Humbug costs lives

In May, the UK government published a draft of the Human Tissue and Embryos Bill for pre-legislative evaluation. The proposals will amend the Human Fertilisation and Embryology Act 1990. The Bill bans the creation of embryos that contain genetic material from both nonhuman animals and humans, including ‘cybrids’ — embryos containing human genetic material but which are created using nonhuman animal eggs, such as rabbit eggs.

There are currently two ongoing applications to the Human Fertilisation and Embryology Authority (HFEA), submitted by scientists at the University of Newcastle and King’s College London, to use somatic cell nuclear transfer, also known as cloning, to create cybrid embryos. The embryos could generate embryonic stem cell lines.

The first phase of this research might be the generation of embryonic stem cell lines with genetic mutations that cause human disease, providing a model for studying the disease in cell culture. Groups in the UK aim to study Parkinson’s and Alzheimer’s diseases.

Why create cybrid embryos? There is a shortage of human embryos (and especially human eggs) for research. Those currently available are surplus from human-assisted reproduction techniques (in vitro fertilization or prenatal genetic diagnosis) and are very rare, often poor quality, and do not contain all the genetic mutations that need to be studied.

While human eggs are potentially available from altruistic or egg-sharing donors, it is extremely unlikely there would ever be enough made available from such sources. Proposals to derive eggs from embryonic stem cell lines are in their infancy and are not realistic at this stage.

Altruistic egg donation for research is not free from ethical controversy due to risks related to the surgical procedure and superovulation. Moreover, the efficiency rate of cloning is likely to be low (less than one per cent), so vast numbers of human eggs would be required for this research.

In contrast, eggs from nonhuman animals such as rabbits are in plentiful supply from farming and food industries. Scientists have lobbied hard to allow this kind of research.

However, the UK’s chief medical officer and a government white paper recommended against creation of such human-nonhuman cybrids. In response, 45 leaders of science (including three Nobel Laureates), ethics, and law petitioned the government in an open letter to allow this research. The letter has created significant public debate. Nonetheless, the draft Bill would ban such research.

The joint parliamentary committee reviewing the draft Bill was cross-party committee consisting of 18 MPs and Peers. They received evidence from 46 expert witnesses and 100 written submissions during its inquiry. They unanimously recommended that the regulatory authority should decide what is permitted and that there be a free vote on this section of the Bill. The report has now been submitted to the Department of Health for consideration.

Creating cybrids as source of disease- specific stem cells has enormous significance for two reasons.

First, it is a leap toward self-transplantation. Using this kind of technology, one day we may be able to take a skin cell from a patient with leukaemia, clone it, derive embryonic stem cells, produce blood stem cells, and transfer the blood cells back as a transplant after chemotherapy.

At that stage, as efficiency is improved, human eggs may be a more suitable source of eggs for the procedure, but the techniques could be developed on cybrids. As the therapeutic technique is developed to use human cells, because the cells would come from the patient there would be no need for drugs to prevent rejection, which can be lethal.

And we could produce tissue to repair damaged organs like the heart and brain with no capacity for regeneration, providing radical new treatments for stroke and heart attack, Parkinson’s disease, and many other diseases. This is regenerative medicine — the holy grail of medicine.

Second, cybrids could be used to study any disease in a culture dish in a radically new way to create ‘cellular models of disease’. Cloning a single skin cell from a patient with a disease could be used to produce inexhaustible amounts of cells and tissue with that disease.

The tissue could be experimented upon to understand why disease occurs. It could be used to understand the genetic contribution to disease and to test vast arrays of new drugs which could not be tested in people. It would also reduce the need for animal experimentation because human cells and tissues, not people or animals, could be used to test new drugs.

These two applications — self-transplantation and the development of cellular models of diseases, which are sometimes called ‘therapeutic cloning’ — mean that cloning may be viewed as one of the most significant scientific accomplishments of our time.

This raises significant ethical issues. To fail to do beneficial research is as wrong as doing harmful research; to fail to release a drug that will save 100,000 lives is morally equivalent to killing 100,000 people; to fail to develop a drug that will save 100,000 lives is the same as failing to release it.

We may not be able to identify those people whose lives would have been saved, but their lives are no less valuable. Through a failure of moral imagination we may continue to hold back cloning research and be responsible for the deaths of many people who perished while we delayed the development of treatments.

