Tuesday, 30 June 2020

Holistic contamination control is central to revised EU GMP Annex 1

The main focal points from the 2020 draft of EU GMP Annex 1 (titled “Manufacture of Sterile Products”) signal to sterile products manufacturers a shift in regulatory thinking towards environmental controls rather than an over-reliance upon monitoring; with risk-based scientific thinking; and looking at contamination control holistically. The main themes are:

  • The expectation for each facility to have in place a formal, holistic contamination control strategy, focused on minimizing contamination control with respect to sterile manufacturing.
  • Additional requirements for cleanroom classification (beyond ISO 14644 requirements).
  • A major focus on risk-based approaches.
  • Recommendations for the wider use of barrier technology.
  • A strong focus on personnel controls, such as gowning, and training.

In relation to this, Tim Sandle has written an article. The reference is:

Sandle, T. (2020) 2020 Annex 1 Draft: Holistic Changes, Cleanroom Technology, 28 (5): 25-27

This article looks into some of the likely changes that will impact sterile products manufacturers, which can help organisations to stay ahead of the regulatory curve.

For details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 29 June 2020

COVID-19 and dental practice

Nobody could fail to miss the media coverage about novel coronavirus COVID-19, with daily and sometimes hourly updates about the ‘killer virus’. What exactly does it mean for dental practices in the UK?

In relation to this, Tim Sandle has written an article. Here is an extract:

"As coronaviruses have a lipid envelope, a wide range of disinfectants are effective. Human coronaviruses can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. A virucidal, ethanol-based disinfector/cleaner such as mikrozid liquid could play a useful role in the cleaning and disinfection of hard surfaces, particularly as it is effective against enveloped viruses within one minute."

The reference is:

Sandle, T. (2020) COVID-19 and dental practice, Dental Nursing, April 2020, pp2-3: https://www.magonlinelibrary.com/doi/full/10.12968/denn.2020.16.4.194

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 28 June 2020

Presence of microbial DNA in blood may indicate signs of cancer

A new study indicates that looking for signs of certain microbial DNA in a patient's blood may be tell-tale sign of cancer. The discovery could help to advance cancer detection.

The new technique, which comes from the University of California - San Diego, works on the basis of a straightforward blood draw. When the blood is analyzed, the presence of microbial DNA could reveal whether the patient has cancer and then which type of cancer. The technique has produced accurate results, even for detecting signs of cancer at the early stages.
The basis of the technique came from an earlier study where it was shown that microorganisms invaded a majority of pancreatic cancers. In addition, certain types of microbes were found to be able to break down chemotherapy drugs. This led to the idea that examining a patient's microbiome could play a role in cancer detection.
This represented a shift in thinking, according to one of the scientists involved, Professor Rob Knight, who says: "Almost all previous cancer research efforts have assumed tumors are sterile environments, and ignored the complex interplay human cancer cells may have with the bacteria, viruses and other microbes that live in and on our bodies."
To develop the technique, the researchers examined 18,116 tumor samples, drawn from 10,481 patients. The patients had 33 different cancer types. By using a computer model, the analysis of the data revealed a series of distinct microbial signatures associated with specific cancer types.
For example, there was a connection between the bacterium Fusobacterium species and gastrointestinal cancers. The anaerobic Gram-negative organism has previously been linked with skin ulcers. As a second example, the researchers found an association between Faecalibacterium species and colon cancer. This Gram-positive anaerobe has previously been linked with Crohn's disease.
Such data is now being used to develop machine learning algorithms and with this the potential for a new, rapid cancer detection technology based on liquid biopsies.
The research has been published in the science journal Nature. The peer-reviewed study is titled: "Microbiome analyses of blood and tissues suggest cancer diagnostic approach."

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 27 June 2020

Artificial intelligence finds new antibiotic

Technologists, working with microbiologists, have made a significant breakthrough in the hunt for new antimicrobials. By using artificial intelligence, a new candidate antibiotic has been identified.

The discovery was made using a machine-learning algorithm. This technology enabled scientists to discover a powerful new antibiotic compound.

