Naegleria fowleri

[chris0033547]

Dear all,

I wanted to ask a question regarding the parasite Naegleria fowleri. Would it be possible to modify this particular parasite using current knowledge in genetics in such a way that it would only eat cancerous brain tissue ( e.g. glioblastoma ) instead of all brain tissue? Basically the modified parasite would be turned into a biomicro-bot.

Quote from the wiki:

"The organism begins to consume cells of the brain, piecemeal, by means of an amoebostome, a unique actin-rich, sucking apparatus extended from its cell surface."

Now imagine it would only do that to cancerous brain cells...

In the case that something like that is currently impossible. What kind of knowledge in genetics is needed in order to make these kind of modifications to existing organisms? And when may this kind of knowledge become available?

[Rynn]

With current knowledge not at all. The parasite doesn't have a mechanism for distinguishing cancer cells from non-cancer cells. This is the crux of pretty much every cancer treatment: how to target only the cancer cells when they are so similar to healthy cells. Heading to bed soon so will have to leave it at this but will post more if time allows.

[chris0033547]

Thanks for the answer, Rynn. So, basically if one could distinguish between cancer cells and healthy cells, one would be able to modify this parasite in such a way that it would only attack cancerous cells? Am I correct that the modification of the parasite itself would be easier than the task to determine the difference between cancer cells and healthy cells?

I just find this parasite intriguing because this life form already has so many requirements for a biomicrobot:

- It has a "propulsion system" to move inside the host's body.
- It apparently has a "navigational system" in order to find the brain.
- It has access to an energy source in order to power up all these systems.
- It can somehow outsmart a (baseline) human's immune system.

All these points are needed in order to construct a biomicrobot, which could combat cancer. In this case brain cancer. The only problem is the last point:

- It eats all brain cells.

One could view this as a sort of malfunction in the parasite and try to fix it, by modifying the parasite so that it would only eat all cancerous brain cells.

Maybe one could try it with natural selection. Take a colony of these parasites and put them in an environment, which contains only cancerous brain cells. Assuming that the parasite will eat the cancer cells (- maybe it won't do that for some reason, because brain cancer cells are too different from normal brain cells ? But in that case it would be interesting to find out, how this lifeform can distinguish between these cell types -), let it eat these kind of cells for a few generations by selecting out the parasites, who ate the most cells and make them the founders of a new generation. Then take the last generation of the colony and put it in an environment with healthy brain cells. Here one would go the other way and select out those parasites, who ate the least amount of healthy brain cells. They would become the founders of a new generation. Then repeat this for a while and put the last generation back into the environment with cancerous brain cells and select out the parasites, who ate the most cancer cells again and so on. Make the parasite "migrate back and forth" between these two environments: the "good" environment with healthy cells and the "bad" environment with cancer cells.

Hopefully the new parasite will start to prefer cancerous brain cells over normal brain cells. If that happens one could compare this new parasite with a natural parasite and try to figure out the genetic differences between them. If one could understand, how these differences work, one could then "optimize" the parasite even further so that it would stop attacking healthy cells altogether and turn it into a biomicrobot to combat brain cancer.

[Rynn]

Thanks for the answer, Rynn. So, basically if one could distinguish between cancer cells and healthy cells, one would be able to modify this parasite in such a way that it would only attack cancerous cells? Am I correct that the modification of the parasite itself would be easier than the task to determine the difference between cancer cells and healthy cells?

No, engineering such a novel and complicated trait into an organism would be much harder (and reliably targeting cancer cells is still a holy grail of cancer research).

There have been interesting efforts to generate organisms that preferentially migrate or hunt cancer. Two examples that spring to mind are using bacteria as vectors and gene-modified white blood cells. In the former case bacteria are introduced that can thrive in tumours due to the hypoxic environment and nutrients provided by tumour-mediated necrosis. The EPR effect causes bacteria to accumulate in tumours. The second is gene modified T-cells. These are immune cells that have been engineered to be far more sensitive to cancer cell antigens, when placed back into the patient they will initiate an immune response against cancer cells.

[Dalex]

The idea itself is good but there is one problem apart from the whole "what is cancer and what not" thing.
You see parasites are living organism and as such produce some waste. This waste would be quite understandably harmful to the patient, especially in brain.
Also you would have to be very careful while gengineering this thing so that it won't cause catastrophic immune reaction.