Here are four common objections to embryonic stem cell research.

First, the research requires large numbers of eggs that must be removed from healthy young women at some small risk of life and health to them; second, the research is said to be a ‘Western luxury’ which will be exotic and expensive, only benefiting the richest countries; third, many argue that adult stem cell research shows great potential and is preferable; finally, recent research shows there may be infectious and other risks, such as occurred with bovine spongiform encephalitis, of transplanting tissue back to people when it is grown on foreign culture material or uses animal eggs.

The creation of cybrids using nonhuman animal eggs to develop cellular models of disease is immune to all of these moral objections. It would require no human eggs to produce vast amounts of tissue for the study of disease; this may result in the development of drugs for common conditions which afflict people all around the world, including the developing world. It is not possible to use adult stem cells in this way.

And finally, there would be no risk of infection from drugs developed by studying tissue in this way, as the drug molecules would be produced pharmaceutically. These objections apply (if they apply at all) only to cloning for self-transplantation. They do not apply to cloning which will help us understand and treat disease. And they do not apply to experimenting on cybrids which will be destroyed.

There are three remaining objections. First, some people believe this research is wrong because it creates human cloned embryos which are destroyed for research. The current regulatory authority, the HFEA, has claimed that these cybrids are effectively human embryos. This claim is debatable in itself — it is unlikely that these cybrids would ever be able to develop into a live-born offspring (although this has not been tested).

However, for argument’s sake, let us grant that these cybrids are human embryos. It is important here to distinguish between the moral status of wanted and unwanted embryos.

Embryos have a special moral status — potential — when they are a part of a project to have a child. When they are not, they have a much lower status: for that reason we permit people to discard embryos in IVF when they have completed their family, have abortion, or use the IUD. This research would not prevent any child coming into existence who would have existed if the research had not been done.

The second objection is that we should not create new human-nonhuman cybrids or chimeras because they are unnatural and cross some kind of profound ethical line.

However, scientists have for over 20 years been inserting human genes into animals to create animal models of the human disease. Indeed, a significant proportion of the budgets of the National Institutes for Health in the US and the UK’s Medical Research Council goes to this research.

More recently, scientists have introduced human embryonic stem cells into animals to study development and disease. For over a decade we have had the power to create human-nonhuman chimeras by fusing embryos. Indeed, we have already created new animals such as the ‘geep’, brought into being by fusing a goat and sheep embryo. Novel life forms have been created and could be created.

Given that, in this case, the research will be closely regulated and the embryos destroyed, their creation does not raise new ethical issues. Indeed, cybrids raise fewer ethical issues than many of the chimeric (hybrid) and transgenic animals routinely created for the study of human disease. They are better seen as biological material or tissue for studying disease.

The third objection is that this research brings us ‘one step closer’ to reproductive cloning — cloning to produce live born babies. Reproductive cloning is unlikely to be safe based on the observation that cloned animals (mostly mice and cows) have hundreds of genes that are abnormally expressed, in particular genes important for foetal development.

The resulting animals have abnormalities during development (which is why 95 per cent or more of cloned embryos abort), at birth (‘large offspring syndrome’), or later in life (even seemingly normal mice often develop obesity, die prematurely, or develop more tumours than controls).

Interestingly, cloning to produce stem cells may be safer because the genes that cause the cloned embryos to be abnormal are not important for the derivation of embryonic stem cell (there is no foetal development).

In addition, the isolation of embryonic stem cells is a selection process where ‘normal’ cells will grow out into an embryonic stem cell line whereas ‘abnormal’ (not fully reprogrammed cells) will be selected against.

The response to fears about reproductive cloning is not to ban cloning. It is to ban reproductive cloning. The UK has already banned reproductive cloning, and any scientist in the UK who lets a cybrid develop longer than 14 days would face criminal charges.

To ban this research because of fears about reproductive cloning or creation of human-nonhuman chimeras is not just to throw the baby out with the bath water. It is possibly to throw millions of babies out.

When it comes to research into lethal diseases, time is not only money; it is human lives. There is a moral imperative to facilitate cybrid research.

Professor Julian Savulescu is Director of the Oxford Uehiro Centre for Practical Ethics and the Programme on the Ethics of the New Biosciences, 21st Century School, University of Oxford.