Dear All,
Pop culture often garbles science in the name of a good storyline but sometimes the truth is stranger than fiction. Let’s today consider the iconic trope of being frozen in time and coming back to life. This sort of feat is usually limited on the screen to the likes of superheroes but a recent report caught my eye regarding the potential for bacteria to snooze through the millennia. Read on…
In November 1980, a Texaco oil rig team in southern Louisiana made a mistake. The team was looking for oil at Lake Peigneur and were aware that there was a salt mine deep beneath the deposits they were seeking. Salt mines are not unusual in petroleum geology and this one raised no concerns until the drill seized, the rig began to fall into the 10-foot deep freshwater lake, and all workers had to jump off to swim to shore. Yow!
Meanwhile in the salt mine below, water was pouring into the mine and its 50 miners knew they didn’t have long to escape from the rapidly filling mine. Luckily no one died! But the 150-foot-high rig sank entirely in less than 2 hours and the lake quickly became an enormous whirlpool sucking down “11 barges, a tug boat, parking lots, 35 hectares of lake front and a portion of a mansion.”
In short order, the entirety of Lake Peigneur’s freshwater was now in the salt mine and was now brackish! The connecting canal that had formerly served to drain the lack began to flow backwards! Seawater direct from the Gulf of Mexico came rushing in! The force of the water was so intense that there was a temporary 167-foot waterfall within the mine and occasional 400-foot geysers!! In the official report, it wasn’t clear if the mistake was from drilling in the wrong place or incorrect maps but the company paid their fines and the former shallow freshwater lake was now a 200-foot-deep saltwater lake.
Now over 40 years later, in a paper by Vreeland et all., it turns out that this human error lead to the awakening of an ancient bacterium. As also summarized in the original paper and as well as an article in the Economist, local scientists were allowed into the flooded mine in 1987 to study the salinity of the water. It was known that the original lake had less than 2% salt. As the rock salt being mined dissolves quickly in water, an increase in the salinity was expected but the new salt content was 32% — almost on par with the Dead Sea’s 34% salt content! And remarkably, a new bacterial species from the class Halobacteria (halo– meaning sea salt) was found alive and well in that incredibly salty water. Indeed, it turned out that this new species grew best at 18% salinity and died when salinity went below 10%. Knowing the lake was only 2% previously, there is no way it could have been alive before the accident. So, how did it get there?
Answer: It seems likely that it had always been there. The salt deposits that were under the lake had formed when a previous salty body of water dried up some 125 million years ago. Trapped in water pockets within the salt crystals, it happily avoided damage to its DNA from oxygen, sunlight, and background radiation until it was freed by the accident.
Amazing! This story reminded me of the way that Acinetobacter baumannii can survive desiccation for months, according to this paper by Green et al. “Remarkably, A. baumannii grown to early-stationary phase retained nearly 100% viability after several days of desiccation, and a fraction of the starting population remained viable after 7 months of desiccation.”
But, I have to say that surviving a few months seems almost trivial by comparison to the 125m-year nap taken by the bacterium described by Vreeland et al. Truly life is stranger than fiction. And, these incidents are not isolated to bacteria: the possibility of similar events with viruses has been raised! To quote the fictional Dr. Ian Malcolm of Jurassic Park, “life finds a way!” … and we better have our antibiotics ready!
All best wishes, –jr
John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.
Postscript 1: Lake Peigneur has been relatively quiet since it became the deepest lake in Louisiana and, while it seems the Rip Van Winkle Gardens on the lakeshore must have been in honor of the new bacteria, the gardens were named for an actor who played Rip Van Winkle, the American folklore character who took a 20-year nap, over 4500 times in the 19th century. Perhaps they need to have an honorable mention for the lake’s naturally occurring version of Rip Van Winkle?
Postscript 2: I have to note that Vreeland et al. had had previously succeeded in reviving a salt-preserved, 250-million-year-old strain of Bacillus! See also this Nature article from 2000. Amazing!
Postscript 3 (added 27 Jan 2024): As another example of the startling resilience of some bacteria, the spores of anthrax (Bacillus anthracis) are known to persist for years. As excerpted from Bacillus by J.E. Thwaite, H.S. Atkins, in Medical Microbiology (18th Ed., 2012):
- “Artificial contamination of Gruinard Island off the northwest coast of Scotland occurred in 1942–1943 as a result of tests of a biological warfare bomb containing live anthrax spores.