However, reengineering an existing organism into a cancer killer is still very interesting. You know what already can:

- It has a "propulsion system" to move inside the host's body.
- It has access to an energy source in order to power up all these systems.
- It can somehow outsmart a (baseline) human's immune system.
?

HIV, if you stripped it of everything but the barest minimum needed to replicate and then changed its RNA so that it could only replicate when cancer-specific transcription factor is present then you would have a cancer killer. The propulsion and energy provided by host own cells and waiting until needed stored in hosts own DNA. In fact if the integration was done in a controlled way, this new immunity to cancer would be inherited by children of original recipient. Well assuming it would get into germline cells.

[iancampbell]

The idea itself is good but there is one problem apart from the whole "what is cancer and what not" thing.
You see parasites are living organism and as such produce some waste. This waste would be quite understandably harmful to the patient, especially in brain.
Also you would have to be very careful while gengineering this thing so that it won't cause catastrophic immune reaction.

However, reengineering an existing organism into a cancer killer is still very interesting. You know what already can:

- It has a "propulsion system" to move inside the host's body.
- It has access to an energy source in order to power up all these systems.
- It can somehow outsmart a (baseline) human's immune system.
?

HIV, if you stripped it of everything but the barest minimum needed to replicate and then changed its RNA so that it could only replicate when cancer-specific transcription factor is present then you would have a cancer killer. The propulsion and energy provided by host own cells and waiting until needed stored in hosts own DNA. In fact if the integration was done in a controlled way, this new immunity to cancer would be inherited by children of original recipient. Well assuming it would get into germline cells.

Interesting. Another way of the children getting their own colony of a symbiont like this is the way that babies get their initial population of intestinal flora. IIRC, the way this usually happens is that the bugs get in on the baby's way down the birth canal. (Yet another reason for avoiding C-sections whenever possible.) Which means that it doesn't have to get into germline cells.

Incidentally, such a symbiote (if transmitted via germ cells) would be transmitted exclusively via the mother. Sperm cells don't have the room - they don't even have the room for mitochondria and other organelles, which means that all the mitochondria are inherited from the mother.

[chris0033547]

Hello all,

Thanks for the links and interesting ideas! Regarding the usage of viruses to fight cancer: I think, they had a limited success with it already, didn't they? I did a google search after you mentioned HIV, Dalex and here's one interesting link :

http://www.vox.com/2014/5/15/5719370/mul...es-vaccine

So even if it is currently impossible to modify complex organisms like Rynn said, maybe the modification of viruses, which turns them into cancer killers, is already feasible? They even mention "different viruses for different cancers" in the article. Perhaps a modified version of Ebola, HIV or even modified smallpox for cancers of the immune system? ( Ebola infects the immune system cells, doesn't it? ). A modified SARS-CoV or MERS-CoV against lung cancer and so on...

EDIT:

Here's one more link:

http://www.messagemedia.co/aitkin/commun...f6878.html

[Dalex]

Interesting. Another way of the children getting their own colony of a symbiont like this is the way that babies get their initial population of intestinal flora. IIRC, the way this usually happens is that the bugs get in on the baby's way down the birth canal. (Yet another reason for avoiding C-sections whenever possible.) Which means that it doesn't have to get into germline cells.

Incidentally, such a symbiote (if transmitted via germ cells) would be transmitted exclusively via the mother. Sperm cells don't have the room - they don't even have the room for mitochondria and other organelles, which means that all the mitochondria are inherited from the mother.

I'm afraid that you misunderstood me. You see an HIV virus is a member of retrovirii group. It is encapsulated RNA which is upon entry into a cell transcribed into DNA and then integrated into DNA of the host cell.

There it remains dormant until needed transcription factors appear.
Because of that the immunity would be passed by both males and females.

HIV virus DNA is 9.2kilobases long that is about 0.00028440443% of human DNA.

[iancampbell]

Dalex, I know about retroviruses. But if I understand you correctly, you're talking about incorporating the complete genome of a multicellular organism into host DNA. I doubt whether that's possible.

[Dalex]

Dalex, I know about retroviruses. But if I understand you correctly, you're talking about incorporating the complete genome of a multicellular organism into host DNA. I doubt whether that's possible.

Ooooh. Now I understand. No I was talking about modified HIV all the time.