Seneca Valley Virus has earned a reputation as a potent oncolytic agent | Hacker News Reader

Seneca Valley Virus has earned a reputation as a potent oncolytic agent

pnas.org

248 pointsknown69 comments

> They used a cryogenic electron microscope to see the link between the virus and the receptor at a resolution of only a few atoms

I would love to see some of those pictures!

Edit: one of them is in the paper linked below,https://www.pnas.org/content/pnas/early/2018/10/30/181066411...

Amazing what the human race can accomplish!

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.

> 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.

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.

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.

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.

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.

Great research. But now I'll have my usual rant based on a quote from the article:

>> Findings from this study, in conjunction with future work on SVV-antibody interaction sites, can provide a promising stage for the development of SVV mutants with improved clinical applications.

In this case "improved clinical applications" means man-made variations that can be patented. I mean, why wait? Sure go ahead and try to improve on it, but in the mean time isn't it recommended for trials (in addition to other treatments) against certain cancers? Or is it and I'm just not aware?

There are other known viruses with the same afinity to cancer cells. See the Newcastle virus affecting chicken. Same problem: usually human immune system does clear it up from the blood, so it can not reach cancer cells and wipe them out. But N.virus-related cancer patient recoveries have been described. Small number studies so far.

I wonder if this isn’t a blessing. Maybe the treatment is to inject the virus near to the tumor. That way it does it’s job but is inevitably removed, thankfully, by the body’s immune system. It shouldn’t remain in the system longer than it’s needed anyway.

> it does it’s job but is inevitably removed, thankfully, by the body’s immune system

Some virus, like herpesviruses are able to fuse with the genetic code of the host and remain there indefinitely. The inmune system will not touch it at this state normally.

Do people ever learn anything from science-fiction movies? This is how every zombie movie starts.

Not if you treat the virus as a magic bullet eliminating metastases in the body. Without that property it is just a method to reduce, at it's best eliminate the primary tumor. Makes sense if surgery is impossible. But then we will probably end up with the effects of tumor necrosis.

Brain storming idea: the brain itself is a special place in some way shielded from the immune system. It would be great if ie injection of the virus in a glioblastoma would work. Probably with some measures to prevent oedema

Inject the virus directly into the tumor(s). It should then be able to inflict maximum damage before the immune system comes along and stops it. Perhaps the use of viruses needs to be in addition to other treatments for this very reason.

If you have an isolated tumor you try to cut it out. Except if it is in the vital parts of ie the brain. Primary tumor is not the biggest problem in most of the cases. Metastases are what kills.

It baffles me that 182 people have upvoted this. I must really be out-of-touch with a large portion of the HN audience because not a word of this report makes sense to me. What's the deal? And what introductory books (or blogs) would HN suggest so this actually makes my brain go "oh, that's neat"?

submission URL was changed, was https://www.healthfoodis.com/2019/01/researchers-have-identi... before

See: https://www.khanacademy.org/science/high-school-biology/hs-h...

Search for 'What is a viral infection?', read down from there to '1. Attachment' and make sure to expand the help tip on that one.

From a 30 sec scan of the article, this is about a specific virus' preferential binding to a site that is expressed in many cancer tumors (anthrax toxin receptor 1, ANTXR1).

This would allow viral-driven targeting of those cells (and few others), one of the hardest problems in oncology. You can't hit what you can't find, or you have to soak the entire body in enough toxic chemicals (chemo) to ensure it reaches the tumor cells.

As with many things in microbiology, it seems we knew this virus could preferentially target cancerous tumors. But we didn't know precisely why (aka "the mechanism") or how. This paper is proposing an answer to that question.

Microbiology is essentially the study of how to build 3d puzzles with chemistry and physics. Doing that is hard.

I'd highly recommend learning the basics of biology at the microbiology and biochemical levels. It's a fascinating world, helps explain everyday macro-medicine (read: what a doctor tells you), and I've found a surprising number of useful parallels in computing systems design.

