The business of discovery

DISCOVERY is a rather magical word, don’t you think, evoking voyages on high, uncharted seas, the delving into ancient, dusty libraries and the witnessing of previously unseen marvels at the end of a microscope lens.

When it comes to scientific discovery, however, there are rules. If we ignore them we do not discover – we only think we have – for science is about revealing truth through a process that does its best to ensure we don’t delude ourselves. Rather like the archaeologist we have evolved a simple set of tools to scrape and brush away the layers of confusion in order to reveal the answer, and our most important tool is the concept of “control”.

So often we read headlines about how a drug has caused a cancer. These stories are convincing because they appeal to our basic human need to find a link between cause and effect. Something happens and then something else happens, so the first event must have caused the second. If our primitive ancestors forgot to pray to their gods and their child died, it was obvious what had happened. We like to think we are more sophisticated, but in truth we still have cavemen’s brains and are still dangerously vulnerable to the fallacy of post hoc ergo propter hoc – after it, therefore because of it. If we are to discover the truth of cause and effect – i.e. did the drug really cause the cancer? – we must resist this way of thinking and find a new and perhaps less intuitive approach. An example may help.

If 10 people have developed a rare form of cancer we look for reasons. We first look for characteristics they share: where do they live, what do they eat, what drugs do they take? The first piece of common ground we discover may be the cause but, equally, it may not; it may merely be a coincidence. Scientific method protects against the power of coincidence. What if these people were receiving the same drug because they all suffered the same symptoms related to their cancer, a cancer they had developed before they had ever been prescribed the drug? How can we resolve this? We can employ a range of observational tools, but none will be conclusive.

The definitive way to test the hypothesis – that the drug causes cancer – is to conduct a randomised controlled trial, or RCT. Here, a group of people are randomly assigned to receive the drug or a matching placebo. By concealing from both participants and researchers the treatment allocations, we perform a so-called “double-blind” study and eliminate as much bias as possible. We will then follow the participants, checking them for signs of cancer. If our study is large enough and long enough we will be able to compare the two groups. Only if the number of cancers in the drug group is significantly higher can we confidently conclude the drug has a causal role in the cancer’s development.

This methodology is regarded by many as one of the most important advances in medicine in the 20th century. Without RCTs we are operating in the half-light, with only observational studies and anecdote to guide us. The scientific rigour applied within the RCT allows us to ‘know’ where before we could only ‘wonder’.

But, RCTs are not without their problems. The example given above, while scientifically sound, may present significant ethical problems. If we really believe a drug might cause cancer is it right to expose people to that risk only to satisfy our curiosity? Of course not, but it is not our curiosity that is at stake. If the drug has important clinical e­ects that could benefit many patients, we must be sure when using it that we are not unwittingly causing more harm than good. The only way we can prescribe with confidence is if we have the data to back it up, and the highest quality data will be derived from a well conducted RCT.

Discovery is wonderful, but it is also difficult. Those who wonder need to be taught how to channel that sense: they need to learn how to ask the right questions, how to design strategies to answer those questions, how to conduct studies with rigour, and within the law, and how to tell the world of their discovery. A cycle of discovery that begins with a thought, a question, a moment of wonder should end with a revelation that we can all share. For discovery belongs to us all – it has allowed us to feed our hungry, light our cities, cure our diseases, and it has allowed us to walk from our caves and step on the Moon.

Dr Allan Gaw is a clinical researcher and writer in Glasgow