#hell angel

To explain it, let's start with the mysterious project the BO started 50 years ago. At the time, Carasuma Renya would have been around 90 years old. As we can imagine at that age, his health must have been declining. Knowing of his selfish and materialistic personality, it's not far-fetched to assume he wanted something to halt or even reverse his ageing and stop his health from deteriorating. That's why I think the research into what we now know as APTX-4869 was launched 50 years ago.

To explain the next part of my theory, I'll be using 'the Gathering of the Great Detectives Case' as an example. In the case resolution, Senma Furuyo explained how her father (who was an archaeologist) was summoned forty years ago along with other archaeologists to find Carasuma the treasure hidden in his Sunset Manor. Carasuma was so impatient and cruel that he began killing the archaeologists to motivate the others to hurry and find the treasure.

If he used such extreme methods to find the hidden treasure, I can only imagine the lengths he went to with the scientists hired for the project, especially if he felt like he was running out of time. He must have been incredibly impatient to find a solution no matter the cost.

Based on all that, I think that there was an old APTX-4869 prototype made by researchers around 40+ years ago. This was the prototype that Carasuma was in a rush to try. I'm guessing the drug's effects weren't what he was looking for, otherwise it wouldn't make sense why the project remained ongoing all the way until the current timeline. Maybe all the first prototype achieved was halt the ageing process but it did not cure his declining health nor did it de-age him. It's not also far-fetched to assume that Carasuma punished the researchers like he did with the archaeologists in Sunset Manor.

If we assume the drug's research came to a halt, Carasuma would have found himself in limbo (his health isn't getting any worse but it isn't improving either). Then came the Miyanos...

A common misconception is the Miyanos joined the BO 30 years ago when Atsushi sold his childhood house to his friend and left to a facility to work on his research. But the truth is at the time, he joined the Shirohato Pharmaceuticals as part of the drug development team. Haibara even mentioned a larger company (the BO) tried to buy the pharmaceuticals company but things did not end well forcing Shirohato pharmaceuticals to close down 25 years ago. Shiho's parents ended up opening a clinic, instead. Anyways, it's safe to assume that the BO noticed Atsushi's research. I'm going to go out on a limb and say his research was to look into ways to cure diseases caused by ageing using apoptosis and telomerase.

This part of my theory is very science-related so please bear with it because it ties a lot to the rest of my theory 🙏🏼

I started to believe Atsushi's research had something to do with curing age-related diseases after I did my own nerdy research into telomeres and telomerase. Like Haibara said, telomerase is an enzyme. Its job is to lengthen 'telomeres'. Telomeres are sequences of DNA at the end of our chromosomes that get shorter every time our cells divide until they get too short causing the cells to die (therefore telomeres act like our own biological countdown timer). So, if telomerase kept lengthening telomeres, our cells will virtually never die and remain healthy. Scientists found that injecting telomerase in mice that lacked the enzyme, resulted in significant improvement in the mice's health and their cells rejuvenated. However, it is worth mentioning that activating telomerase in all body cells will activate uncontrollable cell division (aka triggering cancer). The 'de-ageing' effect was possible only if telomerase was active in stem cells (cells that can generate new specialised body cells). Therefore, selective telomerase activity is important (and I'll explain why this is relevant for my theory later in this post).

(Sources: https://www.nature.com/articles/news.2010.635 , https://www.sciencedaily.com/releases/2018/02/180227142114.htm)

As for Apoptosis, I'm guessing its purpose is to target sick cells, killing them off until telomerase allows the generation of new cells in place of the old cells.

Anyways, I believe Atsushi's goal was to create a drug that helps cells rejuvenate and potentially cure diseases caused by age.

Seeing as Atsushi's research was slightly similar to Carasuma Renya's goals, he became adamant on scouting and hiring the Miyanos. After almost 10 years of pressure from the BO, the Miyanos finally joined. The BO might have given the Miyanos an ultimatum; in return for funding Atshushi's research, they had to take over the project started years ago and advance it or Akemi's life will be in danger.

Based on all this, there were two drugs in the making when Shiho's parents joined the BO:

The first one is: The Silver Bullet - Atsushi's original research about curing diseases caused by old age. (With such a noble goal, it makes sense why Elena called it a "dream drug", a "terrifying drug" and a Bullet of justice.)

So, if the Silver Bullet was such a great drug, why was Haibara crying in regret and felt it was a drug that shouldn't be made? My guess is she was talking about the new APTX-4869 that the BO forced her to make, not the Silver Bullet. She's probably regretful that her parents' drug never got to develop to its full potential and instead the poisonous APTX-4869 was advanced because of the organisation's selfish agenda.

The second drug is APTX-4869 - Based on the BO's demand this drug took priority in drug development compared to Atsushi's research to achieve de-ageing.

One thing I noticed about the APTX-4869 created by Shiho's parents, is unlike Shiho's version, their drug was poisonous and killed victims without leaving any biochemical trace. This could be because of two possibilities:

The balance between the apoptotic activity and telomerase tipped in favour of apoptosis, killing all cells and causing death.

OR Telomerase activation was not selective, triggering cancerous cell division and killing its victim.

Either way, the BO found out about that lethal effect and began using it for untraceable murders such as the case of Haneda Koji and Amanda Hughes.

And just like Shiho disliked the drug being used for murders, maybe her parents opposed the drug to be used for the same means. Fearful the Miyanos could do anything drastic, as well as the lack of their progress, Carasuma probably ordered their death but only after Shiho's birth, so she can be raised by the BO to eventually take over the project again. Meanwhile, the Miyanos sensed their looming death, so Elena recorded tapes hoping Shiho would one day be able to get them and find out the truth about how and why they joined the organisation, as well as the truth behind her father's research.

After her parents' death, the BO hid the truth of Atushi's research from Shiho. And if the BO asked Shiho to create a de-ageing drug unlike the poisonous APTX-4869 her parents created, it makes sense for Shiho to say "what they really wanted me to make was another drug". Basically the BO never told her to create a poison, but a de-ageing drug. This is reinforced by a number of events:

Her visit to Mermaid Island that had rumours of an immortal elder.

Haibara saying there will be punishment for those who try to go against the stream of time.

Pisco being impressed when Shiho shrunk in front of him saying her parents would have been proud she was able to advance the drug to that extent.

I also think Shiho ended up blindly using both sets of data relating to either APTX-4869 or the Silver Bullet, to recreate the current APTX-4869 (which the BO called the incomplete detective). Unlike her parents' APTX-4869, that killed all its victims, so far all those who ingested Shiho's drug, were shrunk and not killed (Shinchi, Shiho and Mary). I don't think the drug Vermouth forced on Mary was Elena's but it was Shiho's. Some would question then why does Mary seem more ill compared to Conan and Haibara? Drug side-effects vary widely among individuals and let's not forget that Mary ingested the drug at a much older age compared to Conan and Haibara. Also, unlike Conan and Haibara, Mary fell into the river after she ingested the drug and that might have had an impact on her health.

Sooo there you have it. I would like to reiterate these are all just assumptions and I could very well be wrong. I've yet to find an explanation for Vermouth's link to the Miyanos' research and Itakura Saguru. Also, Wakasa's access to the APTX-4869 victim list is intriguing.