The Science Bit – Part 10: Pigs lead the way in Cystic Fibrosis research

1 04 2011

Cystic Fibrosis (CF) is a recessive genetic disorder that affects approximately 8,500 people in the UK. It’s the most common life-shortening inherited disease in the world, with around 1 in 20 people being a carrier for the condition.

CF is caused by a mutation in the gene for a protein called the cystic fibrosis transmembrane conductance regulator or (thankfully) CFTR for short. This protein, in its normal state, is a channel protein that controls the movement of salts from the inside of the cell to the fluid surrounding the cells in the lungs, pancreas and other affected organs. In the sweat glands, CFTR usually works by moving salt from the sweat on the skin back into the body. When CFTR does not work properly however, too much salt and not enough water accumulates in the lungs, pancreas etc, and remains on the skin. The lack of water means that the normally lubricating tissue fluid in these organs becomes thick and sticky mucus.

The most recognisable symptoms of CF are to do with the build up of mucus in the airways, which causes unrelenting, mucusy coughing and a difficulty in breathing. Bacteria thrive on the thickened mucus, so lung infections including pneumonia are common, leading to damage of the airways and general poor health because of the inability to exercise properly to maintain fitness.

Mutated CFTR has effects elsewhere in the body, too. In the intestines, severe, chronic constipation caused by a lack of water to soften stools in the bowel can often lead to infection and rectal prolapse. Food cannot be digested properly in the small intestine, so CF patients often have difficulty in maintaining their weight and growth is stunted. The bile ducts may become blocked and cause damage to the liver. Cystic Fibrosis-related diabetes may occur as a result of the blockage of insulin in the pancreas. 97% of CF men are infertile because of an absence of the vas deferens, the tube that supplies sperm to the penis.

Given all these complications, it’s perhaps not surprising that until only a few decades ago, an infant born with CF would have been lucky to reach its first birthday. Now, although still a relatively short life expectancy, a CF sufferer might live well into their 30s and 40s, and with a successful lung transplant, even longer. Advances in treatment, including respiratory therapy, antibiotics, physiotherapy, diet and lifestyle changes have all made significant improvements to the quality of life for CF patients. But while the symptoms of CF can now be more effectively managed, there is still no cure for the disease.

A key to finding a targeted cure for CF is to understand the genetic and molecular processes that go on at the cellular level. Recently, a team of researchers from the University of Iowa made an important discovery that brings us a little step closer to the end goal of curing this disease. Pigs.

Pigs have long been used as an animal model for human disease research because in many organ systems, they have a very similar anatomy. Of course, there is much about a pig that is different, but by genetically engineering a pig model that mimics the faulty CFTR gene, the research team have been able to discover that the mutated protein has the same pathological effects in their pig model as in humans. This breakthrough means that pigs may now be used in further research to more accurately pinpoint what exactly happens to the mutated CFTR protein, and to find a way to treat it or correct it.

Using their new model, the team, whose findings were published in Science Translational Medicine last week, have already identified that the faulty CFTR protein is “misprocessed” in the cell and ends up in the wrong place, compared to the normal protein. Now that we know that pigs are analogous to humans in the manifestation of CF, they can be used to test a variety of potential new treatments, including gene therapy techniques that replace the faulty gene with a working copy, and “corrector” drugs, which aim to move the faulty protein to its proper position in the cell. The development of a pig model for studying this disease opens new doors to finding a way to beat cystic fibrosis, and new hope to its victims.

The Science Bit: Part 9 – The Human Genome Project – 10 years on

25 02 2011

The human genome projectIn 2001, the journals Science and Nature simultaneously published the results of a decade or more of groundbreaking scientific research – the Human Genome Project. But what is the Human Genome Project? Why was it done? And most importantly, what have we learnt from it?

