrapolate that to the human
condition, if we took on board the pig virus, we might expect it to be
incubating as a silent or inapparent infection, perhaps for years before it
came out and caused the disease.
Cancer isn't the only disease that this type of retrovirus can cause. It can
cause a form of immune deficiency. Related viruses can cause
neuro-degenerative diseases, paralysis and encephalopathy -- brain disease.
Related viruses in chickens have caused bone disease. It's quite extraordinary
what a broad range of disease these retroviruses cause. But most of the time,
in most of the animals they infect, they're causing no disease at all.
So, in a sense, for a terminally ill transplant patient, even if it was
provable that some of these pig retroviruses could cause disease, that might
not be unacceptable to someone who is facing a death sentence if their organ
I think the risk of infection and the risk of disease in a transplant patient
is much higher than just getting bitten by a pig, or even a healthy person
being inoculated with the pig virus. By necessity, so that the transplant
patient does not reject his animal organ or animal tissues, he or she is going
to be immunosuppressed. And we know that immunosuppressed people are more
susceptible to unusual infections from animals, as well as to human infections
than the healthy person. So there is an added risk here.
You might say that, at the expense of the transplant patient, we can evaluate
earlier whether these viruses are actually dangerous, because you are doing, so
to speak, just the right experiment to find out. You're putting whole living
pig tissues into people, and you're immunosuppressing the people so that it's
not rejected. If you wanted to design an experiment to test whether such
viruses will get across and will cause disease, you could hardly do it better.
On the other hand, from the point of view of the individual transplant patient,
if they are so severely ill with a life-threatening disease that they need a
pig organ or pig tissue to survive at all, from that individual's point of
view, the risk may well be worth taking. I think if I was in that position,
I'd say, "Go ahead, I'll take the risk, because I'm a goner otherwise, in any
That's the individual perspective. But what's the worst-case scenario of
this from a public health point of view?
We virologists and microbiologists are enjoined to not only think of the
potential benefit to the transplant individual or to the few dozens of patients
that will be treated in the first trials, though that might grow to many
hundreds of thousands if they're successful. We have to think of public
health, as well. And the worst-case scenario is that we could be setting off a
new pandemic that would spread across the world, just like HIV has done. That
is the worst-case scenario. I don't expect it to happen. But I can't say that
What would the PERV virus have to do to create a pandemic? . . .
. . . Well, it's not inconceivable. But you would be asking the virus to
change and adapt to growing in humans to quite a degree. So the virus, when it
gets out of pigs and infects humans, won't become a genetic trait in humans, at
least not for thousands of years. It will insert its DNA into the chromosomes
of human cells. But as an ongoing infection, it's much less likely to do so
into the germ cells. And in any case, the first transplant patients are going
to be strongly advised not to have children, though quite how you control that
stringently is a more difficult question.
So the virus is now going to be in human tissues, and the demands on it are to
propagate itself, and to spread throughout that individual infected person.
The virus can go through millions of replicative cycles, producing its own
progeny, its own daughter viruses, again and again and again. So it's got
plenty of chance to evolve fast. And we've seen that by looking at the
evolution of HIV, which is a recent introduction into mankind. I think PERV,
being the kind of retrovirus it is, won't change quite as rapidly as HIV. But
the potential for it to change is there.
How would it then learn to become transmitted from the first infected patient
to others? Probably, in the first place, by very intimate contact, by sexual
fluids, by contact, by kissing. Different retroviruses in different animals
can be transmitted in many different ways. We don't know of any natural
transmission from animal to animal via aerosols. But there are some
retroviruses that even get transmitted from one mammal to another via biting
insects, so they can get around. They can learn new tricks.
But I would expect that the most probable way of becoming transmitted would be
through sexual contact and through kissing, through the intimate association of
fluids and of mucus membranes. Obviously, the first generation of transplant
patients will not be allowed to donate blood, which could be a very efficient
way of passing it on to others. So it's going to be important to monitor not
only the first patients, but their intimate contacts, their husbands and wives,
their children, household contacts, to see whether there's any evidence, not
only of infection in the patient, but of infection in those they're living with
Does the fact that the pig retrovirus is dormant in the pig guarantee that
it would remain so, if it traveled to a new human host via a transplant?
