YC Bio
blog.ycombinator.com
blog.ycombinator.com
For those brainstorming startup ideas some relatively recently funded companies include:
eGenesis - Dr. George Church's company that uses edited porcine stem lines for human xenotransplantation
Twist Bio - synthetic bio for applications ranging from novel materials to data storage
Denali - focus on age related neurodegenerative disorders such as Parkinson’s and Alzheimer’s
Benchling - molecular bio and gene editing design software
Synthego - free gene knockout kits
But of all the breakthroughs last year. The one that may be most impactful. Editing human genes in the embryo to remove hereditary disease.
Correction of a pathogenic gene mutation in human embryos
https://www.nature.com/articles/d41586-018-00335-8
Maybe the first startup YC should fund is one to mutate the enzyme to avoid immunoreactivity while preserving function...
Tech investors are almost totally unequiped to do the necessary DD. They either therefore go for plays that are easy to understand, largely computational exercises or in the rare cases they do go for something higher risk, they back something crazy (e.g. Theranos) because they don’t do good DD.
Getting an “expert” to vet the play rarely works. Because tech VCs don’t know how to choose good experts.
So most of (all?) these plays will ultimately fail. It won’t matter much to seed round investors though, because they’ll take 10 years to fail and they will likely have at least partially exited by then...
My observation during this dot-com boom is that a lot of the people who did well last round are now part of the VC infrastructure, like our own Paul Graham. My impression is that this time around, money is a lot more competent because of this.
Because this made such a huge impact on my life, I kinda want to extend it: perhaps the first round of any new technology is going to be littered with bad ideas. Perhaps that is necessary. Then perhaps those with experience can look backwards and do better next time.
I personally still think we are headed towards a second dot-com bust, but I've been saying that so long that at this point, I'm just wrong. Unquestionably, the business and money people did their jobs much more skillfully this time around than they did in the '90s.
As a wise man once said[1], “the market can remain irrational a lot longer than you can remain solvent”. At some point, the tech boom will end, and probably for many of the reasons that you have been telling anyone who will listen. The hard part is forecasting precisely when it will end with any range and precision.
My main point was "perhaps the first round failure is necessary" - of course, I weakened that with my assertion that this second tech bubble is also a bubble and bound to burst.
They rarely dig into how the background of the team and their ability to deal with unforeseen problems. That is, in my experience.
There's a huge problem in non-transparent pricing for products. For those outside the industry it's like buying used cars, dealing with sales reps and everything is a quote. Researchers are at a huge informational disadvantage when it comes pricing.
Example, acetone which is a commonly used solvent:
https://i.imgur.com/QyJ1Tj5.png
https://i.imgur.com/mJyfFfX.png
$900 vs. $300
Another example, IPTG:
https://i.imgur.com/tvnVAqO.png
We commonly see 3-5x differences and up to 10x for the exact same item. This makes a huge difference when you're in the range of 500k to 1 mil from YC Bio.
Interestingly, servers seem to be only 1.5x, and if you buy your servers in parts, the variance is even smaller.
If using your tech skills to help battle disease in an ambitious way is interesting and you wanna learn about a new, quiet startup (top-tier funders, world-class bio folks already on board for you to partner with, rare advisors from tech/bio/pharma), ping me: kamens@gmail.com
We're hiring a couple more for our early team and specifically looking for data, infra, and ML engineers. No specific bio background required. Staying quiet for now, can share more when we talk.
Sometimes, we have some promising leads on disease that we can begin to chase down. Most of the time, however, we have no idea where to begin, and so a shotgun basic science approach may ultimately be more fruitful. Every subfield is different and difficult to master, which is why it is so important to engage with the people who actually do the work.
I know the tone of this sounds like I'm beating a dead horse. I'm sorry.
Great to see YC address the lab space issue and give a larger cash/equity cut for biotech focused companies.
I am wondering how early/late stage the desired biotech company should be. Right now, many biotech-y YC applications/interview participants seem to be rejected with the comment that they should come back later.
It's great to see some targeted support for bio, though! It seems like a harder market division to get into than a pure tech company.
https://doi.org/10.1006/jtbi.2001.2430
You will see that there is no good way to compress the tail end of mortality and consequences resulting from accumulated unrepaired damage. The only cost-effective path is to postpone it indefinitely through periodic repair of that damage.
Aging is damage, and mortality/disability rises with damage. Effective treatments for aging are forms of repair of damage, of which only senolytics presently exist in any form that is available. Once you accept this model, you can start to reason about the effects of various approaches, and everything makes a lot more sense.
