Cinema to Inspire Antibiotic Discovery: Holiday Edition

Dear All,

The holidays are upon us, and this seems like a timely reason to send an update to the Movies to Discover Antibiotics By newsletter from 2020. Since sending that particular newsletter, suggestions from readers have been added to the list and I’ve also created YouTube videos exploring some of them. If you are in search of some cinematic recommendations this holiday season, here is a list that will entertain and inspire your antibiotic-related activities:

In the mood for a who-dunnit?

  • The Third Man is based on a novel by Graham Greene and is considered to be one of the best films of all time. Set in Vienna in the late 1940s, just after the end of World War II, the book and movie are based on a real-life story about sales of counterfeit penicillin. Penicillin was very scarce at the time, highly prized, and hence a tempting opportunity for the ever-present counterfeit drug industry. For a quick summary, see the YouTube vignette from our Antibiotics Could Have Changed the Plot series). There is also a superb BMJ article (link) that provides an extended discussion of the backstory. 

A fan of America’s iconic Wild West? 

Need a holiday action movie that isn’t Die Hard? (And yes, Die Hard is a holiday movie!)

  • Raiders of the Lost Ark has a behind-the-scenes antibiotic story from filming the famous 1930s Cairo marketplace scene when Indiana (Harrison Ford) confronts a master swordsman. The original plan in the script was for an extended duel pitting Indiana’s whip against his foe’s whirling sword … but Harrison Ford was so ill at the time with a GI syndrome (said to have been dysentery … no further details) that he really did not have the strength to film the planned scene! It was the summer of 1980, the crew had gone to a lot of trouble to be in a great desert location …. what to do? Well, Ford and Spielberg agreed to cut the scene down to a gunshot, with Ford saying to Spielberg, “Let’s just shoot the sucker.” And thus was created one of the most memorable scenes in a memorable movie … I can still remember the startled amazement I felt the first time I saw that scene! I have no idea what antibiotic(s) he received, but I’m sure at least one was involved — if you look closely, Ford really does not look very well. Go here for an additional article, here for a YouTube vignette from our Antibiotics Could Have Changed the Plot series, here for a YouTube interview with Terry Richards, the stuntman who played the swordsman, and here for an informative article (sadly, his obituary) on Mr. Richards.

Want some drama?

Sci-fi fan?

  • The Martian staring Matt Damon would have been an awful lot shorter without antibiotics! I made a very short YouTube video about this as the book by Andy Weir has the antibiotic mention rather than the film. 
  • 2001: A Space Odyssey is based on a book by Arthur C. Clarke and is part of the inspirations for the newsletter series Chemicals vs Drugs. Filmed in 1968 and set mostly in the near-future of 2001, we meet HAL, the deep-thinking computer who drives a key plot element. Coming back from 2001 to the present (!!), we have the 2020 paper by Stokes et al. in which machine-learning is explored as a tool for antibiotic discovery. Halicin, the resulting compound, was named after HAL and served as the idea for the cover of that issue of Cell. Although halicin probably isn’t a systemic antibiotic, the ideas behind this approach are certainly tantalizing. See the Chemicals vs Drugs newsletter series on this topic: onetwothree, four, and five!

Need a romantic date night movie?