The importance of the antibiotic has been shown through various tests, where the chemical was challenged against several disease-causing bacteria. Among the microbial cohort were some organisms previously identified to be resistant to mot antibiotics. Further studies were undertaken using mice, yielding similarly successful results.

READ MORE: Genetic testing can identify antibiotic resistance

The reason why there is strong scientific interest in finding new antibiotics is due to the phenomenon of antimicrobial resistance. This is a significant global health issue since the pace at which bacteria are becoming resistant to common antibiotic treatments is increasing. This means that infections that were once easy to treat are no longer certain of being tackled through existing medications. The consequence is that routine operations or transplants now present additional risks.

With the new discovery from MIT, the algorithm processed millions of chemical compounds, processing this vast data set in just a few days. This approach also avoided the necessity of running thousands of experiments; only those compounds selected by the machine learning program as having strong potential need be tested.

The use of computer models for drug screening and other applications is captured by the term “in silico.”

According to lead researcher Professor James Collins: “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.”

He molecule selected has been named halicin (with a reference to the computer in 2001: A Space Odyssey). The drug was shown to be effective against Escherichia coli, as part of the tests. Further bacterial killing effects were demonstrated using other organisms of concern, such as Clostridium difficile, Acinetobacter baumannii, and Mycobacterium tuberculosis.

The bacterial killing properties of halicin arise from the compound’s ability to disrupt the electrochemical gradient across bacterial cell membranes, which triggers cell death.

ALSO READ: Antibiotic use may lead to heart problems

The research has been published in the journal Cell. The research paper is titled “A Deep Learning Approach to Antibiotic Discovery.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday, 26 June 2020

Life Science Blogs To Follow

From BioPharma Trends:

"We have decided to summarize a list of niche blogs, mostly personal, run by the Life Science professionals - scientists, business leaders. Such blogs often provide personalized insights into certain areas of drug discovery, biotech, and business, which are not properly covered by the mainstream media, or covered in very general strokes. Reading blogs is a great way to explore nuances of the industry -- through the prism of personal opinions and experiences of the authors."

I'm pleased that this website - Pharmaceutical Microbiology resources - is featured in the list:

Pharmaceutical Microbiology

The site was created by Dr. Tim Sandle in 2009 to discuss pharmaceutical microbiology and healthcare. The posts are published every day. There is a lot of interesting information regarding microbes, bacteria, and disinfection, laboratory techniques, vaccines, antibiotics, and more. Sometimes, Dr. Sandle creates videos, where he explains different topics, including the latest series related to the COVID_19 pandemic.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 25 June 2020

Additional safety protections relating to COVID-19 for faecal microbiota transplant (FMT) products

The Australian TGA has issued a document titled “Additional safety protections relating to COVID-19 for faecal microbiota transplant (FMT) products.”

The Therapeutic Goods Administration (TGA) is providing advice on safety protections to faecal microbiota transplant (FMT) providers since there is the potential to transmit the SARS-CoV-2 virus via FMT through shedding in stool.

FMT products comprise, contain, or are derived from donated human stool and are introduced into a recipient person for a therapeutic use. Human stool is collected from a screened donor by defaecation. This stool is then processed into an FMT product and provided to the recipient via enema, colonoscopy, nasoenteric tube, or orally (e.g. capsules).

This advice follows a recent safety alert from the US FDA that highlighted the additional safety precautions that should be in place for COVID-19 disease screening of potential stool donors for FMT products in order to prevent the spread of the SARS-CoV-2 virus.

See: https://www.tga.gov.au/alert/additional-safety-protections-relating-covid-19-faecal-microbiota-transplant-fmt-products

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 24 June 2020

Compilation of QRD decisions on stylistic matters in product information

The European Medicines Agency has issued a compilation of ‘stylistic matters in product information’.

The document can be found here: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/compilation-quality-review-documents-decisions-stylistic-matters-product-information_en.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 23 June 2020

Advanced therapy medicinal products: Overview

The European Medicines Agency has issued guidance on Advanced therapy medicinal products. Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer ground-breaking new opportunities for the treatment of disease and injury.

