Here an independent expert responds.

Feel free to use these quotes in your stories.  If you would like to speak to an expert, please don’t hesitate to contact us on (08) 7120 8666 or by email.

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Prof Justin St. John is Professor and Director of the Centre for Reproduction & Development, Monash Institute of Medical Research, Monash University, Victoria - Prof St. John is available for interview

“I am very keen for Australian law to embrace these new technological approaches (see below), however, I am also concerned that this story could offer a lot of false hope! We have a long way to go in determining safety and effectiveness and the process still requires a considerable amount of validation. It will be at least a few years before we know whether this is a sensible route.”

Mitochondrial DNA disease is distinct to other diseases as we inherit our mitochondrial genes from our mothers’ eggs. These genes are packaged in very small bodies called mitochondria, which are found in the cytoplasm of nearly all cells, including eggs. The mitochondria are the powerhouses of the cell as they generate energy, which our cells use for their everyday functions and ensure that we function normally. The mitochondrial genes contribute to this process. However, if one of these genes is mutated then the individual can suffer from very debilitating diseases that can affect, for example, muscle and nerve function with an increasing number of diseases being associated with these mutations. These mitochondrial genes are quite distinct from chromosomal genes, which we inherit from both our mothers and fathers.

The dilemma for a woman who is a carrier of a mitochondrial DNA mutation or deletion is that she will not know how much damaged mitochondrial DNA is present in her eggs and it is likely that the amount of mutation differs between each of her eggs. So, if she and her partner choose to have a family, they will not know if their child is going to be affected or not.

Scientists are now developing two approaches to try and prevent children from inheriting these diseases. The first of these techniques proposes to transfer the mother’s chromosomes into an egg from a donor. The donor egg would have had its chromosomes removed but have healthy mitochondrial DNA present. Then, as with normal IVF treatment, the eggs would be fertilised with sperm and the resultant embryo could develop.

The second technique is similar but would first allow the father’s sperm to fertilise the egg and then transfer the mother’s and father’s chromosomes to a healthy donor egg.

There are a number of questions that need to be answered before these procedures can be introduced into the clinic. The first is whether any of the mutant mitochondrial DNA accompanies the chromosomes as they are transferred into the donor egg. This is very important to know as this could result in the baby suffering from mitochondrial disease. The second is whether these techniques would lead to the baby suffering from any harmful side-effects.

It is imperative for scientists to determine whether these techniques can be conducted and to determine the safety of these approaches. This requires the use of human eggs and embryos. However, the overall safety also needs to be determined in model systems before we offer these options to women as a means to having healthy children.”

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UK scientists were able to treat liver disease in mice with a combination of stem cells and genetic correction therapy. The research, to be published in Nature, demonstrates the feasibility of combining human induced pluripotent stem cells (iPSCs) with genetic correction to generate clinically relevant cells for cell-based therapies. The scientists edited the genome in human iPSCs taken from patients with a protein deficiency. These corrected iPSCs were given to mice where they were able to colonize their livers, restoring normal structure and function.

*Targeted gene correction of a1-antitrypsin deficiency in induced pluripotent stem cells, Yusa et al., Nature, doi:10.1038/nature10424

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Dr Andrew Laslett is Research Group Leader, Stem Cells, CSIRO Materials Science & Engineering

“This paper demonstrates for the first time the feasibility of combining gene therapy approaches with iPS cell technology to correct a simple genetic mutation that causes human liver disease. The corrected cell lines produced will require stringent safety and stability testing and the removal of all non-human proteins before they would be suitable for human clinical safety trials. This approach may be applicable to other human diseases which have a known and simple genetic mutation.”

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Dr Bryce Vissel is Head of Research into Neural plasticity and Regeneration, Garvan Institute of medical research

“This exciting study from Allan Bradley and Ludovic Vallier offers enormous hope for recovery for people suffering from genetic disorders. The study demonstrates for the first time that it is possible to take skin cells from a person with a genetic liver disorder, turn those skin cells into stem cells (called IPSCs) and then fix the genetic defect. Quite amazingly, the repaired cells could be turned into functionally corrected transplantable liver cells that have potential to correct the original liver defect. This amazing discovery builds on extensive studies over recent years of the potential of IPSCs. This study offers the possibility not only to repair genetic disorders of the liver but possibly also to repair numerous types of genetic disorders. As with all scientific progress, there will be major challenges to overcome before we see this new technology widely applied to people. It is important to note that the study does not yet cure a human condition; in this study the exciting result was shown in mice. Also there were important problems raised in the study. It will take scientific rigour, persistence, patience, perhaps even some failures, to overcome the challenges from here and achieve an outcome in people. Nevertheless, the study is an important step towards the goal of treating disease with stem cells. We are on the edge of a revolution in medicine – regenerative medicine – that could help people worldwide.”

