Biology 446    Unsolved Problems Fall 2020

The Dreaded Erroneous (i.e. Misinterpreted) Research Paper Assignment:


Many students find this assignment the most challenging, difficult and time-consuming component of the course. Most students say it was a good experience, others hate it.

You do this particular assignment as individuals, without help or collaboration from others, except me. If you need help, I will give it. But don't ask others without permission. The goal is to find a research paper in one of the following three journals: Science, Nature or PNAS (= the Proceedings of the National Academy of Sciences of the USA). All three of these journals contain research articles in all fields of science and even advanced mathematics in the case of PNAS.

Please concentrate on articles in some area of cell biology. Also, be careful not to bother with news articles or even reviews or theoretical papers. PNAS has (almost) only research papers, with some of these purely theoretical. Nature and Science contain many news articles, with actual research papers only being a fraction of their content. Make sure you can tell the difference.

PNAS is available free on line []. For Science and Nature, you will need to log in through your UNC account.

Please do NOT use a paper from a different journal, or a paper published after about 2000, without checking with me first.

Once you have selected what you think will be a suitable topic, please check with me to make sure it's OK.

Find a research article that is based on some paradigm that has subsequently turned out to be mistaken.

A systematic approach that some students have used in previous years is to choose some biological subject which you are reasonably confident that you understand, and then find out approximately when certain major discoveries were made, or theories proposed/accepted. Most such papers dated before the new paradigm will be based, often explicitly based, on the earlier paradigm. This can be a liberating experience, like visiting a "parallel universe" in which actin and myosin literally contract (instead of sliding) or in which antibodies are shaped around antigens instructively, or in which mitochondrial membranes don't have electrochemical gradients.

Focus on major breakthroughs (Kuhn's "Paradigm Shifts"), when revolutionary changes occurred in beliefs about any particular biological phenomenon. Then find published research papers on that subject before the breakthrough occurred.

A good strategy for finding good erroneous papers to report on:

#1) Make yourself a short list of 4 or 5 phenomena within cell biology (or genetics) about which there were some major conceptual changes (Kuhn's "Paradigm Shifts") in the 20th century. For example, muscle contraction is now known to be driven by active sliding of myosin along actin fibers, but before this was discovered, nearly everyone believed that muscle proteins actually contracted; and before the clonal selection hypothesis, people thought antibody binding sites were either molded around antigens, or (before that) that antibody specificities evolved by Darwinian natural selection, like other genes. Likewise, genes were thought to be proteins, etc. etc.

#2) Use PubMed, Science Direct, Google, Wikipedia or other sites to find out approximately when these breakthroughs occurred.

#3) Make a short list of keywords to search for to find papers on these phenomena.

#4) Then use the search features on the web sites for specifically for PNAS, Science, or Nature to find articles a) that mention keywords appropriate to your topic, and b) that were published BEFORE (or during) these different breakthroughs (paradigm shifts). Take a quick look at each of the papers that you retrieve that fit these criteria. Many of the papers you find won't be useful for this report, but some will be, and you only need one.

Your report should consist of the following:

First) A summary in your own words of what the authors observed and reported. Besides putting this in your own words, also try to separate what they actually observed as distinct from what they thought it meant. People may see blue lights in the sky; and they may think it's a flying saucer; and they may SAY that they saw a flying saucer; and somebody else would say that they saw the Aurora Borealis. But what they saw was blue light coming from the sky. In a biological experiment, the scientists may have seen some cells becoming more round when they added ATP. Would you say that they saw a force? Maybe it was really the cells' adhesions that changed, instead of their contractility? Or maybe cytoplasmic viscosity changed? It is good practice in critical thinking to sort out observations from interpretations, while realizing that even blue light is somewhat of an interpretation! Judgment is required.

Second) Summarize the authors' interpretation of their observations. This should include the paradigm (or perhaps several paradigms) on which they seem to be basing their interpretation and which may very likely have motivated their research program in the first place. They may or may not be explicit about what this paradigm is. The more confident people were about it in those years, the more "obvious" it may seem to them that it is true; and the less likely they are to explain their underlying assumptions. That is because they may not have regarded these as assumptions, but merely as "common sense".