ATMPs can be classified into three main types:

gene therapy medicines: these contain genes that lead to a therapeutic, prophylactic or diagnostic effect. They work by inserting 'recombinant' genes into the body, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases. A recombinant gene is a stretch of DNA that is created in the laboratory, bringing together DNA from different sources; somatic-cell therapy medicines: these contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. They can be used to cure, diagnose or prevent diseases; tissue-engineered medicines: these contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue.

In addition, some ATMPs may contain one or more medical devices as an integral part of the medicine, which are referred to as combined ATMPs. An example of this is cells embedded in a biodegradable matrix or scaffold.

See: https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overview

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 22 June 2020

MHRA: Feedback from GMP inspections

To assist pharmaceutical manufacturers and distributors to understand the areas where good manufacturing practice (GMP) inspectors have found compliance problems during GMP inspections in the UK and overseas, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) GMP Inspectorate has issued data, during October 2019, relating to common deficiencies from previous GMP inspections conducted during 2018.

While the anonymised raw data provided by the GMP Inspectorate is of general interest, additional analysis is required to draw meaningful inferences. In this article, the data has been reviewed and presented, in order to obtain an overview of key trends.

These trends have bene captured in an article, written by Tim Sandle for GMP Review. The reference is:

Sandle, T. (2019) MHRA: Feedback from GMP inspections, GMP Review, 18 (3): 8-14

For further details, please contact Tim Sandle.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 21 June 2020

Detecting anti-virus antibody in 20 minutes

Researchers have succeeded in detecting anti-avian influenza virus antibody in blood serum within 20 minutes, using a portable analyzer they have developed to conduct rapid on-site bio tests. If a suitable reagent is developed, this technology could be used to detect antibodies against SARS-CoV-2, the causative virus of COVID-19.

Avian influenza is a poultry disease caused by influenza A virus infection. Rapid initial response for a suspected infection and continuous surveillance are essential to mitigate the damage from highly pathogenic, transmittable pathogens such as avian influenza viruses.
Generally, the polymerase chain reaction (PCR) method is used to detect the viral genome, but its complicated procedure requires a considerable amount of time. Another method involves detecting antibodies produced in the body in reaction to virus infection. However, widely used antibody detection methods can be inaccurate because the antibodies' existence is generally determined by eyesight.

Researchers have developed a new method and analyzer capable of rapid, facile and selective detection of antibodies. The method is based on conventional fluorescence polarization immunoassay (FPIA) but applies a different measurement mechanism to make the analyzer much smaller and portable. The analyzer weighs only 5.5 kilograms.

The combined use of liquid crystal molecules, an image sensor and the microfluidic device makes it possible to simultaneously examine multiple samples and reduces the volume of each sample required. Liquid crystal molecules are capable of controlling the polarization direction of fluorescent light, while the microfluidic device has a number of microchannels as a measurement vessel.

The group also developed a reagent to detect anti-H5 avian influenza virus antibody, a fluorescein-labeled protein that binds only with the antibody. The reagent was made by reproducing hemagglutinin (HA) protein fragments, which are expressed on the surface of H5 avian influenza virus, through gene recombination and by labeling fluorescent molecules to the fragments.

Keine Nishiyama, Yohei Takeda, Masatoshi Maeki, Akihiko Ishida, Hirofumi Tani, Koji Shigemura, Akihide Hibara, Yutaka Yonezawa, Kunitoshi Imai, Haruko Ogawa, Manabu Tokeshi. Rapid detection of anti-H5 avian influenza virus antibody by fluorescence polarization immunoassay using a portable fluorescence polarization analyzer. Sensors and Actuators B: Chemical, 2020; 316: 128160 DOI: 10.1016/j.snb.2020.128160

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 20 June 2020

Microbial cyborgs: Bacteria supplying power

One day "microbial cyborgs" might be used in fuel cells, biosensors, or bioreactors. Scientists of Karlsruhe Institute of Technology (KIT) have created the necessary prerequisite by developing a programmable, biohybrid system consisting of a nanocomposite and the Shewanella oneidensis bacterium that produces electrons. The material serves as a scaffold for the bacteria and, at the same time, conducts the microbially produced current.

