The team, at the Pest Animal Control Cooperative Research Centre (PAC CRC) in Canberra, has already applied for permission to carry out field trials with a similar virus that makes European mice infertile. Advocates of this form of biological control say it is more humane than existing strategies such as poisoning, shooting or spreading lethal diseases.

From cats to camels, feral mammals cost Australia hundreds of millions of dollars each year in lost agricultural production and environmental damage, and have driven some native mammals and birds to extinction.

“Australia has lost more mammal species than the rest of the world combined in the past 400 years,” says project director Tony Peacock. But the prospect of genetically engineered viruses being released into the wild is still likely to spark a fierce debate.

Damaged eggs

The viruses make females infertile because they have an added gene for a protein from the zona pellucida, the thick layer surrounding the egg. Females infected with one of the transgenic viruses produce antibodies against their own eggs, damaging them and blocking fertilisation – a process called immunocontraception.

For rabbits, geneticists chose to engineer the myxoma virus, which devastated populations when it was released in Australia half century ago. But many rabbits have become resistant, and less lethal strains have edged out the original virus.

Four years ago, researchers selected the rabbit ZPB gene as the most promising of three zona pellucida genes to insert into the myxoma virus. But this sterilised less than 25 per cent of rabbits. Now they have switched to the ZPC gene, with much better results.

In two trials in May, ��è����Ƶ has learned, the latest transgenic myxoma virus sterilised eight out of 11 female domestic rabbits, while a ninth carried only a single embryo – a success rate of over 70 per cent. It is a highly infectious but non-lethal strain that should give most rabbits no more than a fever for a few days.

Peacock says if the virus could sterilise 70 to 80 per cent of wild females, rabbits would decline to densities similar to those in Europe and become a relatively minor pest. But even if it were only 50 per cent successful, it would still end the episodic plagues that have ravaged the country.

House mouse

The immunocontraception idea has already been proved in another major pest, the European house mouse (��è����Ƶ print edition, 26 April 1997). An engineered herpes virus, murine cytomegalovirus, has consistently produced 100 per cent sterilisation of female mice in lab trials.

The PAC CRC will apply to the Office of the Gene Technology Regulator later this year for permission to conduct the first contained field trial of the transgenic mouse virus at Walpeup, in north-western Victoria. Peacock says extensive consultation would precede any release.

The virus appears to sterilise female mice for life, but it is too early to know if the same will be true with rabbits, which are longer lived. So the team plans to add other genes to the myxoma virus to try to boost the contraceptive effect.

If the government decides to release such viruses, Peacock thinks populations should decline rapidly as breeding slows and natural mortality and predation take their toll. Other researchers think the effects will only be temporary, as natural selection will favour animals with a mutated zona pellucida protein that evades the immune response.

But Peacock points out that sperm can only fertilise eggs if the proteins on their head bind to the ZP proteins. So for resistance to appear, both egg and sperm proteins would have to mutate simultaneously yet still be able to bind to each other, which is extremely unlikely.

Species barrier

However, the viruses could be accidentally – or deliberately – transferred to another continent. Another worry is that the viruses could spread to other species, but the modified viruses are no more likely to jump the species barrier than wild strains. And the myxoma virus has not done this in the 50 years it is been in the country.

For Australia’s worst feral predator, the fox, the PAC CRC team has not been able to identify a virus that does not also infect domestic and wild dogs, including dingoes. So the plan is to modify a canine herpes virus so it can only replicate when an antibiotic such as tetracyline is present.

The virus and antibiotic would be added to baits that are irresistible to foxes, but are shunned by dogs and dingoes. Because the virus doesn’t infect any native mammals, they would be safe even if they ate the baits.

The PAC CRC is also working with a New Zealand research team to develop an immunocontraceptive virus for New Zealand’s worst feral predator, the stoat, which also inflicts a heavy toll in Hawaii.

Even people who have recently suffered a bout of flu can be laid low
by new strains. Their immune systems cannot anticipate the changes in the
virus. And despite its trivial, if tiresome, symptoms in healthy people,
flu is a killer of the elderly and people with impaired immune systems.
In 1989, a flu epidemic in Britain killed about 25 000 people.

