Science In Action – Breakthrough Antivirals and Fresh US Grant Cancellations

Date: March 27, 2025
Host: Roland Pease (BBC World Service)

Main Theme and Purpose

This episode investigates two critical science stories: the development of groundbreaking antiviral drugs that could transform responses to current and future coronavirus pandemics, and the abrupt cancellation of major US federal grants supporting antiviral research post-COVID. The show also explores tantalizing new evidence of complex organic molecules on Mars and evolutionary science revealing what makes horses remarkable runners.

Key Discussion Points and Insights

1. Antiviral Breakthroughs: New Hope for Pandemic Preparedness

[03:00–09:12]

• The Antiviral Discovery Challenge:

  • Antivirals effective against coronaviruses, particularly COVID-19, have been slow to develop.
  • Two promising antivirals have emerged, both at the preclinical stage, showing strong efficacy in cell cultures and animal models, but require further refinement and human trials.

• Innovative Screening Approach:

  • Johann Naitz's team at the Rega Institute, Leuven University, tested 350,000 candidate molecules using an automated robotic chemistry lab.
    • "Today, actually, we can on average test 25,000 molecules a day against a virus infection in cells ... that allowed us to test these 350,000 compounds and then from those, pick a few molecules that block the replication of the virus." — Johann Naitz [03:50]
  • The process involves using multi-well plates, robotic platforms, and automated microscopes to rapidly assess which compounds inhibit viral replication.

• The Novel “Achilles Heel” Approach:

  • Unlike existing antivirals that prevent the replication of viral genetic material or inhibit critical viral enzymes, the new compound blocks the assembly of new virus particles inside infected cells.
    • "By using this approach, we can basically identify novel ... Achilles heels of this virus ... putting [the components] together, the assembly into a infectious particle, is not happening." — Johann Naitz [06:10]

• Progress and Potential:

  • Tested in mice and hamsters, the new compound is as potent as nirmatrelvir (in Paxlovid).
  • Ongoing work is enhancing potency and extending its action to cover the family of coronaviruses, potentially preparing for "SARS-CoV-3."
    • "If it would have been right now in midst of the pandemic, I think the molecules that we have right now have the qualities to go into clinical trials in humans." — Johann Naitz [08:08]

Memorable Moment:

• Roland Pease marvels at how discovering vulnerabilities (“Achilles heels”) at later stages of the viral lifecycle could revolutionize antiviral strategies.

2. US Grant Cancellations: Threat to Pandemic Readiness

[09:12–15:18]

• Sudden Federal Funding Cuts:

  • NIH abruptly terminated all COVID-related research grants, including the AVID Antiviral Drug Discovery Support program ($500 million supporting 9 consortia, such as the UK-US-led ASAP project).
    • "The end of the pandemic provides cause to terminate Covid related grant funds." — Official wording read by Caroline Freycinet [09:49]

• Consequences of Halting Projects:

  • Ed Griffin (Med Chemica) and Annette von Delft (Oxford) explain the challenge of stopping ongoing projects:
    • "It's a little bit like we've started building a bridge and we are halfway there. And ... it will be very difficult to complete this bridge without significant funding into the area. But you can't walk over a bridge that only has been half built." — Annette von Delft [11:34]

• Preparedness vs. Complacency:

  • Early-stage antiviral research is crucial to prevent outbreaks from becoming pandemics.
    • "Outbreaks are inevitable. Pandemics aren't. So if we can catch a virus ... really early and you can do that with antivirals, if you already have them ready to ship, you can catch it before it's a pandemic..." — Ed Griffin [10:44]
  • Private sector disincentivized to invest in antivirals for non-existent diseases—public funding thus vital.
    • "If there isn't a market now, why are you working on it? So this is where the AVID centres were particularly different because we're trying to get ahead of the game." — Ed Griffin [14:05]

• Salvaging Results:

  • Despite the funding cut, the ASAP team plans to share their rich datasets for wider benefit.
    • "We have generated very, very rich data sets. So it's something that we hope will help other people, maybe ourselves, but maybe others, to find drugs that will be effective against pandemics in the future." — Annette von Delft [14:47]

Notable Quote:

• Roland Pease observes the dangerous cycle: researchers unable to sustain slow, complex antiviral discovery unless crises are ongoing—a lesson from past pandemics.

