Loop-mediated isothermal amplification (LAMP) for pandemic pathogen diagnostics

This project won the "Simple Explainer" prize on our Pandemics (May 2024) course. The text below is an excerpt from the final project.

tl;dr

The methods:

• Correctly designed and with optimised protocols, LAMP is a cheaper, faster, more robust and thus better scalable alternative to PCR with comparable accuracy.
• The molecular mechanism of LAMP is significantly harder to understand than PCR.

Why I think LAMP isn’t more widely used:

• Designing and optimising a LAMP assay is much harder than conducting a pre-designed assay.
• LAMP can outperform PCR specifically in diagnostics, but not in many other applications of PCR, and may thus be less well known.
• PCR is particularly well-established, especially in the industrialised world, and there seems to be significant potential for catching up on establishment and standardisation of LAMP protocols through further research.
• Offering cheaper testing methods than PCR, especially in low-income countries, might not pose enough commercial incentives for the market to fill the gap.
• Pandemic preparedness is generally underfunded, and state actors are slow to implement new methods, indicating a need for public advocacy.

Introduction

Past pandemics have killed up to ~10% of the world population[1] and have severely affected human wellbeing, society and economies. Catastrophic pandemics could threaten the existence of present-day humanity and thus many future generations. The risk of catastrophic pandemics has recently increased with the advent of advanced artificial intelligence and thus a greater risk for engineered pathogens with enhanced pandemic potential. Preventing catastrophic pandemics is therefore one of the most pressing challenges of our time[2].

A key aspect of pandemic prevention is rapid and accurate detection of infections to contain local outbreaks and prevent them from growing into epidemics or (catastrophic) pandemics. The most accurate way of detecting infections to date is to amplify (i.e. to make copies of) pathogen-specific genetic material from patient samples and visualise the result to determine the presence or absence of the pathogen.

The first method described for amplifying genetic material is polymerase chain reaction (PCR) and was discovered by Kary B. Mullis in 1993[3]. To this date, PCR is the gold standard for DNA amplification and is used in biolabs around the world for research with small amounts of target DNA. Even though many modifications have been made to PCR to improve its accuracy and adjust it to more specialised purposes, the basic method is still the same as 30 years ago. While PCR is highly accurate, it is comparatively slow, requires specialised lab equipment and training and is thus expensive.

As pandemic preparedness and response are global concerns, there is a critical need for low-cost and low-tech, yet highly reliable and scalable testing methods, especially for low- and middle-income countries.

In 2000, Tsugunori Notomi and colleagues published another DNA amplification method called loop-mediated isothermal amplification (LAMP)[4]. It is faster, more robust, and cheaper than PCR and might thus be a better method to detect infections. However, having existed for almost 25 years, it has not developed into the new gold standard for DNA amplification and is still fairly unknown to the scientific community[5].

In this report, I give simple explainers for PCR and LAMP used for pathogen detection and work out their differences. I focus specifically on the key goals for biosecurity technology development laid out in “A framework for technical progress in biosecurity”, which are for methods to be fast, general, cheap, robust and scalable. I summarise current applications of LAMP, discuss why it is not more widely used and elaborate potential for adopting it more widely.

The report is aimed at readers who are interested in preventing (catastrophic) pandemics and who might have skills to further the development and wider adoption of LAMP. I expect readers with such skills to come from various backgrounds, which is why the report is set out to be understandable without a background in biology. Feel free to skip any parts that you are already familiar with.

Full project

You can read the full project here.

Footnotes

1. 80.000 Hours. Preventing catastrophic pandemics – 80,000 Hours. https://80000hours.org/problem-profiles/preventing-catastrophic-pandemics/ (2023).

2. 80.000 Hours. What are the most pressing world problems? https://80000hours.org/problem-profiles/ (2023).

3. He won the Nobel Prize in Chemistry for his discovery.

4. Notomi, T. et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 28, 63 (2000).

5. Roberts, P. LAMP Part 1: Advantages, Limitations and Future Prospects. https://www.youdobio.com/lamp-part-1-advantages-limitations-and-future-prospects/ (2021).