Agenda - Réseau Sénégalais"Droit ,Ethique,Santé"

incandescentnonBiotechnology

Dec 10, 2012 (4 years and 8 months ago)

2,578 views

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

1

-

Comité d’éthique en recherche médicale et en
santé

䕲bÉs



卯mmai牥

䅧Énda

⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮
⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮
⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮
⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮
⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮⸮
⸮⸮

O

La révolution de la mort

................................
................................
................................
................................
....

2

60 ans après : le procès des médecins de Nuremberg

................................
................................
....................

2

Cobayes humains. Le grand secret des essais pharmaceutiques.

................................
................................
...

2

Progrès incrémental et éthique

: parlons
-
en

................................
................................
................................
.....

2

Rencontre avec le philosophe André Comte
-
Sponville
................................
................................
.....................

3

Reche
rche

................................
................................
................................
................................
...............................

3

Budget : des mesures fiscales pour la recherche et l'innovation

................................
................................
......

3

Recherche clinique

................................
................................
................................
................................
..................

3

Vaccination and Enrollment Are Discontinued in Phase II Trials of Merck's Investigational HIV Vaccine
Candidate Interim

................................
................................
................................
................................
.............

3

Espoirs déçus d'un vaccin contre le sida

................................
................................
................................
..........

5

Le laboratoire Merck annonce l'échec d'un essai de vaccin contre le sida

................................
.......................

6

Merck abandons HIV vaccine trials

................................
................................
................................
..................

6

South African HIV trial suffers setback

................................
................................
................................
.............

7

Nouvelle réglementation de la recherche clinique

................................
................................
............................

7

Beauty clinics accused of using their customers as guinea pigs

................................
................................
......

7

Report Assails F.D.A. Oversight of Clinical Trials

................................
................................
.............................

8

Cellules souches, clonage, recherche sur l’embryon

................................
................................
...............................

9

The Future (R)evolution of Preimplantation Genetic Diagnosis/Human Leukocyte Antigen Testing: Ethical
....

9

France

................................
................................
................................
................................
................................

15

Inauguration de deux nouveaux laboratoires à Genopole (Evry) en présence de Valérie Pécresse,

.............

15

Allemagne

................................
................................
................................
................................
..........................

16

Scientists criticize adult stem cell claim

................................
................................
................................
..........

16

The long and winding road

................................
................................
................................
.............................

17

Royaume Uni

................................
................................
................................
................................
.....................

18

Stem cell therapy ‘will be commonplace’

................................
................................
................................
........

18

Warning for UK stem cell research

if US relaxes rules

................................
................................
...................

19

Etats Unis

................................
................................
................................
................................
...........................

19

Stem cells by any other name

................................
................................
................................
........................

20

Of Animal Eggs and Human Embryos

................................
................................
................................
............

20

Thaïlande

................................
................................
................................
................................
...........................

21

Stem
-
cell fraudster 'is working in Thailand'

................................
................................
................................
.....

21

Génétique, OGM

................................
................................
................................
................................
...................

21

Immigration: le test ADN «n'est pas un tabou»
................................
................................
...............................

22

Aux orties

................................
................................
................................
................................
.......................

22

Non au contrôle génétique de l’immigration

................................
................................
................................
...

23

Breast cancer gene test advert sparks criticism

................................
................................
.............................

23

ADN et immigration, d'abord une question de morale.

................................
................................
...................

24

L'amendement sur les tests ADN supprimé en commission au Sénat

................................
...........................

25

Myriad Genetics launches BRCA testing ad campaign in Northeast

................................
..............................

25

LA COMMISSION DES LOIS DU SÉNAT REJETTE LES TESTS ADN ET MODIFIE LA CONDITION DE
RESSOURCES POUR LE REGR
OUPEMENT FAMILIAL

................................
................................
.............

27

L'amendement instaurant des tests ADN pour les étrangers pourrait être supprimé au Sénat

......................

27

Vingt
-
huit fois

non !

................................
................................
................................
................................
.........

28

Human Genetics Commission response to the Discrimination Law Review consultation, A Framework for
Fairness: Proposals for a Single Equality Bill for Great Britain

................................
................................
.......

28

Will Genomics Widen or Help Heal the Schism Between Medicine and Public Health?

................................
.

29

STATEMENT ON DIRECT
-
TO
-
CONSUMER GENETIC TESTING
................................
................................

37

THÉRAPIE GÉNIQUE : PROMESSES ET RÉALITÉ

................................
................................
.....................

38

Pharmacogénétique

................................
................................
................................
................................
..............

40

Personaliz
ed Medicine' Comes to Mt. Sinai

................................
................................
................................
...

40

Society, health system need to prepare for era of personal genomes: experts

................................
..............

41

Gene informati
on opens new frontier in privacy debate
................................
................................
..................

42

Biobanque

................................
................................
................................
................................
.............................

43

Neurosciences

................................
................................
................................
................................
.......................

43

Médicaments, industrie pharmaceutique

................................
................................
................................
...............

43

L’OMS souligne la nécessité de veiller à l’innocuité des médicaments destinés à l'enfant

............................

43

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

2

-

Drug Makers Seek Clues to Side Effects in Genes

................................
................................
........................

44

Pays en développement

................................
................................
................................
................................
........

45

Nanotechnologies

................................
................................
................................
................................
..................

45

Recherche : les nanotechnologies raflent la mise

................................
................................
..........................

45

Projet européen de cours d'été de formation à la nanoéthique

................................
................................
......

47

Expérimentation animale

................................
................................
................................
................................
.......

47

Les Etats
-
Unis vont
-
ils cesser de tester les produits chimiques sur des animaux ?

................................
.......

47

Written declaration on primates in scientific experiments

................................
................................
...............

48

Intégrité scientifique

................................
................................
................................
................................
...............

49

Profound ethical issues

were smoothed over

................................
................................
................................
.

49

Savants au bord de la crise de nerfs

................................
................................
................................
..............

49

Conflit d’intérêt

................................
................................
................................
................................
.......................

50

Conflict of interest or contravention of science?

................................
................................
.............................

51

Brevet

................................
................................
................................
................................
................................
....

52

New Peer Review Website Offers Path to Patent

Reform

................................
................................
..............

52

Expertise
................................
................................
................................
................................
................................

53

Ethique

................................
................................
................................
................................
................................
..

53

Détection des cellules cancér
euses dans le sang

: le comité d’éthique réservé sur les tests

........................

53

Le CEA signe la charte européenne du chercheur

................................
................................
.........................

53

The Declarat
ion of Helsinki

................................
................................
................................
.............................

54

Traitement compassionnel
................................
................................
................................
................................
.....

55

Publication, open access

................................
................................
................................
................................
.......

55

How to resolve authorship disputes

................................
................................
................................
................

55

Divers

................................
................................
................................
................................
................................
....

56

Biosafety lapses prompt govt. review

................................
................................
................................
.............

56

Panel Wants U.S. Program to Retain Its Russian Roots

................................
................................
................

57

Accidents Spur a Closer Look at Risks at Biodefense Labs

................................
................................
...........

58


Agenda


1er octobre 2007, 18H30
-
21H, Hôpital européen Georges Pompidou/AP
-
HP


La révolution de la mort

Nouvelles approches de la mort en société.

http://www.espace
-
ethique.o
rg/doc2007/Revolution_Mort_011007_Pompidou.pdf





8 octobre 2007, 20H
-
22H, Fondation Rothschild


60 ans après : le procès des médecins de Nuremberg

L’irruption de l’éthique médicale.

http://www.espace
-
ethique.org/doc2007/Nuremberg_081007.pdf





Les éditions Demopolis vous invitent à assister à la conférence
-
débat qui se tiendra à l’ENS le 16 octobre autour
du livre de Sonia Shah,

Cobayes humains. Le grand secret des essais phar
maceutiques.