The bacterium Shewanella oneidensis belongs to the so-called exoelectrogenic bacteria. These bacteria can produce electrons in the metabolic process and transport them to the cell's exterior. However, use of this type of electricity has always been limited by the restricted interaction of organisms and electrode. Contrary to conventional batteries, the material of this "organic battery" does not only have to conduct electrons to an electrode, but also to optimally connect as many bacteria as possible to this electrode. So far, conductive materials in which bacteria can be embedded have been inefficient or it has been impossible to control the electric current.

Researchers have succeeded in developing a nanocomposite that supports the growth of exoelectrogenic bacteria and, at the same time, conducts current in a controlled way. "We produced a porous hydrogel that consists of carbon nanotubes and silica nanoparticles interwoven by DNA strands," Niemeyer says. Then, the group added the bacterium Shewanella oneidensis and a liquid nutrient medium to the scaffold. And this combination of materials and microbes worked. "Cultivation of Shewanella oneidensis in conductive materials demonstrates that exoelectrogenic bacteria settle on the scaffold, while other bacteria, such as Escherichia coli, remain on the surface of the matrix," microbiologist Professor Johannes Gescher explains. In addition, the team proved that electron flow increased with an increasing number of bacterial cells settling on the conductive, synthetic matrix. This biohybrid composite remained stable for several days and exhibited electrochemical activity, which confirms that the composite can efficiently conduct electrons produced by the bacteria to an electrode.

Such a system does not only have to be conductive, it also must be able to control the process. This was achieved in the experiment: To switch off the current, the researchers added an enzyme that cuts the DNA strands, as a result of which the composite is decomposed.


Yong Hu, David Rehnlund, Edina Klein, Johannes Gescher, Christof M. Niemeyer. Cultivation of Exoelectrogenic Bacteria in Conductive DNA Nanocomposite Hydrogels Yields a Programmable Biohybrid Materials System. ACS Applied Materials & Interfaces, 2020; 12 (13): 14806 DOI: 10.1021/acsami.9b22116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday, 19 June 2020

Terrestrial bacteria can grow on nutrients from space

For this study, four non-fastidious environment-derived bacterial species with pathogenic features were selected, including Klebsiella pneumoniae and Pseudomonas aeruginosa. A minimal 'diet' based on nitrogen, phosphorus, sulphur, iron and water to which carbohydrates found in carbonaceous meteorites were added was made to determine whether extraterrestrial survival and growth were possible. The four bacterial species were shown to survive and multiply on this minimal 'diet'.

In follow-up experiments, the team of researchers observed that the adaptation of bacteria, especially in the case of K. pneumoniae, caused changes in the cell membrane -- the shell of the cell -- as a result of which the immune system reacted more strongly to the bacteria. In short, the bacteria become more immunogenic. Research in cell culture, but also in mice, showed that the bacteria survive on extra-terrestrial nutrients and become less virulent as a result of this necessary adaptation. At the same time, this research shows that bacteria can survive under these conditions, which means that the risk of infection among space travellers remains, precisely because -- as other researchers have shown -- a space journey has negative effects on the functioning of the immune system, making astronauts more susceptible to infections.


Jorge Domínguez-Andrés, Marc Eleveld, Georgios Renieris, Thomas J. Boltje, Rob J. Mesman, Laura van Niftrik, Sam J. Moons, Petra Rettberg, Jos W.M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Huub J.M. Op den Camp, Marien I. de Jonge, Mihai G. Netea. Growth on Carbohydrates from Carbonaceous Meteorites Alters the Immunogenicity of Environment-Derived Bacterial Pathogens. Astrobiology, 2020; DOI: 10.1089/ast.2019.2173

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 18 June 2020

Evolution of coronavirus SARS-CoV-2

A team of scientists studying the origin of SARS-CoV-2, the virus that has caused the COVID-19 pandemic, found that it was especially well-suited to jump from animals to humans by shapeshifting as it gained the ability to infect human cells.

