@AlexHarding7i
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An internist in biotech
Boston, MA
Joined March 2012
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Alex Harding retweeted
Some data we recently assembled on entrepreneurship/compute in Europe: eudata.vercel.app.
We hope that one of the useful roles that Stripe can play is in collecting and publishing empirical data pertaining to entrepreneurship and industry in Europe. There's growing appetite to get Europe on a better footing, and cross-sectional comparisons can often shine light on where opportunities lie. If you're interested in this kind of thing, we publish more at stripeeconomics.substack.com.
Verification makes discovery matter | Science science.org/doi/10.1126/scie…
Alex Harding retweeted
As someone who did this kind of genome mining work during my PhD, some thoughts on this Anthropic announcement:
First, the very simplified version of what they did is that they noticed two genes (one known, one new) sitting next to a weird repeating piece of DNA. More specifically, they described an unusual reverse transcriptase (RT) associated with a repetitive DNA array and an unknown accessory protein. This kind of process was used to understand CRISPR back in 2002 and was key to the gene editing tools we use today.
To put this into context, though, people have been finding RTs associated with CRISPR arrays since 2008, and this general kind of genome-neighborhood mining has been used to discover new biological systems for decades. The basic genome-mining strategy is well established, and there are now mature tools and published pipelines for doing much of this. There are papers that discover and experimentally validate dozens of new systems using this approach in a single study. Doing it in bacteriophage genomes is also nothing new (eg CasPhi).
Finding a weird cluster of genes and repeats is often the easy part. The hard part, and where the real discoveries come from, is figuring out what the system actually does. Eg for the bridge-RNA discovery in 2024 from @arcinstitute or the discovery of CasPhi in 2020 from @DoudnaJennifer they figured out the pieces of the system and the rules for what makes it work so it can be used.
Anthropic does not yet know what this does. They’ve shown that the repeat array produces RNAs, but not what those RNAs do, what the RT does with them, or whether the system has any of the programmable properties that make the CRISPR comparison justified.
I’m genuinely rooting for all of the frontier labs to seriously get into biological discovery, and I’m excited about what comes out of it. But announcing these very early, incremental findings with the framing of a major discovery doesn’t help. I’d much rather they set the bar high now, so that when an AI actually discovers a fundamentally new biological mechanism, everyone appreciates how big a deal it is.
Claude has discovered a previously unknown enzyme system hidden in the DNA of bacteriophages. Beside the enzyme’s gene sits a long array of repeating DNA—a structure that looks somewhat similar to CRISPR.
We don’t yet understand what this system does, but only a handful of known systems share its features, and all of them are able to cut, copy, and paste DNA. Historically, the discovery of such programmable systems has helped revolutionize medicine. CRISPR, for instance, is now the foundation of genetic medicines. But it will take much more work to learn what this system does, and whether it can be put to similar use.
Read more: anthropic.com/news/claude-di…
Alex Harding retweeted
The beauty of biology is it is SO EASY to discover something new. We don't know what 30% of E. coli genes do. 6000 new insect species are discovered each year. They just found a new cat!
The hard part is discovering something that is new AND noteworthy. This... isn't that.
There are countless CRISPR-like sequences hidden in genomes of many organisms (eg @Basecamp_Res). Well-known. Vast majority not interesting.
This isn’t a noteworthy discovery.
The hype level leads me to question how serious @AnthropicAI is about its biotech effort (I really hope it’s more than a PR stunt).
There are countless CRISPR-like sequences hidden in genomes of many organisms (eg @Basecamp_Res). Well-known. Vast majority not interesting.
This isn’t a noteworthy discovery.
The hype level leads me to question how serious @AnthropicAI is about its biotech effort (I really hope it’s more than a PR stunt).
Today we announced the Claude-led discovery of a molecular machine that we suspect could represent a new gene editing mechanism. Its precise function, biotechnological utility (if any), or level of significance is not yet clear, but at minimum it is work I would have been proud to do as a PhD student. The work was done mostly, though not entirely, by Claude: our life sciences team suggested a broad area of research, Claude read through the literature and a bunch of genome data and discovered something interesting, then Claude proposed experiments to verify the discovery and our team carried them out.
It’s easy to dismiss this as a one-off or curiosity, but we’ve repeatedly seen a pattern where AI performance in new intellectual domains goes from weak to superhuman in a matter of a few years. In 2023 models struggled to do math at the level of an average high-school student. In 2024 they started to do well on math competitions for the best high-schoolers in the country, in 2025 they started to solve minor open problems, in early 2026 more significant open problems, and in late 2026 they are beginning to solve the top few open problems in all of mathematics. We believe AI for biology is on a similar exponential trend.
The main difference between biology and mathematics, of course, is that math can be done purely theoretically, while biology requires experimentation. Some have used this to draw the conclusion that AI’s utility in biology will be limited. We think this is wrong. As we’ve demonstrated today, humans can collaborate with AI to perform the experiments, validate key results in a few weeks and, if necessary, work with the AI to iterate on what they find. Eventually it may even be possible for Claude itself to safely perform the experiments by autonomously controlling lab equipment, with appropriate safeguards in place, but we aren’t doing that today (our lab is also a BSL1/BSL2 facility that doesn't handle materials dangerous to humans).
