Weekly Dose of Optimism #147

Hi friends 👋,

Happy Friday and welcome back to our 147th Weekly Dose of Optimism. Another action packed week of scientific breakthroughs across cancer treatments, gene therapies, and the ways in which science itself is conducted.

We won’t be covering the Elon/Trump drama, although our lawyers have advised us that we can no longer call ourselves a technology newsletter if we don’t at least mention it. So we will say this: we are happy to have Elon back focused on his companies (more on Neuralink below) with something to prove.

Let’s get to it.

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(1) Structured Exercise after Adjuvant Chemotherapy for Colon Cancer

Courneya et al in The New England Journal of Medicine

A 3-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer resulted in significantly longer disease-free survival and findings consistent with longer overall survival.

This may or may not surprise you at this point, but exercise is good for you. Across almost every measure of quality of life including happiness, healthspan, and mortality risk, it turns out exercise is crucial. And new research now shows that exercise may even help post-chemotherapy cancer patients live longer.

The new landmark phase 3 trial, called CHALLENGE, has shown that structured exercise significantly improves survival in colon cancer patients post-chemotherapy. The 900 patient study found that those in a three-year supervised exercise program had a 28% lower risk of cancer recurrence and a 37% lower risk of death over eight years compared to those receiving only health education materials. Basically, the risk of the cancer returning or causing death reduced by 1/3rd due to the exercise protocol.

Trial participants followed personalized regimens with goals of at least 150 minutes of moderate-to-vigorous aerobic activity per week and two or more resistance training sessions weekly. I am no doctor or even a personal trainer, but I’d bet that if they swapped out some of that cardio time for another 1-2 lifting sessions per week, results would be even better.

(Packy note: don’t besmirch cardio like that. long live running.)

Notably, however, even this protocol rivaled many standard drug treatments, with fewer side effects and lower costs.

Call somebody you love today and tell them to exercise.

(2) Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma

Jagganath et al in The Journal of Clinical Oncology

One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative and imaging-negative at year 5 or later after cilta-cel. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.

Researchers may have discovered a cure for multiple myeloma, a deadly blood cancer, for some patients. The treatment studied is ciltacabtagene autoleucel (cilta-cel), a personalized CAR-T cell therapy which involves collecting a patient's own T-cells, genetically modifying them to target the BCMA protein on myeloma cells, and infusing them back into the patient as a one-time treatment. While most patients with relapsed or treatment-resistant multiple myeloma die within a year, nearly 1/3rd of treatment recipients were still alive and cancer-free five years after treatment, without needing any ongoing therapy. Even more impressively, a subgroup of these patients showed no trace of the cancer, suggesting the disease was fully gone.

While this type of durable cancer remission in multiple myeloma has never been achieved before, it’s important to note that the initial treatment did not work for everybody: it was more effective for patients that had stronger immune systems, low initial tumor burden, and a healthy blood profile going into the treatment. That said, unlike other therapies that require ongoing drugs and still result in relapse, cilta-cel offers a one-and-done possibility. These results are the first real signal that a cure may be possible for some multiple myeloma patients.

Say it with me now folks: Get Fucked, Cancer.

(3) Neuralink raises $650 million Series E

From Neuralink

We’ve closed our Series E funding round of $650 million with participation from key investors…This funding will accelerate our efforts to expand patient access and innovate future devices that deepen the connection between biological and artificial intelligence.

Neuralink closed a massive round this week to double down on the progress its made over the last couple of years. The brain-computer interface company has indeed made some notable advancements since its last funding round of August 2023. Notably, during this time the company successfully implanted its first human device, enabled a paralyzed person to control a computer cursor with thoughts, built a custom surgical robot for precise implantation, achieved wireless data transmission from the brain, and received FDA approval for human trials. Elon’s companies move…fast.

I’ll admit it: I am super bullish on the work that Neuralink is doing. Could a cynic paint a scary picture of how a Musk-owned company is going to implant brain chips into every human and control their minds for evil? Sure, I guess there is a small probability of that occurring many years in the future. What’s much more likely, however, is that in the relatively short-term Neuralink is going to all-but-cure blindness, deafness, and any number of other severe neurological conditions. And in the longer term, it could enable the merging of human brains with super AI which would transform just about every way we humans learn, work, and communicate (and in my view, for the better.)