- “Even by 1979 spores could still be detected in a 3-hectare area of the island.
- “In the 1980s the area was decontaminated by burning the vegetation and spraying with 5% formaldehyde in seawater.”
- BARDA’s long-running BAA (Broad Agency Announcement) for medical countermeasures (MCMs) for chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza, and emerging infectious diseases is now BAA-23-100-SOL-00004 and offers support for both antibacterial and antifungal agents (as well as antivirals, antitoxins, diagnostics, and more). Note especially these Areas of Interest: Area 3.1 (MDR Bacteria and Biothreat Pathogens), Area 3.2 (MDR Fungal Infections), and Area 7.2 (Antibiotic Resistance Diagnostics for Priority Bacterial Pathogens). Although prior BAAs used a rolling cycle of 4 deadlines/year, the updated BAA released 26 Sep 2023 has a 5-year application period that ends 25 Sep 2028 and is open to applicants regardless of location: BARDA seeks the best science from anywhere in the world! See also this newsletter for further comments on the BAA and its areas of interest.
- FDA have released a BAA covering a wide variety of regulatory topics. See this newsletter for general details; also note in particular an RFP for work on urine-specific breakpoints for uUTI. Early concept papers are due 6 Nov 2023; full proposals are due 19 Feb 2024.
- NIAID have a BAA open through 13 Mar 2024 for projects covering vaccines, therapeutics vs. selected pathogens (specific viruses, fungi, and bacteria), and sequencing-based diagnostics. See this newsletter for further details.
- JPIAMR have an AMR Interventions call that is open for pre-applications through 14 Mar 2024. The call covers interventions for both fungi and bacteria. Go here for full details. Note that there is an informational 24 Jan 2024 webinar for applicants.
- ARPA-H have an Open BAA that is accepting applications through 14 March 2024. It is quite wide-ranging in its scope and definitely includes AMR-related projects. See this newsletter for discussion of the BAA and an AMR project that it now supports.
- HERA Invest was launched August 2023 with €100 million to support innovative EU-based SMEs in the early and late phases of clinical trials. Part of the InvestEU program supporting sustainable investment, innovation, and job creation in Europe, HERA Invest is open for application to companies developing medical countermeasures that address one of the following cross-border health threats: (i) Pathogens with pandemic or epidemic potential, (ii) Chemical, biological, radiological and nuclear (CBRN) threats originating from accidental or deliberate release, and (iii) Antimicrobial resistance (AMR). Non-dilutive venture loans covering up to 50% of investment costs are available. A closing date is not posted insofar as I can see — applications are accepted on a rolling basis; go here for more details.
- The ENABLE-2 consortium has announced a call to support hit-to-lead compound development by researchers at publicly-funded European universities. The call is focused on molecules with the potential to be direct-acting therapies for one or more of the following priority pathogens: ESBL-producing/carbapenem-resistant Enterobacteriaceae (E. coli, K. pneumoniae), P. aeruginosa, A. baumannii, methicillin-resistant S. aureus, or vancomycin-resistant E. faecium. The Call is open continuously, applications are reviewed at intervals, and funding is non-dilutive. Expressions of interest received before 30 Sep 2023 would be considered in November 2023. Applications received after this date will be evaluated in the spring of 2024 (date to be decided). Go to https://www.ilk.uu.se/enable2/apply/ for further details.
- The AMR Action Fund is open on an ongoing basis to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
- INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
- These things aren’t sources of funds but would help you develop funding applications
- AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
- The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
- Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
- In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).
John’s Top Recurring Meetings
Virtual meetings are easy to attend, but regular attendance at annual in-person events is the key to building your network and gaining deeper insight. My personal favorites for such in-person meetings are below. Of particular value for developers are the AMR Conference and the ASM-ESCMID conference. Hope to see you there!
- 6-7 Mar 2024 (Basel, Switzerland): The 8th AMR Conference 2024. Go here to register!
- 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details.
- 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here for the meeting’s general website. You can’t register (yet) for the 2024 event, but save the date!
- 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. Save the date! More details to come!