Inside almost every one of our cells are chromosomes made up of DNA. DNA is a long, twisted molecule made up of units of 4 chemicals called adenine, thymine, cytosine and guanine and (A, T, C and G respectively), plus some sugar and phosphate molecules to hold it all together. We’ve known for many years that small sections of DNA, called genes, provide the instructions to make different proteins, and proteins are important because they are involved in just about every chemical, mechanical and structural function in the body.

The primary aim of the Human Genome Project (HGP) was to “spell out” the sequences of As, Ts, Cs and Gs for every single human gene. It was hoped that if we can do this and discover what a “normal” gene looks like, then we would also discover the genetic mutations and abnormalities that cause human diseases. Not only that, but by mapping the location of each gene on each chromosome, we might be able to use targeted drug and gene therapy to treat or even cure some of these diseases.

The announcement, in February 2001, that the human genome had been sequenced was front page news. After years of trying, and $3 billion of funding, it had finally been done. Researchers heralded the beginning of a “golden age” for genomic research, and the media were in a frenzy speculating on all the terrible diseases that may now be cured, all the wonderful new drugs that might be developed. But then, after the hype, it all went quiet.

So what has the HGP achieved in the last 10 years? We still haven’t cured cancer, or AIDS, or Alzheimer’s, and stem cell therapy is still a rather experimental treatment for some diseases rather than the miracle cure-all we hoped it would be. Was the HGP a waste of time and money?

Of course the answer to this is “no”. Though, as a result of the HGP, medicine has not advanced as much as we might like in the last decade, our underlying understanding of genomics has made great leaps and bounds. As The Economist’s Science Editor Geoffrey Carr wrote recently, the race (between rival research teams Celera and the International Human Genome Sequencing Consortium) to sequence the human genome “was not a race to the finish line, but a race to the starting line”.

So what have we learned from the HGP? Well, the very fact that the entire human genome – some 3 billion As, Ts, Cs and Gs long – could be sequenced and mapped is in itself a marvellous achievement for scientific research, and the sequencing process has been refined so that it is now much quicker, cheaper and more efficient. Despite humans being one of the most complex organisms on Earth, we’ve learned that the human genome is much smaller than we originally thought – we have around 22,000 genes, in comparison to the very recently-sequenced and very tiny water flea (Daphnia pulex), which has 31,000.

Though the head of pharmaceutical company Novartis once quipped that the HGP had yielded “data, data everywhere, and not a drug, I think”, we are now beginning to see advances in medicine too. While we have not yet witnessed a “revolution” in terms of “the diagnosis, prevention and treatment of most, if not all, human diseases”, as predicted by then-President Bill Clinton in June 2000, we have pinpointed the genetic defects that cause around 850 diseases and this is slowly but surely leading to advances in their treatment. Thanks to HGP research, several new drugs for cancer, osteoporosis and lupus are now beginning to enter the market after a decade of trials, and genetic screening is becoming more widely available for a greater range of diseases.

Despite the deficit in new discoveries that have been sensational enough to rouse the interest of the general public, the Human Genome Project and the ongoing research stemming from it, is still plugging away and helping to increase our overall understanding of genomics. If sequencing the human genome was a sprint to the start line, the race from here on is a marathon, but one that will ultimately impact greatly on biology, medicine and science as a whole.

The Science Bit: Part 7 – Oh deer! Christmas trees’ battle with Rudolph

24 12 2010

A lighthearted and seasonal Science Bit for you this month!

Ah, there’s nothing like a real Christmas tree. You can keep your plastic trees, sprayed white and gold or with fibre optic lights – for me, the annual trip to choose and collect our perfect pine tree symbolises Christmas itself and the beginning of festive few weeks of fun with friends and family.

But for some people in North America who also love the real thing, the humble Christmas tree is under threat from a very seasonal character that usually helps Santa rather than hinders him. Forests of Fraser firs in North Carolina are often frequented by deer who damage the Christmas tree crops by butting them with their antlers in order to mark their territory and by nibbling on the young shoots and buds. According to Christmas tree production specialist and agricultural researcher Jeff Owen from North Carolina State University, a single deer can munch a young Christmas tree down to the size of a pencil in no time at all.