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Dr William Sievert is Director of the Gastroenterology and Hepatology Unit, Southern Health and Professor of Medicine, Monash University

“Patients with alpha-1 antitrypsin (A1AT) deficiency develop serious lung disease such as emphysema because of low blood levels of A1AT; some also develop liver disease because the A1AT protein gets trapped in liver cells and damages them. Currently the only treatment available for people who develop serious liver disease is transplantation but what if you only needed to transplant normal liver cells instead of the whole liver? These investigators have taken skin cells from people with A1AT deficiency and done two things – corrected the genetic mutation in those cells that caused low levels of A1AT and changed the skin cells into liver cells (hepatocytes) that now make normal levels of A1AT. So this is a giant first step to treating this important genetic disease with cells (rather than an entire liver) that will continue to grow in the patient without the need for drugs to prevent rejection (since they came from the patient in the first place) and will provide the patient with enough A1AT to protect their lungs and liver.

The next steps will be to take this discovery from the laboratory, where it was tested in mice, to clinical trials where safety and effectiveness can be properly evaluated in people. There will be many challenges to overcome such as how to make enough cells to treat a person, in understanding at what age to start treatment for this genetic disease, determining how long the cells will continue to function and which individuals are most likely to benefit. Long-term safety considerations, such as whether tumour formation will occur, are very important. If these questions can be answered, then someday people with serious liver damage from other causes, such as viruses, alcohol or obesity, might benefit from this process of making skin cells into functional liver cells that could support or even regenerate a damaged liver, rather than having to replace it.”

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US scientists have questioned GM monitoring protocols in the US after investigating escapee canola plants living outside of cultivated fields. These populations were found to persist from year to year and reach thousands of individuals. The authors also found that the escaped plants could hybridise with each other. Below several Australian scientists independent of the study respond.

Feel free to use these quotes in your stories. If you would like to speak to an expert or for a copy of the embargoed research, please don’t hesitate to contact us on (08) 7120 8666 or by email.

Other resources:

There is an Office of the Gene Technology Regulator fact sheet on GM canola approved for commercial release in Australia online here, including key dates for state approvals.

The Regulator is currently considering an application for the commercial release of another GM canola line into the environment. Information on this application is available here.

The Risk Assessment and Risk Management Plans for each of the canola lines approved for commercial release in Australia are also available through the GMO Record on the OGTR website here, including question and answer sheets.

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Professor Mike Wilkinson is  Professor of Genetics in the School of Agriculture, Food and Wine at the University of Adelaide

“The findings of this research first emerged in August last year following presentation of the results in a meeting of the Ecological Society of America in Pittsburg (for more details see http://www.nature.com/news/2010/100806/full/news.2010.393.html). This paper provides formal peer-reviewed publication of the same work.

In essence, it reports on the appearance of GM canola (oilseed rape) in roadside verges and field margins in much the same way that has been reported previously (since the 1990s) for GM and non-GM canola in other parts of the world. However, the authors then state that this appearance is unprecedented in scale and that it “raises questions of whether adequate oversight and monitoring protocols are in place in the U.S. to track the environmental impact of biotech products”. So, time for alarm?

Well, in all honesty, no. The presence of these plants was predicted more than a decade earlier and even the scale of their presence is not surprising given the scale of GM canola cultivation in North Dakota. The real issue facing the regulators and those charged with GM oversight everywhere, as the authors themselves acknowledge, is whether these plants are (or are likely to) lead to any real ecological harm? This issue is not addressed by this study in any way. Thus, whilst mildy interesting from an academic standpoint, from a regulatory stance, I very much doubt it will necessitate any changes to the current practice of focussing on the potential for harm rather than on the mere presence of the GM plants.”

