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Startup developing HIV/AIDS vaccine is 2nd nonprofit accepted into Y Combinator (venturebeat.com)
334 points by playhard on Jan 23, 2014 | hide | past | favorite | 130 comments

Lest anyone be confused by that headline, there are 6 other nonprofits in the current batch. So there is a 7-way tie for 2nd nonprofit.

I have been at times vocal in opposition to the type of companies that YC has funded in the past few batches, as the possibility of them improving life quality for people that actually need the improvement seemed quite small, largely based on a prospect of trickle down technology, which turns out to be as likely as trickle down economics, in that it rarely trickles out of San Francisco. Not saying those start-ups were easy, or not worth doing, as doing any start-up is by nature incredibly hard, and following your passion is always worth doing. But, YC's prominent role seemed ideal for doing something more, and it just didn't come.

I'll be equally vocal in support now. Watsi was the first sign of light, Immunity Project the second. This is what needs support, what needs money and hype. Realistically it won't get as much money as it needs, but with someone like YC pushing nonprofits like this, it's a huge step in the right direction. I can't wait to see the other nonprofits.

I know I sound like a bitter communist (is there any other kind?), but this really feels like an island of reason in the bubbly ocean of SF. Good luck to this batch.

Out of curiosity, how do you approach non-profits from an investment point of view? Is there some equivalent to equity? Is the goal to break even, or are you essentially just providing a large initial donation?

Really cool to see yc taking things in this direction.

Maybe I'm blind or searchiotic but cliffs on what the other 6 are doing?

I think YC is one of the few places that could actually disrupt the academic publishing and reputation-bargaining field so I'm hoping some nonprofit will tackle this eventually.

They haven't all announced we funded them yet, but another one that did today is Zidisha: http://techcrunch.com/2014/01/23/zidisha-launches-a-kickstar...

Incidentally, Scribd started out as a way to disrupt academic publishing. To do it they wrote a lot of stuff for handling PDFs, and as often happens in startups that became the tail that wagged the dog.

Looks pretty cool. Having lived in Africa for a bit I like this idea (and hope they can get around certain issues). Just created an account and completed a loan request by one of the borrowers (might be the first 0% loan I have ever given outside of my family) :)

Do you have a link to the startups? As an International Development grad this is very exciting.

Making the world better, one batch at a time!

Has YC considered any sort of broader access to the non-profits' portion of demo day for potential donors?

Well done, pg.

Does anyone know why this approach is "viewed as a rogue project by the immunology community"? Is it just because it's new, or is there something more fundamental that conflicts with established immunology?

Hi all, this is Naveen from Immunity Project YC team. The fact that we are using ML to identify epitopes that are the preferred targets on the virus for HIV controllers is key to what makes our project unique. This is a newer approach for developing a vaccine and therefore makes it "rogue."

By the way. That "rouge" approach is what would I have go through as a sysadmin if this was an computer related problem. I think you deserve to be a case study in immunology and be very very successful.

Sometimes thinking out of the box and letting go of established ways will lead to results.

Edit: Also in computer sciences we use differentiating between two known states to find out how to change on state to the other one perfectly. In immunology do you use similar approaches?

Hey Naveen, I know that there are some epitopes that can only be recognized if there's a weird domain swap that happens, causing antibodies to be "four-pronged" instead of "two pronged". I think it's a proline substitution in the conserved neck region. Did you screen out those epitopes from your ML?

Also good luck! I'm chipping in now. I'm relaunching my own crowd-funded nonprofit research in the biomedical space (and will be partnering with crowdhoster/crowdtilt)... I'm magnifying your message. When the dust settles a little bit I'd love to be in touch with you guys.

Good luck with your relaunch! I'll look for it, so I can support it again!

I can easily find plenty of papers using ML for HIV epitope analysis.

Mind linking to a few you find particularly insightful? I'm sure many of us would be more than appreciative.

This sounds pretty fascinating. Do you have any links/resources that dives more in depth into this approach?

This talk at GitHub makes good watching http://www.youtube.com/watch?v=8syV5t2_3QI&feature=youtu.be


Yes, it stands for machine learning. The one comment I saw the phrase "Mind linking" in looks as if it was short for "Do you mind linking to...".

mainly because lots of money and time got wasted in finding a vaccine. HIV vaccine would be very very risky to use thats why research is looking for a cure

Hey everyone! Ian Cinnamon here from the Immunity Project YC team. The crowdfunding link in the article appears broken (we're working on getting them to fix it). In the meantime, you can visit our campaign here: https://pledge.immunityproject.org/

I'm trying to understand what if any overlap a pharmaceutical nonprofit has with any value YC could add, from the scale of funds required, to product advice, to business model - everything seems entirely out of the range of YC's expertise.

