Research papers are an essential part of all scientific research. When a scientist, group of researchers, or organization makes a discovery that they believe is novel and significant, they publish their findings in a scientific journal to share their work with the world. In the drug discovery space, a publication might cover a new discovery about the causes of a disease, a new drug target, preclinical data about a promising treatment in development, or the results of a clinical trial.

For those without extensive education in the field, papers about ALS research can be intimidating. They are often written in very technical language and go into precise detail about the complex biological processes involved in treating the disease. Still, reading new publications is one of the best ways to keep up with the latest research.

To help explain how people with a limited scientific background can best read and interpret publications about ALS Research, we spoke to Dr. Kyle Denton, Ph.D., the Director of Cell Biology at the ALS Therapy Development Institute (ALS TDI).


If someone is interested in learning more about ALS research and drug discovery, what kinds of research papers do you think they should be paying attention to?

Dr. Denton: There are four main categories of publications that are relevant. The first is basic science research, which is mostly what we do here at ALS TDI. It's usually either experiments in which researchers are working in a lab to study a disease with either cell lines or animal models, or working with digital models on a computer.

Then, there are meta-review articles, in which researchers aggregate data from multiple previous publications or large data repositories, and then do additional analyses. This can allow them to identify things that a single publication may not see because they don't have access to such a large number of samples.

In review articles, researchers or authors will give a summary of the current state of research on a certain subject and provide a list of references that are worth reading if you are interested in learning more. Review articles are a great starting point if you’re interested in a new subject.

Lastly, there are clinical trial publications. These are reports about whether or not a clinical trial resulted in beneficial effects, or if researchers can see any improvement in pharmacodynamic endpoints, such as certain biomarkers.

Can you explain the structure of most research papers? Are there any particular sections you think are most important for laypeople to pay attention to?

All papers begin with an abstract. Abstracts are the main summary of the paper that includes a hypothesis, a little bit of background information, a description of the experiments in the paper, and the main conclusions. They are generally short and most have a word limit, sometimes under 500 words. That's always a good spot to start.

After the abstract, generally, is the background. In the background section, authors will present information about the area that they're studying and also lay out their particular hypotheses. The methods section is where the authors explain the details of how their experiments were performed. Next is the results section, which presents the data gathered by the experiments in figures and tables. That's where you’ll find information on what statistical methods were used to interpret the data.

One of the more important sections for someone who might not have a scientific background is the discussion section. That is where the authors will go into more detail about what the data means in the context of the area they're studying. This is also where they will often voice any concerns with their experiments. A lot of times researchers will do an experiment and interpret it in a certain way, but they know that there could have been a different interpretation, or the experiment could have been done slightly in a superior manner if you had either more resources or more time.

If you read a news article saying some paper is an amazing breakthrough, I like to compare it to this section. Most of the time in the discussion, the authors will actually say, “we have all of these caveats with our data, so don't over-interpret it.”

Then the conclusion is a summary of what was done and what should be looked at in the future, potentially. Conclusions are pretty similar to the abstracts, generally.

I think the abstract is definitely the most important spot to start when reading a paper. Then the discussion section as well. I think going through the abstract, then reading the discussion will give you a good idea of how strong the findings are in that paper.

For many non-scientists, we learn about ALS research from news articles about newly published findings. What should people look for to make sure that a published paper covered in a news story is coming from a reputable source?

I think it's important to not just read a news article, but to actually look at the original publication.

It's always good to go to the abstract and see if what the paper is actually saying is the same as what is reflected in the news article. You can also look at the list of authors of the paper and see if they're from a reputable institution and if they've published in that area previously.

One other thing to look for is if the research paper is peer-reviewed or not. There are journals that are not peer-reviewed, where you simply pay some amount of money, and the journal will publish it for you. Without the peer review process, you don't know if other experts in the field agree with the findings in the paper. Most of the time, if you go to the journal’s webpage, they'll explicitly say if it is a peer-reviewed journal.

What do you look for in a paper to decide if you believe the study was well-designed, and the conclusions are reasonable?

For basic science research, it's always good to look at whether or not appropriate positive and negative controls were included. Say they're treating some cells or animals with a drug. You need to make sure that they include control treatment, either animals that were left untreated or treated with what's called a "vehicle control," which is essentially a placebo, so that you can confirm that the drug is having an effect on the animal model’s disease.

You also want to look at the number of replicates. Authors will often explicitly mention that they repeated an experiment several times. So, if they don't say that, you might want to be skeptical of how believable the results are. It's often good to repeat an experiment at least three times and see if the same results reoccur each time, to make sure other factors such as an error in your methods or analysis didn’t affect the outcome.

And then for clinical trial publications, it's good to look at how many participants were in the treatment arm and the placebo arm, and also how long the trial lasted. Generally, the longer it lasts, in more patients, the more believable the findings are. But of course, costs rise as you do both of those things. There's always a balance of costs versus keeping things smaller and publishing faster in clinical trials, especially in the ALS research space.

Where is a good place for people looking to follow new research to find out about the latest publications?

I would recommend making a PubMed account [a database of life sciences and biomedical research maintained by the National Institute of Health], which just takes a few minutes. Then you can find the areas of research that you're interested in following and create alerts with keywords. You could just use "ALS" if you want to get a lot of papers. If you're more interested in SOD1-related ALS, you can do "SOD1" and you can set it up to give you either daily, weekly, or monthly email alerts with a list of papers.

You also get commentaries sent to you that way. If a paper comes out that's really impactful to the field, generally, there'll be a commentary article that describes the paper in more simplified terms and puts it in the context of the field. That gives you an idea of when a certain paper is really important to other researchers.

Many research articles require a journal subscription or a one-time fee to read. These can sometimes be very expensive. How can people find articles they can access for free?

A lot of research articles are behind a paywall. However, there is a movement toward more open-access publications. A lot of articles that come from research that's funded by taxpayer money are now required to be open access. Some journals are moving toward being fully open-access, where anyone can download the article for free. Sometimes even journals that aren't fully open access will allow the authors to pay a fee to make their article open access. There are also journals, like PLOS ONE, that are exclusively open-access. You can also always try emailing the corresponding author – they may be willing to send you a copy of the manuscript.

What kinds of research papers would you say are the best for people learning about ALS to start with?

I think one of the best places to start is to look at review articles. Nature Reviews Neuroscience has really good review articles on ALS that seem to come out every few years. They have them in different areas: past clinical trial successes and failures, research on the genetic basis of ALS, new potential therapies, and new cellular models of ALS, which I’m really interested in.

You can often find good review articles by picking a key leader in the field of ALS and looking at their past publications. Or you can go to PubMed and type in “ALS,” and whatever else you're interested in. There's a checkbox for review articles, and then you can dig through those.

Would you say it’s ever worth reaching out to a paper’s author if you have questions about the study?

I think it is worth getting in touch. Even as a researcher, if you have a question, you read a paper and something looks interesting to you, or you're confused about how the authors did a particular experiment, we'll reach out to the corresponding author.

Generally, when you're looking at a paper they’ll list the email address of the corresponding author. So, if you just send them an email and say, "I was reading your paper and I had this question." It's really rare that an author of the corresponding author will not want to answer your question because most researchers like to talk about their field of interest.

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