It seems to me a great deal more people face a very different question, "how can I afford to live longer?"
please, please, please, please, please, please, please ensure that at YC the people with money do not try to interpret laboratory data and stay far away from making any kind of project-level decisions.
it's something they (VCs) love to do, in my experience. incorrectly. and it's a massive waste of scientists' time, to have to correct the moneymen's misunderstandings of rudimentary things. then it's a cringe session when you hear them trying to explain it to other moneymen. then it's a big tearjerker when the moneymen's childlike expectations aren't met, and the company suffers.
something about biotech VCs and business types makes them think that they understand their products and products-in-development even if they're unqualified. the reality is that the depths of their ignorance are very embarrassing.
but i digress. i hate to rain on the parade here, but my bet is that most of the early stage biopharmas at YC will fail due to one of two reasons:
1. nature isn't working in the way they need it to.
2. the people with money don't stay out of the way enough and make stupid decisions that they don't understand.
i've seen a few biotechs fail to reason 1-- always tragic, but nature always has another trick that mankind will figure out some other day.
i've also seen a few fail to reason 2. it's very predictable, and saddening every time. non-technical types in leadership positions need to stay far away from biotech, especially at an early stage... they ruin things by cutting funding at the wrong time; they ruin things by forcing idiotic focuses; and they ruin things by believing that manipulating nature is similar to making a faster horse.
i have plenty of ideas on how to make biotech startups work better when they receive funding, however. they are, shall we say, politically incorrect-- both to the society of the scientists as well as the society of the VCs. perhaps i will share them on some other evening.
In the embedded/IoT industry, the majority of medical device innovation is centered around home monitoring/care for older patients in nursing homes, or for preventative/medicine.
Can anyone with experience in the bio/chem/pharma startup world point to good resources where we can get up to date on the most exciting/promising new bio tech/startups of the past 20 years or so? Also related - has anything come out of Alphabet Calico [1]?
E.g. some resources in which people are less than complimentary:
http://www.sens.org/research/research-blog/question-month-16...
https://www.technologyreview.com/s/603087/googles-long-stran...
https://www.vox.com/science-and-health/2017/4/27/15409672/go...
There are plenty of others if you want to go look for them.
There was a startup trying to make autoluminescent plants with jellyfish genes before CRISPR even existed, just using ordinary plasmid creation and transfection techniques.[1] That particular effort failed commercially, but I believe they recently reincorporated as 'GLEAUX'.
Anyways, Biology is messy and difficult, but I really think that we are getting to a reasonably solid understanding of genetically engineering plants. And once someone turns that into a '1, 2, 3' process...well I don't think you need more than a 5-figure investment for equipment/space.
[1]: http://journals.plos.org/plosone/article?id=10.1371/journal....
Short answer: there is a "perfect storm" of innovation right now in bio. Tech from the 2000s genomic bubble is entering the mature phase of the hype cycle and ushering in a new era of potential curative therapy (gene therapy, cell therapy, personalized medicine). Avexis, a company treating a devastating neurological disease affecting infants using gene therapy, is ky favorite example to this
There is also the more widely hyped tech, AI, wearables, synthetic bio, etc, with massive potential, but these techs haven't had much impact on patients yet
Post here: http://newbio.tech/blog.html
The perspective one takes on the biological system in question is vastly different depending on where you are coming from. Biologist understands bigger picture ideas about the system and can narrow down potential solutions. Tech injects more rigor and organization into how data is collected and analyzed. The skills are very complementary.
I am optimistic because I am seeing more people coming up in the field who are trying to do both molecular biology and data science.
I'm a professor at WashU and am interested, but I live in St. Louis.
YC's "move to the bay area" requirement makes sense for software startups, but less so for bio (at least for most of the good ideas).
https://techcrunch.com/2017/12/14/gingko-bioworks-secures-27...
That said, they said they've learned some lessons and they are providing more capital, and I'm sure if any organization can fix the biopharma seed exosystem it's them
The most important thing for them will be to get the right group of mentors. If you go off on the wrong scientific direction at the start of the company, it's much harder to salvage things with a pivot, so you need good eyes on all details of your experiments before you deploy capital
Biology is a very different field; stuff that is wonderfully promising can get help up for years based on trivial mistakes or simple strategic errors. And on top of that, 95% of the stuff that sounds great won't amount to anything, and you can't tell until a few years have passed.
Our understanding of molecular biology isn't nearly as plug-and-play as many would like it to be.
What could be better than glowing monkey grass leading up to your house? But as always, devil is in the details.