Just had the same thoughts... They try to get crowdfunding - so this is maybe just a kind of good PR ;-) [Edit] Just to make it clear: Nothing against the project itself. Any chance of getting a HIV vaccine should be used!

I agree it seems on the surface like a mutually beneficial PR stunt, which would be pathetically shallow.

On the other hand, this could be YC's foot in the door to disrupt the high margin, high investment, treatment over cure model of the health industry, in which case more power to them. We can expect to see YC spinning off a health division. That seems like quite the challenge - hope they know what they are getting themselves into.

We do need more altruism in the health research market that will bring unpatentable cures to market instead of expensive long term treatments.

I think exposure and access to investors is a pretty big one. I also think that YC should be able to bring some of the 'startup culture' to a domain that has historically been very enterprise-y (perhaps for good reasons of heavy capital needs).


Anyone know how much YC is contributing and what they get in exchange? Some kind of ownership of the company?

Do people taking part in the $482,000 fund raiser get ownership of the company?

Why doesn't YC just donate money as part of the fund raiser?

They don't get anything.


Seems strange that non-profits have to "pitch" to validate themselves. If they have a mission, and believe in it, why do they need a bunch of money from men in suits?

Looks like easy PR and Goodwill for YC. Reminds me of all the big banks who take out full-page ads every Christmas and send out press releases touting how they're helping society by taking part in a Christmas fund raiser.

Non-profits don't have shareholders.

I'd like to understand why organisations like the Gates Foundation / NIH aren't excited by this approach? I'm assuming they've rejected this, which would explain the need to crowdfinance the next part. If they haven't rejected it, why aren't they being approached for grants?

Also, where's the science? Having something in the FAQ that states "We're awaiting publication in a peer-reviewed journal" is, to be blunt, pretty lame. Is the data and research open access? If not, why not?

We are pursuing all major funders we know of for funding for our work (including Bill and Melinda Gates Foundation etc.). The challenge is that it takes significant time to prepare grants apps, and go through the process. Some large funders such as EJAF only accept grant applications once a year. HIV/AIDS is an urgent challenge. Therefore we are crowd funding these dollars now to move our project forward immediately. In terms of the PRJ question, the bottom line is its a chicken and egg problem. Its harder to get published if you release all of the data prior to publication. Post publication, our goal is to make our project as open access as humanely possible. All of that being said, we do have more information about our work on our site: http://www.immunityproject.org. If you have specific questions about our approach please feel free to ask them.

I'm confused as to why you would encourage anyone to donate money to your organization without providing any data. I'm also confused about why you care about publication in traditional scientific mediums. You are starting a company and it would be in your interest to release as much data as possible about your successes in an attempt to raise money.

Not to mention, there are some journals that will publish pre-printed data. Here's a partial list (http://en.wikipedia.org/wiki/List_of_academic_journals_by_pr...) although take that list with a grain of salt because the pre-print policies may only really apply to math/physics publications.

there was veeery recently a bio paper that got pushed to arXiv. I don't have the link, since I saw it float by on a facebook feed, but I will look for it.

> Its harder to get published if you release all of the data prior to publication.

IF you succeed (and I hope you will).. just think how AWESOME would it be that the authors of one of the most significant achievements of the 21st century boicoted those greedy journals.

You'll probably win a Nobel prize if you succeed, why care about a journal publication?!

> You'll probably win a Nobel prize if you succeed, why care about a journal publication?!

Presumably because getting published opens up large number of potential funding sources that would otherwise ignore them.

In some areas it’s usual to publish the preprints, for example in the arXiv: http://arxiv.org/ “Open access to 909,134 e-prints in Physics, Mathematics, Computer Science, Quantitative Biology, Quantitative Finance and Statistics”

In some other areas, the journals have more strictly policies, and don’t like preprints, reprints, free author pdf copies, ...

I’d really like to see a peer-review article, even if that means waiting to see the research data. There is a lot of bullshit inside per-review articles, but there is even more bullshit outside per-review articles. A per-review is not a guaranty that the article is correct, but at least it guaranty that some expert in that area had read the article and had no found any major fault.

In a fair amount of Biology and Medicine, it's not at all common practice to place a pre-print in arXiv. It doesn't surprise me even a little that the folks here haven't done so.

According to the article Microsoft Research contributed $1M in 2011 (not the Gates Foundation but related)

A very large amount of weight, at least in NIH grants of the size we'd be talking about, is preliminary data.