Sonia Shah est une journaliste d’investigation américaine qui a enquêté plusieurs années sur l’évolution des
essais thérapeutiques dans le monde, avant et après la promulgation des textes internationaux et codes
d’éthique. Ses recherches l’ont

menée aussi bien en Europe de l’Est qu’en Inde et dans différents pays d’Afrique
sans négliger pour autant l’histoire des essais aux États
-
Unis. En quelques années, la situation de ces pays a
changé et le développement des essais pose de nombreuses questi
ons. Á l’heure où l’on célèbre le 60ème
anniversaire du Code de Nuremberg, ce débat propose de les aborder sans fard.

École Normale Supérieure

45, rue d’Ulm Paris 75005 salle des Actes

mardi 16 octobre 19 h


21 h30

inscription obligatoire avant le 15 oc
tobre :
lklejman@demopolis.fr


CRIP

Progrès incrémental et éthique

: parlons
-
en

Mercredi 17 octobre 2007 de 16h30 à 17h30 salle atrium à l’étoile Saint
-
Honoré

URL
http://www.orpha.net/actor/Orphanews/2007/doc/increm.pdf


Café santé Inserm

Avec Jean
-
Claude Ameisen et Yvan Brohard au café des éditeurs

Le mercredi 17 octobre à 18 heures

C
aroline.petit@broca.inserm.fr


24 octobre 2007, 18h30
-
21h, Ministère de la Santé

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

3

-


Rencontre avec le philosophe André Comte
-
Sponville

Alzheimer 2007.

http://www.espace
-
ethiq
ue.org/doc2007/AComte
-
Sponville_241007.pdf


Recherche


Source LE MONDE | 26.09.07 | 13h06 • Mis à jour le 26.09.07 | 13h06

URL
www.lemonde.fr


Budget : des mesures fiscales pour la recherche et l'innovation

La loi
du 21 août sur le travail, l'emploi et le pouvoir d'achat (TEPA), dans laquelle figurent la détaxation des
heures supplémentaires et des baisses d'impôts, coûtera 8,9 milliards d'euros en 2008.

Ce "paquet fiscal" mobilisera une bonne partie des marges de
manœuvre budgétaires du gouvernement.

Onze autres dispositions fiscales figurent dans le budget. Les principales concernent la recherche et l'innovation.

Claire Guélaud

Crédit d'impôt recherche

Déplafonné, le crédit d'impôt recherche (CIR) s'appliquera dé
sormais à la totalité des dépenses de recherche.

Il est simplifié et recentré sur les petites et moyennes entreprises (PME).

Son taux est porté à 30 % jusqu'à 100 millions d'euros de dépenses (puis 5 % au
-
delà de ce seuil).

Il est majoré à 50 % lorsque les

entreprises en bénéficient pour la première fois ou n'en ont pas bénéficié depuis
cinq ans.

Ainsi réformée, la mesure coûtera 2,7 milliards en régime de croisière.

Fiscalité sur les brevets

La fiscalité sur les brevets est allégée, notamment via l'extensi
on du bénéfice du taux réduit de l'impôt sur les
sociétés aux cessions de brevets.

Les jeunes entreprises universitaires se verront appliquer le même régime fiscal et social que les jeunes
entreprises innovantes, exonérées, partiellement ou totalement, de
certains impôts.

Crédit d'impôt sur les intérêts d'emprunt

Intégré à la loi TEPA, le crédit d'impôt sur les intérêts d'emprunt a été revu pour tenir compte de la décision du
Conseil constitutionnel d'en limiter le bénéfice aux personnes qui ont signé un ac
te authentique de vente devant
notaire à partir du 6 mai.

Porté de 20 % à 40 % du montant des intérêts payés la première année, il atteindra au maximum 3 000 euros
pour un couple, 1 500 euros pour une personne seule, plus 200 euros par personne à charge.

P
rime pour l'emploi

Destinée à favoriser le travail des personnes plus modestes, la prime pour l'emploi (PPE), dont plus de 8 millions
de foyers fiscaux ont bénéficié en 2006, est revalorisée de 1,3 % pour tenir compte de l'évolution des prix.

Il en est de

même pour le barème de l'impôt sur le revenu.

Prélèvement à la source sur les dividendes

Un prélèvement à la source sur les dividendes, libératoire de l'impôt sur le revenu, au taux de 16 %, est institué.

La même modalité de paiement vaudra pour les prélè
vements sociaux.

Régime de solidarité fiscale

Le régime de solidarité fiscale entre époux et partenaires liés par un pacs change avec la création d'un droit à
décharge de responsabilité solidaire (DRS) en cas de séparation.

Régime fiscal des pactes d'actio
nnaires

Le régime fiscal des pactes d'actionnaires est harmonisé et assoupli dans le cas de la transmission des titres de
sociétés ou d'une entreprise individuelle, et en matière d'exonération partielle d'impôt de solidarité sur la fortune.


Recherche clin
ique


Source Laboratoire Merck 21/09/2007

URL
http://www.merck.com/newsroom/press_releases/research_and_development/2007_0921.html


Vaccination and Enroll
ment Are Discontinued in Phase II Trials of Merck's Investigational HIV
Vaccine Candidate

Interim

Analysis of STEP Study Shows Vaccine was not Effective

WHITEHOUSE STATION, N.J., and Seattle, Sept. 21, 2007
-

Vaccination in a phase II clinical trial of Me
rck &
Co., Inc.'s investigational HIV vaccine (V520) is being discontinued because the vaccine was not effective. The
announcement was made today by the co
-
sponsors of this clinical trial, Merck & Co., Inc., and the HIV Vaccine
Trials Network (HVTN), whic
h is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part
of the U.S. National Institutes of Health.

The trial, called STEP, was an international phase II "test of concept" trial in uninfected volunteers at high risk for
acquir
ing HIV infection. The independent Data Safety Monitoring Board (DSMB) for STEP reviewed safety data
and results of an interim efficacy analysis of the study, and recommended that vaccination be discontinued
because the STEP trial will not meet its efficac
y endpoints. Study investigators have been instructed to
discontinue vaccinating volunteers in this study and to monitor them in accordance with the study protocol.
Enrollment and vaccination in a second Phase II trial of this vaccine being conducted by
the HVTN in South Africa
called Phambili, and two additional Phase I trials, have been discontinued. The DSMB for the Phambili trial will
evaluate the available data.

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

4

-

The Merck vaccine candidate is a mixture of three components, each made with a weakened
version of a
common virus (adenovirus type 5), that serves as a carrier, or delivery vector, along with three synthetically
produced HIV genes known as gag, pol and nef.

The STEP study (HVTN 502, Merck V520 Protocol 023) was a multicenter, randomized, doub
le
-
blind, placebo
-
controlled phase II test
-
of
-
concept clinical trial. The trial enrolled 3,000 HIV
-
negative volunteers from diverse
backgrounds between 18 and 45 years of age at high risk of HIV infection.

The study evaluated two primary efficacy endpoint
s: whether the vaccine prevented HIV infection and whether
the vaccine reduced the amount of virus in those who developed infection. As planned, an interim efficacy
analysis was conducted in the approximately 1,500 volunteers expected to have the best re
sponse to the vaccine
because they had low levels of pre
-
existing immunity to adenovirus 5.

The vaccine did not prevent infection: in volunteers who received at least one dose of the three
-
dose vaccine
series, 24 cases of HIV infection were observed in th
e 741 volunteers who received vaccine and 21 cases of HIV
infection were observed in the 762 participants in the placebo group. In the subgroup who had received at least
two vaccinations and who were HIV negative for at least the first 12 weeks of the tria
l, 19 cases of HIV infection
were observed in the 672 volunteers who received vaccine and 11 cases were observed in the 691 volunteers
who received placebo. In addition, the vaccine did not reduce the amount of virus in the bloodstream of those
who became

infected; HIV RNA levels approximately 8 to 12 weeks after diagnosis of infection were similar in the
vaccine and the placebo arms. The geometric means of the HIV RNA levels in the blood of infected individuals,
the standard measure of ongoing HIV replic
ation, were approximately 40,000 copies/mL in the vaccine group and
approximately 37,000 copies/mL in the placebo group. Additional analyses will be conducted on the entire study
population and will be shared with the scientific community.