More broadly, biomedical advancement has many stages — from fundamental biology discoveries, to translational research, to drug discovery, clinical trials, and finally the actual delivery of medicines and health care to patients. We are also interested in these later stages, but even simply accelerating the first stage of fundamental biological discoveries has the potential to speed up and broaden the entire pipeline. Improving our understanding of biology and sharpening biologists’ tools can drive forward all of the later stages, for example by identifying new drug targets, finding new therapeutic modalities, allowing for more precise measurement, and speeding up the experimental loop which itself further accelerates our understanding of biology. This will not in itself speed up clinical trial times, but if it succeeds it could greatly increase the number of promising candidates that go into the pipeline — an increase in throughput even though latency remains.
In Machines of Loving Grace, I wrote about AI’s potential to “cure most diseases in 5-10 years” — a goal that sounds impossible, but one I believe is just barely possible if AI is applied to every stage of the pipeline. The first step is showing that AI can first help with, and then drive, biological discoveries.
Claude’s discovery is the latest in a line of related prior work that goes back decades, beginning with systems like CRISPR, and continuing with discoveries like the bridge recombinase and VIPR in the past few years. Recently, there has been heightened interest in systems based on reverse transcriptase (RT) enzymes, the enzyme underlying the system Claude identified. And most recently, a Stanford team working independently described a novel RT system with an associated non-coding array that is in some ways similar to the one Claude found, though they are distinct systems that evolved independently from each other. I believe that we’re at the very beginning of finding such systems and developing them into powerful tools for biotechnology.
I’m proud of the resources Anthropic has invested in accelerating the public benefits of AI through the life sciences, and we’re aiming both to grow our life sciences team and to work with other scientists to extend this approach to a broad range of problems. If you have a proposal for a research collaboration or are interested in joining our life sciences team, please reach out.
This is not controversial. For KD targets in the cytoplasm, siRNA is the way to go.
Which are better therapeutics: antisense oligonucleotides (ASO) or small interfering RNAs (siRNAs)? A review of these and related molecular entities which have led to over 20 FDA approvals and many more to come
cell.com/cell-reports-medici…
Great news for patients with FUS ALS!
ir.ionis.com/news-releases/n…
Alex Harding retweeted
Very concerning!
Breaking News: Federal officials are drafting an executive order that would help cement President Trump’s ability to control billions of dollars in scientific grants funded by the National Institutes of Health. nyti.ms/4yhi6RS
Alex Harding retweeted
multi-target RNAi has so much potential. PCSK9 drugs dramatically lower LDL but have modest effects on triglycerides. substantially lowering both with one drug is exciting.
heart disease is the leading cause of death in the US and globally. cardiovascular patients are entering a golden age of treatment options!
$ARWR out with dual-targeting PCSK9/ApoC3 RNAi dimer for mixed hyperlipidemia.
Mean max following single admin:
ApoC3 -88% --> -73% trig
PCSK9 -72% (gene not just expressed in liver) --> -54% LDLc
ApoB -50%
Not much, if any competition between RNAi triggers.
Now waiting for the big CNS data release.
Easy explanation, LDL-C was already too low for Lp(a) to matter
The interaction between statin use and the Lp(a) score was not significant (p=0.76)
Stratifying further by LDL-C genetic burden: p=0.78 and p=0.12.The benefit of lowering Lp(a) does not depend on the LDL background
Couldn’t agree more—lack of better medicines is an urgent patient safety issue, and it should be treated as such by regulators.
We are on the cusp of a wave of new therapies for some of the worst diseases. But the world won’t benefit unless the US fixes its drug regulatory system. My new essay for @nytimes, on how slow clinical trials are now the biggest obstacle to curing cancer.
nytimes.com/2026/09/04/opini…
- I interviewed dozens of researchers, especially oncologists at leading U.S. centers. A striking consensus emerged: science is no longer the main bottleneck to new cancer drugs. It is our ability to test discoveries in patients through clinical trials.
- The cost of starting a Phase 1 trial in America has roughly doubled over the past decade. As a result, companies increasingly take early trials abroad: Australia’s Phase 1 trial volume has nearly doubled in a decade, driven mainly by U.S. companies.
- Unfortunately, the underlying incentives are badly asymmetric: Institutions can be blamed for harms caused by moving too fast, but almost no one is blamed when patients deteriorate during avoidable delays. One doctor called the emerging system “ritualized safety over actual risk assessment.” Or as, @DavidHongMD put it: "We often forget that the biggest risk is the cancer itself."
- This problem is becoming more urgent because medicine itself is changing. Sequencing, biological engineering and A.I. make increasingly personalized therapies possible. But our regulatory system was mostly built for standardized drugs tested in large populations.
