Show Notes
The pharmaceutical industry has a dirty secret: it takes $2 billion and a decade to approve the average drug, and these numbers are getting exponentially worse. While computing power doubles every few years, drug development costs double every decade—a phenomenon called Eroom’s Law (Moore’s Law backwards). Lindus Health was founded to fix this crisis. Named after James Lind, the Royal Navy surgeon who ran the first randomized controlled trial in 1747 (discovering that citrus prevents scurvy and accidentally creating the Sicilian Mafia in the process), the London-based company is slashing clinical trial costs and timelines through better software, smarter processes, and a willingness to actually keep up with FDA guidance—which, remarkably, the industry ignores. In this first part of our conversation, we explore why pharmaceutical shelves are lined with miracle drugs gathering dust, how the NHS simultaneously possesses world-class health data while being catastrophically bad at purchasing new treatments, and what Britain could gain by becoming the world’s biotech testing ground. Tom, Calum, and Meri discuss: * Why drug development costs are doubling every decade: Eroom’s Law means $2 billion and 10-12 years per drug on average. “A tech bro would say ‘it one shot me’ right? How have we got this incredibly important industry getting exponentially less efficient when all the inputs—genome sequencing, compute—are getting exponentially more efficient?” The vast majority of costs are in phase 1-3 clinical trials, * The COVID vaccine trials were archaic: Meri volunteered and “it was like stepping back 30 years.” He had to download Microsoft Edge because the signup website didn’t have an SSL certificate. “That sounds trivial and silly, but that probably puts off at least half of potential volunteers, which makes it twice as long to enroll and potentially twice as expensive.”, * Pharma shelves are lined with miracle drugs gathering dust: “You would be shocked. There are just umpteen compounds sitting on shelves gathering dust.” Often shelved for ridiculous reasons: “This was a pet project of this guy who got fired and no one else wants to touch it.” Or outdated NPV thresholds. Because trials are so expensive, it’s not worth their time, * The regulations are surprisingly permissive: “This will sound controversial but I think the regulations have an appropriate level of risk modulation. You can literally go on the FDA’s website and see briefing documents where they are admonishing pharma for not being innovative enough. What other industry is the regulator trying to force private companies to be more innovative?” Most barriers are self-imposed, * James Lind and the Sicilian Mafia: In 1747, Lind ran the first RCT to cure scurvy—up to 50% of sailors on long voyages just died. Six treatment arms, oranges and lemons won. “One of the key innovations that powered the British Empire.” The demand for citrus was so great the Royal Navy went to Sicily, and “the Sicilian Mafia formed as a collective bargaining organization to help producers get a fair price.”, * The low-hanging fruit argument is cope: “Most people would say ‘oh well maybe we’ve discovered all the early targets and all that’s left is really hard to drug.’ That just seemed like terrible cope. 30-40 years ago we discovered medicines by zapping them into mice randomly. Now we’ve sequenced the human genome.”, * Britain has incredible advantages it’s squandering: The NHS has “probably the best health data set in the world. Completely longitudinal cradle to grave, all one system, records coded the same way.” UK Biobank is world-class. “There’s a lot of early phase research that originates in the UK. But when you’re running later trials, you want a good early adopter market. That unfortunately is not the UK.”, * The NHS purchasing problem: NICE has decided its role is to get the lowest price possible “even at the expense of waiting five years to acquire a drug that could be life-saving. We’l
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Rodolfo Rosini, co-founder and CEO of Vaire Computing, joins Tom and Calum to make the case that the future of computing has to run in reverse. A conventional chip gets hot because it throws information away, dumping each transistor's charge to ground. Vaire's chips store that charge and send it back, like a pendulum. That trick could keep the computing curve climbing long after Moore's law runs out of road, at the moment AI's appetite for energy is exploding.
The King Charles III Space Station is broadcasting almost live, with Aeron at ground control ready to cut the transmission at the first sign of blackpilling. Tom and Calum inaugurate a new format of news roundups and shorter interviews with a mixed report from the home planet: manufacturing is growing, the pubs keep disappearing, and Britain still needs to find itself an Antarctic patrol ship.