Study volunteer
s were followed for approximately 13 months. Overall adverse event rates were generally similar
among the two groups, except for a higher rate of local injection
-
site related reactions in the vaccine group.

"We share in the disappointment of the research
and HIV communities today. Sadly, developing an effective
AIDS vaccine remains one of the most challenging tasks facing modern medicine," said Peter S. Kim, Ph.D.,
president, Merck Research Laboratories. "Merck's 20
-
year HIV research program has led to i
mproved scientific
understanding of HIV and to true breakthrough medicines. We are committed to studying the data closely and
sharing it with the scientific community to inform the on
-
going search for an effective HIV vaccine."

"HVTN is a global network o
f scientists, staff and community members whose mission is to speed the rapid
development of a safe and effective preventative HIV vaccine," said Larry Corey, M.D., principal investigator of
the HVTN. "This trial was the first test of concept trial that p
rovided us information on this vaccine more quickly
and efficiently than with a traditional Phase III design.

While we are very disappointed that this vaccine candidate did not demonstrate protection, the data from this trial
will provide critical insights

into this disease and future vaccine development."

"This is a huge disappointment for all of us who have been involved in the search for an HIV vaccine," said
Glenda Gray, M.D., principal investigator of the HVTN sponsored Phambili trial. "HIV is ravagin
g our
communities, and all the scientists, participants and communities involved in HIV vaccine studies have been
affected by this epidemic. The scientific community must continue the race to find a vaccine to help secure an
HIV free generation for the fu
ture."

The Merck adenovirus
-
based vaccine used a cell
-
mediated immune response approach; it was hypothesized that
the HIV genes in the vaccine would stimulate the body to generate an HIV
-
specific immune response through the
body's own CD8 T
-
cells, which be
come programmed to recognize and kill HIV infected cells.

Adenoviruses are among the causes of common cold; the type 5 adenovirus used in this investigational vaccine
had been modified so that it was unable to replicate and could not cause a cold. Also, b
ecause the vaccine did
not contain live HIV and contained only three HIV genes, volunteers could not become infected with HIV from the
vaccination. This vaccine had previously been tested in several smaller clinical trials and was found to be
generally we
ll tolerated and capable of inducing significant levels of HIV
-
specific cell
-
mediated immune
responses.

STEP included multiple clinical trial sites in North and South America, the Caribbean and Australia, where HIV
subtype B, the subtype of HIV from which
the HIV genes included in the vaccine, is predominant. Half the study
participants received three doses of the vaccine over six months, while the other half were given three doses of a
placebo. The first volunteer enrolled in the study in December 2004,
and enrollment was completed in March
2007.

The second phase II trial of this vaccine candidate, the Phambili trial, (HVTN 503, Merck V 520 Protocol 026) was
begun in 2007 in South Africa by the HVTN to explore whether Merck's vaccine would be effective at

preventing
infection, reducing viral levels, or both, from HIV subtype C, which is more common in southern Africa.

About Merck and Merck's HIV research program

Merck's efforts to develop investigational treatments and a vaccine against HIV/AIDS have been
under way for
more than 20 years and continue today; our HIV research program began in 1986. Merck scientists were the first
to characterize the role of HIV protease in the HIV life cycle and to publish the crystal structure of the HIV
protease enzyme, wh
ich helped the research community design protease inhibitors to block HIV infection by this
mechanism. In the 1990s, Merck scientists discovered the protease inhibitor, CRIXIVAN® (indinavir sulfate), and
the non
-
nucleoside reverse transcriptase inhibitor,

STOCRIN® (efavirenz). In addition, on September 5, 2007, an
advisory committee to the Food and Drug Administration unanimously recommended approval of ISENTRESS™
(raltegravir), Merck's investigational integrase inhibitor for the treatment of HIV infectio
n. The FDA is not bound
by the committee's recommendation but takes its advice into consideration when reviewing investigational
medicines and vaccines.

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

5

-

Merck & Co., Inc. is a global research
-
driven pharmaceutical company dedicated to putting patients fir
st.
Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to
address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through
far
-
reaching programs that not onl
y donate Merck medicines but help deliver them to the people who need them.
Merck also publishes unbiased health information as a not
-
for
-
profit service. For more information, visit
www.merck.com.

About the HIV Vaccine Trials Network

The HVTN is an inte
rnational collaboration of scientists and institutions whose goal is to accelerate the search for
an HIV vaccine by sharing trial results and facilitating parallel, concurrent testing. The HVTN is a unique hybrid
that combines the depth and diversity of t
he academic community and the flexibility of a commercial drug
company. Working with industry and government, the HVTN seeks to expedite and coordinate the trial process,
advancing vaccine candidates and building a body of knowledge about HIV vaccine tria
ls.

The HIV Vaccine Trials Network is supported through a cooperative agreement with the National Institute of
Allergy and Infectious Diseases (NIAID), which is a component of the U.S. National Institutes of Health (NIH).
The Network and NIAID have a clos
e, cooperative working relationship, with shared attention to the intellectual
and scientific issues. The Network's headquarters are at Fred Hutchinson Cancer Research Center in Seattle,
Washington.

Merck forward
-
looking statement

This press release conta
ins "forward
-
looking statements" as that term is defined in the Private Securities Litigation
Reform Act of 1995. These statements are based on management's current expectations and involve risks and
uncertainties, which may cause results to differ materi
ally from those set forth in the statements. The forward
-
looking statements may include statements regarding product development, product potential or financial
performance. No forward
-
looking statement can be guaranteed, and actual results may differ ma
terially from
those projected. Merck undertakes no obligation to publicly update any forward
-
looking statement, whether as a
result of new information, future events, or otherwise. Forward
-
looking statements in this press release should be
evaluated toget
her with the many uncertainties that affect Merck's business, particularly those mentioned in the
risk factors and cautionary statements in Item 1A of Merck's Form 10
-
K for the year ended Dec. 31, 2006, and in
its periodic reports on Form 10
-
Q and Form 8
-
K
, which the company incorporates by reference.


Source Le Figaro 24/09/2007

URL
http://www.lefigaro.fr/sciences/20070924.FIG000000139_espoir
s_decus_d_un_vaccin_contre_le_sida.html


Espoirs déçus d'un vaccin contre le sida

JEAN
-
LUC NOTHIAS. Publié le 24 septembre 2007 Actualisé le 24 septembre 2007 : 07h47

Le laboratoire Merck a annoncé qu'il abandonnait les essais de phase II du V520, faute d
e résultats.

ON DISAIT que c'était l'un des candidats vaccins contre le sida les plus prometteurs. Mais après trois ans
d'essais sur des milliers de volontaires, force a été aux chercheurs du laboratoire pharmaceutique Merck et à
ceux de l'Institut nation
al américain des allergies et des maladies infectieuses (Niaid) qui menaient conjointement
l'étude, de se rendre à l'évidence : le candidat vaccin ne marche pas.

« Ce vaccin était vu comme la stratégie la plus prometteuse et je pense que cet échec est une
déception pour
nous et pour tous ceux travaillant sur des vaccins », a déclaré le Dr Mark Feinberg, vice
-
président de Merck, cité
par le New York Times. De son côté, Anthony Fauci, directeur du Niaid, tout en jugeant « les résultats de ce test
évidemment d
écevants », a estimé qu'il était cependant trop tôt pour jeter au feu cette nouvelle classe de vaccins
antisida.

Car, contrairement aux vaccins classiques qui consistent à « doper » de façon générale l'immunité de l'organisme
afin d'augmenter la production

d'anticorps, le vaccin de Merck visait à stimuler de façon ciblée un certain type de
cellules, les lymphocytes T. Des études précédentes ont en effet montré que ceux qui résistent le mieux au virus
et à la maladie sont ceux qui présentent le taux de lymph
ocytes T le plus important.