(Correct me if I'm off on anything, it's been a while since microbiology)

HN crowd is more diverse in skills and professions that it would seem at first glance, and even more diverse in interests. Personally, I frequently upvote things I don't understand well, just to keep them on the front page longer, to maximize the chance that someone with the necessary knowledge posts a comment with an explanation or tangent that I can understand.

Always felt in my science-gut that the body’s ability to produce new tissues of any-type anywhere in any amount for any reason was probably of great benefit to us for the most part, and that treating it like a plague to burn out was on the wrong track, and that treating it like something to attack at its mechanistic route would probably bite us in the ass twice as hard

> Always felt in my science-gut that the body’s ability to produce new tissues of any-type anywhere in any amount for any reason was probably of great benefit to us for the most part

Except, of course, for being the second-leading cause of death. The problem is being attacked from every angle, I'm not sure what you suggest they do better. The plague-burn-out methods might save your life someday.

Well, let's observe the run for the patent.

When an article presents findings about curing cancer it's an immediate red flag. Cancer is not a single disease but plethora of different diseases/types of tumours with different behaviours and cures. You don't treat a breast cancer the same way as a lung cancer or brain cancer. Even talking about "brain cancer" is very generic and covers a wide range of tumours that are treated differently.

From the article:

"In an attempt to understand how the virus works, researchers at the University of Otago in New Zealand discovered in 2017 that the virus binds to a receptor called ANTXR1, which is active in more than 60 percent of the cancers in humans."

"Such a move may be dangerous, as it will improve the virus's ability to destroy cancer cells, but also produce a virus that is completely resistant to the immune system, and if it builds up mutations, it might become dangerous."

Much better premise than the Umbrella corp. of Resident Evil or all the other cliche zombie tropes

This is the premise of the film adaptation of I am Legend;

> The story is set in New York City after a virus, which was originally created to cure cancer, has wiped out most of mankind, leaving Neville as the last human in New York, other than nocturnal mutants.

https://en.wikipedia.org/wiki/I_Am_Legend_(film)

Mostly, Just Another Generic Zombie Film, though.

Wow

the book was so much better.

The alternative ending to the film significantly improves it. You can easily find it online. (I'm not going to spoil it.)

The directors cut? That was a wild ending

Generic after when zombies turned into speed demons.

The book is superior in every way.

The Omega Man is also a much better film adaptation than the Will Smith effort. Killer soundtrack too: https://en.wikipedia.org/wiki/The_Omega_Man

"Horrible virus used to cure xxx disease ends up destroying humanity" is becoming a common trope in fiction. Rise of the Planet of the Apes, The Passage, etc.

Fiction hasn't been accurate at predicting good things in the future, but it sure has been spot on when predicting the bad stuff. It feels like we're living in one of those frustrating horror films where the protagonists ignore obvious warning signs and put themselves in the worst possible situations.

I'm dubious about modifying a virus to escape our immune system - seems like that could come around to bite us in the ass. But they basically identified a receptor unique to cancer cells and what's different about binding to it vs binding to the similar version in healthy cells. Seems like a great drug target. You could even probably make a drug that binds to it and triggers an immune response, get the immune system on side. I'm not an expert in the field by any means, but I'd rather see that than a super virus.

For those that prefer primary sources the original paper from Oct 2018 is available at PNAS (Proceedings of the National Academy of Sciences) here: https://www.pnas.org/content/pnas/early/2018/10/30/181066411...

Thank you for doing the lord's work of looking up primary sources

It was linked as a reference at the bottom of this article. I agree this should be the source though.

Thanks! We've updated the link from https://www.healthfoodis.com/2019/01/researchers-have-identi....

Not sure that was the best move since it's now a paper full of deeply technical terms, hard to understand what it's even saying...

That's fair, but on the other hand Hacker News readers often lament the state of science journalism. Is there something in the middle between the originally submitted lightweight article and the actual paper?

This does not seam like a legitimate article. This is most likely fake news. The website cant even spell Nutrition right.

You should have at least looked at the reference section before criticizing.

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