- @sytse, the co-founder of GitLab, shows what personalized medicine can achieve: after relapsed osteosarcoma and being told there were no options left, he pursued a highly individualized approach and has now been cancer-free for a year. But doing so required extraordinary resources and regulatory expertise.
- Pierce Ogden’s father was less lucky. After molecular analysis identified a drug that might target his glioblastoma, the manufacturer agreed to provide it. But administrative barriers delayed access until it was too late. “My dad was ready to try anything,” Pierce told me. “But the system is paternalistic.”
- The A.I. revolution is making this bottleneck more important, not less. A.I. relies on relevant data. Information from early-stage trials could compound with A.I. tools to achieve truly revolutionary medicines. Without the data, this is far less likely to happen.
- Another important shift is that innovation increasingly comes from academic labs and small biotech companies rather than Big Pharma. These small companies find it far harder to unable to absorb delays and regulatory barriers.
- Apart from cancer, China is the biggest winner from America's outdated medical regulations. China has a much faster trial system, with testing often starting a full year earlier. This allows Chinese pharmaceutical companies to experiment and improve medicines while American companies play with mice. Today, half of all drugs licensed by major pharmaceutical companies originate there, up from less than 5 percent only a decade ago.
- But we don't need to copy China. The best model is Australia: lots of on-site scientific and ethics reviews, and requirements that are proportionate to small, early-stage trials. Phase 1 studies there begin roughly 6–12 months faster, without any notable increases in adverse safety events.
- Operation TrialBlazer, a 2026 HHS initiative is a good start in this direction, but we need legislative action by Congress to truly make Phase I trials faster and more efficient!
I want to thank everyone who helped me with this article: everyone I interviewed and the amazing editors at the Times. This is the result of a months long journey of extensive interviews and research.
Special thanks go to those who came on the record. One of the features of the system is an atmosphere of fear, where practitioners are afraid to publicly come out and explain these issues. So anyone who does is a hero in my book!
Alex Harding retweeted
One month into my time at @Amgen from academia, many have asked me what has surprised me the most.
I’m most surprised that any medicine makes it through the rigorous gauntlet of Research & Development!
I’ve spent my time in academia discovering and curating biological hypotheses. But so much has to go right to turn a compelling scientific idea into an important medicine for patients.
It starts with amassing and generating evidence for strong human biological conviction, but also continual scrutiny and challenges as new evidence emerges. The investments in the next steps are substantial and prioritizing important patient impact among all activities is critical.
The coordinated execution across interdependent functions, each bringing distinct expertise to the same overarching problem, is remarkable. Tackling complex and important problems in human health within a large organization requires structures that enable rigorous decisions and coordinated execution without sacrificing agility. And the role of data integration for teams to align, coordinate, and execute and to gain new insights is quite powerful.
A culture that enables high-quality teamwork, ongoing dialogue, a willingness to challenge assumptions, a healthy competitive spirit, and leadership that can bring different perspectives and expertise together appears to be the special sauce.
Experiencing how all of these pieces come together has been intellectually stimulating in so many new ways. Also, I feel privileged in being able to bring the expertise and perspective I’ve developed into a new environment and, at the same time, to expand my horizons, develop new skills, and learn from colleagues with very different areas of expertise.
I have much to learn and much I hope to contribute to generate great science and then it into great medicines.
[Pictured sharing my perspectives with new colleagues at our site in Reykjavik, Iceland @decodegenetics]
Why have we collectively decided that "invite" should replace "invitation" as a noun?
We save ourselves 4 keystrokes but the cost is our dignity!
Alex Harding retweeted
Replying to @BiotechCH @daphnezohar @soowannaway @EricSchmidt151 @SamFazeli8 @gline @JMaraganore @LifeSciVC @bradloncar @MatteisPaul @TimOpler @t_lorriman
The hosts discuss the broader regulatory and policy implications of China’s biotech presence. @daphnezohar notes “@AlexHarding7 wrote a nice piece in response to Operation Trailblazer, which the HHS announced in June to try to keep early trials in the U.S. And one stat that Alex mentioned that stuck with me is that U.S. INDs are down more than 10% since 2020, while China's Phase 1 trial count nearly doubled over the same period from about 600 to over 1,100.” #BiotechHangout
Read the article: lifescivc.com/2026/08/make-u…
Whether or not COVID-19 was a lab leak, we should be doing more to regulate gain-of-function virus research. The risks outweigh the benefits in most cases.
How to Stop a Lab Leak From Starting the Next Pandemic nytimes.com/interactive/2026… via @NYTOpinion
Alex Harding retweeted
For those interesting in learning more, here’s a great article by @AlexHarding7: lifescivc.com/2026/08/make-u…
$amlx great comeback story.
I hope they come back to ALS at some point!
Alex Harding retweeted
Make US INDs Great Again - What will and will not work to regain US strength in phase 1 clinical trials
Great new blog post from @AlexHarding7 exploring the right solutions for US regulatory approaches to early clinical development
lifescivc.com/2026/08/make-u…