A Revolution in R&D

will not only help to make the trials faster and
cheaper, but also allow some drugs to pass that
would otherwise have failed owing to poor efficacy
or side effects.
High-Risk, High-Reward Research
In the near-to-medium term, genetics promises to
reduce R&D costs dramatically. Or does it? Our
model shows that the application of disease genetics
and pharmacogenetics together could, in the very
best case, save as much as two-thirds of the current
cost to develop a drug and nearly two years. Of
these potential savings, the vast majority comes
from disease genetics. Of the remainder, some cannot
be clearly apportioned to either disease genetics
or pharmacogenetics but must be credited to
their joint efforts, being the product of synergies
realized when disease genetics information is incorporated
into pharmacogenetics-driven clinical trials.
(Although genetics can be combined with the
genomics technologies described in the previous
chapter, the potential savings are not additive. In
the next chapter, we will assess the total savings realistically
achievable through the application of genomics
and genetics.)
Our model also shows that realizing this potential
will be far from straightforward and is far from
guaranteed. The high-end savings estimate assumes
a positive resolution of several scientific, technical,
and market risks. With every setback, the savings
diminish. Too many setbacks, and the savings fall to
zero. Implementing genetics could even turn out to
have a negative impact on value, owing to adverse
market dynamics.
Such a double-edged sword is awkward to wield. If
companies fail to grasp it at all, they forfeit the
opportunity to reap enormous rewards—nearly
double the savings possible with genomics technologies.
If they do grasp it, they put themselves in
some danger, and will need to develop a genetics
strategy aligned with their risk profile and with specific
market conditions. As an approach to research
and development, genetics remains risky, but full of
promise, too. This chapter assesses the promise and
the risk alike.
Disease Genetics
Underlying many diseases are genetic variants, or
polymorphisms—alterations in the DNA sequence
of a given gene that influence individual risk of disease.
(The term polymorphism usually refers to a
common variant—one found in more than 1 percent
of the population.) Often the genetic difference
consists of just a single altered letter in the
genetic code (the variant is then known as a single
nucleotide polymorphism, or SNP). Such a tiny alteration
can have fatal consequences; for example, the
substitution of an A for a T in the hemoglobin ß
gene is responsible for sickle cell anemia. The goal
of disease genetics is to identify such DNA alterations;
so far, this goal has proved elusive for all but
the most strongly inherited conditions. (See sidebar,
“Disease Genetics—Various Approaches to
Variants.”) But researchers persevere, since finding
the causal variants can be a major step to finding a
treatment—and potentially a cure.
Uncertainty persists: the technologies have yet to
prove their full worth by producing the necessary
quota of practical results. But if all goes according
to plan, the savings realized by pharmaceutical
companies will be enormous.
The Potential
The savings would come partially from improved
efficiency in discovery, but principally from
improved success in target validation and clinical
trials. The improvements in efficiency result from
the consolidation of target discovery into a single
step; the improved success rates result from the
refining of target identification, making it possible
to pinpoint the targets associated with disease susceptibility
in humans.
Once the targets have been located, they can boast
a collective superiority in three particular respects.
First, their relevance to human disease is certain.
They have, after all, been validated in humans,
showing directly that modulation of gene activity
leads to alteration in the intensity or duration of
disease. (By contrast, other targets are usually iden-
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