We could argue that the retrovirus in the pig is dormant, just sitting quietly
in the chromosomes. Actually, it's turned out to be less quiet than we
thought. Dr. Walid Heneine and his colleagues at the CDC in Atlanta have
shown that the average farm pig has quite active virus production. You can
interpret that in two ways. One is that for the last 6,000 or 7,000 years that
we've lived with domestic pigs, we haven't become infected, although pigs have
the virus around. Or, we could say, "My goodness, if those pig cells or organs
get inside us, they're readily producing virus, and they're not so dormant."
But once a virus gets into a new host, it's very difficult to judge whether it
will grow towards latency, dormancy, or whether it will hot up, whether it's
likely to become more active. I would guess -- but it is pure guesswork --
that with this kind of virus, it will go the second way, and could well become
more active. Because it's in a new host where there's no age-old host-
parasite-evolutionary controls in play. And so the virus really has virgin
territory in which to do what it likes.
On the other hand, from the limited investigations we've done with the
infection of human cells in culture, these viruses grow in a rather wimpy way,
as retroviruses go. In human cells, they have not grown to high levels. And
we're wondering why they grow so poorly, when retroviruses quite closely
related to them can grow to very much higher levels in human cells.
However, one of our colleagues, Caroline Wilson at the FDA labs, has shown that
the level of virus increases as you pass them through human cells after two or
three passages of putting the viruses in human cells, taking the progeny virus,
and putting it on new human cells. So there is possibly a mechanism for these
viruses to adapt to growing in humans and getting on with their business rather
faster than they otherwise might have done.
We have to be careful about this, because xenotransplant as a treatment is
aimed not for the few, but for the many, isn't it? We could find ourselves a
great many opportunities for the virus to evolve within one person. But
actually this is being touted as a possible solution to the worldwide donor
organ shortage. Does that put an extra facet of caution in your thinking on
. . . The biotechnology and pharmaceutical industries have not been slow to see
those opportunities and have, collectively, invested billions of dollars into
developing xenotransplantation possibilities. So if these viruses are not
highly contagious and, therefore, if the first handful of xenotransplant
recipients do not become infected, then the pressure will be to do
To my mind, that's when the problems actually become more complex. In some
ways, we may be reassured if people don't become infected. But we don't know
whether one in a thousand or one in a million people will, and what will then
happen to that virus once it's adapted to grow in humans. I would say to be
forewarned is to be forearmed.
And we do know quite a lot about retroviruses these days. For example, one
study that we have been involved in collaboration with the CDC is to say that
these viruses, as I've mentioned, are second cousins to HIV. And we're asking
if there any anti-HIV drugs already licensed for use in humans that might also
prevent the replication, the growth of pig retrovirus. And indeed, one of them
is quite good at doing this. Most of the ones that are tailored to knock HIV
on the head don't touch PERV. But the fact that we've already got one is
something to be saved up. If one of the early xenotransplant patients proved
to have a roaring infection of PERV, we already have a drug licensed to use in
people. . . .
In the history of microbiology, have you ever offered a virus an opportunity
We have known about animal-to-human infections -- zoonoses -- since ancient
times. I know of an old cuneiform tablet from ancient Babylonia that talks
about the fine if you let your dog bite a human and the human dies from rabies.
Rabies is an interesting example. If you do catch rabies from a bite, you die.
It's almost invariably fatal. But there are very few cases of human-to-human
transmission of rabies. So long as you can prevent the rabid person from
biting the people who are caring for him, then that infection stops dead with
the first human death.
It's the viruses that perhaps are not so acute, that you can't detect so easily
and have time to spread before symptoms appear, that turn out to be the major
difficulties. And HIV is an obvious example. Some others have crossed over
from animals to man and have set off epidemics more rapidly. New strains of
influenza virus, of flu, probably come from birds, but pigs may be the
so-called mixing vessel. They may adapt to become flu-like and to be
transmissible through coughing and sneezing as they pass through a pig, and
then get more readily picked up by people. So we do have a number of examples
And new ones occur as well. Just because we've lived together with pigs for so
many thousands of years doesn't mean that there aren't new viruses. This could
be a genuinely new virus, like the outbreak in Malaysia that started in 1998.