Conducting a genetic analysis, researchers from Duke University, Los Alamos National Laboratory, the University of Texas at El Paso and New York University confirmed that the closest relative of the virus was a coronavirus that infects bats. But that virus's ability to infect humans was gained through exchanging a critical gene fragment from a coronavirus that infects a scaly mammal called a pangolin, which made it possible for the virus to infect humans.

The researchers report that this jump from species-to-species was the result of the virus's ability to bind to host cells through alterations in its genetic material. By analogy, it is as if the virus retooled the key that enables it to unlock a host cell's door -- in this case a human cell. In the case of SARS-CoV-2, the "key" is a spike protein found on the surface of the virus. Coronaviruses use this protein to attach to cells and infect them.

Very much like the original SARS that jumped from bats to civets, or MERS that went from bats to dromedary camels, and then to humans, the progenitor of this pandemic coronavirus underwent evolutionary changes in its genetic material that enabled it to eventually infect humans.

The researchers said tracing the virus's evolutionary pathway will help deter future pandemics arising from the virus and possibly guide vaccine research. The researchers found that typical pangolin coronaviruses are too different from SARS-CoV-2 for them to have directly caused the human pandemic.


Xiaojun Li, Elena E. Giorgi, Manukumar Honnayakanahalli Marichannegowda, Brian Foley, Chuan Xiao, Xiang-Peng Kong, Yue Chen, S. Gnanakaran, Bette Korber, Feng Gao. Emergence of SARS-CoV-2 through recombination and strong purifying selection. Science Advances, May 29, 2020: eabb9153 DOI: 10.1126/sciadv.abb9153

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 17 June 2020

How bacteria purge toxic metals

In E. coli bacterium, the inner membrane sensor protein CusS mobilizes from a clustered form upon sensing copper ions in the environment. CusS recruits the transcription regulator protein CusR and then breaks down ATP to phosphorylate CusR, which then proceeds to activate gene expression to help the cell defend against the toxic copper ions.

Cornell researchers combined genetic engineering, single-molecule tracking and protein quantitation to get a closer look at this mechanism and understand how it functions. The knowledge could lead to the development of more effective antibacterial treatments.

The bacteria's resistance is actually a tag-team operation, with two proteins working together inside the cell. One protein (CusS), in the inner membrane, senses the presence of the chemical or metal and sends a signal to a regulator protein (CusR) in the cytosol, or intercellular fluid. The regulator protein binds to DNA and activates a gene that generates transport proteins, which purge the toxin from the cell.

Microbiologists analyze these functions by using biochemical assays that remove the protein from the cell. However, that process prevents the scientists from observing the proteins in their native environment, and certain details, such as the spatial arrangement between proteins, have remained murky.

For a deeper analysis, researchers used single-cell imaging, whereby they tagged individual proteins in living E. coli with a fluorescent signal and imaged the proteins one at a time, tracking their motions. The procedure yielded millions of images and, ultimately, a finely detailed, qualitative map of the proteins' movement.


Bing Fu, Kushal Sengupta, Lauren A. Genova, Ace George Santiago, Won Jung, Łukasz Krzemiński, Udit Kumar Chakraborty, Wenyao Zhang, Peng Chen. Metal-induced sensor mobilization turns on affinity to activate regulator for metal detoxification in live bacteria. Proceedings of the National Academy of Sciences, 2020; 201919816 DOI: 10.1073/pnas.1919816117

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 16 June 2020

Efficient biosolar cells modelled on nature

Potential sources of renewable energy include protein complexes that are responsible for photosynthesis. However, their efficiency in technical applications still leaves much to be desired. For example, they cannot convert green light into energy. A research team has successfully closed this so-called green gap by combining a photosynthesis protein complex with a light-collecting protein from cyanobacteria.