The new compounds inhibit an enzyme called neuraminidase, which is part
of the flu virus and is essential for it to spread. Flu virus replicates
inside animal cells. New virus particles are transported to the outer surfaces
of the cells, where they are temporarily bound. Neuraminidase acts as a
molecular scalpel, cleaving the bonds and freeing new viruses to infect
other cells.

A small Australian company, Biota Holdings, owns intellectual rights
to the new compounds, but has licensed the British pharmaceutical company
Glaxo to test and develop them commercially.

The drugs are the result of more than a decade of research by scientists
in Melbourne into the molecular structure of neuraminidase. In the early
1980s, Peter Colman of the CSIRO Division of Biomolecular Engineering in
Melbourne, and Graeme Laver of the Australian National University in Canberra,
succeeded in purifying and crystallising flu neuraminidase.

Colman and George Varghese later worked out the structure of the enzyme
using X-ray crystallography, and identified a pocket-like structure that
is present in all this century’s major strains of flu virus.

Neuraminidase and a second protein, haemagglutinin, are the principal
antigens on the protein coat of the virus that are targeted by the immune
systems of animals. It is when the genes that encode these proteins mutate
that new strains of virus are generated.

The new compounds were specifically designed by chemists at the Victorian
College of Pharmacy in Melbourne to complement the three-dimensional shape
and chemistry of the neuraminidase ‘pocket’. They bind strongly to the enzyme,
preventing it from cutting new virus particles loose.

The patent describes a class of compounds that are all synthetic variants
of neuraminic acid. This compound has been shown to inhibit the action of
neuraminidase in the laboratory but, like other early candidate drugs, either
failed to protect animals against flu, or turned out to be toxic.

Animal trials conducted by Glaxo show the new compounds to be potent
neura-minidase inhibitors and reportedly protected animals against infection.
The patent says that the compounds have low toxicity.

The drugs have yet to be tested in humans but, given their highly selective
activity, Glaxo researchers believe they will prove effective. Glaxo has
developed a nasal spray to deliver the drugs directly to the cells lining
the nasal and respiratory tracts which are targeted by the virus.

Photographers produced the first 360-degree landscape in 1840, only
a few years after the invention of photography. However panoramic photography
has traditionally been limited to distant landscapes. The images tend to
be very wide and low, making them difficult to enlarge and publish.

The new camera, developed by Steve Morton, a scientific photographer,
and Alan Holland, an engineering technician, produces images that approximate
closely to what a human observer would see while pivoting through 360 degrees.
The camera was developed following an inquiry from a scientist who wanted
to publish a 360-degree image of a closed eucalypt forest, at a width that
would fit into a normal book.

The few commercial 120 and 70 millimetre medium-format panorama cameras
available today commonly use lenses with focal lengths of 50 or 65 millimetres,
or even longer. The images they produce are striking, but too wide for most
publications. They are also quite shallow, because the vertical angle of
view is only about 50 degrees, compared with almost 180 degrees for the
human eye.

For someone standing in a forest glade, the horizon is defined by the
nearby vegetation, and the eye must move vertically through a much larger
arc to take in the view from the forest floor to the canopy. This view can
only be approximated by an image with much greater depth in relation to
its width, since this demands a lens of much shorter focal length with a
wide covering power.

Designing a camera to obtain images of closed-in environments poses
new problems. For example, it must employ long exposure times since closed
environments, by their very nature, offer less light than an open landscape.

Any pronounced variation in exposure from one part of the scene to another
– whether due to unevenness in ambient light levels or to slight variations
in the camera’s panning speed – results in an uneven exposure.

Morton decided to design a panoramic camera around a 28mm perspective
correcting lens, which could reduce a 360-degree swap to less than the width
of a single page, yet provide improved coverage in the vertical plane.

He employed a Nikon 28mm PC lens, which produces a 360-degree image
56mm high and 180mm wide. The lens has a vertical angle of view of 110 degrees,
which is about two-thirds of the vertical arc seen by a human observer.

