The Commerce of Human Genes

Nearly a fifth of all known human genes have been patented in the US, the majority by private companies, a new study reveals. The research, published in the journal Science, matched patented genes to their locations in the human genome. It showed that almost 4382 of the 23,688 genes present in the National Center for Biotechnology Information (NCBI) Gene database are claimed in 4270 different patents. Around 63 per cent of them are assigned to private firms, say authors Kyle Jensen and Fiona Murray of the Massachusetts Institute of Technology.

Critics of gene patenting argue that it stifles research, slows down the development of new medicines and increases the cost of genetic diagnostic tests. The worldwide patenting of two genes involved in hereditary breast cancer, BRCA1 and BRCA2, by US firm Myriad Genetics, was met with strong opposition by scientists in Europe. Following a series of challenges, nearly all the patents were either revoked or amended, so that most BRCA gene testing can now be carried out free of charge in European laboratories.

However, supporters of gene patenting say that protecting intellectual property is crucial for securing investment in later research, and central to the success of the biotech industry. In the latest study, the researchers wanted to gain an accurate picture of the gene patents taken out in the US. They found that the 4270 patents are owned by 1156 different assignees, with nine of the top ten being US-based. The top patent assignee is Incyte Pharmaceuticals/Incyte Genomics, whose intellectual property rights cover 2000 human genes.

The researchers found that many genes were claimed by several different patents - CDKN2A, a gene involved in cancer, and the bone growth gene BMP7 are the most patented genes in the genome, with 20 patents each. 'Our data raise a number of concerns about gene patents, particularly for heavily patented genes', said Murray. 'We worry about the costs to society if academic scientists and industry have to walk through a complex maze of patents in order to make more progress in their research', she told National Geographic magazine.

Commenting on the study, Helen Wallace, of the UK pressure group Genewatch, told the Guardian newspaper that gene patenting 'encourages a search for genes, when many problems with health could be addressed by better research into diet, social and economic factors'. UK bioethicist John Harris said that the pharmaceutical industry argues that they need to protect the products of their research, otherwise they would not invest in future research. 'However, I worry this kind of patenting could have impacts on the cost of health and the freedom to access it', he added.

The charity Cancer Research UK (CRUK) has obtained a Europe-wide patent on the BRCA2 gene, which is involved in hereditary breast and ovarian cancer. It intends to make the patent freely available to publicly-funded laboratories across the continent, so that research and diagnostic work on the gene can continue. The situation was previously complicated by patents held by US firm Myriad Genetics, on BRCA2 and another gene involved in breast cancer, called BRCA1.

Most breast and ovarian cancers are not inherited, but around 5-10 per cent are caused by inherited mutations - many of them in one of two genes, called BRCA1 and BRCA2. Myriad Genetics has faced criticism from scientists, governments and patient groups opposed to the patents that it holds on tests that look for mutations in these two genes. However, CRUK holds a UK patent on BRCA2, which is apparently wider than Myriad's and so covers more applications.

Cancer Research Technologies Limited (CRT), the commercial subsidiary of CRUK, has now successfully applied for a European patent on BRCA2, and has agreed to waive the fees for all public laboratories wishing to work on the gene. 'Myriad had been trying to offer commercial deals to researchers working on BRCA1 and 2' said John Toy, medical director of CRUK, adding that 'our patents will break that gridlock'.

CRUK was granted the BRCA2 patent on the basis that it funded much of the work that lead to the gene's discovery, at the Institute of Cancer Research, London, in 1995. The announcement was welcomed by Gert Matthijs, of University Hospital Leuven, in Belgium, speaking on behalf of the European Society of Human Genetics. He told The Scientist magazine that the BRCA2 patent issue illustrates why Europe needs new legislation on the licensing of genes and genetic tests. 'If someone holds a patent on a gene, it creates a monopoly because no-one can invent a competing product as they could with other items, such as drugs' he explained.

Celebration Time

A chicken farmer went into a local tavern and took a seat at the bar next to a woman patron and orders a glass of champagne.
The woman perks up and says "How about that? I just ordered a glass of champagne, too!" He turned to her and said, "What a coincidence. This is a special day for me, I'm celebrating."

This is a special day for me, too, and I'm also celebrating!" said the woman. "What a coincidence." said the man. They clinked glasses and he asked, "What are you celebrating?" "My husband and I have been trying to have a child. Today, my gynecologist told me I'm pregnant!"

"What a coincidence." said the man. "I'm a chicken farmer. For years all my hens were infertile, but today they're finally fertile."
"That's great!" said the woman, "How did your chickens become fertile?"

"I switched cocks." he replied.

"What a coincidence," she said.

Odds and Ends

Two doctors opened an office in a small town and put up a sign reading "Dr. Smith and Dr. Jones, Psychiatry and Proctology."

The town council was not happy with the sign, so the doctors changed it to "Hysterias and Posteriors."

This was not acceptable either, so in an effort to satisfy the council they changed the sign to "Schizoids and Hemorrhoids." No go.

Next, they tried "Catatonics and High Colonics." Thumbs down again.

Then came "Manic Depressives and Anal Retentives." Still not good.

