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generis
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I settled on E as the right answer.

Two ideas contrast each other in the sentence. It is better to present these ideas in a manner that emphasizes this contrast. As a result, options A and B can be eliminated.

The use of the past perfect tense in C is inappropriate. The past perfect tense is used to distinguish an earlier event from a latter event. However, the timestamp until the twentieth century clearly enables us to know the sequence of events. We can clearly see that the first clause talks about the fact that the invention of antibiotics did not take place until the twentieth century. The second clause talks about what took place prior to this era. So in a sense, we can say that the earlier event is rather stated in the second clause. C can be eliminated.

The use of the present perfect is D is inappropriate. We can't express a past event whose effects are not valid today in the present perfect tense. Antibiotics have since been invented so it is wrong to express an idea of a period when antibiotics were not available in the present perfect tense. Per the logic of the first clause in D, antibiotics have still not been invented even today. This clearly not the case. D can be eliminated.

E is correct. We can clearly see the sequence of events from the meaning of the sentence. It is surprising that prior to the invention of antibiotics in the twentieth century, many cultures used specially selected mold and plant extracts to treat infections.

Quote:
A) Antibiotics not being invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.
The contrast is missing in A. The use of being is questionable.

Quote:
B) Antibiotics had not been invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.
The contrast in the sentence is missing. The use of the past perfect tense is inappropriate to describe the later event.

Quote:
C) While antibiotics had not been invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.
The use of the past perfect tense is inappropriate to describe a latter event.

Quote:
D) Although antibiotics have not been invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.
The use of the present perfect tense is inappropriate to describe a situation that occurred in the past and that is no longer relevant today.

Quote:
E) Although antibiotics were not invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.
Correct per the explanation above.
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I will go with option E . My analysis for each answer choice is as below

A) Antibiotics not being invented - not being is akward

B) Antibiotics had not been invented - Verb tense HAD is not corectly used here. HAD is used to show sequence of 2 related events in past. The intended meaning of the sentence is that even though antibiotics were not invented in past , many ancient cultures used....

C) While antibiotics had not been invented - While is not the correct conjunction to be used here

D) Although antibiotics have not been invented - Incorrect verb tense ; according to this choice it seems that antibiotics have still not been invented

E) Although antibiotics were not invented - this is correct
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The official explanation is here
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Antibiotics not being invented until the twentieth century, many ancient cultures used specially selected mold and plant extracts in order to treat infections.

A) Antibiotics not being invented

this sentence needs a "although" according to its meaning. in addition, "being" is wrong.

B) Antibiotics had not been invented

In addition to the lacking of "although", this is run-on by connecting two sentences with only a comma.

C) While antibiotics had not been invented

"while" makes it feel like two things happen together. However, they happen in different time period. In addition, past perfect is not necessary since "until 20th century" already demonstrates the timeline.

D) Although antibiotics have not been invented

present tense "have" means that it is still happening. However, "until 20th century" means that it is happening in the past.

E) Although antibiotics were not invented

past perfect is correct here. And it is ok to use past perfect in "until" sentences. For example: he did not go to the store until he finished his homework.
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