Although it would have been easier to build a wide-format 70mm camera,
few fast emulsions are available for low-light conditions in this format.
The 120 film is easier to process, and long enough for a continuous exposure
spanning more than four complete rotations.

Light enters the camera via a thin slit 56mm in width, and falls upon
the surface of the film as it is smoothly advanced. A mechanically-driven
capstan holds the film taut by pressing it against one of the spools. A
clutch mechanism compensates for the progressive change in the effective
diameter of the spool as the film winds on.

Gears link the drive roller to the main drive, synchronising the film-advance
speed with the camera’s rotation as it pivots through 360 degrees. Planetary
gear modules can be combined to provide exposure times ranging from 1/30th
of a second to 2 minutes. At these exposure rates, a 360-degree rotation
may take from 5 seconds to 5 hours, depending on ambient light.

An Australian company has launched an erasable computer memory chip
that retains data when its power source is switched off. The chip could
revolutionise the design of computers and other electronic devices by doing
away with the bulky magnetic disc memories that are currently used to store
data permanently.

Current computers rely on a selection of memory devices. These include
chips known as read-only memories or ROMs that store preprogrammed data
without power but cannot be erased, and instantly erasable chips that require
constant power, known as random-access memory or RAMs. To store more data
and programs when the power is off, most computers use magnetics discs.

The new chip is known as a ferroelectric random-access memory or FRAM.
If it proves as successful as its developer, Ramtron, claims, it could replace
all other types of data storage.

Ross Lyndon-James of Ramtron says: ‘All other memory devices have either
inflexible static memories, or require information to be shuffled in and
out of the chip.’ Data stored in RAM chips while the computer is on must
be moved to a disc before the power is switched off. ‘That requires a large
software overhead,’ he says. ‘The software must contain instructions to
handle all the communication between the chip and the disc.’

Such data management operations take up a lot of the computer’s operating
time; in a computer based on FRAMs they would be reduced to a minimum. ‘You
don’t have to switch on the computer, load the program and recall a file
from disc – you just switch on and it’s there,’ Lyndon-James says.

Programs stored in normal ROMs cannot be changed. Data in erasable programmable
read-only memory (EPROM) chips can be updated many times, but only by removing
the chips, erasing the original program with ultraviolet light, and then
reprogramming.

Ramtron claims that mass-storage FRAMs could make hard and floppy discs
unnecessary in smaller computers, especially laptops, making them more compact.
Batteries will last longer because they will not need to drive the discs
or maintain data when the main current has been switched off.

In current FRAMs, Ramtron have deposited a layer of a ferroelectric
ceramic on top of a conventional silicon memory chip known as a static RAM,
or SRAM. Ramtron use a ceramic called PZT, which consists mainly of lead,
zircon and titanium oxides, with traces of other elements. The ceramic’s
crystals polarise in one of two alternate states when energised by an electric
field.

SRAMs store data by circulating a current through one of two circuits
of transistors. A small amount of power is needed – such as from a battery
– to keep the current moving. In a FRAM chip based on an SRAM, the current
provides an electric field to switch the state of the ceramic. When the
power is switched off, the ceramic above each memory cell is switched to
a state representing the digital ‘one’ or ‘zero’ of the cell.

The polarity of the crystal is preserved for at least a year and, in
theory, as long as 10 years after power to the cell is switched off.

In the more widely used dynamic RAM chips, or DRAMs, the bits of digital
code are represented by the presence or absence of static electric charge
in a capacitor on the chip’s surface. The charge is let in or out of each
capacitor by its own switch but the charge continually drains away so it
needs to be constantly topped up from the mains or battery.

But the capacitors on DRAM chips take up a large amount of space; the
ceramic of an FRAM chip is capable of storing data in a much smaller space.
Ramtron aims in future to actually replace the capacitor with a small amount
of ceramic embedded in the chip.

The ferroelectric effect exploited in the FRAM chip was discovered in
the 1920s. An American electronics engineer, George Rohrer, first conceived
the idea of a ferroelectronic memory chip in the 1960s, but could not find
commerical backing for its development. However, Ramtron formed a partnership
with Rohrer in 1983.