D'autres expériences en cours

D'où la conception du candidat vaccin nommé V520. Il s'agit d'un virus du rhume atténué auquel on a adjoint trois
gènes synthétiques du VIH (gag, pol et nef), censés entraîner une forte réponse des
lymphocytes T. Ainsi, en
2004, l'essai clinique du V520 était lancé sur 3 000 volontaires séronégatifs de 18 à 45 ans aux États
-
Unis, en
Australie, au Pérou, au Brésil, à Porto Rico et, un peu plus tard, en Afrique du Sud. La moitié des volontaires, des
pe
rsonnes saines mais à la vie plus à risque que d'autres (homosexuels, prostituées...), ont reçu trois injections
du V520 en six mois, tandis que l'autre moitié recevait, sans le savoir, trois doses d'un « faux » vaccin.

Retournés à leur vie normale, les vo
lontaires étaient régulièrement suivis pour savoir s'ils avaient été infectés par
le VIH au cours de leurs activités. C'est un premier bilan intermédiaire portant sur 1 500 volontaires qui a décidé
de l'interruption de l'essai. En effet, sur les 741 person
nes ayant reçu au moins une dose du V520, 24 cas
d'infection au VIH ont été constatés. Et sur les 762 n'ayant reçu qu'un vaccin placebo, 21 cas d'infection ont été
relevés. Conclusion, le candidat vaccin ne protège pas. De plus, on espérait que le V520 aur
ait au moins un effet
de réduction de la charge virale, mais cela n'a pas été le cas non plus.

Pour les spécialistes, cette double déception ne doit pas faire baisser les bras. Si elle confirme que le virus du
sida est décidément très différent de tous les

autres pathogènes contre lesquels la médecine a pu développer
des vaccins, ce n'est pas la fin des recherches. « Pour nous, c'est accablant, mais nous devons continuer à
avancer », a ainsi souligné Glenda Gray, qui supervisait l'essai en Afrique du Sud et

dirige également l'unité de
recherche sur le sida à l'hôpital Chris
-
Hani de Soweto, au sud
-
ouest de Johannesbourg.

Ainsi, une trentaine d'autres essais de vaccins contre le sida sont encore en cours, bien qu'à des stades
d'avancement différents. Le Niaid
par exemple a un test en cours depuis le début de l'année avec une version «
Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

6

-

améliorée » du V520 dans laquelle ont été rajoutés d'autres constituants génétiques du VIH. Il devrait aussi
lancer un test avec un vaccin « double » : une première injection avec

des gènes du VIH, suivie par une injection
d'un produit similaire au V520.

Depuis l'identification du VIH en 1981, le nombre de porteurs du virus ne cesse d'augmenter avec près de 40
millions de personnes dans le monde, dont plus de 4 millions de nouvelle
s infections chaque année, à 90 % dans
les pays en développement. En vingt
-
cinq ans, le sida a fait plus de 25 millions de morts, dont la majorité en
Afrique subsaharienne.

Source LE MONDE | 22.09.07 | 14h37 • Mis à jour le 22.09.07 | 14h37

URL
www.lemonde.fr


MÉDECINE 24 CAS D'INFECTION SUR 741 VOLONTAIRES

Le laboratoire Merck annonce l'échec d'un essai de vaccin contre le sida

C'EST une fort mauvaise nouvelle dans le domaine de la recherche vaccinale contre l'infec
tion contre le virus du
sida : la multinationale pharmaceutique américaine Merck a annoncé, vendredi 21 septembre, qu'elle avait décidé
de mettre un terme à ses essais cliniques d'un candidat vaccin après la découverte que ce dernier n'apportait
nullement
la protection escomptée. "Le Groupe de surveillance indépendant a recommandé qu'il soit mis fin aux
essais du vaccin car ces essais n'ont pas démontré son efficacité", a indiqué la firme dans un communiqué.

Les responsables de Merck ont précisé que 24 des
741 personnes du groupe qui avaient reçu le candidat vaccin
avaient été infectées par le VIH. Par comparaison dans le groupe ayant reçu un placebo 21 personnes sur 762
ont été infectées.

La décision de Merck est d'autant plus marquante que ce vaccin expéri
mental
-

dénommé V520
-

était
généralement perçu comme l'un des plus prometteurs parmi tous ceux qui sont en cours d'élaboration ou
d'évaluation. A ce titre tous les spécialistes de la lutte contre le sida lui portaient un très vif intérêt.

Cet essai vacci
nal international était mené sur près de 1 500 volontaires et était conduit sous l'égide des Instituts
nationaux américains de la santé (NIH). Tous les volontaires étaient, au départ, séronégatifs mais tous étaient
aussi plus exposés que la moyenne de la p
opulation au risque de contamination par le VIH.

Il s'agissait pour l'essentiel d'homosexuels masculins et de prostituées. L'essai avait commencé en décembre
2004 et devait au total concerner 3 000 volontaires en Australie, au Brésil, au Canada, en Républi
que
Dominicaine, en Haïti, en Jamaïque, au Pérou, à Parto
-
Rico ainsi qu'au Etats
-
Unis. Le même vaccin était en
cours d'évaluation en Afrique du sud et les essais dans ce pays ont également été arrêtés.

Comme dans tous les essais cliniques de ce type les re
sponsables avaient, pour des raisons éthiques, expliqué
que le fait de participer à cette recherche ne devait aucunement conduire à un relâchement vis
-
à
-
vis des
méthodes de protection, à commencer par l'usage systématique du préservatif lors des relations
sexuelles. Pour
autant rien ne permet au promoteur de l'essai de savoir si ses recommandations sont en pratique suivies ou si le
fait d'être "vacciné" conduit à une modification de comportement.

"Ce sont là des nouvelles très décevantes, a déclaré Keith Go
ttesdiener, chef du groupe spécialisé de Merck sur
les recherches cliniques vaccinales et des maladies infectieuses. Un effort majeur pour développer un vaccin
protecteur contre l'infection par le VIH n'a en définitive pas tenu ses promesses."

Alors que le
s vaccins expérimentaux de première génération cherchaient à stimuler la production par l'organisme
d'anticorps dirigés contre le VIH, le vaccin de Merck visait à induire la production de cellules immunitaires
spécialisées dans la défense antivirale, les l
ymphocytes T "tueurs".

Michael Zwick, du Scripps Research Institute, estime qu'il est encore trop tôt pour savoir si ce résultat négatif
signifie que les tous les candidats vaccins fondé sur la même stratégie conduiront aux mêmes conclusions.

Le docteur An
thony Fauci, chef de l'Institut national américain des allergies et des maladies infectieuses, a
précisé que ces vaccins expérimentaux en cours d'expérimentation comportent des différences importantes par
rapport à celui de Merck.

L'un d'entre eux, dévelop
pé par les NIH et qui fait l'objet d'un essai clinique qui débuté en janvier, comporte les
trois mêmes gènes viraux que le V520, mais qu'il contient aussi trois versions d'un autre gène. Rien ne permet
toutefois de savoir si ce profil différent permettra d
e fournir une protection contre l'infection.

D'autres recherches sont en cours dans le domaine des vaccins préventifs ainsi que dans celui de vaccins
thérapeutiques.

Jean
-
Yves Nau

Article paru dans l'édition du 23.09.07


Source BBC News 21/09/2007

URL
http://news.bbc.co.uk/go/pr/fr/
-
/2/hi/health/7007734.stm


Merck abandons HIV vaccine trials

International drug company Merck has halted trials on an HIV vaccine that was regarded as on
e of the most
promising in the fight against Aids.

Merck stopped testing the vaccine after it was judged to be ineffective.

In trials, the vaccine failed to prevent HIV infections among volunteers who were at risk of catching the virus,
including gay men

and sex workers.

Merck had previously expressed high hopes for the drug, which it spent 10 years developing.

'Headed for failure'

Merck's international trial, called Step, began in 2004 and involved 3,000 HIV
-
negative volunteers from diverse
background
s, between the ages of 18 and 45.

Merck said that 24 of 741 volunteers who got the vaccine became infected with HIV, the virus that causes Aids.