That said, it's true that we do also need to address healthcare costs - that is a huge problem and we would love to fund companies working on it.
I wrote about the opportunity in bio earlier this week and run a program connecting top tier scientists with life sci VCs. If you are interested in bio and don't have a science background, this is the best time ever to get involved: http://newbio.tech/blog.html
It's still not perfect, though, so the things we're trying in this experiment, like providing lab space for companies, are the next step.
I also can see no means to turn it into a business model or income stream, nor even get anyone interested in benefiting from what I know for free. It isn't the magic bullet people are looking for. A spartan life, eating better and lots of walking is not an answer people want. It also isn't an answer that investors will fund.
Meanwhile, hey, lung transplants and $300k/year new drugs for CF are all the rage. That makes headlines and apparently makes money.
A business model for healthcare seems to produce Frankensteinian outcomes. Things that are actually health promoting, like having a full-time parent to care for the kids and primary breadwinner, eating right, exercise etc are boring and don't make VCs rich. They are actually quite challenging to promote at all.
I wish I saw it differently.
There was just a huge wave of Alzheimer's treatments that people were so hopeful might make any dent in the disease. They all failed, apparently because the breakthrough we thought we had made in understanding the disease turned out to be specious. Had the drugs made ANY improvement they'd be on the market and we'd all be bitching about how pharma "likes to make bandaids rather than cures," and that would have been a disservice to the years of toil people put into these drugs.
Not every pharma actor is a good actor. But overall the space is mostly filled with scientists and doctors trying to make people healthier, and mostly failing.
He also survived colon cancer in his late 60s for the same reason and I flew out and took care of my sister after her first mastectomy with her first round of cancer. The doctors attributed my father's survival after they wrote him off for dead to my mother's care. They interviewed her on tape and changed the practices at their clinic based on what she had to say. From what I gather, two different cancer clinics began offering patients German Penaten cream to help their surgical scars heal because that was why my father's 16 inch surgical scar did so well.
I have zero reason to believe you are correct. There are some differences between different diseases. But my life's experience suggests that a) getting fed right b) getting proper care from someone who actually cares about you and c) adequate control over your environment are pretty universal beneficial, regardless of your exact diagnosis.
(But I'm just a woman, so not likely to be listened to. Yes, I'm feeling pretty bitter about that at the moment.)
Not sure what your point is. Those things are helpful, can extend healthspan a bit, but they're also completely orthogonal to medicine, and are not solutions.
This explains a lot of what is wrong with medicine today. It was different when I was growing up. Doctors would treat all the kids in the family at one time so some infection didn't simply get passed around endlessly. We seem to have stopped doing that, and we wonder why drug resistance is such a problem.
> Things that are actually health promoting, like having a full-time parent to care for the kids and primary breadwinner, eating right, exercise etc are boring and don't make VCs rich.
Correct me if I'm wrong, but I see you implying something like "why do medicine, if we could eat less 'junk food', work less and smile more instead".
> curing Rickets and Scurvy by identifying the nutritional deficiencies behind then us totally not an advance in medicine
That's indeed the domain of medicine. Which will tell you, "you need more nutrient $X in your diet" as a solution to the problem, instead of "eat healthier" (for values of 'healthier' determined by current fitness fashion).
That sounds just really arbitrarily personally hostile towards me.
I have gone through multiple blogs in which I have tried to lay out specific nutritional recommendations for people with CF. The few people who have tried it have gotten results.
I have done everything within my own power to try to elucidate specifics no different from the examples of Rickets and Scurvy being caused by nutritional deficiencies. But it does not get taken seriously and I can find no path forward for that, and not due to lack of trying. One woman said she would write a paper with me on the subject, then arbitrarily changed her mind. Her son died of CF. She was a smoker. I don't think she really wants to admit that her smoking helped kill him. She wants to find a pill that makes everything OK and absolves whatever guilt she carries.
The CF community is not interested in what I am doing. So there probably is no path forward here. I fully expect to die in obscurity having never accomplished anything at all with my life.
But this arbitrary validation of nutrition as medicine, unless I am doing it and then it is somehow hokum, is just one of the craziest things I have ever seen on HN.
But, some people on blogs trying it and then some of them saying a diet works is not really scientific. What would be needed is a larger scientific study. You can argue that such a study should be funded.
In fact, there does appear to be some scientific research, based on some quick googling [1]. If your goal is to increase the adoption diets based on those studies, then I would cite them directly. Promoting that work might work better.
[1] https://www.sciencedirect.com/science/article/pii/S156919930...