Biosolar cells are an innovative concept for converting sunlight into electrical energy. They are manufactured using biological components from nature. At their core are so-called photosystems: large protein complexes that are responsible for energy conversion in plants, algae and cyanobacteria. Photosystem II, PSII for short, plays a central role in the process, because it can use water as an electron source for the generation of electricity.

The researchers stabilised these super complexes using short-chain chemical crosslinkers that permanently fix the proteins at a very short distance from each other. In the next step, they inserted them into appropriate electrode structure.

This design enabled the researchers to use twice as many photons within the green gap, compared to a system without any light collection complexes.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 15 June 2020

Endotoxin control in depyrogenation tunnels

Understanding the way glassware is depyrogenated and how high concentrations of endotoxin can be used to assess how well depyrogenation tunnels are functioning is key to quality control.

In a new article, Tim Sandle explains:

Sandle, T. (2020) Endotoxin control in depyrogenation tunnels, Cleanroom Technology, February 2020. At: https://www.cleanroomtechnology.com/news/article_page/Endotoxin_control_in_depyrogenation_tunnels/162489

Here is an extract:

“The regulatory standard for validation of an endotoxin inactivation (depyrogenation) process is that it should be capable of reducing an endotoxin challenge through 3 log10 reduction. To ensure this limit works, it is required to clean materials before dry heat depyrogenation with WFI. Otherwise, at least in theory, you could have an item contaminated with 10,000 endotoxin units (EU) entering a validated endotoxin inactivation process and still emerging with 10 EU intact and ready to contaminate your product.

Dry heat depyrogenation is a complex process and is still poorly understood with contradictory research data. The phenomenon that complicates the picture is that inactivation may approximate to Second Order chemical kinetics with a high initial rate of inactivation, then tail off to nothing. In practice, this means that at any particular depyrogenating temperature you will get some degree of inactivation in some period of time or other, but beyond that point, you will get no further inactivation by holding the material at that temperature.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 14 June 2020

Observing a continuous pathway to building blocks of life

A new study conducted by scientists at the Institute for Advanced Study, the Earth-Life Science Institute (ELSI), and the University of New South Wales marks an important step forward in the effort to understand the chemical origins of life. The findings of this study demonstrate how "continuous reaction networks" are capable of producing RNA precursors and possibly ultimately RNA itself -- a critical bridge to life.

While many of the mechanisms that propagate life are well understood, the transition from a prebiotic Earth to the era of biology remains shrouded in mystery. Previous experiments have demonstrated that simple organic compounds can be produced from the reactions of chemicals understood to exist in the primitive Earth environment. However, many of these experiments relied on coordinated experimenter interventions. This study goes further by employing a model that is minimally manipulated to most accurately simulate a natural environment.

To conduct this work, the team exposed a mixture of very simple small molecules -- common table salt, ammonia, phosphate, and hydrogen cyanide -- to a high energy gamma radiation source. These conditions simulate radioactive environments made possible by naturally occurring radioactive minerals, which were likely much more prevalent on early Earth. The team also allowed the reactions to intermittently dry out, simulating evaporation in shallow puddles and beaches. These experiments returned a variety of compounds that may have been important for the origins of life, including precursors to amino acids and other small compounds known to be useful for producing RNA.

The authors use the term "continuous reaction network" to describe an environment in which intermediates are not purified, side products are not removed, and no new reagents are added after the initial starting materials. In other words, the synthesis of molecules occurs in a dynamic environment in which widely varied compounds are continuously being formed and destroyed, and these products react with each other to form new compounds.

Future work will focus on mapping out reaction pathways for other chemical substances and testing whether further cycles of radiolysis followed by dry-down can generate higher order chemical products.


Ruiqin Yi, Quoc Phuong Tran, Sarfaraz Ali, Isao Yoda, Zachary R. Adam, H. James Cleaves, Albert C. Fahrenbach. A continuous reaction network that produces RNA precursors. Proceedings of the National Academy of Sciences, 2020; 201922139 DOI: 10.1073/pnas.1922139117

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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