Out of a group of 762 volunteers who were given a dummy version of the jab, 21 became infected with HIV.

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

7

-

An
independent monitoring panel recommended discontinuing the vaccination of volunteers, saying the trial was
headed for failure.

Most of the volunteers were at high risk of HIV infection.

They were repeatedly given advice about how to practise safe sex, ac
cording to Merck.

The vaccine contained a common cold virus loaded with copies of three HIV genes.

The hope was that exposure to the genes would prompt an immune response in the body so that cells containing
HIV virus would be recognised and destroyed.

"Today is a very sad day for the industry because Merck's vaccine had shown an ability to turn on the immune
system, which gave many people optimism it would work," said Sarah Alexander, from the HIV Vaccine Trials
Network.

Doctors have said a preventativ
e vaccine would be the best way to control the spread of HIV.

Story from BBC NEWS


Source SciDev 21/09/2007

URL
http://www.scidev.net/content/news/eng/south
-
african
-
hiv
-
trial
-
suffers
-
setback.cfm


South African HIV trial suffers setback


Christina Scott

Africa's biggest HIV vaccine trial were stopped today (21 September) after a sister study testing the same
experimental vaccine in US men found no protection

against infection.

Glenda Gray, from the Chris Hani Baragwanath Hospital in Johannesburg, South Africa, and a lead researcher
with the Phambili vaccine trials, confirmed that 700 volunteers from five sites in South Africa had already begun a
series of thr
ee injections spaced over 12 weeks.

''Not one volunteer has been put at risk or harmed in any way,'' she emphasised.

The South African tests, intended to recruit 3000 people, have been ''paused'' until local researchers have studied
the American data, bas
ed on men who have sex with men.

''This is a good sign in a way,'' Gray told SciDev.Net. ''This virus is elusive. We learn from these setbacks. We
learn new ways, new ideas about to find a vaccine. We change our strategies as we learn more."

But Gray also
said the stoppage was ''a tragedy which has put us back twenty years''.

The Phambili tests were "the largest vaccine trial so far in South Africa and in Africa", according to microbiologist
Koleka Mlisana of the Centre for the AIDS Programme of Research in

South Africa (CAPRISA). The vaccine was
based on an adenovirus


the common cold virus


so carried no risk of transmitting HIV itself.

This week (17

19 September) the Bio2Biz biotechnology conference in Cape Town heard that only one HIV
vaccine, in Thai
land, has progressed to the final stage, phase III clinical trials.

Jim Sherwood, of the Johannesburg offices of the International AIDS Vaccine Initiative (IAVI), said the lack of
progress was a "sad state". But he praised researchers for ''casting a wide
r net'' by using second level phase II
trials to check vaccine effectiveness earlier.

IAVI's introductory double vaccine trial


which uses naked DNA and a different type of adenovirus from the
Phambili vaccine


was originally due to begin next week in Ke
nya, Rwanda, Uganda and Zambia. It, too, may
be delayed while researchers study the US data.


Source
La Lettre de la Recherche Clinique d'Ile
-
de
-
France 2007

DIRC Ile de France 2007
-
2

URL
ht
tp://www.dirc.aphp.fr/lettre_drc/2007/2007_2.pdf


Nouvelle réglementation de la recherche clinique


Source The Independent 28/09/2007

URL
http://news.independent.co.uk/health/article3
007138.ece


Beauty clinics accused of using their customers as guinea pigs

By Jeremy Laurance, Health Editor

Published: 28 September 2007

Customers of high
-
street beauty clinics are being used as guinea pigs for unproven cosmetic techniques peddled
by
cowboy practitioners, doctors have claimed.

Injectable fillers to remove wrinkles, fat
-
busting treatments for the overweight and microwaves to tauten slack skin
are being introduced without proper controls or adequate testing, said the British Association

for Aesthetic Plastic
Surgeons (BAAPS).

Many firms now offer products and techniques which they claim can improve appearance, reduce weight and tone
skin without the need for surgery. Non
-
surgical treatments are cheaper, simpler to administer and many can

be
carried out by anyone with a modicum of training, such as hairdressers.

At the start of their annual conference in London yesterday, surgeons condemned the high
-
pressure sales tactics
adopted by some firms and warned that patients were being put at ris
k. Douglas McGeorge, president of BAAPS,
said: "Lack of regulation is allowing treatments on the market which are not in patients' best interests. The
concern is that people are being used as guinea pigs."

Botox, the anti
-
wrinkle treatment costing £300 to
£400 a time, was sold through mail
-
order catalogues and a
home
-
visiting service which was inappropriate, the surgeons said. One firm advertised "Botox at your place"
which involved a "motorcycle courier coming round with a box of arrows and injecting you o
n the spot".

Isolagen, marketed as a way to "grow your own facelift" was introduced in Britain in 2002, despite having been
withdrawn from the US market in 1999. It was withdrawn from the UK last year but not before a group of at least
Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

8

-

50 women claiming to

have been injured by the treatment had launched a class action for compensation. The
technique involved taking a biopsy, a small sample of skin from behind the ear, growing the cells in the laboratory
and re
-
injecting them to smooth out wrinkles. There wa
s no evidence the procedure worked and some women
claimed to have suffered lasting side effects, the surgeons said.

Adam Searle, past
-
president of BAAPS, said: "These techniques are being hijacked from the lab well in advance
of their efficacy being clarif
ied. The women involved in the class action mostly have inflammatory joint pain. That
is anecdotal evidence but it illustrates how closely we skirt significant dangers."

Thermage, a technique using microwaves to shrink the tissues in the face, tightening t
he skin and providing a
simple facelift, was being widely championed as a "sexy and successful" treatment. It cost £3,000 to £4,000 but
evidence from the US showed that 70 per cent of patients who had tried it said it had made no difference. Normal
Lewis,
a tutor in cosmetic surgery at the Royal College of Surgeons, said: "That is just not good enough. You
wouldn't get away with results like that in any other service."

The Department of Health said the safety and quality of cosmetic treatments were top prio
rities but self
-
regulation
was the best way to manage them


Source The New York
T
imes 28/09/2007

URL
http://www.nytimes.com


September 28, 2007

Report Assails F.D.A. Oversight of Clinical Trials

By GARDINER HARRIS

W
ASHINGTON, Sept. 27


The Food and Drug Administration does very little to ensure the safety of the millions
of people who participate in clinical trials, a federal investigator has found.

In a report due to be released Friday, the inspector general of th
e Department of Health and Human Services,
Daniel R. Levinson, said federal health officials did not know how many clinical trials were being conducted,
audited fewer than 1 percent of the testing sites and, on the rare occasions when inspectors did appear
, generally
showed up long after the tests had been completed.

The F.D.A. has 200 inspectors, some of whom audit clinical trials part time, to police an estimated 350,000 testing
sites. Even when those inspectors found serious problems in human trials, top

drug officials in Washington
downgraded their findings 68 percent of the time, the report found. Among the remaining cases, the agency
almost never followed up with inspections to determine whether the corrective actions that the agency demanded
had occur
red, the report found.

“In many ways, rats and mice get greater protection as research subjects in the United States than do humans,”
said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania.

Animal research ce
nters have to register with the federal government, keep track of subject numbers, have
unannounced spot inspections and address problems speedily or risk closing, none of which is true in human
research, Mr. Caplan said.

Because no one collects the data
systematically, there is no way to tell how safe the nation’s clinical research is
or ever has been.

The drug agency oversees just the safety of trials by companies seeking approval to sell drugs or devices. Using
an entirely different set of rules, the Of
fice for Human Research Protections oversees trials financed by the
federal government.

Privately financed noncommercial trials have no federal oversight.

“It’s crazy that we have all these different sets of rules,” said Dr. Ezekiel J. Emanuel, chairman of

the bioethics
department at the National Institutes of Health. “It would facilitate things a lot if we had one agency overseeing
things.”

Dr. Janet Woodcock, chief medical officer at the drug agency, acknowledged that it needs to put more “teeth” in
its
enforcement. “We are working to address these problems very aggressively,” Dr. Woodcock said.

