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by sytse 79 days ago
Thanks for posting this. Happy to answer questions!
21 comments

I have worked as an architect in HCLS technology for 10 years with Google and AWS.

Listening to you stitch all the technology and innovation together, moving from the information world to the physical world, as a patient, almost brought me to tears.

You said this will be the standard of care in 30-years, but the capability is here today. Listening to your recording is a profound moment in my life.

Thank you for sharing your journey.

Really appreciate it. I agree the capability is here today. I'm trying to get it to more people so that the learning effects and economies of scale can bring the costs down.
Is there a way I can start using this tech for myself as a solo dev? Is there some OSS project?
Your cancel journey is incredibly inspirational and I will share it on.

But actually, I'm writing to tell you that many of the OTHER things you have done have had a huge positive impact. Gitlab foundation, for example, has been extraordinarily impactful on our organization and many others.

This is the way!

Glad to hear that!
Sid, Thank you for funding Arden Bio. Rheumatology patients and their clinicians are often left to throwing darts from afar, in series and often with significant & permanent function loss with each dart. Moreover, proper care of refractory rare diseases is not something that insurance funds: my otherwise excellent coverage expressly denies "investigatory" treatments, for example. As a small fiber neuropathic vasculitus patient with secondary Sjögren's I really look forward to progress in this field, it cannot happen soon enough. Best of luck in your own care and profile. - Clark
Such an inspiring read. As a bioinformatics researcher I'm awed by the depth of the deck. How do feel about the process of learning cancer biology and bioinformatics?

Ps. I work for BillionToOne oncology and we build some of the most sensitive liquid biopsy tests (https://www.northstaronc.com/). Feel free to reach out if it pique your interest!

It wasn’t easy to learn it while dealing with the side effects of chemo. But AI helped a lot, also see the OpenAI forum talked linked on the page. Love BillionToOne, also see https://osteosarc.com/timeline/ MRD Northstar for my results with it.
Wow, honored to be a part of this.
Thanks for your interest, we use Northstar monthly to track for Sid.
how do you handle GitLab + Kilo + all this personal work? what system have you figured out? sorry if you've written about this somewhere, i think there's a meta lesson you have that we all can use.
All of these companies (including the Even One Ventures and Open Core Ventures ones) have CEOs who run them day to day. I try to help with positioning and setting ambitious goals. Y Combinator really opened my eyes to how helpful setting clear and hard to reach goals is.
thanks Sid! i think a lot of people incl myself aspire to be where you are - I have effectively 3 businesses and have only hired one GM (on track to be CEO), but the other 2 I am effectively CEOing. yet I have this maybe misguided asian/protestant theory that I haven't "earned the right" to multicompany yet, and if i take my hands off the wheel the whole thing might be at risk. With GitLab obviously you were driving for many years and it feels like only with your cancer diagnosis you started letting go.

no question in there, just a comment, love your openness and giving back to the community, wish you full success and recovery.

I wish you the best, my brother-in-law (also a close friend) lost his fight against cancer in 2019, it changed my perception of life forever. What we live is a bit like how we die, I had some of the best moments with him while he was more aware than myself about how we are all going to die, he changed my perception of caring much more about the uniqueness and the present moment. One of my favorite quotes is from Buckminster Fuller, "You belong to the Universe. Your significance will remain forever obscure to you ... (see full quote on Wikipedia)". Thank you so much for all the creation you have done in this world Sid, just for Gitlab it's plenty. I am a long time & very satisfied Gitlab customer, I switched a long time ago for its superior CI/CD integration and its super inspiring handbook. Another favorite quote is actually from you ... "My reasoning was I got to tell everyone what I do, and I want it to be a really good story." Lately I fundamentally changed my perception, the most important computer of all is the planet Earth, you seem to be aligned with this vision as well, correct me if my perception is wrong. I hope you keep going on with all those beautiful stories, we are lucky to have you with us.
Full quote from Fuller for others

> You do not have the right to eliminate yourself, you do not belong to you. You belong to the universe. The significance of you will forever remain obscure to you, but you may assume that you are fulfilling your significance if you apply yourself to converting all your experience to highest advantage of others. You and all men are here for the sake of other men.