One paper that's not even in press yet isn't going to set off any fireworks in a grant review committee, especially with funding as tight as it is right now.

Given the high cost (hundreds of millions) of taking a vaccine through clinical trials, FDA approval and production I'm curious why the choice to go the non-profit route.

Is the growth plan to raise the money from large donors (Gates foundation, Wellcome Trust, etc.) or to licence the technology to more traditional pharma firms ?

Most of the people who are living w/ HIV worldwide can't afford to pay for treatment. From our perspective it doesn't make sense to charge for something that the people who need it most just can't pay for. By making our project non profit we can focus on the real goal, which is ending HIV/AIDS and not creating ROI for shareholders. Yes we will need to raise significant funding over the lifetime of the project to complete this goal. The good news is that our team is very efficient. The current experiment we are hoping to execute will be done at a fraction of the price and in a fraction of the time then what it would typically cost / take at a major pharma company.

Is there some special "trick" that makes your team/approach so efficient or (just) the usual ones, e.g. less overhead due to small size, less bureaucracy than big pharma and so on?

Yes our overhead is far lower. Our other "trick" is that several members of our team are multi-talented. For example Dr. Herst can do tissue culture work, formulation development, analytical chemistry, and immunochemistry.

I really really from all of my heart wish that your project will work. Seriously, the idea of a free HIV vaccine is amazing. But honestly, I believe that you might all be a bit naive when it comes to doing proper molecular biology experiments. There's a reason why most PhD students need several years to finish their studies and they mostly use just a few techniques. Doing experiments with humanized mice and HIV might sound easy on paper, but will turn out to be way more complicated than what you believe it to be now. Trust me, been there, done that. Anyways, I wish you all the best, I love it when people challenge old dogmas with new ideas. I'd appreciate it a lot if you could put some more information about the biology, especially the role if the immune system, online.

While I appreciate that it's possible to cut down the upfront costs with talented staff, it still seems that things like clinical trials will cost hundreds of millions of dollars (at least that's the price range I've seen for anti-malarial vaccination clinical trials) and still have a substantial chance of failure at later stage trials.

It would seem difficult to raise that kind of money from other than big pharma or typical pharma capital market sources who would want to see a large pay-off from such an risky investment (i.e. selling it in countries which could afford it).

Best of luck in any case!

It is not unlikely that some developing country like India, Brazil or Nigeria could pony up the money and provide access to regulatory fast tracks if the research seems promising enough.

That said, what's your bus factor like?


Further answer: Yes the plan is to raise funds from all possible sources over time. We are open to talking to traditional pharma firms as well but we aim to keep the vaccine free to the end consumer.

Great, that's what I was looking for. Saying "provide the vaccine for free" on the site, I was cynical and assumed it just meant the results/formulation would be published but someone would still have to create it and ultimately it would be a product that is sold. It's good to hear your goal is to have the vaccine be actually free to the end consumer, that's awesome.

From the FAQ: "But, there are certain spots on HIV that rarely mutate, and these are the same highly specific targets that controller immune systems already recognize naturally. Our vaccine trains your immune system to attack those weak spots so that the virus is crippled even when it mutates. In other words, our vaccine shows the prime targets to your immune system so that it does not have to waste time and energy trying to figure out which ones are the best points of attack."

How does the vaccine train your immune system? My (very limited) understanding of vaccines is that you would normally train the immune system to target these weak spots by creating an antibody that would bind to said weak spot. But from elsewhere on the page, it says that the project isn't working on an antibody approach. What am I missing?

Instead of using standard vaccine practices (a dead/damaged/live version of the virus) to train your immune system, we are using these synthetic entities called microspheres. They are made of the same material as internal sutures, and your body takes them up and is able to have a memory response. Check out this youtube clip of the microspheres in action: http://www.youtube.com/watch?v=0XKy9byo67w

The advantage of using microspheres is that the vaccine is now monumentally safer than previous gene therapy or other vaccine attempts.

I think they mean they train the immune system by creating an antigen, not an antibody, that mimics or is identical to the nonmutating antigen on the virus. Your immune system upregulates appropriate antibodies on its own through a feedback effect when certain cells (B cell?) that have randomly generated embedded antibodies on their cell membranes come across an antigen.

These cells begin to divide faster, and the children code for and generate the same antibody as the parent. This ups the amount of cells with that particular antibody, increasing the probability that the antigen will be targeted. They trigger inflammation to increase the flow of blood, letting more immune cells per second pass through scan the area (probably not helpful for aids, but for a cut, a splinter or a tumor that is fixed in place it is useful). They also release freestanding antibodies with the same binding profile that can disable viruses and trigger other immune cells to come slurp them up.