The case of Audine Graybill demonstrates the flaws in the system. According to the F.D.A., in the spring of 2005,
she decided to try an experimental drug to treat

mania associated with bipolar disorder. The consent form that
she signed on May 29 stated that she could change her mind at any point in the study.

She checked into High Pointe Healthcare in Oklahoma City, a psychiatric center owned by a psychiatrist, Dr.

David Linden. On June 3, Ms. Graybill changed her mind and asked to leave.

Dr. Linden refused to let her go.

On June 6, she was given the experimental medicine. Ms. Graybill’s lawyer, Anthony Sykes, obtained a writ of
habeas corpus for her to appear in
court and took the writ to the hospital, where the staff refused to honor it and
said it would not give it to Dr. Linden, Mr. Sykes said.

Mr. Sykes tracked Dr. Linden to another office and had him served with the writ, Mr. Sykes said. Within hours, Dr.
Lin
den’s lawyer called Mr. Sykes and said Ms. Graybill was free to go. Mr. Sykes took her home on June 7.

Ms. Graybill could not be reached.

More than nine months later, an F.D.A. inspector appeared at Dr. Linden’s research center and uncovered myriad
other p
roblems.

The agency sent its warning letter more than two years after Ms. Graybill’s experience.

Last November, the Oklahoma Board of Medical Licensure and Supervision suspended Dr. Linden’s license for
three months because he had sex with two patients and

gave them genital herpes infections, according to board
records. Dr. Linden, who also owns a psychiatric center in Las Vegas, did not return repeated telephone
messages.

Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

9

-

Dr. Linden has conducted clinical trials for most major pharmaceutical companies and

continues to do research,
according to his Web site.

The F.D.A. disqualified investigators from conducting further clinical trials 26 times from 2000 to 2005 and
disqualified their data just twice even though the agency found serious problems at trial si
tes 348 times in that
period, the inspector general found.

While some of the report’s findings surprised ethicists, its conclusion that the agency’s oversight of clinical trials is
disorganized and underfinanced has long been known and is, in many ways, id
entical to criticisms leveled at other
agency functions, including its oversight of imported food, foreign drug manufacturers, animal food and the safety
of older medicines.

In each case, the size and complexity of the tasks facing the agency have grown e
normously as the number of
inspectors for those tasks has generally declined.

An inspector general’s report in 2000 criticized the oversight of clinical trials and noted that the inspections mostly
focused on whether study information was accurate and not
on whether human subjects were protected. That is
still true.

In the present report, the inspector general recommended that the agency create a registry of all continuing
clinical trials, an idea signed into law by President Bush on Thursday.

The report a
lso recommended that the agency create a complete registry of research ethics boards, create a
single comprehensive database to track its research inspections and obtain greater authority to regulate research
assistants.

Senator Charles E. Grassley, Republ
ican of Iowa, said the agency “needs to implement these recommendations
to meet its duty.”

Representative Rosa DeLauro, Democrat of Connecticut, said it needed more money and guts.

“They’re passive, they’re reactive, and they often side with industry over

public health,” Ms. DeLauro said.

The agency’s reserve is apparent in some of its warning letters.

On May 24, 2005, an inspector, Barbara Breithaupt, went to the office of Dr. Frank A. Wingrove of Ames, Iowa,
and for weeks asked to see records of his stu
dy of an experimental topical treatment for periodontal disease. Dr.
Wingrove refused. Dr. Wingrove did not return telephone messages seeking comment.

More than two years later, the agency sent Dr. Wingrove a warning letter. The inspector general’s report
suggests
that if Dr. Wingrove promised to reform, the agency was unlikely to show up again to see whether he had followed
through.


Cellules souches, clonage, recherche sur l’embryon


Source Stem Cells Vol. 25 No. 9 September 2007, pp. 2167
-
2172

URL
http://stemcells.alphamedpress.org.gate2.inist.fr/cgi/reprint/25/9/2167.pdf


The Future (R)evolution of Preimplantation Genetic Diagnosis/Human Leukocyte Antigen Testin
g: Ethical

Reflections

Guido de Werta, Inge Liebaersb, Hilde Van de Veldeb

aResearch Institute Growth and Development, Faculty of Health, Medicine and Life Sciences, Section Health,
Ethics and Society, Maastricht University, Maastricht, The Netherlands;

bResearch Centre Reproduction and Genetics, Universitair Ziekenhuis Brussel, Brussels, Belgium

Key Words. Human leukocyte antigen typing • Ethics • Embryonic stem cells • Hematopoietic stem cells
Preimplantation genetic diagnosis

Correspondence: Guido de
Wert, Ph.D., Faculty of Health, Medicine and Life Sciences, Research Institute Growth
& Development, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Telephone:
0031.433882145; Fax: 0031.433884171; e
-
mail:
g.dewert@zw.unimaas.nl


Received October 5, 2006; accepted for publication March 29, 2007.

First published online in STEM CELLS EXPRESS


May 24, 2007.

There has been increasing support for combining preimplantation genetic diagnosis (PGD) for specific diseases
with a test for human leukocyte antigens (HLA) because the generation of HLA
-
matched umbilical cord blood cells
may save the life

of a diseased sibling. To date, this procedure has taken place in the context of conceiving
another child

PGD/HLA testing type 1. However, it may well become possible to perform PGD/HLA testing
outside this context, that is, to select matched embryos from

which embryonic stem cells could be derived and
used in cell therapy

PGD/HLA testing type 2. A proactive ethical analysis is needed and is presented in this
article. Although PGD/HLA testing type 1 can be morally justified, the risks, pitfalls, and practi
cal limitations of this
procedure make it necessary to develop alternative strategies. PGD/HLA testing type 2 may provide an
alternative strategy. From an ethical point of view, the controversial issue is that this procedure creates embryos
purely for inst
rumental use. However, given the dominant view that the preimplantation embryo has only limited
moral value, this alternative may be as morally justified as PGD/HLA testing type 1.

Disclosure of potential conflicts of interest is found at the end of this
article.


INTRODUCTION

Recently, there was a strong consensus that preimplantation genetic diagnosis (PGD), like prenatal diagnosis
(PD), should be restricted to the detection of mutations/chromosomal abnormalities that (may) affect the health of
the

particular prospective child or adult in question

a view called the medical model. The increasing support for
combining PGD for a particular disease with a test for human leukocyte antigens (PGD/HLA testing) illustrates
that a more permissive interpretati
on of this guiding principle is emerging, allowing preimplantation testing and
selection for genetic characteristics that (may) affect the health of "third parties," more specifically a diseased sib
Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

10

-

[1]. PGD/HLA testing currently takes place in the context

of conceiving another child, sometimes called "parity for
donation"; parity is the medical term used to refer to a woman who has given birth [2]. We define this strategy
here as PGD/HLA testing type 1. In the future, however, it may well become possible t
o use the same PGD
procedure to select matched embryos that will not be transferred into the uterus but will be used to derive
embryonic stem cells for cell therapy. We will define this as PGD/HLA testing type 2. PGD/HLA testing type 2
would represent a co
mpletely new step in the ongoing technical evolution [1].

Before PGD/HLA testing type 2 comes into clinical practice, a proactive ethical analysis is needed and presented
in this article. We will focus on hematopoietic stem cell (HSC) transplantation, rec
all the rationale for the need of
HLA
-
identical HSC donors, and summarize the technical advances in hematopoietic differentiation from ESC
lines. In the ethical discussion, we will first review the possible hurdles, pitfalls, and moral problems of PGD/HLA
testing type 1. Secondly, we will compare the type 1 and type 2 cases from an ethical standpoint. We argue that,
although type 1 is morally acceptable, type 2 may be a good alternative option for parents.


