20 May 2018: What Do Scientists Do?

Progress Report
20 May 2018

What do scientists do? With many questioning the value of scientists regarding climate change, vaccinations and other matters, I thought it might be worthwhile to document my scientific life. Before I entered medical school, I had limited exposure to scientists in a social setting, and even now, talk to few people outside of my professional life who write papers or do research to advance scientific understanding.

Alas, I am not a typical scientist. I graduated medical school (University of Michigan 1983) and did a residency and fellowship in pathology (Wayne State University 2000). Most scientists work for a university or research institute, but I do not. I own a business which publishes a free online pathology textbook and am currently its Editor, although I recently hired a Deputy Editor who is much smarter than me and more attuned to the academic world.

Here are the projects / papers I am working on:

1. The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia (see natpernick.com/TheLawsJune2017.pdf).

This was my first complexity and cancer paper, initially published in 2011 and updated in 2017. I submitted it to several pathology conferences but it was repeatedly rejected. In fairness, it did not fit any of the categories for papers at the conferences, which logically suggests that the paper will not be well received.

This paper was accepted for presentation at the International Conference on Complex Systems in Boston in July 2018 (see http://www.necsi.edu/events/iccs2018/). I had to shrink the abstract (summary) to 250 words. I am starting my preparation for a 12 minute talk, which will be followed by 3 minutes of questions. The purpose of the talk is to get feedback, leading to new insights, corrections of errors and possibly new directions to study. The questions often are impossible to answer in that setting other than “I don’t know, I will follow up”. Sometimes, the questioner is really giving a speech about his/her own work.

I also submitted my complete paper for their published proceedings. Using their very wide margins my paper was 18 pages, which I have chopped to their limit of 10 pages.

2. How Cancer Arises Based on Complexity Theory (see natpernick.com/HowCancerArises.pdf)

A revised abstract of this paper (currently 37 pages) will be submitted to the 2019 ASCO conference (American Society of Clinical Oncology) in May 2019. I tried in 2018 but the hurdles were (a) I had to find an ASCO member to sponsor me and (b) I had previously posted the paper on my personal website and prior publication was prohibited. But I eventually found a sponsor and will revise the paper for 2019 based on the findings in the other papers I am working on, as described below. I will also try to find a medical center (Wayne State, University of Michigan, Oakland University) where I can give a talk about it, to get feedback.

3. How lung cancer arises based on complexity theory
I am writing papers on the  top 20 leading causes of cancer death in the US, beginning with lung cancer, applying the knowledge / theory derived from my first 2 cancer and complexity papers. This paper has been through many drafts, and is now complete. I submitted an abstract for this paper to a pathology conference for presentation, and they should accept or reject it this month for an October 2018 conference.

4. How colon cancer arises based on complexity theory (under development)
I am working on the first draft of this paper. The plan is to finish this paper by September 30, 2018, completing one paper every 3 months. At this rate, it will take 5 years to write papers on the top 20 causes of cancer death.

5. Preinvasive neoplasia
I published a Letter to the Editor (see http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2017-0581-LE) about how complexity theory suggests that tumors such as glioblastoma, which currently do not have a known premalignant condition, likely do have one. I suggested that although we have not identified microscopic features of premalignancy, there probably are molecular patterns.

This was my first Letter to the Editor of a scientific journal in many years. It is a quite complicated task compared to preparing a Facebook post. There is much back and forth with the editor over formatting and references. Sometimes their copy editor changes the text to make it more “readable”, although in my case they completely changed the meaning. Fortunately they corrected it.

That’s it for now.

10May18: Preinvasive cancer, update

I received this response to my prior post about Preinvasive Cancer, see https://natpernickhealth.blogspot.com/2018/:

Thanks Nat. What can you say about the implications of these ideas for treatment of cancer?

This was my response: 

Better understanding of how cancer arises suggests new treatment options. When I was a pathology resident (1995-2000), there was no known precursor lesion for ovarian cancer. Subsequently, by studying BRCA1/2 mutation carriers, it was discovered that there is a premalignant condition, but in the fallopian tubes (https://www.ncbi.nlm.nih.gov/pubmed/22706539), suggesting that their removal (salpingectomy) may reduce ovarian cancer risk (https://www.ncbi.nlm.nih.gov/pubmed/25628372). Similarly, identifying precursors for glioblastoma may suggest new therapies to prevent or treat this devastating disease.

6 May 2018: Preinvasive cancer

I recently published a Letter to the Editor, entitled Focusing on Preinvasive Neoplasia, that may be of interest. Neoplasia is the abnormal growth of tissue due to uncontrolled division by one or more cells. It includes cancer as well as benign tumors. Preinvasive neoplasia means growths that have not yet demonstrated the ability to infiltrate adjacent tissue, a property relatively specific for cancer.

To understand cancer, it is helpful to think about how life arose. According to Kauffman, life is the emergent collective property of a modestly complex mix of biomolecules (DNA, RNA, proteins and others), confined to a closed space, which catalyze each other’s formation (The Origins of Order 1993). Networks of biomolecules with this property are relatively resistant to change from internal or external stressors (The Laws of Complexity 2017). In addition, natural selection has added additional control features that make deviations less likely. As a result, a cell cannot quickly change from normal to malignant. I previously proposed that most cancers are caused, typically over decades, by nine chronic stressors (chronic inflammation, carcinogen exposure, reproductive hormones, Western diet, aging, radiation, immune system dysfunction, germ line changes and random chronic stress / bad luck), acting together and in the appropriate context (How Cancer Arises Based on Complexity Theory 2017).

Cancer arises through stepwise progression. Although intuitively it might seem that the microscopic appearance would be slightly different at each step, this may not be true. For example, glioblastoma and Hodgkin lymphoma have no known intermediate or premalignant states based on microscopic examination. However, the Letter to the Editor suggested that intermediate states may be identified based on analysis of molecular patterns. They are also predicted by complexity theory, which discusses the requirement for stable intermediate states for cancer to develop.