I think when they say they aren't taking an antibody approach they mean they aren't making an artificial antibody and just injecting it for passive immunity (sort of like injecting an immune system that can't do its own adaptation and upregulation)

The main thing with vaccines I am still confused about is what the difference between them and allergy shots is, and how do the two end up with opposite effects? I guess there is somehow a different reaction to a spike of something vs a repeated presence.

(Edit: never mind.. microspheres.. who knew?)

Fascinating! What do you think the best resource is for brushing up on this stuff? I haven't had a good biology class for a while.

I'd say watch the Kahn academy biology videos, his wife is an immunologist or something so it had a big focus on the adaptive immune system. Goodsell's "The Machinery of Life" is really good too, but for molecular bio in general.

Those and just random magazine articles, etc. are really the only two things read/watched though, so others may know of some better options.

On one hand, it's clearly great news that this work is being funded.

But, maybe I'm the odd guy, here. At a higher level, does it bother anyone else even slightly that more and more of the world's priorities are being set by fewer and fewer people? This is how it's been to some extent for millennia. But, with increasing income/wealth disparity in the world, its effect is amplified.

This, of course, is a terrible example because I'm sure most can agree that attempting to cure such a devastating disease is worthy of funding. This is also not to disparage wealthy individuals (indeed, many would include me in the bunch).

It just seems that very little sees the light of day unless an increasingly small group of people deem it so worthy. And, something about seeing the priorities of even our non-profits dictated by these few gives me pause. Yes, I know that philanthropy, foundations, etc. have always existed but, again, the rate of increase of absolute power and control accreting back to so few people like the days of yore seems inconsistent with freedom, democracy, and all the other good stuff so many have come to idealize for good reason.

I get what you're talking about, but right now I personally feel happy that this effect is increasing, and I hope to be the part of this small group at some point.

It's because, to be honest, majority of humans just doesn't give a crap about anything that's further than 10cm from the end of their noses. The opposite of world priorities being set by fewer and fewer people is not lots of good things happening, it's nothing of importance ever happening. Want a proof? Just look at internal politics of every democratic state. Tons of resources get wasted, and nothing ever gets done, because people just can't agree on anything.

>I personally feel happy that this effect is increasing

Well, it's all good until it isn't. If the priorities of a few people impact so many (including you) and you no longer agree with them, then what do you do?

>I hope to be the part of this small group at some point.

I think it's actually a shame that you'd need to be a part of the "small group" in order to have a voice. Ideally, we'd all have at least the capacity to participate in our world without first requiring the blessing of a handful of gatekeepers.

And, the irony is that's the thing: It's actually harder for you to make it into the small group sans the blessing of the few who are in it. For instance, where is the real democratizing effect of the Net? For a recent, specific example, look at Bitcoin. What was once a libertarian's dream has already been co-opted by the same VCs and interests such that they will now provide the services and "real infrastructure" to grow wealthy from what was once considered an almost subversive concept. Business as usual.

>majority of humans just doesn't give a crap about anything that's further than 10cm from the end of their noses

That's true, but I think that's due to the quite purposeful orientation of our society towards mass distraction, which seems to be part of an apparent desire to limit critical thought. Witness the U.S. education system which emphasizes rote-memorization and the creation of "cogs for the machine". I actually think it's endemic to the wealth/income polarization problem. That is, such a societal structure that seeks to create a consumer class that serves as mere unthinking cogs works to someone's benefit.

>Just look at internal politics of every democratic state

I'm not sure how many truly democratic states there are. The "shining example" (US) is controlled by a relative few people through special interests, insane campaign funding laws, and revolving-door civil-servants/lobbyists. Again, all of these examples point back to the very discomfort I have: the increasing concentration of power and wealth away from "the masses" into the hands of a few whose agenda and priorities shape our world.

> Well, it's all good until it isn't. If the priorities of a few people impact so many (including you) and you no longer agree with them, then what do you do?

You have a good point here, but...

> I think it's actually a shame that you'd need to be a part of the "small group" in order to have a voice.

> It's actually harder for you to make it into the small group sans the blessing of the few who are in it.

... but I don't think it works like that. The "small group" I'm talking about is not a group of special people, either born into it or allowed to join. I'm thinking about a subset of humanity that actually gives a damn, and works towards a change. It seems that the entry exam for joining this "small group" is just getting out and doing anything - starting a company, starting a movement, starting a research project, etc. Because most people don't do anything, you can join the minority by just trying to fix something.