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Professor Graham King is Professor of Plant Genomics & Epigenetics at Southern Cross University

“Crop plants have been domesticated and selected to provide nutrition and plant-based products that underpin human civilisation and modern economies

Rotations of crops such as wheat and canola maximise soil fertility and long-term health, but often suffer from ‘volunteers’ (e.g. canola plants growing within wheat and vice versa), as well as many weed species that drastically reduce yields and waste energy in food production. Crops tolerant to weed-killers (herbicides) enable farmers to reduce energy wastage in crop production. Herbicide tolerant crops have been generated using both non-GM and GM methods.

Feral populations of canola (a species of Brassica) occur regularly in regions where the crop is grown and alongside roads where the harvested seed is transported. Their presence is not at all surprising. Feral canola tends to be more noticeable and prominent (due to yellow flowers) than feral wheat populations.

The potential for cross-fertilisation (hybridisation) with other feral populations will always exist, as will cross-fertilisation with other species of Brassica- the latter has been documented in many studies. However, Brassica species do not occur in the native flora of Australia.

There are different classes of herbicide, and each herbicide-resistant cultivar is typically resistant to a single class. GM populations may therefore be controlled using other herbicides. However, the finding in the Schafer paper indicates that that hybridisation appeared to have occurred between different GM cultivars. Over time this may pose more complex issues for weed control.

Research into the impact of GM (or other forms of herbicide resistant plants) has been carried out in many countries.

There is some value in research to understand the wider environmental impacts and extent of any specific weed populations in un-natural roadside environments.

However, this has to be set against the continuing need to understand the regional impacts ofnotadopting GM to feed the world, and the beneficial consequences in terms of reduced pesticide and energy use. In particular, weed control needs to be set in the context ofglobal crop production, food security, and energy efficiency.”

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Professor Peter Langridge is CEO of the Australian Centre for Plant Functional Genomics (ACPFG) at the University of Adelaide

“There is no great surprise from this study. Canola is known to establish along roadsides in many parts of the world and the GM canola is no different from normal canola in this respect.

Generally crops are not invasive and rarely become weeds because they have been bred and selected to grow in highly managed farm environments. Many key traits needed for wild plants, and particularly weeds, have been largely removed from our crops – such as seed dormancy and shattering (seed dispersal). This limits the likelihood of crop species becoming weeds in natural ecosystems. However, roadsides provide a special environment where crop species often flourish due to the extra water from runoff from the roads and regular mowing. This is why we often see wheat, barley and canola growing alongside roads.

It was always expected that the GM canola would behave in the same way and, as the area sown to GM canola grew, the incidence of roadside populations would expand. This does not present an environmental or safety problem for the community. The GM canola has been rigorous evaluated and presents no health issues and the roadside populations are essentially the same as the non-GM roadside populations. However, councils that use herbicides to control weeds along roads, will need to ensure they use the appropriate herbicides to also control the GM canola.”

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Professor Rick Roush is Dean of the Melbourne School of Land and Environment at the University of Melbourne

“This paper is unremarkable and not at all surprising. The authors have presented no evidence that GM canola is any more weedy or problematic than non-GM canola, or that any harms whatsoever have resulted.

All of the results documented in the paper have been made elsewhere, and repeated now in the US state of North Dakota.

The survey was explicitly only for roadsides and neighbouring highly disturbed habitats.

These are not important to biodiversity, and no claims were made for adverse environmental impacts on roadsides or anywhere else.

Herbicide resistance in canola is of no consequence if the canola is not sprayed, and that’s not likely in habitats of environmental significance.

Canola has been known to persist along roadsides in Europe, North America and Australia for decades, including French and Canadian research from 2001 and 2003, as cited in the paper.

We can expect to find GM canola growing on roadsides in NSW, Victoria and Western Australia, alongside non-GM canola, with no more consequence than brightening the roadsides with yellow during their flowering.

Hybridisation between canola lines of different GM and non-GM herbicide resistances was documented by Dr Linda Hall in Canada more than 10 years ago, and is still not a problem of any sort in Canada.

Many other feral crop plant species can be found on roadsides, including lucerne, without causing harm. The more important threats come from weeds such as wild radish and escaped garden plants, such as Pattersons Curse, and many more recent but not yet as well-known weeds.”