Third): Try to re-explain the observations in terms of whatever theory is NOW the accepted paradigm with regard to that class of phenomena. Sometimes the observations fit new theories even better. This is an ultimate test of scientists' reliability. There are always temptations to discard data that doesn't fit. "Run number 6" may have been the time the voltage fluctuated because of the thunderstorm; or it may have been the time that some medium had been accidentally left out of the refrigerator the night before. So if their measurements fell outside expected ranges, the authors of your chosen paper may have been misled; therefore try to figure out (and explain) how and why they went wrong.

Fourth): Save it as a pdf file, and include a copy with your report..

Guidelines for Your Erroneous Paper Report

Don't report on topics that have been discussed in class, for example papers that directly preceded Watson and Crick (i.e. anything mentioned in the "What Watson Knew" page of notes), Helicobacter as the cause of ulcers, or retraction fibers vs. filopodia.

Autoimmune diseases, the immune system in general, and formation of cartilage and bone are all broad topics within which you could potentially find a suitable paper on an aspect or phenomenon that we haven't discussed. However, please check with me before going ahead with any of these.

Here are some examples of suitable topics from past years.

Reports that actin and/or myosin fibers literally contract (in the sense of shortening in length, instead of sliding past each other.

Reports of actual contraction of fibers inside flagella and/or cilia (again, instead of sliding filaments).

Reports that bacterial flagella undulate, like miniature versions of eukaryotic flagella.

Reports that proteins are synthesized by proteases surrounded by very high concentrations of free amino acids. (You CAN make them that way, but you just get random sequences of amino acids).

Interpretations of mitochondrial and/or chloroplast structure (and ATP synthesis) that were made before the chemiosmotic hypothesis was proposed and (10 years later!) became generally accepted.

Please do not ask librarians, faculty members, or other people for help on this project. For one thing, it is somewhat unfair to other students. In the past, when students went to the library to do this report, librarians consistently gave bad advice, such as steering them to examples of fraud. Hardly any of them can grasp the idea of seeking out examples of research that reached mistaken conclusions that were plausible, convincing and often for a long time, but which have turned out to be wrong.

Consider that about 10% of concepts that we now accept (and teach) as certainties, will eventually be disproven, perhaps by you. Most breakthroughs are replacement of one kind of explanation by a very different one. Please notice that the purpose is to study the process by which breakthrough discoveries get made. We should realize that few major discoveries replace nothing; scientists usually had some other explanation, that they confidently accepted as proven. Before that explanation became accepted, there was usually some earlier explanation, that also seemed certain, until a better idea came along. Such previous explanations can often be so ingenious, and so plausible, they can almost convince you. If you like "alternative futures" science fiction, you should enjoy this assignment.

(But that many students in the past have thought would be OK).

Don't report on fraudulent papers, that turned out to be deliberate fakes. Examples of honest mistakes are what we want, i.e. cases where the authors had good data but misinterpreted it. These papers demonstrate how plausible previous paradigms were, and how difficult it was to make breakthroughs.

Don't report on Beadle and Tatum's "one gene, one enzyme" concept, because they were making a big forward step.
I admit that many genes code for structural proteins, transcription factors, adhesion proteins, etc. but Beadle and Tatum successfully explained a whole bunch of eye color mutants in flies, and auxotrophic (amino acid requiring, etc.) mutations in Neurospora; indeed a large fraction of the genes that people were studying before WW II.

Don't report on changes in definitions. One student reported on a paper that discovered that AIDS is caused by (I forget the name exactly; some kind of leukemia virus) which was the name originally given to HIV.

Don't report that Hans Krebs originally claimed that his tricarboxylic acid cycle started with a seven carbon sugar, instead of a 6 carbon sugar. He was much closer to the truth than anyone else at the time.