Actually, it's the whole Snowdengate thing that got me thinking about this issue. There's a popular meme here that "the solution must be political in nature, not technological", a statement I strongly disagree with. I've come to realize that an effective solution will have to be technological in nature, because politics means lots of talking that never gets you anywhere, while a simple technological solution can simply shift the problem landscape under people's feet. You don't have to ask anyone; you deploy, and they'll have to cope. It's exactly the kind of thinking you're worried about, but I can't really see any alternative.

You see, the world is full of short-sighted, uncaring, or sometimes outright stupid people who, if given the chance, will burn this planet down to the ground thanks to their sheer incompetence. I would love them to have the freedom and the equal influence over the world's priorities, but I also don't want my future kids to die a painful death because of a combination of stupidity and democracy.

>The "small group" I'm talking about is not a group of special people, either born into it or allowed to join. I'm thinking about a subset of humanity that actually gives a damn, and works towards a change.

Yeah, I think we're talking about two different groups. The group I'm talking about is specifically those with capital/wealth--in part, the "investor class" if you will. This group does materially dictate the world's various agendas/priorities.

OTOH, I would say that you're already a member of "your group" (i.e. the group that gives a damn), just by virtue of the fact that you seem to give a damn. So, when you mentioned that you hoped to join the "small group" at some point, I took that as an acknowledgment of my position: that is, giving a damn and having your own priorities is not enough, without the capital/access to actually do something.

>There's a popular meme here that "the solution must be political in nature, not technological"

I'd say legal in nature, not technological. And, that's purely a practical matter. That is, it's not that I'm overjoyed about the state of our legal system. It's more that I don't think it's practical to play technological cat-and-mouse with our own government and expect to win. So, IMO, if we don't at least attempt to constrain the government legally, then we've lost hope.

But, I digress. To your bigger point, yes, seeking legal redress does have political implications. And there's no doubt that we need to fix our politics, but again, I think the problems are one and the same: the few moneyed interests I mentioned dictate our agenda, in part through our politics. So, while our politics appear to be broken due to sheer incompetence, they actually are not. They simply serve an agenda that is not "for the people", while attempting to maintain the facade that they are.

>...will burn this planet down to the ground. I would love them to have the freedom and the equal influence over the world's priorities, but I also don't want my future kids to die a painful death because of a combination of stupidity and democracy.

Well said and I agree to some extent. Beyond mere politics though, I'm lamenting the access to power to all but a few. That is to say, there are certainly also many thoughtful, caring people in the world whose ideas/actions could help to shape it and make it a better place for all. In other words, it's not simply a world of a few moneyed people who know what's best for everyone on one side vs. a slew of completely ignorant, incompetent, malicious dullards on the other. There are many in the middle whose priorities also deserve the light of day. I would imagine that you and I, as well as many others who post here fall somewhere on that spectrum.

This is going to be really inconvenient for all the people who say "sure, you are good at making photo sharing apps and dating sites, but you don't cure cancer or anything."

I suspect that those people value the fact that this is happening more than the fact that they don't "get" to complain about it not happening.

Being one of those people, and an Epidemiologist, if this team manages to succeed, I'll happily shut up.

Yeah, lets wait and see how fast they get their $25M. Giiven that photo sharing apps can get billions of dollars just like that, if the Immunity Project will have to struggle for their $25M, I'm giving up on SV altogether.

Photo sharing apps get money from VCs. Why would you expect that VCs would fund a non-profit millions of dollars?

God forbid the people doing the actual work would get the credit.

I'm a bit confused. Who is the "you" here?

How heavily does the project depend on obtaining correct target epitopes from Heckerman's protein Gibbs free energy simulation?

Is there a chance that HIV won't be controlled even if we can induce the immune system to be capable of targeting some of the peptide sequences that controllers often target? (i.e., might there be something else at work in controllers?)

Thanks for working on an important project!

Right now the project is only relying epitopes derived from actual controller targets. Our hypothesis is that if we go after the epitopes that HIV controllers preferentially target that we will get an immune response with memory in humans just as we have so far in our animal studies. The only way to test this is to execute on our clinical trial in humans. The current experiment we are aiming to perform is a good middle ground since we will be immunizing human blood against HIV in a controlled environment and then testing that immunity.

The experiment in blood sounds interesting, I hope it works!

It looks like there might be differences between controller immune systems and regular ones that don't have to do with choice of epitope:


Does this make it less likely that targeting specific epitopes is all there is to the picture? (I'm happy to assume that we'll get an immune response with memory in humans -- the question is, how confident should we be that that response will control HIV?)