NEW TECHNOLOGIES TO OBTAIN HLA
-
IDENTICAL HEMAT
OPOIETIC STEM CELLS

HSC transplantation is an accepted treatment for a number of malignant and nonmalignant diseases of the
hematopoietic/lymphoid system [3]. The HSC must be derived from an HLA
-
compatible donor source, which is
ideally an HLA
-
identical
sibling. Depending on the indication for transplantation and the source of the stem cells,
some HLA mismatch could or should be allowed. In practice, unrelated donors of closely matched peripheral
blood
-

or marrow
-
derived HSC can be found for 50% of the pa
tients. In the case of cord blood, less stringent
compatibility criteria may be applied; in the case of adults, a sufficiently matched cord blood graft or an acceptable
combination of several cord blood grafts can be found for most of the patients. Unrelat
ed HSC transplantation,
however, including cord blood transplantation, holds an increased risk of transplant
-
related morbidity and mortality
compared with HLA
-
identical transplantation. This is particularly pertinent to nonmalignant diseases (e.g., ß
-
thala
ssemia, sickle cell disease) where transplantation is not urgent, graft
-
versus
-
leukemia activity is not required,
and other treatment modalities may temporarily offer relatively adequate, although not curative, alternatives.
When a sufficiently compatible
unrelated donor source cannot be found and/or when an HLA
-
identical sibling is
the only or best treatment option, conceiving another child as a potential donor of HLA
-
identical HSC may be
considered.

Planning an additional child with the intention and hop
e of using it as a "donor" of HSC for an affected sib has
been done for years [2]. In these cases, parents have decided to have another child by natural conception, hoping
that it would be a good match. More recently, it has become possible to determine th
e suitability of the fetus as a
future donor in utero [4, 5] in order to abort the fetus when there was no HLA
-
match. The newest step in this
evolution is PGD/HLA testing type 1 [6

13]. This strategy has some clear advantages above natural conception.
Firs
t, although in theory only 1/4 embryos are HLA
-
identical and, in the case of PGD/HLA, 3/16 embryos (for
autosomal recessive inheritance) or 2/16 (for X
-
linked recessive inheritance) are both healthy and HLA
-
identical,
the chance of conceiving a matched don
or increases substantially compared with a spontaneous conception
because only the healthy (in case of PGD) HLA
-
matched embryos are transferred into the uterus. Second,
selective transfer of a matched embryo avoids the problem of aborting a nonmatched fetu
s.

Pluripotent ESC may become a source of HSC in the near future. ESC can now be derived from the inner cell
mass from human blastocysts with a reasonable efficiency [14

18]. Human ESC can also be induced to
differentiate in vitro into multiple cell types

including hematopoietic precursor cells [19, 20]. After further
differentiation in vitro, the formation of erythrocytes, dendritic cells, B cells, natural killer cells, macrophages, and
granulocytes has been reported [21

23]. These hematopoietic precursor
s are capable of long
-
term engraftment
(homing) in a xenogeneic mouse transplantation model with no evidence of teratoma [24]. However, the capacity
of the cells to maintain a completely functional hematopoietic
-
lymphoid system in patients remains to be
de
monstrated. In addition, the derivation and culture of human ESC lines in pathogen
-
free and animal
-
free
conditions are a prerequisite for further therapeutic use, and several recent reports describe significant advances
in this direction [25]. Considering
this evolution in techniques, PGD/HLA testing type 2 may be a realistic
alternative in the future because it would result in perfectly matched (healthy) ESC/HSC for transplantation.


THE ETHICS OF PGD/HLA TESTING TYPE 1

Questions

Three moral question
s are identified. The first question is whether it is morally justified to use a child (an
incompetent minor) who cannot decide for himself as a "donor" of a transplant. Clearly, the harm/probability ratio
of the specific procedure(s) is of utmost importan
ce. From a medical, moral, and legal perspective, the use of
stem cells isolated from umbilical cord blood (usually 80

150 ml) is the simple case, as the cells are not part of
the child and the procedure is noninvasive. Nevertheless, this procedure may rai
se moral questions. First, the
timing of umbilical cord clamping may be important. Immediate or early cord clamping will probably best serve the
interests of the recipient of HSC from the cord blood, as this method optimizes HSC collection. There are some
recent claims, however, that delaying cord clamping (accompanied by lowering the infant to hasten the placental
transfusion) offers protection to children, particularly for preterm and very low birth weight (VLBW) children [26

29]. The finding that intrave
ntricular hemorrhage and late
-
onset sepsis are more frequent in immediately clamped
preterm infants is especially worrisome.

After early and, possibly, late clamping, the number of HSC may be insufficient to treat the diseased sibling
properly. If this is

the case, in vitro expansion of the HSC may become an option for some conditions, although
this procedure needs to be further investigated [30, 31]. Today, a more pragmatic way to solve the problem is to
opt for a repeat donation. The question is then whe
ther the donor's bone marrow HSC can be collected. In young
children, bone marrow aspiration, performed under general anesthesia, is necessary to obtain these HSC.
Although this procedure is widely accepted, it is controversial. According to some ethicists
, this can only be
Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

11

-

morally justified when there is evidence of a positive emotional relationship between the candidate donor and the
potential recipient to ground an expectation of psychological benefit to the donor [32]. This strict view means that
neonat
es and very young children should not be used as bone marrow donors.

The second question is whether it is acceptable to conceive a child (partly) in order to obtain cells for
transplantation. Critics have various objections. The first objection concerns h
uman dignity: the child would be
used instrumentally, which is contrary to Kant's categorical imperative that "one should act in such a way that you
always treat humanity, whether in your own person or in the person of another, never simply as a means, but

always at the same time as an end" [33]. This criticism is, however, problematic. It is wrongly assumed that the
only motive for having another baby is to obtain the required transplant material. Empirical research suggests that
parents often have mixed m
otives for enlarging the family [34]. Furthermore, Kant's proscription is against using
people solely as a means. What matters, then, is whether the parents will value the future child only as a
transplant source or whether they will also love the child fo
r itself [2]. The second objection concerns the
psychosocial risks for all parties involved, particularly the well
-
being of the child born after HLA typing. The
magnitude of this risk probably depends most on the quality of the relationships within the fam
ily; if the child feels
that it is wanted just as much as the other children are, there is no reason to expect serious problems. It has been
suggested that the child may feel empowered if the transplantation is successful but devalued if the sick child die
s
[35]. Follow
-
up studies will provide more information in the future. Another risk is that parents may feel pressure to
opt for parity for donation. This could, clearly, endanger the welfare of both parents and children, especially if the
parents cannot s
upport more children for financial, medical, and/or psychosocial reasons. These pitfalls and risks
underscore the importance of adequate psychological counseling to verify, as far as reasonably possible, the
motives of the parents, their ability to fulfill

additional parental responsibilities, and to assist them in making well
-
considered procreative decisions. In individual cases, significant uncertainties may remain around these issues.

Apart from the concerns above, it is important to realize that parity

for donation carries substantial practical
hurdles. Most importantly, the procedure is time consuming; even if the woman becomes pregnant immediately,
there is a real risk that the diseased sib will die during the nine months before the donor is born. It
is possible that,
in the case of fast progressing diseases, parents (and doctors) might even be tempted to induce labor early in
order to save the sib. Needless to say, this would be morally problematic, if not completely unacceptable, since it
could serio
usly harm the donor child.

The third and most pertinent question is whether it can be morally justified to select an HLA
-
matched embryo for
transfer in order to ensure that suitable transplant material may be acquired after birth. The objection of critics

is
that PGD/HLA testing is contrary to the medical model since the HLA type has nothing to do with the health of the
future child. A first argument for adhering to the medical model strictly is the wedge or "slippery slope" argument:
"Beware of designer b
abies!" This is not convincing. Although in case of HLA testing type 1 the medical model in
the strict sense is abandoned, this does not mean that the "designer model" is embraced. After all, the baby is not
being genetically molded to fit the parental pic
ture of the perfect child. In view of this, the premise that anyone
who rejects the designer baby model must, for the sake of consistency, also reject PGD/HLA testing type 1 is
debatable. Furthermore, the argument that this strategy inevitably leads to des
igner babies in the future also looks
problematic, since it assumes a certain automatism. The second argument not to make an exception to the
medical model is that this procedure implies a huge wastage of "normal," healthy in vitro fertilization (IVF)
-
embr
yos; in most cases, both affected embryos and unaffected embryos that are unsuitable for transplantation
purposes will not be transferred (although couples having moral objections against the destruction of their healthy
embryos may be offered to cryoprese
rve them in order to replace them later). This objection, however, is not
convincing in view of both the dominant view that the moral status of preimplantation embryos is relatively low and
the pending tragedy for the parents and the terminally ill child.
Furthermore, most societies accept the loss of
healthy embryos in regular IVF.

