123. Read the following passage, then answer the question below.

A placebo is a treatment with no active ingredient, such as a sugar pill, yet in many studies patients who receive one report real improvement. The effect was noted as early as the eighteenth century, but it gained scientific attention after the American physician Henry Beecher published a famous paper in 1955 arguing that about a third of patients improved after placebo treatment. Later analyses showed that Beecher had overstated the case, since many patients would have improved on their own as an illness ran its natural course. To tell the effect of a placebo from natural recovery, researchers need a comparison group that receives no treatment at all.

Studies that include such a group suggest that the placebo response is real but narrower than its reputation. It is strongest for conditions in which symptoms are subjective, such as pain, nausea, and fatigue, and weak or absent for measurable outcomes such as tumor size or infection. Brain imaging gives a partial explanation: when volunteers expect pain relief, regions involved in pain processing show reduced activity, and the brain releases its own natural painkillers, endorphins. Expectation seems to be the key. Larger pills, injections, and expensive-looking packaging produce stronger effects than small tablets, apparently because people expect more from them.

Perhaps the most surprising result is that placebos may work even when patients know they are taking them. In trials of such open-label placebos for conditions like irritable bowel syndrome, participants who were told honestly that the pills contained no medicine still reported more relief than those who received nothing. Ethicists welcome the idea that honest treatment is possible, but caution remains: the studies are small, and researchers cannot yet say whether the improvements last.

The word 'them' in paragraph 3 refers to