My most recent health blog is easy to find if anyone is genuinely interested. I have absolutely no reason to believe such interest exists.
I didn't make my comment to promote my blogs. I wish I knew how to promote my work and monetize it. I remain very poor and this is an ongoing source of stress in my life. But I don't know how to fix that. I see the current monetization schemes of health stuff as part of the problem. So to my mind that is a non starter.
I keep hoping someone will prove I am just stupid and it is possible to both do the right thing (in this specific domain) and also make money. But, so far, I am failing to find a path forward on that.
I wish I felt your suggestion was a good one. But 17 years of online drama suggests otherwise.
I can't see any logical reason to agree with your standpoint based on what you've said...
Yeah, nutrition as in "you need more vitamin C, or else scurvy", not as in "eat salads, drink no coffee, consume only 'natural', no processed".
Anyway, you're talking it personally way beyond what was intended. Nobody is discounting your opinions because you're you, or because you're a woman (in fact, people were probably positively biased towards them by the virtue of your karma score on the previous HN account, before you ditched it). You started your subthread here with, "Color me skeptical", towards the outcome of sponsoring biomedical R&D, based on your experience with one form of one disease that (you think) you figured out how to manage with healthy lifestyle. But there are plenty other forms of that disease, and plenty other diseases, and you can't cure them all by healthy lifestyle - and most importantly, people are not living healthy lifestyles for some reasons - reasons that are fully orthogonal to what medical research is doing.
Anyway, I'm going to drop it, as I'm no wordsmith, and 'dokein happened to make the same point I want to make much better than I ever could.
One thing I highly recommend for people with CF is the right kind of high quality salt. This is very much like taking vitamin D for Rickets or vitamin C for Scurvy.
But you just assume that I have nothing that specific to say and facts be damned.
Every nutrition as medicine claim on HN is highly controversial. Sure, there's some people that tend to vocally buy into even the most unscientific of them usually people that are personally invested in the claims made, which are often quite general in applicability. I suspect the reason you see less of that for yours isn't either a specific bias against you or anything about your particular claims except that the popular to whom they are applicable is fairly narrow. So you get the skeptics, but not the eager adopters.
Anyway, it is probably pointless to engage here. I did not expect my initial comment to get any upvotes at all, much less engender discussion. I expected it to be downvoted to hell and end up at the bottom of the page.
I meant it when I said that speaking to these issues on HN is evidence that I have snapped. I am, in fact, having a huge personal crisis that seems unsolvable. Spouting off is just me falling apart in public, basically. I already am very well aware that I will never be taken seriously. That isn't news to me.
Here is a Kaplan-Meier curve for statins:
http://www.bmj.com/content/bmj/337/bmj.a2423/F2.large.jpg?wi...
That is a lot of life that these drugs have given a whole lot of people.
AIDS is largely a managed disease now, thanks to therapeutics, starting with AZT.
Steve Jobs thought that he needed better nutrition to manage his disease, and he was wrong. He had a chance of living a much longer life had he let medicine intervene earlier.
(And I had no idea what your gender was until you mentioned it. I'm sorry that you don't feel heard.)
The first is, anecdotes are interesting, but is there data that supports this? It seems like there are too many variables, and that at home care may not help in all circumstances anyway.
Secondly, "getting proper care from someone who actually cares about you" by which I guess you mean a family member or close friend. Is not viable is many circumstances...
Finally, I guess it comes down to "what do you actually do". If it proves helpful, what can you do to promote this? Fund family member to quit their jobs to care for relations? It seems like that would be open to abuse and difficult to administer.
I would be fine if we provided parental leave for both parents when a child is born. But I would be happy with just bringing the US into the 21st century and getting on the same page as basically the rest of the planet and just starting with maternity leave. I only mention parental leave because if I don't, you can guarantee someone will accuse me of something nefarious for not explicitly stating that.
But it seems like a very different issues that increasing health care outcomes in general.
The gratuitous personal attack only deepens the problem.
Which seems valuable for many reasons. But I would be interested in seeing data which supports that this results in better health outcomes for mother and child. However, I'm not sure this specific case tells us much about the general case of patients (you cited CF) being cared for by friends or family members...
You're not backing up your statements with data, and not making a reasoned objective [1] logical argument... people do that all the time of course. But it doesn't really help advance a discussion or change anything. It's probably why you've ran into issues getting your point across in general.
[1] You might feel you have sufficient subjective reasons to believe what you state. But it doesn't help convince others, for that objective proof is required.