  • Sense and Sensibility is one of Jane Austen’s best known novels and was made into an Oscar-winning movie in 1995 and a miniseries in 2008. Crushed in love, the younger Dashwood sister lies down to die in a rainstorm, thus setting off hypothermia, pneumococcal pneumonia, and the recognition of true love (see the YouTube vignette from our Antibiotics Could Have Changed the Plot series). Set in the early 1800s, the movie is spot-on with its depiction of the rapid onset of obtundation and then the crisis in the 2nd week of the illness when victims would either die or experience a resolution of the fever.
    • The story of the younger sister’s illness is one I often tell … this healthy young woman’s story is prototypical for the high mortality of this common infection in the pre-antibiotic era: mortality rates were 1 in 6 for young people and 2 in 3 for the 60+ patient.
    • Osler’s 1910 Principles and Practice of Medicine has a great description of the clinical syndrome leading up to the crisis during the 2nd week. Go here for an excerpt: search for the word ‘crisis’ at the bottom of page 10. 
    • And while it’s not a movie, I have to note that Jane Austen herself died in 1817 (link) with a syndrome that strongly suggests Addison’s disease due to adrenal destruction by tuberculosis. The debate has raged on regarding the precise cause (see this 2009 summary in The Guardian and this 2009 paper in BMJ Medical Humanities), but it seems plausible.
    • Relatedly, we also have the well-documented deaths of the Brontë sisters (link) in the early 1800s with tuberculosis.
    • And then there’s Mimi who dies of tuberculosis in La Bohème (link to a discussion of the opera; link to a 2008 movie adaptation)…
  • Little Women has many adaptions of Louisa May Alcott’s novel but the only one I’ve seen is the 2019 version. We follow the coming of age story of four young women during the 1860s in Civil War America and sadly one of the sisters, Beth, progressively declines during the movie due to complications of scarlet fever (my guess would be cardiac injury; see the YouTube vignette from our Antibiotics Could Have Changed the Plot series).
  • Wives and Daughters is a four-part miniseries based on the novel by Elizabeth Gaskell. Set in the mid-1800s, the protagonists Molly and Roger realize their love for each other only at the end of the novel … and then a scarlet fever scare prevents them from speaking before Roger must depart for a trip to Africa! Although the book leaves the story hanging here due the death of the author, the movie adds a satisfying conclusion in which the young lovers are ultimately reunited (and don’t miss our YouTube vignette from our Antibiotics Could Have Changed the Plot series).
  • Out of Africa is set in the early 1900s and based on the autobiographical novel by Karen Blixen. A young Danish woman living in Africa discovers she needs to return to Denmark to be treated for syphilis with the arsenical arsephenamine (aka Salvarsan or Compound 606). Discovered by Ehrlich in 1907, this was the very first “magic bullet” antibiotic!
    • To learn more about the discovery of Salvarsan, try this 2017 article in the Smithsonian Magazine (link) as well as the YouTube vignette from our Antibiotics Could Have Changed the Plot series.
    • Even better, the chapter on Ehrlich in Paul de Kruif’s Microbe Hunters (link to book on Amazon, also available for Kindle) is a fun tour of how Ehrlich went from trypanosomes and Trypan Red to Salvarsan. 
    • It’s further worth noting that first uses of the next class of antibiotics (the sulfas, as explored at length in Hager’s The Demon Under the Microscope) were 25 years in the future … and the first uses of penicillin were almost 30 years away. For more, see the timelines chart in this newsletter.

Want a documentary to sink your teeth into?

  • A Doctor’s Dream is a short film that follows the development of fexinidazole, an all-oral regimen for Human African Trypanosomiasis (HAT, aka sleeping sickness). I realize this is not a bacterial infection, but the theme of the power of a good antimicrobial is universal. Highly recommended!
  • Salt in My Soul is a remarkable movie in which Mallory Smith, a patient with CF who ultimately succumbed to infection, documents her struggle “to live fully while dying.” The full length movie is available for free on YouTube!

Really just want another holiday movie?

  • The Santa Clause doesn’t have an antibiotic twist per se but, at ~7 min into the movie, Tim Allen uses a fire extinguisher and reminds us all why it is important to have one available when you need it. Make sure you put the whole fire out or it might come back!

Happy holidays, let’s hear it for the #FireExtinguishersOfMedicine, and see you in 2024, –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.

Current funding opportunities

  • 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.
  • 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-XC-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!

  • [Registration is open] 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).
  • 22 Jan 2024 (virtual, 5p-6.30p CET): ‘What do the various non-commercial actors in the antibiotics R&D ecosystem do?’ with Erin Duffy (CARB-X), Peter Beyer (GARDP) and Laura Marin (JPIAMR). Click here to register.
  • 24 Jan 2024 (online, 9a-1p London): Webinar entitled “Priorities and next steps for tackling antimicrobial resistance in the UK”, sponsored by the Westminster Health Forum. Featured speakers include Dame Sally Davies and the focus is on the UK’s 20-year vision and 5-year action plan for AMR. Go here for details and to register.
  • 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] 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.
  • 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.
  • [NEW] 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. 
  • [NEW] 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 intense soup-to-nuts training covers all aspects of antimicrobials 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.

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This is the fifth of a 5-part newsletter series. There is an initial 27 Sep 2023 newsletter introducing the EPA concept note, a second (28 Sep 2023) newsletter that expands on the EPA concept note, a third (12 Jan 2024) newsletter about ending the use of streptomycin spray on citrus crops, and a 4th newsletter (27 Jan 2024) containing some additional resources. Dear All, Excitingly, the US EPA

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Without action, AMR costs go from $66b to $159b/yr by 2050

Dear All, A new paper from Anthony McDonnell and a team led by the Center for Global Development extends estimates of the health-related impact of AMR (e.g., death) to a consideration of the economic ($) cost of AMR. To follow the plot, here are the links you will need: The new paper: “Forecasting the Fallout

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Dear All, The AMR HLM (High-Level Meeting) at the UN General Assembly starts at 10a ET today.  You can watch it here on UN TV: https://webtv.un.org/en/asset/k11/k11knc6w2t Addendum: It’s available for replay at that same link. See also the 1 Oct 2024 newsletter for a review of the HLM. All best wishes, –jr John H. Rex, MD

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