Our Reality
On the 1st of April in 2013, the front cover of Time Magazine was adorned with a bold proclamation: “How to Cure Cancer *Yes it’s now possible”. No this wasn’t an April Fools joke, and while the accompanying article was more nuanced than this headline, the damage was done. Cancer is not one single disease, but hundreds of diseases, each with different genetic origins and treatment strategies. Researchers and clinicians already struggle to manage the expectations of funding bodies not to mention cancer patients and their families and headlines like these trivialise the complexity of our work and makes it harder for scientists to do our jobs.
However If we take a moment to consider the general public’s perspective, there doesn’t appear to be a lack of high-profile scientific projects that (in their eyes at least) over-promised and under-delivered. Take the Human Genome project, involving an international consortium of scientists across 20 countries over a decade and $3 billion US dollars to complete. It aimed to sequence a reference human genome from human donors and promised to “crack the human genetic code” and unlock cures to all sorts of disease including cancer. It was an incredible achievement in the historical context of biology, and now we somewhat take it for granted that we can “google” the DNA sequence of almost gene you can think of. However unless you are working in the field of genetics or molecular biology, it can be difficult to appreciate the impact on your everyday life. What’s the disconnect here, and why are advancements in medical research not happening at the rate we were promised?
Why do the general public’s expectations not match our scientific reality?
The Human Genome project had a transformative impact on health and molecular biosciences, but it can be difficult to appreciate this without understanding the underlying principles. In BioLab Collective’s latest video, I walk through the basics of DNA sequencing, with specific emphasis on “traditional” sequencing – also known as Sanger sequencing. This is the approach they took in the Human Genome Project, and it is still routinely carried out in DNA sequencing facilities. The field has moved on from this in many respects into Next-Generation DNA sequencing platforms that have taken over the industry.
Sanger sequencing machines can run up to 384 samples at a time, and sequence 1 million bases per day. Next-generation DNA sequencing has the potential to run 13 billion samples at a time and sequence 4 trillion bases per day. It is worth considering on a holistic level how these platforms were able to increase their sequencing throughput. Instead of free-floating within a reaction mix, the template DNA can be organised in a consistent and reproducible way that can speed up the readout. Cleaning up the DNA after a sequencing reaction has never been easier, and you can even use magnetic beads for the nucleic acids to bind to. Also we can use fluorescent tags to automate the sequence readout by a laser detector. Each of these efficiencies also makes it more accessible for multiplexing, using liquid handling robotics to deal with hundred and thousands of wells across multiple plates.
As the processing power goes up and the cost of DNA sequencing comes down, how close are we to realising the potential of the original Human Genome Project? With the benefit of hindsight, we know that there’s still a big gap between knowing a gene’s DNA sequence and being able to predict or change its function within a human being.
How is the gene made into protein, and how much protein is needed for the process to function?
Do multiple genes perform the same function, and are there redundancies built in if any of them stop working?
How many variations of the same gene exist across a human population, and what impact do they have?
The original human genome project sequenced the DNA from only a handful of individual donors, and we need to sequence millions of other humans to get a better sense of the genetic base of diseases and the inherent variation within our species. There is a lot of nuance and complexity in biology, which is often difficult to relay to the general public. It is up to scientists to bridge this gap and communicate the significance of our work at every turn.
Jack.