Accusing me of being at fault for catching a lot of flak while posting as openly female on an overwhelmingly male forum is, at best, clueless. I have a handle on the leaderboard that I recently retired. I appear to be the only woman to ever have had a handle on the leaderboard. This is objective evidence that my performance here is vastly better than that of most women. So, no, it probably isn't some personal deficiency causing my difficulties.
And stress is a significant factor in mortality rates. Its a major predictor for long life and health. It impacts metabolism, pain reception and recovery rates, and reduced stress in surgical patients is a universal good regardless of diagnosis. Its not a cure. It won't stop an infection or cure cancer, but the benefits are very real and has a good bit of research behind it.
Just curious, on what do you base this opinion? Do you work in cancer research, or another biomedical field? These tools will definitely advance our understanding, but my feeling (as someone who worked in genomics for several years, though not in cancer) is that if you think "we are really close" to curing cancer (pardon me if I misinterpreted your statement) with these technologies, you are buying into a lot of hype around them. It's natural that that hype exists, though, given how much VC money is being poured into this area right now.
1 and 3 imply we may be able to drive clonal evolution to a place where we can indefinitely treat patients. 2 gives us a lot more options.
Failing flat, i.e., not making people healthier but not making them sicker either, is not a problem. Failing down, i.e. trying to make people healthier but making them sicker instead, is and has been a huge problem with modern medicine, even when done with the best of intentions.
Yes, the past century has seen great progress in neutralizing infectious disease (though it is likely that the HIV epidemic itself was an "own goal" of basically iatrogenic origin [1]), but nearly everything else, including cancer, is a wash.
Unfortunately, a sober analysis of the benefits and harms of actors in the medical space cannot afford to give much credit for effort or good intentions.
Are families with two working parents actually less healthy? Do you have a source for that?
We are seeing a huge rise in problem pregnancies, birth defects, etc. There are likely a number of contributing factors to that reality. It isn't PC to wonder if maybe the rise of female careers is at related. That is viewed as antifeminist and so on.
Women routinely take time off work to care for relatives, whether their own children or other relatives. They get no credit for this vital work and how it impacts the health of people.
My experience suggests there isn't any point in trying to prove it. It won't get taken seriously anyway.
It is common knowledge that small kids in daycare have more health issues. My sister, who has a career and works for the CDC, used to quote studies at me about that. She managed to stay home with her only child for the first few years.
But, of course, in searching for info to support the idea that small kids in daycare get sick more, one of the most prominent pieces I can find is a PC piece assuring parents that the increased negative health effects of early daycare "has a protective effect later." Meanwhile, the study completely excludes data on, for example, hospital stays. Looks nicely spun to me.
Other pieces outright admit that staying home is simply not an option for many women and go on to talk about how best to protect your child from germs at daycare rather than exploring statistics. Yet the fact that you can google the question and there are pieces trying to address it at all suggests it is a real issue and parents ask about the problem a lot. But society can't fix it, so it isn't really comfortable to admit that it is a real issue.
Home cooked meals are also generally healthier than takeout, microwave meals, etc. Two career couples tend to not do a lot of cooking from scratch. Diet significantly impacts health.
But it is also the case that the human immune system remembers various kinds of foreign agents that it has seen and is more effective fighting them off later (hence immunization as an idea), and there seems to be some evidence that excessive hygiene results in allergies, autoimmune diseases, etc. See for a start https://en.wikipedia.org/wiki/Hygiene_hypothesis
It is pretty unfortunate if parents can’t afford to keep their kids home for a week or two if they get seriously sick, though.
We do nothing to really account for this being a historical aberration for the species and then wonder why we have antibiotic resistant infections. They get that way in part by running through many, many people and having vastly more chances to evolve.
Folks living on farms or in the forest generally don’t have autoimmune problems because they have constant exposure to animals, a wide variety of plants, etc. On average (especially the peasants) they have poorer health than folks living in cities, but the distribution of health problems is fairly different between the three groups.
Deadly plagues (viral and bacterial) have ripped through through and decimated agricultural societies relatively often, at least in the past couple millennia. Many crippling diseases have also been endemic in many places (especially tropical regions) as far back as we have records. Modern medicine and lifestyle (indoor plumbing, vaccines, antibiotics, refrigeration, mosquito control, medicines for killing parasites, ...) have done an amazing job preventing those in wealthy countries.
Does anyone wonder why we have antibiotic resistant bacteria? I thought that was pretty widely understood (at least by those who accept the science of evolution)...