This episode is sponsored by Isembard, the industrial base for the West. If you want to own and operate a factory in Britain, America, Germany or France, email [email protected] and go reindustrialise the West. No guest makes it through the airlock this week, which is fortunate because Tom has brought a better visitor: pictures of potato-sized black lumps from the bottom of the Pacific. Calum keeps finding him in the sitting room gazing at manganese nodules. Tom would prefer the real thing. Our hosts set out to explain why the metals embedded in those improbable objects matter to every magnet, battery, submarine, missile and wind turbine Britain hopes to build. The story begins with a message from Queen Victoria that took nearly seventeen hours to crawl across the first transatlantic cable. Its failure started a quarrel between Wildman Whitehouse, who wanted to solve the problem with more voltage, and the future Lord Kelvin, who wanted to understand the ocean. That quarrel opens a path for the sickly naturalist Charles Wyville Thomson, his deep-sea dredges and a succession of Royal Navy vessels culminating in HMS Challenger: a 200-foot corvette stripped of fifteen of its seventeen guns and refitted as a floating laboratory. Four years, tens of thousands of specimens and thousands of new species later, the expedition has found the deepest known point in the ocean and hauled up strange, metal-rich nodules wrapped around teeth, bones and fragments of sponge. The Victorians went looking for a cable route and discovered a resource frontier. A century later, Malta’s Arvid Pardo declares the seabed beyond national jurisdiction the common heritage of mankind. The principle becomes an international regime, complete with a proposed UN mining enterprise, compulsory technology transfer, Ronald Reagan’s refusal to sign and, eventually, the International Seabed Authority. While that system spends decades debating a mining code, China becomes what the hosts call an electrostate: a country whose command of critical-mineral supply chains gives it the geopolitical leverage that oil once gave petrostates. The environmental question is real. Mining machines are giant underwater Henry Hoovers, sediment plumes do not respect claim boundaries, and the nodules are habitat for sponges, corals and the ghostly “Casper” octopus. But leaving the seabed untouched does not make the mineral demand disappear. It only moves the damage out of sight. Britain now occupies a peculiarly British position. The government supports a moratorium on commercial deep-sea exploitation while continuing to sponsor two exploration contracts in the Clarion-Clipperton Zone, now held through UK Seabed Resources by Glomar Minerals. To Calum and Tom, that tension is not a reason to surrender the option. It is a reason to decide what the option is for. Should Britain remain inside the UN system and shape it, align with an American route around it, or accept that China will write the rules by being the country prepared to act? And what does it say that the government’s own 2035 ambition is to meet only 10 per cent of annual critical-mineral demand through domestic production? Recycling yesterday’s stock cannot supply an economy that intends to build several times more of everything. The Anglofuturist answer runs from the ocean floor to the edge of the possible: rebuild the Royal School of Mines, train mining engineers, specialise in autonomous excavation robots, carry those machines from the North Sea to the Pacific and eventually to asteroids, and treat scientific data with the same seriousness as physical resources. There is, Tom observes, more stuff Britain chooses not to do than it actually does. Fifty years from now, Britain could be one of the world’s major electrostates — rich in energy, minerals, machines and the leverage to set its own course. We have business in the Clarion-Clipperton Zone. The episode explores — Tom’s habit of gazing longingly at pictures of manganese
Space is tight in the King Charles III Space Station’s dining room this week — ten million pounds a square metre, the collapse in housebuilding having consequences even in orbit — which is fitting, because coming through the airlock are two men who tried harder than most to fix it. Jamie Rumbelow and Henry Dashwood founded Tract, the venture-backed startup that set out to speed Britain’s planning system up with software. Two years later they returned the capital and wrote the postmortem everyone in British tech has read. But this episode isn’t about that postmortem. It is about what Jamie and Henry learned when they pulled back the curtain on the people who are meant to be building Britain’s homes. With sincere apologies from production, this interview has sat in our backlog since last autumn. Nevertheless it is, perhaps unsurprisingly given the subject, utterly timeless. Our thanks to Henry and Jamie for being so patient. The episode explores * How Jamie was radicalised by The Housing Theory of Everything * Why £1,600 a month makes housing a moral issue * What a land promoter actually does: title deeds, unanswered letters to farmers, and a month of knocking before anyone will talk * Twenty thousand pounds a hectare until planning permission touches it * Forty types of document for a small builder, versus the 1990s red-line sketch that got you an agreement * The land-banking myth: housebuilders aren’t hoarding, they’re terrified of paying subcontractors to do nothing * NIMBYs have a legitimate point: traffic, GP waiting times, and Section 106 as a feudal tribute system * Abolish stamp duty first — the quickest win in housing, and the one that sorts everyone into the right house * Why not Birmingham? * Reading every single Paul Graham essay, making all the same mistakes anyway, and the unglamorous responsibility to build a very big company very quickly * Victorian railways approved by committees of six MPs forbidden from owning land on the route * Thirty million Londoners at the density of Paris, “we could be Taiwan”, and the ten-storey Sloaney Pony Jamie and Henry’s postmortem of Tract is at buildwithtract.com. Henry writes at henrydashwood.com and Jamie is at jamierumbelow.net. Anglofuturism remains open to sponsors — get in touch with [email protected].
No guest at the airlock this week — no radar contact at all, in fact, because Tom is patching in from a French heatwave, leaving Calum alone in the captain’s seat. Domestic matters first: the long-foretold big score has finally materialised (34 runs, since you ask), and England are in a World Cup semi-final. Which turns out to be geopolitically relevant, because Britain’s principal adversary this century could well be Argentina. The last country to declare war on us has a standing claim on the Antarctic Peninsula and a date circled for 2048, when the treaty system parking everyone’s claims comes up for review. Elsewhere: Tom, broadcasting from a continental-sized armpit at nearly forty degrees, discovers France is having a full culture war about air conditioning while Britain quietly makes cooling near-impossible to permit and calls the heat character-building. And a new Acemoglu paper hands the show a victory lap on a long-running thesis: labour scarcity forces innovation. The episode explores: * Why Britain’s principal adversary this century might be Argentina, with 2048 circled in the diary * “The Antarctic Peninsula is British and it shall remain British. I am sending a task force to Port Lockroy” — the duelling Thatcher impressions * The dream of an episode entitled simply Gotcha * Why there is still no British city on the Falklands despite ten trillion pounds of oil in the neighbourhood * Harry Kane, the Chagos Islands, and the Diego Garcia tattoo * How England should handle Messi (flood the midfield; he doesn’t run very much) * France’s aircon culture war: Le Pen promising cooling for all, Mélenchon scandalised * Air conditioning as civilisational technology — the most important thing Lee Kuan Yew did for Singapore’s civil service * Barocal, the Cambridge spinout doing solid-state barocaloric cooling with no refrigerant and 2-3x the efficiency of commercial HVAC * The Acemoglu natural experiment: wartime labour loss, 9.1 per cent higher GDP per capita fifty years on * The automated car wash you never build while labour stays artificially cheap * The Motor Car Act, the Isle of Man TT, and what the CAA could accidentally do for drones * Politics as downstream of TFR: pensions eating the state and Luttwak’s end of the heroic generation This one is a salon for our paid subscribers — thank you for keeping the station pressurised. Anglofuturism remains open to sponsors: get in touch with [email protected].