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*The Establishment of Genetically Engineered Canola Populations in the U.S., Schafer et al., PLoS ONE, doi:10.1371/journal.pone.0025736.g001, 2011

Feel free to use the quotes below in your stories. Any further comments will be posted here. If you would like to speak to an expert, please don’t hesitate to contact us on (08) 7120 8666 or by email.

Dr Robert Sparrow, Centre for Human Bioethics, Monash University.

“It’s life Jim, but much as we know it..

“This publication does not demonstrate the creation of “artificial life”. Instead, scientists have manipulated existing organisms to cause them to take up a synthetic genome, which itself was constructed on the basis of knowledge of existing, naturally evolved, genetic sequences.  While this is a remarkable achievement and demonstration of technological ingenuity it falls well short of the “creation of life”.

A useful analogy for understanding what Venter’s team have done might be to imagine buying a clock radio from the hardware store, taking it apart, and then building a copy using parts ordered over the Internet. While, in a sense, you would have “built” a “new” radio, it is also clear that you would have a long way to go before you could design your own radio from scratch.  Taking this next step in the biological sciences will require understanding a lot more than scientists curently do about the functions and interactions of genes and the way they work in different cellular environments.

For the same reason, the applications that Venter imagines, involving synthetic organisms designed to achieve various medical and environmental benefits, are a long way yet from being realised. Researchers and corporations working with recombinant DNA technology that has been available for a number of decades now have made the same claims and we are yet to see many of the promised benefits. Again, it is one thing to be able to modify or synthesise genes, it is quite another to understand, let alone control, the outcomes of these modifications in a living organism.

Like any research that holds out the prospect of a new technology this reseach does raise ethical issues.  In particular, research in synthetic biology raises issues relating to the appropriateness of allowing researchers to claim intellectual property in genetic sequences and the dangers of novel organisms escaping into the larger environment.  However, these issues are already raised by the creation-and increasingly, release-of genetically modified organisms and are probably more urgent in that context.  Of course, if Venter’s research really has the significance he claims, we might need to worry more.  The more scientists claim that their research might change the world the more reason the public have to worry and to want a say in whether the world gets changed or how. Ultimately, then, in relation to this announcement, like many others, the life we need to be most concerned about is our own. “

Comments from UK experts:

Professor Dek Woolfson, University of Bristol and Principal Investigator, BBSRC Synthetic Components Network

“Craig Venter’s step forward is to show that genomes – the stuff that programmes natural cells and organisms – can be made chemically in the lab and then transplanted and ‘booted up’ in another cellular host. This could eventually allow the genes for the synthesis of drugs or biofuels to be smuggled into bacterial or yeast cells, which could then be made to produce these useful products. This is one end of synthetic biology that might be termed ‘genome engineering’.

Other groups, including those in the UK, are working at understanding how we might design and engineer biological systems at the more-basic molecular level; e.g., can we make miniature motors out of proteins and other molecules from first principles? This is a very exciting time for the emerging field of Synthetic Biology, and the UK has a key role to play in it.

The aim of Synthetic Biology is to design and engineer new biological building blocks that allow the reliable and predictable construction of biological or biologically inspired systems. In turn, these systems could be used to produce new biomaterials, biofuels, or drugs more cheaply, efficiently and in environmentally friendly ways.”

Professor David Delpy, Chief Executive of the Engineering and Physical Sciences Research Council (EPSRC)

“This latest announcement demonstrates the crucial role that engineering, chemistry, physics and maths play in driving forward developments in synthetic biology and that the range of UK research activities that we are supporting in this area will contribute to the advancement of this new technology.

In synthetic biology we have a whole set of new possibilities to move from hypothesis to reality in areas as diverse as disease diagnosis, vaccines, fuel production or neutralising contaminants such as oil spills.

EPSRC, together with BBSRC, have been mindful of the concerns that the public may have over what is a relatively new area of research, and from the outset have encouraged our researchers in the synthetic biology networks to actively consider the ethics of their work and discuss it with the public.”

Professor Julian Savulescu, Uehiro Chair in Practical Ethics and Uehiro Centre Director, University of Oxford

“Venter is creaking open the most profound door in humanity’s history, potentially peeking into its destiny. He is not merely copying life artificially as Wilmut did or modifying it radically by genetic engineering. He is going towards the role of a god: creating artificial life that could never have existed naturally. Creating life from the ground up using basic building blocks. At the moment it is basic bacteria just capable of replicating. This is a step towards something much more controversial: creation of living beings with capacities and natures that could never have naturally evolved. The potential is in the far future, but real and significant: dealing with pollution, new energy sources, new forms of communication. But the risks are also unparalleled. We need new standards of safety evaluation for this kind of radical research and protections from military or terrorist misuse and abuse. These could be used in the future to make the most powerful bioweapons imaginable. The challenge is to eat the fruit without the worm.”

