The secret to running repairs

THEY are masters at regenerating their own limbs, tails, jaws, retina and heart. They can recover from spinal chord and brain injury and can easily tolerate organ transplants. And to top things off, they don't get cancer. Meet the axolotl, otherwise known as the Mexican walking fish..

''This animal guards so many interesting biological secrets,'' says James Godwin, a senior research fellow at Monash University's Australian Regenerative Medicine Institute. ''Things that would leave humans in a wheelchair or dead they can just repair in no time at all.''

And there's more to this extraordinary amphibian, which was named after an Aztec god who transformed into a water animal to avoid being sacrificed. The skin of the albino axolotl is transparent enough so that you can actually watch the organs and blood vessels as they pump and pulse under the surface. In juveniles, it is possible to distinguish between the left and right hemispheres of the brain when peering thorough the translucent skin.

But what most excites researchers working with the Mexican walking fish is the amphibian's regenerative capabilities. Regeneration - the faithful replacement of damaged or missing tissue - is not uncommon in invertebrates. Worms and starfish are just some that can re-grow body parts and organs. But axolotls are in a league of their own because they, like us, are vertebrates. This makes them the closest thing to humans that are able to regenerate.

In Mexican walking fish, limbs can be removed and re-grown without so much as a scar and, amazingly, the heart can regenerate after having a third of it removed. Similarly, it can have sections of its spinal chord ''cut and pasted'' without killing it. Try doing that to a lab rat - let alone any other mammal.

However, this amphibian, which can live to 25 years of age in captivity and grow up to 40 centimetres long, is something of an outsider among the science establishment.

The few researchers who devote their energies to understanding what makes this creature tick often struggle to get funding for their work - from the government or the private sector - because conventional thinking is that research using mammals can be better translated to to humans.

It's a view echoed among some traditionally minded journals, which dismiss submissions or refuse to publish papers believing the leap between such an eccentric-looking ''walking fish'' and humans is too great.

Godwin sees it differently. ''In order to get results for human health, we need to study a diverse set of animals,'' he argues. ''If we only work on mice, we won't get the answers.''

Since returning to Melbourne from University College London in 2009, Godwin has mapped the axolotl's immune system and established an 1000-strong axolotl colony from 20 animals at the Clayton institute. It was a process not without its challenges. First, he had to petition for federal law to be changed to add the creature to a list of live species allowed to be brought into the country - this took 17 months.

But it was essential, as Godwin needed what are known as trans-genic populations: genetically modified animals from Germany and the US.

A trans-genic creature is created by injecting a piece of DNA into a fertilised egg. This enables the integration of the DNA into the developing embryo; an enzyme is then added to ensure that the introduced DNA becomes part of the chromosome.

''Once the piece of DNA is inserted in the chromosome, it carries the information to express a florescent protein in a particular type of cell,'' Godwin says.

''So you can get one that directs it towards the blood cell, the muscle or the skin. We use this to paint different cells different colours to track cell movement and interactions.''

He has since created six trans-genic populations at Clayton - including groups that have been genetically modified so certain cells in the body become florescent: for example muscle cells in some animals glow bright red while in others immune cells glow green.

This kind of work - being able to track cells in a living animal - is impossible with mammals. And Godwin thinks this will be one of the key attributes that will help the Mexican walking fish become more widely seen as an asset to medical and scientific research.

First described in 1789, they have been studied for many years. But science is yet to fully explore what the Mexican walking fish has to offer modern medicine.

''The best thing about axolotls is that they can do a lot of things that we wish that we could - and we need to understand how they do their clever tricks and why humans can't,'' Godwin says.

There are about dozen laboratories worldwide that study the axolotl, mainly in the US, Japan, Germany and Canada. ''Now we can add Australia to the list,'' Godwin says. ''That's one for the region.''

Located at Monash University's Clayton campus, the Australian Regenerative Medicine Institute is the only place in the country with a research team dedicated to unravelling the mysteries of the axolotl.

Next month, the amphibians that call Clayton home will finally move to their own permanent, purpose-built, $1.8 million premises. It's a milestone Godwin hopes will usher in a new era of increased research into, and renewed respect for, the much overlooked axolotl.

