New technologies: ethical aspects

1. New technologies:ethical aspects Luiz Cláudio Arraes

2. “In the construction of concepts, one shall work, as we have seen, the language, and later, the science” Nietzsche

3. “Spleen and conclusions It is spleen. Or even, the other element. Jorge Luís Borges said that one can only consider a literary text as finished and definitive for two reasons: tiredness or religious faith. The same occurs in scientific experiments”

4. “Differences and similarities We can kill the mosquito or we can point it and say: Mosquito. The classifications and the categories begin in the lack of harmony”

5. “Feelings and science A science that does not investigate feelings: what is it for? It is for everything but feelings. Is it, then, for manhood? It is for everytihng in man that is not feeling”

6. “Familiar Science does not walk into Mistery. Nor into the Bizarre. Science walks into the Familiar”

7. “The history of science Scientific investigations depend, therefore, of God, Chance or Destiny (or what one wish to call it). But besides it all, it depends of the Reason”

8. “The minimum and the great To the minimal things science adds greatness. To the great, science adds small things”

9. Gonçalo M. Tavares Portuguese writer Born in 1970

10. Ethics • Aims and principles • Clinical experiments • The interest of the individual • The interest of science • Social benefits

11. Clinical trials -Greatest care: interventions and prospective evaluation. -Conflicts of interest - Investigator: Interests of science x economics x the cure of patients Research in developing countries. - Studies that are not locally relevant - Pretext: training of personnel

12. Conceptual basis - Principialism: beneficence, non-malfeasance, justice, autonomy - Utilitarism: exclusive dependence on consequences - Kantian philosophies: commitment with the patients

13. Ethics / methodology - Study designs that confirm treatment equivalence (non-inferiority) as opposed to placebo controlled trials • Benefits • To subjects, voluntaries and community

14. Fair benefits • Locally relevant research projects (HIV/AIDS) • Vulnerability is not the excuse • Few risks or benefits clearly superior to risks • Actions to create infrastructure and improve people's health

15. Historical landmarks - Nuremberg Code • Helsinki declaration – Hong Kong • In Brazil: Local ethics committees and National Council for Research Ethics

16. Individual Community

17. Science and technology

18. Dendritic-cell based vaccines for treating HIV infection In vitro studies 2000-2001 Macaques studies 2001-2003 Human studies 2002-2005

19. Viral suppression by SIV-DC vaccine

20. Lymph nodes examination at week 42 a, destruction of lymphoid follicles in a control monkey b, preservation of lymphoid follicles architecture in an immunized monkey

21. Dendritic-cell vaccine in HIV infection Nature Medicine, December 2004 Wei Lu,Luiz Claudio Arraes, Willa Ferreira, and Jean Marie Andrieu

22. Participating sites — Patients recruitment Recife — Viral culture/inactivation Paris [P3/class D] — Cytapheresis Recife — Dendritic cell culture Recife [P3/class D] — Vaccine preparation Recife [P3/class D] — Vaccine injections Recife — Immunological studies Paris

23. Patients were separated in two groups according totheir one- year viral load decrease Green:>90% Red:<90% • .

24. Cellular HIV-1 DNA load evolution Cellular viralloads (left) , CD4 T cells (circles) and CD8 T cells ( triangles) according to plasma viral load decrease <90% or >90%

25. Major problems with the HIV vaccine development model No conclusive evidence of human immunity to HIV Poorly defined correlates of protection High cost of pre-clinical development, requires development of SIV antigens as surrogate for challenge protection models Poor correlation of the SIV/SHIV non-human primate model with HIVAIDS human disease.= Very long and costly efficacy studies (phase III) Several difficult ethical issues regarding clinical design of the phase III studies.