Which Conditions Should Be Imposed?

There is a growing support for the view that PGD/HLA testing type 1 may be morally justified [36]. The real issue,
then, concerns the condit
ions that should be imposed. In the "standard" case, parents hope to save a sib affected
with a hereditary condition and the HLA type selected for has no adverse consequences for the health of the
future donor child. Three alternative scenarios complicate
the ethical discussion. The first variant concerns the
situation where the child suffers from a nonhereditary condition, like leukemia. There is dissent with regard to the
ethics of PGD/HLA testing type 1 in this situation. Some consider this type of testi
ng to be acceptable only in the
context of IVF/PGD on genetic indication, that is, in addition to PGD of a genetic disease that may affect the
future child. Outside of that context, so the argument runs, the possible health risks of IVF/PGD, especially of
the
biopsy, are disproportional. Recently, the Dutch Secretary of Public Health took this position [37]. The Human
Fertilization and Embryology Authority, who originally imposed this restrictive policy in the United Kingdom,
however, recently decided to op
t for a more liberal guidance in view of the lack of evidence of harm caused by the
biopsy procedure [38

41].

The second and very exceptional variant would concern a diseased parent who is in need of HSC. Some
commentators reject PGD/HLA testing type 1 in

this situation because balanced parental decision making is
compromised. They presumably fear that parents are not sufficiently able to consider the best interests of the
donor child when their own lives are at stake. The parents may be more likely to cho
ose another child while they
are not able to take on additional parental responsibilities. This risk would, however, seem to be an additional
reason for adequate counseling on a case
-
by
-
case basis rather than for a categorical rejection of the procedure.

Third, in exceptional cases, specific HLA types may carry substantial health risks for the future child. Several
associations between various HLA types and specific disorders have been identified. One of the strongest
associations is the one between the HL
A
-
B27 polymorphism and Bechterew disease [42]. If Bechterew runs in the
Ce

dossier

est destiné exclusivement à usage privé,
suivant l'article
L.122
-
5 du code de la propriété intellectuelle
.
Quelque autre utilisation que ce soit est formellement interdite. Sont également interdits le prêt, la duplication et la
copie partielle ou totale de ce dossier Tous les droits de cette oeuvre sont réservés




Bénédicte de Boischevalier

envoi du 28 septembre 2007

-

12

-

family, the carrier's risk may be as high as 20%. Would the current procedure be morally justified if the perfectly
matched HLA type would impose substantially increased health risks t
o the future child [1]? A somewhat similar
situation may occur in the case of insulin
-
dependent diabetes mellitus type 1, which is strongly associated (OR
21.5) with certain HLA class II alleles [43].

A Summary of the Obstacles

Clearly, PGD/HLA testing ty
pe 1 is a complex and demanding procedure for the parents. Pitfalls and problems are
both practical and moral, and there is some overlap.

Practical problems/hurdles include: (a) Some parents cannot support another child for medical, economical,
and/or psy
chosocial reasons; (b) The procedure has only a moderate take home baby rate (THBR) (10%) ([12,
13] and our unpublished data), and this is mainly due to the low number of embryos available for transfer. In the
standard case, where PGD/HLA testing will be u
sed to select embryos that are both free of a specific disease and
a perfect HLA match, the chance of an embryo being both healthy and a suitable match is only 18.75% in the
case of autosomal recessive conditions, such as ß
-
thalassemia, and only 12.5% in c
ase of sex selection for an X
-
linked disease; (c) Since the development of the HLA testing, establishing pregnancy, and pregnancy itself are
time consuming, the diseased child will sometimes die before the HSC become available [34].

Ethically relevant ris
ks for parents and donor child include the following: (a) Parents may feel under pressure to
opt for this procedure while they cannot afford another child ("an offer you cannot refuse"); (b) The donor child
might feel devalued (although clearly the opposit
e may be true); (c) Possible health risks for the future donor child
are related to the blastomere biopsy (a risk so far considered to be low) [38

41], specific HLA types that are
associated with familial disorders [42, 43], and early umbilical cord clampi
ng, which may have adverse effects to
premature and/or VLBW babies [26

29].

In view of these problems, it is necessary to develop possible alternative solutions. One future option might be
PGD/HLA testing in order to select matched embryos from which ESC
could be derived to produce HSC for cell
therapy

PGD/HLA testing type 2.


THE ETHICS OF PGD/HLA TESTING TYPE 2

Research on the controlled differentiation of ESC, for example to HSC, is advancing rapidly [21

23]; therefore, a
proactive debate on the p
ractical and ethical pros and cons of the type 2 case is important. Can this procedure be
morally justified and, if so, under which conditions?

Pros

The first advantage of PGD/HLA testing type 2 is that it will increase the number of therapeutic options.
For those
parents who cannot support another child, this procedure may be the only real option. Other parents, if given the
choice, may prefer PGD/HLA testing type 2 to type 1, especially if they consider their family to be complete. For
these parents, the

type 1 case will be second best.

Second, PGD/HLA testing type 2 may have substantial medical/practical advantages if it were to have a higher
success rate than the type 1 procedure in terms of saving the diseased sib. Clearly, this remains to be seen. On
e
may need fewer embryos to obtain the cells needed for transplantation: the THBR after PGD/HLA is only 10%
([12, 13] and our unpublished data), whereas the derivation rate of a stable ESC line from an embryo after PGD is
approximately 20% [18]. Furthermor
e, a successful pregnancy takes 9 months, whereas the type 2 procedure
may be less time consuming; generally, it takes 3 months to derive and characterize a stable ESC line and 2

3
weeks to differentiate these cells into a heterogeneous population containi
ng hematopoietic progenitor cells [19,
24]. However, before it can be used for HSC transplantation in patients, a high number of cells would be required,
and the safety of the ex vivo expansion and the transplantation still need to be evaluated. Finally, t
he availability
of HLA
-
matched ESC could perhaps make it possible in the long
-
term to derive other tissues/organs in case
another transplantation is required (e.g., kidney).

Third, the child
-
related objections and concerns regarding type 1 would be circum
vented. These include the
presumed instrumental use of children and the possible psychosocial and medical risks for the future donor. As a
consequence, the debate about the conditions to be imposed in view of the additional complications inherent in
the va
riants mentioned above would become irrelevant. The cases of a diseased parent, a nonhereditary
disorder, and possible additional tissue donation would become nonissues in the context of PGD/HLA testing type
2. Likewise, the selected HLA type would never i
mply a health risk for future donors.

Cons

The primary normative issue regarding PGD/HLA testing type 2 concerns the creation of (human) preimplantation
embryos solely for so
-
called instrumental use, particularly, to obtain ESC/HSC for cell therapy. It is

important to
distinguish between a legal and an ethical perspective. Many countries prohibit the creation of embryos for
instrumental use in accordance with Article 18 of the European Convention on Human Rights and Biomedicine of
the Council of Europe: (1
) Where the law allows research on embryos in vitro, it shall ensure adequate protection
of the embryo; (2) The creation of human embryos for research purposes is prohibited [44]. At the same time,
many countries accept the instrumental use of so
-
called su
rplus or spare embryos, which remain after IVF or
IVF/PGD. From an ethical perspective, the question arises as to whether there is a decisive moral difference
between the instrumental use of spare embryos and the creation of embryos for instrumental use [4
5]. Why
accept the former and categorically prohibit the latter? The ethical and societal debate about this issue often
focuses exclusively on the moral status and the protection of the embryo. It is important, however, not to treat