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Comment by klevertree | Hacker News Reader

I wrote a long essay about the same topic and came to similar conclusions as Derek Lowe: https://trevorklee.com/are-mrna-therapies-the-future-of-phar...

One thing that I'd like to emphasize is how unbelievably tiny mRNA therapeutics have to be. It's probably around 30 mg, and it's hard to do it more than once every few weeks, at least judging by siRNA therapeutics (which have similar immune issues).

30 mg is really tiny. It's hard to come up with a meaningful therapeutic in such a small amount of material. People have been hyping up self-replicating mRNA as a solution, but that's still in its infancy, and has its own problems regarding the "compilers"/polymerases that need to be packaged with it.

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I think you meant 30 µg (micrograms).

And it is indeed tiny. Even for LSD "the only drug measured in micrograms", a typical dose is around 100µg. Most drugs (both the legal and illegal kind) are in the tens of milligram range.

I don't think it is correct to say only one drug is measured in µg.

Levothyroxine (for underactive thyroid) is typically administered in µg doses - but patient confusion with the more common mg means most medical staff will translate any mg dose a patient claims to be taking to µg automatically.

It may be atypical, but it's certainly not rare for drugs to be µg doses.

I think the earlier commenter meant ‘drug’ as in street drug. But though that may have once been true, these days there are plenty of other designer drugs that come in tiny doses, many of them not as friendly as LSD.

I don't understand why both are called drugs in English. My language also has the word "drugs" but it's used exclusively for street drugs.

Drugs having to be government approved is a relatively recent development.

Perhaps about a hundred years, give or take. See https://en.wikipedia.org/wiki/International_Opium_Convention

The English language just hasn't caught on, yet. At least not completely.

In eg German, people generally differentiate between Medikamente and Drogen, but they still have a Drogerie which is essentially the same as a drug store.

'Medicine'? 'Medications'? 'Prescriptions'? I'd say 'drugs' does lean quite strongly towards the illicit kind.

If a doctor asked me if I was 'taking any drugs', I would assume they wanted to know in confidence about anything recreational; not prescriptions/off the shelf medicine.

Yes, it depends on context.

Eg if your wife asks you whether you've taken your drugs yet, she means the same thing as meds.

> In eg German, people generally differentiate between Medikamente and Drogen, but they still have a Drogerie which is essentially the same as a drug store.

To add a little additional context 'Drogerie' mostly sells hygiene products, supplements and the like. They only sell 'Medikamente' which are allowed to be sold over the counter in Germany, which basically is Aspirin and everything that is even more harmless. You will not find the kind of drugs you typically get in a CVS in a German Drogerie.

Every serious drug is only sold in what is called 'Apotheke' = pharmacy.

In Germany Apotheke (pharmacy) and Drogerie (drug store) are very different. I think there is no real distinction between drug store and pharmacy in English, but I'm not sure. There is also Reformhaus which is pretty similar to a small Drogerie with a focus on healthy living.

EDIT: I checked my claim about the Aspirin and it seems I'm wrong. They are not even allowed to sell that. But it kind of reinforces my point: Drogerie doesn't really sell drugs in the sense the word is used in English.

> I think there is no real distinction between drug store and pharmacy in English, but I'm not sure.

This is... oversimplified, at least. I'm sure usage differs by region, even within the United States, but where I am a "drug store" is a convenience store which either contains or historically contained a pharmacy (in the latter case, there appears to be a decent chance the store is an historical soda fountain/cafe). A pharmacy is a place where one buys prescription medications, often only being a section/counter of a larger store. I would never use the terms interchangeably: one does not buy household goods at a pharmacy, nor does a place become a "drug store" by the filling and sale of prescription medication.

Now that I read you comment I remember having seen this pharmacy within the drug store thing. I also remember that the lady there gave sort of medical advice to the customers and that I wondered if she was an MD or not.

That's a whole other discussion about the nature of pharmacies too. The pharmacists themselves have specific degrees and I always assume they're more knowledgeable about things like drug interactions than even the prescribing doctors, if that's the kind of medical advice you mean. One probably works with pharmacy technicians at the desk though; I'm not sure about their qualifications. At the very least the techs can help me find the right OTC medicine if I want it as drug stores tend to locate those strategically near the pharmacy.

But many US pharmacy chains also have RNs onsite providing services, part time, for vaccines and such. That's not quite the same as an MD but it's different than pharmacology.

In Germany, pharmacies have specific legal monopolies, and weird regulations, eg that forbid running a pharmacy chain. (It's a bit like unit banking in the US of yore.)

The pharmacists' lobby always defends them with 'oh, you need a proper pharmacist in a pharmacy to give people proper advice'. But whenever some intrepid journalist goes and tests the actual advice given by pharmacies in some bout of investigative journalism, the majority of pharmacies tested always fail dramatically.

Same in France. "Médicament" is what you get from your doctor and "drogue" is what you get from your dealer.

As for the shops, the one that sells prescription and over-the-counter drugs is called "pharamacie", the next tier is "parapharamacie", which sells vitamins, essential oils, hygiene products, etc... "Drogueries" are actually hardware stores.

> LSD "the only drug measured in micrograms"

Carfentanil is probably more potent then LSD, here is a lethal dose:

https://mediad.publicbroadcasting.net/p/wosu2/files/styles/x...

"For pain relief, a unit of carfentanil is one hundred times as potent as the fentanyl, five thousand times as potent as heroin, and ten thousand times as potent as morphine, despite having only 14 to 135 times the affinity for the mu receptor."

That carfentanil looks like about a milligram, but impossible to say without knowing its density.

"The New York Times warns that a particle of carfentanil as small as a grain of salt or piece of dust can be deadly and that the drug is lethal in a dose as minuscule as 0.02 milligrams. "

so about 1/50th of a milligram is deadly... not sure what's the maximum dose before it kills you

1.0 µg of carfentanil is equivalent to 10 mg of morphine

Read through some of the links in the linked article it must be micrograms.

> 30 mg is really tiny. It's hard to come up with a meaningful therapeutic in such a small amount of material.

I'm going to echo others and ask what you mean here. A lot of drugs have effective doses lower than 30mg. Are you saying that 30mg is an unusually small dose for a pharmaceutical? Because I don't think that's true.

micrograms

Everyone seems to be focusing on your first comment at the dose must to be limited to 30 µg to avoid lipid toxicities. But the second issue is an even bigger issue—-the immune system will remove cells expressing proteins not found in the patient’s genome.

Under what circumstances does this occur? Is this something the cell itself signals to the immune system?

it's one of the most extraordinary details I've learned in biology. The thymus expresses cell types from around the body and trains the immune system to not recognize them as foreign:

https://en.wikipedia.org/wiki/Central_tolerance

it's not for genes, but for epitopes

> 30 mg is really tiny

Not really. For example the amount of beta blocker I take for my heart problems is 5mg per day - the pill size goes down to 2.5mg.

Not to mention LSD, which is a well below 1mg thing.

Also not sure why it matters at all, if it's under 1g you can administer it pretty much any way you need to.

Pretty sure they meant micrograms, not milligrams.

Then they should not have used the SI milli- prefix.

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