Can You Trust chatGPT When It Says It Loves You?

chatGPT and its cousins have been making news lately. The media seems enthralled with attempts to hack GPT based systems into producing outrageous statements. It's somewhat like ten year olds saying dirty words into a recorder and giggling when the recorder repeats them. It doesn't seem like much of  a trick.

What follows isn't much of a trick either. It should come as no surprise that large language models (LLMs) trained on the internet might produce output that is less than factual. They are trained to produce plausible not factual text. 

I have read about the supposed dangers of students using LLMs to submit essays in academic classes. I thought I might try to get GPT to produce a short paper on a medical subject.

I signed up for an account with OpenAI and obtained an API key so I could connect with one of the LLMs without going through the public website.

There are a large number of  GPT models, 66 in total, to choose from when selecting a text generator. I chose text-davinci-003, one of the more recent models. For my first attempts, I prompted the model with

write a paper describing how to test a pancreatic tumor for sensitivity to folfirinox.

Folfirinox is a chemotherapy for treatment of advanced pancreatic cancer.

Here is the Python code for requesting the paper.

#!/usr/bin/env python
# -*- coding: utf-8 -*-
"""
test_chatGPT.py - test chatGPT3
author: Bill Thompson
license: GPL 3
copyright: 2023-02-11
"""
import openai

def main():
    openai.api_key = ""  # your OpenAI API key goes here

    prompt = "write a python function to download metadata from GISAID"
    temperature = 1
    max_tokens = 3000    

    prompt = "write a paper describing how to test a pancreatic tumor for sensitivity to folfirinox"
    temperature = 1
    max_tokens = 3000

    tag_line = openai.Completion.create(
        model = "text-davinci-003",
        prompt = prompt,
        max_tokens = max_tokens,
        temperature = temperature,
        n = 1
    )

    print(tag_line['choices'][0]['text'])

if __name__ == "__main__":
    main()

temperature is an adjustable parameter, ranging from 0 to 1, allowing the model to sample from a wider distribution of tokens for the next word. 0 causes the model to choose the optimal word, 1 allows proportional sampling from the full distribution of possible words.

This attempt produced the following.

Introduction

Pancreatic tumors are aggressive tumors that are most often found in the pancreas, the organ that regulates blood glucose and digestive enzymes. The most commonly used treatments for pancreatic tumors are chemotherapy, radiation, and surgery. One newer chemotherapy option that has been used in patients with advanced and/or metastatic pancreatic cancer is folfirinox. Folfirinox is a multi-drug therapy regimen that consists of two chemotherapy drugs; one being a fluoropyrimidine (5-FU and/or capecitabine) and the other being a platinum drug (oxaliplatin). The purpose of this paper is to outline a method for testing a pancreatic tumor for sensitivity to folfirinox.

Materials and Methods

The first step in testing a pancreatic tumor for sensitivity to folfirinox is to obtain a biopsy of one of the tumor cells. This biopsy should be obtained at the same time or shortly after the initial pancreatic tumor diagnosis is made. The biopsy sample should be preserved in a sterile container and sent to a clinical laboratory for further analysis. The biopsy sample should be tested for various genetic markers to identify whether or not it is likely to respond to folfirinox.

Once a sample is received by the clinical laboratory, the tumor cells should be cultured and grown in a specialized media to determine their sensitivities to the individual chemotherapeutic agents and the multi-drug combinations found within folfirinox. The cultures should be exposed to a range of concentrations of the chemotherapy drugs specific to folfirinox and observed over a period of time to assess the response of the tumor cell to the drugs.

Results

If the cancer cells demonstrate strong and consistent sensitivities to either the individual chemotherapy drugs or to the multi-drug combinations, then the tumor is likely to demonstrate a high degree of tumor sensitivity to folfirinox. On the other hand, if the cell cultures do not respond strongly to the drugs found within folfirinox or show signs of resistance, then the tumor may not be sensitive to the folfirinox regimen.

Conclusion

In conclusion, testing a pancreatic tumor for sensitivity to folfirinox requires obtaining a biopsy to acquire cancer cells, culturing the cells, and exposing them to the individual drugs and multi-drug combinations found in the folfirinox therapy regimen. Responding to the drugs indicates that the tumor is likely to be sensitive to folfirinox; however, a lack of response could indicate that the tumor is resistant to this type of therapy.

Certainly, this is a plausible explanation.

In a scientific paper, you expect definitive statements to either be backed up with references or data. Lets' see if we can get some backup for the claims in the paper.

I changed the prompt slightly.

prompt = "write a paper with references describing how to test a pancreatic tumor for sensitivity to folfirinox" to this type of therapy.

Here are the results.

Introduction

Folfirinox is a chemotherapy regimen often used to treat advanced pancreatic tumors. Pancreatic tumors are difficult to treat because they are surrounded by healthy tissue, making accurate diagnosis and treatment essential. To ensure the most effective treatment possible, it is important to determine the sensitivity of the tumor to specific treatments, such as Folfirinox. This paper will discuss the testing methods that can be used to evaluate the sensitivity of pancreatic tumors to Folfirinox.

Testing Methods for Pancreatic Tumor Sensitivity to Folfirinox

A variety of testing methods can be used to determine the sensitivity of pancreatic tumors to Folfirinox. These tests are designed to measure the ability of the tumor to respond to the chemotherapy.