Of course, a simple way to keep Rudolph out of the forests would be to erect good quality fencing, perhaps even electrified barriers, however with over 350 Christmas tree farms producing more than 20,000 acres of Christmas trees each year, fencing and fence maintenance is extremely expensive. An alternative is to use commercial deer repellents, but again, this can be prohibitively expensive, with 1lb of repellent costing around $18 USD, and up to 10lbs of product used per acre, two or three times a year.

Funded by the North Carolina Christmas Tree Association, Owen and his team have been researching effective deer repellents that would make a viable and cheaper alternative to the existing commercially-available products. Old wives’ tales recommend hair clippings, cayenne pepper and raw eggs to keep deer away, and it turns out that the latter of these isn’t far from the truth. The scientists discovered that a prepared mixture of dried blood and egg powder is the perfect deterrent for Bambi and friends, and can be bought very cheaply at a cost of just $2 per lb of product thanks to the fact that these are common, inedible by-products of the pet-food industry.

Owen says, “These products have an unappealing taste, but the decaying smell actually elicits a fear response in the deer and keeps them away from the crops”.  It is hoped that dried blood and powdered egg could save threatened Christmas tree stocks in North Carolina, and with the team now making headway on extending their research to see if other pet food waste products, like liver powder and fishmeal, are as effective deer repellents, tree farmers all over the States could be spoilt for choice and assured of a sustainable future. Sorry Rudolph!

The Science Bit: Part 6 – A Nobel way for infertile couples to conceive

30 11 2010

British physiologist Professor Robert Edwards has recently been awarded the Nobel Prize for Medicine for his pioneering development of the In Vitro Fertilisation (IVF) technique. IVF has given hope – and children – to thousands of childless couples over the last 30 years, and the procedure is being improved all the time.

There are many reasons why some couples can’t conceive the baby that they so long for, and until fairly recently, childless couples had adoption as their only hope of bringing up children. However, in the mid 1960s, Cambridge Professor Robert Edwards began to study human fertilisation and was successful in creating the first embryo outside of the uterus in 1968. Ten years later, and the technique had been developed and improved so much that on 25th July 1978, Louise Brown, the world’s first “test-tube baby” was born. Since then, it is estimated that more than 4 million children worldwide have been born as a result of this life-changing procedure.

Normally, a female’s eggs are released into the uterus one at a time over the course of the normal menstrual cycle. In order to obtain the highest possible chance of pregnancy however, a woman who wants to undergo IVF will first need to start a course of hormone treatment in order to “ripen” a number of eggs all at once. These are then extracted from the ovaries and mixed with sperm collected from the father where, hopefully, fertilisation occurs.

The embryos are grown in an incubator for a few days and a maximum of 3 are then selected to be implanted into the mother’s uterus – the rest are frozen in case of future need. Only 1 in 5 embryos will successfully implant into the uterus and result in a pregnancy and while this doesn’t sound like very good odds, it’s actually very close the number of pregnancies achieved without IVF.

One of the problems with IVF is that it carries an increased risk of multiple pregnancy. Because of the high cost of IVF – around £4000 to £8000 per cycle, it is something that many couples can only afford to do once, and if using more than embryo gives the greatest chance of success, then this is the option most parents choose. While 8 babies in one go – like “Octomom” Nadya Suleman – is very rare, twins or even triplets are fairly common, but though it may be a blessing for some, a multiple pregnancy carries a much greater risk of gestational complications for the mother, a low birth weight and premature birth for the babies, along with an increased risk of congenital abnormalities. Is it worth risking the health of the mother and the babies to get it right first time?