Another attempt resulted in "Minds and Behinds." Unacceptable again.

So they tried "Lost Souls and Ass Holes." No way.

"Analysis and Anal Cysts?" Nope.

"Nuts and Butts?" Uh uh.

"Freaks and Cheeks?" Still no go.

"Loons and Moons?" Forget it.

Almost at their wit's end, the doctors finally came up with: "Dr. Smith and Dr. Jones, Odds and Ends."

And they loved it.

Roman Catholic Bishops say hybrid embryos have right to life

The human-animal hybrid embryo is formed from an animal egg cell (most likely from cows or rabbits). Scientists want to use such embryos to create genetically human embryonic stem (ES) cells. This method would overcome difficulties associated with the collection of human eggs from donors, and would provide a much more fruitful source of embryos for scientists.This egg cell's nuclear DNA is removed and replaced with nuclear DNA from an adult human. The cell is then 'kick-started' - with a small electric shock - into commencing cell division. The embryo would be almost 100 per cent human - the only non-human DNA in the cell comes as part of the cell's mitochondria: apparatus for providing the cell with energy.

Currently, the vast majority of human eggs given by donors are for IVF treatment and not for research. A recent consultation by the HFEA entitled 'Donating Eggs for Research: Safeguarding Donors' stressed both the ethical and safety concerns associated with methods used to collect human eggs. The creation of human-animal hybrid embryos is safe in that it involves no human participant, except for the collection of a few skin cells. The voices arguing against the work are few; indeed there has been a distinct lack of comment pieces in the press supporting a potential ban. Naysayers rely on two arguments: a moral argument, and the prediction that this avenue of research will be useless. The practise of creating human-animal hybrid embryos is, they say, unnatural, and therefore immoral. This is a familiar reaction to new biological technology: IVF is 'unnatural', but is now accepted as a useful technology to aid fertility treatment. And although no one yet knows whether this research will prove fruitful, this should not be used as argument for banning the work. The proper action should be to let the research commence, and to monitor the results for potential benefits, or ethical concerns.

Two important points must be brought to the attention of the public:

1) The enormous potential that this avenue of research could hold. The 'could' should also be stressed. Nothing tangible has resulted from this work at this stage, but scientists agree that this line of research should not be closed before its potential fruits can be assessed.
2) The fact that there is absolutely no likelihood that this work could result in a 'hybrid-human' or any other 'Frankenstein's monster' type result. The subject of the research is cells, not animals. These embryos are a potentially useful research tool, and the potential for exploring new avenues of research should be welcomed.

The Roman Catholic Bishops of England (RCBE) have told the UK parliament that inter-species embryos - those containing genetic information from both human and animals - should not be treated any differently from 'normal' embryos, and that women should be given the chance to carry their genetic offspring to term.

There is currently a real shortage of human eggs for use in embryonic stem (ES) cell research. It is hoped the problem can be overcome through creating embryos by transferring human genetic material into 'hollowed out' animal eggs. The resulting entity - a 'cybrid' - would be over 99 per cent genetically human and less than one per cent animal. As it stands, the new draft Human Tissue and Embryos Bill in the UK will ban the creation of embryos that contain genetic material from both animals and humans, but will make an exception for certain types of research, including cybrid embryos. The draft Bill imposes a strict 14 day time limit on the use of these entities in research, at which point they must be destroyed.

The RCBE and the Linacre Centre for Healthcare Ethics told the parliamentary committee who are scrutinising the draft Bill: 'At the very least, embryos with a preponderance of human genes should be assumed to be embryonic human beings, and should be treated accordingly. In particular, it should not be a crime to transfer them, or other human embryos, to the body of the women providing the ovum, in cases where a human ovum has been used to create them'.

The RCBE have been accused of misunderstanding the science involved in creating such embryos. Cybrid embryos will have no 'mother'; rather, an animal ovum will be stripped of its genetic identity and used as an empty vessel to cultivate hES cells from cloned human cells. It is hoped that such research will lead to advances in treatment for devastating diseases such as Parkinson's and Alzheimer's.

Liberal Democrat MP, Dr Evan Harris, has described the RCBE's position as 'absurd' and 'inconsistent', adding: 'Most of these embryos will be created using animal eggs, but even if they were created using human eggs, they would be created by cloning and the Catholic Church has previously opposed reproductive cloning of even fully human embryos'.

An IVF mortality: Lessons to learn

A report on the circumstances surrounding the 2003 death of Irish IVF patient Jacqueline Rushton has been published. The report was commissioned by the Republic of Ireland's Health Service Executive (HSE), and written by Alison Murdoch of the Newcastle Fertility Centre and independent healthcare consultant Stuart Emslie. Rushton, a 32-year-old nurse, was treated at the Human Assisted Reproduction Ireland unit of Dublin's Rotunda Hospital. She was admitted to this same hospital on 8 December 2002, after she was found to be overreacting to her IVF treatment, and was subsequently transferred to Dublin's Mater Private Hospital. Despite initially appearing to make a recovery, she collapsed and was placed on a ventilator, which was switched off on 14 January 2003. The cause of Rushton's death was found to be acute respiratory distress syndrome, a rare complication of ovarian hyperstimulation syndrome - itself a complication associated with IVF, where fluid from the bloodstream leaks into the abdominal cavity and causes it to swell.