I see zero reason to suggest that trying to keep small kids home and out if public daycare somehow us weird, aberrant, helicopter parenting. Small kids being at home with family was the norm for most of human history.
Tossing in stats in how bad life was for peasants isn't genuinely a rebuttal. It is, at best, smoke and mirrors to deflect the point.
Keep kids home for the first 5 years and don’t let them play with other kids if you want, but I haven’t ever seen careful research showing that e.g. preschool or playground time leads to widespread permanent health problems, either for the kids at the time or later in their lives. I admit I have never tried to research this question, so it’s possible it has been studied.
Basically you are speaking from prejudice while acting like it is science. You only want scientific proof for things you disagree with, not for your personal preferences.
> The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001).
Other possible explanations include: You need a certain baseline of health for both parents to successfully pursue careers. Older siblings actively help care for younger siblings. Wealthier families are likely to be generally better educated and better cared for.
Your position was openly hostile from the start. You posit that I am talking about a hermetically sealed bubble and not allowing children to have any contact whatsoever with anyone but the parents. It is hyperbolic and not a good faith engagement. Defending myself against this de facto attack forces me to sound more and more like the extremist nutcase you intentionally painted me as.
I don't plan to engage further. This is not a constructive discussion.
“Hermetically sealed bubble” was a bit of an extreme description of your (largely unspecified) alternative to sending kids out into public, but personally I feel there are many good reasons to send kids out to e.g. the park, the grocery store, the street, the bus, the library, later to occasional organized classes, etc. (e.g. so they can learn many skills including socializing with peers and the community at large) without all that much evidence of significant risks. Small children living among communities of humans pretty much inevitably get sick at least several times per year, even in relatively small and isolated agrarian societies. By most objective measures (and especially if we disregard effects from terrible diet and sitting staring at screens a whole lot) children today are incredibly safe and healthy compared to past children.
I agree it hasn’t been especially constructive, but I’m not quite sure why you were and are so wound up and negative about the conversation here.
kids who live in a hermetically sealed bubble, never share toys, and only ever interact with a couple of adults.
You now assume that I am suggesting kids never go to a park or grocery store etc. I see no means to find common ground here. Your assumptions about me are so extreme that it is impossible to engage you effectively. And there is zero reason for you to assume I am talking about such an extremely isolating lifestyle choice.
I go to public places, usually daily. I am not a hermit. I cannot fathom where you are getting this from.
If you made fewer assumptions and parsed other people’s comments more carefully, critically, and charitably, not looking for personal attacks under every rock, you might find fewer discussions offensive. YMMV.
Happy new year. I hope all is well with you and your family.
And you said you want to stop being someone who cares. Don't ever do that! Well, I'm sure you won't. Best wishes. (Sorry if I put words in your mouth or sound condescending etc. I could see both sides of this..discussion, and I hope these words aren't a total waste of time or worse.)
Modern rural living in the developed world is not much like rural living in most of history, so, no the modern rural living the GP criticized was not the “default norm” for most of history.
> The aberration here is not people with limited contact to others. The aberration is that in recent decades it is the new norm to work at a job that exposes you to many people every day and attend a public school that exposes you to many people every day.
From the various descriptions of historical rural life (e.g., medieval European village life) I've seen, neither adults nor children having daily contact with numbers of other people rather than being isolated with their nuclear family was at all uncommon; for most of history that wouldn't be school for children or wage labor for adults, but it would still happen.
Like you, I spend a lot of time figuring out how to live better. But also grateful for the medicine I got for illnesses when they do arise.
I use and apply free health advice. Then again, I also use gym and supplements, which may have made VCs rich. Likewise, in cures, I appreciate that they are available in the low probability I get seriously ill. I am sure many suffering from alzheimer, cancer or other age-related diseases, would want there to be cures.
In the goal increasing healthspan, can't one favour the all-of-the-above approach? Primarily rely on healthy living like you suggest, yet support people developing cures for diseases.
PS. Almost all cures come from the US, 57 % of them, and 13 % from Switzerland. While this health care system is dysfunctional in many ways, it also is the market new cures are being developed for. In Europe, where I am from, most drugs are purchased by a single large purchaser, which has negotiation power to buy a drug at close to marginal cost. This makes drugs cheaper, but also makes less people try to invent new cures. So, it's a bit of a trade-off between the present and the future.
I quit taking the flu vax years ago and have done better since. In the eyes of some people, this makes me a nutcase antivaxxer even though flu vaccines are not required.
When I was growing up, anyone getting vaccinated was a success. People who didn't weren't all that uncommon. Now we are shooting for 100% of the population being vaccinated and you need to justify not getting it.