The most commonly used tests for assessing sensitivity to Folfirinox are molecular tests. These tests measure the presence of specific mutations in tumor cells, which can indicate the tumor's sensitivity to chemotherapy. Molecular tests such as body fluid cytology, tumor mutational analysis and expression profiling can be used to identify mutations that can predict a tumor's responsiveness to Folfirinox. 

In addition to molecular tests, there are also commonly used functional assays that test how the tumor responds to Folfirinox. These include cell viability assays, cell death assays, and biochemical assays. These tests measure how the tumor cells respond to the treatment with Folfirinox, giving insight into its effectiveness. 

Conclusion

In conclusion, Folfirinox is an effective treatment for pancreatic tumors, but it is important to determine the tumor's sensitivity to the treatment in order to maximize its effectiveness. Molecular and functional tests can be used to assess the responsiveness of the tumor to Folfirinox. With the help of these tests, it is possible to accurately diagnose and treat pancreatic tumors in the most effective way possible. 

References 

Ando, S., Fischbach, W., Quain-Sande, L., Milosavljevic, T., Merker, A., Weibel, T., ... & Ditsch, N. (2019). Functional assays to evaluate tumors sensitivity to chemotherapy with Folfirinox. In Methods in Molecular Biology (pp. 73-84). Humana, New York, NY.

Bhatt, M., Chintagumpala, M. M., & Schulze, S. M. (2016). Utility of biomarker detection in advanced pancreatic cancer. World journal of gastroenterology, 22(19), 4856.

Chae, Y. K., Lee, J. H., Choi, M. E., Kim, S. J., & Kim, S. W. (2012). Body fluid cytology analysis and prediction of chemosensitivity in advanced pancreatic cancers. Cancer research and treatment: official journal of Korean Cancer Association, 44(3), 162-169.

Voduc, N., & Malyukova, A. (2020). Use of Molecular Tests to Predict Pancreatic Tumor Response to Folfirinox. Journal of Advances in Medicine, 2(1).

It looks good, except none of these references exist; plausible text, not factual. 

I guess if chatGPT tells you it's in love with you, be careful.

I made another attempt at temperature = 0.

Pancreatic tumors, or pancreatic ductal adenocarcinomas (PDAC), are one of the most difficult cancer types to treat due to their aggressive behavior and resistance to chemotherapy and radiation. Fortunately, recent research has identified a few treatments that demonstrate efficacy in treating advanced pancreatic tumors, including folfirinox. Folfirinox is a combination of the drugs 5-fluorouracil (5-FU), oxaliplatin, irinotecan, and leucovorin and has been used effectively in the treatment of advanced pancreatic adenocarcinomas. Thus, it is important to determine the levels of sensitivity to folfirinox for pancreatic tumors prior to treatment.

To test for sensitivity to folfirinox, a tissue sample from an individual’s pancreatic tumor must be collected. The sample should be sent for immunohistochemistry (IHC) testing to detect the expression of proteins related to gene mutations such as KRAS, NRAS, and BRAF, which are associated with the tumor’s resistance to folfirinox treatment. If the tumor cells are found to be KRAS, NRAS, orBRAF mutation positive, this indicates that the tumor is likely to be resistant to folfirinox and other commonly used chemotherapy drugs. Additionally, PCR (polymerase chain reaction) testing should also be carried out to detect KRAS, NRAS, and BRAF mutations in the tissue sample. 

In addition to genetic testing, folfirinox sensitivity can also be determined in vitro. A cell line derived from the patient’s tumor should be established and treated with folfirinox for a period of time and the cytotoxic effects of the drug analyzed. Cells should also be treated with a control drug to compare the efficacy of folfirinox. From there, the IC50 (the concentration of a drug at which half of the cells are inhibited from growth) of folfirinox can be calculated and used to determine the sensitivity of the tumor to the drug.

Overall, identifying the sensitivity of a patient’s pancreatic tumor to folfirinox is essential for effective treatment. It is important to utilize multiple methods for testing, such as immunohistochemistry, PCR, and in vitro testing to accurately determine the tumor’s sensitivity to the drug and to optimize treatment response.

References:

1. Vincenzo Todaro, Alfredo Finocchiaro, Giuseppe Portale, & Livia Biancone (2020). Current Panacea of Folfirinox in Pancreatic Cancer. Frontiers in Oncology, 10, 1445. https://doi.org/10.3389/fonc.2020.01445

2. Lee, Eun Kyung, Sun-Hee Kim, Hm-Suk Ahn, & Do-Hyoung Park (2017). Current Molecular Therapeutic Targets in Pancreatic Cancer. Journal of Pathology and Translational Medicine, 51(2), 134–140. doi:10.4132/jptm.2017.02.11

3. Serna Gallardo, Ivan & Khan, Atique Ullah & Gornals, Jordi & Vargas, Antonio. (2020). Pancreatic Cancer and Immunohistochemistry: A Practical Guide. Cancers. 12. 2703. 10.3390/cancers12122703. 

4. Lee, Andy W. & Siegel, Michael D. & Dickson, Melissa A. (2020). Establishing Cell Lines from Patient-Derived Solid Tumor Specimens to Study Drug Resistance. Advances in Experimental Medicine and Biology. 1179. 299-329. 10.1007/978-3-030-41119-1_11. 

5. Nunes, S. C., Martinho, O., & Cravo, M. (2011). Polymerase Chain Reaction and Its Application in Clinical Practice. Diagnostics, 1(2), 84–93. https://doi.org/10.3390/diagnostics1020084

Again, the references look legitimate, but are not.