More than 250 people have died from this pig virus. Well, in fact, it looks as
if that virus was new to pigs, as well as new to people. And it's believed
that the natural reservoir is in fruit bats living in the tropical forest. It
may have started through the massive lumbering, cutting down the tropical
forest when the new international airport outside Kuala Lumpur began to be
built. The bats that can fly took flight from the falling trees and the trees
that were still standing were those around the farmsteads. That's how it got
from the bats to the pigs. This is speculation, but it's quite reasonable
speculation. So we don't know when a new virus might get into pigs.
. . . There are other viruses that might have been there all the time, but we
simply didn't know about them, like the pig retrovirus, or the newly discovered
pig virus that's related to human Hepatitis E. That was only discovered in
1997 in America. It turns out that this virus is extraordinarily widespread in
pigs. And there's some evidence that it does infect people, and that people
who work in abattoirs and who are pig farmers are more likely to have signs of
infection than others are.
So there might be viruses that are there all the time [but] not yet known to
medical or veterinary knowledge that could still cause a problem. All of these
are problems that can be worked out, but they need to be studied very
thoroughly. . . .
. . . In xenotransplantation . . . the pig organs and the pig cells will be
"humanized" by the insertion of human DNA to try and overcome the rejection
process. Is that significant, in terms of what viruses could potentially do in
In considering the use of pig organs and tissues for xenotransplantation, I've
been concerned that the very medical developments that may allow those pig
tissues to be accepted by the transplant recipient could increase the risk of
transmission of viruses. On the one hand, the type of husbandry, keeping them
in contained units, will tend to exclude most of the infectious viruses that
travel from pig to pig. But the fact that the pigs are humanized, that they
are made transgenic to express certain human proteins on the surface of the pig
cells, could allow some pig viruses to more readily adapt to cross into humans.
This is for two quite distinct reasons. First of all, it seems to have escaped
the notice of the scientists developing these transgenic pigs that the very
human genes they were breeding into them can code for proteins that act as
virus receptors. After all, they're not virologists; they weren't reading that
type of research report. But it's odd that that is the case.
The second reason is that those human genes have been put into pigs to protect
against hyperacute rejection, which is a type of rejection that's mediated by
factors in the human blood, including complement. Many viruses, including the
pig retrovirus, mature from cells by budding through the cell membrane. So
they have the same outer envelope as cells do. And they can also be
susceptible to inactivation by these blood factors, such as complement.
If you breed the human genes into pigs that protect the cell membrane from
being destroyed in hyper-acute rejection, any virus that has a cell membrane --
like outer envelope-like retroviruses, like influenza viruses, like measles
viruses -- may well also be protected. And we have to ask why humans have this
hyper-rejection phenomenon against foreign tissues. It's probably evolved to
protect us against animal viruses. So we are deliberately breeding pigs where
that type of barrier is going to be broken down. And that is another area that
I think needs to be looked at.
What I am saying is speculation. But it's speculation that can lead to the
design of investigations that could bring solid answers and say whether I'm
just a scaremonger, or whether, indeed, I've got an important point to make.
Do you think we should be looking to do that urgently?
I think this is an important question, and one of our students is currently
setting up to investigate this problem.
Have there been any recent studies showing that pig retrovirus can cross
over, for example, in mice?
After our initial report that the pig retroviruses could grow in human cells,
there was very much concern, even alarm, about proceeding with
xenotransplantation. Several other groups were able to confirm our results and
extend them to other cell types and other conditions quite rapidly.
However, surveys of people who had already been exposed to living pig cells for
one reason or another showed no evidence that any of them had picked up a pig
retrovirus infection so far as we could tell. And we used really quite
sensitive techniques. Our characterization of the virus allowed very sensitive
detection methods to be developed. So we thought, well, maybe this virus isn't
so dangerous after all. We don't know whether it causes disease, and the
160-odd people who have been investigated, who have been exposed to living pig
tissue through experimental xenotransplantation -- through having pig skin to
protect from third-degree burns; through a rather odd practice in Russia of
allowing patients' blood to be pumped through pigs' spleens -- none of these
people seem to have picked up infection. That looked pretty good. . .
The significance of this new report from the USA and the UK is that the
infection was seen not just for cells and culture, but in the living animal, in
the mouse. And the mouse was not deliberately injected with purified virus.
