Can we switch off diseases?

siRNA drugs are, in my view and @JacobTref’s too, one of the most exciting developments in medicine. So we decided to do an episode!

It’s a technology that can ‘silence’ harmful genes in the body. And there are lots of cases where you might want to tious diseases, where you can silence pathogen proteins or human proteins that pathogens depend on
- Rare genetic diseases, where you can silence the production of mutated proteins
- Cardiovascular diseases, by silencing proteins that raise cholesterol
- Cancers, by silencing proteins that help tumour cells grow, survive, metabolize, metastasize, or resist treatment
- and more!

What’s even better is that siRNA drugs are:

• Potentially tunable, meaning you could reduce the production of a protein, rather than silencing it entirely
• Programmable, meaning you can quickly switch out which gene it targets by changing its sequence
• Long-lasting: some drugs last for months, even half a year, with a single injection
• Off-the-shelf: they typically don’t involve complicated surgeries or procedures, because of the way they’re delivered in the body

Today, siRNA drugs are largely used to treat liver diseases, partly because that’s the easiest starting point.

And they are extremely effective at it. One example is as a cholesterol drug: siRNAs can reduce PCSK9 levels by around 70%, reducing cholesterol levels by 50-60%, beyond the effect of statins.

But we think it’s just a matter of time before they can be used to target other organs too.

Will siRNA treat diseases of other organs? And what’s the catch?

Listen to our latest episode of HARD DRUGS to find out!

Chapters:
00:00 Introduction
09:58 siRNA trivia
28:14 The 20 year journey to make siRNA drugs
36:07 Which diseases could siRNA treat?
50:45 Programmable, long-lasting, scaleable drugs
54:32 The limits of siRNA
1:08:23 Conclusion

🫀 Can coronary atherosclerosis actually regress?

Our new randomized FLOWPROMOTE trial analysis, published TODAY in JAMA Cardiology, shows remarkable coronary plaque regression with intensive LDL-C lowering!

Atherosclerosis is not necessarily a one-way process.

📄 JAMA o/a48M9gXtWl
#Atherosclerosis #LDL #Cardiology #CCTA

Launching RNAFoundry.com – we manufacture personalized cancer vaccines.

Why might the frontier labs be interested in biotech? x.com/i/article/2116…

Join Works in Progress at Building Abundance: How Britain can flourish in the age of AI, a day of ideas for rebuilding Britain’s economy and state so it can adapt to and embrace artificial intelligence and other opportunities for growth.

luma.com/ria1khmw

Sessions 6 and Morgan McSweeney in conversation on the decline and fall of British state capacity,
- @JohnFingleton1 on the Nuclear Taskforce and its implementation by the government, one year on from its pledge to implement it in full.
- @bswud, @SCP_Hughes and me on why nearly every attempt to get Britain building has failed;
- @rachelwolf on what the public really thinks about economic growth and AI;
- @lugaricano on messy jobs and Britain’s labour market;
- @jujulemons on why Britain needs gigawatt-scale compute, and how to get it built here;
- @salonium on why fixing clinical trials is the best industrial policy Britain could have;
- @MichaelDnes1 on building the first new tunnel under the Pennines since 1954;
- @RobertBoswall on how to finance and power the data centre buildout; and
- @daisychristo on why VAR matters for state capacity.

​It will be held on Thursday 3rd December at the LSE, from 1pm to 7:30pm (doors open 1pm for a 1:20pm start). We're hosting it in association with the LSE Law School and School of Public Policy. Tickets are free.

See you there!

luma.com/ria1khmw

What is life like at different levels of GDP per capita?

In this new chart I visualised it for 12 different dimensions.

Original Article: In Vitro Fertilization or Intrauterine Insemination in Unexplained Infertility (FIIX) nej.md/4zjmDnL

#OBGYN | @ASRM_org

New working paper: Can AI forecast treatment effects in economics from pre-registration documents?

Answer: Yes. 1/

I’m hiring an NYC-based Managing Editor for @stripepress. The ideal person for this role has substantial editorial experience at a publishing imprint or another publication and is fluent in our universe of ideas, but ideally isn’t my (or our) ideological twin.

Stripe Press is a small team with an unusual amount of autonomy. Right now we’re obsessively focused on the future: expanding our catalogue, rethinking our assumptions about the kinds of books we publish (fiction!?), and thinking about how to connect our readers w/ one another beyond the pop-ups we’ve been hosting since 2022.

Hoping to meet a lot of brilliant people who love books and are excited about building a world-class publishing institution: stripe.com/careers/listin…

The Wikipedia community has built a tool that makes it possible to embed our interactive Our World in Data charts right in any Wikipedia page.