The report concludes that there were problems with the management of Rushton's care, compounded by a lack of senior supervision and inconsistent compliance with official guidelines for treating her condition. The report recommends regular care audits, in which it is incumbent upon hospitals to prove standards rather than merely claiming to have them, together with and a review of in-house protocol in all general hospitals and IVF clinics.

Rushton's family have declared themselves satisfied with the outcome of the report, and they have instructed their solicitors to drop legal proceedings against the health authorities. They have also expressed their hope that the report's recommendations will prevent another family from going through the same ordeal. The Irish Patient Association has said that the episode raises significant questions about patient care. Irish health minister Mary Harney has announced that immediate steps are being taken to implement these recommendations across HSE hospitals.

The statement, issued by the Master of the Rotunda Hospital Dr Michael Geary acknowleged "lessons have been learned". "In all medical treatments, one cannot always be guaranteed that the outcome will be positive and every effort is made along the way to comply with best practice in patient care and treatment," Dr Geary said. "We sincerely hope, with the new insights and learnings available to us, that a similar incident can be prevented from occurring again in the future," he concluded. "There is always an onus on any healthcare provider to review their processes and systems and this report underlines again this requirement. It is very important for us to learn from this tragic event."

OHSS is the only medical emergency that a Fertility physician faces in his/her career. This report is important because it highlights the possibility of death in the event OHSS is not managed properly. For bloggers interested in the subject, Rotunda is hosting an International Congress on PCOS at Goa in August 2008. There will be an entire video session dedicated to the management of OHSS. The link to follow will be www.sisab.net/pcos2008

The Laser Printer

Bad news, office drones: That laser printer sitting in your cubicle might be doing some serious damage to your health.

The humble office laser printer can damage lungs in much the same way as smoke particles from cigarettes, a team of Australian scientists has found. An investigation of a range of printer models showed that almost a third emit potentially dangerous levels of toner into the air. The Queensland University of Technology scientists have called on ministers to regulate these kinds of emissions. They say some printers should come with a health warning.

The researchers carried out tests on more than 60 machines. Almost one-third were found to emit ultra-tiny particles of toner-like material, so small that they can infiltrate the lungs and cause a range of health problems from respiratory irritation to more chronic illnesses. Conducted in an open-plan office, the test revealed that particle levels increased five-fold during working hours, a rise blamed on printer use. The problem was worse when new cartridges were used and when graphics and images required higher quantities of toner. The researchers have called on governments to regulate air quality in offices. They also want companies to ensure that printers are based in well-ventilated areas so that particles disperse.

That's such fun news, isn't it? And here you were eating salads, jogging and not smoking, and it's going to be your laser printer that does you in. Life sure is hilarious sometimes.

Artificial Wombs

Preliminary research, presented at the European Society for Human Reproduction and Embryology annual meeting held in Lyon, France, last month, suggests that a novel 'womb-on-a-chip' device may help to improve IVF success rates. The 2 millimetre wide chip, developed by Dr Teruo Fuji and colleagues at the University of Tokyo in Japan, acts like an artificial womb to nurture fertilised embryos - up to 20 at a time - to the stage at which they can be implanted into a real womb. According to the UK Human Fertilisation and Embryology Authority, over 30,000 women in the UK undergo IVF each year. However the success rates associated with conventional IVF methods are as low as 1 in 5, meaning that most of these expensive IVF cycles do not result in a successful pregnancy. Washing or moving the eggs during IVF treatment, a process which can cause harmful temperature or acidity changes, might be one possible reason for the low success rates seen in IVF says Dr Matt Wheeler from the University of Illinois in Urbana-Champaign, who is also working on automated IVF systems. Fuji's team believe that the new chip, which avoids these disruptive washing and moving processes, is closer to the real thing: 'We are providing the embryos with a much more comfortable environment, mimicking what happens in the body', he told New Scientist. Inside the chip, cells from the lining of the womb are cultured to provide nutrients to the growing embryos, helping them to develop to the stage at which they can be implanted into a real womb.

To test the device, the researchers carried out several experiments on mice, comparing the chip-grown embryos with those produced using conventional IVF. Their findings suggest that the chip-grown embryos outperformed conventional IVF embryos in several ways:
-More were successfully fertilised (43 out of 50, compared with 41 out 50).
-More developed to the stage at which they could be implanted into a real mother (35 out of 50 compared to 32 out of 50).
-Grew faster (containing around 77-119 cells compared to 58-94 cells, after 2 days).
-More continued to develop when implanted into female mice (44% compared to 40%).

Dr Wheeler commented: 'It's not just about more embryos surviving to be implanted...They also seem to be doing better once they are implanted'. Following these successful experiments in mice, Fuji's team have now been granted permission to begin trials on human embryos later this year. The next five years are going to see many path-breaking discoveries in the field of IVF. I personally believe that just a couple of years down the line all IVF culture systems will be automated based on principles such as the subject system.