The Human Genome Project changed everything

The author
Richard Gibbs, AC, PhD is a human geneticist and the 
Founding Director of the Baylor College of Medicine 
Human Genome Sequencing Center (HGSC). He grad-
uated from the University of Melbourne in Genetics 
and Radiation Biology and moved to Houston, TX,
to study the molecular basis of genetic disease. He 
developed basic methods for DNA and mutation 
ana lysis and was an early contributor to the Human 
Genome Project (HGP), leading one of five sites that 
generated the majority of the sequence. Since the 
completion of the HGP, he has led multiple genome 
projects including the generation of the first person-
alized whole-genome diploid human sequences. His 
group pioneered the oligonucleotide exon-capture 
methods that are widely used today for whole-exome 
sequencing, and he is currently leading programmes 
for translation of genomic data into the clinic.
 
volUMe 21 | oCToBeR 2020 | 
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new for biology, and it was apparent that future pro-
grammes would benefit from HGP lessons in logistics. 
These ambitions were the backdrop for the knowledge of 
how difficult the task would be, without advanced com-
puters, automated sequencing or any roadmap from a 
similar effort.
A 25-plus-year timetable
There was also a realistic insiders’ view of likely 
post-HGP rates of progress and how difficult biological 
discovery can be, in the best of circumstances. The HGP 
was foundational and the project would lead to new ways 
to do things, but not all thought progress would be easy. 
The HGP took just 13 years, as after the 2000 announce-
ment we all worked an extra 3 years to finish the ‘essen-
tially complete genome’, and it is interesting to compare 
that period to other transitional milestones in biology. 
In 1987, the groups of Francis Collins and Lap-Chee 
Tsui discovered the gene that contains the variants that 
underlie cystic fibrosis
6
. That discovery (pre-HGP) was 
appropriately hailed as the first step towards a cure.
In 2012, the first resulting drug to treat a subset of 
patients with cystic fibrosis was approved by the FDA. 
For Huntington disease, a similar time span was needed 
to go from gene discovery to a new treatment that is 
only now being tested
7
. The familial breast cancer gene 
is another example of the time between discovery and 
action; linkage to 
BRCA1
was identified in the 1990s 
with initial hopes that isolating the gene underlying 
the 1% of cases that were familial would give insights 
into the vast majority of sufferers with sporadic disease. 
That connection was not obvious, and the complicated 
relationship between this gene, its germline and somatic 
variants, related genes and interacting proteins, and 
the consequences for cancer are still being unraveled
8
.  
A 25–30-year period between discovery and impact on 
health care is more the rule than the exception.