TMIT:
Isolation is a tricky case. Firstly the value of the early astro bulb run is not to be overlooked. As far as I know, no bulb shot is nearly as powerful nor as early with GM for isolation (as an additional benifit their, the GL allows you to get very good GSc production without going caste; nothing spares you that with merchants). Unless I'm missing the numbers, I don't see how you can use settling or missions to get that huge of a bang for the immediate term pre-optics. Post optics, you are going to hit the same concerns: it takes five to ten turns to get the mission under way (unless you have some screwy caravel chain) and again gets you a risk that you will either lose a good portion of the cash to extortion or face the diplo hit to deny (part of the reason I don't use 0/100 research values with certain diplo situations).
Likewise, in isolation a greater percentage of your early economy is in transition so equavalent multipliers becomes even more disadvantageous.
All that being said, I have had good shots before using isolation merchants, not to offset research, but production. Flipping up to CRII grenades or rifles let's you skimp on serious military production for the early game, but go kill some backwards AI and get mass land to drive home a solid US/FS economy without having to dip into PS, Nat, or even unit building B. Working 4 merchants in your future WS/GPfarm city allows you to get off a war before your production is made decent by US. Power promoting either warriors (no hunting or linked metal), spears (no linked iron) or maces/pike can be viable. Ragnar, obviously owns with this; Izzy does surprisingly well with this also.
Shafi:
Slider is the easiest thing in the game to change. In the current immortal university I dumped my slider several times to 0% in spite of having strong (+75%) science mods against weak (+50%) gold.
The problems that using merchants early have are:
1. It takes time to leverage them back into
. You often may get higher net returns by doing the trade mission than bulbing a GSc, but it takes longer to get the returns and inter-civ dynamics makes the absolute efficiency moot.
2. You risk an AI, with whom you need to make nice, demand the cash. Note, some AIs (like wrong religion Monty), you may as well tell to go suck an egg, however getting +1 for some petty cash is an easy way to get to friendly while getting -1 to protect 500
is not so easy.
3. Multipliers matter. Early on (pre-currency) you have +25% on
and zilch on
. In addition an early academy weights more towards science. Up until banking you normally will have either unis or obs which tends to mean you get a bit more bang out of science.
4. Rep merchants are a mixed output. In order to get full use you need a lib and a market; which is not always a trivial amount of production.
Generally, merch specs are always good in WS (though if you have high slider to
, cottages become better) and trade missions ove time become more powerful than GSc Bulbs.
You should always have a plan on to best maximize the individual yields of specs and how to best use the GP generated. Merchants a longer term than scientists for both of the above.