The article is describing one of the many explanations that has been brought forward to explain why controllers do what they do. If you are looking for a common denominator across controllers broadly, the selective epitope targeting explanation seems to make the most sense to us and does not appear to be constrained by anything but the individual's HLA type which essentially determines what epitopes a particular individual's immune system can "see."

This is a really interesting project. I have so many questions and it seems others too. It would be great to do an AMA on Reddit or something.

So one question: This "targetting capability" that HIV controllers have, which your goals is to give it to all of us, does it also have any other benefits? Does it also help protect us from other viruses?

We're absolutely planning on doing an AMA on reddit in the near future!

The "targetting capability", definitely does have implications for other types of viruses. While this vaccine focuses on giving the power of HIV controllers to everybody, other controllers do exist. For example, there may be controllers for other viruses like Hepatitis, HPV, Herpes, or even things like other viruses that cause cancer.

This is one of those times when you take a step back, reflect, and look at the big picture. However much excited I am about my project, I realize that the stuff these guys are working on hits all the right notes. And then some.

Thanks, jjoe! We really appreciate your support.

Very interesting. I noticed the article mentions that the algorithm used is "similar to the techniques of spam filtering" (paraphrasing). Would it happen to be a Bayesian Network or a logical agent?

So have they developed a vaccine, but they need money for trials, delivery..? How exactly would they go about and test if it works on humans? Are there people who volunteer to get infected with HIV?

I'm Ian Cinnamon, one of the members of the Immunity Project YC team. We have in fact developed the vaccine. We've completed 2 years of animal testing, and we have one final experiment to run before we start our Phase I Clinical Trials in humans. In order to test the efficacy of the vaccine in human trials, we go to Durban, South Africa, where HIV has a prevalence rate of ~15%. We dose a wide range of healthy volunteers, and we check back again at regular intervals to make sure they have no contracted HIV. We're also able to perform a wide range of laboratory tests to show the dosed human blood is now immune to HIV.

Ian- YOU developed the vaccine for HIV? Were you part of some team from a university? Or did some other company develop the real science and you are partnering with them? How can you offer everyone in the world a free vaccine for your crowdfunding target of only $500K? where does the money you raise go?

Our Immunity Project Science team, led by Dr. Reid Rubsamen, developed the vaccine. The $500K pays for our final experiment before we begin our Phase I Clinical Trials. We've already conducted over a decade of research and two years of pre-clinical trials with overwhelming success.

If you look at the fundraising page they have a budget but it looks like the $500k just pays for the next experiment it wont even get them to Phase 1. Microsoft Research gave them $1M to get this far.

I did some more research and would really like a clarifcation of this project.

First of all - Flow Pharma is the inventor of the vsaccine - they are a FOR PROFIT angel backed company. Why do they need crowdfunding?

Second - How does Immunity project work? It seems that the real non-profit is "Until there is a cure". So you are donating money to them, which then give the money to the immunity project which pays for a trial of an unproven drug for a FOR prfit company.

This is a fantastic project and I promise I will donate if you have full disclosure. thank you for doing this.

More then happy to give you the full details on how we've set this up: the vaccine is being developed by Flow Pharma Inc. Instead of setting up our own 501(c)3, we setup a fiscal sponsorship agreement with Until There's A Cure, a leading HIV/AIDS focused 501(c)3. We are operating the project as a non profit even though our entity type is technically a corp. In other words we are obligated to follow 501(c)3 rules and regulations, and we are obligated to give our vaccine away for free regardless of our entity type. The primary reason we did this is because its much better to work with a well established 501(c)3 that has team members who can help provide validation and support then to start from scratch on your own. It is also much faster to do this then setup your own 501(c)3.

Thank you very much for your response! Unfortunately, I do not think you actually answered my questions!

* Why does Flow Pharma need crowdfunding when they are FOR PROFIT? * How can you guarantee FREE vaccines for everyone for only $500k? * What will the crowd founding be spent on and will there be follow on investing needed? * What is the future of Immunity Project? Have you begun your application to be your own official non-profit?

EDIT: I seem that someone else answered a part "Dr. Reid Rubsamen, developed the vaccine is part of the Immunity Project", but does not explain the exact relationship with Flow Pharma?

> How exactly would they go about and test if it works on humans?

Presumably, the same as the other HIV vaccines that are in trials.

> Are there people who volunteer to get infected with HIV?

There are people who volunteer for vaccine trials. They don't need to volunteer to get infected with HIV -- basically, you get a large enough experimental and control group, study risk factors in the groups, and track infection rates, and evaluate whether, based on that, the vaccine reduces infection rates.

For human trials of this nature, typically at-risk populations can be used, and it's seen if there's a reduction in infection rates.