How do you deal with setbacks both in work and life, and show resilience and belief you can find a solution? Is this innate or something you worked on? Also, are there things you think are impossible for you to do?
I have a stoic mindset, I try to not care about things that are outside my sphere of influence. While the cancer was unfortunate it was out of my control. Having my YCW15 batchmate step up for me during my initial set of treatments to get me Shasqi opened my eyes that I could help create and take new medicines. It was within my sphere of influence. When I reached the end of standard of care I stepped down from the CEO role of GitLab and pushed to do this for me. While it was hard it was easier than I expected and I created companies to help other patients in the same way (maximum diagnostics and single patient IND pathway).
Philosphical treatments have got a bad rap because it is so easy for conmen to convert them into fake hope, but when properly applied they are still amazingly effective. It's just that "properly applied" is very often not profitable because all the applicable texts and practices have been quite literally known for thousands of years and are available through well known texts in the public domain.

And Sytse if you read this: beterschap en als dat niet helpt: sterkte. Cancer sucks.

Dank je!
Sorry if this is too specific/personal, but I've been wondering, why does the treatment timeline include antibiotics (dalbavancin)? Does dalbavancin have any suspected antitumor effects, or was it simply to treat complications of surgery / catheter infections?

(edit: actually now that I checked the treatment timeline again it seems to be gone now. It was there 2 weeks ago!)

Chiming in from Sid’s care team, the Dalbavancin was used to treat an infection post surgery, thanks for asking!
in light of everything you've learned about the pharmaceutical industry and biotech venture, is there anything in particular about oncology that makes it well suited to venture?

like why is it people with cancer? why isn't it people with muscular diseases?

My pleasure! How does someone support someone going through cancer? I would especially like to know how to best support someone upon initial diagnosis. It seems like you have an amazing support system and I would like to be that for someone.
Of course it depends on what they need but please email cancer@sytse.com with a screenshot of this message and we can discuss.
This is very impressive, top labs doing research often don't have experimental designs that are this elaborate. Was the TCR and BCR-seq you conducted helpful to design cell therapies, neoantigen vaccines, and monitor progress?

Given that you carry the HLA-B*27:05 allele, you might have been blessed by being predisposed to a better response. But probably you want to keep an eye on future autoimmunity issues. Talking from experience...

Thanks for the warning, I hope that it wasn't a personal experience for you.

Thanks for the compliment about the elaborate design. I think that when you make something for one or a few patients it is easier to be more elaborate, even with the same knowledge and equipment.

Maybe the TCR and BCR-seq was most helpful for mRNA design and effectiveness monitoring, but hopefully someone else on my team will answer that better.

The TCR sequencing has been helpful for downselecting TCRs for a TCR based cell therapy, and for monitoring response to various immune therapies (including the vaccines)
Interesting, thanks for your replies.

You should consider publishing a patient case report somewhere, as I believe there are lots of valuable conclusions to be extracted from your work.

Love how you approached and presented this. The data vis on https://osteosarc.com/ is outstanding; such good explorability (is this some open source framework?)

I do have concerns regarding the proposals for scaling personalized medicine. They mostly boil down to "how do you scale the skill set required to operate in high-noise-low-signal domains". In my experience, these are places where poor data/incentives/critical-thinking can easily overshadow the signal; e.g., compelling stories outnumber correct stories.

There seems to be a trade-off: you can walk a bit further than others by keeping the probability distributions for low-quality results in your head, but go too far and everything starts getting overwhelmed by noise. It seems like the FDA's heavy gatekeeping is one way to solve this problem. If you forgo that gatekeeping, then you probably need to deal with the cascading quality issues that result.

Personalized treatments will probably be much harder to evaluate. At least a black-box algorithm that maps `situation → suggested treatment` can have statistics applied to it. But how do you evaluate "individuals made their own decision; here's the list of `situation × outcome`"? Or is the idea that there's currently a wealth of good-solutions, and that we should be relaxing regulations for a while?

Or perhaps we just want to push the regulator burden from "before small trials" to "before medium trials"? Then, these will be treated as case studies: good for experts to pull ideas from, but not high quality evidence for proving anything the third parties? I notice that your diagnostics were numerous, but the treatments were sparse and more sequential than parallel. If that's the norm, then maybe fairly usable data will emerge.

