On the nature of the PhD and learning to be a scientist

September, 1986. I am a rotation student visiting a lab in the Medical Sciences Building here at the University of Toronto. Students are gathered around Dr. Rob Dunn who was inspecting a piece of X-ray film bearing the results of a DNA sequencing experiment carried out by a student in his lab. The experiment was notable because it was one of the first conducted at U of T using the newly introduced ‘Sequenase’ technology. Sequenase came in an easy-to-use kit that was revolutionary for several reasons. It provided pre-made mixes of deoxynucleotides and dideoxynucleotides, buffers and sterile water needed for chain termination sequencing. Until then, these reagents were unstandardized and preparing them was a tedious job; their precise make-up varied considerably from one lab to the next. Sequenase also replaced the Klenow fragment with a version of T7 polymerase engineered for high processivity and used a 35S label in place of 32P. The result was an astounding 300 or even 350 bp of sequence data from a single reaction. “5 years ago you would have got your PhD for this one experiment”, Rob announced.

And so it goes. Students in my lab now do single experiments with results that are hundreds of thousands of times more data-rich than my entire PhD thesis. Technology advances inexorably. But it strikes me that the fundamental question of what it takes to become a scientist remains more or less the same.

There are many opinions about what makes being a scientist different from other professions. The following are my impressions of a few things that scientists need to learn along the way. I make no claim that this list is comprehensive.

I think it’s important for students to ask themselves “what does it mean to think scientifically?” In fact, scientific reasoning does not come naturally to most people. Many scientists don’t really do it and all scientists struggle with it from time to time. This may be one explanation for the surprisingly widespread problem of reproducibility in published scientific results. Everything about our upbringings and cultures undermines the drive to dispassionate, scientific inquiry. Confirmation bias rules most decision-making.

In theory, scientists are supposed to test their ideas in a manner that is dispassionate and unbiased. That is, they start with a credible hypothesis and ask whether it is correct or not. All too often however, we freight our experiments with the hope that our hypothesis is correct; being wrong, even about something magnificently abstract, makes most of us uncomfortable. I cannot count the number of times I’ve heard a student (or PI) say “the experiment didn’t work”, as in it did not confirm that their idea was correct.

…it strikes me that the fundamental question of what it takes to become a scientist remains more or less the same.

Even more problematically, this biased hypothetical framework can skew and undermine our experimental design. We set up experiments designed to confirm rather than to question – ending up with “results” that contain no meaningful data. So, achieving that emotional distance is an important task.

People should also ask themselves “is this important?” I think this question can refer to anything and everything. You see a 20% drop in the level of a transcript – does it matter? Are you seeing something that matters to the organism?

Another way to approach this is to ask yourself “what is the most important question I can ask about the thing that I’m studying?” It is very easy simply to circle around the edge of an idea without zeroing in on the core of it. This can be framed in very grant-proposal-y terms: “is my project important?” or “what is important about my project?” You should make a point of gravitating to the things that matter the most. The really big discoveries are those that provide a fundamentally new insight. These are rare events and if you’re not even asking the right questions, then you’ll literally never arrive at them. For every Nobel Prize there are many also-rans who were close but distracted by trivia.

I think this question of the importance of particular questions and lines of research is a particularly serious one in the big-data era. So many experiments have no underlying hypothesis – they are more like expeditions to describe everything that happens in a cell or organism in response to a particular stimulus. This approach often bears fruit however there is an attendant trap: it’s easy to spend many thousands of CIHR dollars asking questions about nothing.

I tell graduate students (and grant writers) that they need to explain the importance of their work from either a scientific perspective or a medical perspective – ideally both. If you don’t do this then you risk going nowhere as a scientist.

Starting something is easy: finishing is hard

Finally, it is important to ask yourself “when will I be finished?” If you’ve never published a paper or written a doctoral thesis then it’s a tougher question than it might seem. Once you’ve repeated an experiment a few times, how do you know when you have a definite result? How do you know when you’re ready to write up your work for publication? I would argue that the sooner you answer ‘yes’ to all of these questions the better – even if you’re kidding yourself.

One approach is to integrate completion into the doing of things. The chemist George Whiteside encourages his trainees to start writing up their work before they’re finished the experiments: “The major issue is to consider writing as part of the research process”.  This can prevent you from dithering about in the hinterland of ideas and helps you zero in on the critical steps you need to get where you need to go. [Whiteside is someone worth watching]. Starting something is easy: finishing is hard.

Scientific thinking is vital to the future of this planet. It’s not the only mode of thinking that matters but, for solving many critical kinds of problems it’s the only one that works. A PhD in Biochemistry (or any other discipline) is a unique opportunity to learn this vital craft and the more you think about what is behind the metamorphosis into a scientist, the quicker your work will proceed and the more successful you’ll be in the long run.