The new axolotl facility is next door to another of the institute's laboratories. Known as FishCore, it's the biggest zebrafish facility in the southern hemisphere with more than 6000 tanks. Of all things, it's the aptly named zebrafish that is being held up as a role model. Like the Mexican walking fish, the tiny freshwater creature was scientifically sidelined for a decade as scientists worked hard to prove it was a species medical researchers could learn from.

Those working closest with the tropical fish championed its attributes but had to convince an often sceptical, conservative scientific community.

''For the new thing on the block to gain some credence and some credibility, there is some groundwork to be done by those investigators to prove that it is worth investing in and that it's not a fly-by-nighter,'' says Professor Peter Currie, deputy director of the institute.

Growing more vocal, and with increasing evidence to back up its convictions, the zebrafish research community managed to prove its point: that zebrafish biology allows ready access to all developmental stages, including the ability to see the inner workings of embryos and larvae, while genetic mutations can be introduced with ease.

They also develop rapidly: scientists can observe heart valves form within 48 hours in the transparent embryo, compared to 10 days in mice.

Zebrafish have also been found to be a valuable species to study disease. For example they share similar types of muscle degeneration to humans, making them the ideal animal species to study Duchenne muscular dystrophy - a muscle-wasting disease that affects about one in 3600 boys and for which there is no known cure.

''The fish get a dystrophy that is more closely similar to the human disease than in mice,'' Currie says.

This has made the fish the fastest growing animal model in biomedical research. Currie, whose research centres on how the small fresh water fish can build and regenerate both skeletal and cardiac muscle, says between 1990 and 2006 there was a 40-fold increase in the number of zebrafish-based research published in scientific journals.

By contrast the number of mouse-based research published in journals little more than doubled over the same period.''It's an established model now,'' Currie says. ''Every research institute worth its salt now has a zebrafish researcher.''

It's this sort of mainstream scientific acceptance that Godwin hopes the axolotl will emulate.

Certainly, progress has been made. Some of the key genes that regulate spinal chord regeneration in axolotls have been established and compared with that of the mouse and rat.

Chief among the questions surrounding the axolotl is whether a cure for cancer might lie beneath the translucent skin of the albino axolotl.

Essentially, controlling cancer is about controlling cell growth. ''Cancer is like a wound that never heals and how the immune cells deals with this perpetuates cancer and allows rogue cells to proliferate and grow crazy,'' Godwin says.

''How axolotls can suppress cancer and activate regeneration is one of the things I would like to get to.''

But such questions are best answered at a genetic and molecular level. To do this, the genome - or genetic blueprint - of the axolotl needs to be sequenced and compared with the human genome.

To date, scientists have identified about 22,000 axolotl genes from a genome which is 10 times the size of ours.

Because of the increased scale and complexity - as well as an absence of funding - sequencing the genome isn't a mainstream scientific priority. However, the US defence department is increasingly interested in limb regeneration research as more soldiers return from war having lost a limb.

More than 1570 Americans have lost a leg or arm in combat in Iraq or Afghanistan. Most are in their 20s and will require a lifetime of medical care: for a start amputees need new prosthetics fitted every few years.

''The US Department of Defence is very keen to get involved with limb regeneration,'' Godwin says.

Modern warfare means superior flack jackets now protect soldier's chests and heads. But roadside bombs inflict devastating injuries to the limbs, which are not similarly protected. In this context, Godwin argues, the social and economic benefits of regeneration medicine are immense.

While the Defence Science and Technology Organisation in Australia is not actively pursuing regenerative research, it is keeping a close eye on what is being done by Godwin and his team.

And it's outside interest which is most needed to take the axolotl where the zebrafish has already gone.

Godwin believes it's a matter of when, not if, things will change and there will be more funding for axolotl research.

''It's not science fiction it's science fact. Axolotls can do these things and we can't,'' Godwin said.

''But if we can find out how they do it, then apply these proven biological strategies we may get insights that help people recover from surgeries, accidents or any sort of regenerative disease.''

Bridie Smith is science reporter.

The story The secret to running repairs first appeared on The Sydney Morning Herald.