to what extent proposed research meets the expected ethical standards. the distinction between therapeutic and non-therapeutic research introduced in the original document, criticised by levine was removed to emphasize the more general application of ethical principles, but the application of the principles to healthy volunteers is spelt out in articles 18–9, and they are referred to in article 8 ('those who will not benefit personally from the research') as being especially vulnerable. the scope of ethical review was increased to include human tissue and data (article 1), the necessity to challenge accepted care was added (article 6), as well as establishing the primacy of the ethical requirements over laws and regulations (article 9). amongst the many changes was an increased emphasis on the need to benefit the communities in which research is undertaken, and to draw attention to the ethical problems of experimenting on those who would not benefit from the research, such as developing countries in which innovative medications would not be available. article 19 first introduces the concept of social justice, and extends the scope from individuals to the community as a whole by stating that 'research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research'. this new role for the declaration has been both denounced and praised, macklin r. future challenges for the declaration of helsinki: maintaining credibility in the face of ethical controversies. address to scientific session, world medical association general assembly, september 2003, helsinki and even considered for a clarification footnote. article 27 expanded the concept of publication ethics, adding the necessity to disclose conflict of interest (echoed in articles 13 and 22), and to include publication bias amongst ethically problematic behavior. additional principles the most controversial revisions (articles 29, 30) were placed in this new category. these predictably were those that like the fourth revision were related to the ongoing debate in international health research. the discussions indicate that there was felt a need to send a strong signal that exploitation of poor populations as a means to an end, by research from which they would not benefit, was unacceptable. in this sense the declaration endorsed ethical universalism. article 29 restates the use of placebo where 'no proven' intervention exists. surprisingly, although the wording was virtually unchanged, this created far more protest in this revision. the implication being that placebos are not permitted where proven interventions are available. the placebo question was already an active debate prior to the fourth revision but had intensified, while at the same time the placebo question was still causing controversy in the international setting. this revision implies that in choosing a study design, developed-world standards of care should apply to any research conducted on human subjects, including those in developing countries. the wording of the fourth and fifth revisions reflect the position taken by rothman and michel and freedman et al., known as 'active-control orthodoxy'. the opposing view, as expressed by levine and by temple and ellenberg is referred to as 'placebo orthodoxy', insisting that placebo controls are more scientifically efficient and are justifiable where the risk of harm is low. this viewpoint argues that where no standards of care exist, as for instance in developing countries, then placebo-controlled trials are appropriate. the utilitarian argument held that the disadvantage to a few (such as denial of potentially beneficial interventions) was justifiable for the advantage of many future patients. these arguments are intimately tied to the concept of distributive justice, the equitable distribution of the burdens of research. as with much of the declaration, there is room for interpretation of words. 'best current' has been variously held to refer to either global or local contexts. article 30 introduced another new concept, that after the conclusion of the study patients 'should be assured of access to the best proven' intervention arising from the study, a justice issue. arguments over this have dealt with whether subjects derive benefit from the trial and are no worse off at the end than the status quo prior to the trial, or of not participating, versus the harm of being denied access to that which they have contributed to. there are also operational issues that are unclear. aftermath given the lack of consensus on many issues prior to the fifth revision it is no surprise that the debates continued unabated. the debate over these and related issues also revealed differences in perspectives between developed and developing countries. zion and colleagues (zion 2000) have attempted to frame the debate more carefully, exploring the broader social and ethical issues and the lived realities of potential subjects' lives as well as acknowledging the limitations of absolute universality in a diverse world, particularly those framed in a context that might be considered elitist and structured by gender and geographic identity. as macklin points out, both sides may be right, since justice "is not an unambiguous concept". clarifications of articles 29, 30 (2002–2004) eventually notes of clarification (footnotes) to articles 29 and 30 were added in 2002 and 2004 respectively, predominantly under pressure