Upcoming meetings of interest to the AMR community:
- [Post-meeting video available] 12 Dec 2023 (virtual, 1-2.15p ET): Duke-Margolis held the third and final installment of their webinar series for policymakers combating AMR with a webinar entitled “Improving Regulatory Practices to Sustain Antibiotic Innovation.” The webinar featured perspectives from experts affiliated with the FDA, Industry, GARDP, CARB-X, and the Center for Global Development. The webinar was excellent and is available for streaming; prior webinars occurred on 9 May 2023 on the Need for New Antibiotics, and on 29 Aug 2023 on Preparedness for AMR Threats (also see their related October 2023 report on Preparedness and Post-Market Incentives for Novel Antibiotics).
- 6-7 Feb 2024 (online): Antimicrobial Chemotherapy Conference. This is an annual, free of charge conference that is co-organized by GARDP and the British Society for Antimicrobial Chemotherapy (BSAC). Go here to register.
- 8 Feb 2024 (in person, Liverpool, UK, 8.30a – 4p): 2024 BioInfect Conference. A full-day AMR conference that includes a keynote from Lord Jim O’Neill (Chairman of the UK AMR Review). Go here for details and to register.
- [NEW] 14 Feb 2024 (virtual, 8-9a EST): GARDP’s “SECURE: Improving access to antibiotics through new economic models” webinar about the SECURE project. Click here to register.
- [NEW and HIGHLY RECOMMENDED] 15 Feb 2024 (virtual, 8.30a-10.00a EST, 2.30-4p CET, 10.30p-12.00a JST): Entitled “AMR Preparedness Index: 2024 Progress Report”, this will be the launch of a major report by the Global Coalition on Aging (GCOA) and IDSA, and sponsored by IFPMA. Speakers are global (US, EU, Brazil) and feature Dame Sally Davies (UK Special Envoy for AMR) plus a panel moderated by Andrew Jack (Financial Times, creator of a marvelous 5-minute AMR video explainer); the discussion will focus on high-level policy insights from the report in advance of the eagerly anticipated High-Level Meeting on AMR at UNGA 2024 (see 15 Apr 2023 newsletter for background on the HLM). Go here to register. For more on GCOA’s work on AMR, click here.
- [NEW] 27 Feb 2024 (virtual, 8.30a-9.30a EST): GARDP’s “What does the future look like if pull incentives to support antibiotic R&D are insufficient?” webinar. Go here for details.
- 27 Feb 2024 (in person, New York City, 3-6.30p ET): Hosted by the AMR Industry Alliance (AMRIA), “A Call-to-Action in the Fight Against AMR: Priorities for Progress at the 2024 UN High-level Meeting on AMR” is a symposium (3-5.30p) and reception (5.30-6.30p). Precise details are pending … for now, we are advised to hold the date. I’ll post updates as I receive them … presumably this will also appear on AMRIA’s website.
- 6-7 Mar 2024 (Basel, 6-7 Mar 2024): See Recurring Meetings list, above.
- 17-22 Mar 2024 (Ventura Beach, CA, in person): Gordon Research Conference (GRC) entitled “New Antibacterial Discovery and Development” with a 16-17 Mar 2024 pre-conference Gordon Research Seminar (GRS) for young doctoral and post-doctoral researchers. An intensive residential meeting, GRCs are highly recommended for networking and deep research insights. Apply here for the GRC and here for the GRS.
- 26 Apr 2024 (Barcelona, Spain): ESCMID workshop entitled “Using Data Science and Machine Learning for Infection Science: A Hands-on Introduction.” Click here to register or here for more details.
- 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
- 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
- 9-13 June 2024 (in person, Ascona, Switzerland): “New Approaches to Combat Antibiotic-Resistant Bacteria, 2nd Edition” is a Sunday-Thursday residential workshop focused on the deep biology of AMR. Sponsored by NCCR AntiResist (a Swiss National Science Foundation consortium), the scientific program has the feel of a Gordon Conference. Space is limited, so you are encouraged to apply promptly — go here for details.
- 13-17 June 2024 (Atlanta, Georgia): ASM Microbe, the annual meeting of the American Society for Microbiology. You can’t register yet, but you can go here for general details.
- 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. See Recurring Meetings list, above.
- 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. See Recurring Meetings list, above.
- 19-27 Oct 2024 (Annecy, France, residential in-person program): ICARe (Interdisciplinary Course on Antibiotics and Resistance). Now in its 8th year, Patrice Courvalin directs the program with the support of an all-star scientific committee and faculty. The resulting soup-to-nuts training covers all aspects of antimicrobials, is very intense, and routinely gets rave reviews! Seating is limited, so mark your calendars now if you are interested. Applications open in March 2024 — go here for more details.
