The embryo debate

The use of stem cells and embryos in research is among the most
controversial areas of science today. Here Professor Chris Barratt
and Lord Naren Patel outline how science is squaring up the
challenges presented by advanced embryology

Since the vast majority of people spend their initial reproductive years avoiding conceiving a child, it is surprising to know that approximately 1 in 6 couples will experience difficulty in having a baby, that is they'll take more than a year to conceive. Remarkably there are relatively few options for sub fertile couples. The primary treatment is assisted conception - also known as test tube baby treatment or IVF (In Vitro Fertilization). Since 1978 when the first baby was born, IVF has revolutionized treatment. However, despite its widespread use - 44,000 treatment cycles in the UK in 2006 - it has a significant number of drawbacks. For example it is very expensive with an average cost of £4000 per cycle of treatment and many couples will not conceive. 75% fail in each attempt. Therefore, there is a clear demand to determine the reasons for the sub fertility and employ more effective treatments.

Until recently, infertility was considered to be primarily a female issue. However, recent data overturns this misconception. Male infertility is a very significant global problem and, what is most worrying, is that the recent reports suggesting that its prevalence is increasing. Studies using semen assessment as the criteria for sub fertility (where sperm concentration is less than 20 million per ml) show that one in five 18 year olds are classed as sub-fertile! Sperm dysfunction where sperm are present in the ejaculate but don't work very well is the single most common cause of sub fertility. Approximately 40,000 new patients per year present with this problem. However, unfortunately there is no treatment except IVF.

Our research is aimed at understanding how a normal spermatozoon works and address questions such as: What makes a functional cell?

How does a sperm survive in the female reproductive tract (a hostile environment) for up to 7 days? How does a sperm find and interact with the egg? What are there so many sperm? Why not produce one good one instead of millions of poor ones?

In the process of addressing these questions we will be in a position to use our knowledge to determine what goes wrong in the men with sperm dysfunction. Initially we intend to compare the sperm from normal men with those from men with defined defects using proteomic profiling. This will allow us to not only identify key differences but also to develop potential biomarkers that will allow the more accurate diagnosis.

We are very fortunate in the UK to study human reproduction. The UK has a world leading permissive legislative framework for assisted conception which allows, under specific license, a whole host of cutting edge procedures and techniques to be developed. For example, in the UK, under the regulatory authority of the Human Fertilization and Embryology Authority we are allowed to perform research on human embryos which also covers the generation of embryos for research purposes e.g. by somatic cell nuclear transfer. Importantly, this framework also allows for the generation of human embryonic stem cells which hold enormous potential for the treatment of disease using stem cell therapy.

Whilst the legislative framework has been in operation for a long time - it was set up in 1991 - there have been, and remain, a number of continually challenging issue for us to address. Probably the most difficult of these is the degree to which we allow the screening of embryos for example for genetic diseases, prior to replacement in the woman. This debate is only likely to become more intense and sharply focused as our ability to screen for genetic diseases becomes more accurate and widespread.

A primary question is how far should we allow this screening to go? For example, should we only restrict screening of embryos for serious diseases? If so, what do we define as serious? This is a continual debate. What I find most enlightening is that in the UK this debate, often facilitated by the HFEA, is conducted in an informed and open way via high quality consultation documents. (see list at hfea.gov.uk).

Reproductive medicine has undergone a revolution in both treatment options and legislative/regulatory frameworks. Unusually so, the lag time between new developments and treatments and the ethical framework is significantly less in reproduction that any other discipline. It's challenging to keep this synergy going but it's absolutely necessary as we cannot ever get to a situation where the scientists/clinicians undertaking treatment do not have the support of the public.

The first IVF baby was 30 years old in July. It's been a dramatic 30 years and as with all advances there have been significant challenges to deal with. Reproductive medicine, I believe, is unique in being at the forefront of combining the ethical with the scientific debates to allow continued well thought-out progress. The challenges now are for us to make the most of these opportunities to discover the remarkable sequence of events accompanying fertilization and the generation of the early human embryo.

Chris Barratt is Professor of Reproductive Medicine in the Division of Maternal & Child Health Sciences at the University of Dundee, results is hard to predict. an internationally recognized expert on male fertility and is the creator of the first over-the-counter fertility test Fertell.

For more information on the Human Fertilization and Embryology Authority visit the website at www.hfea.gov.uk

As Professor Chris Barratt states in the accompanying article, if scientists are to progress with this research, it is essential they maintain the trust of the public. But how do they do that amidst the blizzard of headlines and mixed messages that often cloud the debate?

The University's Chancellor, Lord Patel of Dunkeld, has been involved in this debate as the embryology legislation has made its way through Parliament. As a noted obstetrician for many years, he has also seen the human side of the many issues which arise across the spectrum of reproductive medicine.