Exactly. In this case, we're lucky enough to use an amazing clinic set up in Durban, South Africa, which has a ~15% prevalence rate of HIV.

This sounds great. I'm genuinely interested, how is the potential vaccine going to be presented to volunteers in Phase I? And do you also deliver a placebo vaccine for blinding?

It seems like believing you are vaccinated would increase risky behaviour. This is bad in itself. It is also bad if the vaccine is only partially effective, since the risk effect might balance the vaccine effect.

With a placebo, knowing you only have a 50/50 chance of getting the actual trial vaccine might also help mitigate the risk effect.

Anyway, just wondering how all this works. Finding an effective vaccine would be fantastic; keep up the good work!

Thank you for your support! Yes it will be presented as a double blind, placebo controlled study. Regarding the risky behavior point, this is a well known challenge with all vaccine studies. And yes telling people that they don't know whether or not they have the actual vaccine helps in mitigating the risk effect.

> It seems like believing you are vaccinated would increase risky behaviour. This is bad in itself. It is also bad if the vaccine is only partially effective, since the risk effect might balance the vaccine effect.

But this will also be true of the vaccine as employed in reality, and thus a useful piece of information to capture.

Yes we've developed a vaccine prototype and we are raising funds for the final experiment before we start working with the FDA to file our IND and start working on our phase I clinical trial. In terms of testing on humans, the first thing you do is dose healthy volunteers and withdraw a blood sample to test for an immune response. Then assuming success in phase I, in a phase II trial we will dose high risk healthy volunteers and see if they get HIV over a time interval.

Monkeys. After all, the HI virus originates from apes and they are similar enough to humans for clinical tests. And as for "ethical research", once you know the vaccine will not harm you, give it to a big enough group of "risk people" in Africa or another HIV hotspot and look if they, compared with a placebo group, are immune from HIV.

I don't get it, isn't the point of investing to get the investment back in many multiples? How do you get your investment back if it's a non-profit?

It's simple, it isn't an investment in the financial sense.

The betterment of the world as a whole?

That's great, but the job of investors is to make money, not to better the world, isn't it?

Investors are humans, like all the other humans, who happen to have the ability to commit significant funds to things, including startups, cars, and charities. There is a well- known challenge of putting large charitable donations effectively to work; that's why Warren Buffett put all his money into the Gates foundation rather than starting The Warren Buffett Foundation or donating it to the Red Cross.

Seen through that lens, it's straightforward to see how enabling people to come up with innovative and effective new charities that startup investors can help fund is a worthwhile project.

The job of investors is to do what they want with their money and make sure they have an alignment of goals with those they give their money to.

I didn't mean to say that they can't do whatever they want, or that they're incapable of helping the world. But if the investor does not expect his investment back, then that would make it a donation, which - as far as I can tell from the article - this is not.

From their page on funding non-profits: http://ycombinator.com/np.html

"Since some people were confused when we funded Watsi, I'd better clarify that the money we're putting into the nonprofits will be a charitable donation, rather than an investment in the narrow sense. We won't have any financial interest in them."

If you need a cynical money-driven motivation, it's more humans to sell things to.

s/make money/build value/g

I assume it's a tax dodge of some sort. I'm sure that investments in non-profits can be offset against capital gains (or something like that).

I'm not an investor and this isn't tax advice!

No, as far as I know we get no tax advantage from this beyond what anyone gets from making any charitable donation (the ability to deduct it).

Why do people think this?

Charitable donations do often result in reduced taxes. The catch is that the reduction in taxes is less than the donation (and at least in the U.S., there is no combination of State and Federal taxes that is greater than 100% of income...).

If you cure AIDS, you're worth probably $50B, so there's that.

Does this mean that contracting the virus with the vaccine will give you HIV but not AIDS? What about being a carrier, would you still be a carrier?

If you're vaccinated, your body would fight off the HIV virus. You would have an upgraded immune system.

In terms of independently curing AIDS, although the vaccine has therapeutic potential, it mostly likely applies only to those particular individuals living with HIV who have normal immune systems – i.e. those successfully managed on HAART medications. The vaccine may prevent AIDS, but it will not cure AIDS.

I'm all for this; more power to them. However, HIV/AIDS is already very preventable and had been on the decline for a decade or more. I'd rather see something like this effort, but for cancer. A disease that affects many more people.

Actually, what I really want to see it a focus on stopping poaching, whaling, habitat destruction and ocean acidification. Even with all the disease, humans don't seem to have issues reproducing. Extending the human population, especially those of developing countries, only leads to more of the above. One day our children are going to say - "Cool, no more HIV, but what's a rainforest? what's a Rhinoceros? why can't we eat fish." Just saying.