Dr Gos Micklem, Department of Genetics at the University of Cambridge

“This is undoubtedly a landmark paper. The group has been building towards this step and, from their earlier published work, are leaders at synthesising and re-assembling large segments of DNA. There is already a wealth of simple, cheap, powerful and mature techniques for genetically engineering a range of organisms. Therefore, for the time being, this approach is unlikely to supplant existing methods for genetic engineering. DNA synthesis is rapidly becoming cheaper and so this could change, but not soon.

The technique could potentially come into its own if one wanted to introduce a large number of changes into an existing genome. However making a system that works predictably after introducing a large number of changes is one of the design challenges of the young field of synthetic biology: in the general case it is a challenge that is unlikely to be solved soon.”

Professor Paul Freemont, Co-Director of the EPSRC Centre for Synthetic Biology at Imperial College London

“The paper published in Science today by Craig Venter and colleagues is a landmark study that represents a major advance in synthetic biology. Venter and colleagues have for the first time demonstrated that a single genome of around 1 million base pairs can be chemically synthesised and assembled correctly and transplanted into a recipient cell. The step change advance, which has alluded them in previous publications, is that they have now demonstrated that the transplanted synthetic DNA can be ‘booted up’ to operate the functions of the new recipient cell in terms of replication and growth. Although the recipient cell is not man-made but is another natural cell, what Venter’s team have shown is that after transplantation and multiple cell divisions the recipient cell take son the characteristics or phenotype of the newly transplanted genome. (This is like taking a Mac computer operating systems and installing it onto a PC and the PC becoming a Mac computer.)

This is a remarkable advance as it now provides a ‘proof of concept’ that we can chemically synthesise and assemble full genomes and transplant them into recipient cells, which after selection contain only the synthetic genome, and after rounds of cell division become a new and one might argue synthetic cell. The applications of this enabling technology are enormous and one might argue this is a key step in the industrialisation of synthetic biology leading to a new era of biotechnology.

Of course one also needs to be cautious, as it is not clear if this approach will work for larger and more complex genomes or for transplantation in different bacterial cells. However, this is a landmark step in our abilities to manufacture man-made cells for man-made purposes.”

Additional information from Professor Freemont:
In detail the paper describes the chemical synthesis and assembly of the 1.08Mbp genome of Mycoplasmamycoides. This organism is a small bacteria and lives as a parasite in cattle and goats. Mycoplasma lack cell walls, have no discernable shape and are the smallest (0.1 µM) known free-living life forms and are most likely to have evolved from Gram-positive bacteria. They are present in both animal and plant kingdoms and act as colonisers. The choice of Mycoplasma by the Venter group for genome synthesis and transplantation is based on the small size of the genome and for the mycoides species has a reasonably fast growth rate. The difficulties they report in terms of getting the synthetic genome booted up were due to a single base pair mutation in an essential gene (dnaA) which they noted after several attempts. Correcting this mutation allowed the synthetic genome to work properly, although its not clear how the mutation occurred – whether in the synthesis or assembly step. The transplantation process involves using an antibiotic selection process where the newly transplanted genomes infer resistance to the transplanted cell to live in the presence of a lethal antibiotic.

Professor Richard Kitney OBE, Co-Director of the EPSRC Centre for Synthetic Biology at Imperial College London & Fellow of the Royal Academy of Engineering

“An important aspect of the paper is that the original natural genome was sequenced and the sequence sent in alphanumeric form to a company call Blue Heron near Seattle. They then synthesised the sequence in 1000 bp cassettes and sent back the biological material to Venter et al, who reconstructed the entire genome and checked for errors. The synthesised genome was then placed in a different natural cell and replication took place. After 2 or 3 generations the second cell population took on the characteristics of the first population (i.e. a different bacterium). The paper has major implications for the harnessing of biology for industrial purposes.”

