28 June 2024

In science for truth, not positive results

Pharma Outreach

Science is often celebrated for its groundbreaking discoveries and the new knowledge it brings to our understanding of the world. However, research is not a straight path to success; it can sometimes wander off in the wrong direction. It is extremely important to question the validity of what is presented as truth and to remain critical about our own methodologies to avoid drawing conclusions from flawed experiments.

Beatriz Cruz Luzon.

Science is all about discovering reality and not about confirming the researcher’s high hopes or bias.

Beatriz Cruz Luzon made a point of this lately at the Lundbeck Brain Battle, winning the competition and the prize of a PhD at Lundbeck. Her experience underscores the importance of transparency and integrity in scientific research.

Beatriz has answered some questions from Pharma Communications:

When did you learn about the competition?

“I found out about the Brain Battle last year when it was held for the first time, but I decided not to apply. At that time, I had serious doubts about the foundation of my project. I did not think that the conclusions derived from our research were valid, and thought it was unethical to present them in front of scientists and high school students.

I spent the following months refining my arguments, running additional controls, and comparing my interpretations with those of external scientists. I am glad I made this decision because things were indeed not looking good—it became evident that two years of research were based on an initial false positive result.  

A flawed foundation invalidates everything built upon it, and I am relieved that it was never published. By the time I had to submit my Master's thesis, I had started working with a different supervisor and wrote my dissertation from a critical perspective.”

What motivated you to apply this year?

“When I heard that Lundbeck was hosting the 2nd Brain Battle, it was a no-brainer. I was in a completely different place: I had understood where my project went wrong, I had already discussed it openly, and I felt confident in my reasoning. With a strong story for the Brain Battle, passion for inspiring curiosity in the audience, and excited about the opportunity to join Lundbeck… I went for it!”

What was important for you when you planned how to communicate your story?

“I had to figure out two things: First, what was my purpose? Second, why should these students listen to me? Our communication coach emphasized that if we wanted the audience to listen to us, we had to offer them something valuable. What could I offer? Negative results are not what I would choose to capture the attention of high school students. There is something much more appealing I could bring: my sense of humor. So, I aimed to connect with the audience by making them laugh.

I gathered the most exciting aspects of my project and built a storyline using humor and analogies. I talked about how microglia, the immune system of the brain, can sometimes "misbehave" and cause a lot of trouble. I brought a huge prop to the stage—a hollow model of a virus that could be opened to take elements in and out—as I explained how these viruses can be modified to control different cell types, like microglia. Finally, I disguised the virus with a silly outfit, so it would not be easily detected and destroyed by the immune system.”

Negative results - or “failure” - can also give us answers

Having caught the audience’s attention, Beatriz could emphasize her main point.

“As we approached the end, with the excitement building up, we just had to answer one question: "Will our virus infect microglia and help us bring peace to the brain…?" The answer was, "Nope." This was my chance to send the following message: Not being afraid of “failure”, because “failed” experiments are an important part of the process.

Everyone is familiar with the theory: failure is an integral part of the scientific process. Yet, in practice, is anyone actually failing? Throughout our education, we are most likely to hear about the things that worked and made it to the textbooks. The picture remains the same in research, where only positive results are worthy of publication. This publication bias distorts the scientific record and conveys a misleading notion of what science is about.

It is relevant for students to hear about this bias and understand the importance of reporting negative results before they encounter a culture that only rewards the positive.

Beatriz Cruz Luzon

I wanted high school students to meet a scientist who is comfortable saying, “Nope, this didn’t work” – so that they know projects can go wrong, and that, by sharing, instead of hiding, it is still possible to create value.

Sharing negative results can inspire new strategies, provide a more comprehensive understanding of complex systems, and save considerable time. By easing the pressure on constantly delivering positive outcomes, we can also reduce questionable research practice, increase the focus on reproducibility, and preserve trust in science.

Many of these students will eventually join research labs and encounter a culture with values that differ from what they expect from science. Students are particularly vulnerable to these pressures, and many may become disillusioned and leave research after years of education.

It is crucial to encourage critical thinking in science, and encourage it early enough so that early career researchers have the tools to navigate these pressures and foster a more honest and unbiased scientific community. Of course, we need to do more than that; we need to establish the right incentives. I believe that raising awareness about "the biased side of science" at any educational level can help change things.”

What will the subject of your new PhD position at Lundbeck be?

“My PhD research will focus on the Blood-Brain Barrier (BBB) in the context of neuroimmunology. The most fascinating aspect about the BBB is that it serves as a link between the brain and the rest of our body. While this barrier typically protects the brain by controlling passage of molecules and preserving homeostasis, it can deteriorate with age and in pathological conditions. This breakdown goes hand in hand with neuroinflammation and neurodegeneration, and it is characteristic of different neurological disorders, such as Multiple Sclerosis, Alzheimer’s, and Parkinson’s Disease."

 

Beatriz describes her PhD project: “Over the next three years, I will work to understand what triggers BBB dysfunction, and how disruption and restoration of the BBB contributes to neurological diseases. We are starting to think about brain disorders as complex conditions stemming from the interplay of different elements across the entire organism.

Looking beyond the limits of the brain might help us identify novel targets for treating neurological diseases – and I am thrilled to have the opportunity to do this within Lundbeck's collaborative and multidisciplinary environment.”

During my PhD, I will study the Blood-Brain Barrier (BBB), and how its disruption and restoration contributes to neurological disorders. The BBB is a layer of cells found in the capillaries of the brain. While this barrier typically protects the brain by controlling passage of molecules from the blood into the brain, it can deteriorate with age and in pathological conditions, becoming leaky and unselective.

This breakdown goes hand in hand with neuroinflammation and neurodegeneration, which are key features of different neurological disorders such as Multiple Sclerosis, Alzheimer´s and Parkinson´s Disease.

The most fascinating aspect about the BBB is that it serves as a link between the brain and the rest of the body. We are starting to think about brain disorders as complex conditions arising from the interplay of different elements across the entire organism.

Looking beyond the limits of the brain might help us identify novel targets for treating neurological diseases – and I am thrilled to have the opportunity to do this within Lundbeck's collaborative and multidisciplinary environment.”

 

A false positive is when a scientist determines something is true when it is actually false.

An experiment can yield positive results due to factors unrelated to the specific treatment being tested. The way to spot a false positive is to test experimental samples together with the appropriate negative controls (for example, a sample with no treatment). If the negative control shows positive, that means that you cannot attribute the effects seen in your experimental samples to the treatment/procedure you tested. If you do not include negative controls in the experiments, there is no chance for you to spot methodological flaws and correct them.

 

 

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