The general medical consensus is no, the best choice is to opt for single embryo transfer, yet around two thirds of parents still choose to implant the maximum number of embryos that they are allowed (in the UK, two for mothers under 40, three for mothers over 40). Researchers from the Radboud University Nijmegen Medical Centre in the Netherlands predicted that this tendency for parents to go against expert opinion was a result of poor pre-natal care and support provision, as well as the cost factor.

In a simple randomised controlled trial, they looked at the effects of providing better means for parents to make an informed choice, as well as the option to undergo a second cycle of single embryo transfer IVF at no extra cost if the first cycle failed.  Indeed, in their findings recently published in the British Medical Journal, they found that uptake of single embryo transfer IVF was increased when this safety net was offered. Though the results were not statistically significant, the researchers are confident that by improving the amount and quality of information available to those considering IVF, ”a multifaceted patient empowerment strategy… could be an important tool to reduce the twin rate after in vitro fertilisation”.

The Science Bit: Part 4 – Sunlight – Friend or Foe?

2 09 2010

At this time of year, when the sun is (hopefully) shining and we’re looking forward to our summer holidays, messages about sun safety abound. In this seasonal Science Bit, Lisa Martin examines new research that suggests some of us play a little too safe in the sun.

In Australia, the oft-quoted “Slip, slap, slop” slogan, reminds us to slip on a t-shirt, slap on a hat and slop on the sunscreen in an effort to educate the public about the dangers of too much exposure to ultra-violet light. It’s common knowledge that this is the single most frequent cause of skin cancer, and has a premature ageing effect as well, but less well known it seems, are the positive effects of exposure to sunlight.

Vitamin D, actually a group of chemicals called secosteroids, is vital for our health.  Vitamin D is used to activate a hormone that performs a number of essential roles in the body, the most significant of which is to fix calcium in the bones, thus making them hard and strong.  A very small amount of vitamin D can be taken in through the diet, but in order to gain enough, we’d have to eat oily fish – even the skin – 3 times a day, every day! I don’t know many people who like sardines that much! Instead, the majority of our vitamin D is actually made as the result of a chemical reaction that uses sunlight.

A substance called 7-dehydrocholesterol, found naturally in the epidermis of the skin, absorbs UV light and is then broken down into vitamin D. If we do not obtain enough vitamin D, a deficiency can lead to several bone disorders, most notably, osteoporosis (brittle bones) and Ricketts (soft bones). People who spend all day indoors, those who work night shifts and those who cover their whole bodies for religious or cultural reasons, as well as children and the elderly, are most at risk of vitamin D deficiency.

A recent article in the Independent newspaper revealed that Cancer Research UK, the country’s leading cancer research and education body, is currently drafting a new position statement to reflect emerging research findings in this high profile area. Traditionally, the advice has always been to avoid going out in the sun between the hours of 11am and 3pm when the intensity of UV radiation from sunlight is strongest, to cover up and to wear a high factor sunscreen. All of these things however, are a barrier to vitamin D production in the skin.

Is it estimated that more than half of the UK population produce insufficient levels of vitamin D. We’re not helped by the fact that the UK is located in the far north of the hemisphere, where the UV radiation in sunlight is weak, but according to health writer and vitamin D campaigner Oliver Gillie, inappropriate sun safety advice is also largely to blame for the state of the nation’s vitamin D levels.

Recent research has shown that vitamin D deficiency could be a major contributing factor to several serious diseases, including heart disease, arthritis and susceptibility to infections. Gillie even believes that multiple sclerosis and insulin-dependent diabetes could both be completely eradicated if breastfeeding mothers took vitamin D supplements or spent enough time in the sun.

Clearly, recommending that people go out in the midday sun without sunscreen is dangerous advice if not communicated properly. It is still more pertinent than ever to prevent burning and the risks of skin cancer and premature ageing should not be underestimated. It only takes a few minutes of unprotected exposure to sunlight in order to make enough vitamin D, so for most people sitting outside for 3 or 4 minutes a day before applying sunscreen will be more than enough to maintain your vitamin D levels and keep you healthy.

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