Friday, August 29, 2008

Medicines from Monotremes

Somewhere in Eastern Australia, I stand on a darkened riverbank, huddled against the frigid wind. It is 2am, and I’m holding a small animal in my hands. It is covered with furry, loose skin, makes a growl like an angry cat, and tries to chew my hand with its soft, duck-like bill. The cold and the early hour are causing my mind to wander, and as I hold the squirming platypus, I reflect on the millions of years of evolution that have led to the strange creature I see before me.

Platypuses and echidnas are members of an ancient group of mammals called Monotremes, which have been around for 166 million years. They lay eggs like a reptile and produce milk like all mammals, and in the case of platypuses, produce venom like a snake, making them very unusual indeed. Little wonder that when platypuses were first discovered they were thought to be the trick of a taxidermist!

I am here on the riverbank to collect samples of platypus genetic material, which I’m going to use to unlock the secrets of its evolution, and maybe even help humans a little along the way. My research involves examining the genes of the platypus to help with understanding how mammals first evolved from their reptilian ancestors. Geneticists like me can investigate how traits like egg-laying were superseded by features such as milk production, and by looking at genes that are in both platypuses and modern mammals like humans, can also work out which genes are really important for us mammals. Although you won’t find humans sprouting a duck-bill any time soon, you might be astonished to learn that more than 80% of the platypus genes are also found in the human genome. In particular we can examine the genes involved in platypus immunity and learn more about how mammalian immune systems function and have evolved. Perhaps we may discover new ways of boosting our own immune systems.

My colleagues and I are studying the platypus genes that code for antimicrobial proteins. Unlike humans, platypus young are born after a short gestation in an immature state. They thus have a very underdeveloped immune system, and yet these fingernail-sized hatchlings still manage to survive in a dirty burrow that is full of microbes. Our team is investigating the possibility that platypus milk contains antimicrobial proteins which protect the developing young from infection. In the future, I hope it will be possible to duplicate these ‘natural antibiotics’ to develop new treatments for human diseases, which are urgently needed to combat existing antibiotic resistant pathogens.

We are also researching another bizarre feature of the platypus: its venom. Males have sharp spurs on each hind leg that are used to deliver a potent chemical poison into victims. Venom is used during fighting between males, but it can also be used for defence against potential predators like foxes and domestic dogs, which if spurred may die, and the occasional unwary human like me! Luckily, the animal I’m holding is a female so has no spurs, because in humans, envenomation causes terrible swelling and excruciating pain that is not relieved by morphine. There must be some very interesting and novel chemicals in the venom to cause such unusual symptoms. I am working to identify the chemicals by decoding the genes that produce them. Snake venoms have already been used to develop drugs to treat human diseases, and I’m hoping that our platypus venom research might also lead to the development of novel drugs. In particular, if we can find the platypus venom chemicals that cause the extreme pain, we may discover new pain receptors and be able to develop novel painkillers to block them.

A shout from a colleague reminds me that it’s time now for my platypus to have her blood sampled. From this I will be able to extract and study her DNA. The procedure is over quickly, and I take her down to the water to release her. She gives one parting growl, and then slips quietly under the water, apparently unaware of the great potential of her genes to help us improve human medicine.


Legs Like A Supermodel

Exceptionally long, slim, and elegant legs are a ticket to a glamorous world of champagne and parades. However, I’m not talking about the world of a supermodel, but rather the world of a Thoroughbred racehorse.

The parallels between racehorses and models go beyond the length of their legs. Both groups are thought to live on a mainly herbivorous diet, neither speaks much in public, and both horses and models have a beautiful mane of hair. There are some important differences, of course: for example, racehorses wear flat shoes not stilettos.

You may have noticed that racehorses are heavier than models too. Racing fit, the average Thoroughbred weighs at least 500 kilograms. Racehorses also run faster than models, travelling at up to 60 kilometres per hour at full gallop. Due to their weight and speed, the bones in racehorses’ legs are subject to enormous forces during a race, and the presence of any flaws in these bones can have catastrophic consequences.

My research focuses on a bone growth disorder in Thoroughbred racehorses, called osteochondrosis. Osteochondrosis causes lesions in the joints of the legs. In a horse suffering from this disease, small regions of the bone growth plates that lie just below the joint surface fail to mature correctly. This leaves cores of weaker cartilage where there should be bone. A racehorse with osteochondrosis lesions has an increased likelihood of suffering both recurrent lameness and catastrophic breakdown.

Because osteochondrosis occurs while the horse is growing, I am following Thoroughbred foals through the first twelve months of their lives. I am recording the pedigree of each foal in the study, and visiting them regularly to observe the different environments in which they are raised. When the young racehorses are twelve to eighteen months old, they will have their legs x-rayed. This is traditionally the method by which vets diagnose osteochondrosis and other bone problems before the horses are sold. I will use this information to calculate the relative contributions that genes and environment make to osteochondrosis in racehorses.

In order to make my study statistically valid, I am following hundreds of foals. Fortunately, most foals are very inquisitive, and getting close to them is not hard. Unfortunately, foals (like babies) seem to follow the steps of 1) briefly observing the novel item – me, and then 2) trying to put it in their mouth or up their nose. As well as studying osteochondrosis, I believe I could track the foals’ increasing curiosity and independence by analysing the amount of saliva left on me at the end of each visit.

Foal spit aside, this research is important. This study should help breeders predict which horses are most likely to develop osteochondrosis, before the lesions occur. Horses that are identified as being at risk could then be managed differently to their healthier counterparts, by altering their diet and other factors that may contribute to the disease. Reducing the rate of occurrence of osteochondrosis will result in less pain and loss of life amongst racehorses, as well as saving money for horse owners, breeders and trainers. Equally importantly, the fact that this research is being carried out at all shows that the racing industry is increasingly embracing scientific research as a way forward.

The horse racing industry is one of the largest industries in the world. In Australia, it contributes more than $8 billion to the economy. In the USA, it is bigger than Hollywood. In the UK, there is almost £100 million of prize-money available for horse races, and one in eight agricultural workers is employed in the horse industry. However, with a few exceptions, it is a highly traditional industry that has not embraced change.

There are many challenges for the horse racing industry to face in coming years. Infectious diseases must be managed and treated, and new farming and training methods will be called for to work with the changing climate. Breeders aiming to create new champions will need information to ensure that their horses remain genetically diverse and healthy. Scientific research will be invaluable in helping the racing industry meet these challenges.