After problems with the original ferroelectric material, Ramtron released
a 4096-bit FRAM chip for evaluation by industry engineers late last year.
At the end of last month the company launched a commercial version of the
chip. The first chip is very limited in capacity but Ramtron announced that
a prototype 256-kilobit chip is already in limited production at its factory
in Colorado Springs in the US, and will be released for evaluation by mid-1991.
A commerical version will follow early in 1992.

Lyndon-Jones says design is well advanced on a 4-megabit chip – the
size of the largest DRAM chip currently on the market – and there are plans
for 16-megabit chip.

The university has also come under criticism for releasing the findings
to the media before the work had been reviewed for publication in the appropriate
journals. Several Australian newspapers last week carried the story on their
front page.

Hiroto Naora, a Japanese-born biologist at the ANU’s Research School
of Biological Sciences, has succeeded in switching off an oncogene that
he had deliberately introduced into mouse cells in the laboratory. No one
disputes that he did this. But Naora’s claim that the oncogene had been
inactivated by competition from an adjacent gene has met with scepticism.

Tony Burgess, head of the Ludwig Institute of Cancer Research in Melbourne,
described the gene-competition hypothesis as ‘unlikely’. He questioned the
ANU for promoting the story before it had been through peer review.

Naora spliced together genetic material which included the human c-H-ras
oncogene, in close proximity to another, quiescent gene called gpt. When
he introduced the spliced material into fibroblast cells from mice, the
cells became cancerous.

Naora’s team then exposed the transformed cells to a drug that activated
the dormant gpt gene. This suppressed the activity of the oncogene and the
cells reverted to their normal state.

Naora explains the phenomenon by speculating that, like two competing
species occupying the same ecological niche, two competing genes cannot
act at the same time. He believes that a change in the DNA of the gpt gene,
activated by the drug, applies tensions to the DNA strand, forcing the neighbouring
ras oncogene out of its active conformation.

Burgess doubts whether this is the case. He says scientists know of
certain stretches of DNA in bacteria that may contain three overlapping
genes. These, he says, can be transcribed into RNA simultaneously, without
disrupting one another.

But Burgess reserved his main criticism for Naora’s suggestion that
doctors could treat people with cancer by exploiting the principle of gene
competition. This, he said, would involve identifying quiescent genes close
to known oncogenes and devising drugs to switch them on, thereby deactivating
the oncogenes.

Anthony Braithwaite, head of the Cell Transformation Laboratory at the
ANU’s John Curtis School of Medical Research, says that Naora’s choice of
a human oncogene for the experiment was ‘purely arbitrary’. It is appropriate
for the experiment because it has a highly measurable effect.

‘A gene for an enzyme that turned the cells blue would have done just
as well,’ said Braithwaite. ‘All he seems to have done is provided an experimental
test system for a hypothesis that he has outlined in several papers in the
1980��.’

Some tumours result from chromosomal translocations, in which stretches
of DNA are ‘swapped’ between chromosomes. Braithwaite said Naora’s theory
offered one explanation for such tumours. ‘If the oncogene is normally active
at a very low level, it may be because it is restricted by its proximity
to a neighbouring gene. When it is translocated, that restriction is removed.’

The team has shown that the newly discovered gene – called SRY for sex-determining
region, Y chromosome – has counterparts on the Y chromosome of other placental
mammals, including chimpanzees, rabbits, pigs, horses, cattle and tigers.
The researchers have also shown that the equivalent of the SRY gene in mice
is active only in the testes. This evidence strongly supports the idea that
the SRY gene is the elusive testes-determining factor.

The discovery, published in today’s edition of Nature (vol 346, p 240),
was made by a team of molecular biologists led by Andrew Sinclair working
in Peter Goodfellow’s laboratory at the Imperial Cancer Research Fund in
London. The team found the gene in a segment of DNA on the short arm of
the Y chromosome which they had cloned last December.

The biologists located the new gene by ‘chromosome walking’ – using
tiny, overlapping DNA clones from their cloned segment of Y chromosome to
reconstruct the region. They worked systematically from the ZFY gene, discovered
about two years ago and once thought to be the testes determining factor,
to the tip of the Y chromosome.