The further we go down this road, the more those options narrow rather than expand. I am some nutter who "lives in a bubble" for preferring to limit my exposure to germs as effective prevention rather than live on prophylactic antibiotics all the time, never mind that one of the outcomes of putting people with CF on antibiotics constantly is a high incidence of C-dif infections which are then treated by surgically removing your colon. Limiting my exposure to other people and their germs is not viewed as a reasonable choice for avoiding that outcome.
I am not seeing similar amounts of muscle put into policy changes that are more family friendly, people friendly etc. Saying there is nothing wrong with developing this stuff ignores the context in which this is occurring. If all of the above were equally accepted answers, I would not get so much ugly and threatening push back for talking about the choices I have made. I should not need to defend the idea that I would just rather not be sick, thanks, and I am willing to limit my social life to have that. But I get outright attacked for that.
So you would be wise to be a tad more skeptical about where such things lead. They tend to lead to promoting one path over another, at the expense of the other, rather than a broadening of options.
How much effort do you think it would take to force the adult population into "healthy lifestyle" (as defined by the usual good diet and lots of exercise, etc.)? How would one even do that? I can't imagine anything over a) upending the industrial revolution and getting us all back to the farmer's life, b) just forcing everyone by arbitrary government restrictions on everything, or c) doing massive brainwashing of everyone. All of those strategies are infeasible, and could have bad side effects.
OTOH money spent on biomedical research can lead to figuring out one cause of one disease, and a subsequent cure. Then another. Then another. A lot of those could allow us to sidestep the lifestyle requirements, which I believe to be a good outcome. It expands options. (This - using medicine to not change lifestyle being good - is where I think our beliefs strongly differ.)
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> I am some nutter who "lives in a bubble" for preferring to limit my exposure to germs as effective prevention rather than live on prophylactic antibiotics all the time,
What? Who on Earth does "prophylactic antibiotics"? I thought this was restricted to surgery and some other very special cases...
> Limiting my exposure to other people and their germs is not viewed as a reasonable choice for avoiding that outcome.
This is a very reasonable strategy and is often used, but has lifestyle costs, so people avoid doing it anyway... No blame to be put on doctors for that one.
> When I was growing up, anyone getting vaccinated was a success. People who didn't weren't all that uncommon. Now we are shooting for 100% of the population being vaccinated and you need to justify not getting it.
When you were growing up, polio was a thing. Now, it isn't. There's not just a correlation there, there's actual causation. We're shooting for 100% vaccination for some of the things, because vaccines work, and happen to work superlinearly - the more people are vaccinated, the more likely it is those who are not vaccinated will not get infected either. And some people can't be vaccinated for health reasons, so they rely on that so-called "herd immunity".
Yet one thing harming health in the US is that most people find that long commutes are not an option. They are a necessity. The time spent behind the wheel is not only bad for your health, it robs you of time to do things like go to the gym or cook from scratch.
Most Americans don't want to spend that time behind the wheel. But there are huge obstacles to arranging to avoid it. Many Americans wish they had other options. If those options were made available, you would not need to force people to take them.
Though I wish you had just dropped it and walked away like you indicated you would do.
> Though I wish you had just dropped it and walked away like you indicated you would do.
Yeah, I should have. Couldn't stop myself. But I'm going to now. No more comments on the health stuff.
I'm not claiming to do better: my "give a motivational speech when I see you in clinic twice a year" approach certainly isn't worth shit.
But just because one approach is important does not mean others are snake oil. CF has a clear biological basis, and there are randomized, controlled trials proving that secretion management (e.g. DNase), glucose control, timely antibiotics and anti-inflammatory meds, and chest physiotherapy work. These trials also establish an average effect size (whereas your anecdote only tells me about you; I have also had patients who took similar measures but still died young). The average person with CF died at age 25 in 1986 -- today it's above 40.
The current mental model is that people with CF overproduce mucus and are drowning in their own mucus. I believe this to be incorrect. We underproduce mucus. Giving the body what it needs to produce enough mucus makes a big difference. Inadequate mucus production is one of the ways the body's immune system is compromised and fixing that is entirely about proper nutrition.
I am well aware of the increase in life expectancy thanks to better drugs. I also used to take about 8 or 9 maintenance drugs and they made life not worth living. I was in constant excruciating pain for 3.5 years. No amount of pain medication really stopped it and my sleep quality was atrocious. I got better in part because I wanted to hurt less and I did not care if that accidentally killed me.
