Principles and Practice of Pharmaceutical Medicine

of misunderstanding. For example, the cloning of
mammals (sheep at Roslin Therapeutics, Scotland;
mice at the University of Hawaii) forces the
consideration of cloning of humans. On one
hand, much of this technology can be used for
genetic screening of fetuses to exclude an inherited
disease. On the other hand, the same techniques
could be used to provide parents with a deliberate
choice of the sex of their next baby. Science is
likely always to be ahead of the lay public and
politicians in creating these dilemmas in the
absence of agreed guidelines or consensus. The
biggest problem for the lay public to grasp is
there is always an ethical continuum, without
bright lines of demarcation or absolute limitations.
If it is the ethical continuum that is the central
difficulty, then there are nonetheless analogies in
the ‘pregenetic engineering’ era of medicine. Con-
sider, for example, the parents of a child who
needs a kidney transplant, and who find themselves
without any suitable living donor. Without any
modern technology at all, they may choose to
have another baby with the hope or intent that the
new child can serve as a suitable donor for their
existing child. In this case, tissue proliferationex
vivoand implantation seem to be a simpler ethical
situation than parents having offspring by entirely
ordinary means. Consensus guidelines are needed,
but in our opinion they must remain flexible in
order to deal with ever faster technological innova-
tion that is not going to stop, and they must also be
consistent with guidelines that have wide accep-
tance in other areas of medicine and have cross-
cultural flexibility.

Informed consent

More prosaically, the difficulties of explaining the
nuances of biotechnology products to potential
clinical trials subjects may be more difficult than
for orthodox small molecule drugs. Often, candi-
date clinical trial patients will be experiencing life-
threatening disease, and the apparent novelty of,
say, a gene therapy, could, under the wrong condi-
tions, create undue hope and bias in deciding to
providewhat should be truly informed consent. It is
crucial that the same principles apply for biotech-

nology as for conventional drugs; the protocol and

therapy must still be clearly explained in a non-

coercive manner that do not raise false hopes in the

patient. Let us not forget that this type of, major

ethical lapse resulted in the death of Jessie

Gelssinger during aclinical trial of abiotechnology

product in the United States.

22.11 Pharmacogenomics as it

applies to biotechnology

product development

At the time of writing (March 2006), it is estimated

that about a third of all investigational new drugs

are the result of pharmacogenomic research. The

science of pharmacogenomics may be defined as

the exploitation of the human genome for the iden-

tification of candidate polypeptides that can serve

either as drugs themselves or as therapeutic targets.

It is contemplated that pathological deficiencies of

such candidate polypeptides might be repaired or

replaced by exogenous administration, abnormal

excessive candidate polypeptide production might

be antagonized or suppressed or that some normal

candidate polypeptide might be overexpressed to

supra-physiological levels in the effective treatment

of disease. The science of pharmacoproteomics is

exactly analogous, except that the database of

human proteins (which exceeds in number the cata-

log of human genes and which roughly equates to one

definition of phenotype) is the thing that is exploited.

This new science has three or four basic compo-

nents: the map of the human genome (which was

essentially completed in 2004), research that

relates genes to proteins (the old one-gene-one-

protein dictum has now been completely aban-

doned), the regulation and pharmacodynamics of

posttranslational protein modification and integra-

tive approaches to identify structural motifs of

putative therapeutic agents. When there is capabil-

ity to predict phenotype accurately (without wait-

ing for drawn-out growth experiments), then the

potential to accelerate process of biological drug

discovery seems to be greatest.

An intrinsic part of the pharmacogenomic enter-

prise is the capability to analyze vast datasets, and

22.11 PHARMACOGENOMICS AS IT APPLIES TO BIOTECHNOLOGY PRODUCT DEVELOPMENT 289