Why medicine is not black and white

As a tall, middle class, white male I don’t normally feel entitled to talk about bias. My impetus for writing this blog came when I realised that the gender bias has exposed a fundamental failure in medical research and laid bare a hidden bias affecting us all.

Gina Rippon, a female professor emeritus of cognitive neuroimaging at Aston University, started her research looking at the difference between male and female brains. This is an age-old method based on there being a weight difference between the brain of men and women. This approach seems logical, since ‘males and females seem so different, let’s look for the difference in their brains’. The social observation implicit in that statement (ie women and men are different) shapes the research question with a gender bias (ie they look and act differently so therefore we will see a difference in their brains).

Rippon, like many neuroscientists before her, found little difference between female and male brains (after accounting for the size). This was her light bulb moment. So perhaps it’s time to drop the age-old belief that there is such a thing as a male and female brain since there are no significant observable differences? Any further research of the male-female divide in brains would be “neuro-foolishness”.

Rippon explains, “The idea of the male brain and the female brain suggests that each is a homogeneous thing so any male brains will have the same kind of aptitudes, preferences and personalities as everyone else with that ‘type’ of brain. We now know that not to be true. The distinction is harmful too as it’s used as a hook to say ‘there is no point in girls doing science because they haven’t got a science brain or boys shouldn’t be emotional and should want to lead'”.

Many researchers before Rippon continued asking the same question as they assumed our observered gender differences are biological destiny. It was the neuroplasticity of the brain, the ever changing connections and routing of brain networks, that debunked the age-old view that our biology is our destiny. Instead our brain is a reflection of our experience. If we learn a new skill our brain will change. Its structure is not predetermined. The conscious brain is social, predictive and forward thinking. Like a Sat-Nav it follows rules, and it picks up these rules or social queues from the outside world. Hence the ‘gender gap’ becomes a self-fulfilling prophecy driven by our society’s hidden biases.

The Achilles’ heel of medical research

Such a hidden bias can be fatal in the process of research to evaluate if a drug is safe and effective. For example, all women were excluded from clinical trials until 1993. Yes you didn’t misread that, half the population was ignored until just over 25 years ago. Insert mind exploding emoji. Many of the medications that we know and trust where tested on men yet are still being prescribed to women. Where is the scientific logic in that?

The reasoning went like this: since women are born with all the eggs they will ever produce, they should be excluded from drug trials in case the drug proves toxic and impedes their ability to reproduce in the future. The result was that all women were excluded from trials, regardless of their age, gender status, sexual orientation, wish or ability to bear children. Men, on the other hand, constantly produce sperm, meaning they represent a reduced risk. The approach treats all women like walking wombs and has introduced a hidden bias into healthcare research.

The Guardian columnist Gabrielle Jackson says, “These policies and practices have often been framed as paternalistic, designed to protect women against the harmful effects of medical research. But history belies this notion. The practice of brutal experimentation of medical treatments on women throughout history makes medicine’s unwillingness to include women in scientific studies seem a lot less like magnanimous paternalism. Rather, we are left with the impression that women are not interesting enough for scientific endeavour but good enough for practice.”

Hidden Bias

More recent research suggests the assumption that both sexes will react in the same way to a prescribed medication has shaped an unsafe framework for medical research. As Alyson McGregor writes in The Pharmaceutical Journal “Decades of ignorant bias cannot be solved by sprinkling a few women into clinical trials…. Research studies that do not specifically formulate the design to detect differences by sex may, in fact, bias the results for both sexes. For example, Cao et al. found that foetal nicotine exposure during pregnancy was associated with the development of various psychiatric disorders and a potential for drug abuse during the child’s adolescence. This gene expression turned out to be dependent on the sex of the foetus: related genes were up-regulated in male offspring and down-regulated in female offspring[1]. If these outcomes had been pooled with consideration of the effect of sex, the combined average would have been a null effect. Exposing differences like these that are related to the sex of the research participant reinforces the need to expect and search for underlying processes, mechanisms and responses that may differ between sexes and to use this information to develop targeted, accurate and effective therapies for both women and men.”

It took the National Institutes of Health (NIH) until 1993 to establish the Revitalisation Act to ensure the efficacy of treatments for women would no longer be extrapolated from data derived from male participants but instead be scientifically determined. This legislation is the cornerstone of the science of sex and gender specific research.

Since then, more women have been included in clinical trials but researchers have not always analysed results by sex and/or gender. Women have also been the victims of unforeseen bad reactions to certain drugs. In a span of three years from 1997 to 2000, 8 of the 10 drugs for which the FDA withdrew its approval had harmful side effects for women. More recently in 2013, the FDA recognised that the active ingredient in Ambien took longer for women to process than men, potentially leaving women dangerously groggy in the morning. Now the agency recommends that women take half-size doses.

Current medical practices are still based on a ‘one-size-fits-all’ approach, which is grounded in research conducted largely by men, on male subjects. The size of the body is a male size; the chromosomes are XY rather than XX; and the results may be irrelevant or harmful to women. Current practice is to order tests and prescribe medicines as we “wait and see”. Will the patient respond, recover or have side effects?

It took until 2014 for the NIH to begin to acknowledge the problem of male bias in preclinical trials, and until 2016 for it to mandate that research money it granted must be for research that includes female animals.

The gender bias in medical research shows us that medicine is not specific to the individual. Many hidden biases, like social conditioning, have dissolved the purity of the science well before the medicine gets prescribed to you.

We are more than solid objects

Before turning to osteopathy, I was originally educated as a Chemical Engineer, so subjects like maths, chemistry and physics are my bedfellows. They are insightful friends but like many friends they do not elucidate all situations. Biology was their estranged brother, connected as a science but classed differently as a natural science. There is a depth to biology that maths struggles to grasp. For example maths struggles to map itself on biology, our best endeavours contain errors and consequently any extrapolations contain these hidden errors. Essentially we can map our blue planet floating through space but not the life on it. Science has taught us much about the material world around us, often referred to as the world of solid bodies but material itself is not nature, it is not biology, it ain’t life.

My concern is that we follow science blindly, as Stephen Fry said in his recent podcast Great Leap Years “science is the new religion”. We like to separate ourselves from nature to feel like we are in control – yet we are nature itself. We love the simple rules and the black and white answers that science provides. However we are fooling ourselves as these answers are bias and contain hidden errors.

I respect science, especially it’s ability to ask hard questions about the unknown. To lessen the burden of this monumental task science formulates hypotheses made on the basis of limited evidence as a starting point for further investigation. Research data is framed by the hypothesis and acts as a type of lens that concentrates our field of view. In psychology and cognitive science, this is called a confirmation bias (or confirmatory bias) and is a tendency to search for or interpret information in a way that confirms one’s preconceptions, leading to statistical errors. Reducing bias and error is fundamental for improvement in medical science. No doubt it is a hard task to see a hidden bias in the lens through which we see the world. However if we acknowledge our flaws and learn from our biases we can safely improve our healthcare systems.

I will write more about the hidden bias and how we humans can choose to remove our blinkers especially when it comes to scientific doctrine. We require a change in seeing to open new doors beyond the world of solid bodies. If you are interested in further reading I suggest The Wholeness of Nature by Henri Bortoft.