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Comment by piokoch | Hacker News Reader

Sounds promising, unfortunately it seems that currently it does not really work.

"The problem was that the experiments also found that the patient's immune system was fighting the virus and effectively removing it from the body within three weeks, thus preventing it from completing its anticancer action."

Anyway, good that they managed to get research to the clinical trials level (it is not one more miracle cure for cancer that makes happy only laboratory mice and rats communities) and extends our knowledge how immune system works.

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> unfortunately it seems that currently it does not really work

As much as I'd like to see cancer defeated and the suffering of millions reduced to nothing, I don't think this is the way.

We have to be VERY careful what we are doing with tools like CRISPR and the like. We now wield instruments to reshape biological life. Anyone who studied biology for a period can attest to the insane complexity and interconnectedness underlying both micro- and macro-level systems in biology. It is next to impossible to predict how any biological system will react as whole over long periods of time. The complexity is akin to predicting the weather years from now.

All our approximations, models and calculations developed over decades running on the toughest new supercomputers can't produce accurate weather forecasts even just 3 days from now. What hubris to believe the same could be done in biology!

The current top comment rightfully points out the danger of giving a virus the ability to fully circumvent all immune defense systems and hand out apoptosis like Santa Claus on Christmas.

not sure why this comment is down voted? it's a completely legitimate point.

the effects of messing with our own biology, let alone releasing a new virus capable of "destroy" cancer would be massive.

>not sure why this comment is down voted? it's a completely legitimate point.

Because people confuse technology with science -- and think that when someone cautions against one, they are against the other.

Or, in the words of Dr. Ian Malcom: "Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they should.".

As a noob in biology - let alone the power of CRISPR - I am often wondering about claims of any GMO being declared safe for wide-scale use 'in the wild'. This while (other) scientists are marveling at the incredible new intricacies they are discovering about the ecosystems they study. I know mutations are occurring all of the time, but to me the ones we humans create seem likely to be more risky / impactful than the natural ones. But, then, I am a noob :)

The analogy I always use is of a computer program - a 700 megabyte program in a language not designed for readability would be bad enough, but there's also epigenetics to consider - every cell in a multicellular organism is essentially forming part of the compiler for the cells next to it, so the actual complexity is probably orders of magnitude larger.

And people want to give it a clean bill of health after three months of beta testing by mice? No games studio would ship something like this.

>No games studio would ship something like this.

Bethesda might

But if they did, we'd be able to patch it at home :D

The main risk in "artificial" GMOs are that the evolved species might be a bit too adapted to the environment and start to replace the original and/or destroy species from the old biome (because new toxins kill usefull insect or small bugs, or because its taking to much from the soil thus kill surounding trees and plants...). Other concerns exist (especially when playing around viruses or other self-repliquant organisms).

I had two really long discussions (hours) with a former PhD in genetic, although he did not wrote anything about DNA: he was studying population of plants, insects and sometime cattle. From what i understood, the issue with GMOs is that the change is too fast, and other organisms from the same ecosystem often can't adapt. But this case sometime appear with "natural" settings too. And human exploitation of ressources have the exact same effect, but often without any scientist to limit the damage, as they are called after most of the damage are done.

We're actually already doing this - in Burkina Faso, researchers now have the permit to release GMO mosquitoes: https://www.scientificamerican.com/article/researchers-to-re...

Obviously, the first papers already are discussing the ethical impact of such actions: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062015/

GMO crops for example are usually quite small changes, frequently genetically less drastic and more controlled than selective crossing of plants to achieve a similar outcome. Sort of like the difference in risk of switching from a bread knife to a scalpel. Its sharper sure so you need to be careful but its fundamentally a more accurate equivalent of what you were already doing before and understandable. What's being discussed here is more like moving to training crocodiles to only bite down on the line you want to cut, and trust them to not eat the patient. The fundamental question anyone working in that gig would ask: "can you actually train crocodiles? will they turn on you?"

I'm curious what will happen when programs for eradicating mosquitoes will be ramp up globally (like releasing genetically engineered one to make them all infertile after few generations).

We probably won't try to eradicate mosquitoes, just the species of mosquitoes that preferentially feed on humans.

As it is we are mostly starting with species that we introduced into new geographies.

There's plenty of noble points that can be made about not playing God and handling the essence of life responsibly, and so on, but I think there's also some risk of losing sight of the fact that we're not just doing this for fun- we're doing it because people are literally dying and we're trying to stop it. If you have a parent or a child of yours that gets cancer, you're not going to be terribly concerned that the cure was created using CRISPR, or that there isn't 100% certainty about what all the side-effects could be.

The fact is that there is not a single medical treatment available that is fully understood; we regularly learn new things about aspirin, which is one of the most studied medications ever, and which has been in use in some form or another since a medieval wise woman chewed on some willow bark. Applying the sort of standards you're trying to hold genetic engineering to would take away every tool in the medical repertoire, aside from perhaps the bone-saw.

the precautionary principle is not a "noble point."

we don't know what we are doing. we have repeatedly - over and over - done things that do grievous damage, some of which (the dumping of megatons of CO2 into the atmosphere) are ongoing and some of which (Diethylstilbestrol, for example) did insane and long-lasting harm to generations of human beings.

Bonesaw is, indeed, reeeaaaaaddyyyy

The immune system can be temporarily suppressed, using e.g. corticosteroids, or, relevantly, chemotherapy drugs like cisplatin. It should be obvious that suppressing the immune system creates far fewer risks than modifying the virus. I am not a doctor, but I feel certain of that: the worst-case is "patient dies" vs. "zombie apocalypse".

> The problem was that the experiments also found that the patient's immune system was fighting the virus

But we already have several proven and frequently used methods for largely knocking out the immune system, i.e. immunosuppressants?

Put that on top of the damage to immune system that traditional ways to deal with cancer do. This does seem to have quite a potential in my untrained eyes.

most of the interesting data on OV at this point is based on immune stimulation rather than 'oncolytic' activity, thought they are intimately related. They have some of the best combination data with anti-PD1 at this point- some clinical data indicates they double response rates with no toxicity (vs anti-PD-1 anti-CTLA4 combinations which double responses rates, but most patients drop off therapy due to tox.). For years, these agents had been sold as ' viruses melting away tumors' which isn't really what is going on. as Immune oncology is better understood, they appear to be pretty good way to get the immune system activated in the tumor environment.

Can't they just keep re-injecting the patient with more virii as the immune system depletes it? Cancer patient's immune systems aren't exactly super strong.

I wonder if it would be helpful to do Chemo or radiation first to kill most of the cancer cells, then run this virus for a few weeks to catch the stragglers.

The negatives with chemo and radiation are so strong that they will always be more costly than alternatives.

I have not read the paper yet, just chiming in quickly that there are immune system-suppressing drugs (e.g. Humira) which could allow the virus to work. The obvious problem (and paradox for this concept) is that humira has been linked to increased cancer through immune suppression.

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