HIV/AIDS is a giant problem. North of 35MM people are living with HIV worldwide and more are infected every day. Yes we have made strides in reducing infection rates, but we are far from solving this problem with existing approaches. To put this in context, nearly 5,000 people a day die from AIDS. That is like 10 747s falling out of the sky every single day. The only solution is a vaccine which is why we are doing what we are doing. There are many big problems for us to solve on our planet. HIV/AIDS is one of the biggest and hardest to solve.

Awesome. I'm certainly glad people care enough to work on these types of real issues.

Bill Gates just addressed this [1], showing the faulty thinking behind this idea that saving lives is ultimately bad for the earth.

"It may be counterintuitive, but the countries with the most deaths have among the fastest-growing populations in the world. This is because the women in these countries tend to have the most births, too.

This pattern of falling death rates followed by falling birth rates applies for the vast majority of the world. Demographers have written a lot about this phenomenon. The French were the first to start this transition, toward the end of the 18th century. In France, average family size went down every decade for 150 years in a row. In Germany, women started having fewer children in the 1880s, and in just 50 years family size had mostly stabilized again. In Southeast Asia and Latin America, average fertility dropped from six or seven children per woman to two or three in a single generation, thanks in large measure to the modern contraceptives available by the 1960s.

Because most countries—with exceptions in sub-Saharan Africa and South Asia—have now gone through this transition, the global population is growing more slowly every year. As Hans Rosling, a professor at the Karolinska Institute in Sweden and one of my favorite data geeks, said, “The amount of children in the world today is probably the most there will be! We are entering into the age of the Peak Child!”"

Saving lives will improve humanity and -- as humanity has discovered -- actually contributes to fewer births. This is one of the reasons we see shrinking populations in 25 nations including Japan, Ukraine, Italy, Greece. [2]

The reality is that saving lives counterintuitively decreases population through lower birth rates, which may ultimately help the earth.

Also, observe that the world is at its highest population today, and yet, billions of humans are totally resource-secure. Why this counter-intuitive phenomenon? It's largely thanks to technological advancements in farming and genetics. There is no reason to believe this trend will not continue.

[1]: http://annualletter.gatesfoundation.org/?cid=bg_gn_ll0_01202...

[2]: http://en.wikipedia.org/wiki/Population_decline

Thanks for all the notes. Great points for me to ponder. Perhaps Mr. Gates is correct to an extent.

highest population today.. yes but what about pollution levels? highest ever too? natural resources also more depleted than ever? your post doesn't address the issue of overpopulation...

Pollution levels are not at their highest [1]. And even if they were, it would not mean we should stop saving lives.

Gates' post shows that saving lives actually helps overpopulation, historically. And through technological advances, we are more resource rich than we ever have been. That you're sitting there in a comfy, heated office with all the food, money, and resources you ever will need is evidence of this. Better yet, the same resource richness you now enjoy is spreading around the world [1].

Natural resources: if you mean things like oil, well, that is a resource only humans need to use; our using that resource isn't a bad thing in itself. Yes, it has some negative side effects, and yes, it will eventually run out. But when it does, we'll move on through more technology.

The "world is doomed because of too many humans" thinking is terribly shortsighted because it assumes humans will never increase resources, solve diseases, and never populate other planets. Those assumptions are increasingly shown to unlikely, if not foolish.

[1]: http://annualletter.gatesfoundation.org/#section=myth-one

Something like this, but for cancer? Here you go: http://www.indysci.org/project-marilyn.html

So make it happen (seriously).

I donate to campaigns that I think believe have a real impact. One of my favorites is http://thetashingainitiative.org/

Wonderful! Good on you for taking action.

Finally an answer to the question: "What do I have to do to get into YCombinator? Cure aids?"

This is very good news. Good luck.

great job guys, keep up the good work. cant wait to see what comes of it.

Just donated. Very cool.

Thank you for your support!

when are we going to start addressing the problem of overpopulation?

There's a lot of non-profits that aim to make birth control more wide-spread, too. Do you have any other ideas how overpopulation can be tackled by a startup with purely legal methods?

I believe that decreased child mortality and increased education/self-sufficiency for women are two of the big triggers for reduced birth rates in developing countries; in other words, increase the chances that the kids they have will survive to support their parents, and decrease the need for mothers to be supported by their children/possibly increase the opportunity cost to them of having children (although I don't think I've heard it described in that last way, it's just how it looks to me).

Good points, thanks! I now see that Bill and Melinda Gates addressed the same points in their annual letter:


That'll never work. It has to involve social media somehow. Or apps.

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