He is all too aware of the need to maintain the public confidence in this area of scientific research.

'Currently the vast majority of the public support this kind of research, and the reasons for that are clear - people hope such research will result in treatments for some major diseases. The public do have confidence in the regulatory systems and bodies such as the Human Fertilisation and Embryology Authority have been put in place and worked well for the past two decades around reproductive techniques,' said Lord Patel.

'The system seems to be effective and works well and having this kind of embryonic research regulated in this way can help maintain that confidence.

'It is also to the benefit of scientists, because they can work safely in the knowledge that they know where the boundaries are set. That is what has happened and it has provided a synergy between the public and scientists.'

However, as the available technology rapidly changes and new issues arise, which challenge the boundaries of the legislation which has worked so well over the past three decades, he acknowledges that the system may be tested, not least by heightened public expectation of what and when the research can deliver.

'We will only maintain this confidence if three things happen:

  1. We have to ensure that no scientists cross the lines which have been firmly established.
  2. The regulatory body has to continue to work well.
  3. The research delivers results.

'The first two are working well. As to when the research will deliver results is hard to predict.

'The public expectation has risen so high that there is a great risk they run ahead of what can be delivered, particularly in terms of the time it may take for positive results to have a real impact, particularly in the time it may take to develop treatments from embryonic stem cells.

'We have to engage with the public and raise the understanding that scientific research takes a long time to deliver results. The results of this research are not going to arrive overnight.

'This research is unusual in that it has come to the public attention and been engaged in a public debate at an extremely early stage. In most circumstances if you are researching a new drug or a new treatment, it only becomes an issue publicly once it moves into the trial stage, which is relatively late in the process - there may have been research on this for twenty years up to that point.

'But when we are talking about stem cells, the public have been brought into this at the earliest stages of development. That is understandable because this is a very important, and very emotive, area. But there has to be the understanding at the same time that we are at the beginning of the science and it could be a long slow process before treatments are delivered.

'We first have to understand the basic physiology and patho-physiology at a cellular level before we can even begin to develop treatments, so this is at a very early stage. Unfortunately there has been a tendency to suggest that some stem cell therapies will be coming very soon, when that may not be the case, and that will have an effect on the public's confidence that this is a worthwhile process.'

The fear is that if scientists lose sight of their responsibility not to make unreasonable claims for their research, then their opponents will make advantage of it when those claims are not fulfilled, thereby placing the whole process several steps backwards.

Therefore clear, responsible communication is absolutely key, as Lord Patel explains.

'We have to continue to articulate to the public why such research is necessary and how it is likely to work - the timescales involved, the processes used and so on. 'This is an area of science which has the potential to make a huge impact on people's lives, in reproductive medicine and across a whole spectrum of diseases.

'Look at something like the work that has been done on treatments for blood pressure, for example - it took twenty years but the end result was new treatments that have made significant improvements to the lives of hundreds of thousands of people.

'I believe it is essential to do this kind of embryonics research - after all this is how we all started! And before we start to correct the things that can go wrong, we have to understand the process and that to me suggests we have to start at the beginning and look at embryos.

'There are some who might say there are other ways of doing it. But my feeling is that we have to allow the scientists to do the research on embryonic stem cells and this is the best way it can be done, including using cyto-plasmic animal-human hybrids. Scientists have already demonstrated they can take an adult cell and try and make it behave like an embryonic stem cell. But to see if these cells behave like embryonic stem cells in every way, we must understand how the embryonic cell works in the first place.

'To use an analogy, it is like finding a yellow metal and thinking it is just like gold. To find out if it is, the first thing you need to do is test it against the properties of gold, and to do that you must know how gold behaves. In a similar way with examining stem cells derived from adult cells, we have to know how embryonic cells work.'

'Investigating a disease like Parkinson's and developing treatments for it, what scientists are looking to do is develop stem cell lines that carry the gene, so that they can see how it behaves in the cell, how it is active and so on,' said Lord Patel.

'Individuals may not develop disease until later in life but the gene fault and how that is activated may be present at birth. We have to find that out.

'The problem is that to develop stem cell lines using cell nuclear transfer technology you need human eggs, and those are obviously very difficult to get. So the alternative is to use animal eggs to produce embryonic stem cell lines that carry the disease genes and cultivate them into stem cell lines.

'The stem cells that result from this process are 99% human, maybe even 99.8%. Maybe 'hybrid' is too big a word for this process. Using a term like 'hybrid', people start to build pictures in their minds of what a combination of animal and human is, when the reality is considerably different. The people who are against these processes are using language which is much stronger than the reality of the situation.

'But this is an extremely emotive area, and therefore the challenge for scientists is to offer clear, concise explanations of the aims and processes, and realistic visions of what might be achieved.'