from the us (cmaj 2003, blackmer 2005). the 2002 clarification to article 29 was in response to many concerns about wma's apparent position on placebos. as wma states in the note, there appeared to be 'diverse interpretations and possibly confusion'. it then outlined circumstances in which a placebo might be 'ethically acceptable', namely 'compelling... methodological reasons', or 'minor conditions' where the 'risk of serious or irreversible harm' was considered low. effectively this shifted the wma position to what has been considered a 'middle ground'. given the previous lack of consensus, this merely shifted the ground of debate, which now extended to the use of the 'or' connector. for this reason the footnote indicates that the wording must be interpreted in the light of all the other principles of the declaration. article 30 was debated further at the 2003 meeting, with another proposed clarification but did not result in any convergence of thought, and so decisions were postponed for another year, but again a commitment was made to protecting the vulnerable. a new working group examined article 30, and recommended not amending it in january 2004. later that year the american medical association proposed a further note of clarification that was incorporated. in this clarification the issue of post trial care now became something to consider, not an absolute assurance. despite these changes, as macklin predicted, consensus was no closer and the declaration was considered by some to be out of touch with contemporary thinking, and even the question of the future of the declaration became a matter for conjecture. sixth revision (2008) the sixth revision cycle commenced in may 2007. this consisted of a call for submissions, completed in august 2007. the terms of reference included only a limited revision compared to 2000. in november 2007 a draft revision was issued for consultation until february 2008, and led to a workshop in helsinki in march. those comments were then incorporated into a second draft in may. further workshops were held in cairo and são paulo and the comments collated in august 2008. a final text was then developed by the working group for consideration by the ethics committee and finally the general assembly, which approved it on october 18. public debate was relatively slight compared to previous cycles, and in general supportive. input was received from a wide number of sources, some of which have been published, such as feminist approaches to bioethics. others include cioms and the us government. seventh revision (2013) the most recent iteration of helsinki (2013) was reflective of the controversy regarding the standard of care that arose from the vertical transmission trials. the revised declaration of 2013 also highlights the need to disseminate research results, including negative and inconclusive studies and also includes a requirement for treatment and compensation for injuries related to research. in addition, the updated version is felt to be more relevant to limited resource settings—specifically addressing the need to ensure access to an intervention if it is proven effective. future the controversies and national divisions over the text have continued. the us fda rejected the 2000 and subsequent revisions, only recognizing the third (1989) revision, and in 2006 announced it would eliminate all reference to the declaration. after consultation, which included expressions of concern, a final rule was issued on april 28, 2008, replacing the declaration of helsinki with good clinical practice effective october 2008. this has raised a number of concerns regarding the apparent weakening of protections for research subjects outside the united states. the nih training in human subject research participant protection no longer refers to the declaration of helsinki. the european union similarly only cites the 1996 version in the eu clinical trials directive published in 2001. the european commission, however, does refer to the 2000 revision. while the declaration has been a central document guiding research practice, its future has been called into question. challenges include the apparent conflict between guides, such as the cioms and nuffield council documents. another is whether it should concentrate on basic principles as opposed to being more prescriptive, and hence controversial. it has continually grown and faced more frequent revisions. the recent controversies undermine the authority of the document, as does the apparent desertion by major bodies, and any rewording must embrace deeply and widely held values, since continual shifts in the text do not imply authority. the actual claim to authority, particularly on a global level, by the insertion of the word "international" in article 10 has been challenged. carlson raises the question as to whether the document's utility should be more formally evaluated, rather than just relying on tradition. timeline (wma meetings) 1964: original version. 18th meeting, helsinki 1975: first revision. 29th meeting, tokyo 1983: second revision. 35th meeting, venice 1989: third revision. 41st meeting, hong kong 1996: fourth revision. 48th meeting, somerset west (south africa) 2000: fifth revision. 52nd meeting, edinburgh 2002: first clarification, washington 2004: second clarification, tokyo 2008: sixth revision, 59th meeting, seoul 2013: seventh revision, 64th meeting, fortaleza