3. Mars Organics: Ancient Hints of Life

[17:32–24:58]

• Curiosity Rover’s Surprising Find:

  • Caroline Freycinet (Institut Pierre Simon Laplace) describes how Curiosity's SAM instrument reanalyzed drilled clay samples from Mars (collected in 2013).
    • "Having those fragile compounds preserved for 3.7 billion years at the surface of Mars, it gives a lot of hope that if life ever appeared or existed at this time, the residue of this life would be preserved until today." — Caroline Freycinet [21:19]

• What Was Discovered:

  • Complex carbon-chain molecules (alkanes of 10–12 carbons) detected, larger than previously found Martian molecules.
  • Likely degraded products of fatty acids, common both in life and in non-biological chemistry.

• Interpreting the Findings:

  • The distinction between chemical and biological origins remains unresolved; both could produce such molecules.
    • "We have no way today ... to differentiate between a chemical origin or a biological origin of those fatty acids. It can be chemical, it can be biological. It will give the same fatty acids." — Caroline Freycinet [23:18]

• Reserves and Future Plans:

  • One more pristine Martian sample (“doggy bag”) remains for a future, carefully optimized experiment.

Notable Moment:

• Freycinet’s reflection: "It's a lot of patience, but it's also a lot of excitement ... we are living on all these small successes that we obtain in the lab..." [24:21]

4. Horse Genetics: Evolution’s Endurance ‘Hack’

[24:58–32:08]

• The Evolution of the Horse:

  • Gianni Castiglioni (Vanderbilt University) explains how horses’ unique mutation allows for exceptional endurance, vital for both escaping predators and their later domestication by humans.
    • "They have so much mitochondria densely packed into their muscle cells, ... really at the physiological limit of how much oxygen you can take in and how much energy you can produce." — Gianni Castiglioni [26:18]

• The Mutation's Impact:

  • A single critical mutation at first appeared “broken,” but instead gives rise to a special form of protein, enabled by further compensatory mutations. This allowed horses to efficiently prevent cellular damage from high oxygen use during intense activity.
    • "We originally thought this protein was broken, that this gene was broken in horses. This is the majesty of evolution. Through trial and error, it will find these really elegant ways to kill two birds with one stone." — Gianni Castiglioni [27:55 and 02:34, repeated for emphasis]

• Broader Implications:

  • Similar mutations in humans often cause disease. Studying the horses’ “genetic patch” could offer new therapeutic ideas for human genetic disorders.
    • "We're not going to take horse genes and put them into you. We're just going to use the design principles that nature has produced and kind of steal that blueprint for our own purposes." — Gianni Castiglioni [32:08]

Timestamps of Important Segments

• Antiviral Discoveries: [03:00–09:12]
• US Grant Cancellations & Research Risks: [09:12–15:18]
• Mars Organics and Origin of Life: [17:32–24:58]
• Horse Evolutionary Mutation: [24:58–32:08]

Notable Quotes & Memorable Moments

• "Outbreaks are inevitable, pandemics aren't. ... The only advantage we can have is by being prepared."
  — Ed Griffin [10:44]
• "You can't walk over a bridge that only has been half built."
  — Annette von Delft [11:34]
• "This is the majesty of evolution. Through trial and error, it will find these really elegant ways to kill two birds with one stone."
  — Gianni Castiglioni [27:55]
• "Having those fragile compounds preserved for 3.7 billion years at the surface of Mars ... gives a lot of hope that if life ever appeared or existed at this time, the residue of this life would be preserved until today."
  — Caroline Freycinet [21:19]

Overall Tone & Style

The conversation maintains a measured, inquisitive, and occasionally wry tone, reflecting both the excitement of scientific discovery and the frustration at bureaucratic setbacks. The scientists, while hopeful and passionate, express concern about the loss of momentum in pandemic preparedness and the slow, incremental nature of both scientific and policy progress.

Summary Flow

Listeners are guided from the cutting edge of antiviral drug discovery (and the systemic challenges it faces with grant cancellations), to the edge of our solar system and the very beginnings of life, back down to Earth for lessons from evolution. The episode seamlessly intertwines urgent biomedical challenges with awe-inspiring cosmic curiosity and the relentless logic of natural selection, showing the breadth—and the vulnerability—of scientific progress.

For listeners seeking more, visit the Science In Action webpage to explore past episodes and further resources.