Sinclair’s group worked closely with another led by Robin Lovell-Badge
at the Medical Research Council’s National Institute for Medical Research
in London. In the same issue of Nature (p 245), Lovell-Badge and his colleagues
virtually clinch the identity of the TDF gene by showing that it becomes
active in embryonic male mice 10.5 days after conception, in a region known
as the urogenital ridge. This region, 11.5 days after conception, makes
the testes in male mice, and causes the embryo’s ambiguous sexual plumbing
and external genitalia to differentiate into the male ducts, testes and
penis.

In the absence of a Y chromosome, and by implication of the TDF gene,
the embryo develops the internal ducts and external genitalia of a female.
So many researchers see the TDF gene as a ‘genetic switch’, which in turn
activates a cascade of genetic events that lead to the formation of the
male reproductive system. ‘Understanding the mode of action of TDF may provide
a general model for the genetic control of developmental decisions in mammals,’
Sinclair and his colleagues suggest.

The newly discovered SRY gene has similarities with genes for certain
DNA-binding proteins, hinting at how the protein coded for by the gene may
work. But the researchers have found an even more intriguing similarity:
when Sinclair’s team searched DNA databases for related sequences in other
species, they found that it shared a small but crucial sequence with a gene
called Mc in a primitive species of yeast, Schizosaccharomyces pombe. The
Mc gene codes for a protein that determines mating type – in these yeast,
only yeast cells of opposite mating type can exchange genetic material during
conjugation. The mammalian TDF gene may thus have descended from a gene
that played a role analogous to sex-determination in single-celled organisms
a billion years ago.

An American group headed by David Page, of the Whitehead Research Institute
in Cambridge, Massachusetts, was also hot on the trail of TDF. Just over
two years ago, Page and his colleagues cloned a gene on the Y chromosomes
called ZFY which they believed was the testes-determining factor. But tests
in Australia by Jenny Graves and her colleagues at La Trobe University in
Melbourne failed to detect any corresponding sequence on the Y chromosomes
of male marsupials. Moreover, she and her colleagues discovered ZFY-like
sequences on two non-sex chromosomes.

The plasma arc furnace destroys toxic chemicals, such as polychlorinated
biphenyls (PCBs) and dioxins, almost instantly at temperatures four times
as hot as the surface of the Sun. While the concept of using an incandescent
electric arc to destroy toxic wastes is not new, S. ‘Rama’ Ramakrishnan’s
research team from the Division of Manufacturing Technology at the CSIRO,
Australia’s government research organisation, has overcome several problems
related to the temperature and stability of the plasma arc.

To destroy complex toxic molecules completely at rates high enough to
be efficient, the waste stream must be directed accurately into the core
of the arc, where temperatures approach 30 000 K. But no metal or ceramic
nozzle could tolerate prolonged exposure to the arc without melting. The
stream of cold wastes also tends to cool the arc, displacing the zone of
maximum temperature away from the core in an unpredictable pattern, resulting
in incomplete combustion.

Ramakrishnan has developed and patented a system that guides the waste
directly into the axis of the arc, which flows between two copper electrodes.
The gases are set swirling so that the arc assumes the shape of a ring-shaped
column and this turbulence ensures a more even temperature distribution.
An external magnetic field is applied which interacts with the ionised gases
and helps to constrain and maintain the shape of the arc, maximising its
temperature.

Conscious of widespread community concern about the transport of toxic
wastes, and the operation of large, centralised waste-disposal centres,
the CSIRO team is developing a compact plasma arc furnace with a power of
150 kilowatts, that could be installed in any plant generating wastes. Much
of the energy could be recovered from the exhaust gases and recycled, either
as electricity or heat.

The intense heat of the exhaust stream and the high degree of ionisation
in the gases means that the exhaust can be used to generate electricity
by magneto-hydrodynamics. The highly ionised exhaust gases, when passed
through a superconducting magnet looped around the exterior of the exhaust,
induce a voltage between a series of paired electrodes. The resulting current,
after being converted to AC, could be used to power the plasma arc, or used
for other electrical devices on the premises.