Professor Douglas Kell, Chief Executive of the UK Biotechnology and Biological Sciences Research Council (BBSRC)

“The ability to do all of the steps of protein synthesis from genome to product in order to make something that has a useful application is an important step in developing the potential of synthetic biology.

Synthetic biology is a relatively new field and within the global research community, including in the UK, there is some truly avant-garde science happening. Together with EPSRC and Sciencewise-ERC, BBSRC has recently been exploring the range of perspectives of the UK public on synthetic biology to ensure that the cutting edge research that is carried out in this field is supported by policies that reflect the views, concerns and aspirations of the people who fund it – the UK taxpayers.

As we become technically better at doing synthetic biology, the potential applications open up. Mainly, what it will allow us to do is harness useful biological processes so that we can make the sorts of products that are difficult to synthesise with traditional chemistry and physics.”

Comments from NZ experts:

Dr Peter Dearden, Director of Genetics Otago

“This paper represents a very significant step forward in engineering life. Ventner’s group have been able to put a fully synthetic genome into a bacterial cell and get it to act as that cell’s genome. The technical skill required to get this to work is immense, and is the culmination of a long series of experiments that pioneered the technology to do this, as well as developing ways to prove that it had been done.

The experiment raises an interesting question, has Venter and his team created life? The answer is no. Venter’s team is relying on the information in a natural genome. While the DNA strand that makes up the genome is synthetic and made in the lab, the information it contains comes from a species of bacterium; and it is the information that is important in a genome. Also Venter’s team needs a bacterial cell, one without a genome, to put their synthetic genome into. This cell, currently, can only be made by a living organism.

However, while Venter and his team haven’t created life, they have carried out a remarkable feat, and put us one further step on the road to completely re-engineering organisms for biotechnological purposes.”

Dr Iain Lamont, Professor of Biochemistry at University of Otago

“This is an amazing technical achievement that in years to come will be seen as a landmark in biology. It provides proof-of-principle that it is possible to make new microorganisms by synthesising their DNA and transplanting it into an existing cell, where it replaces the existing DNA. The very specialist technology allied to our ignorance of many aspects of biochemistry and physiology even in the simplest organisms means that we are very far from creating something completely new. Nonetheless, this work raises important ethical and philosophical questions that deserve wide discussion.”

Dr Neil Pickering, Senior Lecturer in Bioethics at University of Otago

“Ethical issues arise both in questions about the nature of an activity and in questions about the consequences of an activity. And in both sorts of questions, the prospects for agreement on the answers are unclear.

For instance, to describe the scientists in this case as ‘playing God’ is to characterise the nature of what they are doing. However, you may reject this characterisation. And even if you do accept it, depending on your view point, you may find this a fearful description or an invigorating one.

The consequential issues that exercise people in such cases are of broadly two kinds: There are fears that the promised benefits to health, or the environment will be illusory, or outweighed by unintended effects – side effects if you like – of the use of novel organisms; and fears about possible evil intended effects e.g. from bioterrorism.

The problems thinking through these consequential issues are many. But unless we outlaw an activity or allow it to go on unchecked, we have to face these problems. In particular, much is uncertain: what are the possible benefits and what the harms? What the likelihood of their coming about? There will be limitations on how effectively we can investigate these matters and reduce uncertainty.

Moreover, appraising consequences cannot be an altogether objective activity. What to one may seem a risk worth taking for a benefit worth having may seem to another to be quite the opposite.”

Embargo lifted at 3am Australian EST on Thusday 15 April 2010

Treatment options for patients with mtDNA disease are extremely limited and so the results of this study have the potential to help couples where the woman carries a mutation in her mitochondrial DNA that could cause disease in her children. Mitochondrial disease is a debilitating and potentially fatal genetic disorder that affects both children and adults by robbing the body’s cells of energy. Recent research suggests mitochondrial disease may affect one in 200 Australians.

Feel free to use the quotes below in your stories. Any further comments will be posted here.

A fact sheet on mitochondrial disease has been prepared by the Australian Mitochondrial Disease Foundation and is available here.

Info-graphic

The AusSMC has prepared an info-graphic (see below) which any media outlet is free to use provided the Australian Science Media Centre is credited. Various formats of this info-graphic are available here.

PDF | JPG | EPS

If you would like to speak to an expert, please don’t hesitate to contact us on (08) 7120 8666 or by email.