(4) Longevity Is Now a Factor When Picking an Embryo for IVF

From Nucleus

Nucleus plans to charge $5,999 for an analysis of up to 900 conditions, including diseases that occur later in life and are major causes of death in older people such as Alzheimer’s disease, heart disease and cancers. The company will analyze up to 20 embryos. The embryos are given probabilities for the likelihood they will get these chronic conditions. It is up to the parents to decide the qualities most important to them when choosing which embryos to use.

In a world-first, Not Boring Capital portfolio company Nucleus has launched Embryo, a genetic optimization tool that lets IVF parents rank and select embryos based on a complete genomic profile, from disease risk and cancer predisposition to traits like IQ, height, and eye color.

It works by analyzing the genetic data of IVF embryos to assess risk for over 900 diseases and dozens of traits. The analysis combines Mendelian analysis (for rare, high-impact mutations) with polygenic risk scores (for common, complex conditions) and adjusts predictions based on ancestry and assumed adult risk factors. It spits out a ranked, science-backed embryo profile that helps parents make informed decisions during the embryo selection process of IVF.

Embryo is already live, with early adopters using it to guide choices including, in some cases, selecting embryos with lower predicted risk and higher estimated intelligence. While still early and not without controversy (Kian is very good a garnering attention for his company!), the launch marks a major step toward applying consumer genomics to reproductive health. Nucleus is building out its suite of products (Family, Embryo, Health) that unlock genetic information to live longer, healthier, and perhaps even better lives from pre-conception to grave.

It’s important to note, and Nucleus does, that its tests can’t guarantee anything. They deal in probabilities. But with embryos already screened for certain diseases and genetic conditions, Embryo expands what parents can understand about their future children. As we discussed last week when we covered Orchid, “our perspective is that we’d of course rather have the technological capability of doing these things and wrestle with the resulting ethical dilemmas of whether or not we should do these things, than to not have the capability at all.”

Kian broke it all down with Molly O’Shea in this interview on Wednesday. My man has one of the most genetically optimized jawlines you’ll ever see.

(5) Scientific Publishing: Enough is Enough

Seemay Chou for Human Readable

I no longer believe that incremental fixes are enough. Science publishing must be built anew. I help oversee billions of dollars in funding across several science and technology organizations. We are expanding our requirement that all scientific work we fund will not go towards traditional journal publications. Instead, research we support should be released and reviewed more openly, comprehensively, and frequently than the status quo.

Arcadia Science and Astera Institute are no longer funding science built for scientific journals. The two institutes are shifting away from traditional scientific publishing, arguing that the current model distorts research incentives and slows progress. In her essay, Astera’s cofounder Seemay Chou explains how journals prioritize prestige and polished narratives over truth and transparency, leading scientists to selectively report results and delay data sharing. This creates artificial bottlenecks, discourages collaboration, and blocks real-time feedback and reuse. Incentives shape the world, folks.

So what are Arcadia and Astera doing instead? Only funding research that is shared openly, frequently, and transparently, prioritizing real-time feedback, full data access, and iterative publishing over prestige-based narratives. Scientists are encouraged to share failed experiments, raw data, and in-progress work, making science more reproducible and useful. And the early results are promising: faster peer review, more creative and rigorous science, and stronger collaboration.

We’re big fans of Arcadia and Astera here at Not Boring. Earlier this week, Astera CEO Cate Hall went on Hyperlegible to discuss her essay, Crossing the cringe minefield. In the discussion, she explains that the work Astera does “is all in service of trying to create a new pathway for the creation of public goods in the world, which is traditionally a thing that government has done.”

And way back in October 2022, in Gassing the Miracle Machine, Elliot Hershberg wrote that “Arcadia is an applied experiment in metascience.” This is a hell of an applied experiment. Arcadia and Astera are betting that playing with the way we share and build off each other’s knowledge might be the most impactful experiment of all.

We look forward to covering some of these non-journal results in future Doses.

