Video Game Designed to Create Better Test for Tuberculosis

• Scientists use video gamers to identify mRNA (messenger RNA) segments for tuberculosis diagnosis.
• Data obtained meant to be used for simple diagnostic kits.
• The diagnostic tool is meant to be cost effective, fast and accurate.

Researchers from Stanford have found an innovative means of identifying a solution for simpler TB diagnosis. Eterna Medicine is a web based game that can be played by many registered users to identify sequences of mRNA which can ultimately be used for TB diagnosis. Tuberculosis is a respiratory disease that is caused by the bacterium Mycobacterium tuberculosis and it results in the death of 1.5 million people from across the world. It is a major health issue in developing countries and 5 % of people, who receive treatment for tuberculosis, relapse.

Facts About TB

• TB mainly affects the lungs, but it can also affect the brain, kidney or even the spine.
• TB is spread when an affected individual coughs, speaks or sneezes close to an unaffected individual. It spreads through droplet infection.
• It does not spread while shaking hands or while sharing food and bed.
• Two TB related conditions exist based on the virulence of the disease:
• Latent disease - TB can infect the individual, but the body’s immune system will prevent it from growing and resulting in the development of disease symptoms. The Mycobacterium lives in a latent state in the body till the body’s immune system is compromised when the organism grows to cause a full blown infection.
• Active infection - When the body’s immune system is unable to fight the spread of infection in the body, the classic TB infection develops.
• The risk factors for TB:
• HIV infection or other major illness like diabetes that leaves the immune system compromised
• Recent episode of TB
• Abuse of alcohol
• Latent infection that was not treated
• The symptoms of tuberculosis include:
• A persistent cough
• Blood or sputum while coughing
• Weight loss
• Chills
• Fever
• Sweating
• Loss of appetite

Tuberculosis is a cause of major health concern in developing countries as many people are affected by this disease. One of the major reasons for the wide spread of this disease is due to poor diagnostic tests currently available in developing countries.

This motivated Eterna co-creator Dr. Rhiju Das, Associate Professor of Biochemistry Stanford University to develop a gaming model that can be used for identifying specific sequences of mRNA. This game was aimed to support the blood test for TB that was designed by another Associate Professor from Stanford University Dr. Purvesh Khatri. While there are other blood tests being designed for TB, this blood test is experimented on the lines of a home test kit.

According to these researchers, the prevalence of TB in developing countries was largely due to poor diagnosis.

• Current diagnostic procedures were cumbersome.
• The wait for results took days, which meant people from rural areas did not stay back to collect the results.
• Expensive and long diagnostic tests meant that people with latent infection never got tested.
• Requirement of sputum from patients.

Sputum for Diagnosis

Current models of diagnosis require the individual to cough up sputum, which is then used for diagnostic purposes. This is difficult to collect due to factors like:

• Inhibition on the part of individuals
• Inability to cough up the right amount of sputum
• Weak individuals who are unable to sit up and cough
• Patients recovering or in the early stage of the disease for whom the amount of mucus in the lungs is low

The insufficient diagnostic models that are currently available for detecting tuberculosis forces people, especially from the lower income groups to miss out on medical care leading to

• The spread of the disease
• Increase in mortality rates
• Increase in drug resistant variations of TB
• Misdiagnosis with other respiratory diseases with similar symptoms

According to Dr. Jose Gomez Marquez, Head of the Little Devices Lab at MIT, 90% of devices for TB in developing countries are donated by benefactors and a large proportion of them, 60 to 70% stop functioning within a period of 6 to 7 months.

Dr. Khatri aimed at identifying a diagnostic test that would be similar to pregnancy test kits, which can be used even at home, is cost effective and accurate. Moreover, the test was expected to produce results within a couple of hours which would facilitate easier diagnosis and faster access to medication.

Promise of a New Diagnostic Tool for TB

Dr. Purvesh Khatri after detailed study on patients with TB found that three genes were activated in patients with TB. Two genes were over expressed in the blood of people with tuberculosis while one of the genes was always under expressed. A mechanism that would assay the levels of these genes in the blood would prove to be an accurate indicator of the presence of TB in the individual, according to the researchers.

The scientists need a molecule that will detect the presence of the specific mRNA of the genes that are active in TB patients. This where Eterna players come in focus, they will help create various RNA molecules that will then be tested in the lab to find out which one can actually be used in the diagnostic kit.

This is not the first time that Eterna players have been exposed to such a challenge. Many non-scientist video gamers were responsible for identifying biomolecules that can survive successfully in a living cell. They also co-authored an article that was published in the Journal of Molecular Biology.

How the Test Would Function

The molecule that is expected to be identified by the gamers will bind to the three RNA molecules of the genes that are over expressed in TB patients. If the RNA molecules are named A,B and C, then

• If A and B are present in abundance and C in lower concentration, then the molecule will bind to them and form a shape, shape 1.
• If C is also in large concentration, then the molecule will take another shape, shape 2.

Shape 1 molecules will be fluorescently tagged to emit light. The degree of brightness will be used as a measure of the presence of TB in the individual.

Highlights of the Experiment

• The experiment with video gamers taps into the potential of video gamers who are adept at solving puzzles and moving ahead in a ‘game’.
• Instead of a couple of researchers working on solving the sequence of the mRNA molecule, millions of gamers will participate in the challenge.
• A million molecules are expected every month from the gamers which will be synthesized by the super computers in the researchers’ labs.
• More hands lead to shorter period of discovery.
• The diagnostic tool will be cost effective and accurate.
• Latent TB infections will also be detected using this method.

References:

1. http://phys.org/news/2016-05-video-game-tuberculosis.html
2. http://www.cdc.gov/tb/topic/basics/default.htm

Source-Medindia