Or do people just have a moral right to seek out their own treatment, regardless of footguns that may be lying in wait? For myself and my loved ones battling cancer, I deeply agree with these:

> Maximize survival instead of the current practice of minimizing liability to the practitioner

> Parallel treatments wherever reasonable, we don't need to know what cured you

But I'm also glad that daily medical decisions are highly standardized and quality-controlled. It makes it easier to trust my doctor (or my loved ones' doctors) without independently investigating each recommendation.

Thank you for sharing—very inspiring. I'm interested in the operations of starting and managing these companies in parallel. How did you go about finding people to run the companies? How much involvement do you have in their day-to-day operations? Are they "your" companies, or do you consider yourself just Customer #1?
How are you now?
Doing well. We've not seen the cancer for 10 months (not for lack of trying) and I'm enjoying an international trip for pleasure!
Glad to hear! After losing my wife to cancer (highly aggressive brain tumor, she only had six weeks), I'm happy that you had the time, resources, strength, will to take cancer by the lurven
Not my thread, but I just wanted to express my condolences for losing your wife. That must be so tough. My wife is my best friend and I cannot imagine how painful it would be for me to lose her or vice versa.

I’m praying for you both and hoping that you’ve found peace and comfort since she passed. And I hope that you are doing well. I know she would be proud of you for keeping on!

I am so sorry that you had to go through this tragic event, Here's a hug my friend, that must've been incredibly tough on you, I am not religious but I know that She is in Heaven and watching you from above and she will always be within your heart and all the cherished memories you had together.
So sorry to hear that. I'm providing caretaking for my mother, who has GBM now, and we've been lucky to get to month 15 now. It's such a difficult disease to grapple with.
Yea, it is incredible to see what could be accomplished with time and technology.

Someone in my immediate family had Glioblastoma, it felt like fighting a hurricane.

Fantastic. Wishing you all the very best. A very close family member just with Stage 4 just got the pass for the next 3 months. We're 3 years in now. For them, the immunotherapy seems to be working, the radiotherapy has actually left the area affected worse (althogh we'd have never known the outcome if it wasn't tried, so it was a price worth taking).
Can't wait for the movie about this to come out.
Thanks for the inspiration! Is there anything new you've learned about fibrosis in your journey?
I'm not knowledgable able fibrosis except that my tumor expresses a lot of FAP and it is a workable target for radio and immune drugs.
I have sent you an email - any help you can provide in this area.
Thanks, I replied to your email.
I'm humbled. Thank you!
Have you run into other people doing the same ? it could be a nice new movement.

take care

Yes, I’ve met many people already. Feel free to reach out if you have questions cancer@sytse.com
Sid — I’m at FDA and would like to talk to you about your proposals to make industry more patient friendly. Will reach out to this address unless there’s a better one.
cancer@sytse.com is a good address to reach out to. Thanks for reaching out. I look forward to discussing. You can find some of my ideas in slides https://share.icloud.com/photos/020eRAUd5TqDwlypQCT-qhK7w
related: "ChatGPT and AlphaFold Help Design Personalized Vaccine for Dog with Cancer" https://www.the-scientist.com/chatgpt-and-alphafold-help-des...
I've met you at SHA 2017 in NL and I wish you all the Best!
Have you just "ordered the cancer vaccine" or this is not yet that easy?
Not that easy but started Echo to make it easier https://www.echoimmune.com/
Thank you. I've filled the form. I'll be happy to explore this topic together.
Have you ever found out the cause of the cancer?

They say to eat a healthy diet, exercise, get enough sleep, and avoid smoking/alcohol.

Have you discovered more specific reasons over the years?

Were you lacking in any of these?

Why does Gitlab pay employees less based on their location, but doesn't adjust price based on location?
What an incredibly tone deaf question
The question is absolutely legitimate in nature and neutral in tone.
This post is about a man's struggle with a deadly cancer.

I cant understand how you could possibly think this question is not "tone deaf" unless you are genuinely autistic - not using it as an insult, genuinely curious - since such a question would be simply beyond the pale in polite society, given the context.

While factually true, your answer lacks context awareness and decorum. It's not appropriate for this discussion in my opinion.
Sure, but this isn't really an AMA thread [despite the offer to "answer any questions"]. This is about Sid's journey with (extremely advanced) cancer. Airing grievances about Gitlab is just out of place here, you gotta read the room.