BONUS: Elliot Announces $200M Amplify Bio Fund

Packy here. Yesterday, our friend Elliot Hershberg announced that he’s joining Amplify to help build their new $200M fund dedicated to technical founders in bio.

Over the past three years, Elliot worked with me as the Biotech Partner at Not Boring Capital. The plan was: work with me while getting his PhD, get it, and then launch his own small early stage bio fund.

Everything was going according to plan. He led our investments in some exceptional biotech companies including Atomic AI, Unnatural Products, Decade Bio, Cromatic, Neion Bio, Digital Bio, Convoke Bio, Fletcher Biosciences, Biodrive, Exthymic, Euler Biologics, and Sculpta. He wrote pieces like Medicine’s Endgame and Gassing the Miracle Machine, and we worked together on Deep Dives for Atomic AI and Varda. In February, he successfully defended his PhD at Stanford.

One thing didn’t go to plan, though. The market realized what I realized about Elliot getting to work with him closely for three years: he is going to be one of the best investors in biotech, and he should probably be running a larger fund than the one he was planning to run.

Elliot is a rare combination of skills and traits. He combines the rigor of a scientist with the ability to dream like a writer. He’s a biologist and a computer scientist. He’s as thoughtful about fund strategy as he is about clinical strategy. He’s a deeply curious student of whichever game he’s playing. And he connects with biotech founders, who are a different animal than traditional tech founders, in a way that consistently impressed me. I always like to be the dumbest person in a room, but I never felt dumber than when in conversation with Elliot and a biotech founder, and I loved it.

I wasn’t the only person who realized this. I can’t count the number of firms that tried to poach Elliot over the past few years. And as we discussed whether he should take this or that offer seriously, we kept coming back to: it’s tempting, but Elliot has a distinct point of view on biotech investing and writing, and should build his own firm to reflect that point of view.

Then Sunil Dhaliwal and the Amplify Partners team offered him the ability to do just that, with more scale, resources, and teammates than he would have had on his own. Amplify has been one of the best investors in developer tools and infrastructure for over a decade, partnering with “technical founders who would rather write code than PowerPoint.” Along the way, they backed technical founders in bio — Chris Gibson at Recursion, Brandon White and Alex Beatson at Axiom, Nima Alidoust and Johnny Yu at Tahoe Therapeutics, Zvonimir Vrselja and Nenad Sestan at Bexorg, and many more — and they decided it was time to build a dedicated Bio fund. They realized (geniusly, in my opinion) that Elliot was the perfect person to help them build it.

In the Weekly Dose, we often cover breakthroughs in biotech. In the past month alone, we’ve covered multiple miraculous gene therapy breakthroughs. At the same time, it’s been a weird market for investing in biotech companies. Elliot believes and has written many, many words on the idea that this is going to be the Century of Biology. As he writes in the Amplify Bio Manifesto, bio is at the same place tech startups were almost two decades ago, with the infrastructure in place to take really big swings: “Equipped with rented lab benches, cheap cloud compute, and tremendous grit, we believe these brilliant technical founders have the potential to build generational companies.”

I think that Elliot is going to back a disproportionate amount of those generational companies, and that his portfolio will be responsible for making all of our lives longer and healthier. I’m excited to personally be a small LP in Amplify Bio.

When people ask me how I plan on building out the Not Boring Capital team, I always point to Elliot as the prototype: someone with technical depth who can write, someone so talented that it would be impossible for a small fund to hire them full-time, but who I could team up with and learn from part-time while they also pursued other goals (in his case, the PhD). Even as I said it, though, I knew that it would be incredibly hard to find Elliots. The guy is a unicorn.

That said, getting to work with Elliot has been one of the highlights of my career, and I think the most interesting way to build out the Not Boring Capital team is through ephemeral partnerships that turn into a strong network as people go on to run their own funds. So if you’re deeply technical in a category I care about, tell stories that your industry trusts, and want to become a world-class investor while pursuing the thing that keeps you close to the metal, my inbox is always open. You’ll have big shoes to fill.

Have a great weekend y’all.

Thanks to ElevenLabs for sponsoring. Go get yourself (and your business) a voice. We’ll be back in your inbox next week.

Thanks for reading,

Packy + Dan