It was simply xenotransplanted with pig pancreas cells. So it's significant
really, in both ways, that the cells on xenotransplantation really do start to
release virus, and that that virus can take in the living animal. There is
also a report that guinea pigs inoculated with the virus can become infected.
So these are significant. It means xenotransplantation can allow cross-species
Actually, we've known this for about 25 years, when we do xenotransplantation
in reverse. A very useful method in cancer research has been to grow human
cancer cells as xenotransplants in the same kind of immunodeficient mouse. And
we know that mouse retroviruses can then invade the human cancer cells in the
mouse and infect them. So the viruses can go in both directions in situations
In this latest mouse study, are you describing the pig retrovirus taking the
first steps towards becoming a hotter virus? . . .
The recent report showed that mice can become infected, but the infection was
still at a very low level. We don't yet know -- because these are very early
steps made by these investigators -- whether the virus can hot up. We'll have
to wait to know the answer to that. . . .
In public health terms, can we make xenotransplantation risk-free from the
I don't think we can make xenotransplantation risk-free in public health terms.
Any new medical procedure carries a certain element of risk, but so does
crossing the street. So we should not be demanding an entirely risk-free
medical environment. It's not going to happen. More specifically, can we
eradicate the risk of PERV transmission to humans? I don't think we can
eradicate it, eliminate it; not yet. It may become possible in the future,
though it will take many years to cut out the PERV genes that give rise to
infectious virus, one by one, getting rid of them from the pig chromosomes.
That's going to be a big job. But that doesn't mean it shouldn't be tackled.
And we don't know whether it would be successful. I think we should make a
start now. But I cannot say for certain if or when that will be
There are some breeds of pigs -- I'm thinking of the miniature swine -- that
seem to offer at least some hope of having naturally getting rid of some of the
PERV virus. What do you make of that as a possible help for the future?
. . . Some of the miniature swine lack one of the three groups of PERV, the one
that doesn't infect human cells readily, so they still have the other two that
are the real problem. . . . These viruses have been in the pig chromosomes for
a long time, probably about 30 million years. We're not going to get rid of
them that easily.
Do you think that we can only move forward with this and learn by engaging
in some kind of very carefully controlled human clinical trial involving
. . . The potential benefits are enormous, and I think the likelihood of the
worst-case scenario setting off a serious epidemic that can then not be stopped
is very, very remote. And, therefore, I am not against the notion of going
forward step by step, cautiously, but thinking about what we're doing.
I'm not sure that the pioneering transplant surgeons are always good at
thinking ahead about infection. If they were, perhaps those baboon livers
would not have been transplanted into patients and then the patients analyzed
eight years after they died. Only then did they say, "Oh, let's look at this
and that virus and see if they became infected, because their tissues have been
preserved in a freezer since then." I think the right way is to think ahead.
But certain things cannot be found out, cannot be clarified, without doing
limited clinical xenotransplantation.
Is it possible to move forward in this area of science without animal
experiments? And do you think the public needs to understand and appreciate
that they are done in the best possible way?
Can we make medical advances and save lives without using animals
experimentally? In some small areas of medical research, we can. But it's my
opinion, as is the case for most medical researchers, that some use of animals
has been absolutely essential for the progress we've made to date. There is no
drug that's licensed for use that hasn't been tested for toxicity in animals,
and, quite frankly, I prefer them to be tested in mice or rats before use than
tested in my grandchildren.
There are no vaccines today that haven't been tested in animals. We would not
have eradicated smallpox and could not now be eradicating poliomyelitis without
the use of animals. Even today, every batch of polio vaccine that is used,
that is released to give to babies, must be tested on animals first, to check
whether it has reverted to so-called neuro-virulence -- whether it could become
paralytic. Animals are absolutely essential if we are not going to revert back
to Stone Age medicine.
. . . Having said that some use of animals is essential for medical progress, I
do think we need very stringent regulations to make sure we don't abuse animals
any more than is necessary. Not all the procedures are pleasant for animals.
Many of them have to end in the death of the animal. And all this must be done
in a proper manner, and the animals must be treated as humanely as possible.
Cruelty has absolutely no place in medical research.
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