Loane Skene is Professor of Law, University of Melbourne and Deputy Chair of the Lockhart Committee:

“Some people may assume that it would be unlawful for Australian scientists to create embryos with genetic material from more than two people, as the Newcastle scientists have reportedly done in their research on treatment for mitochondrial disease. However, that does not appear to be the case.
In Australia, it is an offence punishable by up to 15 years imprisonment if a person intentionally creates or develops a human embryo that contains genetic material provided by more than two people outside the body of a woman (Prohibition of Human Cloning for Reproduction Act 2002, s 13). However, that section applies only if the embryo is created ‘by a process of the fertilisation of a human egg by a human sperm’ (s 13(a)). If the embryo is created by another process, then it can be done lawfully under licence (s 23(a) of that Act; also Research involving Human Embryos Act 2002, s 20).
In considering whether the Newcastle research would be lawful in Australia the issue is therefore whether the embryo created by the Newcastle method has been created by a means other than fertilisation.

Fertilisation is not defined in the Australian Act. Traditionally it means the fertilisation of an egg by sperm. The resultant embryo has the chromosomes of both the man and the woman whose gametes were used to create it. This is in contrast to creating an ‘embryo’ by somatic cell nuclear transfer (SCNT), when the genetic material of the embryo comes almost entirely from the person whose somatic (body) material was used to create the embryo. After the amendments to the Australian legislation following the Lockhart Committee’s report, human embryos can be lawfully formed for research by SCNT under licence, but not by fertilising an egg with sperm.

In the Newcastle process, as described in the Nature paper, eggs and sperm from two couples were fertilised, forming the donor and recipient zygotes (an early embryo) respectively. Later, the nucleus from one fertilised egg was removed at a pronuclear stage and transferred into the other fertilised egg whose nucleus had also been removed, at the pronuclear stage. In that second step, the zygote that was ‘treated’ then contained genetic material from more than two people, but the resultant embryo was not created ‘by a process of the fertilisation of a human egg by a human sperm’. Thus, none of the steps in the research would seem to be unlawful in Australia under licence, provided they did not contravene other provisions of the legislation.

One possible difficulty concerns the formation of the two initial zygotes. Australian law allows research involving the fertilisation of a human egg by human sperm only in limited circumstances. Under the Research involving Human Embryos Act 2002, s 10B, such research is permitted under licence only if it ceases before the first mitotic division and it is undertaken for the purposes of research or training in ART. Research into mitochondrial disease is probably the type of research that would probably be licensed in Australia and it appears that the nuclear transfer could technically be done at an early stage.

More likely, however, if both couples whose eggs are fertilised for the research were undertaking fertility treatment, they could donate their ‘excess’ embryos for the research, including embryos that are not fit for implantation (as apparently occurred in the Newcastle research). The NHMRC Licensing Committee has granted licences to use abnormally fertilised embryos in research.

The most important point is that legal uncertainty should not be allowed to impede this important research. It would certainly be desirable if women with a family history of mitochondrial disease could have their embryos treated to avoid the transmission of the disease to their own children. These issues should be taken into account in the review of the Australian legislation later this year.”

Professor Justin St John is Director of the Centre for Reproduction and Development at Monash University, Melbourne

“Finding effective assisted reproductive technologies for women who are carriers of mitochondrial disorders is a priority for these patients. Although this work and previous work have addressed some of the issues and provide some promising preliminary outcomes, we do not believe embryos carrying even very low levels of mutant mitochondrial DNA will not give rise to mitochondrial disorders. This is especially as mitochondrial DNA segregates randomly during foetal development. During foetal development mitochondrial DNA is also extensively replicated and selection of mutant and non-mutant mitochondrial DNA for replication is again random. We know from one clinical case that mutant mitochondrial DNA that contributed less than 0.01% of the total mitochondrial DNA population at fertilisation was found in a male patient suffering from a mitochondrial myopathy. Consequently, it is really necessary to eliminate all mutant mitochondrial DNA in any assisted reproductive technology aimed at helping patients with mitochondrial disorders who wish to have children that would not be affected or be subsequent carriers of such severe metabolic disorders.

We inherit our mitochondrial DNA from the population present in the oocyte just before fertilisation. If we are to prevent the transmission of mutant mitochondrial DNA to the offspring then the chromosomes need to be transferred to an egg that does not have mutant mitochondrial DNA. This will result in the offspring effectively having three parents. However, in this case, there is no other option if we want to ensure that mutant mitochondrial DNA is not transmitted.”

