Ethics: What is ESNATS doing to address these ethical issues?
The ESNATS project raises a number of important ethical issues arising from the use of hESCs in testing and in the production of gametes from ESCs. Each partner organisation in ESNATS which is going to be involved in such activities has first had to satisfy the relevant ethical and regulatory bodies in both the EC and in their own country. In addition, within the ESNATS management structure, the Steering Committee includes an experienced ethicist familiar with issues related to stem cell research.
An ethical advisory group is being set up
a) to assess and advise the project on these issues,
b) to make recommendations for researchers,
c) to organise a workshop on the ethical implications, and
d) to offer ethical advice to the partners during the running of the project.
The ESNATS research involves the use of human biological samples, i.e. hepatocytes isolated from surgical samples. Informed consent of the donors will be obtained and the design of the study approved by the local institutional ethics committees (LEC) or review boards. All procedures for the use of human biological samples will be under the control of both the LEC of the participating institution and compliant with the national, European and international regulations as previously outlined. The researchers will be responsible for maintaining the subject's anonymity in accordance with Good Clinical Practice guidelines.
Use of animals
It is the aim of the ESNATS project to significantly reduce the numbers of animals currently used for toxicology testing during drug development by replacing parts of the required animal tests.
A major difficulty in evaluating toxicological risks in vitro is accounting for an in vivo-like metabolism, as complex interactions between metabolic activities may increase or decrease toxicity by more than 1 000-fold depending on the chemical properties of the test substance. An entire subproject (SP4) is thus dedicated to integrating metabolising systems into the test systems for reproductive and CNS toxicity. For the metabolic in vitro studies in the ESNATS project, hepatocytes will be used. It is intended to use hepatocytes derived from existing human embryonic stem cell lines and no longer rely on primary hepatocytes isolated from human surgical tissue samples or obtained from mice.
However, to verify the metabolic potential of such hESC-derived hepatocytes, comparisons
with primary hepatocytes isolated from patients and obtained from mice will first be performed. In case that the differentiation protocols for obtaining hepatocytes from hESCs are not robust enough, primary tissue from human surgical samples and obtained from mice will have to be used for some tests.
Transgenic animals will neither be used nor generated within the ESNATS project.