Read on Twitter
1./ A thread. Will the new Pfizer COVID vaccine work? The obstacles are huge but if it does here's how it could transform medicine in almost unimaginable ways. The bad news is it may usher in a terrifying new problem for which we remain totally unprepared. https://www.theguardian.com/business/2020/nov/09/stock-markets-covid-vaccine-ftse-100-coronavirus
2./ The vaccine inserts genetic material (mRNA) inside human cells with instructions that tell them what proteins to make. Scientists have been trying to perfect techniques like this for decades. Here's the opening of my BBC Horizon from 20 years ago about an earlier attempt. 
3./ The subject of that film -'antisense' technology- offered unbelievable promise. Bits of RNA (tRNA in this case) would be inserted into cells where they would block messages from faulty genes in DNA that were causing disease. Researchers hailed it then as a 'Magic Bullet'
4./ It was Paul Erlich who coined this term in 1906 when he predicted we'd one day be able to create drugs so specific they had no side effects and would effectively switch off diseases at the cellular level. Ever since it's been medicine's Holy Grail. https://www.sciencehistory.org/historical-profile/paul-ehrlich
https://www.sciencehistory.org/historical-profile/paul-ehrlich
5./ Scientists thought they'd found it with 'gene therapy' where genes were injected into patients with instructions to repair or replace diseased cells. Trials were halted by the FDA when, tragically, young Jesse Gelsinger died. https://www.sciencehistory.org/distillations/the-death-of-jesse-gelsinger-20-years-later
https://www.sciencehistory.org/distillations/the-death-of-jesse-gelsinger-20-years-later
6./ The first animal trials of 'antisense' went well and the technology moved confidently forward to testing in primates. Cue: a disaster. Far from having NO side effects, as promised, the drug if given in a single dose could be lethal.
7./ The researchers learned lessons, realising they had to change the way the drug was delivered. They then moved onto their first Phase 1 human trials at the Royal Marsden, which we followed. Cue: failure. The drug just couldn't get inside human cells in a living body.
8./ These lovely people had incurable cancer who hoped a new 'genetic' wonder drug might save their lives. Instead their disease progressed and some, like Jeff, had terrible side effects. Any biotech successes today owe patients like them a huge debt for their sacrifice.
9./ Biotechnology has been transformed since. It's changed as much since 1998 as mobile phones have. Here's a reminder what the hottest phone of that year, the Nokia 6110, could do. A top new feature was ...a calendar.
10./ Biotech can now manipulate cells and genes in ways barely dreamt of then. I recently made a film for @ARTEfr in which researchers took ordinary skin cells and turned them into miniature "human organs" in the laboratory (or 'organoids') including "fetal brains". Astounding.
11./ The Pfizer/BioNTech vaccine is equally amazing. Or so it seems. Here's the best explanation I've seen of how the biochemist @kkariko overcame that perennial obstacle: how to get inside living human cells to let the compound work its magic. https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race
https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race
12./ This @dailytelegraph interview is also fantastic. In it Karikó describes the positive results as a vindication of her 40 years belief in the power of therapeutics that work deep down at the genetic level, in particular messenger RNA (mRNA). https://www.telegraph.co.uk/global-health/science-and-disease/redemption-one-scientists-unwavering-belief-mrna-gave-world/
https://www.telegraph.co.uk/global-health/science-and-disease/redemption-one-scientists-unwavering-belief-mrna-gave-world/
13./ Vaccines designed at this genetic level could have huge advantages over traditional ones. Most flu shots, for example, are made by growing live flu virus in millions of embryonated eggs. The virus has to then be laboriously harvested and inactivated.
14./ In comparison, billions of doses of an mRNA vaccine can effectively be manufactured at will using high-tech, small scale plants. 50 mg of mRNA vaccine could treat 1000 people, 50g one million people. 50g is the total amount of alcohol in half a bottle of wine.
15./ The downside of the new vaccine is that it's the equivalent of a Formula 1 car:high-performance but fragile off the track. The need to store it at -70 Celsius means @pfizer is already developing its own distribution network and containers in the US https://www.pharmaceuticalcommerce.com/latest-news/pfizer-to-coordinate-its-own-coronavirus-vaccine-distribution/
https://www.pharmaceuticalcommerce.com/latest-news/pfizer-to-coordinate-its-own-coronavirus-vaccine-distribution/
16./ Vaccines are usually stored at 2-8 Celsius. This vaccine will come in containers that can only be opened twice a day for a minute at a time, for 10 days in total. Constant monitoring will be required otherwise people may get vaccinated with a dud. https://www.statnews.com/pharmalot/2020/09/08/covid19-vaccine-supply-chain-cold-chain/
17./ I'm an optimist but there isn't a European country that's done, say, test and trace properly. We've had 9 months to get THAT right. And somehow none of our health services have been able to expand to tackle the Second Wave without a sense of crisis. So now?
18./ We're going to get an unprecedented biotech distribution chain to work faultlessly in record time? Too much coverage has suffered from the lack of critical thought that's marked biotech before. "The lack of data is concerning" says @NatGeo Too right https://www.nationalgeographic.com/science/2020/11/pfizer-biontech-interim-report-promising-but-lack-of-data-very-concerning/
https://www.nationalgeographic.com/science/2020/11/pfizer-biontech-interim-report-promising-but-lack-of-data-very-concerning/
19./ It's true the vaccine seems minimally risky (based on the data we have). So people who are greatly at risk from COVID may reduce their overall risk by taking it. Healthy young people by their million? Maybe not. That doesn't mean it isn't a herald of huge things to come.
20./ It could mean science is finally able to deliver Ehrlich's promise of Magic Bullets. We'll enter exact codes into machines that create drugs or vaccines that can slip into cells seamlessly, switching off diseases or manufacturing proteins that prime our immune system. But...
21./ Before that utopian vision can be achieved there's a problem. As we've had to rush this biotech revolution that can use genetic codes to manufacture and adapt infectious agents (or bits of them) we've also made the new technology as widely available as possible.
22./ As this terrifying article in @ForeignPolicy points out the next pandemic may not be gestating as we once feared in a forest clearance or a wet market. It might be getting bio-engineered in someone's garage. https://foreignpolicy.com/2020/09/11/crispr-pandemic-gene-editing-virus/
https://foreignpolicy.com/2020/09/11/crispr-pandemic-gene-editing-virus/
23./ For tiny sums it argues nutjobs and terror groups could very soon access genetic codes and the equipment to manufacture pathogens, then slice and dice them. For peanuts. Like us they may have realised how pathetic our 'unbeatable' pandemic planning was. We know better now.
24./ So what's the solution? The infrastructure we're creating now for THIS pandemic, can't be a temporary effort. The spending on labs and sophisticated distribution, never mind testing, can't be reined in. It'll have to be improved to be ten times faster and more effective.
25./ We'll need to treat COVID not as some astonishing one off, but as a dress rehearsal. We'll have to reorganise ourselves so we can respond to outbreaks the way we do now to terror attacks as immediate existential threats. Not least because soon they might be just that.