I have always admired Wikipedia and all the people contributing to it. And I'm very happy that our work now can get used this way!

Catch me on @MTSlive at 11am PT/2pm ET/6pm UK today!

I'll be chatting medical innovation, AI and clinical trials, and behind the scenes on writing & editing with the crew.

People usually say that the pill caused the sexual revolution but a) people started having premarital sex in the 1950s, a decade before the pill and b) contraception is widely used by people who don't live very post-sexual-revolution lives (like in Asia). I think the sexual revolution, i.e. more permissive attitudes about sex, caused the pill to be invented and not the other way round.

But then, why did the sexual revolution happen? I have cooked up a theory. Just as how women have more casual sex on college campuses with fewer men, I think women, as a collective, responded to the male shortage caused by the Second World War by shortening their hemlines and having premarital sex.

Read my column here: worksinprogress.co/issue/young-pr…

Anyone interested in cancer medicine needs to see the current front page of @NEJM
nejm.org
It's one historic advance after another after another on there right now

"I Just Ran 2 Million Regressions" pt. 2

There is something really concerning (and disappointing) going on in the US right now.
A dangerous and preventable situation.
Let me explain.
nextstrain.org/avian-flu/h5n1…
1/

Out today at Research Policy, with @DShvadron, Lee Fleming, and @HansenZhang13, "Measuring the production of scientific human capital: New data, methods, and evidence on the U.S. scientific training ecosystem."

We parsed acknowledgements from 1.2M US STEM dissertations since tailed reading yet possible on who funds PhD training, down to specific firms or funding agencies and offices (hint: overwhelmingly it's federal agencies, but philanthropies and firms also important at certain times, fields, or programs), who is funding PhDs in critical & emerging tech areas (CETs) which are national priorities + where they're getting trained, and provide evidence of crowd-in from federal support.

Link: sciencedirect.com/science/articl…
(Ungated: dpgross.com/papers/measuri…)

Hard to escape the massive role the USG plays in supporting the training of the future scientific workforce, which is clear in these data. And the level of support is for various reasons probably underreported already---so this is just a lower bound.

This is the starting point for a broader agenda on renewed measurement of the US PhD population. More to come--incl. detailed evidence on international mobility (coming soon), rapidly growing use of AI in dissertation writing (posted), reporting of the graduates different US fed agencies have supported and what they're doing now (in the hopper), and more.

Huge credit to Dror and Hansen for cracking the technology needed to make this possible!

Someone should scoop up Vince before it's too late! He's awesome:

Treasury is right to try to protect national security. But we should watch for broad restrictions that could undermine our public health goals - impacting patient access to global innovation.

The new policy could curtail virtually any investment in Chinese biotech operations, including establishing labs, or entering into joint ventures, thwarting opportunities to bring Chinese innovation to American patients.

We need to focus equal attention on making our own process more efficient and competitive, especially Phase 1 trials and the IND stage. The discussion on this will be important. We must get this balance right and ensure Americans continue to benefit from the best global science.

Seven hundred and fifty eight subjects received a personalized mRNA, not one of which was described in an IND. Each made in 4 weeks from tumor biopsy.
The process is the product.
Hello personal CRISPR cures.

I am the king of supplementation – or used to be. I've given it up, every last supplement. Here is my story why.

worksinprogress.co/issue/against-…

I wager that few people have supplemented more enthusiastically than me, or have subscribed to so many fad or esoteric diets.

I have munched thumb-sized multivitamins. I have eaten ice cream and orange juice before bed to boost my overnight metabolism. I have chowed down on offal of all kinds – nature's multivitamin – for my skin, hair, and even my sleep. I have even consumed individual amino acids, for example glycine, a slightly sweet protein component prominent in skin and bone but not muscle meat, which people online claim improves their sleep.

I have done it all. But I am here to tell you: you need not. In fact, my long-time rival @StuartJRitchie, who has always told me that supplementation is foolish, pointless, madeup, and fake, was more right than wrong when he claimed, again and again, that 'you just piss it oot'.

I have put away my heavily researched list of the ideal supplements, I have given up looking. Why? Because 90% of 'studies' are BS, and you should simply ignore them. They are so often wrong that entire bodies of research often find the opposite of truth – as proven by later evidence.

Read my first column in @WorksInProgMag: worksinprogress.co/issue/against-…

Hard Drugs now has a twitter account!

Follow us here @harddrugspod to hear about new episodes and behind-the-scenes goofs.