Associate Professor David Thorburn is Head of Mitochondrial Research at the Murdoch Children’s Research Institute, Melbourne

“Craven and colleagues describe the first ever transfer of genetic material between fertilised human eggs. The rationale for these studies is to help couples where the woman carries a mutation in her mitochondrial DNA that could cause severe disease in her children. Mitochondrial DNA codes for just 37 of our genes and is located in the cell body away from the 20,000 or so nuclear genes that encode virtually all of our genetic information. Mitochondrial DNA is inherited maternally. This happens because a woman’s eggs all contain at least 100,000 copies of mitochondrial DNA and the small number of mitochondrial DNAs in sperm are lost after fertilisation. Mitochondrial DNA mutations cause severe neurological and other diseases in at least 1 per 10,000 individuals but recent studies show at that least 1 in 250 individuals carry a mitochondrial DNA mutation.

In 2009, a group from Oregon reported using a nuclear transfer method to show it was possible to transfer nuclear material between monkey eggs, without substantial transfer of mitochondrial DNA. They showed that the manipulated eggs could be fertilised, develop into healthy embryos and that implanted embryos developed normally and gave rise to healthy baby monkeys. That approach could potentially be used to prevent mitochondrial DNA disease in humans by allowing couples at risk of mitochondrial DNA disease to have children who carried the nuclear genes from the parents and mitochondrial genes from a healthy donor.

This new study from the UK uses a similar but slightly different approach to show that it is also possible to perform nuclear transfer successfully in fertilised human eggs. The scientists were able to take the nuclear genes from one embryo, leaving nearly all of the mother’s mitochondrial DNA behind and transfer them to another embryo from which the nuclear genes had been removed. The resulting embryos could develop normally to the 100-cell stage. This is a very exciting outcome for affected families because it brings the prospect of preventing mitochondrial disease a big step closer.

The major achievement of this study is that it shows that nuclear transfer in human embryos can allow apparently normal embryonic development. The major technical difference from last year’s monkey study was that the current study used pronuclear transfer between fertilised eggs rather than transfer of the chromosomal spindle complex between unfertilised monkey eggs. Both approaches have advantages and disadvantages so it is not certain yet which method may be technically superior if used in humans in the future.

Apart from the technical success and great potential promise of this study, it is likely to spark further debate about whether it is appropriate to perform such experiments on human embryos. It is important to note that the embryos were not generated for research but for IVF treatment for couples affected by infertility or at risk of a genetic disease. The scientists only used embryos that were unsuitable for IVF because they contained too few or too many copies of nuclear genes from one parent, namely 23 chromosomes or 69 chromosomes rather than 46 chromosomes. In order for the experiments to proceed, my understanding is that they required an amendment of British legislation for this specific purpose, as it otherwise forbids manipulation of the human germ line as part of laws to prevent human reproductive cloning. The scientists received special approval to perform the experiments described and grow the embryos up to the 100-cell stage but no further. The justification was largely on the basis of potential harm versus potential benefit in using this technique to prevent serious genetic diseases.

A second ethical issue that was discussed in relation to the monkey study last year, was whether the resulting children would have 3 genetic parents. Technically this is correct, as the donor egg containing mitochondrial DNA is likely to come from an unrelated woman. However, the mitochondrial DNA contains only a very small number of genes that are essential for converting food energy into chemical energy. They do not appear to play a role in behaviour, appearance or other characteristics. It could be argued that the genetic influence of a third parent is greater in surrogate pregnancies than in this situation, since the environment of the womb is now recognised to program the way various genes are expressed and potentially affect health outcomes in later life.

In addition to the ethical issues, which require further community debate there are some practical issues that will delay the potential introduction of nuclear transfer to prevent mitochondrial DNA disease. This procedure would currently be illegal in virtually all countries so its introduction would require legislative change and approval of specific protocols. Further information needs to be provided on potential safety issues related to the chemicals and proteins used in removing and transferring pronuclei and to the theoretical possibility of so called epigenetic changes that may arise from mixing together the nuclear genes from one embryo with the cytoplasm (cell body) of another. None the less, the study is a major achievement that will give substantial hope to many families affected by mitochondrial DNA disease.”