I had a life before my diagnosis. After my diagnosis, all I had was drugs staving off death. I frankly can't comprehend why more people with CF don't commit suicide. It's a horrible way to live.
All the drugs have a six page handout listing side effects. They trade short term gains for long term costs, take credit for the benefits and blame your genes for long term negative impacts.
I am not against drugs. I was thrilled to get a diagnosis and be able to ask for Zithromax up front. But there are things very, very wrong with our current approach. If anyone but a doctor did such terrible things to someone, they would be charged with a crime.
I think I was unwelcome on CF lists in part because people who had literally tortured themselves or their child balked at hearing that maybe you don't have to be tortured. I think accepting the torture and making their peace with it was a necessary psychological survival mechanism and they probably could not even name their objection to what I was saying.
I don't hate physicians either. I'm having a terrible, terrible day and speaking to these issues on HN is basically evidence that I have finally snapped. I don't like hurting other people. But trying to not hurt other people is essentially killing me. These are things I cannot discuss anywhere. It isn't socially acceptable. And that is part of the problem. Other people not only can't speak of it, many seem incapable of even thinking about it. It isn't acceptable for someone with CF to want a life. Just not dying yet is supposed to be all we aspire to and that's it. And I am incapable of swallowing that.
That is quite probably not at all what you intended but that is how I interpreted that exchange.
Doctors never have any interest whatsoever in how I am getting healthier. They merely assure me it has zero relevance to anyone else on the planet.
Before clinical trials, doctors gave advice based on anecdotes (i.e. "experience"). As a whole we seemed to do no better than random chance, but we made sure to take credit for patients who naturally recovered.
Your experiences are important and 100% relevant to yourself, and nobody can ever devalue that. And it's also true that our understanding of the human body is extremely limited. But it's not clear to me that the magnitude of your personal suffering leads to generalized knowledge or a better mental model.
I have seen at least two discussions online about how vaginal dryness routinely ruins the sex lives of women with CF. I have yet to meet a woman with CF who brags that CF means she can handle 10 men a night at her regular orgies. Yet women with CF also produce a lot of goopy vaginal drainage, no doubt from infection. But it isn't mucus. If it were, vaginal dryness should not ruin their sex life.
I posit that people with CF are coughing up phlegm which is drainage from infection. Helping them produce healthy mucus can eventually put a stop to that.
My oldest son has the same diagnosis. I know other people with CF who have taken some pointers from me. It isn't accurate to say it is merely the anecdotal stories from a single person.
I appreciate you commenting. But our current mental models are inadequate and it is incredibly tiresome to be told for 17 years that I know nothing, my track record of success is just luck or something, etc.
Mental models tend to change only when the old guard dies. This is historical fact.
We probably should not waste anymore of each other's time. The odds are poor that it will be constructive.
Today we have more leisure time than ever before in human history (well ... maybe not the HN crowd) but we're spending that time in increasingly sedentary hobbies/interests.
As a physician, does the idea that manufacturing and robotics will completely eliminate our need to work scare you at all? If the trend continues, will we truly be the space-faring humans in Wall-E - tied to our mechanical chairs and handicapped by our girth while life-spans decrease due to obesity-related diseases?
In the short term, I think there is actually more awareness today of exercise and its benefits than e.g. the 1990s, although there is a large discrepancy between socioeconomic classes and between metropolitan and rural areas.
In the long term, we may be able to reproduce the benefits of exercise. There are a couple drug compounds that are in investigation. This will likely require at least a two-orders-of-magnitude better understanding of the human body--I seriously doubt that targeting a receptor will do the trick.
Alternately, we can just solve the ability to summon willpower.
And work. Don't forget work.
> As a physician, does the idea that manufacturing and robotics will completely eliminate our need to work scare you at all?
Suppose a robot assistant could replace 60% ~ 80% of your time in the office as a physician. You would then have more leisure time to spend as you wish.
Aging biology is all about understanding how diseases develop to begin with, and lifestyle interventions are definitely part of that umbrella of research. Those of us who obsess over aging biology tend to prefer thinking about preventative strategies first, and rejuvenation as a fallback.
Fair enough, but there are also plenty of conditions for which these things don’t work adequately, and we absolutely do need to encourage research. I think this is a great move from YC.
They have all kinds of great food to choose from
a) There's no obligation to work on earthquake-ridden cities over any other issue.
b) Mythical Man Month problem; firefighters might be good at extinguishing flame but not repairing earthquake issues, and there's only so many civil engineers to go around.
c) Your comment is proof that no good deed goes unpunished.