Further down the exhaust, where the gas temperature falls below about
2000 K, the waste heat can be used to vaporise water to drive a steam turbine,
or for process heating.

The research team is now working to analyse the ionised gases emerging
from the plasma arc furnace, with the idea of stripping and reacting them
to form more benign, industrially useful compounds. PCBs, for example, produce
chlorine and hydrogen that could be reacted to yield hydrochloric acid.

Ramakrishnan believes the plasma arc furnace could be particularly attractive
to chemical companies. Last week he was approached by a Melbourne agricultural
chemicals manufacturer, Nufarm, which was recently targeted by Greenpeace
for allegedly discharging dioxins and chlorphenols into Melbourne’s sewers.
Last year Nufarm spent A$250 000 (about Pounds sterling 125 000) monitoring
its own wastes.

The images depend on the phenomenon of diffraction, where the path of
light is bent around the edges of obstacles. Light that is shone through,
or reflected off, a set of fine lines spaced very close together, can be
diffracted in a controlled way that separates the different colours. It
is the diffraction of light from the grooves of a compact disc that give
it its colourful patterns. ��è����Ƶs use a set of fine lines, known as
a diffraction grating, to analyse the spectra of stars and galaxies and
the light emitted by chemical samples.

Lee’s research led to the flexible grating that appears in one corner
of a $10 note to commemorate Australia’s bicentenary. The silvery image
of Captain Cook contains tiny tiles, each of which is a minute diffraction
grating. Lee calls them ‘catastrophe pixels’ because of the way the image
flips from positive to negative at a certain critical angle.

The Australian Reserve Bank initiated the banknote project in 1968 after
forgers managed to copy the country’s decimal currency, still new at the
time. By 1975, scientists at CSIRO had developed a range of anti-forgery
techniques, including plastic notes that changed colour when touched or
others that remained transparent until exposed to light. Still others featured
images that ‘walked’ across the face of the note.

But the bank delayed using any of the new technologies and CSIRO lost
patience in the early 1980s. It sold the patents to the bank, although it
retained rights to the technology of the catastrophe pixel, called CATPIX-I.
The bank eventually launched its commemorative note in January 1989 with
a CATPIX-I image of Captain Cook.

Now Lee has developed CATPIX-II, which has smaller pixels and, unlike
its predecessor constructs the whole image, rather than certain areas of
it, from diffraction gratings. A CATPIX-II image is created by scanning
a colour picture into a computer which then divides the picture into 10,000
cells each 0.25 millimetres across. The detail of the image within each
cell is then presented as thousands of interlocking rectangles, parallelograms
and trapezoids. It is the parallel sides of these shapes that act as diffraction
gratings. The spacing of the parallel lines defines how the light is diffracted
and what colour it appears to be. The final image contains 2.6 billion of
these shapes.

The pattern is then etched onto a surface using an electron beam, a
technique borrowed from the manufacturers of semiconductor chips. The resulting
original is a negative and is used to press positive copies on thin metallised
foil which are then coated with plastic.

Lee believes it will be virtually impossible to forge the images. Any
forger who wanted to make a copy would have to remove the layer of plastic,
take a pressing from the film and use that negative pressing to print positive
copies. These second-generation copies would contain many tiny errors in
the precision grating and the characteristic flip from positive to negative
would be smeared and indistinct. A viewer would see a mosaic of tiny positive
and negative tiles mixed together.

It would also be difficult for counterfeiters to make their own original
because of the complexity of the production process. By choosing an image
that was difficult to copy, such as the face of a recognisable person, the
bank could make it harder still.

The gratings cost A$10,000 to produce and would probably be sold to
companies at A$200,000 each for them to print their own foils for credit
cards, banknotes and the like.

However, CSIRO’s intention to market the technology may be complicated
by the fact that the Reserve Bank has just started trying to sell CATPIX-I
to other countries. CSIRO feels an obligation not to make the bank’s technology
obsolete by launching its own newer technology.